DK175618B1

DK175618B1 - Pyrrole derivatives, their preparation and preparation of intermediates therefor, as well as compositions for controlling arthropods, plant nematodes, helminths or protozoa, method for controlling harmful arthropods ...............

Info

Publication number: DK175618B1
Application number: DK198906203A
Authority: DK
Inventors: Anibal Lopes; Philip Timmons; Russel Outcalt; Susan Cramp; Patricia Kwiatkowski; David Sinodis; Paul Cain
Original assignee: Rhone Poulenc Agrochimie
Priority date: 1988-12-09
Filing date: 1989-12-08
Publication date: 2004-12-27
Also published as: PT92521A; BG90609A; ZA899418B; CN1043500A; FI95462B; MY105867A; RO105644B1; UA37172C2; NO894905L; NO174344C; DK620389A; CN1028475C; CZ689989A3; FI895886A0; DK620389D0; BG60842B1; MA21689A1; CZ284089B6; IL92507A; NO894905D0

Description

DK 175618 B1 iDK 175618 B1 i

Opfindelsen angår hidtil ukendte pyrrolderivater som angivet i krav 1-7, en fremgangsmåde til fremstilling af disse forbindelser som angivet i krav 8, en fremgangsmåde ^ til fremstilling af mellemproduktforbindelser, der kan an-5 vendes til fremstilling af pyrrolderivaterne, hvilken fremgangsmåde er angivet i krav 9, en arthropodisk, plantene-matodicid, anthelmintisk eller antiprotozoisk sammensætning som angivet i krav 10-11, en insekticid, akaracid eller nematodicid sammensætning som angivet i krav 12-13, en frem-10 gangsmåde til anvendelse i veterinærmedicin og husdyrhold eller ved opretholdelse af folkesundhed som angivet i krav 14-15, samt nye mellemproduktforbindelser som angivet i krav 16.The invention relates to novel pyrrole derivatives as set forth in claims 1-7, a process for the preparation of these compounds as set forth in claim 8, a process for the preparation of intermediate compounds which can be used to prepare the pyrrole derivatives, the process of Claim 9, an arthropodic, plant matodicide, anthelmintic or antiprotozoal composition as claimed in claims 10-11, an insecticide, acaracid or nematodicide composition as claimed in claims 12-13, a method of use in veterinary medicine and animal husbandry or in the field of veterinary medicine. maintaining public health as set forth in claims 14-15, as well as new intermediate compounds as set forth in claim 16.

Mange pyrazoler (heterocycliske forbindelser indehol-15 dende to nitrogenatomer) er velkendte som insecticider.Many pyrazoles (heterocyclic compounds containing two nitrogen atoms) are well known as insecticides.

Også nogle forbindelser, der indeholder pyrrolgruppen (en heterocyclisk ring indeholdende ét nitrogenatom) er kendt som insecticider. De indeholder imidlertid almindeligvis også en anden kemisk gruppe i deres formel, der er velkendt 20 som havende insecticide egenskaber i sig selv, f.eks. en pyrethroidgruppe, eller en carbamatgruppe eller en organo-phosphorsyregruppe. Simple substituerede pyrrolderivater er blevet beskrevet som landbrugskemisk anvendelige forbindelser, f.eks. i GB patentskrift nr. 2.189.242, men til fungicid 25 anvendelse.Also, some compounds containing the pyrrole group (a heterocyclic ring containing one nitrogen atom) are known as insecticides. However, they generally also contain another chemical group in their formula which is well known as having insecticidal properties per se, e.g. a pyrethroid group, or a carbamate group or an organophosphoric acid group. Simple substituted pyrrole derivatives have been described as agricultural chemically useful compounds, e.g. in GB Patent No. 2,189,242, but for fungicide use.

De hidtil ukendte pyrrolderivater ifølge den foreliggende opfindelse har den almene formel χΙ-Aj-X« (I) Χ2-^5γ!ΐ-χ3The novel pyrrole derivatives of the present invention have the general formula χΙ-Aj-X «(I) Χ2- ^ 5γ !ΐ-χ3

YY

35 i hvilken X betyder et halogenatom, cyano, halogenalkyl, alkoxy,Wherein X represents a halogen atom, cyano, haloalkyl, alkoxy,

I DK 175618 B1 II DK 175618 B1 I

I 2 II 2 I

I halogenalkoxy, alkylthio, alkylsulfinyl,-alkylsulfo- IIn haloalkoxy, alkylthio, alkylsulfinyl, -alkylsulfo-I

I nyl, halogenalkylthio, halogenalkylsulfinyl eller IIn nyl, haloalkylthio, haloalkylsulfinyl or I

I halogenalkylsulfonyl, hvor alkyl-, halogenalkyl-, IIn haloalkylsulfonyl, where alkyl, haloalkyl, I

I alkoxy- og halogenalkoxygrupperne har lineær eller IIn the alkoxy and haloalkoxy groups have linear or I

I 5 forgrenet kæde og mindre end 10 carbonatomer, og IIn 5 branched chain and less than 10 carbon atoms, and I

I halogensubstitutionen i alle disse grupper består af IThe halogen substitution in all these groups consists of I

I et eller flere halogenatomer, der er ens eller for- IIn one or more halogen atoms that are the same or different

I skellige, fra mono- op til fuldstændig polysubstitu- IIn various, from mono-up to complete polysubstitution

I tion, II tion, I

I 10 R1, R2 og R2 er hver især valgt blandt samme sæt substituen- IIn R 1, R 2 and R 2 are each selected from the same set of substituent-I

I ter som beskrevet for X, et hydrogenatom, en alkyl- IIters as described for X, a hydrogen atom, an alkyl I

I gruppe og en substituent, hvor ikke mere end en af IIn group and a substituent where not more than one of I

disse (R1, R2 og R2) er valgt fra gruppen bestående Ithese (R1, R2 and R2) are selected from the group consisting of I

I af formyl, amino, alkylamino og dialkylamino, hvori II of formyl, amino, alkylamino and dialkylamino, wherein I

I 15 alkylgrupperne er lineære eller forgrenede og har IIn the alkyl groups are linear or branched and have

I mindre end 10 carbonatomer, IIn less than 10 carbon atoms, I

I Y betegner et halogenatom eller cyano, alkyl, halogenal- IIn Y represents a halogen atom or cyano, alkyl, halogenal I

I kyl, alkoxy eller halogenalkoxy, hvor alkyl-, halogen- IIn cooling, alkoxy or haloalkoxy, wherein alkyl, halo-I

I alkyl-, alkoxy- og halogenalkoxygrupperne er lineære IIn the alkyl, alkoxy and haloalkoxy groups are linear I

I 20 eller forgrenede og har mindre end 10 carbonatomer, I20 or branched and having less than 10 carbon atoms, I

I og halogensubstitutionen i alle disse grupper består II and the halogen substitution in all these groups

I af et eller flere halogenatomer, der er ens eller II of one or more halogen atoms which are the same or I

I forskellige, fra mono- og op til fuldstændig polysub- IIn various, from mono- and up to completely polysub- I

I stitution, eller IIn stitution, or

I 25 Y betegner et hydrogenatom, når IY represents a hydrogen atom when I

I X betyder et halogenatom eller en gruppe R5S(0)n, IIn X, a halogen atom or group represents R 5 S (0) n, I

I hvor n betyder 0, 1 eller 2, og R^ betyder alkyl IIn which n is 0, 1 or 2 and R 1 is alkyl I

I eller halogenalkyl, og alkylcarbonkæderne og halogen- II or haloalkyl, and the alkyl carbon chains and halo- I

I substitutionen er som ovenfor defineret, IIn the substitution as defined above, I

I 30 R^ og R3 hver betegner et hydrogenatom, og II 30 and R3 each represent a hydrogen atom and I

I R2 betyder cyano, IIn R2, cyano means I

I X2, X2, X2 og X4 er hver for sig valgt fra samme sæt sub- IIn X2, X2, X2 and X4 are separately selected from the same set of sub-I

I stituenter som beskrevet for Y og et hydrogenatom, IIn stituents as described for Y and a hydrogen atom, I

I med følgende forbehold: II have the following reservations:

I 35 mindst en af substituent erne R·1-, R2 og R2 er valgt IIn at least one of the substituents R 1, R 2 and R 2 are selected

I fra samme sæt substituenter som beskrevet for X, II from the same set of substituents as described for X, I

DK 175618 B1 3 såfremt X4 og X1 betyder hydrogen, og X betyder halogen eller cyano, er R2 forskellig fra X, og såfremt X4 og X1 betyder hydrogen, og Y betyder methyl, er X forskellig fra brom, 5 med undtagelse af den forbindelse, i hvilken X4=X1=Y=R1=X=R2=R3=C1 og samtidig X2=X3=H.If X4 and X1 are hydrogen and X is halogen or cyano, R2 is different from X and if X4 and X1 are hydrogen and Y is methyl, X is different from bromine, with the exception of the compound, in which X4 = X1 = Y = R1 = X = R2 = R3 = C1 and at the same time X2 = X3 = H.

Mere specifikke hidtil ukendte pyrrolderivater med formlen I ifølge opfindelsen er de følgende forbindelser, hvor 10 X er et halogenatom eller cyano, halogenalkyl, alkoxy, halogenalkoxy, alkylthio, alkylsulfinyl, alkylsul-fonyl, halogenalkylthio, halogenalkylsulfinyl eller halogenalkylsulfonyl, hvor alkyl-, halogenalkyl-, alkoxy- og halogenalkoxygrupperne er lineære eller 15 forgrenede og har mindre end 10 carbonatomer, og halo gensubstitutionen i alle disse grupper er monosubstitution eller op til fuldstændig polysubstitution,More specific novel pyrrole derivatives of formula I according to the invention are the following compounds wherein 10 X is a halogen atom or cyano, haloalkyl, alkoxy, haloalkoxy, alkylthio, alkylsulfinyl, alkylsulphonyl, haloalkylthio, haloalkylsulfinyl or haloalkylsulfonyl, , the alkoxy and haloalkoxy groups are linear or branched and have less than 10 carbon atoms and the halo gene substitution in all these groups is monosubstitution or up to complete polysubstitution,

R1, R2 og R3 er hver især valgt blandt de samme substituen- IR 1, R 2 and R 3 are each selected from the same substituent I

ter som beskrevet for X, et hydrogenatom, en alkyl-20 gruppe og en substituent, hvor ikke mere end en af disse (R1, R2, R3) er valgt fra gruppen bestående af formyl, amino, alkylamino og dialkylamino, hvor alkyl-grupperne er lineære eller forgrenede og har mindre end 10 carbonatomer, 25 Y betyder et halogenatom eller cyano, alkyl, halogenal kyl, alkoxy eller halogenalkoxy, hvor alkyl-, halogenalkyl-, alkoxy- og halogenalkoxygrupperne er lineære eller forgrenede og har mindre end 10 carbonatomer, og halogensubstitutionen i alle disse grupper 30 er monosubstitution eller op til fuldstændig polysub- stitution, og X1, X2, X3 og X4 er som angivet i krav 1.are as selected for X, a hydrogen atom, an alkyl group and a substituent wherein no more than one of these (R1, R2, R3) is selected from the group consisting of formyl, amino, alkylamino and dialkylamino, wherein the alkyl groups Y is a halogen atom or cyano, alkyl, haloalkyl, alkoxy or haloalkoxy, wherein the alkyl, haloalkyl, alkoxy and haloalkoxy groups are linear or branched and have less than 10 carbon atoms, and the halogen substitution in all of these groups is monosubstitution or up to complete polysubstitution, and X1, X2, X3 and X4 are as defined in claim 1.

I almindelighed foretrukne forbindelser med formlen I, der er af interesse som insecticider og acaricider, er for-35 bindeiser med formlen I, i hvilken X betyder et halogenatom eller en gruppe R^S(0)n, iGenerally preferred compounds of formula I which are of interest as insecticides and acaricides are compounds of formula I wherein X represents a halogen atom or a group R 2 S (O) n

I DK 175618 B1 II DK 175618 B1 I

I II I

I hvilken n betyder O, l eller 2, og R5 betyder alkyl IIn which n is 0, 1 or 2, and R 5 is alkyl I

I eller halogenalkyl, II or haloalkyl, I

I R1 betyder et hydrogenatom, et halogenatom eller alkyl- IIn R 1, a hydrogen atom, a halogen atom or alkyl I means

I thio, II thio, I

I 5 R2 betyder cyano, IIn 5 R2 means cyano, I

I R3 betyder et hydrogenatom eller et halogenatom, IIn R3, a hydrogen atom or a halogen atom means I

I Y betyder et hydrogenatom, et halogenatom, halogenalkyl IIn Y means a hydrogen atom, a halogen atom, haloalkyl I

I eller halogenalkoxy, idet dog Y er et hydrogenatom som II or haloalkoxy, however Y is a hydrogen atom such as I

I defineret i krav 1, og II defined in claim 1, and

I 10 X1, X2, X3 og X4 hver for sig er valgt fra gruppen bestående IIn X1, X2, X3 and X4 are individually selected from the group consisting of I

I af et hydrogenatom, et halogenatom, C1-C3-alkyl, II of a hydrogen atom, a halogen atom, C1-C3 alkyl, I

I C1-C3~alkoxy og Ci-C3-alkylthio. IIn C1-C3 alkoxy and C1-C3 alkylthio. IN

I Mere specifikke forbindelser med den almene formel I, IMore specific compounds of general formula I, I

der er foretrukne og er af særlig interesse, er forbindel- Iwhich are preferred and of particular interest are compounds I

I 15 serne med den almene formel II, der udviser en høj insecticid IIn the 15 of the general formula II, which exhibits a high insecticide I

I aktivitet: IIn activity: I

I 20 j {II) II 20 j {II) I

I x,^rI x, ^ r

I y II y I

I 25 i hvilken II 25 in which I

I X betyder R5S(0)n, i hvilken n betyder 0, 1 eller 2, IIn X, R 5S (0) means n, in which n means 0, 1 or 2, I

I og R5 betyder CH3, CF3, CF2CI, CFC12» CF2Br, CHF2, II and R5 are CH3, CF3, CF2Cl, CFC12 »CF2Br, CHF2, I

I CHC12 eller CHClF, IIn CHCl2 or CHClF, I

I R2 betyder cyano, IIn R2, cyano means I

I 30 R1 betyder H, F, Cl eller Br, . IIn R 1, H, F, Cl or Br,. IN

I R3 betyder H, F, Cl eller Br, IIn R3, H, F, Cl or Br, I means

X1 betyder H eller Cl, og IX1 means H or Cl, and I

Y betyder CF3 eller CF3O. IY means CF3 or CF3O. IN

DK 175618 B1 5 Særligt foretrukne forbindelser med formlen (I) er sådanne, hvori R.1 er et hydrogenatom eller et halogenatom, R2 v er cyano, 5 X er en halogenalkyl-S(0)n-gruppe, hvor n er 0, 1 eller 2, X1 og X4 er forskellige fra et hydrogenatom, Y er en halogenalkyl- eller halogenalkoxygruppe, ogParticularly preferred compounds of formula (I) are those wherein R 1 is a hydrogen atom or a halogen atom, R 2 is cyano, 5 X is a haloalkyl-S (O) n group where n is 0, 1 or 2, X 1 and X 4 are different from a hydrogen atom, Y is a haloalkyl or haloalkoxy group, and

X2 og X3 er et hydrogenatom. IX2 and X3 are a hydrogen atom. IN

10 Særligt foretrukne forbindelser med formlen (II) er sådanne, hvori X betyder R5S{0)n, hvor n er 0, 1 eller 2, og R^ er CH3, CF3, CF2C1 eller CFC12, R2 er cyano, 15 R1 er H, F, Cl, Br eller NH2, R3 er H, F, Cl, Br, CF3 eller CN, χΐ er H eller Cl, og Y er CF3 eller CF30.Particularly preferred compounds of formula (II) are those wherein X is R 5 S (O) n, where n is 0, 1 or 2 and R 1 is CH 3, CF 3, CF 2 Cl or CFC 12, R 2 is cyano, R 1 is H , F, Cl, Br or NH2, R3 is H, F, Cl, Br, CF3 or CN, χΐ is H or Cl, and Y is CF3 or CF30.

Blandt forbindelserne ifølge opfindelsen er særligt 20 foretrukne forbindelser følgende: 1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-3-cyano-4-{trifluormethylthio)-pyrrol; 1-(2,6-dichlor-4-trifluormethoxyphenyl) -2-chlor-3-cyano-4-(trifluormethylsulfonyl)-pyrrol; 25 1-(2,6-dichlor-4-trifluormethylphenyl) -2-chlor-3- cyano-4-(dichlorfluormethylthio)-pyrrol; 1-(2,6-dichlor-4 -trifluormethylphenyl) -2-chlor-3-cyano-4-(dichlorfluormethylsulfinyl)-pyrrol; 1-(2,6-dichlor-4 - trif luormethylphenyl) -2-chlor-3-30 cyano-4-(dichlorfluormethylsulfonyl)-pyrrol; 1-(2,6-dichlor-4-trifluormethylphenyl) -2-chlor-3-cyano-4-(chlordifluormethylsulfonyl)-pyrrol; 1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-3-cya-no-4- (chlordifluormethylsulfinyl) -pyrrol; 35 1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-3- cyano-4-(chlordifluormethylthio)-pyrrol; I DK 175618 B1Among the compounds of the invention, particularly preferred compounds are the following: 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (trifluoromethylthio) pyrrole; 1- (2,6-dichloro-4-trifluoromethoxyphenyl) -2-chloro-3-cyano-4- (trifluoromethylsulfonyl) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (dichlorofluoromethylthio) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (dichlorofluoromethylsulfinyl) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-30 cyano-4- (dichlorofluoromethylsulfonyl) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (chlorodifluoromethylsulfonyl) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (chlorodifluoromethylsulfinyl) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (chlorodifluoromethylthio) pyrrole; I DK 175618 B1

I II I

I 1-(2,6-dichlor-4-trif 1 uormethylphenyl) -2-brom-3-cyano- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-1

I 4-(trifluormethylsulfinyl)-pyrrol; IIn 4- (trifluoromethylsulfinyl) pyrrole; IN

I 1-(2, S-dichlor-4-trifluormethylphenyl) -2-brom-3-cyano- I1- (2, 5-Dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-1

I 4-(trifluormethylsulfonyl)-pyrrol; IIn 4- (trifluoromethylsulfonyl) pyrrole; IN

I 5 1-(2,6-dichlor-4-trifluormethylphenyl) -2-brom-3-cyano- ' I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-1

I 4-(dichlorfluormethylthio)-pyrrol; IIn 4- (dichlorofluoromethylthio) pyrrole; IN

I 1-(2,6-dichlor-4-trifluormethylphenyl) -2-brom-3-cyano- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-1

I 4-(dichlorfluormethylsulfonyl)-pyrrol; IIn 4- (dichlorofluoromethylsulfonyl) pyrrole; IN

I 10 4-(dichlorfluormethylsulfinyl)-pyrrol; IIn 4- (dichlorofluoromethylsulfinyl) pyrrole; IN

I 1-(2,6-dichlor-4-trif luormethylphenyl)-2-brom-3-cyano- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-1

I 4-(chlordifluormethylthio)-pyrrol; IIn 4- (chlorodifluoromethylthio) pyrrole; IN

4-(chlordifluormethylsulfinyl)-pyrrol; I4- (chlorodifluoromethylsulfinyl) pyrrole; IN

15 1-(2,6-dichlor-4-trif luormethylphenyl)-2-chlor-3- I1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I

cyano-4-(dichlorfluormethylsulfonyl)-5-brompyrrol; Icyano-4- (dichlorofluoromethylsulphonyl) -5-brompyrrol; IN

I 1-(2,6-dichlor-4-trif luormethylphenyl) -2-brom-3-cyano- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-1

I 4-(chlordifluormethylsulfonyl)-pyrrol; IIn 4- (chlorodifluoromethylsulfonyl) pyrrole; IN

1-(2,6-dichlor-4-trif luormethoxyphenyl) -2-chlor-3- I1- (2,6-Dichloro-4-trifluoromethoxyphenyl) -2-chloro-3- I

H 20 cyano-4-(dichlorfluormethylsulfinyl)-pyrrol; IH cyano-4- (dichlorofluoromethylsulfinyl) pyrrole; IN

I 1-(2,6-dichlor-4-trif luormethoxyphenyl)-2-chlor-3- IIn 1- (2,6-dichloro-4-trifluoromethoxyphenyl) -2-chloro-3- I

cyano-4-(dichlorfluormethylsulfonyl)-pyrrol; Icyano-4- (dichlorofluoromethylsulphonyl) pyrrole; IN

1-(2-chlor-4-trifluormethylphenyl) -2-chlor-3-cyano- I1- (2-Chloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-I

I 25 1- (2-chlor-4-trifluormethylphenyl)-2-chlor-3-cyano- I1- (2-Chloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-1

4-(dichlorfluormethylsulfinyl)-pyrrol; I4- (dichlorfluormethylsulfinyl) pyrrole; IN

I 1-(2-chlor-4-trifluormethylphenyl) -2-brom-3-cyano- I1- (2-Chloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-1

I 1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-3- IIn 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I

I 30 cyano-4-(dichlorf luormethylthio)-5-methyl thiopyrrol; IIn cyano-4- (dichlorofluoromethylthio) -5-methyl thiopyrrole; IN

1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-3- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-chloro-3- I

cyano-4-(bromdifluormethylthio)-pyrrol; Icyano-4- (bromodifluoromethylthio) pyrrole; IN

I 1 - (2,6-dichlor-4-trif luormethylphenyl)-2-chlor-3- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-chloro-3- I

cyano-4-(bromdifluormethylsulfinyl)-pyrrol; Icyano-4- (bromdifluormethylsulfinyl) pyrrole; IN

I 35 1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-3- IIn 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I

I cyano-4-(bromdifluormethylsulfonyl)-pyrrol; IIn cyano-4- (bromodifluoromethylsulfonyl) pyrrole; IN

DK 175618 B1 IDK 175618 B1 I

7 I7 I

I cyano-4-(methylsulfinyl)-pyrrol; ' IIn cyano-4- (methylsulfinyl) pyrrole; 'I

I cyano-4-(methylsulfonyl)-pyrrol; IIn cyano-4- (methylsulfonyl) pyrrole; IN

I 5 l-(4-brom-2,6-dichlorphenyl)-3-cyano-4-(chlordifluor- I1- (4-Bromo-2,6-dichlorophenyl) -3-cyano-4- (chlorodifluoro-1

I methylthlo)-pyrrol; IIn methylthlo) pyrrole; IN

I l-(4-brom-2,6-dichlorphenyl)-3-cyano-4-(trifluor- I1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (trifluoro-1

I methylthio)-pyrrol; IIn methylthio) pyrrole; IN

I 1-(2,4,6-trichlorphenyl)-3-cyano-4-(chlordifluor- II 1- (2,4,6-Trichlorophenyl) -3-cyano-4- (chlorodifluoro-1

I 10 methylthio)-pyrrol; IIn methylthio) pyrrole; IN

I 1 - (2,4 , 6 - trichlorphenyl) - 3 - cyano-4 - (chlordif luor- I1- (2,4,6-trichlorophenyl) -3-cyano-4 - (chlorodifluoro-1

I methylsulfinyl)-pyrrol; IIn methylsulfinyl) pyrrole; IN

I i-(2,4,6-trichlorphenyl)-3-cyano-4-(dichlorfluor- I1- (2,4,6-Trichlorophenyl) -3-cyano-4- (dichlorofluoro-1

I methylthio)-pyrrol; IIn methylthio) pyrrole; IN

I 15 1 - (2,4,6-trichlorphenyl)-3-cyano-4 - (dichlorfluor- I1- (2,4,6-Trichlorophenyl) -3-cyano-4- (dichlorofluoro-1

I methylsulfinyl)-pyrrol; IIn methylsulfinyl) pyrrole; IN

I 1 - (2,4,6-trichlorphenyl)-3-cyano-4 - (dichlorfluor- I1- (2,4,6-Trichlorophenyl) -3-cyano-4- (dichlorofluoro-1

I methylsulfonyl)-pyrrol? IIn methylsulfonyl) pyrrole? IN

I 1-(4-brom-2# 6-dichlorphenyl)-3-cyano-4-(dichlorfluor- I1- (4-bromo-2 # 6-dichlorophenyl) -3-cyano-4- (dichlorofluoro-1

I 20 methylthio)-pyrrol; IIn methylthio) pyrrole; IN

I 1-(4-brom-2f 6-dichlorphenyl)-3-cyano-4-(dichlorfluor- I1- (4-bromo-2-6-dichlorophenyl) -3-cyano-4- (dichlorofluoro-1

I methylsulfinyl)-pyrrol; IIn methylsulfinyl) pyrrole; IN

I 1-(4-brom-2,6-dichlorphenyl) -3-cyano-4-(dichlorfluor- I1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (dichlorofluoro-1

I methylsulfonyl)-pyrrol; I 25 1-(2,4,6-trichlorphenyl)-3-cyano-4-(trifluormethyl- I thio)-pyrrol; I - 1-(2,4,6-trichlorphenyl)-3-cyano-4-(trifluormethyl- I sulfinyl)-pyrrol; I l-(2,4,6-trichlorphenyl)-3-cyano-4-(trifluormethyl- I 30 sulfonyl)-pyrrol; I 1-(2,4,6-trichlorphenyl)-3-cyano-4-(trichlormethyl- thio)-pyrrol; 1-(2,4-dichlorphenyl)-3-cyano-4-(dichlorfluormethyl- thio)-pyrrol; 35 1-(2,4,6-trichlorphenyl)-3-cyano-4-chlorpyrrol; I 1-(2,4,6-trichlorphenyl) -3-cyano-4- (chlordifluor- I DK 175618 B1In methylsulfonyl) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (trifluoromethyl-thio) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (trifluoromethyl-sulfinyl) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (trifluoromethyl-sulfonyl) pyrrole; In 1- (2,4,6-trichlorophenyl) -3-cyano-4- (trichloromethylthio) pyrrole; 1- (2,4-dichlorophenyl) -3-cyano-4- (dichlorofluoromethylthio) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4-chloropyrrole; In 1- (2,4,6-trichlorophenyl) -3-cyano-4- (chlorodifluoro)

methylsulfonyl)-pyrrol; Imethylsulfonyl) pyrrole; IN

1-(2,6-dichlorphenyl)-3-cyano-4-(dichlorfluormethyl- I1- (2,6-dichlorophenyl) -3-cyano-4- (dichlorofluoromethyl-1

H thio)-pyrrol; IH thio) pyrrole; IN

1-(4-brom-2,6-dichlorphenyl)-3-cyano-4-{trifluor- I1- (4-Bromo-2,6-dichlorophenyl) -3-cyano-4- {trifluoro-1

5 methylsulfinyl)-pyrrol; IMethylsulfinyl) pyrrole; IN

I 1-(4-brom-2,6-dichlorphenyl)-3-cyano-4-(trifluor- IIn 1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (trifluoro-1

methylsulfonyl)-pyrrol; Imethylsulfonyl) pyrrole; IN

I 1-(4-brom-2,6-dichlorphenyl)-3-cyano-4-(chlordifluor- I1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (chlorodifluoro-1

I methylsulfinyl)-pyrrol; IIn methylsulfinyl) pyrrole; IN

I 10 1-(4-brom-2,6-dichlorphenyl)-3-cyano-4-(chlordifluor- I1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (chlorodifluoro-1

I methylsulfonyl)-pyrrol; IIn methylsulfonyl) pyrrole; IN

1 - (4-brom-2 , 6-dimethylphenyl) -3-cyano-4- (trifluor- I1- (4-Bromo-2,6-dimethylphenyl) -3-cyano-4- (trifluoro-1

methylsulfinyl)-pyrrol; Imethylsulfinyl) pyrrole; IN

I 1-(4-brom-2,6-dimethylphenyl) -3-cyano-4-(trifluor- IIn 1- (4-bromo-2,6-dimethylphenyl) -3-cyano-4- (trifluoro-1

15 methylsulfonyl)-pyrrol; IMethylsulfonyl) pyrrole; IN

1- (4-brom-2,6-difluorphenyl) -3-cyano-4- (dichlorfluor- I1- (4-Bromo-2,6-difluorophenyl) -3-cyano-4- (dichlorofluoro-1

methylthio)-pyrrol; Imethylthio) pyrrole; IN

1-(2,6-dichlorT4-trifluormethylphenyl)-2-chlor-3- I1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I

cyano-4-(trifluormethylsulfonyl)-pyrrol; Icyano-4- (trifluoromethylsulfonyl) pyrrole; IN

20 1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-3- I1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I

cyano-4-(trifluormethylsulfinyl)-pyrrol; Icyano-4- (trifluoromethylsulfinyl) pyrrole; IN

cyano-4-trifluormethylsulfinyl-5-brompyrrol; Icyano-4-trifluoromethylsulfinyl-5-brompyrrol; IN

25 cyano-4-trifluormethylsulfonyl-5-brompyrrol, ICyano-4-trifluoromethylsulfonyl-5-bromopyrrole, I

cyano-4-trifluormethylthio-pyrrol; Icyano-4-trifluoromethylthio-pyrrole; IN

1-(2,6-dichlor-4-trifluormethylphenyl)-2-brom-3-tri- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-bromo-3-tri-I

fluormethylthio-4-cyano-5-chlorpyrrol; Ifluoromethylthio-4-cyano-5-chloropyrrole; IN

30 1-(2,6-dichlor-4-trifluormethylphenyl)-2-[(trifluor- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2 - [(trifluoro-1

methyl)carbonylamino]-3-trifluormethylthio-4-cyano-5-chlor- Imethyl) carbonylamino] -3-trifluoromethylthio-4-cyano-5-chloro-I

pyrrol; Ipyrrole; IN

1- (2,6-dichlor-4-trif luormethylphenyl) -2- (methylcar- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2- (methylcar-I

bonylamino)-3-trifluormethylthio-4-cyano-5-chlorpyrrol; Ibonylamino) -3-trifluoromethylthio-4-cyano-5-chloropyrrole; IN

35 1-(2,6-dichlor-4-trifluormethylphenyl)-2-amino-3- I1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3- I

trifluormethylthio-4-cyano-5-chlorpyrrol; Itrifluoromethylthio-4-cyano-5-chloropyrrole; IN

DK 175618 B1 IDK 175618 B1 I

l-^2-chlor-4-trifluormethylphenyl)-2-amino-3-tri- I1- (2-Chloro-4-trifluoromethylphenyl) -2-amino-3-tri-I

1- (2,6-dichlor-4-trif luormethylphenyl) -2-amino-3- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-amino-3- I

dichlorfluormethylthio-4-cyano-5-chlorpyrrol; Idichlorofluoromethylthio-4-cyano-5-chloropyrrole; IN

5 1-(2,6-dichlor-4-trifluormethylphenyl)-2,4-bis-(tri- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2,4-bis- (tri-I)

fluormethylthio-3-cyano-5-aminopyrrol; Ifluoromethylthio-3-cyano-5-aminopyrrole; IN

1-(2,6-dichlor-4-trifluormethylphenyl)-2-amino-3- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-amino-3- I

trifluormethylthio-4-cyano-5-brompyrrol; Itrifluoromethylthio-4-cyano-5-brompyrrol; IN

I 10 trifluormethylthio-4-cyanopyrrol; IIn trifluoromethylthio-4-cyanopyrrole; IN

I 1-(4-trifluormethylphenyl)-2-amino-3-trifluormethyl- IIn 1- (4-trifluoromethylphenyl) -2-amino-3-trifluoromethyl-I

I thio-4-cyano-5-brompyrrol; IIn thio-4-cyano-5-bromopyrrole; IN

I 1-(2-chlor-4-trifluormethylphenyl)-2-amino-3-trifluor- I1- (2-Chloro-4-trifluoromethylphenyl) -2-amino-3-trifluoro-1

I methylthio-4-cyano-5-brompyrrol; IIn methylthio-4-cyano-5-bromopyrrole; IN

I 15 1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-3- IIn 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I

I cyano-4-(dichlorfluormethylthio)-pyrrol; IIn cyano-4- (dichlorofluoromethylthio) pyrrole; IN

I 1-(2,6-dichlor-4-trifluormethylphenyl) -2-chlor-3- IIn 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I

I cyano-4-(dichlorfluormethylsulfinyl)-pyrrol; IIn cyano-4- (dichlorofluoromethylsulfinyl) pyrrole; IN

I 1-(2,6-dichlor-4-trif luormethylphenyl)-2-chlor-3- IIn 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I

I 20 cyano-4-(dichlorfluormethylsulfony1)-pyrrol; IIn cyano-4- (dichlorofluoromethylsulfonyl) pyrrole; IN

I 1-(2,6-dichlor-4-trif luormethylphenyl)-3-cyano-4- IIn 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-cyano-4- I

(dichlorfluormethylthio)-pyrrol; I(Dichlorofluoromethylthio) pyrrole; IN

I 1-(2,6-dichlor-4-trifluormethylphenyl)-3-cyano-4- IIn 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-cyano-4- I

I (dichlorfluormethylsulfinyl)-pyrrol eller I 25 1-(2 , 6-dichlor-4-trifluormethoxyphenyl)-2-chlor-3- I cyano-4-(trifluormethylsulfonyl)-pyrrol.In (dichlorofluoromethylsulfinyl) pyrrole or In 1- (2,6-dichloro-4-trifluoromethoxyphenyl) -2-chloro-3- In cyano-4- (trifluoromethylsulfonyl) pyrrole.

I Det er et formål med den foreliggende opfindelse at I tilvejebringe hidtil ukendte insecticider og acaricider af I pyrrolgruppen samt mellemprodukter til fremstilling deraf.It is an object of the present invention to provide novel insecticides and acaricides of the pyrrole group as well as intermediates for their preparation.

I 30 Et yderligere formål med opfindelsen er at tilveje- I bringe særdeles aktive forbindelser. Disse og andre formål I med opfindelsen opnås helt eller delvis med de i det følgende I nærmere beskrevne hidtil ukendte forbindelser.A further object of the invention is to provide highly active compounds. These and other objects of the invention are achieved, in whole or in part, with the novel compounds described hereinafter.

I 35 I DK 175618 B1 I 10I 35 I DK 175618 B1 I 10

Beskrivelse af de foretrukne udførelsesformer IDescription of the Preferred Embodiments I

I Metoder eller fremgangsmåder til syntese ! IIn Methods or Methods of Synthesis! IN

I Forbindelserne med den almene formel I kan fremstilles IThe compounds of general formula I may be prepared

5 ved anvendelse eller tilpasning af kendte metoder, dvs. I5 using or adapting known methods, i. IN

metoder, der tidligere er anvendt eller beskrevet i den Imethods previously used or described in the I

I kemiske litteratur: generelt pyrrol-ringdanneIse, efterfulgt IIn chemical literature: generally pyrrole ring formation, followed by I

I om nødvendigt af ombytning af substituenter. Det vil også IIf necessary by substituting substituents. So will you

forstås, at ved beskrivelsen af de følgende fremgangsmåder IIt is understood that by the description of the following methods I

10 kan rækkefølgerne for indførelsen af de forskellige grupper I10, the sequences for the introduction of the different groups I can be

I på pyrrol ringen udføres i en anden orden, og a't egnede be- IThe on the pyrrole ring is carried out in a different order and the appropriate treatment

skyttelsesgrupper kan være nødvendige, hvilket vil være Iprotecting groups may be necessary, as will I

I åbenbart for fagmanden. Forbindelser med den almene formel I IObviously for the skilled person. Compounds of general formula I

kan også ved kendte metoder omdannes til andre forbindelser Ican also be converted to other compounds I by known methods

15 med den almene formel I. I15 of general formula I.

I Når der i den følgende beskrivelse af fremgangsmåderne IIn the following description of the methods I

er tale om symboler i formlerne, der ikke er specifikt defi- Iare symbols in formulas that are not specifically defined

neret, vil det forstås, at de er som defineret i det fore- IOtherwise, it will be understood that they are as defined herein

gående i overensstemmelse med den først angivne definition Igoing in accordance with the first definition I

20 for hvert symbol. Udtrykket "beskyttelse" skal omfatte omdan- I20 for each symbol. The term "protection" shall include the transformation

nelse til en egnet ikke-reaktiv gruppe, der om ønsket kan Ito a suitable non-reactive group which, if desired, can

genomdannes, samt tilførslen eller additionen af grupper, Igenome formation, as well as the addition or addition of groups, I

der bevirker, at funktionaliteten bliver ikke-reaktiv. Inden Icausing the functionality to become non-reactive. Before I

for fremgangsmådedefinitionerne refererer udtrykket "amino", Ifor the process definitions, the term "amino" refers to I

25 såfremt andet ikke er angivet, til den usubstituerede amino- I25, unless otherwise stated, to the unsubstituted amino I

gruppe. Igroup. IN

Opfindelsen angår især mellemproduktforbindelser, IThe invention relates in particular to intermediate compounds, I

der kan anvendes til fremstilling af visse af de her om- Iwhich may be used in the manufacture of certain of these

handlede forbindelser. Sådanne foretrukne me11emproduktfor- Itraded connections. Such preferred metal product forms

30 bindeiser, der fremstilles som her beskrevet, har den almene I30 binders prepared as described herein have the general I

formel Iformula I

-4-ςΓ"-4-ςΓ "

35 , I (Illa) I35, I (Illa) I

χ1~ΤιΓχ4 Iχ1 ~ ΤιΓχ4 I

VV

y Iy I

11 DK 175618 B1 i hvilken Y betyder H, Cl, Br, CF3 eller OCF3, og X1 og X4 hver for sig betyder H, Cl, F, CH3 eller SCH3, idet dog såfremt X1 og X4 hver betyder H, er Y forskellig fra H eller Cl. Sådanne forbindelser som defineret ved det nævnte for-5 behold er ikke omfattet af den foreliggende opfindelse, men kan stadig anvendes som mellemprodukter til fremstilling af forbindelser med formlen I ifølge opfindelsen.B1 in which Y means H, Cl, Br, CF3 or OCF3, and X1 and X4 each mean H, Cl, F, CH3 or SCH3, however, if X1 and X4 each means H, Y is different from H or Cl. Such compounds as defined by the foregoing proviso are not included in the present invention, but can still be used as intermediates for the preparation of compounds of formula I according to the invention.

Forbindelser med formlen Illa, der specifikt foretrækkes som mellemprodukter, er de forbindelser, hvor Y 10 betyder CF3 eller OCF3, X1 betyder H eller Cl, og X4 betyder Cl.Compounds of formula IIa, which are specifically preferred as intermediates, are those compounds where Y 10 represents CF3 or OCF3, X1 means H or Cl, and X4 means Cl.

FREMGANGSMÅDE 1 15 Ifølge en udførelsesform for opfindelsen kan forbin delserne med formlen I, i hvilken R* og R^ betegner hydrogen, X betyder cyano, og R3 er en amino (NH2)-gruppe, og X1, X3, X3, X4 og Y har de samme definitioner som angivet i den generelle definition for opfindelsen, dvs. forbindelser med 20 den almene formel V-ζΓ" K. (III) 25 x1—fT^x4 x2-\J-x3PROCEDURE 1 According to one embodiment of the invention, the compounds of formula I, in which R * and R have the same definitions as set forth in the general definition of the invention, i. compounds of general formula V-ζΓ "K. (III) 25 x1-fT ^ x4 x2- \ J-x3

YY

fremstilles ud fra dicyanopropenderivater med den almene 30 formelare prepared from dicyanopropene derivatives of the general formula

NH-CH=C—CH2—CNNH-CH = C-CH2-CN

x'-Av-x4" (IV) 35 X2—liy^Lx3x'-Av-x4 "(IV) X2-liy ^ Lx3

YY

I DK 175618 B1I DK 175618 B1

. 12 I. 12 I

i hvilken de forskellige symboler har den i det foregående Iin which the various symbols have it in the preceding I

H angivne betydning, ved omsætning med et basisk middel, for- IH meaning, by reaction with a basic agent, for I

trinsvis et alkalisk middel, f.eks. en tertiær amin eller Istepwise an alkaline agent, e.g. a tertiary amine or I

et hydroxid eller carbonat af et alkalimetal. Reaktionen Ia hydroxide or carbonate of an alkali metal. Reaction I

I 5 udføres med fordel ved en temperatur mellem -80 og 150°C, II 5 is advantageously carried out at a temperature between -80 and 150 ° C, I

I fortrinsvis ved en temperatur fra 40 til 100°C. Opløsnings- IPreferably at a temperature of 40 to 100 ° C. Solution I

I midler kan anvendes, f.eks. flydende alkoholer, carbonhydri- IMeans may be used, e.g. liquid alcohols, hydrocarbons I

I der, halogencarbonhydrider, ethere, ketoner, amider, f.eks. IIn it, halohydrocarbons, ethers, ketones, amides, e.g. IN

N-methylpyrrolidon, eller vand. IN-methylpyrrolidone, or water. IN

I 10 II 10 I

I FREMGANGSMÅDE 2 IIN PROCEDURE 2 I

Ifølge en anden udførelsesform for opfindelsen kan IAccording to another embodiment of the invention, you can

forbindelserne med den almene formel IV fremstilles ud fra Ithe compounds of general formula IV are prepared from I

I 15 et anilinderivat med den almene formel V, hvor X1, X2, X3, IIn an aniline derivative of the general formula V, wherein X1, X2, X3, I

I X4 og Y har de samme definitioner som angivet i den generelle IIn X4 and Y have the same definitions as given in general I

I definition for opfindelsen IIn the definition of the invention

I 35 II 35 I

nh2 Inh2 I

I 20 (v)I (v)

I X2J1J-X3 II X2J1J-X3 I

2 i γ i 32 i γ i 3

ved omsætning med formylsuccinonitril eller et alkalimetal- Iby reaction with formylsuccinonitrile or an alkali metal I

44

I 25 salt af formylsuccinonitril. Denne reaktion udføres i almin- IIn 25 salt of formylsuccinonitrile. This reaction is carried out in general

I delighed i et organisk opløsningsmiddel eller i vand ved en IIn partition in an organic solvent or in water by an I

temperatur mellem 10 og 120°C, fortrinsvis ved tilbagesva- Itemperature between 10 and 120 ° C, preferably at reflux

lingstemperatur. Iprocessing temperature. IN

I Formylsuccinonitril er en kendt forbindelse, der IIn Formylsuccinonitrile is a known compound which I

I 30 almindeligvis fremstilles ved syrning af dens alkaliske II generally is produced by acidification of its alkaline I

salt, der fås ved omsætning af succinonitril med et lavere Isalt obtained by reaction of succinonitrile with a lower I

alkylformiat i nærværelse af et alkalisk middel, jvf. K. Ialkyl formate in the presence of an alkaline agent, cf. K. I

I Gewald, Z. Chem., 1961, 1, 349. II Violence, Z. Chem., 1961, 1, 349. I

DK 175618 B1 13 FREMGANGSMÅDE 3GB 175618 B1 13 PROCEDURE 3

Forbindelser med den almene formel I, i hvilken X betyder halogen, betyder amino, R2 betyder cyano, og R3 5 betyder hydrogen, og de øvrige substituenter har de betydninger, der er angivet i den generelle beskrivelse af opfindelsen, kan fremstilles ved behandling af forbindelser med den almene formel III med halogeneringsmidler, f.eks. sul-furylchlorid, N-chlorsuccinimid, N-bromsuccinimid, N-iodsuc-10 cinimid, pyridiniumbromidperbromid eller molekylært fluor, chlor, brom eller iod. Egnede organiske opløsningsmidler til disse omdannelser omfatter dichlormethan og acetonitril. Reaktionerne udføres ved temperaturer mellem -80 og 80°C, fortrinsvis mellem -30 og 25°C. Det kan være fordelagtigt 15 at beskytte aminogruppen i form af trifluoracetamid-derivatet under behandling med elementært fluor.Compounds of general formula I in which X is halogen, amino, R2 is cyano, and R3 is hydrogen, and the other substituents have the meanings given in the general description of the invention can be prepared by treating compounds. of the general formula III with halogenating agents, e.g. sulfuryl chloride, N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, pyridinium bromide perbromide or molecular fluorine, chlorine, bromine or iodine. Suitable organic solvents for these conversions include dichloromethane and acetonitrile. The reactions are carried out at temperatures between -80 and 80 ° C, preferably between -30 and 25 ° C. It may be advantageous to protect the amino group in the form of the trifluoroacetamide derivative during treatment with elemental fluorine.

FREMGANGSMÅDE 4PROCEDURE 4

20 A) Forbindelser med den almene formel I, i hvilken XA) Compounds of general formula I in which X

betyder en cyanogruppe, R1 betyder amino, R2 betyder cyano, og R3 betyder hydrogen, og de øvrige substituenter har de betydninger, der er angivet i den generelle beskrivelse af opfindelsen, kan fås ud fra de tilsvarende forbindelser, i 25 hvilke X er en gruppe C=NOH, ved dehydratisering med midler såsom eddikesyreanhydrid, cyanursyrechlorid eller phosphor-pentoxid. Ved anvendelse af visse af disse dehydratiserings-midler kan det være nødvendigt at beskytte aminogruppen med en egnet beskyttelsesgruppe.represents a cyano group, R1 represents amino, R2 represents cyano, and R3 represents hydrogen, and the other substituents having the meanings given in the general description of the invention can be obtained from the corresponding compounds in which X is a group C = NOH, by dehydration with agents such as acetic anhydride, cyanuric acid chloride or phosphorus pentoxide. Using some of these dehydrating agents, it may be necessary to protect the amino group with a suitable protecting group.

30 B) De ovenfor angivne mellemprodukter, hvor X betyder en gruppe C=N0H, kan fås ved kondensation af hydroxylamin med de tilsvarende forbindelser, hvor X betegner formyl.B) The above intermediates, where X is a group C = NOH, can be obtained by condensation of hydroxylamine with the corresponding compounds where X represents formyl.

C) Mellemproduktforbindelserne, i hvilke X betyder en formylgruppe (med formlen VI som vist i det følgende) , 35 kan fås ved hydrolyse af de tilsvarende forbindelser, hvor X betyder en bis-(alkylthio) -methyl- eller en bis-(arylthio) -C) The intermediate compounds in which X represents a formyl group (of formula VI as shown below) may be obtained by hydrolysis of the corresponding compounds wherein X represents a bis (alkylthio) methyl or a bis (arylthio) -

14 I14 I

DK 175618 B1 IDK 175618 B1 I

methylgruppe, eller ved behandling med et passende alkyl- Imethyl group, or by treatment with an appropriate alkyl I

nitrit, efterfulgt af hydrolyse ifølge E. Fujita, K. Ichikawa og K. Fuji, Tetrahedron Letters, 1978. 3561. Beskyttelse af aminofunktionen med en passende beskyttelsesgruppe kan værenitrite, followed by hydrolysis according to E. Fujita, K. Ichikawa, and K. Fuji, Tetrahedron Letters, 1978. 3561. Protection of the amino function by an appropriate protecting group may be

5 nødvendig under omsætningen med alkylnitritter. I5 necessary during the reaction with alkyl nitrite. IN

D) Mellemproduktforbindelserne med den almene for- ID) The intermediate compounds with the general formula I

mel I, i hvilken X betyder en bis-(alkylthio)-methyl- ellerflour I, in which X means a bis- (alkylthio) -methyl- or

en bis-(arylthio)-methylgruppe, og de øvrige grupper er som Ia bis (arylthio) methyl group and the other groups are as I

ovenfor defineret, kan fremstilles ved omsætning af en for- Iabove defined, can be prepared by reacting a form I

10 bindelse med formlen III med en tris-(alkylthio)-methan ICompound of formula III with a tris- (alkylthio) -methane I

eller en tris-(arylthio)-methan i nærværelse af en Lewis- Hor a tris (arylthio) methane in the presence of a Lewis-H

-syre, fortrinsvis et sulfoniumsalt såsom dimethyl-(methyl- Ηacid, preferably a sulfonium salt such as dimethyl- (methyl- Η

thio)-sulfonium-tetrafluorborat. De almindelige betingelser Ithio) -sulfonium tetrafluoroborate. The general conditions

for sådanne omdannelser er beskrevet i Synthesis, 1984. Hfor such conversions is described in Synthesis, 1984. H

15 '166. I15 '166. IN

FREMGANGSMÅDE 5 IPROCEDURE 5 I

A) Nyttige mellemproduktforbindelser med den almene HA) Useful intermediate compounds with the general H

20 formel I, i hvilken X betyder hydroxy, R1 er en eventuelt HIn formula I, in which X is hydroxy, R1 is optionally H

beskyttet aminogruppe, R2 er en cyanogruppe, R3 er et hydro- Hprotected amino group, R2 is a cyano group, R3 is a hydro-H

genatom, og X1, X2, X3, X4 og Y har de betydninger, der er Igenome, and X1, X2, X3, X4 and Y have the meanings that are I

angivet i den generelle definition af opfindelsen, kan frem- Idisclosed in the general definition of the invention,

stilles ud fra de tilsvarende forbindelser, i hvilke X bety- Iis determined from the corresponding compounds in which X means I

25 der halogen, ved omdannelse til et Grignard-reagens eller et lithiumderivat ved standardmetoder, efterfulgt af behand-Halogen, by conversion to a Grignard reagent or a lithium derivative by standard methods, followed by treatment.

ling med oxodiperoxymolybden-(pyridin)-(hexamethylphosphor- Iwith oxodiperoxymolybdenum (pyridine) - (hexamethylphosphorus)

syretriamid) (MoOPH) ved metoder, der svarer til de, der er Hacid triamide) (MoOPH) by methods similar to those of H

beskrevet af N.J. Lewis et al. i J. Org. Chem., 1977, 42, Idescribed by N.J. Lewis et al. in J. Org. Chem., 1977, 42, I

30 1479. Det kan være nødvendigt at omdanne cyanogruppen i den H30 1479. It may be necessary to convert the cyano group into the H

ovennævnte forbindelse, i hvilken X betyder halogen, til et Ithe above compound, in which X means halogen, to an I

på passende måde beskyttet derivat, f .eks. et oxaz olinder i vat Iappropriately protected derivative, e.g. an oxaz oil in vat I

af den tilsvarende forbindelse, i hvilken cyanogruppen er Iof the corresponding compound in which the cyano group is I

hydrolyseret til en carboxylsyre, forud for dannelsen af Ihydrolyzed to a carboxylic acid, prior to the formation of I

35 Grignard-reagenset eller lithiumderivatet. Alternativt kan I35 The Grignard reagent or lithium derivative. Alternatively, you can

det ovenfor beskrevne Grignard-reagens eller lithiumderivat Ithe Grignard reagent or lithium derivative I described above

15 DK 175618 B1 omsættes med et trialkylborat, efterfulgt af oxidation med hydrogenperoxid ved en fremgangsmåde, der er analog med den, der er beskrevet af M.F. Hawthorne i J. Org. Chem., 1957, 22, 1001 eller af R.w. Hoffmann og K. Ditrich i Syn-5 thesis, 1983, 107.B1 is reacted with a trialkyl borate, followed by oxidation with hydrogen peroxide by a method analogous to that described by M.F. Hawthorne in J. Org. Chem., 1957, 22, 1001 or by R.w. Hoffmann and K. Ditrich in Synthesis, 1983, 107.

B) Forbindelser med den almene formel I, i hvilken X betegner cyanato, R1 betyder amino, R2 betyder cyano, R3 er et hydrogenatom, og X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, 10 kan fremstilles ud fra de tilsvarende forbindelser, hvor X betyder hydroxy, R1 er en eventuelt beskyttet aminogruppe, R3 er et hydrogenatom, og X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, ved behandling med cyanogenhalogenider i nærværelse 15 af en base under anvendelse af metoder, der svarer til de, der er beskrevet af D. Martin og M. Bauer i Org. Synth. 61, 35, efterfulgt af afbeskyttelsestrin, såfremt dette er nødvendigt .B) Compounds of general formula I in which X represents cyanato, R 1 is amino, R 2 is cyano, R 3 is a hydrogen atom, and X 1, X 2, X 3, X 4 and Y have the meanings given in the general definition of the invention, 10 may be prepared from the corresponding compounds wherein X is hydroxy, R1 is an optionally protected amino group, R3 is a hydrogen atom and X1, X2, X3, X4 and Y have the meanings given in the general definition of the invention, by treating with cyanogen halides in the presence of a base using methods similar to those described by D. Martin and M. Bauer in Org. Synth. 61, 35, followed by deprotection steps, if necessary.

C) Forbindelser med den almene formel I, i hvilken X 20 betyder alkoxy, R1 betyder amino, R2 betyder cyano, R3 betyder hydrogen, og X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, kan fremstilles ud fra de tilsvarende forbindelser, hvor X betyder hydroxy, R3 er en eventuelt beskyttet aminogruppe, 25 R3 er et hydrogenatom, og X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, ved behandling med et alkylhalogenid, et alkylsul-fonat, et dialkylsulfat eller lignende, eventuelt i nærværelse af en base i et opløsningsmiddel såsom acetone eller 30 dimethyl formamid ved en temperatur mellem 25°C og opløsningsmidlets tilbagesvalingstemperatur, efterfulgt af et afbeskyttelsestrin, såfremt dette er nødvendigt.C) Compounds of general formula I in which X is alkoxy, R1 is amino, R2 is cyano, R3 is hydrogen, and X1, X2, X3, X4 and Y have the meanings given in the general definition of the invention can be prepared from the corresponding compounds wherein X is hydroxy, R3 is an optionally protected amino group, R3 is a hydrogen atom and X1, X2, X3, X4 and Y have the meanings given in the general definition of the invention, by treatment with an alkyl halide, an alkyl sulfonate, a dialkyl sulfate or the like, optionally in the presence of a base in a solvent such as acetone or dimethyl formamide at a temperature between 25 ° C and the reflux temperature of the solvent, followed by a deprotection step, if this is necessary.

D) Forbindelser med den almene formel I, i hvilken X betyder halogenalkoxy, R1 betyder amino, R2 betyder cyano, 35 R3 betyder hydrogen, og X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfin- - — — I — I DK 175618 B1D) Compounds of general formula I in which X is haloalkoxy, R1 is amino, R2 is cyano, R3 is hydrogen, and X1, X2, X3, X4 and Y have the meanings given in the general definition of invent - - - - I - I DK 175618 B1

I 16 II 16 I

I delsen, kan fremstilles ud fra de tilsvarende forbindelser, IIn the portion, may be prepared from the corresponding compounds, I

I hvor X betyder hydroxy, R1 er en eventuelt beskyttet amino- IIn which X represents hydroxy, R 1 is an optionally protected amino I

I gruppe, R3 er et hydrogenatom, og X1, X2, X3, X4 og Y har IIn group, R3 is a hydrogen atom and X1, X2, X3, X4 and Y have I

I de betydninger, der er angivet i den generelle definition IFor the purposes of the general definition I

I 5 af opfindelsen, ved forskellige halogenalkyleringsmetoder · IIn 5 of the invention, by various haloalkylation methods · I

I som beskrevet i Synthesis of Fluoroorganic Compounds, II as described in the Synthesis of Fluoroorganic Compounds, I

I Knunyants, I.L. og Yakobson, G.G., Ed., Springer-Verlag, IIn Knunyants, I.L. and Yakobson, G.G., Ed., Springer-Verlag, I

I Berlin, 1985, side 263-269, efterfulgt af et afbeskyttel- IIn Berlin, 1985, pages 263-269, followed by a deprotection

I sestrin, såfremt dette er nødvendigt. IIn step, if necessary. IN

I 10 II 10 I

I FREMGANGSMÅDE 6 IIN PROCEDURE 6 I

I Forbindelser med den almene formel I, i hvilken X er II Compounds of general formula I in which X is I

I en halogenalkylgruppe, R1 er en aminogruppe, R2 er en cyano- IIn a haloalkyl group, R1 is an amino group, R2 is a cyano-I

I 15 gruppe, R3 er et hydrogenatom, og X1, X2, X3, X4 og Y har IIn group R3 is a hydrogen atom and X1, X2, X3, X4 and Y have I

de betydninger, der er angivet i den generelle definition Ithe meanings given in the general definition

I af opfindelsen, kan fremstilles ud fra de tilsvarende for- II of the invention can be prepared from the corresponding forms

I bindeiser, hvor X er en formylgruppe, en carboxyl syrefunktion IIn binders where X is a formyl group, a carboxylic acid function I

I eller et halogenatom, og aminogruppen eventuelt er beskyttet. II or a halogen atom and the amino group is optionally protected. IN

I 20 Eksempelvis giver behandling af formylforbindelserne med IFor example, treating the formyl compounds with I

I diethylaminosvovltrifluorid på en måde, der er analog med IIn diethylaminosulfur trifluoride in a manner analogous to I

I den, der er beskrevet af W.J. Middleton i J. Org. Chem. IIn the one described by W.J. Middleton in J. Org. Chem. IN

I 1975, 40, 574, forbindelser med den almene formel I, i hvil- IIn 1975, 40, 574, compounds of the general formula I, in which I

I ken X er en difluormethylgruppe, og de øvrige substituenter IIn ken X is a difluoromethyl group and the other substituents I

I 25 er som ovenfor defineret. Oxidation af de ovennævnte mel- II 25 is as defined above. Oxidation of the above-mentioned flour

I lemproduktforbindelser med den almene formel I, i hvilken X IIn limb compounds of general formula I in which X I

I betyder formyl, med oxidationsmidler, f.eks. chromtrioxid i II means formyl, with oxidizing agents, e.g. chromium trioxide in I

I svovlsyre (Jones' reagens), giver mellemproduktforbindelser IIn sulfuric acid (Jones' reagent), intermediate compounds give I

I med den almene formel I, i hvilken X betegner en carboxyl- II of the general formula I, in which X represents a carboxyl-I

I 30 syrefunktion, R1 er en aminogruppe, R2 er en cyanogruppe, IIn acid function, R1 is an amino group, R2 is a cyano group, I

I R3 er et hydrogenatom, og X1, X2, X3, X4 og Y har de betyd- IIn R3 is a hydrogen atom and X1, X2, X3, X4 and Y have the meaning

I ninger, der er angivet i den generelle definition af opfin- IFor the purposes of the general definition of the invention

I delsen. Det kan være fordelagtigt at beskytte aminofunktio- IIn the settlement. It may be advantageous to protect amino function I

I nen, f.eks. i form af et trifluoracetamid-derivat, under IIn the nen, e.g. in the form of a trifluoroacetamide derivative, under I

I 35 sådanne oxidationsreaktioner. Omsætning af de ovennævnte IIn 35 such oxidation reactions. Turnover of the above

I forbindelser, hvor X betegner en carboxylsyregruppe, med IIn compounds where X represents a carboxylic acid group, with I

17 I17 I

DK 175618 B1 IDK 175618 B1 I

svovltetrafluorid som beskrevet af G.A. Boswell et al., Isulfur tetrafluoride as described by G.A. Boswell et al.,

Org. React., 1974, 21, 1-124, giver forbindelser, hvor X IOrg. React., 1974, 21, 1-124, provides compounds wherein X I

betyder en trifluormethylgruppe, og de øvrige grupper har Imeans a trifluoromethyl group and the other groups have I

den ovenfor angivne betydning. Ithe meaning given above. IN

5 Alternativt kan forbindelser med den almene formel I, IAlternatively, compounds of general formula I, I

i hvilken X betyder trifluormethyl, R1 er en aminogruppe, Iin which X means trifluoromethyl, R1 is an amino group, I

R2 er en cyanogruppe, R3 er et hydrogenatom, og X1, X2, X3, IR2 is a cyano group, R3 is a hydrogen atom, and X1, X2, X3, I

X4 og Y har de betydninger, der er angivet i den generelle IX4 and Y have the meanings given in general I

definition af opfindelsen, fremstilles ud fra forbindelser Idefinition of the invention is prepared from compounds I

10 med den almene formel I, i hvilken X betyder halogen, for- I10 of the general formula I, in which X means halogen, for I

trinsvis iod, og de øvrige substituenter er som ovenfor Istepwise iodine and the other substituents are as above I

defineret, ved omsætning med trifluormethyl-kobber under Idefined, by reaction with trifluoromethyl copper under I

betingelser, der svarer til de, der er beskrevet af D.J. Iconditions similar to those described by D.J. IN

Burton og D.M. Wiemers i J. Am. Chem. Soc., 1986, 108, 832. IBurton and D.M. Wiemers in J. Am. Chem. Soc., 1986, 108, 832. I

15 I15 I

FREMGANGSMÅDE 7 IPROCEDURE 7 I

Forbindelser med den almene formel I, i hvilken X . ICompounds of general formula I in which X. IN

betyder en brommethyl- eller en chlormethylgruppe, R1 er en Imeans a bromomethyl or a chloromethyl group, R1 is an I

20 aminogruppe, R2 er en cyanogruppe, R3 er et hydrogenatom, I20 is a cyano group, R3 is a hydrogen atom, I

og X1, X2, X3, X4 og Y har de betydninger, der er angivet i Iand X1, X2, X3, X4 and Y have the meanings given in I

den generelle definition af opfindelsen, kan fås ved behand- IThe general definition of the invention can be obtained by treating it

ling af de tilsvarende mellemproduktforbindelser, hvor X Iof the corresponding intermediate compounds where X I

I betyder en methylgruppe, og aminogruppen eventuelt.er beskyt- IYou mean a methyl group and the amino group is optionally protected

I 25 tet, med N-bromsuccinimid eller N-chlorsuccinimid i opløs- I ningsmidler, f.eks. carbontetrachlorid, ved temperaturer I mellem 0°C og opløsningsmidlets tilbagesvalingstemperatur.In the case of N-bromosuccinimide or N-chlorosuccinimide in solvents, e.g. carbon tetrachloride, at temperatures of between 0 ° C and the reflux temperature of the solvent.

I De ovennævnte forbindelser, i hvilke X betyder en methyl- I gruppe, kan fås ud fra mellemprodukt forbindelserne med den I 30 almene formel I, i hvilken X betyder formyl, og de øvrige I substituenter har den ovenfor angivne betydning, ved behand- I ling i rækkefølge med p-toluensulfonylhydrazin og natrium- I cyanoborhydrid under anvendelse af en fremgangsmåde, der I svarer til den, der er beskrevet i J. Am. Chem. Soc., 1971, I 35 93, 1793.In the above compounds, in which X represents a methyl I group, the compounds of the general formula I in which X means formyl and the other I substituents have the meaning given above can be obtained from the intermediate. in sequence with p-toluenesulfonylhydrazine and sodium I cyanoborohydride using a procedure similar to that described in J. Am. Chem. Soc., 1971, I 35 93, 1793.

I DK 175618 B1 FREMGANGSMÅDE 8I DK 175618 B1 PROCEDURE 8

Η A) Forbindelser med den almene formel I, i hvilken XΗ A) Compounds of general formula I in which X

er halogenalkylcarbonyl, R1 er en aminogruppe, R2 er enis haloalkylcarbonyl, R1 is an amino group, R2 is one

5 cyanogruppe, R3 er et hydrogenatom, og X1, X2, X3, X4 og Y5 is a hydrogen atom, R3 is a hydrogen atom, and X1, X2, X3, X4 and Y

H har de betydninger, der er angivet i den generelle definition H af opfindelsen, dvs. forbindelser med den almene formel H Vin, kan fås ved sekventiel behandling af de tilsvarende H forbindelser med den almene formel VI, i hvilke aminogruppen H 10 eventuelt er beskyttet, med et halogenalkylmetalderivat, H til tilvejebringelse af forbindelser med den almene formel VII, i hvilken X er en halogenalkylcarbinol, efterfulgt af oxidation ifølge fremgangsmåden beskrevet af R.J. Linderman og D.M. Graves i Tetrahedron Lett., 1987, 28, 4259, efter- H 15 fulgt af et afbeskyttelsestrin, såfremt dette er nødvendigt.H has the meanings given in the general definition H of the invention, i. compounds of the general formula H Vin, may be obtained by sequential treatment of the corresponding H compounds of the general formula VI, in which the amino group H 10 is optionally protected, with a haloalkyl metal derivative, H to provide compounds of the general formula VII, in which X is a haloalkylcarbinol, followed by oxidation according to the process described by RJ Linderman and D.M. Excavated in Tetrahedron Lett., 1987, 28, 4259, followed by a deprotection step, if necessary.

Egnede halogenalkylmetalderivater omfatter perfluoralkyl- lithiumderivater, der kan fremstilles ifølge P.G. Gassman og N.J. 0'Reilley, J. Org. Chem., 1987, 52, 2481-2490, eller trimethyltrifluormethylsilan fremstillet og anvendt i over- 20 ensstemmelse med G.A. Olah et al., J. Am. Chem. Soc., 1989, I 11, 393. Henvisninger til andre halogenalkylmetalderivater kan også findes i dette litteratursted. Med trimethyltri- fluormethylsilan som eksempel kan denne fremgangsmåde illu- I streres som følger: I 25 I ψ ° I ztjc"_"-ζχχ* I 30 ICHJ,S1CF·Suitable haloalkyl metal derivatives include perfluoroalkyl lithium derivatives which can be prepared according to P.G. Gassman and N.J. 0'Reilley, J. Org. Chem., 1987, 52, 2481-2490, or trimethyltrifluoromethylsilane prepared and used in accordance with G.A. Olah et al., J. Am. Chem. Soc., 1989, I 11, 393. References to other haloalkyl metal derivatives can also be found in this literature. Using trimethyl trifluoromethylsilane as an example, this procedure can be illustrated as follows: I 25 I ψ ° I ztjc "_" - ζχχ * I 30 ICHJ, S1CF ·

I Y Y YI Y Y Y

I (VI) (Vila) (Villa) 35 DK 175618 B1I (VI) (Vila) (Villa) 35 DK 175618 B1

19 I19 I

I B) Forbindelserne med den almene formel VIII kan IB) The compounds of general formula VIII may

I omdannes til forbindelser med den almene formel I, i hvilken IYou are converted into compounds of the general formula I in which I

I X betyder en halogenalkylthiocarbonylgruppe, R1 er en amino- IIn X means a haloalkylthiocarbonyl group, R 1 is an amino I

I gruppe, R2 er en cyanogruppe, R3 er et hydrogenatom, og X1, IIn group, R2 is a cyano group, R3 is a hydrogen atom, and X1, I

I 5 X2, X3, X4 og Y har de betydninger, der er angivet i den IIn 5 X2, X3, X4 and Y have the meanings given in that I

I generelle definition af opfindelsen, ved behandling med IIn a general definition of the invention, by treatment with I

I [2,4-bis-(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetan-2,4- IIn [2,4-Bis- (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane-2,4-I

I disulfid] (Lawesson's reagens). IIn disulfide] (Lawesson's reagent). IN

I 10 FREMGANGSMÅDE 9 II PROCEDURE 9 I

I II I

I Forbindelserne med den almene formel VII kan omdannes IThe compounds of general formula VII can be converted to

I til andre forbindelser med den almene formel I, i hvilken X II to other compounds of the general formula I in which X I

I betegner en halogenalkylgruppe, især en halogenmethylgruppe, IYou denote a haloalkyl group, especially a halomethyl group, I

I 15 ved behandling med halogeneringsmidler såsom thionylchlorid II by treatment with halogenating agents such as thionyl chloride I

I eller hydrogenbromid. Det kan være fordelagtigt at beskytte II or hydrogen bromide. It may be advantageous to protect you

I aminofunktionen, f.eks. i form af et trifluoracetamid-deri- IIn the amino function, e.g. in the form of a trifluoroacetamide derivative

vat, til hindring af halogenering af pyrrolringen under Ivat, to prevent halogenation of the pyrrole ring under I

sådanne halogeneringer. Isuch halogenations. IN

I 20 II 20 I

I FREMGANGSMÅDE 10 IIN PROCEDURE 10 I

A) Forbindelser med den almene formel I, i hvilken X IA) Compounds of general formula I in which X I

I er thiocyanato, R3 er en aminogruppe, R2 er en cyanogruppe, II is thiocyanato, R3 is an amino group, R2 is a cyano group, I

I 25 R3 er et hydrogenatom, og X1, X2, X3, X4 og Y har de betyd- I ninger, der er angivet i den generelle definition af opfin- · delsen, kan fremstilles ved behandling af forbindelser med I den almene formel III med MSCN, hvor M betegner et alkali- I metalatom, i nærværelse af brom i et opløsningsmiddel såsom I 30 methanol.In R3 is a hydrogen atom and X1, X2, X3, X4 and Y have the meanings given in the general definition of the invention can be prepared by treating compounds of general formula III with MSCN, where M represents an alkali metal atom, in the presence of bromine in a solvent such as methanol.

I B) Forbindelser med den almene formel I, i hvilken XI B) Compounds of general formula I in which X

I betyder en alkylthio-, halogenalkylthio-, alkenylthio-, I halogenalkenylthio-, phenylthio- eller heteroarylthiogruppe, 2I means an alkylthio, haloalkylthio, alkenylthio, I halogenalkenylthio, phenylthio or heteroarylthio group, 2

I Rl er en aminogruppe, R2 er en cyanogruppe, R3 er et hydro- ! IIn R1, an amino group, R2 is a cyano group, R3 is a hydrochloride. IN

3 I 3 5 genatom, og X3, X2, X3, X4 og Y har de betydninger, der er 4 I angivet i den generelle definition af opfindelsen, og phenyl- I DK 175618 B1 I 20 og heteroarylgrupperne er sammensat og/eller substitueret som her beskrevet, dvs. forbindelser med den almene for- mel IX, jvf. det følgende, kan fremstilles ved omsætning af en forbindelse med den almene formel III med et sulfenyl- I 5 halogenid med formlen RSHal, i hvilken R betegner alkyl, halogenalkyl, alkenyl, halogenalkenyl, phenyl eller hetero- I aryl som ovenfor defineret, og Hal betyder et halogenatom,3 I 35 gene and X3, X2, X3, X4 and Y have the meanings given in I in the general definition of the invention, and the phenyl and heteroaryl groups are composed and / or substituted as described herein, i.e. Compounds of general formula IX, cf. the following, can be prepared by reacting a compound of general formula III with a sulphenyl halide of formula RSHal, wherein R represents alkyl, haloalkyl, alkenyl, haloalkenyl, phenyl or hetero-aryl as defined above and Hal represents a halogen atom,

I i et flydende reaktionsmedium. Der anvendes fortrinsvis et II in a liquid reaction medium. Preferably an I is used

organisk opløsningsmiddel, f.eks. dichlormethan, ved en Iorganic solvent, e.g. dichloromethane, by an I

I 10 temperatur på fra -100 til 100°C, fortrinsvis fra -80 til IAt a temperature of from -100 to 100 ° C, preferably from -80 to 1

H 25°C. Denne reaktion kan eventuelt udføres i nærværelse af IH 25 ° C. This reaction may optionally be carried out in the presence of I

I en syreacceptor, f.eks. en tertiær amin såsom pyridin. Alkyl- IIn an acid acceptor, e.g. a tertiary amine such as pyridine. Alkyl- I

I sulfenylchloriderne kan fremstilles ifølge S. Thea og G. IIn the sulfenyl chlorides can be prepared according to S. Thea and G. I

I Cevasco, Tetrahedron Letters, 1988, 2865. Når der anvendes IIn Cevasco, Tetrahedron Letters, 1988, 2865. When used I

I 15 et sulfenylchlorid, kan fremgangsmåden illustreres ved føl-, IIn a sulfenyl chloride, the process can be illustrated by fol

I gende reaktionsskema: IIn the reaction scheme:

I FTCN ^ i.- |i cw- II FTCN ^ i.- | i cw- I

I 20 Η2Ν_^Ν^ H2N-llNjl jI 20 Η2Ν_ ^ Ν ^ H2N-llNjl j

I Χ2-γ-Χ3 χ2ΐ1ί^ΤΓχ3 II Χ2-γ-Χ3 χ2ΐ1ί ^ ΤΓχ3 I

I v v II v v I

I 25 (1I1) (IX) II 25 (1I1) (IX) I

I FREMGANGSMÅDE 11 IIN PROCEDURE 11 I

Forbindelser med den almene formel I, i hvilken X er ICompounds of general formula I in which X is I

I 30 thiocyanato, R1 er en aminogruppe, R2 er en cyanogruppe, R3 IIn thiocyanato, R1 is an amino group, R2 is a cyano group, R3 is

I er et hydrogenatom, og X1, X2, X3, X4 og Y har de betydnin- IYou are a hydrogen atom and X1, X2, X3, X4 and Y have the meaning I

I get, der er angivet i den generelle definition af opfindel- II, which is given in the general definition of the invention

I sen, kan yderligere omdannes til forbindelser med den almene IIn the late, further can be converted into compounds of the general I

I formel I, i hvilken X er en alkylthiogruppe, R1 er en amino- IIn formula I, in which X is an alkylthio group, R 1 is an amino I

35 gruppe, R2 er en cyanogruppe, R3 er et hydrogenatom, og X1, IR 2 is a cyano group, R 3 is a hydrogen atom, and X 1, I

X2, X3, X4 og Y har de betydninger, der er angivet i den IX2, X3, X4 and Y have the meanings given in that I

DK 175618 B1 21 j i j generelle definition af opfindelsen, ved behandling med en base, f.eks. natrium- eller kaliumhydroxid, i nærværelse af f.eks. et alkylhalogenid eller et dialkylsulfat i et opløsningsmiddel . ; 5 I · FREMGANGSMÅDE 12 I Forbindelser med den almene formel IX kan oxideres I til dannelse af forbindelser med den almene formel X, i I 10 hvilken X, jvf. det følgende, betegner en gruppe med formlen I RS(O)n, hvor n betyder 1 eller 2, og R har den i det fore- I gående angivne betydning. De oxidationsmidler, der kan anven- I des, omfatter hydrogenperoxid, peroxyeddikesyre, trifluor- I peroxyeddikesyre og m-chlorperoxybenzoesyre, i opløsnings- I 15 midler såsom dichlormethan, eddikesyre eller trifluored- I dikesyre, ved temperaturer mellem -40 og 80°C, fortrinsvis j I ved temperaturer fra 0 til 25°C. De anvendte reaktionsbetin- I gelser, dvs. temperatur, reaktionstidens længde og mængden I af oxidationsmiddel, kan ændres til dannelse af sulfenyl- 20 derivaterne (n=l) eller sulfonylderivaterne (n=2) efter I ønske. Det er også muligt at fremstille sulfonylderivaterne I ud fra sulfinylforbindelserne, hvilket vil være åbenbart I for fagmanden. Med visse halogenalkylthiogrupper, f.eks.In general definition of the invention, by treatment with a base, e.g. sodium or potassium hydroxide, in the presence of e.g. an alkyl halide or dialkyl sulfate in a solvent. ; PROCEDURE 12 I Compounds of general formula IX can be oxidized to form compounds of general formula X, in I 10 which X, cf. the following, represents a group of formula I RS (O) n, where n means 1 or 2, and R has the meaning given above. The oxidizing agents which can be used include hydrogen peroxide, peroxyacetic acid, trifluoro-peroxyacetic acid and m-chloroperoxybenzoic acid, in solvents such as dichloromethane, acetic acid or trifluoro-lactic acid, at temperatures between -40 and 80 ° C. preferably, at temperatures of from 0 to 25 ° C. The reaction conditions used, i.e. temperature, length of reaction, and amount of oxidant may be changed to form the sulfenyl derivatives (n = 1) or sulfonyl derivatives (n = 2) as desired. It is also possible to prepare the sulfonyl derivatives I from the sulfinyl compounds, which will be apparent to those skilled in the art. With certain haloalkylthio groups, e.g.

trifluormethylthio, kan det være fordelagtigt at beskytte I 25 aminofunktionen, f.eks. i form af trifluoracetamid-derivatet.trifluoromethylthio, it may be advantageous to protect the amino function, e.g. in the form of the trifluoroacetamide derivative.

I Såfremt eksempelvis trifluorperoxyeddikesyre vælges som I oxidationsmiddel, kan fremgangsmåden illustreres ved følgende I reaktionsskema: 30For example, if trifluoroperoxyacetic acid is selected as an oxidizing agent, the process can be illustrated by the following reaction scheme:

R.TnTTCN ra0lnSTTCNR.TnTTCN ra0lnSTTCN

I . CF,C03H -► / I „ sAsI. CF, CO 3 H -► / I

35 Y T35 Y T

I (VII) (X) I DK 175618 B1 |I (VII) (X) I DK 175618 B1 |

I 22 II 22 I

FREMGANGSMÅDE 13PROCEDURE 13

Forbindelser med den almene formel I, i hvilken R3Compounds of general formula I in which R 3

er halogen, R1 er amino, R2 er cyano, og X, X1, X2, X·*, X4 Iis halogen, R1 is amino, R2 is cyano, and X, X1, X2, X · *, X4 I

I 5 og Y har de betydninger, der er angivet i den generelle II and Y have the meanings given in general I

definition af opfindelsen, kan fremstilles ved behandling Idefinition of the invention may be prepared by treatment I

af forbindelser med den almene formel I, i hvilken R1 er Iof compounds of general formula I in which R 1 is I

I amino, R2 er cyano, R3 er hydrogen, og X, X1, X2, X3, X4 og IIn amino, R2 is cyano, R3 is hydrogen, and X, X1, X2, X3, X4 and I

B Y har de betydninger, der er angivet i den generelle defini- IB Y has the meanings given in the general definition

B 10 tion af opfindelsen, dvs. forbindelser med den almene for- IB 10 tion of the invention, i.e. connections with the general business

B mel XI som vist i det følgende, ved behandling med haloge- IB flour XI as shown below, by treatment with halogen I

B neringsmidler under betingelser, der svarer til de, der er IAgents under conditions similar to those of I

B beskrevet i forbindelse med fremgangsmåde 3. Den generelle IB described in connection with method 3. The general I

I omdannelse er vist i det følgende: IIn transformation, the following is shown:

I 15 II 15 I

I X"TTCN xirxCNIn X "TTCN xirxCN

h2n-vn^ η2ν-Ι!.νΛη>ι Ih2n-vn ^ η2ν-Ι! .νΛη> ι I

I I -► I Hal = Halogen II I -► I Hal = Halogen I

I 2 0 χ1_ΙιΓχ4 II 2 0 χ1_ΙιΓχ4 I

I x2—x2-<v^J-x3 II x2-x2- <v ^ J-x3 I

I Y Y II Y Y I

I (XI) (XII) II (XI) (XII) I

I 25 II 25 I

I FREMGANGSMÅDE 14 IIN PROCEDURE 14 I

Forbindelser med den almene formel I, i hvilken R3 ICompounds of general formula I in which R 3 I

22

I er en bis-(alkylthio) -methyl- eller en bis- (arylthio) -methyl- II is a bis (alkylthio) methyl or a bis (arylthio) methyl I

30 -gruppe, R1 er amino, R2 er cyano, og X, X1, X2, X3, X4 og I30 group, R1 is amino, R2 is cyano, and X, X1, X2, X3, X4 and I

Y har de betydninger, der er angivet i den generelle defini- IY has the meanings given in the general definition

tion af opfindelsen, kan fremstilles ved omsætning af en IThe invention may be prepared by reacting an I

forbindelse med formlen XI med en tris-(alkylthio)-methan Icompound of formula XI with a tris- (alkylthio) -methane I

eller en tris-(arylthio)-methan, (RaS)3CH, hvor Ra er alkyl Ior a tris- (arylthio) -methane, (RaS) 3CH, where Ra is alkyl I

35 eller aryl, i nærværelse af en Lewis-syre, fortrinsvis et IOr aryl, in the presence of a Lewis acid, preferably an I

sulfoniumsalt, i et opløsningsmiddel ved en temperatur mellem Isulfonium salt, in a solvent at a temperature between I

DK 175618 B1 IDK 175618 B1 I

23 I23 I

0°C og opløsningsmidlets tilbagesvalingstemperatur, eventuelt I0 ° C and the reflux temperature of the solvent, optionally I

i nærværelse af en syreacceptor såsom pyridin. Ved en mere Iin the presence of an acid acceptor such as pyridine. By one more I

I foretrukken fremgangsmåde anvendes der acetonitril som opløs- IIn preferred method, acetonitrile is used as the solution I

I ningsmiddel ved 25°C med tris-(methylthio)-methan som tris- IAdditive at 25 ° C with tris- (methylthio) -methane as tris- I

I 5 (alkylthio)-methanen og dimethyl-(methylthio)-sulfonium- IIn the 5 (alkylthio) methane and dimethyl (methylthio) sulfonium I

I tetrafluorborat som Lewis-syren uden anvendelse af en syre- IIn tetrafluoroborate as the Lewis acid without the use of an acid I

I acceptor. Fremgangsmåden kan generelt illustreres som følger: IIn the acceptor. The process can generally be illustrated as follows:

I Χ-Π—n~CN X-r tf-CN II Χ-Π — n ~ CN X-r tf-CN I

I H2N—Jl H2N-JlN ji—CH(RaS), II H2N-Jl H2N-JlN ji-CH (RaS), I

I χ1-ΐΛτχ4 + -* x1-Arx4 II χ1-ΐΛτχ4 + - * x1-Arx4 I

I x2^J-x3 x2JlsXx3 II x2 ^ J-x3 x2JlsXx3 I

I Y y II Y y I

I 15 (XI) (XIII) II (XI) (XIII) I

I FREMGANGSMÅDE 15 IIN PROCEDURE 15 I

I 20 Nyttige mellemproduktforbindelser med den almene II Useful intermediate compounds with the general I

I formel I, i hvilken er formyl, R1 er amino, R2 er cyano, IIn Formula I, in which is Formyl, R 1 is amino, R 2 is cyano, I

I og X, X1, X2, X3, X4 og Y har de betydninger, der er angivet II and X, X1, X2, X3, X4 and Y have the meanings given to I

I II I

I i den generelle definition af opfindelsen, dvs. forbindelser IIn the general definition of the invention, i. compounds I

I med den almene formel XIV som vist i det følgende, kan frem- IIn general formula XIV as shown below,

I 25 stilles ved hydrolyse af forbindelser med den almene for- II is added by hydrolysis of compounds of the general formula

I mel XIII eller ved behandling med alkylnitritter under betin- I gelser, der svarer til de, der er beskrevet i forbindelse I med fremgangsmåde 4C. Fremgangsmåden kan generelt illustreres I som følger: I 30In flour XIII or by treatment with alkyl nitrites under conditions similar to those described in compound I of method 4C. The process can generally be illustrated as follows: I 30

I XTTCN XTTCNIn XTTCN XTTCN

I H2N-llNjJ-CH(Rasi, H2N-iLN>-CHOIn H2N-11NjJ-CH (Rasi, H2N-iLN> -CHO

I x1-r''W-x4 -► x'-A-x1 I 35 x2dlXx3 I V v I (XIII) (XIV) I DK 175618 B1 ] Η H FREMGANGSMÅDE 16 Η Me11emproduktforbindelser med den almene formel I, i H 5 hvilken R3 er hydroxyiminoalkylidenyl eller alkoxyiminoal- kylidenyl, R1 er amino, R2 er cyano, og X, X1, X2, χ3, χ4 H og Υ har de betydninger, der er angivet i den generelle definition af opfindelsen, hvilke forbindelser'er nyttige H som mellemprodukter, kan fremstilles ved kondensation af en H 10 forbindelse med den almene formel I, i hvilken R3 er alkyl- H carbonyl eller formyl, R1 er amino, R2 er cyano, og X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i den H generelle definition af opfindelsen, med hydroxylamin eller en O-alkylhydroxylamin eller et syreadditionssalt deraf i H 15 et opløsningsmiddel såsom ethanol. De ovennævnte forbindel- ser, i hvilke R3 er alkylcarbonyl, fremstilles på samme måde som forbindelserne med formlen XIV under endelig anven- delse af en 1,1,1-tris-(alkylthio eller arylthio)-alkan som et udgangsmateriale.I x1-r''W-x4 -► x'-A-x1 I 35 x2dlXx3 IV v I (XIII) (XIV) I DK 175618 B1] Η H PROCEDURE 16 Η Me11em Product Compounds of General Formula I, in H 5 which R 3 is hydroxyiminoalkylidenyl or alkoxyiminoalkylidenyl, R1 is amino, R2 is cyano, and X, X1, X2, χ3, χ4 H and Υ have the meanings given in the general definition of the invention which compounds are useful H as intermediates can be prepared by condensing an H 10 compound of the general formula I in which R 3 is alkyl-H carbonyl or formyl, R 1 is amino, R 2 is cyano, and X, X 1, X 2, X 3, X 4 and Y have the meanings given in the H general definition of the invention with hydroxylamine or an O-alkyl hydroxylamine or an acid addition salt thereof in H 15 a solvent such as ethanol. The above compounds, in which R 3 is alkylcarbonyl, are prepared in the same way as the compounds of formula XIV, finally using a 1,1,1-tris (alkylthio or arylthio) alkane as a starting material.

I FREMGANGSMÅDE 17IN PROCEDURE 17

Nyttige mellemproduktforbindelser med den almene B formel I, i hvilken R3 er amino, R1 er amino, R2 er cyano, B 25 og X, X1, X2, X3, X4 og Y har de betydninger, der er angivet B i den generelle definition af opfindelsen, hvilke forbindel- B ser er nyttige som mellemprodukter, kan fremstilles ved B reduktion af de tilsvarende forbindelser, hvor R3 betyder nitro, med f.eks. hydrogen i nærværelse af en ædelmetalka- I 30 talysator, f.eks. platin eller palladium, eller under anven- I delse af hydrazin og Raney-nikkel. I tilfælde af visse kom- I binationer af R2- og X-substituenter kan forbindelserne med formlen I, i hvilken R1 og R2 samtidig betegner amino, I have begrænset stabilitet og kan kræve beskyttelse af en af 35 aminogrupperne under anvendelse af en passende beskyttel- I sesgruppe. Forbindelserne med den almene formel I, i hvilken 25 DK 175618 B1Useful intermediate compounds of the general B formula I in which R 3 is amino, R 1 is amino, R 2 is cyano, B 25 and X, X 1, X 2, X 3, X 4 and Y have the meanings given B in the general definition of the invention, which compounds B are useful as intermediates, can be prepared by B reducing the corresponding compounds wherein R 3 is nitro, e.g. hydrogen in the presence of a precious metal catalyst, e.g. platinum or palladium, or using hydrazine and Raney nickel. In the case of certain combinations of R 2 and X substituents, the compounds of formula I, wherein R 1 and R 2 simultaneously represent amino, may have limited stability and may require protection of one of the 35 amino groups using an appropriate protecting agent. In sight group. The compounds of the general formula I in which B1

R3 er nitro, R1 er amino, R2 er cyano, og X, Xl, X2, X3, X4 IR 3 is nitro, R 1 is amino, R 2 is cyano, and X, X 1, X 2, X 3, X 4 I

og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, kan fremstilles ved nitrering af forbindelser med formlen XI ved indvirkning af salpetersyre 5 og svovlsyre eller salpetersyre i eddikesyreanhydrid eller ved anvendelse af andre nitreringsmidler. Det kan under visse nitreringsreaktioner være fordelagtigt at beskytte aminofunktionen i forbindelsen med formlen XI med en egnet beskyttelsesgruppe, f.eks. en acetyl- eller en trifluorace-10 tylgruppe.and Y has the meanings given in the general definition of the invention can be prepared by nitrating compounds of formula XI by the action of nitric acid 5 and sulfuric acid or nitric acid in acetic anhydride or by using other nitrating agents. Under certain nitration reactions, it may be advantageous to protect the amino function of the compound of formula XI with a suitable protecting group, e.g. an acetyl or a trifluoroacetyl group.

FREMGANGSMÅDE 18PROCEDURE 18

Forskellige derivater, der kan anvendes som mellem-15 produkter, af en forbindelse med den almene formel XV, jvf. det følgende, kan fremstilles ved anvendelse af de følgende fremgangsmåder: A) Forbindelser med den almene formel I, i hvilken R3 er alkylamino, dialkylamino eller aralkylamino, R3 er 20 amino, R2 er cyano, og X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, kan fremstilles ud fra de tilsvarende forbindelser, hvor R3 betyder amino, og de øvrige substituenter er som ovenfor defineret, ved alkylering med alkyl- eller aralkyl-25 halogenider eller -sulfonater i organiske opløsningsmidler såsom ethanol, acetonitril eller toluen.Various derivatives which can be used as intermediates of a compound of general formula XV, cf. the following, can be prepared using the following methods: A) Compounds of general formula I in which R 3 is alkylamino; dialkylamino or aralkylamino, R3 is 20 amino, R2 is cyano, and X, X1, X2, X3, X4 and Y have the meanings given in the general definition of the invention can be prepared from the corresponding compounds wherein R3 is amino and the other substituents are as defined above by alkylation with alkyl or aralkyl halides or sulfonates in organic solvents such as ethanol, acetonitrile or toluene.

Fremstillingen af mono- eller dialkylerede produkter kan reguleres ved manipulation af de støkiometriske betingelser eller reaktionsbetingelserne. Alternativt kan man, 30 såfremt der ønskes monoalkylamin-produkter, anvende andre metoder, f.eks. omdannelsen af aminogruppen til en alkoxy-alkylideniminogruppe, véd behandling med en alkylorthoester, efterfulgt af reduktion. Såfremt de ønskede slutprodukter indeholder som den usubs ti tuerede aminogruppe, kan det 3 5 være nødvendigt at beskytte aminogruppen forud for en sådan behandling med en egnet beskyttelsesgruppe. I sådanne til- iThe production of mono- or dialkylated products can be regulated by manipulation of the stoichiometric or reaction conditions. Alternatively, if monoalkylamine products are desired, other methods, e.g. the conversion of the amino group to an alkoxy-alkylideneimino group, by treatment with an alkyl ortho ester, followed by reduction. If the desired end products contain as the unsubsidized amino group, it may be necessary to protect the amino group prior to such treatment with a suitable protecting group. In such cases

I DK 175618 B1 II DK 175618 B1 I

I 26 II 26 I

I fælde fremstiller man og anvender som en reaktant en forbin- IIn the trap, a compound is prepared and used as a reactant

I delse med den almene formel I, i hvilken R3 er amino, R1 er IIn the compound of the general formula I in which R 3 is amino, R 1 is I

I en egnet, beskyttet aminogruppe, og de øvrige substituenter IIn a suitable protected amino group and the other substituents I

I er som ovenfor defineret, dvs. en forbindelse med den almene IYou are as defined above, i.e. a connection with the general I

I 5 formel XV. Den beskyttende gruppe i forbindelsen med form- IIn Formula XV. The protecting group in the compound of form I

I len XV tilføres normalt forud for nitro-reduktionstrinnet IIn lane XV is normally supplied prior to the nitro-reduction stage I

I som diskuteret i forbindelse med fremgangsmåde 17. Afhængigt II as discussed in connection with process 17. Depending on I

I af den efterfølgende omdannelse, der påtænkes for aminogrup- II of the subsequent conversion contemplated for amino group I

I pen ved R3, kan der vælges forskellige beskyttelsesgrupper, IIn pen at R3, different protecting groups can be selected, I

I 10 hvilket fremgår af de følgende eksempler. II 10 as shown by the following examples. IN

B) Forbindelser med den almene formel I, i hvilken IB) Compounds of general formula I in which I

I R3 er aminocarbonylamino, R1 er amino, R2 er cyano, og X, IIn R3, aminocarbonylamino, R1 is amino, R2 is cyano, and X, I

I X1, X2, X3, X4 og Y har de betydninger, der er angivet i IIn X1, X2, X3, X4 and Y have the meanings given in I

I den generelle definition af opfindelsen, kan fremstilles ud IIn the general definition of the invention, can be made out

I 15 fra forbindelser med den almene formel XV ved behandling II from compounds of the general formula XV in treatment I

I med phosgen, efterfulgt af ammoniak og efterfulgt af et II with phosgene, followed by ammonia and followed by an I

I afbeskyttelsestrin. IIn the deprotection step. IN

I C) Forbindelser med den almene formel I, i hvilken ICompounds of general formula I in which I

I R3 er alkylcarbonylamino, halogencarbonylamino eller aryl- IIn R 3 is alkylcarbonylamino, halocarbonylamino or aryl-I

I 20 carbonylamino, R1 er amino, R2 er cyano, og X, X1, X2, X3, IIn carbonylamino, R1 is amino, R2 is cyano, and X, X1, X2, X3, I

I X4 og Y har de betydninger, der er angivet i den generelle IIn X4 and Y have the meanings given in general I

I definition af opfindelsen, kan fremstilles ved omsætning af IIn the definition of the invention, can be prepared by reacting I

I en forbindelse med formlen XV med syrechlorider med formlen IIn a compound of formula XV with acid chlorides of formula I

I Rl3(C=0)Cl eller syreanhydrider formlen [R^(C=0)]20, hvor IIn R13 (C = O) Cl or acid anhydrides of formula [R 2 (C = O)] 20, wherein I

I 25 betyder alkyl, halogenalkyl eller aryl som defineret i den II 25 means alkyl, haloalkyl or aryl as defined in I

første definition svarende til den almene formel I, efter- Ifirst definition corresponding to the general formula I, after- I

I fulgt af et afbeskyttelsestrin. Der kan anvendes opløsnings- IFollowed by a deprotection step. Solution I can be used

I midler såsom acetonitril og syreacceptorer, f.eks. pyridin, IIn agents such as acetonitrile and acid acceptors, e.g. pyridine, I

I under passende betingelser. IIn appropriate conditions. IN

I 30 D) Ligeledes kan forbindelser med den almene formel I, ID) Likewise, compounds of general formula I, I

I i hvilken R3 er alkylsulfonylamino eller halogenalkylsul- IIn which R 3 is alkylsulfonylamino or haloalkylsul-I

I fonylamino, R1 er amino, R2 er cyano, og X, X1, X2, X3, X4 IIn phonylamino, R1 is amino, R2 is cyano, and X, X1, X2, X3, X4 I

I og Y har de betydninger, der er angivet i den generelle II and Y have the meanings given in general I

I definition af opfindelsen, fremstilles ud fra beskyttede IIn the definition of the invention, is prepared from protected I

I 35 aminoforbindelser med formlen XV ved omsætning med alkyl- IIn 35 amino compounds of formula XV by reaction with alkyl-I

I eller halogenalkyl-sulfonylhalogenider eller sulfonsyre- II or haloalkyl sulfonyl halides or sulfonic acid I

27 DK 175618 B1 anhydrider under passende betingelser, efterfulgt af et afbeskyttelsestrin. Egnede aminobeskyttelsesgrupper ved sådanne reaktioner omfatter den alkoxyalkylideniminogruppe, der fås ved behandling af aminoforbindelsen med alkylor-5 thoformiat. Afbeskyttelsesmetoder for sådanne grupper omfatter typisk en vandig hydrolyse.B1 anhydrides under appropriate conditions, followed by a deprotection step. Suitable amino protecting groups in such reactions include the alkoxyalkylidene imino group obtained by treating the amino compound with alkyl orthoformate. Deprotection methods for such groups typically include an aqueous hydrolysis.

E) Forbindelser med den almene formel I, i hvilken R3 betyder alkylaminocarbonylamino eller arylaminocarbonyl-amino, R1 er amino, R2 er cyano,og X, X1, X2, X3, X4 og YE) Compounds of general formula I in which R3 is alkylaminocarbonylamino or arylaminocarbonylamino, R1 is amino, R2 is cyano, and X, X1, X2, X3, X4 and Y

10 har de betydninger, der er angivet i den generelle definition af opfindelsen, kan fremstilles ud fra en på passende måde beskyttet aminoforbindelse med formlen XV ved omsætning med et alkyl- eller arylisocyanat, i hvilket alkyl- eller aryl-grupperne er som defineret i den første opfindelsesdefini-15 tion, efterfulgt af afbeskyttelse. Passende betingelser for dannelsen af urinstoffer er beskrevet af J. March i "Advanced Organic Chemistry", McGraw-Hill publ. (1985), side 802 samt deri angivne referencer. Egnede aminobeskyttelsesgrupper ved sådanne reaktioner omfatter alkoxyalkylideniminogruppen 20 med afbeskyttelse som beskrevet i det foregående.10 has the meanings given in the general definition of the invention can be prepared from a suitably protected amino compound of formula XV by reaction with an alkyl or aryl isocyanate in which the alkyl or aryl groups are as defined in the first invention definition, followed by deprotection. Appropriate conditions for the formation of urea are described by J. March in "Advanced Organic Chemistry", McGraw-Hill publ. (1985), page 802 and references cited therein. Suitable amino protecting groups in such reactions include the alkoxyalkylidene imino group 20 with deprotection as described above.

F) Forbindelser med den almene formel I, i hvilken R3 betyder alkoxycarbonylamino eller halogenalkoxycarbonyl-amino, R1 er amino, R2 er cyano, og X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition 25 af opfindelsen, kan fremstilles ud fra en på passende måde . beskyttet aminoforbindelse med formlen XV ved omsætning med et alkylchlorformiat eller halogenalkylchlorformiat, efterfulgt af et afbeskyttelsestrin.F) Compounds of general formula I in which R3 is alkoxycarbonylamino or haloalkoxycarbonylamino, R1 is amino, R2 is cyano and X, X1, X2, X3, X4 and Y have the meanings given in the general definition. 25 of the invention may be prepared from an appropriate manner. protected amino compound of formula XV by reaction with an alkyl chloroformate or haloalkyl chloroformate, followed by a deprotection step.

G) Forbindelser med den almene formel I, i hvilken 30 R3 betyder alkylidenimino eller benzylidenimino, R·*· er amino, R2 er cyano, og X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, kan fremstilles ved kondensation af en på passende måde beskyttet aminoforbindelse med formlen XV med et alkyl-35 eller arylaldehyd, i hvilket alkyl- eller arylgrupperne er som defineret i den første definition af opfindelsen, efter- I DK 175618 B1 I .28 I fulgt af et afbeskyttelsestrin. Passende betingelser for I dannelsen af Schiff'ske baser vælges til kondensationstrinnet som beskrevet af J. March i ibid., side 1165, samt deriG) Compounds of general formula I in which R 3 is alkylidenimino or benzylidenimino, R 2 is amino, R 2 is cyano and X, X 1, X 2, X 3, X 4 and Y have the meanings given in it. general definition of the invention can be prepared by condensing an appropriately protected amino compound of formula XV with an alkyl-35 or aryl aldehyde in which the alkyl or aryl groups are as defined in the first definition of the invention, after I-175618 B1 I .28 Followed by a deprotection step. Appropriate conditions for the formation of Schiff's bases are selected for the condensation step as described by J. March in ibid., Page 1165, and therein.

I nævnte referencer. Egnede aminobeskyttelsesgrupper omfatter IIn said references. Suitable amino protecting groups include I

I 5 acetyl- eller trifluoracetylgrupper, og afbeskyttelse kan · IIn 5 acetyl or trifluoroacetyl groups and deprotection can · I

I udføres ved alkalisk hydrolyse eller andre metoder som be- IYou are carried out by alkaline hydrolysis or other methods such as I

I skrevet af T.W. Greene i "Protective Groups in Organic Syn- IIn written by T.W. Greene in "Protective Groups in Organic Syn- I

thesis" J. Wiley publ. (1981), side 254, samt deri angivne Ithesis "J. Wiley publ. (1981), page 254, as well as cited therein

I referencer. IIn references. IN

I 10 H) Forbindelser med den almene formel I, i hvilken IH) Compounds of general formula I in which I

I R3 betyder alkoxyalkylidenimino, R1 er amino, R2 er cyano, IIn R3, alkoxyalkylideneimino means, R1 is amino, R2 is cyano, I

i den generelle definition af opfindelsen, kan fremstilles Iin the general definition of the invention can be prepared

I ud fra en beskyttet aminoforbindelse med formlen XV ved II from a protected amino compound of formula XV at I

I 15 kondensation med en alkylorthoester, efterfulgt af en afbe- IIn condensation with an alkyl orthoester, followed by a precipitate

I skyttelsesreaktion. Egnede beskyttelsesgrupper omfatter IIn shooting reaction. Suitable protecting groups include I

I amid- eller carbamatderivater som anført af T.W. Greene, IIn amide or carbamate derivatives as stated by T.W. Greene, I

I ibid., side 223 og 249. IIn ibid., Pages 223 and 249. I

I I) Forbindelser med den almene formel I, i hvilken ICompounds of general formula I in which I

I 20 R3 betyder dialkylaminoalkylidenimino, R1 er amino, R2 er IIn R3, dialkylaminoalkylideneimino means, R1 is amino, R2 is I

I cyano, og X, X1, X2, X3, X4 og Y har de betydninger, der er IIn cyano, and X, X1, X2, X3, X4 and Y have the meanings that I

I angivet i den generelle definition af opfindelsen, kan frem- IAs set forth in the general definition of the invention,

I stilles ved omsætning af en forbindelse med formlen XV med IYou are substituted by reacting a compound of formula XV with I

I et dialkylacetal-derivat af et Ν,Ν-dialkylformamid som be- IIn a dialkyl acetal derivative of a Ν, Ν-dialkylformamide as be- I

I 25 skrevet af T.W. Greene, ibid., side 275, efterfulgt af et IIn 25 written by T.W. Greene, ibid., Page 275, followed by an I

I afbeskyttelsestrin. Alternativt kan der udføres en omsætning IIn the deprotection step. Alternatively, a turnover I can be carried out

I af en forbindelse med formlen XV med et N,N-dialkylformamid II of a compound of formula XV with an N, N-dialkylformamide I

I i nærværelse af et middel, f.eks. phosphoroxychlorid under IIn the presence of an agent, e.g. phosphorus oxychloride under I

I Vilsmeier-betingelser. Egnede beskyttende grupper omfatter IIn Vilsmeier conditions. Suitable protecting groups include I

I 30 amid- eller carbamat-derivater. IIn 30 amide or carbamate derivatives. IN

I J) Forbindelser med den almene formel I, i hvilken ICompounds of general formula I in which I

I R3 betyder alkylthioalkylidenimino, R1 er amino, R2 er cyano,In R3, alkylthioalkylideneimino means R1 is amino, R2 is cyano,

I i den generelle definition af opfindelsen, kan fremstilles IIn the general definition of the invention, can be made

I 35 ved omsætning af en forbindelse med formlen XV med en tris- II by reacting a compound of formula XV with a tris- I

I (alkylthio)-methan i pyridin som opløsningsmiddel, eventuelt II (alkylthio) -methane in pyridine as solvent, optionally I

29 DK 175618 B1 i nærværelse af en egnet katalysator, f.eks. dimethyl-(me-thylthio)-sulfonium-tetrafluorborat.B1 in the presence of a suitable catalyst, e.g. dimethyl- (Me-methylthio) -sulfonium tetrafluoroborate.

K) Forbindelser med den almene formel I, i hvilken R3 er azido, R^ er amino, R2 er cyano, og X, X1, X2, X3, χ4 5 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, kan fremstilles ved omsætning af en forbindelse med formlen XV med p-toluensulfonylazid under betingelser beskrevet af J. March, ibid., side 573, samt deri angivne referencer, efterfulgt af et a fbe skyttel sest rin.K) Compounds of general formula I in which R 3 is azido, R 1 is amino, R 2 is cyano, and X, X 1, X 2, X 3, χ 45 and Y have the meanings given in the general definition of the invention , can be prepared by reacting a compound of formula XV with p-toluenesulfonylazide under conditions described by J. March, ibid., page 573, and references cited therein, followed by an alpha shuttle test.

10 Alternativt kan de ovenfor angivne forbindelser, i hvilke R3 betyder azido, fremstilles ud fra en forbindelse med formlen XV ved omdannelse af aminogruppen til et diazonium-I salt, efterfulgt af reduktion til en hydrazinogruppe, efter- I fulgt af behandling med salpetersyrling til dannelse af I 15 azidet, efterfulgt af et afbeskyttelsestrin.Alternatively, the above compounds, in which R 3 represents azido, can be prepared from a compound of formula XV by converting the amino group into a diazonium-I salt, followed by reduction to a hydrazino group, followed by treatment with nitric acid to form of the I azide, followed by a deprotection step.

I FREMGANGSMÅDE 19 I A) Nyttige mellemproduktforbindelser med den almene I 20 formel I, i hvilken R3 betyder phenyl eller heteroaryl, der I er substitueret som beskrevet i den generelle definition af I opfindelsen, R1 er amino, R2 er cyano, og X, X^, X2, X3, X4 I og Y har de betydninger, der er angivet i den generelle I definition af opfindelsen, kan fremstilles ud fra en forbin- I 25 delse med formlen XI, i hvilken aminogruppen eventuelt er I beskyttet med en egnet beskyttelsesgruppe, ved behandling I med en på passende måde substitueret phenylgruppe eller et I heteroaryl-diazoniumsalt, under betingelserne for Gomberg- I Bachmann-reaktionen som beskrevet af M. Swainsbury i Tetra- I 30 hedron, 1980, 36, 3327-3359, samt deri angivne referencer.PROCEDURE 19 IA) Useful intermediate compounds of the general formula I wherein R 3 is phenyl or heteroaryl substituted I as described in the general definition of the invention, R1 is amino, R2 is cyano, and X, X X2, X3, X4 I and Y have the meanings given in the general definition of the invention can be prepared from a compound of formula XI in which the amino group is optionally protected by a suitable protecting group, by treatment I with a suitably substituted phenyl group or a heteroaryl diazonium salt, under the conditions of the Gomberg-I Bachmann reaction as described by M. Swainsbury in Tetra-I-hedron, 1980, 36, 3327-3359, and disclosed therein. references.

I B) Alternativt kan mellemproduktforbindelserne med I den almene formel I, i hvilken R3 betyder phenyl eller hete- I roaryl, der er substitueret som angivet i den generelle I definition af opfindelsen, R3 er amino, R2 er cyano, og X, I 35 X1, X2, X3, X4 og Y har de betydninger, der er angivet i I den generelle definition af opfindelsen, fremstilles ud fra I DK 175618 B1 I 30 iIB) Alternatively, the intermediate compounds of I of general formula I wherein R 3 is phenyl or heteroaryl substituted as defined in the general I definition of the invention, R 3 is amino, R 2 is cyano, and X is X , X2, X3, X4 and Y have the meanings given in the general definition of the invention, prepared from I DK 175618 B1 I 30 in

en forbindelse med formlen XII, i hvilken aminogruppen even- Ia compound of formula XII in which the amino group is even I

H tuelt er beskyttet med en egnet beskyttelsesgruppe, ved IH tually is protected with a suitable protecting group, by I

behandling med et på passende måde substitueret phenyl- Itreatment with an appropriately substituted phenyl-I

I eller heteroarylhalogenid, fortrinsvis et bromid eller iodid, II or heteroaryl halide, preferably a bromide or iodide, I

5 i nærværelse af kobber under betingelserne for Ullmann-reak- I5 in the presence of copper under the conditions of the Ullmann reaction

I tionen som beskrevet af M. Swainsbury, ibid. IIn the tion as described by M. Swainsbury, ibid

I C) Alternativt kan mellemproduktforbindelserne med IAlternatively, the intermediate compounds with I

I den almene formel I, i hvilken R3 betyder phenyl eller hete- IIn the general formula I in which R 3 is phenyl or hetero I

roaryl, der er substitueret som angivet i den generelle Iroaryl substituted as set out in general I

10 definition af opfindelsen, R1 er amino, R2 er cyano, og X, IIn the definition of the invention, R1 is amino, R2 is cyano, and X, I

den generelle definition af opfindelsen, fremstilles ud fra Ithe general definition of the invention is prepared from I

en forbindelse med formlen XII, fortrinsvis et bromid eller Ia compound of formula XII, preferably a bromide or I

H iodid, ved behandling med en på passende måde substitueret IH iodide, by treatment with a suitably substituted I

15 phenyl- eller heteroaryl-boronsyre i nærværelse af palla- I15 phenyl or heteroaryl boronic acid in the presence of palladium I

dium(O) under betingelser, der svarer til de, der er be- Idium (O) under conditions similar to those employed

I skrevet af V. Snieckus et al. i Tetrahedron Letters, 1988, IIn written by V. Snieckus et al. in Tetrahedron Letters, 1988, I

I 29, 2135, samt deri angivne referencer. II 29, 2135, and references cited therein. IN

I 20 FREMGANGSMÅDE 20 I20 PROCEDURE 20 I

Forbindelser med den almene formel (I), i hvilken R3 ICompounds of general formula (I) in which R3 I

I er en cyanogruppe, R* er amino, R2 er cyano, og X, X1, X2, II is a cyano group, R * is amino, R 2 is cyano, and X, X 1, X 2, I

X3, X4 og Y har de betydninger, der er angivet i den gene- IX3, X4 and Y have the meanings given in the gene I

25 relle definition af opfindelsen, kan fremstilles ud fra I25 definitions of the invention may be prepared from I

forbindelserne med den almene formel I, i hvilken R3 betyder Ithe compounds of general formula I in which R 3 means I

I hydroxyiminomethylidenyl eller alkoxyiminomethylidenyl, der IIn hydroxyiminomethylidenyl or alkoxyiminomethylidenyl, wherein I

I er beskrevet i forbindelse med fremgangsmåde 16, ved dehydra- II is described in connection with process 16, by dehydration

tisering i overensstemmelse med de fremgangsmåder, der er Itisation according to the methods I

30 beskrevet i forbindelse med fremgangsmåde 4A. I30 described in connection with method 4A. IN

FREMGANGSMÅDE 21 IPROCEDURE 21 I

35 betyder halogenalkylcarbonyl eller halogenalkylthiocarbonyl, I35 is haloalkylcarbonyl or haloalkylthiocarbonyl, I

R1 betyder amino, R2 er cyano, og X, X1, X2, X3, X4 og Y IR 1 is amino, R 2 is cyano, and X, X 1, X 2, X 3, X 4 and Y I

DK 175618 B1 IDK 175618 B1 I

31 I31 I

har de betydninger, der er angivet i den generelle definition Ihave the meanings given in the general definition I

af opfindelsen, kan fremstilles ud fra en eventuel amino- Iof the invention may be prepared from any amino I

-beskyttet forbindelse med formlen XIV ved de metoder, der I-protected compound of formula XIV by the methods which I

er omtalt i forbindelse med fremgangsmåde 8, efterfulgt af Iis discussed in connection with method 8, followed by I

5 et afbeskyttelsestrin, såfremt dette er nødvendigt. I5, a deprotection step, if necessary. IN

FREMGANGSMÅDE 22 IPROCEDURE 22 I

A) Forbindelser med den almene formel I, i hvilken IA) Compounds of general formula I in which I

10 R3 er halogenalkyl, R1 er amino, R2 er cyano, og X, X1, X2, IR 3 is haloalkyl, R 1 is amino, R 2 is cyano, and X, X 1, X 2, I

relle definition af opfindelsen, kan fremstilles ud fra IThe very definition of the invention can be prepared from I

forbindelser med formlen XII eller formlen XIV, hvor amino- Icompounds of formula XII or formula XIV wherein amino I

gruppen eventuelt er beskyttet, ved de fremgangsmåder, der ; Ithe group is optionally protected by the methods provided; IN

15 er beskrevet i forbindelse med fremgangsmåderne 6, 7 og 9, I15 are described in connection with Methods 6, 7 and 9, I

I efterfulgt af afbeskyttelse, såfremt dette er nødvendigt. IFollowed by deprotection, if necessary. IN

I B) Forbindelser med den almene formel I, i hvilken ICompounds of general formula I in which I

I R3 er alkyl, R1 er amino, R2 er cyano, og X, X1, X2, X3, X4 I og Y har de betydninger, der er angivet i den generelle I 20 definition af opfindelsen, kan fremstilles ud fra forbindel- 1 I ser med formlen XIV, i hvilken aminogruppen eventuelt er I beskyttet, ved omsætning med et Grignard-reagens, der er I afledt af et alkylhalogenid eller en alkyllithium-forbin- I delse, til dannelse af en carbinol, efterfulgt af.et dehydra- I 25 tiseringstrin til dannelse af.en forbindelse, i hvilken R3 _ j I er alkenyl, efterfulgt af reduktion. Forbindelser med den i I almene formel I, i hvilken R3 er methyl, og de øvrige sub- I stituenter er som ovenfor beskrevet, kan fremstilles ud fra I forbindelser med formlen XIV ved den fremgangsmåde, der er I 30 beskrevet i forbindelse med fremgangsmåde 7. j I FREMGANGSMÅDE 23 I Forbindelser med den almene formel I, i hvilken R3 i I 35 er thiocyanato, alkylthio, halogenalkylthio, alkenylthio, ! I halogenalkenylthio, phenylthio eller heteroarylthio, R1 er !In R 3 is alkyl, R 1 is amino, R 2 is cyano, and X, X 1, X 2, X 3, X 4 I and Y have the meanings given in the general definition of the invention can be prepared from compound I of formula XIV, in which the amino group is optionally protected, by reaction with a Grignard reagent derived from an alkyl halide or an alkyl lithium compound to form a carbinol, followed by the dehydrogenase 25 to form a compound in which R 3 is alkenyl, followed by reduction. Compounds of the general formula I in which R 3 is methyl and the other substituents are as described above can be prepared from I compounds of formula XIV by the process described in connection with process 7 PROCEDURE 23 I Compounds of general formula I in which R 3 in I 35 is thiocyanato, alkylthio, haloalkylthio, alkenylthio, In haloalkenylthio, phenylthio or heteroarylthio, R1 is!

I DK 175618 B1 II DK 175618 B1 I

I 32 II 32 I

I amino, R2 er cyano, og X, X1, X2, X3, X4 og Y har de betyd- IIn amino, R2 is cyano, and X, X1, X2, X3, X4 and Y are

I delsen, idet phenyl- og heteroarylgrupperne er sammensat IIn the partition, wherein the phenyl and heteroaryl groups are composed I

I og/eller substitueret som her beskrevet, dvs. forbindelser II and / or substituted as described herein, i.e. compounds I

I 5 med formlen XVI, jvf. det følgende, kan fremstilles ud fra II 5 of formula XVI, cf. the following, can be prepared from I

I forbindelser med formlen XI under betingelser, der svarer IIn compounds of formula XI under conditions corresponding to I

I til de, der er beskrevet i forbindelse med fremgangsmåde 10. ITo those described in connection with method 10. I

I Den samlede fremgangsmåde kan illustreres ved hjælp af det j II The overall method can be illustrated by means of the j I

I følgende reaktionsskema: j IIn the following reaction scheme: j I

I 10 ! II 10! IN

I H2N-HNjLsR : II H2N-HNjLsR: I

I * II * I

(XI) (XVI) I(XI) (XVI) I

20 Forbindelser med formlen XVI, i hvilken R betegner ICompounds of formula XVI in which R represents I

alkyl, kan også fremstilles ud fra forbindelser med den Ialkyl, can also be prepared from compounds with the I

almene formel I, i hvilken R3 betyder thiocyanato, og de Igeneral formula I in which R 3 means thiocyanato and those I

øvrige substituenter er defineret som i formlen XVI, ved Iother substituents are defined as in formula XVI, by I

behandling med alkylhalogenider eller lignende ved frem- Itreatment with alkyl halides or the like by prod

25 gangsmåder, der svarer til de, der er beskrevet i forbindelse I25 procedures similar to those described in compound I

med fremgangsmåde 11. Iwith method 11. I

FREMGANGSMÅDE 24 IPROCEDURE 24 I

30 Forbindelser med den almene formel I, i hvilken R3 ICompounds of general formula I in which R 3 I

er alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkenyl- Iare alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkenyl-I

sulfonyl, halogenalkylsulfinyl, halogenalkylsulfonyl, halo- Isulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, halo-I

genalkenylsulfinyl, halogenalkenylsulfonyl, phenylsulfinyl, Igenalkenylsulfinyl, halogenalkenylsulfonyl, phenylsulfinyl, I

phenylsulfonyl, heteroarylsulfinyl eller heteroarylsulfonyl, Iphenylsulfonyl, heteroarylsulfinyl or heteroarylsulfonyl, I

35 R1 er amino, R2 er cyano, og X, X1, X2, X3, X4 og Y har de IR1 is amino, R2 is cyano, and X, X1, X2, X3, X4 and Y have the I

betydninger, der er angivet i den generelle definition af Imeanings given in the general definition of I

33 DK 175618 B1 opfindelsen, og phenyl- og heteroarylgrupperne er sammensat og/eller substitueret som beskrevet, kan fremstilles ved oxidation af forbindelser med formlen XVI under anvendelse af metoder, der svarer til de, der er beskrevet i fremgangs-5 made 12. I de tilfælde, hvor X betegner en RS-gruppe, der kan undergå uønsket kompetitiv oxidation, kan sulfenylering i overensstemmelse med de ovennævnte metoder udføres med en forbindelse med formlen I, i hvilken X er halogen, fortrinsvis brom eller iod, R1 er amino, R2 er cyano, R3 er hydrogen, 10 og de øvrige substituenter har de betydninger, der er angivet i den generelle beskrivelse af opfindelsen, efterfulgt af oxidation, efterfulgt af behandling med en alkyllithium-forbindelse, ved en fremgangsmåde, der svarer til de, der er beskrevet af C.. Kruse et al. i Heterocycles, 1989, 29, 79, 15 -efterfulgt af en tilsætning af vand til.fremstilling af en forbindelse med formlen XVII. En forbindelse med formlen XVII kan derefter sulfenyleres til dannelse af forbindelser med formlen XVIII. Den samlede fremgangsmåde kan illustreres som følger: 20The invention, and the phenyl and heteroaryl groups are composed and / or substituted as described, can be prepared by oxidation of compounds of formula XVI using methods similar to those described in process 12. I in cases where X represents an RS group which may undergo undesirable competitive oxidation, sulfenylation according to the above methods may be carried out with a compound of formula I in which X is halogen, preferably bromine or iodine, R1 is amino, R2 is cyano, R 3 is hydrogen, and the other substituents have the meanings given in the general description of the invention, followed by oxidation, followed by treatment with an alkyl lithium compound, by a method similar to those of the present invention. described by C .. Kruse et al. in Heterocycles, 1989, 29, 79, 15 followed by the addition of water to prepare a compound of formula XVII. A compound of formula XVII can then be sulfenylated to form compounds of formula XVIII. The overall approach can be illustrated as follows: 20

HaljTCN HaiTTCN Hal“r~rCNHaljTCN HaiTTCN Hal «r ~ rCN

H2N-^nJ H2N-^NjJ-SR H2N-ilNJJ-S(0)nRH2N- ^ nJ H2N- ^ NjJ-SR H2N-ilNJJ-S (0) nR

_ _ ^“ΤιΓ^ X1-|f'W-X4 25 χ*4Χχ3 Χ24ΐχ3 X*4lX3 γ y γ HTTCN «ΊΠΓ®_ _ ^ “ΤιΓ ^ X1- | f'W-X4 25 χ * 4Χχ3 Χ24ΐχ3 X * 4lX3 γ y γ HTTCN« ΊΠΓ®

H2N-tL >-SlO)nR H2N —s* SlO)nRH2N-tL> -SlO) nR H2N —s * SlO) nR

30 N *· N30 N * · N

x1—fpVX4 * X1-r<W-X4 X2-<yJ-X3 X2—ti^^J-x3x1-fpVX4 * X1-r <W-X4 X2- <yJ-X3 X2-ti ^^ J-x3

Y YY Y

35 (XVII) (XVIII)35 (XVII) (XVIII)

I DK 175618 B1 II DK 175618 B1 I

I 34 II 34 I

I FREMGANGSMÅDE 25 IIN PROCEDURE 25 I

I Forbindelser med den almene formel I, i hvilken R3 ICompounds of general formula I in which R 3 I

I 5 betyder cyanato, alkoxy eller halogenalkoxy, R1 er amino, II 5 means cyanato, alkoxy or haloalkoxy, R 1 is amino, I

R2 er cyano, og X, X1, X2, X3, X4 og Y har de betydninger, IR2 is cyano and X, X1, X2, X3, X4 and Y have the meanings I

I der er angivet i den generelle definition af opfindelsen, IIn the general definition of the invention, I

I kan fremstilles ud fra forbindelser med formlen XII, i hvil- IYou can be prepared from compounds of formula XII in which I

I ken aminogruppen eventuelt er beskyttet, under anvendelse IIf any, the amino group is optionally protected, using I

I 10 af metoder, der svarer til de, der er beskrevet i forbindelse IIn 10 methods similar to those described in compound I

I med fremgangsmåde 5, efterfulgt af afbeskyttelse efter behov. IFollow Method 5, followed by deprotection as needed. IN

I FREMGANGSMÅDE 26 IIN PROCEDURE 26 I

15 A) Forbindelser med den almene formel I, i hvilken IA) Compounds of general formula I in which I

I R1 er hydrogen, R2 er cyano, og R3, X, X1, X2, X3, X4 og Y IIn R 1 is hydrogen, R 2 is cyano, and R 3, X, X 1, X 2, X 3, X 4 and Y I

I har de betydninger, der er angivet i den generelle definition IYou have the meanings given in the general definition

I af opfindelsen, dvs. forbindelser med den almene formel XX, : II of the invention, i.e. compounds of general formula XX:

I jvf. det følgende, kan fremstilles ud fra forbindelser med IThe following, may be prepared from compounds of I

I 20 den almene formel I, i hvilken R1 er amino, R2 er cyano, IIn the general formula I in which R 1 is amino, R 2 is cyano, I

I og R3, X, X1, X2, X3, X4 og Y har de betydninger, der er II and R3, X, X1, X2, X3, X4 and Y have the meanings that are I

I angivet i den generelle definition af opfindelsen, dvs. IAs set forth in the general definition of the invention, i. IN

I forbindelser med den almene formel XIX, jvf. det følgende, IIn compounds of the general formula XIX, cf.

I ved diazotering, fortrinsvis med et alkylnitrit, f.eks. II by diazotizing, preferably with an alkyl nitrite, e.g. IN

I 25 tert.butylnitrit, i et indifferent opløsningsmiddel, såsom IIn tert.butyl nitrite, in an inert solvent such as I

I tetrahydrofuran eller acetonitril. Denne reaktion kan udføres IIn tetrahydrofuran or acetonitrile. This reaction can be carried out

I ved en temperatur mellem -80°C og opløsningsmidlets tilbage- IAt a temperature between -80 ° C and the solvent back

I svalingstemperatur, fortrinsvis mellem 0 og 25°C. IAt cooling temperature, preferably between 0 and 25 ° C. IN

I 30 R1 betyder halogen, R2 er cyano, og R3, X, X1, X2, X3, X4 IIn R 1, halogen means, R 2 is cyano, and R 3, X, X 1, X 2, X 3, X 4 I

I definition, dvs. forbindelser med den almene formel XXI, IBy definition, i.e. compounds of general formula XXI, I

I jfr. det følgende, kan fremstilles ud fra en forbindelse II cf. The following may be prepared from a compound I

I med den almene formel XIX ved diazotering med et alkylnitrit, II of general formula XIX by diazotization with an alkyl nitrite, I

I 35 f.eks. tert.butylnitrit, i nærværelse af en halogenatom- IFor example, in 35 tert.butyl nitrite, in the presence of a halogen atom- I

I -donor, f.eks. bromoform, carbontetrachlorid, vandfrit cupri- II-donor, e.g. bromoform, carbon tetrachloride, anhydrous cupri- I

35 DK 175618 B1 chlorid eller iod.Chloride or iodine.

C) Forbindelser med den almene formel I, i hvilken R1 er thiocyanato, alkylthio, halogenalkylthio, alkenylthio, halogenalkenylthio, phenylthio eller heteroarylthio, R2 er 5 cyano, og R3 , X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition, og phenyl- og heteroarylgrupperne er sammensat og/eller substitueret som beskrevet deri, dvs. forbindelser med formlen XXII, jvf. det følgende, kan fremstilles ud fra en forbindelse med 10 formlen XIX ved behandling med et alkylnitrit i nærværelse af (SCN)2 eller et disulfid med formlen RSSR, hvor R betegner alkyl, halogenalkyl, alkenyl, halogenalkenyl, phenyl eller heteroaryl, som ovenfor defineret. Omsætningen udføres typisk i et opløsningsmiddel, såsom chloroform, ved en temperatur 15 på 0°C, med 1-5 ækvivalenter af alkylnitrittet og 2-5 ækvivalenter af disulfidet.C) Compounds of general formula I in which R1 is thiocyanato, alkylthio, haloalkylthio, alkenylthio, haloalkenylthio, phenylthio or heteroarylthio, R2 is cyano, and R3, X, X1, X2, X3, X4 and Y have the meanings, as defined in the general definition and the phenyl and heteroaryl groups are composed and / or substituted as described therein, i.e. compounds of formula XXII, cf. the following, may be prepared from a compound of formula XIX by treatment with an alkyl nitrite in the presence of (SCN) 2 or a disulfide of formula RSSR wherein R represents alkyl, haloalkyl, alkenyl, haloalkenyl, phenyl or heteroaryl, as defined above. The reaction is typically carried out in a solvent such as chloroform at a temperature of 0 ° C, with 1-5 equivalents of the alkyl nitrite and 2-5 equivalents of the disulfide.

De samlede fremgangsmåder kan illustreres som vist i det følgende formelskema:The overall methods can be illustrated as shown in the following formula:

20 X I, 1~CN X I, .1 CN20 X I, 1 ~ CN X I, .1 CN

η2ν-%^-*3 _„ RC-JLnJLr3 χ1-[ιΓχ4 x'-ifV*4η2ν -% ^ - * 3 _ "RC-JLnJLr3 χ1- [ιΓχ4 x'-ifV * 4

25 Y Y25 Y Y

(XIX) poo RC = H(XIX) poo RC = H

(XXI) Rc = Halogen(XXI) Rc = Halogen

(XXII) Rc = SR(XXII) Rc = SR

30 FREMGANGSMÅDE 27PROCEDURE 27

Alternativt kan mange af forbindelserne med formlen XXII fremstilles ud fra en forbindelse med den almene 35 formel XX, i hvilken R3 betyder amino, ved en fremgangsmåde, der svarer til den, der er beskrevet i forbindelse med frem-Alternatively, many of the compounds of formula XXII can be prepared from a compound of general formula XX in which R 3 represents amino, by a method similar to that described in connection with the invention.

I DK 175618 B1 | II DK 175618 B1 | IN

I II I

I 36 II 36 I

I gangsmåde 10. Omdannelse af aminogruppen til andre funktio- IProcedure 10. Conversion of the amino group to other functions

I nelle grupper ifølge opfindelsen kan derefter gennemføres ISubsequent groups of the invention can then be carried out

I ved anvendelse af en af de tidligere beskrevne metoder. IIn using one of the methods previously described. IN

I 5 FREMGANGSMÅDE 28 II PROCEDURE 28 I

I Forbindelser med den almene formel I > i hvilken R1 ICompounds of the general formula I> in which R1 is

I betyder alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alke- II means alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkene I

I nyl sul fonyl, halogenalkylsulfinyl, halogénalkylsulfonyl, IIn nyl sulphonyl, haloalkylsulphinyl, haloalkylsulphonyl, I

I 10 halogenalkenylsulfinyl, halogenalkenylsulfonyl, phenylsul- IIn haloalkenylsulfinyl, haloalkenylsulfonyl, phenylsul-I

I finyl, phenylsulfonyl, heteroarylsulfinyl eller heteroaryl- IIn finyl, phenylsulfonyl, heteroarylsulfinyl or heteroaryl-I

I sulfonyl, R2 er cyano, og R3, X, X1, X2, X3, X4 og Y har IIn sulfonyl, R2 is cyano and R3, X, X1, X2, X3, X4 and Y have I

I de betydninger, der er angivet i den generelle definition, IIn the meanings given in the general definition,

I og phenyl- og heteroarylgrupperne er sammensat og/eller IThe I and the phenyl and heteroaryl groups are composed and / or I

I 15 substitueret som her beskrevet, kan fremstilles ved oxidation IIn the substituted as described herein can be prepared by oxidation I

I af forbindelser med formlen XXII i overensstemmelse med de | II of compounds of formula XXII according to the | IN

I metoder, der er beskrevet i forbindelse med fremgangsmåde 24. IIn methods described in connection with method 24. I

I Såfremt X- og R3-grupperne også er SR-grupper, der skal II If the X and R3 groups are also SR groups, then I

I opretholdes på sulfidoxidationsniveauet, kan der anvendes IYou are maintained at the sulfide oxidation level, I can be used

I 20 en tilsvarende strategi som beskrevet i fremgangsmåde 24 II 20 has a similar strategy as described in Method 24 I

I i I til frembringelse af de ønskede forbindelser. iI in I to produce the desired compounds. in

I FREMGANGSMÅDE 29 1 IIN PROCEDURE 29 1 I

25 Forbindelser med den almene formel I, i hvlken R1 er ICompounds of general formula I, wherein R 1 is I

I alkylamino, dialkylamino, aralkylamino, aminocarbonylamino, IIn alkylamino, dialkylamino, aralkylamino, aminocarbonylamino, I

I alkylcarbonylamino, halogenalkylcarbonylamino, arylcarbonyl- IIn alkylcarbonylamino, haloalkylcarbonylamino, arylcarbonyl-I

I amino, alkylsulfonylamino, halogenalkylsulfonylamino, alkyl- IIn amino, alkylsulfonylamino, haloalkylsulfonylamino, alkyl-I

I aminocarbonylamino, arylaminocarbonylamino, alkoxycarbonyl- IIn aminocarbonylamino, arylaminocarbonylamino, alkoxycarbonyl-I

I 30 amino, halogenalkoxycarbonylamino, alkylidenimino, benzyli- IIn amino, haloalkoxycarbonylamino, alkylidenimino, benzyl-I

I denimino, alkoxyalkylidenimino, dialkylaminoalkylidenimino, IIn denimino, alkoxyalkylideneimino, dialkylaminoalkylideneimino, I

I alkylthioalkylidenimino eller azido, R2 er cyano, og R3, X, IIn alkylthioalkylidenimino or azido, R2 is cyano, and R3, X, I

22

33

I 35 fra en forbindelse med den almene formel XIX under anvendelse II from a compound of general formula XIX using I

44

I af fremgangsmåder, der svarer til de, der er beskrevet i II of methods similar to those described in I

37 DK 175618 B1 forbindelse med fremgangsmåde 18.37 in accordance with method 18.

FREMGANGSMÅDE 30PROCEDURE 30

A) Forbindelser med den almene formel I, i hvilken 5 R1 er formyl, R2 er cyano, og R3, X, X1, X2, X3, X4 og YA) Compounds of general formula I wherein R 1 is formyl, R 2 is cyano, and R 3, X, X 1, X 2, X 3, X 4 and Y

har de betydninger, der er angivet i den generelle definition af opfindelsen, kan fremstilles ud fra en forbindelse med den almene formel XIX ved behandling med natriumnitrit, HC=NOH, kobbersulfat og HCl på en måde, der er analog med 10 den, der er beskrevet af W.F. Beech, J·. Chem. Soc., 1954, 1297. Såfremt R3 er en aminogruppe i forbindelsen med formlen XIX, kan der anvendes en passende beskyttelse. Den ovennævnte forbindelse, i hvilken R* er formyl, kan omdannes til en forbindelse, i hvilken R1 er en bis-(alkylthio)-15 methyl- eller en bis-(arylthio)-methylgruppe, ved anvendelse af standardmetoder til thioacetalisering, som beskrevet af T.W. Greene, ibid., side 130, samt deri angivne referencer. Alternativt kan forbindelser med den almene formel I, i hvilken R^- betyder bis-(alkylthio)-methyl eller bis-(aryl-20 thio) -methyl, R2 er cyano, R3 er amino, og X, X3, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, fremstilles ud fra en forbindelse med den almene formel XX, i hvilken R3 er amino, ved en fremgangsmåde, der svarer til den, der er beskrevet i for-25 bindelse med fremgangsmåde 14. Omdannelse af bis-(alkylthio)-methyl- eller bis-(arylthio)-methyl-gruppen til formyl kan udføres ved anvendelse af metoder, der er analoge med de, der er beskrevet i forbindelse med fremgangsmåde 15. Omdannelse af aminofunktionen til andre funktionelle grupper 30 ifølge opfindelsen kan udføres ved anvendelse af en af de i det foregående beskrevne metoder.have the meanings given in the general definition of the invention can be prepared from a compound of general formula XIX by treatment with sodium nitrite, HC = NOH, copper sulfate and HCl in a manner analogous to that of described by WF Beech, J ·. Chem. Soc., 1954, 1297. If R 3 is an amino group of the compound of formula XIX, appropriate protection may be used. The above compound, in which R * is formyl, can be converted to a compound in which R 1 is a bis (alkylthio) methyl or a bis (arylthio) methyl group, using standard thioacetalization methods as described. by TW Greene, ibid., Page 130, and references cited therein. Alternatively, compounds of the general formula I in which R 1 - represents bis (alkylthio) methyl or bis (aryl-20-thio) methyl, R 2 is cyano, R 3 is amino, and X, X 3, X 2, X 3 X4 and Y have the meanings given in the general definition of the invention are prepared from a compound of the general formula XX in which R3 is amino by a method similar to that described in the foregoing. Conjugation of Process 14. Conversion of the bis (alkylthio) methyl or bis (arylthio) methyl group to formyl can be carried out using methods analogous to those described in connection with process 15. Conversion of the amino function to other functional groups 30 of the invention can be carried out using one of the methods described above.

B) Forbindelser med den almene formel I, i hvilken R* betyder hydroxyiminoalkylideny1 eller alkoxyiminoalkyli-denyl, R2 er cyano, og R3, X, X1, X2, X3, X4 og Y har de 35 betydninger, der er angivet i den generelle definition af opfindelsen, kan fremstilles ud fra forbindelser med denB) Compounds of general formula I wherein R * is hydroxyiminoalkylidenyl or alkoxyiminoalkylidenyl, R of the invention may be prepared from compounds thereof

I DK 175618 B1 II DK 175618 B1 I

I 38 II 38 I

I almene formel I, i hvilken R1 betyder alkylcarbonyl eller IIn general formula I, wherein R 1 is alkylcarbonyl or I

I formyl, og de øvrige substituenter er som ovenfor defineret, IIn formyl, and the other substituents are as defined above, I

ved anvendelse af fremgangsmåder, der svarer til de, der er Iusing methods similar to those of I

I beskrevet i forbindelse med fremgangsmåde 16. De ovennævnte II described in connection with method 16. The above-mentioned I

5 forbindelser, i hvilke R1 betegner alkylcarbonyl, kan frem- I5 compounds in which R 1 represents alkylcarbonyl can be prepared

I stilles ud fra de tilsvarende forbindelser, i hvilke R* IYou are made from the corresponding compounds in which R * I

betegner halogen, ved omdannelse til et Grignard-reagens Irepresents halogen, upon conversion to a Grignard reagent I

I eller et lithium-derivat, med eventuel beskyttelse af cyano- II or a lithium derivative, with possible protection of cyano-I

I gruppen som omtalt i forbindelse med fremgangsmåde 5, efter- IIn the group as discussed in connection with method 5, post-I

10 fulgt af omsætning med et aliphatisk syrechlorid eller -anhy- I10 followed by reaction with an aliphatic acid chloride or anhydride

I drid eller alternativt kondensation med et aliphatisk aide- IIn dredge or alternate condensation with an aliphatic aide

I hyd, efterfulgt af oxidation. Alternativt kan de forbindel- IIn hyd, followed by oxidation. Alternatively, they can be I-linked

I ser, i hvilke R1 betyder alkylcarbonyl, fremstilles ud fra IYou see, in which R 1 is alkylcarbonyl, is prepared from I

I de tilsvarende forbindelser, i hvilke R1 betyder formyl, IIn the corresponding compounds in which R 1 represents formyl, I

I 15 ved omsætning med et alkyl-Grignard-reagens, efterfulgt af II by reaction with an alkyl-Grignard reagent, followed by I

oxidation. Ioxidation. IN

I R1 er cyano, R2 er cyano, og R3, X, X1, X2, χ3, X4 og Y har IIn R1 is cyano, R2 is cyano, and R3, X, X1, X2, χ3, X4 and Y have I

I 20 af opfindelsen, kan fremstilles ud fra de tilsvarende for- IIn 20 of the invention, can be prepared from the corresponding methods

I bindeiser, i hvilke R1 betyder hydroxyiminomethylidenyl IIn binders wherein R 1 is hydroxyiminomethylidenyl I

I eller alkoxyiminomethylidenyl, ved fremgangsmåder, der svarer II or alkoxyiminomethylidenyl, by methods corresponding to I

I til de, der er beskrevet i forbindelse med fremgangsmåde 4A. II to those described in connection with method 4A. IN

I D) Forbindelser med den almene formel I, i hvilken ICompounds of general formula I in which I

I 25 R1 betyder halogenalkylcarbonyl eller halogenalkylthiocar- IIn R 1, haloalkylcarbonyl or haloalkylthiocar- I means

I bonyl, R2 er cyano, og R3, X, X1, X2, X3, X4 og Y har de IIn bonyl, R2 is cyano and R3, X, X1, X2, X3, X4 and Y have the I

I betydninger, der er angivet i den generelle definition af IIn the meanings given in the general definition of I

opfindelsen, kan fremstilles ud fra en forbindelse med den IThe invention may be prepared from a compound of the invention

almene formel I, i hvilken R1 betyder formyl, og de øvrige Igeneral formula I in which R 1 means formula and the other I

30 substituenter er som ovenfor defineret, ved behandling under IThirty substituents are as defined above by treatment under I

betingelser svarende til de, der er beskrevet i forbindelse Iconditions similar to those described in compound I

med fremgangsmåde 8. Iwith method 8. I

E) Forbindelser med den almene formel I, i hvilken IE) Compounds of general formula I in which I

R1 betyder halogenalkyl eller alkyl, R2 er cyano, og R3, X, IR 1 is haloalkyl or alkyl, R 2 is cyano, and R 3, X, I

35 X1, X2, X3, X4 og Y har de betydninger, der er angivet i IX1, X2, X3, X4 and Y have the meanings given in I

den generelle definition af opfindelsen, kan fremstilles ud Ithe general definition of the invention may be embodied

39 I39 I

DK 175618 B1 IDK 175618 B1 I

fra en forbindelse med den almene formel I, i hvilken R1 er Ifrom a compound of general formula I in which R 1 is I

I formyl eller halogen, og de øvrige substituenter er som IIn formyl or halogen, and the other substituents are like I

I defineret ovenfor, ved behandling under betingelser svarende II defined above, by treatment under conditions similar to I

I til de, der er beskrevet i forbindelse med fremgangsmåde 22. ITo those described in connection with method 22. I

I 5 II 5 I

I FREMGANGSMÅDE 31 IIN PROCEDURE 31 I

I Forbindelser med den almene formel I, i hvilken R1 ICompounds of general formula I in which R1 is

I betyder phenyl eller heteroaryl, der er substitueret som II means phenyl or heteroaryl substituted as I

I 10 beskrevet i den generelle definition af opfindelsen, R2 er IIn 10 described in the general definition of the invention, R2 is I

I cyano, og R3, X, X1, X2, X3, X4 og Y har de betydninger, IIn cyano, and R3, X, X1, X2, X3, X4 and Y have the meanings I

I kan fremstilles ud fra forbindelser med den almene formel I, IYou can be prepared from compounds of general formula I, I

I i hvilken R1 er halogen, og de øvrige substituenter er som II in which R1 is halogen and the other substituents are like I

I 15 ovenfor defineret, ved fremgangsmåder, der svarer til de, II, as defined above, by methods similar to those I

I der er beskrevet i forbindelse med fremgangsmåderne 19B og IAs described in connection with Methods 19B and I

I 19C. IIn 19C. IN

I FREMGANGSMÅDE 32 IIN PROCEDURE 32 I

I 20 II 20 I

I er cyanato, alkoxy eller halogenalkoxy, R2 er cyano, og R3, II is cyano, alkoxy or haloalkoxy, R2 is cyano, and R3, I

I X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i IIn X, X1, X2, X3, X4 and Y have the meanings given in I

I 25 fra forbindelser med formlen XXI under anvendelse af metoder, I der svarer til de, der er beskrevet i forbindelse med frem- I gangsmåde 5.I from compounds of formula XXI using methods similar to those described in connection with Method 5.

FREMGANGSMÅDE 33 I 30 I Forbindelser med den almene formel I, i hvilken R2 I er formyl, R1, R3, X,' X1, X2, X3, X4 og Y har de betydninger, I der er angivet i den generelle definition af opfindelsen, 2 I dvs. forbindelser med den almene formel XXIV, jvf. det føl- 3 35 gende, kan fremstilles ud fra forbindelser med den almene 4 I formel I, i hvilken R2 er cyano, R3, R3, X, X1, X3, X3, X4 I DK 175618 B1METHOD 33 I 30 I Compounds of general formula I in which R2 is formyl, R1, R3, X, X1, X2, X3, X4 and Y have the meanings given in the general definition of the invention. 2 I ie. Compounds of general formula XXIV, cf. the following, can be prepared from compounds of general formula I in which R2 is cyano, R3, R3, X, X1, X3, X3, X4 in DK 175618 B1

I 40 II 40 I

og Y har de betydninger, der er angivet i den generelle Iand Y has the meanings given in the general I

definition af opfindelsen, dvs. forbindelser.med den almene Idefinition of the invention, i.e. connections with the general I

I formel XXIII, jvf. det følgende, ved behandling med et reduk- IIn formula XXIII, cf. the following, by treatment with a reducing agent

I tionsmiddel, fortrinsvis diisobutylaluminiumhydrid i et IIn a detergent, preferably diisobutyl aluminum hydride in an I

5 opløsningsmiddel, fortrinsvis en blanding af toluen og hexan I5, preferably a mixture of toluene and hexane I

i forholdet 1:1, ved en fremgangsmåde, der svarer til den, Iin a 1: 1 ratio, by a method similar to that, I

I der er beskrevet af S. Trofimenko i J. Org. Chem., 1964, IIn that described by S. Trofimenko in J. Org. Chem., 1964, I

I 29, 3046. Den samlede fremgangsmåde er illustreret i det II 29, 3046. The overall method is illustrated in I

I følgende reaktionsskema: IIn the following reaction scheme:

I 10 II 10 I

I ZTJS0I ZTJS0

N -► IN -► I

I X2~1iT^ χ1'Ίί^Τχ4 II X2 ~ 1iT ^ χ1'Ίί ^ Τχ4 I

15 X x2J!J_x3 I15 X x2J! J_x3 I

I Y y II Y y I

(XXIII} (XXIV) I(XXIII} (XXIV) I

20 FREMGANGSMÅDE 34 IMETHOD 34 I

Nyttige mellemproduktforbindelser med den almene IUseful intermediate compounds with the general I

formel I, i hvilken R2 er en carboxylsyre-funktion, R^·, R3, Iformula I in which R 2 is a carboxylic acid function, R 2, R 3, I

X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i IX, X1, X2, X3, X4 and Y have the meanings given in I

25 den generelle definition af opfindelsen, dvs. forbindelser I25 the general definition of the invention, i. compounds I

med den almene formel XXV, jvf. det følgende, kan fremstilles Iof general formula XXV, cf. the following, can be prepared I

ved oxidation af forbindelserne med formlen XXIV, under Iby oxidation of the compounds of formula XXIV, under I

anvendelse af Jones' reagens. Den samlede fremgangsmåde kan Iuse of Jones' reagent. The overall method can be

illustreres som følger: Iis illustrated as follows:

30 I30 I

X1—ΪΓ0*0 xi—π-00*” IX1 — ΪΓ0 * 0 xi — π-00 * ”I

r1A^J-r3 R1-4n jl-R3 Ir1A ^ J-r3 R1-4n jl-R3 I

x’-irV^ * χ’-Α-χ4 Ix'-irV ^ * χ'-Α-χ4 I

35 X2-<o^-X3 X2_|ILX3 I35 X2- <o ^ -X3 X2_ | ILX3 I

y y Iy y I

[xxrv] pcxvj I[xxrv] pcxvj I

41 DK 175618 B1 FREMGANGSMÅDE 3541 GB 175618 B1 PROCEDURE 35

Forbindelser med den almene formel I, i hvilken R2 5 er hydroxy iminoal kyl i deny 1, alkoxyiminoalkylidenyl, halogenal kylcarbonyl, halogenalkylthiocarbonyl, alkyl, bis-{alkyl-thio)-methyl, bis-(arylthio)-methyl eller halogenalkyl, og R1, R3, X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, kan frem-10 stilles ud fra forbindelser med formlen XXIV eller forbindelser med den almene formel I, i hvilken R2 er halogen, og de øvrige substituenter er som ovenfor defineret, hvis fremstilling er beskrevet i forbindelse med fremgangsmåde 38, under anvendelse af metoder, der svarer til de, der er beskrevet 15 i forbindelse med fremgangsmåde 30A, 30B, 30D og 30E.Compounds of the general formula I in which R , R3, X, X1, X2, X3, X4 and Y have the meanings given in the general definition of the invention can be prepared from compounds of formula XXIV or compounds of general formula I in which R2 is halogen and the other substituents are as defined above, the preparation of which is described in connection with process 38, using methods similar to those described 15 in connection with processes 30A, 30B, 30D and 30E.

FREMGANGSMÅDE 36PROCEDURE 36

Forbindelser med den almene formel I, i hvilken R2 20 er amino, R1, R3, X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, dvs. forbindelser med den almene formel XXVII, jvf. det j følgende, kan fremstilles ud fra forbindelserne med formlen XXV ved behandling med diphenylphosphorylazid i nær-25 værelse af en organisk base, f.eks. triethylamin, i et alkoholisk opløsningsmiddel, f.eks. tert.butanol, til dannelse af et carbamat med formlen XXVI, efterfulgt af hydrolyse,Compounds of general formula I wherein R 2 is amino, R 1, R 3, X, X 1, X 2, X 3, X 4 and Y have the meanings given in the general definition of the invention, i. Compounds of general formula XXVII, cf. the following, can be prepared from the compounds of formula XXV by treatment with diphenylphosphoryl azide in the presence of an organic base, e.g. triethylamine, in an alcoholic solvent, e.g. tert.butanol to form a carbamate of formula XXVI, followed by hydrolysis,

Andre metoder til fremstilling af en forbindelse med formlen XXVII ud fra en forbindelse med formlen XXV via en Cur-30 tius-omlejring omfatter omdannelse til syrechloridet, efterfulgt af omsætning med azidion og behandling med en alkohol som beskrevet af J. March i "Advanced Organic Chemistry", McGraw-Hill publ., (1985), side 984. Den samlede omdannelse kan illustreres som følger: 35Other methods of preparing a compound of formula XXVII from a compound of formula XXV via a Cur-30 tius rearrangement include conversion to the acid chloride, followed by reaction with azide ion and treatment with an alcohol as described by J. March in "Advanced Organic Chemistry ", McGraw-Hill publ., (1985), page 984. The overall transformation can be illustrated as follows: 35

I DK 175618 B1 II DK 175618 B1 I

I 42 II 42 I

I X_n Γ00^ Χ-Γ—pNHCO^c X-Tj ipNH, II X_n Γ00 ^ Χ-Γ — pNHCO ^ c X-Tj ipNH, I

I RlJ.NjLR3 R.JInJLr3 R1-11nJJ-R3 II RlJ.NjLR3 R.JInJLr3 R1-11nJJ-R3 I

I 5 x’-rf^Vx4 xl-fAiv-x4 * x’-r^W-X4 II 5 x'-rf ^ Vx4 xl-fAiv-x4 * x'-r ^ W-X4 I

I Χ«χ3 χ^χ3 X2-\^Lx3 II Χ «χ3 χ ^ χ3 X2 - \ ^ Lx3 I

I Y y Y -II Y y Y -I

I (XXV) (XXVI) (XXVII) II (XXV) (XXVI) (XXVII) I

I 10 II 10 I

I FREMGANGSMÅDE 37 IPROCEDURE 37 I

I Forbindelser med den almene formel I, i hvilken R2 ICompounds of general formula I in which R 2

I er alkylamino, dialkylamino, aralkylamino, aminocarbonyl- IYou are alkylamino, dialkylamino, aralkylamino, aminocarbonyl-I

I 15 amino, alkylcarbonylamino, halogenalkylcarbonylamino, aryl- IIn amino, alkylcarbonylamino, haloalkylcarbonylamino, aryl-I

I carbonyl amino, alkyl sul fonylamino, halogenalkylsulfonylamino, IIn carbonyl amino, alkyl sulphonylamino, haloalkylsulfonylamino, I

I alkylaminocarbonylamino, arylaminocarbonylamino, alkoxycar- IIn alkylaminocarbonylamino, arylaminocarbonylamino, alkoxycarl

I bonylamino, halogenalkoxycarbonylamino, alkylidenimino, IIn bonylamino, haloalkoxycarbonylamino, alkylidenimino, I

I benzylidenimino, alkoxyalkylidenimino, dialkylaminoalkyli- IIn benzylideneimino, alkoxyalkylideneimino, dialkylaminoalkyl-I

I 20 denimino, alkylthioalkylidenimino eller azido, rA, R3, X, IIn denimino, alkylthioalkylidenimino or azido, rA, R3, X, I

I fra forbindelserne med formlen XXVII, under anvendelse af II from the compounds of formula XXVII, using I

I fremgangsmåder, der svarer til de, der er beskrevet i for- IIn methods similar to those described in Form I

I 25 bindelse med fremgangsmåde 18. IIn connection with method 18. I

I FREMGANGSMÅDE 38 IIN PROCEDURE 38 I

I 30 er hydrogen, halogen, thiocyanato, alkylthio, halogenalkyl^- II is hydrogen, halogen, thiocyanato, alkylthio, haloalkyl ^ - I

thio, alkenylthio, halogenalkenylthio, phenylthio eller Ithio, alkenylthio, haloalkenylthio, phenylthio or I

heteroarylthio, R1, R3, X, X*, X2, X3, X4 og Y har de betyd- Iheteroarylthio, R1, R3, X, X *, X2, X3, X4 and Y

ninger, der er angivet i den generelle definition af opfin- IThe invention is defined in the general definition of the invention

delsen, kan fremstilles ud fra forbindelserne med formlen Ican be prepared from the compounds of formula I

35 XXVII under anvendelse af fremgangsmåder, der svarer til I35 XXVII using methods similar to I

de, der er beskrevet i forbindelse med fremgangsmåde 26. Ithose described in connection with method 26. I

43 DK 175618 B143 DK 175618 B1

Alternativt kan forbindelserne med den almene formel I, i hvilken R2 betyder hydrogen, og R1, R3 , X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i forbindelse med den generelle definition af opfindelsen, fremstilles ud fra 5 forbindelser med formlen XXV ved opvarmning med 48% HBr i iseddikesyre ved tilbagesvaling eller opvarmning i et højt-kogende opløsningsmiddel, f.eks. decalin eller quinolin, i nærværelse af kobber.Alternatively, the compounds of general formula I wherein R 2 is hydrogen and R 1, R 3, X, X 1, X 2, X 3, X 4 and Y have the meanings given in connection with the general definition of the invention can be prepared from 5 compounds of formula XXV by heating with 48% HBr in glacial acetic acid at reflux or heating in a high boiling solvent, e.g. decalin or quinoline, in the presence of copper.

10 FREMGANGSMÅDE 39PROCEDURE 39

Forbindelser med den almene formel I, i hvilken R2 betyder alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkenyl sul fonyl, halogenalkylsulfinyl, halogenalkylsulfonyl, 15 halogenalkenylsulfinyl, halogenalkenylsulfonyl, phenylsul-finyl, phenylsulfonyl, heteroarylsulfinyl eller heteroa-rylsulfonyl, og R1, R3, X, X^, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, kan fremstilles ved oxidation af forbindelser med 20 den almene formel I, i hvilken R2 betyder alkylthio, halo-genalkylthio, alkenylthio, halogenalkenylthio, phenylthio eller heteroarylthio, ved anvendelse af fremgangsmåder, der svarer til de, der er beskrevet i forbindelse med fremgangsmåde 24 .Compounds of general formula I in which R 2 is alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkenylsulfonyl, haloalkylsulphinyl, haloalkylsulphonyl, haloalkenylsulphinyl, haloalkenylsulphonyl, phenylsulphonyl, hetero-sulfonyl, phenylsulphonyl, phenylsulphonyl, X, X 2, X 3, X 4 and Y have the meanings given in the general definition of the invention can be prepared by the oxidation of compounds of general formula I wherein R 2 is alkylthio, haloalkylthio, alkenylthio, haloalkenylthio, phenylthio or heteroarylthio, using methods similar to those described in connection with process 24.

25 FREMGANGSMÅDE 40METHOD 40

Forbindelser med den almene formel I, i hvilken R2 betyder phenyl eller heteroaryl, substitueret som angivet i 30 den generelle definition af opfindelsen, og R1, R3, X, X1, X2, X3, X4 og Y har de betydninger, der er angivet i den generelle definition af opfindelsen, kan fremstilles ud fra forbindelser med den almene formel I, i hvilken R2 betyder halogen, og de øvrige substituenter er som ovenfor defineret, 35 ved anvendelse af fremgangsmåder, der svarer til de, der er beskrevet i forbindelse med fremgangsmåde 19B og 19C.Compounds of general formula I in which R 2 is phenyl or heteroaryl substituted as defined in the general definition of the invention and R 1, R 3, X, X 1, X 2, X 3, X 4 and Y have the meanings given in the general definition of the invention may be prepared from compounds of the general formula I in which R 2 is halogen and the other substituents are as defined above using methods similar to those described in connection with process 19B and 19C.

I DK 175618 B1 II DK 175618 B1 I

I 44 II 44 I

I FREMGANGSMÅDE 41 IIN PROCEDURE 41 I

I Forbindelser med formlen I, i hvilken betyder IIn compounds of formula I, in which you mean

I cyanato, alkoxy eller halogenalkoxy, og R1, R^, X, X^·, X2 , IIn cyanato, alkoxy or haloalkoxy, and R 1, R 2, X, X 2, X 2, I

I 5 X3, X4 og Y har de betydninger, der er angivet i den gene- IIn 5 X3, X4 and Y have the meanings given in the gene I

I relle definition af opfindelsen, kan fremstilles ud fra IIn the true definition of the invention, may be prepared from I

I forbindelser med den almene formel I, i hvilken R2 betyder IIn compounds of the general formula I in which R 2 means I

I halogen, og de øvrige substituenter er som ovenfor defineret, IIn halogen, and the other substituents are as defined above, I

I ved anvendelse af fremgangsmåder, der svarer til de, der er II using methods similar to those I

I 10 beskrevet i forbindelse med fremgangsmåde 5. II 10 described in connection with method 5. I

I På generel måde kan fremgangsmåden ifølge opfindelsen IIn general, the method of the invention can be I

I defineres som angivet i det følgende: II is defined as follows:

I P2. En fremgangsmåde til fremstilling af forbindelser IIn P2. A process for the preparation of compounds I

I 15 med den almene formel IIn general formula I

I xttcn II xttcn I

I h2nJ.nJ iI h2nJ.nJ i

I i (la) II i (la) I

I y II y I

I i hvilken X1, X2, X2, x4 og Y har den i forbindelse med IIn which X1, X2, X2, x4 and Y are associated with I

I 25 fremgangsmåde 1 angivne betydning, og X betyder halogen, IIn method 1, meaning is given and X is halogen, I

I trifluormethyl, cyano, thiocyanato, alkylthio, alkylsulfinyl, IIn trifluoromethyl, cyano, thiocyanato, alkylthio, alkylsulfinyl, I

I alkylsulfonyl, halogenalkylthio, halogenalkylsulfinyl, halo- IIn alkylsulfonyl, haloalkylthio, haloalkylsulfinyl, halo-I

I genalkylsulfonyl, alkenylthio, halogenalkenylthio, halogen- IIn gene alkylsulfonyl, alkenylthio, halogenalkenylthio, halogen-I

I alkenylsulfinyl, halogenalkenylsulfonyl, phenylthio, phenyl- IIn alkenylsulfinyl, halogenalkenylsulfonyl, phenylthio, phenyl-I

I 30 sulfinyl, phenylsulfony1, heteroarylthio, heteroarylsulfinyl IIn sulfinyl, phenylsulfonyl, heteroarylthio, heteroarylsulfinyl I

I eller heteroarylsulfonyl, ved hvilken en forbindelse med II or heteroarylsulfonyl, wherein a compound of I

I den almene formel . IIn the general formula. IN

I 45 II 45 I

DK 175618 B1 IDK 175618 B1 I

H2NTjTCNH2NTjTCN

I 2 N II 2 N I

I X1—rf^Y'X4 II X1 — rf ^ Y'X4 I

I 5 tfjl-xS (III> II 5 tfjl-xS (III> I

I y iI y i

I i hvilken aminogruppen eventuelt er beskyttet, IIn which the amino group is optionally protected,

I 10 a) omsættes med et halogeneringsmiddel, eventuelt i II a) is reacted with a halogenating agent, optionally in I

I nærværelse af et opløsningsmiddel, til dannelse af en forbin- IIn the presence of a solvent to form a compound

I delse med formlen la, i hvilken X betyder halogen, hvorefter IIn the formula Ia, in which X means halogen, then I

I denne forbindelse om ønsket omsættes med trifluormethyl-kob- IIn this connection, if desired, react with trifluoromethyl-copper-I

I ber på kendt måde til dannelse af forbindelser med form- IYou ask in known manner to form compounds of Form I

I 15 len la, hvor X betyder trifluormethyl, IIn the Ia 1a, where X is trifluoromethyl, I

I b) omsættes med en tris-(alkylthio)-methan eller II b) is reacted with a tris (alkylthio) methane or I

I tris-(arylthio)-methan i nærværelse af en Lewis-syre, hvor- IIn tris (arylthio) -methane in the presence of a Lewis acid, where- I

I efter den dannede forbindelse med formlen XXXVI, hvor X IIn the compound of formula XXXVI formed, where X I

I betyder bis-(alkylthio)-methyl eller bis-(arylthio)-methyl, II means bis- (alkylthio) -methyl or bis- (arylthio) -methyl, I

I 20 omsættes med et alkylnitrit, efterfulgt af hydrolyse, til II 20 is reacted with an alkyl nitrite followed by hydrolysis to I

opnåelse af en forbindelse med formlen XXXVII, i hvilken X Iobtaining a compound of formula XXXVII in which X I

I betyder formyl, hvorefter denne forbindelse bringes i kontakt II means formula and then this compound is contacted

I med hydroxylamin, efterfulgt af dehydratisering med egnede II with hydroxylamine, followed by dehydration with suitable I

I midler såsom P2C>5 på kendt måde til dannelse af en forbin- IIn agents such as P2C> 5 in known manner to form a compound I

25 deIse med formlen la, hvor X betegner en cyanogruppe, c) omsættes med en forbindelse med formlen MSCN, I hvor M betegner et alkalimetalatom, i nærværelse af brom i I et opløsningsmiddel, f.eks. methanol, til dannelse af en I forbindelse med formlen la, hvor X er en thiocyanatogruppe, I 30 hvorefter man om ønsket omsætter denne forbindelse med et I alkylhalogenid eller et dialkylsulfat i nærværelse af en base, f.eks. NaOH eller KOH, i et opløsningsmiddel, til I dannelse af en forbindelse med formlen la, i hvilken X bety- I der alkylthio, eller I 35 d) omsættes med et sulfenylhalogenid med formlen I RSHal, i hvilken R betyder alkyl, halogenalkyl, phenyl eller I DK 175618 B1 Η H heteroaryl, og Hal er et halogenatom, i et organisk væske- formigt reaktionsmedium, eventuelt i nærværelse af en syre- acceptor, f.eks. en tertiær amin, til dannelse af en forbin- H delse med formlen la, i hvilken X betyder alkylthio, halogen- 5 alkylthio, alkenylthio, halogenalkenylthio, phenylthio eller H heteroarylthio, hvorefter den dannede forbindelse eventuelt oxideres på kendt måde til dannelse af en forbindelse med formlen la, i hvilken X betyder RS(0)n, hvor X betyder 1 eller 2, afhængigt af reaktionsbetingelserne.Wherein X represents a cyano group, c) is reacted with a compound of formula MSCN, I wherein M represents an alkali metal atom, in the presence of bromine in a solvent, e.g. methanol to form a compound of formula Ia, wherein X is a thiocyanato group, and then, if desired, this compound is reacted with an I alkyl halide or a dialkyl sulfate in the presence of a base, e.g. NaOH or KOH, in a solvent, to give a compound of formula Ia in which X means alkylthio, or I d) is reacted with a sulfenyl halide of formula I RSHal in which R is alkyl, haloalkyl, phenyl or I is 175618 B1 Η H heteroaryl, and Hal is a halogen atom, in an organic liquid reaction medium, optionally in the presence of an acid acceptor, e.g. a tertiary amine to form a compound of formula Ia in which X represents alkylthio, haloalkylthio, alkenylthio, haloalkenylthio, phenylthio or H heteroarylthio, whereupon the resulting compound is optionally oxidized in a known manner to form a compound of formula Ia, in which X means RS (0) n, where X means 1 or 2, depending on the reaction conditions.

10 P2. En fremgangsmåde til fremstilling af forbindel- serne med formlen la, i hvilken X1, X^, χ3, χ4 Qg γ har den samme betydning som angivet i forbindelse med fremgangs- måde 1, og X betyder cyanato, alkoxy eller halogenalkoxy, 15 idet en forbindelse med den almene formel I “TT“ h2n-< y 7 (XXVIII) 20 Jt'-fV*4 X2JlJ-X310 P2. A process for preparing the compounds of formula Ia in which X1, X1, ,3, χ4 Qg γ have the same meaning given in connection with process 1, and X means cyanato, alkoxy or haloalkoxy, wherein compound of the general formula I "TT" h2n- <y 7 (XXVIII) 20 Jt'-fV * 4 X2JlJ-X3

YY

hvor amino- og cyanogrupperne er passende beskyttet, såfremt 25 dette er nødvendigt, a) omsættes med et cyanogenhalogenid i nærværelse af en syreacceptor til dannelse af en forbindelse med formlen la, i hvilken X er cyanato, b) omsættes med et alkyleringsmiddel, eventuelt i 30 nærværelse af en base, til dannelse af forbindelser med formlen la, i hvilken X betyder alkoxy, eller c) halogenalkyleres på kendt måde, i overensstemmelse med Syntheses of Fluoroorganic Compounds, Knunyants, I.L. og Yakobson, G.G., Ed., Springer-Verlag, Berlin, 1985, 35 side 263-2690, til dannelse af forbindelser med formlen la, i hvilken X betyder halogenalkoxy.wherein the amino and cyano groups are suitably protected, if necessary, a) reacting with a cyanogen halide in the presence of an acid acceptor to form a compound of formula Ia in which X is cyano, b) reacting with an alkylating agent, optionally in In the presence of a base, to form compounds of formula Ia in which X is alkoxy, or c) is haloalkylated in known manner, according to Syntheses of Fluoroorganic Compounds, Knunyants, IL and Yakobson, G.G., Ed., Springer-Verlag, Berlin, 1985, pages 263-2690, to form compounds of formula Ia in which X represents haloalkoxy.

47 DK 175618 B1 P3. En fremgangsmåde til fremstilling af forbindelser med formlen la, i hvilken X*, X2, X3, X4 og Y har i forbindelse med fremgangsmåde 1 angivne betydning, og X betyder halogenalkyl (CF2H, CF3, BrCH2 eller C1CH2), halogenalkyl-5 carbonyl, halogenalkylthiocarbonyl eller en halogenalkyl--gruppe, fortrinsvis en halogenmethylgruppe, ved hvilken en forbindelse med den almene formel47 DK 175618 B1 P3. A process for the preparation of compounds of formula Ia, wherein X *, X2, X3, X4 and Y have the meaning given in connection with process 1, and X is haloalkyl (CF2H, CF3, BrCH2 or C1CH2), haloalkylcarbonyl, haloalkylthiocarbonyl or a haloalkyl group, preferably a halogenomethyl group, wherein a compound of the general formula

OHC~n—TCNOHC ~ n-TCN

10 h,n-IL JJ10 h, n-IL JJ

1 {VI) x1VVx4 X2-iiyJi-X31 {VI) x1VVx4 X2-iiyJi-X3

YY

15 i hvilken amino- og cyanogruppen om ønsket er beskyttet på passende måde, (a) omsættes med et fluoreringsmiddel, f.eks. diethyl-aminosvovl-trifluorid på kendt måde til dannelse af en for- 2 0 bindelse med formlen la, i hvilken X er en difluormethylgruppe , (b) omsættes med et egnet oxidationsmiddel, f.eks. chromtrioxid i svovlsyre, til dannelse af forbindelser, hvor X betyder en carboxylsyregruppe, hvorefter de nævnte 25 forbindelser underkastes indvirkning af et fluoreringsmiddel, f.eks. svovltetrafluorid, på kendt måde, til dannelse af en forbindelse med formlen la, hvor X betyder trifluormethyl, (c) omsættes under Wolff-Kishner-betingelser eller en variant deraf, f.eks. behandling med p-toluensulfonyl- 30 hydrazid, efterfulgt af behandling med natriumcyanoborhydrid, til dannelse af en forbindelse, i hvilken X betyder en methylgruppe, hvorefter forbindelsen underkastes behandling med et halogeneringsmiddel, f.eks. N-bromsuccinimid eller N-chlorsuccinimid, i et egnet opløsningsmiddel til dannelse 35 af en forbindelse med formlen la, hvor X betyder brommethyl eller chlormethyl, ellerWherein the amino and cyano group are suitably protected if desired; (a) reacted with a fluorinating agent, e.g. diethylamino sulfur trifluoride in known manner to form a compound of formula Ia in which X is a difluoromethyl group; (b) is reacted with a suitable oxidizing agent, e.g. chromium trioxide in sulfuric acid, to form compounds wherein X represents a carboxylic acid group, after which said compounds are subjected to the action of a fluorinating agent, e.g. sulfur tetrafluoride, in known manner, to form a compound of formula Ia wherein X is trifluoromethyl, (c) is reacted under Wolff-Kishner conditions or a variant thereof, e.g. treatment with p-toluenesulfonylhydrazide, followed by treatment with sodium cyanoborohydride, to form a compound in which X represents a methyl group, after which the compound is treated with a halogenating agent, e.g. N-bromosuccinimide or N-chlorosuccinimide, in a suitable solvent to form a compound of formula Ia wherein X is bromomethyl or chloromethyl, or

I DK 175618 B1 II DK 175618 B1 I

I 48 II 48 I

I (d) omsættes i rækkefølge med et halogenalkyl-metal- II (d) is reacted sequentially with a haloalkyl metal I

I derivat eller trifluormethyltrimethylsilan til dannelse af IIn derivative or trifluoromethyltrimethylsilane to give I

I forbindelser med formlen la, hvor X betyder halogenalkylcar- IIn compounds of formula Ia, where X is haloalkylcar-I

I binol, efterfulgt af oxidation på kendt måde til dannelse IIn binol, followed by oxidation in known manner to form I

I 5 af forbindelser med formlen la, hvor X betyder halogenalkyl- IIn 5 of compounds of formula Ia, where X is haloalkyl-I

I carbonyl, hvorefter denne forbindelse om ønsket underkastes IIn carbonyl, and if desired, this compound is subjected to I

I behandling med Lawesson's reagens til dannelse af forbindel- IIn treatment with Lawesson's reagent to form compound I

I ser med formlen la, hvor X betyder halogenalkyl-(thiocar- IYou see the formula Ia, where X is haloalkyl (thiocar- I)

binol), eller forbindelsen, hvor X betyder halogenalkylcar- Ibinol), or the compound wherein X is haloalkylcar-I

I 10 bonyl, omsættes med halogeneringsmidler, f.eks. thionylchlo- IIn bonyl, react with halogenating agents, e.g. thionylchlo- I

I rid eller hydrogenbromid, til dannelse af forbindelser med IIn riding or hydrogen bromide, to form compounds with I

I formlen la, hvor X betyder a-halogenalkyl-a-halogenmethyl, IIn the formula Ia, where X is α-haloalkyl-α-halomethyl, I

I idet alle de forudgående trin om ønsket efterfølges af et IIn that all the preceding steps, if desired, are followed by an I

I afbeskyttelsestrin. IIn the deprotection step. IN

I 15 II 15 I

I P4. En fremgangsmåde til fremstilling af forbindelser IIn P4. A process for the preparation of compounds I

I med formlen II of formula I

49 DK 175618 B1 eventuelt beskyttet på passende måde, såfremt dette er nødvendigt, (a) omsættes ifølge fremgangsmåde P]_ (a) til dannelse af forbindelser med formlen Ib, hvor R3 betyder halogen, 5 hvorpå den nævnte forbindelse om ønsket omsættes med et eventuelt substitueret heteroaryl- eller phenylhalogenid, fortrinsvis et bromid eller iodid, i nærværelse af kobber på kendt måde, eller den nævnte forbindelse, i hvilken R3 betyder fortrinsvis bromid eller iodid, dernæst eventuelt 10 omsættes med en eventuelt substitueret phenyl- eller hetero-I aryl-boronsyre i nærværelse af palladium på kendt måde til I dannelse af. forbindelser med formlen Ib, hvor R3 er en even- I tuelt substitueret phenyl- eller heteroarylgruppe, eller en I forbindelse med formlen la, hvor R3 betyder halogen, dernæst 15 omsættes ifølge fremgangsmåde P^ (a) til dannelse af forbin- I delser med formlen Ib, hvor R3 betyder trifluormethyl, I (b) omsættes ifølge fremgangsmåde (b) til dannelse af en forbindelse med formlen Ib, hvor R3 er en bis-{alkyl- I thio)-methylgruppe eller en bis-(arylthio)-methylgruppe, og I 20 eventuelt dernæst en forbindelse med formlen Ib, i hvilken I R3 betyder formyl, {c} omsættes med et eventuelt substitueret phenyl- I eller heteroaryldiazoniumsalt på kendt måde til dannelse af I forbindelser med formlen Ib, hvor R3 betyder eventuelt sub- 25 stitueret phenyl eller heteroaryl, eller I (d) omsættes ifølge fremgangsmåde Ρ-^ίο,ά) til dannelse af forbindelser med formlen Ib, hvor R3 er thiocyanato, I alkylthio, halogenalkylthio, alkenylthio, halogenalkenylthio, phenylthio eller heteroarylthio, hvorpå der eventuelt oxi- 30 deres i overensstemmelse med fremgangsmåde P^ (d) til dannelse I af forbindelserne med formlen Ib, hvor R3 betyder alkylsul- I finyl, alkylsulfonyi, alkenylsulfinyl, alkenylsulfonyl, halogenalkylsulfinyl, halogenalkylsulfonyl, halogenalkenyl- I sulfinyl, halogenalkenylsulfonyl, phenylsulfinyl, phenylsul-Optionally protected, if necessary, (a) reacting according to process P1 (a) to form compounds of formula Ib wherein R3 is halogen, and if desired, said compound is reacted with a optionally substituted heteroaryl or phenyl halide, preferably a bromide or iodide, in the presence of copper in known manner, or said compound, wherein R3 preferably represents bromide or iodide, then optionally reacting with an optionally substituted phenyl or heteroaryl -boronic acid in the presence of palladium in known manner to form. compounds of formula Ib wherein R 3 is an optionally substituted phenyl or heteroaryl group, or a compound of formula Ia, wherein R 3 is halogen, then reacted according to process P 1 (a) to form compounds of Formula Ib wherein R 3 is trifluoromethyl, I (b) is reacted according to process (b) to form a compound of Formula Ib wherein R 3 is a bis (alkyl-thio) methyl group or a bis (arylthio) methyl group and, optionally, then, a compound of formula Ib in which I R 3 means formyl, {c} is reacted with an optionally substituted phenyl-I or heteroaryldiazonium salt in known manner to form I compounds of formula Ib wherein R Or phenyl or heteroaryl, or I (d) is reacted according to process Ρ- ^ ίο, ά) to form compounds of formula Ib wherein R 3 is thiocyanato, I alkylthio, haloalkylthio, alkenylthio, haloalkenylthio, phenylthio or heteroarylthi and optionally oxidized in accordance with process P1 (d) to form I of the compounds of formula Ib wherein R3 is alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkenylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, haloalkenylsulfinyl, haloalkenylsulfonyl, phenylsulfinyl, phenylsulphonyl

I 35 fonyl, heteroarylsulfinyl eller heteroarylsulfonyl, idet XIn phonyl, heteroarylsulfinyl or heteroarylsulfonyl, with X

I ikke er en RS-gruppe, der kan undergå uønsket oxidation, I DK 175618 B1You are not an RS group that can undergo unwanted oxidation, I DK 175618 B1

I BOI BO

og, når X betegner et halogenatom, eventuel behandling med en alkyll'ithium-forbindelse på kendt måde, efterfulgt af behandling med vand og sulfenylering i overensstemmelse med fremgangsmåde P^(c,d) til dannelse af forbindelser med form- H 5 len Ib, hvor X betyder thiocyanato, alkylthio, halogenalkyl- thio, alkenylthio, halogenalkenylthio, phenylthio eller I heteroarylthio.and, when X represents a halogen atom, optionally treating with an alkyl lithium compound in a known manner, followed by treatment with water and sulfenylation according to process P ^ (c, d) to form compounds of the formula H wherein X represents thiocyanato, alkylthio, haloalkylthio, alkenylthio, haloalkenylthio, phenylthio or I heteroarylthio.

P5. En fremgangsmåde til fremstilling af forbindelser IP5. A process for the preparation of compounds I

I 10 med formlen Ib, i hvilken X, X1, X2, X3, χ4 og Y har den II in the formula Ib in which X, X1, X2, X3, χ4 and Y have I

I samme betydning som angivet i forbindelse med fremgangs- IIn the same sense as stated in connection with progress I

måde 1, og R3 betyder hydroxyiminoalkylidenyl, alkoxyimino- Iand R3 is hydroxyiminoalkylidenyl, alkoxyimino-I

I alkylidényl, cyano, halogenalkylcarbonyl eller halogenalkyl- IIn alkylidenyl, cyano, haloalkylcarbonyl or haloalkyl-I

thiocarbonyl eller alkyl, ved hvilken en forbindelse med Ithiocarbonyl or alkyl, wherein a compound of I

15 den almene formel I15 of the general formula I

I x il TCN II x il TCN I

I Η2Ν“<ν^κ3 II Η2Ν “<ν ^ κ3 I

I χΐΧχ4 (XXIX) I 20 x2Jv^L-x3 iI χΐΧχ4 (XXIX) I 20 x2Jv ^ L-x3 i

Y IY I

hvilken R3 betyder formyl eller alkylcarbonyl, og X betyder Iwhich R 3 represents formyl or alkylcarbonyl and X means I

25 cyano eller amino, der om ønsket er beskyttet på passende I25 cyano or amino, which if desired is suitably protected

22

måde, Iway, I

(a) kondenseres med hydroxylamin eller O-alkylhy- I(a) is condensed with hydroxylamine or O-alkyl hy-I

droxylamin eller additionssalte deraf i et opløsningsmiddel, Idroxylamine or addition salts thereof in a solvent, I

33

f.eks. ethanol, til dannelse af en forbindelse med form- Ieg. ethanol to form a compound of Form I

30 len Ib, hvor R3 betyder hydroxyiminoalkylidenyl eller alkoxy- IWherein R3 is hydroxyiminoalkylidenyl or alkoxy-I

44

iminoalkylidenyl, og hvor R3 er hydroxyiminomethylidenyl Iiminoalkylidenyl, and wherein R 3 is hydroxyiminomethylidenyl I

eller alkoxyiminomethylidenyl, idet vand eller en alkohol Ior alkoxyiminomethylidenyl, with water or an alcohol I

om ønsket elimineres i overensstemmelse med fremgangsmåde Iif desired, eliminated in accordance with method I

Pi (b) til dannelse af en forbindelse med formlen Ib, hvor IPi (b) to form a compound of formula Ib wherein I

35 R3 er en cyanogruppe, IR 3 is a cyano group, I

(b) omsættes, når R3 betegner formyl, ifølge frem- I(b) is reacted when R 3 represents formyl according to method I

51 DK 175618 B1 gangsmåde P3(a,b,c,d) til dannelse af en forbindelse med formlen Ib, i hvilken R3 betegner methyl eller halogenalkyl eller halogenalkylcarbonyl eller halogenalkylthiocarbonyl, eller 5 (c), når R3 er formyl, omsættes med et Grignard-rea-B1 procedure P3 (a, b, c, d) to form a compound of formula Ib in which R3 represents methyl or haloalkyl or haloalkylcarbonyl or haloalkylthiocarbonyl, or 5 (c) when R3 is formyl is reacted with a Grignard react

gens, der er afledt af et alkylhalogenid eller en alkyl- Igens derived from an alkyl halide or an alkyl I

lithium-forbindelse, til dannelse af en carbinolforbindelse, Ilithium compound to form a carbinol compound, I

efterfulgt af et dehydratiseringstrin til dannelse af en Ifollowed by a dehydration step to form an I

forbindelse, i hvilken R3 betegner alkenyl, efterfulgt af Icompound in which R 3 represents alkenyl, followed by I

10 reduktion til opnåelse af forbindelser med Ib, hvor R3 beteg- I10 to obtain compounds of Ib, wherein R 3 represents I

ner alkyl, eventuelt efterfulgt af et afbeskyttelsestrin. Ilower alkyl, optionally followed by a deprotection step. IN

Pg. En fremgangsmåde til fremstilling af forbindelser IPg. A process for the preparation of compounds I

med den almene formel Iwith the general formula I

15 I15 I

I ΧΊΓ~Γ0Ν I H2N-iL JLr3I ΧΊΓ ~ Γ0Ν I H2N-iL JLr3

I J (XXXIV) II J (XXXIV) I

I χ1~ΙιΓχ4 II χ1 ~ ΙιΓχ4 I

I 20I 20

I v II v I

I der er nyttige som mellemprodukter, hvor X, X1, X2, X3, X4 IIn which are useful as intermediates wherein X, X1, X2, X3, X4 I

I og Y har den i forbindelse med fremgangsmåde 1 angivne betyd- II and Y have the meaning given in connection with method 1

I 25 ning, og R3 betegner amino, alkylamino, dialkylamino, aral- IAnd R3 represents amino, alkylamino, dialkylamino, aral-I

I kylamino, aminocarbonylamino, alkylcarbonylamino, halogen- I alkylcarbonylamino, arylcarbonylamino, alkylsulfonylamino, I halogenalkylsulfonylamino, alkylaminocarbonylamino, aryl- I aminocarbonylamino, alkoxycarbonylamino, halogenalkoxycar- I 30 bonylamino, alkylidenimino, benzylidenimino, alkoxyalkyliden- imino, dialkylaminoalkylidenimino, alkylthioalkylidenimino I eller azido, ved hvilken en forbindelse med den almene formel 35 I DK 175618 B1 Η I 52In alkylamino, aminocarbonylamino, alkylcarbonylamino, halo- In alkylcarbonylamino, arylcarbonylamino, alkylsulfonylamino, haloalkylsulfonylamino I, alkylaminocarbonylamino, aryl In aminocarbonylamino, alkoxycarbonylamino, halogenalkoxycar- I 30 bonylamino, alkylideneimino, benzylideneimino, alkoxyalkyliden- imino, dialkylaminoalkylideneimino, alkylthioalkylideneimino or azido I, by which is a compound of the general formula 35 I DK 175618 B1 Η I 52

I xTTXCNIn xTTXCN

HjnA^JLno,HjnA ^ JLno,

H NH N

I x1—r^W-x4 {xxx) I 5 x24nJ-x3 I *I x1-r ^ W-x4 {xxx) I 5 x24nJ-x3 I *

I i hvilken aminogruppen er beskyttet på passende måde, redu- IIn which the amino group is suitably protected, I-

I ceres til dannelse af forbindelser med den almene, formel II ceres to form compounds of the general formula I

10 XXXIV, hvor R3 betegner amino, hvilke forbindelser omsættes IWherein R3 represents amino, which compounds are reacted I

I ' (a) med egnede alkyleringsmidler i organiske opløs- II '(a) with suitable alkylating agents in organic solvents

I ningsmidler, idet den dannede mono- eller disubstituerede IIn composition agents, the mono- or disubstituted I formed

aminogruppe fås afhængigt af det støkiometriske forhold Iamino group is obtained depending on the stoichiometric ratio I

I eller reaktionsbetingelserne eller ved omdannelse af amino- II or reaction conditions or by conversion of amino-I

I 15 gruppen til en alkoxyalkylideniminogruppe, efterfulgt af IIn the group of an alkoxyalkylideneimino group, followed by I

I reduktion til dannelse af forbindelser med formlen XXXIV, i IIn reduction to form compounds of formula XXXIV, in I

I hvilken R3 betyder alkylamino, dialkylamino eller aralkyl- IIn which R 3 is alkylamino, dialkylamino or aralkyl-I

I amino, IIn amino, I

I (b) med phosgen, efterfulgt af ammoniak, til dannelse II (b) with phosgene, followed by ammonia, to form I

I 20 af en forbindelse med formlen XXXIV, i hvilken R3 betyder IIn a compound of formula XXXIV in which R3 means I

aminocarbonylamino, Iaminocarbonylamino, I

(c) med alkylsyrechlorider eller halogenalkylsyrechlo- I(c) with alkyl acid chlorides or haloalkyl acid chloro-I

rider eller arylsyrechlorider eller anhydrider deraf, even- Irides or arylic acid chlorides or their anhydrides, even- I

tuelt i nærværelse af opløsningsmiddel og/eller organiske Iin the presence of solvent and / or organic I

25 syreacceptorer til dannelse af en forbindelse med formlen I25 acid acceptors to form a compound of formula I

XXXIV, i hvilken R3 betyder alkylcarbonylamino, halogenalkyl- IXXXIV, wherein R3 is alkylcarbonylamino, haloalkyl-I

carbonylamino eller arylcarbonylamino, Icarbonylamino or arylcarbonylamino, I

(d) med alkyl- eller halogenalkylsulfonylhalogenider I(d) with alkyl or haloalkylsulfonyl halides I

eller anhydrider deraf under passende betingelser til opnå- Ior anhydrides thereof under appropriate conditions to obtain I

30 else af forbindelser med formlen XXXIV, i hvilken R3 betyder I30 of compounds of formula XXXIV in which R3 means I

alkylsulfonylamino eller halogenalkylsulfonylamino, Ialkylsulfonylamino or haloalkylsulfonylamino, I

(e) med alkyl- eller arylisocyanater på kendt måde I(e) with alkyl or aryl isocyanates in known manner I

til opnåelse af forbindelser med formlen XXXIV, hvor R3 Ito obtain compounds of formula XXXIV wherein R3 is I

betegner (alkylamino eller arylamino)-carbonylamino, Irepresents (alkylamino or arylamino) -carbonylamino, I

35 (f) med et alkylchlorformiat eller halogenalkylchlor- I(F) with an alkyl chloroformate or haloalkyl chloro-I

formiat på kendt måde til dannelse af forbindelser med form- Iformate in known manner to form compounds of form I

DK 175618 B1 IDK 175618 B1 I

I 53 II 53 I

I len XXXIV, hvor R3 betyder alkoxycarbonylamino eller halogen- IIn lane XXXIV, where R3 is alkoxycarbonylamino or halogen-I

I alkoxycarbonylamino, IIn alkoxycarbonylamino, I

I (g) med et alkyl- eller arylaldehyd på kendt måde II (g) with an alkyl or aryl aldehyde in known manner I

I til dannelse af forbindelser med formlen XXXIV, i hvilken II to form compounds of formula XXXIV in which I

I 5 R3 betyder alkylidenimino eller benzylidenimino, IIn R 3, alkylidenimino or benzylidenimino, I

I (h) med en alkylorthoester til dannelse af en forbin- II (h) with an alkyl orthoester to form a compound I

I delse med formlen XXXIV, i hvilken R3 betyder alkoxyalkyli- IIn the compound of formula XXXIV, wherein R3 is alkoxyalkyl-I

I denimino, ' IIn denimino, 'I

I (i) med et Ν,Ν-dialkylformamid- eller dialkylacetal- II (i) with a Ν, Ν-dialkylformamide or dialkyl acetal-I

I 10 -derivat deraf til dannelse af forbindelser med formlen II 10 derivative thereof to form compounds of formula I

I XXXIV, i hvilken R3 betyder dialkylaminoalkylidenimino, IIn XXXIV, wherein R3 is dialkylaminoalkylidenimino, I

I (j) med en tris-(alkylthio)-methan i et organisk II (j) with a tris (alkylthio) methane in an organic I

I opløsningsmiddel til dannelse af forbindelser med formlen IIn solvent to form compounds of formula I

I XXXIV, i hvilken R3 betyder alkylthioalkylidenimino, eller IIn XXXIV, wherein R3 is alkylthioalkylidenimino, or I

I .15 (k) med p-toluensulfonyl-azid på kendt måde eller II .15 (k) with p-toluenesulfonyl azide in known manner or I

I ved omdannelse til et diazoniumsalt, efterfulgt af reduktion II by conversion to a diazonium salt, followed by reduction I

I til en hydrazinogruppe, efterfulgt af behandling med sal- II to a hydrazino group, followed by treatment with sal-I

I petersyre til dannelse af en forbindelse med formlen XXXIV, IIn nitric acid to give a compound of formula XXXIV, I

I i hvilken R3 er en azidogruppe, efterfulgt af et afbeskyttel- IIn which R 3 is an azido group, followed by a deprotection I

I 20 sestrin, såfremt et sådant er nødvendigt. IIn 20 stages, if necessary. IN

I P7. En fremgangsmåde til fremstilling af en forbin- IIn P7. A method of preparing a compound I

I delse med formlen Ib, i hvilken X, X1, X2, X3, X4 og Y har I den i forbindelse med fremgangsmåde 1 angivne betydning, og 25 R3 betyder cyanato, alkoxy eller halogenalkoxy, ved hvilken I en forbindelse med den almene formelIn the compound of formula Ib, in which X, X1, X2, X3, X4 and Y have the meaning given in connection with process 1, and R3 is cyano, alkoxy or haloalkoxy, wherein in a compound of the general formula

I XTTCNIn XTTCN

I - - η2ν-^νΛ-οη I 30 x’JLx* (XXXI) I x2 Jyj-X3I - - η2ν- ^ νΛ-οη I 30 x'JLx * (XXXI) I x2 Jyj-X3

I YI Y

I 35 i hvilken amino, cyano og X eventuelt er beskyttet på pas- I sende måde, omsættes i overensstemmelse med fremgangsmåde I DK 175618 B1 I 54 iIn which amino, cyano and X are optionally protected suitably, react in accordance with method I

P2(a), (b), (c), til dannelse af en forbindelse med formlen IP2 (a), (b), (c) to form a compound of formula I

I Ib, i hvilken R3 er cyanato, alkoxy eller halogenalkoxy. IIn Ib, wherein R 3 is cyano, alkoxy or haloalkoxy. IN

I Pg. En fremgangsmåde til fremstilling af forbindelser IIn Pg. A process for the preparation of compounds I

I 5 med formlen II of formula I

I £ΓΧ£I £ ΓΧ £

N IN I

I , I , (IC) II, I, (IC) I

I 10 xaiin:$I 10 xaiin: $

x2—IX2-I

I y II y I

I i hvilken X, R3, X1, X2, X3, X4 og Y har den i forbindelse IIn which X, R3, X1, X2, X3, X4 and Y have it in compound I

I . 15 med fremgangsmåde 1 angivne betydning, og R1 betyder hydro- II. 15 with the meaning of process 1 and R1 means hydro-I

gen, halogen, thiocyanato, alkylthio, halogenalkylthio, Igene, halogen, thiocyanato, alkylthio, haloalkylthio, I

I alkenylthio, halogenalkenylthio, phenylthio, heteroarylthio, IIn alkenylthio, haloalkenylthio, phenylthio, heteroarylthio, I

alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkenylsul- Ialkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkenylsul-I

I fonyl, halogenalkylsulfinyl, halogenalkylsulfony 1, halogen- IIn phonyl, haloalkylsulfinyl, haloalkylsulfony 1, halogen-I

20 alkenylsulf inyl, halogenalkenylsulfonyl, phenyl sul f inyl, IAlkenylsulfonyl, halogenalkenylsulfonyl, phenylsulfinyl, I

phenylsulf onyl, heteroarylsulf inyl, heteroaryl sul fonyl, Iphenylsulfonyl, heteroarylsulfonyl, heteroaryl sulphonyl, I

eventuelt substitueret phenyl eller heteroaryl, alkylcar- Ioptionally substituted phenyl or heteroaryl, alkylcar-I

bonyl, alkylamino, dialkylamino, aralkylamino, aminocar- Ibonyl, alkylamino, dialkylamino, aralkylamino, aminocarl

bonylamino, al kyl carbonyl amino, halogenalkylcarbonylamino, Ibonylamino, alkyl carbonyl amino, haloalkylcarbonylamino, I

25 arylcarbonylamino, al kyl sul fonyl amino, hal ogenalkyl sul fonyl- IArylcarbonylamino, alkyl sulphonyl amino, haloalkyl sulphonyl-I

amino, alkylaminocarbonylamino, arylaminocarbonylamino, Iamino, alkylaminocarbonylamino, arylaminocarbonylamino, I

alkoxycarbonylamino, halogenalkoxycarbonylamino, alkyliden- Ialkoxycarbonylamino, haloalkoxycarbonylamino, alkylidene-I

imino, benzylidenimino, alkoxyalkylidenimino, dialkylamino- Iimino, benzylidenimino, alkoxyalkylidenimino, dialkylamino-I

alkylidenimino, alkylthioalkylidenimino, azido, bis-(alkyl- Ialkylidenimino, alkylthioalkylidenimino, azido, bis- (alkyl- I

30 thio eller arylthio)-methyl, formyl, halogenalkylcarbonyl, IThio or arylthio) methyl, formyl, haloalkylcarbonyl, I

halogenalkylthiocarbonyl, halogenalkyl eller alkyl, ved Ihaloalkylthiocarbonyl, haloalkyl or alkyl, at I

hvilken en forbindelse med den almene formel Iwhich is a compound of general formula I

35 I35 I

DK 175618 B1 I 55 xttcn I pi I . ^-A-X4 (Ib) eller (XXXIV) 5 x2-1Utx3 I y I fremstillet ifølge fremgangsmåde P4-P7, hvor aminogruppen I er afbeskyttet, efter beskyttelse af X, R3 eller cyanogrup- I 10 pen, såfremt dette er nødvendigt, I (a) omsættes med et diazoteringsmiddel, fortrinsvis I med et alkylnitrit, i et indifferent opløsningsmiddel til I dannelse af en forbindelse med formlen Ic, i hvilken R1 I betyder H, I 15 (b) omsættes med et diazoteringsmiddel, fortrinsvis I med et alkylnitrit, i nærværelse af en halogen-donor til I dannelse af en forbindelse med formlen Ic, hvor R1 betyder I halogen, hvorefter denne forbindelse om ønsket omsættes med I et Grignard-reagens eller et lithiumderivat, efterfulgt af I 20 omsætning med et aliphatisk syrechlorid eller -anhydrid I deraf til omdannelse til en forbindelse med formlen Ic, i I hvilken R1 betyder alkylcarbonyl, eller omsætning af den nævnte forbindelse ifølge fremgangsmåde P4(a) til dannelse I af forbindelser med formlen Ic, i hvilken betyder phenyl I 25 eller heteroaryl, I (c) omsættes med et diazoteringsmiddel, fortrinsvis I med et alkylnitrit, i nærværelse af (SCN)2 eller et disulfid I i et opløsningsmiddel, f.eks. chloroform, til dannelse af I forbindelser med formlen Ic, hvor R1 betyder thiocyanato, I 30 alkylthio, halogenalkylthio, alkenylthio, halogenalkenylthio, I phenylthio eller heteroarylthio, hvorefter der eventuelt I oxideres i overensstemmelse med fremgangsmåde P^(d) til I dannelse af en forbindelse med formlen Ic, i hvilken R1 I betyder alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alke- I 35 nylsulfonyl, halogenalkylsulfinyl, halogenalkylsulfonyl, I halogenalkenylsulfinyl, halogenalkenylsulfonyl, phenylsul-DK 175618 B1 I 55 xttcn I pi I. Β -A-X4 (Ib) or (XXXIV) 5 x2-1Utx3 I y I prepared according to method P4-P7, wherein the amino group I is deprotected, after protection of the X, R3 or cyanogroup, if necessary, I (a) is reacted with a diazotizing agent, preferably I with an alkyl nitrite, in an inert solvent to form a compound of formula Ic in which R 1 is H, I (b) is reacted with a diazotizing agent, preferably I with a alkyl nitrite, in the presence of a halogen donor to form a compound of formula Ic, wherein R 1 means I halogen, and if desired, this compound is reacted with I a Grignard reagent or lithium derivative, followed by reaction with an aliphatic acid chloride or anhydride I thereof for conversion to a compound of formula Ic, in which R 1 is alkylcarbonyl, or reacting said compound according to process P4 (a) to form I of compounds of formula Ic, wherein phenyl In I or heteroaryl, I (c) is reacted with a diazotizing agent, preferably I with an alkyl nitrite, in the presence of (SCN) 2 or a disulfide I in a solvent, e.g. chloroform, to form I compounds of formula Ic, wherein R 1 compound of formula Ic wherein R 1 represents alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkenylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, halogenalkenylsulfinyl, halogenalkenylsulfonyl, phenylsulfonyl,

I DK 175618 B1 II DK 175618 B1 I

I 56 II 56 I

I sulfonyl, IIn sulfonyl, I

I (d) omsættes ifølge fremgangsmåde Pg (a-k) til dannelse II (d) is converted according to process Pg (a-k) to form I

I af forbindelser med formlen Ic, i hvilken R1 betyder alkyl- II of compounds of formula Ic in which R 1 is alkyl-I

I 5 amino, dialkylamino, aralkylamino, aminocarbonylamino, alkyl- IIn amino, dialkylamino, aralkylamino, aminocarbonylamino, alkyl-I

carbonyl amino, halogenalkylcarbonylamino, airylcarbonylamino, Icarbonyl amino, haloalkylcarbonylamino, airylcarbonylamino, I

I alkylsulfonylamino, halogenalkylsulfonylamino, alkylamino- IIn alkylsulfonylamino, haloalkylsulfonylamino, alkylamino-I

I carbonylamino, arylaminocarbonylamino, alkoxycarbonylamino, IIn carbonylamino, arylaminocarbonylamino, alkoxycarbonylamino, I

I halogenalkoxycarbonylamino, alkylidenimino, benzylidenimino, IIn haloalkoxycarbonylamino, alkylidenimino, benzylidenimino, I

I 10 alkoxyalkylidenimino, dialkylaminoalkylidenimino, alkyl- IIn alkoxyalkylideneimino, dialkylaminoalkylideneimino, alkyl-I

thioalkylidenimino eller azido, eller Ithioalkylidenimino or azido, or I

I -(e) omsættes med natriumnitrit og formaldoxim, kobber- II - (e) react with sodium nitrite and formaldexime, copper I

I sulfat og HC1 på kendt måde til dannelse af forbindelser IIn sulfate and HCl in known manner to form compounds I

I med formlen Ic, i hvilken R1 betyder formyl, hvorefter man II with the formula Ic, in which R 1 means formula, after which I

I 15 om ønsket (i) omsætter med et alkyl-Grignard-reagens og II if desired (i) react with an alkyl-Grignard reagent and I

I derpå oxiderer til omdannelse til forbindelser med form- IYou then oxidize to convert into compounds of Form I

I len Ic, i hvilken R1 betyder alkylcarbonyl, fii) omsætter IIn the case of Ic, in which R 1 is alkylcarbonyl, i) reactor I

I ifølge fremgangsmåde P5 til dannelse af en forbindelse med II according to method P5 to form a compound with I

I formlen Ic, hvor R1 betyder -hydroxyiminoalkylidenyl, alkoxy- IIn the formula Ic, wherein R 1 is -hydroxyiminoalkylidenyl, alkoxy-I

I 20 iminoalkylidenyl eller cyano, eller (iii) omsættes ifølge IIn 20 iminoalkylidenyl or cyano, or (iii) react according to I

I fremgangsmåde P3(a-d) til dannelse af en forbindelse med IIn process P3 (a-d) to form a compound of I

I formlen Ic, hvor R1 betyder halogenalkylcarbonyl, halogen- IIn the formula Ic, wherein R 1 is haloalkylcarbonyl, halogen-I

I alkylthiocarbonyl, halogenalkyl eller alkyl, om ønsket efter- IIn alkylthiocarbonyl, haloalkyl or alkyl, if desired, post-I

I fulgt af et afbeskyttelsestrin, eller den ovennævnte forbin- IFollowed by a deprotection step, or the aforementioned compound

I 25 delse, i hvilken R* betyder formyl, på kendt måde omdannes IIn a form in which R * means formula, in a known manner, I is converted

I til en forbindelse med formlen Ic, i hvilken R^ betyder II to a compound of formula Ic in which R 1 is I

I bis-(alkylthio eller arylthio)-methyl. IIn bis (alkylthio or arylthio) methyl. IN

I 35 II 35 I

P9. En fremgangsmåde til fremstilling af forbindelser IP9. A process for the preparation of compounds I

I 3 0 med formlen Ic, i hvilken X, R2, X1, X3, X2, X4 og Y har II of the formula Ic in which X, R2, X1, X3, X2, X4 and Y have I

22

I R1 betyder cyarlato, alkoxy eller halogenalkoxy, ved hvilken IIn R 1, cyarlato means alkoxy or haloalkoxy, wherein I

33

I den i forbindelse med fremgangsmåde 1 angivne betydning, og IIn the meaning of method 1, and I

44

I en forbindelse med den almene formel IIn a compound of the general formula I

57 I57 I

DK 175618 B1 »TT£DK 175618 B1 »TT £

N ^ IN ^ I

χΙ-As-X* (XXXII)χΙ-As-X * (XXXII)

5 XSJ^J-X3 I5 XSJ ^ J-X3 I

Y IY I

i hvilken X, cyano eller R3 eventuelt er beskyttet på kendt Iwherein X, cyano or R3 are optionally protected in known I

måde, omsættes ifølge fremgangsmåde P2(a,b,c) til dannelse Imethod, is reacted according to process P2 (a, b, c) to form I

10 af en forbindelse med formlen Ic, i hvilken R1 betyder cya- I10 of a compound of formula Ic in which R1 represents cyano-I

nato, alkoxy eller halogenalkoxy, efterfulgt af et eventuelt Inato, alkoxy or haloalkoxy, followed by an optional I

afbeskyttelsestrin. Ideprotection step. IN

P^q. En fremgangsmåde til fremstilling af forbindelser I 15 med formlen I, i hvilken X, R1, R3, X1, X2, X3, X4 og Y har I den i forbindelse med fremgangsmåde 1 angivne betydning, og I R2 betyder CHO, ved hvilken en forbindelse med formlen Ic I behandles med et reduktionsmiddel, fortrinsvis diisobutyl- I aluminiumhydrid, i et opløsningsmiddel til dannelse af en I 20 forbindelse, i hvilken R2 betegner CHO, hvilken forbindelse I eventuelt oxideres på kendt måde til dannelse af den tilsva- I rende forbindelse med formlenP ^ q. A process for the preparation of compounds I of formula I in which X, R1, R3, X1, X2, X3, X4 and Y have the meaning given in connection with process 1 and I R2 means CHO wherein a compound of the formula Ic I is treated with a reducing agent, preferably diisobutyl-aluminum hydride, in a solvent to form a compound, in which R 2 represents CHO, which compound I is optionally oxidized in the known manner to form the corresponding compound with formula

xTTCOlHxTTCOlH

I. <xxxv) I y I 30 I pll· En fremgangsmåde til fremstilling af forbindelser I med formlen I, i hvilken X, R^, R3, X1, X2, X3, X4 og Y har den i forbindelse med fremgangsmåde 1 angivne betydning, og R2 betyder hydroxyiminoalkylideny1, alkoxyiminoalkylidenyl, I 35 halogenalkylcarbonyl, halogenalkylthiocarbonyl, alkyl, halo- 2 I genalkyl, bis-(alkylthio eller arylthio)-methyl eller cyano, I DK 175618 B1 I 58 I ved hvilken en forbindelse med formlen I, i hvilken R2 bety-A process for preparing compounds I of formula I in which X, R 2, R 3, X 1, X 2, X 3, X 4 and Y have the meaning given in connection with process 1 and R 2 is hydroxyiminoalkylidenyl, alkoxyiminoalkylidenyl, haloalkylcarbonyl, haloalkylthiocarbonyl, alkyl, haloalkyl, bis- (alkylthio or arylthio) methyl or cyano, wherein a compound of formula I, in which R2 means

H dér CHO, efter eventuel beskyttelse af X, R1 eller R3 på IH there CHO, after possible protection of X, R1 or R3 on I

I kendt måde, omsættes ifølge fremgangsmåde P3(a,b,c,d), IIn known manner, according to method P3 (a, b, c, d), I are reacted

I p5(a,b) eller P8(e), efterfulgt af et afbeskyttelsestrin, IIn p5 (a, b) or P8 (e), followed by a deprotection step, I

5 såfremt dette er nødvendigt. I5 if this is necessary. IN

I ^12· En fremgangsmåde til fremstilling af forbindelser IA process for the preparation of compounds I

med formlen I, i hvilken X, R1, R3, X1, X2, X3, X4 og Y har Iof formula I in which X, R1, R3, X1, X2, X3, X4 and Y have I

den i forbindelse med fremgangsmåde 1 angivne betydning, og Ithe meaning given in connection with method 1, and I

10 R2 betegner amino, alkylamino, dialkylamino, aralkylamino, IR 2 represents amino, alkylamino, dialkylamino, aralkylamino, I

I aminocarbonylamino, al kyl carbonyl amino, halogenalkylcar- IIn aminocarbonylamino, alkyl carbonyl amino, haloalkylcarl

I bonylamino, arylcarbonylamino, alkylsulfonylamino, halogen- IIn bonylamino, arylcarbonylamino, alkylsulfonylamino, halogen-I

I alkylsulfonylamino, alkylaminocarbonylamino, arylaminocar- IIn alkylsulfonylamino, alkylaminocarbonylamino, arylaminocarl

bonylamino, alkoxycarbonylamino, halogenalkoxycarbonylamino, Ibonylamino, alkoxycarbonylamino, haloalkoxycarbonylamino, I

I 15 alkylidenimino, benzylidenimino, alkoxyalkylidenimino, dial- IIn alkylideneimino, benzylideneimino, alkoxyalkylideneimino, dial-I

I kylaminoalkyl idenimino, alkyl thioalkyl idenimino, azido, IIn chylaminoalkyl idenimino, alkyl thioalkyl idenimino, azido, I

hydrogen, halogen, thiocyanato, alkylthio, halogenalkylthio, Ihydrogen, halogen, thiocyanato, alkylthio, haloalkylthio, I

I alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkenylsul- IIn alkylsulfinyl, alkylsulfonyl, alkenylsulfinyl, alkenylsul-I

I 20 fonyl, halogenalkylsulfinyl, halogenalkylsulfonyl, halogen- IIn phonyl, haloalkylsulfinyl, haloalkylsulfonyl, halogen-I

I alkenylsulfinyl, halogenalkenylsulfonyl, phenylsulfinyl, IIn alkenylsulfinyl, haloalkenylsulfonyl, phenylsulfinyl, I

I phenylsulf onyl, heteroarylsulfinyl, heteroaryl sul fonyl, IIn phenylsulfonyl, heteroarylsulfinyl, heteroaryl sulphonyl, I

I eventuelt substitueret phenyl eller heteroaryl eller tri- IIn optionally substituted phenyl or heteroaryl or tri-I

fluormethyl, ved hvilken en forbindelse med formlen XXXV, Ifluoromethyl, wherein a compound of formula XXXV, I

I 25 efter eventuel beskyttelse af X, R1 eller R3, såfremt dette II 25 after any protection of X, R1 or R3, if this I

I er nødvendigt, på kendt måde omsættes under betingelserne IYou are required, in a known manner, to react under conditions I

I for Curtius-omlejringen, f.eks. ved omdannelse til et syre- IIn for the Curtius rearrangement, e.g. upon conversion to an acid I

I chlorid, efterfulgt af omsætning med et alkalimetalazid, IIn chloride, followed by reaction with an alkali metal azide, I

eller med diphenylphosphorylazid, i nærværelse af en organisk Ior with diphenylphosphoryl azide, in the presence of an organic I

30 base, f.eks. triethylamin, i et alkoholisk opløsningsmiddel, I30 base, e.g. triethylamine, in an alcoholic solvent, I

til dannelse af et carbamat, som derefter kan hydrolyseres Ito form a carbamate which can then be hydrolyzed I

til dannelse af den tilsvarende forbindelse, i hvilken R2 Ito form the corresponding compound in which R2 I

betegner amino, som derpå eventuelt omsættes ifølge frem- Irepresents amino which is then optionally reacted according to formula I

gangsmåde P6{a-k) eller Pg(a-c), hvorefter, når R2 betyder Iprocedure P6 {a-k) or Pg (a-c), then when R2 means I

35 halogen, der eventuelt omsættes ifølge fremgangsmåde P4(a), I35 halogen optionally reacted according to process P4 (a), I

efterfulgt af et afbeskyttelsestrin, såfremt dette er nød- Ifollowed by a deprotection step, if necessary

DK 175618 B1 I 59DK 175618 B1 I 59

I vendigt. IIn turn. IN

I £*13- En fremgangsmåde til fremstilling af forbindelser IA process for the preparation of compounds I

I med formlen I, i hvilken X, R1, R3, X1, X2, X3, X4 og Y har II of formula I wherein X, R1, R3, X1, X2, X3, X4 and Y have I

I 5 den i forbindelse med fremgangsmåde 1 angivne betydning, og IIn the meaning given in connection with method 1, and I

I R2 betyder cyanato, alkoxy eller halogenalkoxy, ved hvilken IIn R 2 is cyanato, alkoxy or haloalkoxy, by which I

I en forbindelse med den almene formel IIn a compound of the general formula I

I X-T-T~OHIn X-T-T ~ OH

I 10 R1-T1-R3 I (XXXVI)I R1-T1-R3 I (XXXVI)

I X2—VjjJ-X3 II X2 — VjjJ-X3 I

I γ II γ I

I 15 II 15 I

I efter eventuel beskyttelse af X-, R1- eller R3-grupperne, IAfter any protection of the X, R1 or R3 groups, I

såfremt dette er nødvendigt, omsættes ifølge fremgangsmå- Iif necessary, react according to method I

I de P7, efterfulgt af et afbeskyttelsestrin, såfremt dette IIn the P7, followed by a deprotection step, if this I

er nødvendigt. Iis required. IN

I 20 II 20 I

I p14 · En fremgangsmåde til fremstilling af forbindelser IA process for the preparation of compounds I

I med formlerne XXVIII, XXXI, XXXVI og XXXVII ifølge frem- I gangsmåderne Ρ2» P7, P^q eller P13, ved hvilken den tilsva- I rende halogenerede forbindelse ifølge fremgangsmåde P^(a) , I 25 P4(a), Pg(b) eller P^» efter beskyttelse af aminogruppen, I såfremt denne er til stede, omdannes til et Grignard-reagens I eller lithiumderivat, efterfulgt af omsætning med et tri- I alkylborat og oxidation på kendt måde, efterfulgt af et I afbeskyttelsestrin, såfremt dette er nødvendigt.I of formulas XXVIII, XXXI, XXXVI and XXXVII according to processes Ρ2 »P7, P ^ q or P13, wherein the corresponding halogenated compound according to process P ^ (a), I P4 (a), Pg (b) or P 1, after protection of the amino group, if present, is converted to a Grignard reagent I or lithium derivative, followed by reaction with a tri-L alkylborate and oxidation in a known manner, followed by a I deprotection step if necessary.

I 30 I p15· En fremgangsmåde til fremstilling af en forbin- I delse med formlen 35 I DK 175618 B1 I' 60 ' I ·£ζΓ" I χ!-νΛ*_χ4 (III) I 5 X2-JILx3 I * H i hvilken X1, X2, X3, X4 og Y har den i forbindelse med formlen I angivne betydning, ved hvilken et dicyanopropen- 10 -derivat med den almene formelA process for the preparation of a compound of formula 35 I I · 60 £ I £ Λ I I I χ! -ΝΛ * _χ4 (III) I 5 X2-JILx3 I * H which X1, X2, X3, X4 and Y have the meaning given in connection with formula I, in which a dicyanopropylene derivative of the general formula

I NH -CH rC—CH2—CNIn NH -CH rC-CH2-CN

I x*—CN (IV) I is x*Jy-x3I x * —CN (IV) I is x * You-x3

I YI Y

I omsættes med et basisk middel. IYou react with a basic agent. IN

I 20 P16. Opfindelsen angår også forbindelser med form- II 20 P16. The invention also relates to compounds of formula I

I lerne III og XXVIII til XXXVII, hvor de forskellige sub- IIn clays III and XXVIII to XXXVII, where the various sub- I

I stituenter har samme betydning som ved de tidligere frem- IIn statuary the same meaning as in previous studies

gangsmåder, hvilke forbindelser navnlig er anvendelige som Imethods which compounds are particularly useful as I

mellemproduktforbindelser til fremstilling af forbindelser Iintermediate compounds for the preparation of compounds I

25 med formlen I ifølge fremgangsmåderne P1-P15· I25 of formula I according to methods P1-P15 · I

Andre fremgangsmåder IOther Methods I

Forbindelser med formlen I, i hvilken X er en per- ICompounds of formula I in which X is a per-I

30 halogenalkylthiogruppe, fremstilles yderligere ved den føl- I30 haloalkylthio group, is further prepared by the following

gende chlorsulfoneringsmetode, reduktion til et disulfid og Iby chlorosulfonation method, reduction to a disulfide and I

til slut fri radikal-fremmet reduktion. Fremgangsmåden udfø- Ifinally free radical-induced reduction. The procedure is carried out

res på følgende måde: Iis as follows:

A) Forbindelser med den almene formel XXXIX, jvf. IA) Compounds of general formula XXXIX, cf.

35 det følgende, i hvilken R1, R2, R3, Y, X1, X2, X3 og X4 har I35 in which R1, R2, R3, Y, X1, X2, X3 and X4 have I

de betydninger, der er angivet ovenfor i forbindelse med Ithe meanings given above in connection with I

DK 175618 B1 IDK 175618 B1 I

61 I61 I

I formel I, kan fremstilles ud fra forbindelser med den almene IIn formula I, can be prepared from compounds of the general I

I formel XXXVIII, jvf. det følgende, i hvilken X betegner IIn formula XXXVIII, cf. the following, in which X represents I

I hydrogen, ved behandling med chlorsulfonsyre, enten i ren IIn hydrogen, by treatment with chlorosulfonic acid, either in pure I

I form eller i nærværelse af et organisk opløsningsmiddel, IIn the form or in the presence of an organic solvent,

I 5 f.eks. chloroform, dichlormethan, carbontetrachlorid eller IIn 5 e.g. chloroform, dichloromethane, carbon tetrachloride or I

I dimethyl formamid, ved en reaktionstemperatur fra 0 til 150°C. IIn dimethyl formamide, at a reaction temperature of 0 to 150 ° C. IN

I Et mere specifikt eksempel, er fremstillingen af en forbin- IIn a more specific example, the preparation of a compound I

I delse med den almene formel XXXIX, jvf. det følgende, i IIn accordance with the general formula XXXIX, cf.

I hvilken R1 betyder amino, alkylcarbonylamino eller halogen- IIn which R1 represents amino, alkylcarbonylamino or halogen-I

I 10 alkylcarbonylamino, R2 er cyano, og R2 er hydrogen, ud fra IIn 10 alkylcarbonylamino, R 2 is cyano and R 2 is hydrogen from I

I forbindelser med den almene formel XXXVIII, i hvilken R1 er IIn compounds of the general formula XXXVIII in which R1 is I

I amino, alkylcarbonylamino eller halogenalkylcarbonylamino, IIn amino, alkylcarbonylamino or haloalkylcarbonylamino, I

I R2 er cyano, R2 er hydrogen, og X er hydrogen, ved behandling IIn R 2, cyano, R 2 is hydrogen, and X is hydrogen, by treatment I

I med chlorsulfonsyre. En repræsentativ fremgangsmåde til IIn with chlorosulfonic acid. A representative approach to I

I 15 chlorsulfonering af en aromatisk forbindelse er angivet af IIn chlorosulfonation of an aromatic compound is indicated by I

I J. March, "Advanced Organic Chemistry", McGraw-Hill publ. IIn J. March, "Advanced Organic Chemistry," McGraw-Hill publ

I (1968), side 402. II (1968), page 402. I

I x_nrR2 cl02S_ii—irR2 II x_nrR2 cl02S_ii — irR2 I

I 20 R'—CISO3H Rl—tN^-R3 II R 1 -CISO 3 H R 1 -N N 1 -R 3 I

I x2^SlS x’7[tS:^ II x2 ^ SlS x'7 [tS: ^ I

x2—x2-t^i-x3 Ix2-x2-t ^ i-x3 I

I y y I 25 (XXXVni) (XXXIX)I y y I 25 (XXXVni) (XXXIX)

Forbindelser med den almene formel XL, jvf. det føl- I gende, i hvilken R1, R2, Y, X^-, X2, X2 og X4 har de betyd- I 30 ninger, der er angivet ovenfor i forbindelse med formel I, I kan fremstilles ud fra forbindelser med den almene formel I XXXIX, i hvilken R2 betyder hydrogen, ved behandling med et I chloreringsmiddel, f.eks. chlor, N-chlorsuccinimid eller 2 I sulfurylchlorid, i et organisk opløsningsmiddel, f.eks.Compounds of general formula XL, cf. the following, in which R1, R2, Y, X4, X2, X2 and X4 have the meanings given above in connection with formula I, You can be prepared from compounds of general formula I XXXIX, in which R 2 is hydrogen, by treatment with a chlorinating agent, e.g. chlorine, N-chlorosuccinimide or 2 L sulfuryl chloride, in an organic solvent, e.g.

3 I 35 diethylether, acetonitril eller dichlormethan, ved en reak- 4 I tionstemperatur fra -70 til 25°C. Et mere specifikt eksempel I DK 175618 B13 in 35 diethyl ether, acetonitrile or dichloromethane, at a reaction temperature of 4 liters from -70 to 25 ° C. A more specific example in DK 175618 B1

I 62 II 62 I

er fremstillingen af en forbindelse med den almene formel XL, H i hvilken R1 betyder amino, alkylamido eller halogenalkyl- amido, og R2 er cyano, ved behandling af en forbindelse med den almene formel XXXIX, i hvilken R1 betyder amino, alkyl-is the preparation of a compound of general formula XL, H in which R 1 is amino, alkylamido or haloalkylamido, and R 2 is cyano, by treatment of a compound of general formula XXXIX wherein R 1

I 5 carbonylamino eller halogenalkylcarbonylamino, og R2 er IIn 5 carbonylamino or haloalkylcarbonylamino and R2 is I

I cyano, og R3 er hydrogen, med sulfurylchlorid i diethylether I ved -40 °C: I CJ02S r n—R2 C102S-T- -pR2 10 Rl-41 ji-R3 . Rl-JL JLdIn cyano, and R 3 is hydrogen, with sulfuryl chloride in diethyl ether I at -40 ° C: I CJO 2 S r n-R 2 C 10 Rl-JL JLd

H ehlorerlngsmiddel ^ IHydrochloride agent

I : ΊώI: Ίώ

I Y Y II Y Y I

I 15 (XXXIX) QCL)I (XXXIX) QCL)

B) Forbindelser med den almene formel XLI, jvf. det IB) Compounds of general formula XLI, cf.

følgende, i hvilken R1, R2, Y, X1, X2, X3 og X4 har de betyd- Ithe following, in which R1, R2, Y, X1, X2, X3 and X4 have the meaning

20 ninger, der er angivet ovenfor i forbindelse med formel I, I20 as defined above in connection with Formula I, I

kan fremstilles ud fra forbindelser med den almene formel Imay be prepared from compounds of general formula I

XXXIX ved behandling med et reduktionsmiddel, f.eks. triphe- IXXXIX by treatment with a reducing agent, e.g. triphe- I

nylphosphin, i nærværelse af et organisk opløsningsmiddel,. Inylphosphine, in the presence of an organic solvent,. IN

f.eks. tetrahydrofuran, toluen eller dichlormethan, ved en Ieg. tetrahydrofuran, toluene or dichloromethane, at an I

22

25 reakt ions temperatur fra 0 til 110°C. Et mere specifikt eksem- IThe reaction temperature is from 0 to 110 ° C. A more specific example

pel er fremstillingen af en forbindelse med den almene formel Ipel is the preparation of a compound of general formula I

XLI, i hvilken R1 betyder hydrogen, amino, alkylcarbonylamino IXLI, wherein R 1 is hydrogen, amino, alkylcarbonylamino I

eller halogenalkylcarbonylamino, R2 betyder cyano, og R3 Ior haloalkylcarbonylamino, R2 means cyano, and R3 I

betyder hydrogen eller chlor, ud fra en forbindelse med den Imeans hydrogen or chlorine, based on a compound with the I

33

30 almene formel XXXIX, i hvilken R1 betyder hydrogen, amino, IWherein R 1 is hydrogen, amino, I

alkylcarbonylamino eller halogenalkylcarbonylamino, R2 er Ialkylcarbonylamino or haloalkylcarbonylamino, R 2 is I

cyano, og R3 r hydrogen eller chlor, ved behandling med Icyano, and R 3 is hydrogen or chlorine, by treatment with I

triphenylphosphin i tetrahydrofuran ved 25°C. Et repræsen- Itriphenylphosphine in tetrahydrofuran at 25 ° C. A representation- I

tativt eksempel på en fremgangsmåde til reduktion af toluen Iexample of a method for reducing toluene I

44

35 til p-tolyldisulfid er angivet af G.A. Olah et al., J. Org. I35 for p-tolyl disulfide is disclosed by G.A. Olah et al., J. Org. IN

Chern., 1980, 45, 4792: IChern., 1980, 45, 4792: I

63 I63 I

DK 175618 B1DK 175618 B1

CIO2S—r x-R2 , 1 --s“7i tT"R2 IC102S-r x-R2, 1 - s “7i tT" R2 I

"’ΛΑ·* ιιί£ΐοη" «ΛΛ«3"'ΛΑ · * ιιί £ ΐοη" «ΛΛ« 3

opi^snings- χ1 IOpening ^ nings1 I

X2!^^ middel X2^^ IX2! ^^ middle X2 ^^ I

γ L y J2γ L y J2

(XXXIX) (XLI) I(XXXIX) (XLI) I

10 I10 I

C) Forbindelser med den almene formel I, i hvilken IC) Compounds of general formula I in which I

R1, R2, Y, X1, X2, X2 og X4 har de i forbindelse med form- IR 1, R 2, Y, X 1, X 2, X 2 and X 4 are those of Form I

len I angivne betydninger, og X betyder en perhalogenalkyl- II represents X and a perhaloalkyl I

15 thiogruppe, R6S, i hvilken R6 betyder CFR7R8, og R7 betyder IThio group, R6S, in which R6 is CFR7R8 and R7 is I

I F, Cl eller Br, og R8 betyder F, Cl, Br eller en perfluor- IIn F, Cl or Br, and R8 means F, Cl, Br or a perfluoro-I

I alkylgruppe, kan fremstilles ved omsætning af en forbindelse IIn alkyl group, can be prepared by reaction of a compound I

I med den almene formel XLI og en perhalogenalkanforbindelse II of general formula XLI and a perhaloalkane compound I

I med den almene formel XLII, 2CFR7R8, i hvilken Z betyder II of general formula XLII, 2CFR7R8, in which Z means I

I 20 Cl, Br eller I, R7 betyder F, Cl eller Br, og R8 betyder F, IIn 20 Cl, Br or I, R7 means F, Cl or Br, and R8 means F, I

I Cl, Br eller en perfluoralkylgruppe, med et reduktionsmiddel, I der kan fremme dannelsen af det frie radikal CFR7R8 ud fra I ZCFR7R8, fortrinsvis valgt blandt metallerne zink, cadmium, I aluminium, mangan og en forbindelse med et oxid af svovl, 25 f.eks. dithionitterne eller hydroxymethylsulfinateme. Metal- I dithionittet, f.eks. alkalimetaldithionit eller jordalkali- metaldithionit, svarer til den almene formel XLIII, Mn(S204) , I i hvilken n kan være 1 eller 2, afhængigt af valensen af I metallet M. Når der anvendes et dithionit med den almene I 30 formel XLIII eller et hydroxymethylsulfinat, skal der til- sættes en base, f.eks. valgt blandt alkalimetalhydroxider, I jordalkalimetalhydroxider, ammoniak, triethylbenzylammonium I eller salte af.svage syrer såsom dinatriumphosphat, natrium- I metabisulfit, natriumhydrogensulfit eller natriumborat.In C1, Br or a perfluoroalkyl group, with a reducing agent, which can promote the formation of the free radical CFR7R8 from I ZCFR7R8, preferably selected from the metals zinc, cadmium, aluminum, manganese and a compound with an oxide of sulfur, .g. the dithionites or hydroxymethyl sulfinates. The metal I dithionite, e.g. alkali metal dithionite or alkaline earth metal dithionite, corresponds to the general formula XLIII, Mn (S204), in which n may be 1 or 2, depending on the valence of the I metal M. When using a dithionite of the general formula XLIII or a hydroxymethyl sulfinate, a base, e.g. selected from alkali metal hydroxides, alkaline earth metal hydroxides, ammonia, triethylbenzylammonium I or salts of weak acids such as disodium phosphate, sodium I metabisulfite, sodium hydrogen sulfite or sodium borate.

I 35 Reaktionen udføres i almindelighed i et opløsningsmiddel, j I der kan opløseliggøre dithionittet eller hydroxymethylsul- I DK 175618 B1 I 64The reaction is generally carried out in a solvent capable of solubilizing the dithionite or hydroxymethyl sulphide.

finatet og forbindelsen med formlen XLII, ZCFR7R8, f.eks. Ithe finate and the compound of formula XLII, ZCFR7R8, e.g. IN

acetonitril, formamid, dimethylformamid, dimethylacetamid, Iacetonitrile, formamide, dimethylformamide, dimethylacetamide, I

hexamethylphosphoramid, N-methylpyrrolidon, dimethylsulfoxid Ihexamethylphosphoramide, N-methylpyrrolidone, dimethylsulfoxide I

I eller sulfolan, ved en reaktionstemperatur fra 20 til 85°C. II or sulfolane, at a reaction temperature of 20 to 85 ° C. IN

5 Alkalimetaldithionittet kan sættes til reaktionsblandingen IThe alkali metal dithionite can be added to the reaction mixture I

I som en mættet opløsning i vand eller formamid. Det er også IIn as a saturated solution in water or formamide. So are you

muligt at tilsætte dithionittet i form af et fast stof. Når Ipossible to add the dithionite in the form of a solid. When you

der arbejdes med en gas, der kun er lidt opløselig i reak- Iworking with a gas that is only slightly soluble in reaction

I tionsopløsningsmidlet, kan reaktionstrykket forøges fra IIn the reaction solvent, the reaction pressure can be increased from 1

I 10 f.eks. 1 atmosfære til 50 atmosfærer. Et mere specifikt IIn 10 e.g. 1 atmosphere to 50 atmospheres. A more specific I

I eksempel er fremstillingen af forbindelsen med den almene IFor example, the preparation of the compound with the general I

formel I, i hvilken R1 betyder hydrogen, amino, alkylcar- Iformula I wherein R 1 is hydrogen, amino, alkylcar-I

bonylamino eller halogenalkylcarbonylamino, R2 er cyano, R3 Ibonylamino or haloalkylcarbonylamino, R 2 is cyano, R 3 I

I er hydrogen eller Cl, og X er en perhalogenalkylthiogruppe, II is hydrogen or Cl and X is a perhaloalkylthio group, I

I 15 R6S, i hvilken R6 er CFR7R8, og R7 er F, Cl eller Br, og R8 IIn R6S, wherein R6 is CFR7R8 and R7 is F, Cl or Br, and R8 is

I er F, Cl , Br eller en perfluoralkylgruppe, ved omsætning II is F, Cl, Br or a perfluoroalkyl group, by reaction I

I af en forbindelse med den almene formel XLI, i hvilken R1 II of a compound of the general formula XLI in which R1

I betyder hydrogen, amino, alkylamido eller halogenalkylamido, II means hydrogen, amino, alkylamido or haloalkylamido, I

I R2 er cyano, og R3 er hydrogen eller Cl, med en forbindelse IIn R 2 is cyano and R 3 is hydrogen or Cl, with a compound I

I 20 med den almene formel XLII, ZCFR7R8, i hvilken Z betyuder IIn 20 of the general formula XLII, ZCFR7R8, in which Z means I

I Cl, Br eller I, R7 betyder F, Cl eller Br, og R8 betyder F, IIn Cl, Br or I, R7 means F, Cl or Br, and R8 means F, I

I Cl, Br eller en perfluoralkylgruppe, med natriumdithionit IIn Cl, Br or a perfluoroalkyl group, with sodium dithionite I

I og dinatriumphosphat i dimethylformamid ved 25°C. Reaktionen II and disodium phosphate in dimethylformamide at 25 ° C. Reaction I

I ' kan illustreres ved den følgende reaktionsligning: II 'can be illustrated by the following reaction equation:

I 25 II 25 I

I "f^Jl JLrsI ? n reduktions- Ri—JLr3 ' IIn "f ^ Jl JLrsI? A reduction Ri-JLr3 'I

I . ZCFR7R8 ' middel^ II. ZCFR7R8 'means ^ I

I χ!_ίΛ>Γχ4 base χ1_χΛ^_χ4 II χ! _ΊΛ> Γχ4 base χ1_χΛ ^ _χ4 I

I 30 x2JlIx3 ^-U-x3 , II 30 x2JlIx3 ^ -U-x3, I

I y y II y y I

I L J2 II L J2 I

I 35 II 35 I

(XLI) (XLII) Π) I(XLI) (XLII) Π) I

DK 175618 B1DK 175618 B1

65 I65 I

Mellemprodukt-chlorsulfonylforbindelsen med formlen IThe intermediate chlorosulfonyl compound of formula I

XXXIX og mellemprodukt-disulfidforbindelsen med formlen XLI IXXXIX and the intermediate disulfide compound of formula XLI I

er også omfattet af den foreliggende opfindelse. Iare also encompassed by the present invention. IN

I 5 Repræsentative forbindelser ifølge opfindelsen IRepresentative Compounds of the Invention I

I Specifikke repræsentative pyrrolforbindelser (RPC), ISpecific Representative Pyrrole Compounds (RPC), I

I der er omfattet af den foreliggende opfindelse, er forbin- IIn the scope of the present invention, compounds I

I delser med formlen I, i hvilken R2 er cyano, og de øvrige IIn compounds of formula I in which R2 is cyano and the other I

I 10 substituenter har de betydninger, der er angivet i Tabel I IIn 10 substituents have the meanings given in Table I I

I (RPC nr. 1-389). II (RPC No. 1-389). IN

I Andre specifikke, repræsentative pyrrolforbindelser IOther specific, representative pyrrole compounds

I {RPC), der er omfattet af opfindelsen, er forbindelser med IIn the {RPC) encompassed by the invention are compounds with I

I formlen I, i hvilken X2 og X3 er hydrogen, X1 og X4 er chlor, I 15 Y er CF3, og X, R1, R2 og R3 har de betydninger, der er I angivet i tabel II (RPC nr. 390-491).In Formula I in which X2 and X3 are hydrogen, X1 and X4 are chlorine, I Y is CF3 and X, R1, R2 and R3 have the meanings set forth in Table II (RPC Nos. 390-491 ).

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I oIn Island

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I DK 175618 B1 II DK 175618 B1 I

I 94 II 94 I

I Tabel II IIn Table II I

I Andre repræsentative pyrrolforbindelser (RPC) med formlen I, IIn Other Representative Pyrrole Compounds (RPC) of Formula I, I

I i hvilken X2 & X3=H, X1 & X4=C1 og Y=CF3 IIn which X2 & X3 = H, X1 & X4 = C1 and Y = CF3 I

I Substituent-grupper IIn Substituent Groups I

I RPC-nr. R1 X R3 R2 IIn RPC no. R1 X R3 R2 I

I 390. H SCF3 α H II 390. H SCF3 α H I

I 391. H SOCF3 Cl H II 391. H SOCF3 Cl H I

I 392. H S°2CF3 Cl Η II 392. H S ° 2CF3 Cl Η I

I 393. H SCF3 F H II 393. H SCF3 F H I

I 394. H SOCF3 F h II 394. H SOCF3 F h I

I 395. H SC>2CF3 F H II 395. H SC> 2CF3 F H I

I 396. H SCF3 CN H II 396. H SCF3 CN H I

I 397. H SOCF3 CN Η II 397. H SOCF3 CN Η I

I 398. H CN H II 398. H CN H I

I 399. H SCF3 CF3 H II 399. H SCF3 CF3 H I

I 400. H SOCF3 CF3 Η II 400. H SOCF3 CF3 Η I

I 401. H SC^CFg CF3 Η II 401. H SC ^ CFg CF3 Η I

I 402. H SCF3 S02CF3 H II 402. H SCF3 S02CF3 H I

I 403. H SOCF3 s°2CF3 Η II 403. H SOCF3 s ° 2CF3 Η I

I 404. H S02cf3 S02cf3 H II 404. H S02cf3 S02cf3 H I

I 405. Cl SCF3 α H II 405. Cl SCF3 α H I

I 406. Cl SOCF3 Cl H II 406. Cl SOCF3 Cl H I

I 407. Cl SO2CF3 α H II 407. Cl SO2CF3 α H I

I 408. Cl SCF3 F H II 408. Cl SCF3 F H I

I 409. Cl SOCF3 F Η II 409. Cl SOCF3 F Η I

Tabel IITable II

95 DK 175618 B195 DK 175618 B1

Andre repræsentative pyrrolforbindelser (RPC) med formlen I, i hvilken X2 & X3=H, X1 & X4=C1 og Y=CF^Other representative pyrrole compounds (RPC) of formula I in which X2 & X3 = H, X1 & X4 = C1 and Y = CF

Substituent-grupper RPC-nr. Ri X R3 R2Substituent groups RPC no. Ri X R3 R2

410. Cl SCF3 CN H410. Cl SCF3 CN H

411. Cl SOCF3 CN H411. Cl SOCF3 CN H

412. Cl S02CF3 CN H412. Cl S02CF3 CN H

413. CN SCF3 Cl H413. CN SCF3 Cl H

414. CN SOCF3 Cl H414. CN SOCF3 Cl H

415. CN SC>2CF3 C1 H415. CN SC> 2CF3 C1 H

416. CN SCF3 * F H416. CN SCF3 * F H

417. CN SOCF3 F H417. CN SOCF3 F H

418. CN . s°2CF3 F H418. CN. s ° 2CF3 F H

419. CN SCF3 CF3 H419. CN SCF3 CF3 H

420. CN SOCF3 CF3 H420. CN SOCF3 CF3 H

421. CN S02CF3 CF3 H421. CN S02CF3 CF3 H

422. F SCF3 Cl H422. F SCF3 Cl H

423. F SOCFg Q H423. F SOCFg Q H

424. F S°2CF3 Q H424. F S ° 2CF3 Q H

425. H SCF3 Q Cl 426. H SOCF3 Cl Cl 427. H SC^CFa Cl Cl 428. H SCF3 F Cl 429. H SOCF3 F Cl425. H SCF3 Q Cl 426. H SOCF3 Cl Cl 427. H SC ^ CFa Cl Cl 428. H SCF3 F Cl 429. H SOCF3 F Cl

I DK 175618 B1 II DK 175618 B1 I

i 96 Iin 96 I

I Tabel II IIn Table II I

I Andre repræsentative pyrrolforbindelser (RPC) med formlen 1,- IOther Representative Pyrrole Compounds (RPC) of Formula 1, - I

I i hvilken X2 & X3=H, X1 & X4=G1 og Y=CF3 IIn which X2 & X3 = H, X1 & X4 = G1 and Y = CF3 I

Substituent-grupper ISubstituent groups I

I RPC-nr. r! X R3 R2 IIn RPC no. r! X R3 R2 I

I 430. h so2cf3 f alI 430. h so2cf3 f al

I 431. H SCF3 cn a II 431. H SCF3 cn a I

I 432. H SOCF3 CN Cl II 432. H SOCF3 CN Cl I

I 433. H ^°2CF3 CN C1 II 433. H ^ ° 2CF3 CN C1 I

I 434. H SCF3 CF3 Cl II 434. H SCF3 CF3 Cl I

I 435. h socf3 cf3 a II 435. h socf3 cf3 a I

I 436. H S02cf3 CF3 Cl II 436. H S02cf3 CF3 Cl I

I 437. Cl SCF3 Cl Cl II 437. Cl SCF3 Cl Cl I

I 438. Cl socf3 Cl a II 438. Cl socf3 Cl a I

I 439. Cl $°2cf3 σ a II 439. Cl $ ° 2cf3 σ and I

I 440. Cl SCF3 F Cl II 440. Cl SCF3 F Cl I

I 441. Cl S0CF3 F Cl II 441. Cl S0CF3 F Cl I

I 442. Cl S00CFo F C? II 442. Cl S00CFo F C? IN

2 5 il2 5 il

I 443. a scf3 cn a II 443. a scf3 cn a I

I 444. Cl SOCF3 CN Cl II 444. Cl SOCF3 CN Cl I

I 445. Cl S02CF3 CN C1 II 445. Cl S02CF3 CN C1 I

I 446. Cl SCF3 CF3 Cl II 446. Cl SCF3 CF3 Cl I

I 447. Cl S0CF3 CF3 Cl II 447. Cl S0CF3 CF3 Cl I

I 448. Cl SC>2CF3 CF3 Cl II 448. Cl SC> 2CF3 CF3 Cl I

I 449. CN SCF3 Cl Cl II 449. CN SCF3 Cl Cl I

9797

Tabel IITable II

DK 175618 B1DK 175618 B1

Andre repræsentative pyrrolforbindelser (RPC) med formlen I, i hvilken X2 & X3=H, X1 & X4=C1 og Y=CF3Other representative pyrrole compounds (RPC) of formula I in which X2 & X3 = H, X1 & X4 = C1 and Y = CF3

Substituent-grupper RPC-nr. R* X R3 r2 450. CN SOCFg α Cl 451. CN 3°20¥3 C1 C1 452. CN SCF3 F Cl 453. CN SOCF3 F Cl 454. CN S02CF3 F Cl 455. CN SCF3 CN Cl 456. CN SOCF3 CN Cl 457. CN SC>2CF3 CN α 458. CN SCF3 CFg ClSubstituent groups RPC no. R * X R3 r2 450. CN SOCFg α Cl 451. CN 3 ° 20 ¥ 3 C1 C1 452. CN SCF3 F Cl 453. CN SOCF3 F Cl 454. CN S02CF3 F Cl 455. CN SCF3 CN Cl 456. CN SOCF3 CN Cl 457. CN SC> 2CF3 CN α 458. CN SCF3 CFg Cl

459. Cl SO2CF3 F H459. Cl SO2CF3 F H

460. CN SOCF3 CF3 Cl 461. CN S°2CF3 CF3 Cl 462. H SCF3 O CF3 463. H SCF3 F CF3 464. H SOCF3 F CF3 465. H ^2^3 F CF3 466. H SCF3 CN CF3 467. H SOCFg CN CF3 468. H S°2CF3 CN CF3 469. H SCF3 Cl CF3460. CN SOCF3 CF3 Cl 461. CN S ° 2CF3 CF3 Cl 462. H SCF3 O CF3 463. H SCF3 F CF3 464. H SOCF3 F CF3 465. H ^ 2 ^ 3 F CF3 466. H SCF3 CN CF3 467. H SOCFg CN CF3 468. HS ° 2CF3 CN CF3 469. H SCF3 Cl CF3

I DK 175618 B1 II DK 175618 B1 I

I 96 II 96 I

I Tabel II . IIn Table II. IN

Substituent-grupper ISubstituent groups I

I RPC-nr. R* X R3 R2 IIn RPC no. R * X R3 R2 I

I 470. H SOCF3 Cl CF3 II 470. H SOCF3 Cl CF3 I

I 471. H C1 II 471. H C1 I

I 472. H SCF3 a CH3 II 472. H SCF3 and CH3 I

I 473. H SOCF3 Cl CH3 II 473. H SOCF3 Cl CH3 I

I 474. Η &°2€Γ3 Q CH3 II 474. Η & ° 2 € Γ3 Q CH3 I

I 475. H SCF3 F CH3 II 475. H SCF3 F CH3 I

I 476. H SOCF3 F CH3 II 476. H SOCF3 F CH3 I

I 477. H ^2°¾ F CH3 II 477. H ^ 2 ° ¾ F CH3 I

I 478. H SCHF2 Cl CN II 478. H SCHF2 Cl CN I

I 479. H SOCHF2 Cl CN II 479. H SOCHF2 Cl CN I

I 480. H SO2CHF2 Cl CN II 480. H SO2CHF2 Cl CN I

I 481. H SCHF2 H CN II 481. H SCHF2 H CN I

I 482. H SOCHF2 H CN II 482. H SOCHF2 H CN I

I 483. H SO2CHF2 H CN II 483. H SO2CHF2 H CN I

I 484. H SO2CHCI2 Cl CN II 484. H SO2CHCI2 Cl CN I

I 485. H SOCHC12 Cl CN II 485. H SOCHC12 Cl CN I

I 486. H SOCHC1F a CN II 486. H SOCHC1F and CN I

I 487. H SO2CHCIF O CN II 487. H SO2CHCIF O CN I

I 488. H SCHF2 Cl Cl II 488. H SCHF2 Cl Cl I

I 489. H SO2CHF2 Cl Cl II 489. H SO2CHF2 Cl Cl I

Tabel IITable II

99 DK 175618 B199 DK 175618 B1

Substituent-grupper RPC-nr. R* X R3 R2 490. H SOCHF2 Br CH3 491. Cl SO2CHF2 Cl CF3Substituent groups RPC no. R * X R3 R2 490. H SOCHF2 Br CH3 491. Cl SO2CHF2 Cl CF3

I DK 175618 B1 II DK 175618 B1 I

I 100 II 100 I

I Detaljerede eksempler på syntese af forbindelser IDetailed Examples of Synthesis of Compounds I

I De følgende eksempler 1-22 illustrerer yderligere IThe following Examples 1-22 further illustrate I

I fremgangsmåderne til syntese af og de fysiske egenskaber af IIn the methods of synthesis and the physical properties of I

I 5 de insecticide forbindelser (og deres kemiske mellemproduk- IIn the insecticidal compounds (and their chemical intermediates - I)

I ter) ifølge den foreliggende opfindelse. IIn ter) according to the present invention. IN

I . Eksempel 1 II. Example 1 I

I 10 En opløsning af 910 mg (2,07 mmol) 1-(2,6-dichlor-4- II A solution of 910 mg (2.07 mmol) of 1- (2,6-dichloro-4-I)

I trifluormethylphenyl)-2-chlor-3-cyano-4-trifluormethylthio- IIn trifluoromethylphenyl) -2-chloro-3-cyano-4-trifluoromethylthio-1

I pyrrol (fremstillet ved den fremgangsmåde, der er beskrevet IIn pyrrole (prepared by the method described in

I i eksempel 4) og 492 mg 80%'s m-chlorperoxybenzoesyre IIn Example 4) and 492 mg of 80% m-chloroperoxybenzoic acid I

I (394 mg, 2,28 mmol) i 25 ml chloroform omrøres ved omgivel- II (394 mg, 2.28 mmol) in 25 ml of chloroform is stirred at ambient I

I 15 sernes temperatur i 1¾ time og opvarmes dernæst til tilbage- IAt room temperature for 1 temperatur hour and then heated to reflux

I svaling natten over. Der tilsættes yderligere 45 mg IIn cooling overnight. An additional 45 mg of I is added

I (0,21 mmol) m-chlorperoxybenzoesyre, og tilbagesvalingen II (0.21 mmol) m-chloroperoxybenzoic acid, and the reflux I

I fortsættes i 1 time. Opvarmningen standses derefter, og IYou continue for 1 hour. The heating is then stopped and I

I reaktionsblandingen fortyndes med dichlormethan og vaskes IIn the reaction mixture, dilute with dichloromethane and wash

I 20 med vandig natriumbicarbonatopløsning. Det organiske lag IIn 20 with aqueous sodium bicarbonate solution. The organic layer I

I tørres med vandfrit magnesiumsulfat og koncentreres under IYou are dried over anhydrous magnesium sulfate and concentrated under 1

I formindsket tryk, hvorved der fås en farveløs, fast remanens. IAt reduced pressure to give a colorless solid residue. IN

I Denne fremgangsmåde gentages, således at der i alt fås 950 mg IThis procedure is repeated so as to obtain a total of 950 mg of I

I produkt, der chromatograferes på silicagel, .idet der elueres IIn product chromatographed on silica gel, eluting with I

I 25 med en blanding af dichlormethan og hexan i rumfang s forholdet IIn 25 with a mixture of dichloromethane and hexane in volume I ratio

I 2:1. De første fraktioner indeholder 310 mg (24%) 1-(2,6- II 2: 1. The first fractions contain 310 mg (24%) of 1- (2.6-I)

I dichlor-4-trifluormethylphenyl)-2-chlor-3-cyano-4-trifluor- IIn dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4-trifluoro-1

I methylsulfonylpyrrol (eksempel 1) i form af et farveløst, IIn methylsulfonylpyrrole (Example 1) in the form of a colorless, I

I fast stof. Ved omkrystallisation fra en blanding af hexan IIn solid. By recrystallization from a mixture of hexane I

30 og ethylacetat fas der 240 mg af sulfonen i form af farveløse I30 and ethyl acetate are added 240 mg of the sulfone as colorless I

nåle med smp. 198°C. Ineedles with m.p. 198 ° C. IN

Eksempel 2 IExample 2 I

35 Den i slutningen af eksempel 1 angivne chromatografe- IThe chromatograph I indicated at the end of Example 1

ring fortsættes. Senere fraktioner fra chromatografien giver Iring continues. Later fractions from the chromatography give I

101 DK 175618 B1 600 mg (48%) 1-(2,6-dichlor-4-trif luormethylphenyl)-2-chlor-3-cyano-4-trifluormethylsulfinylpyrrol (eksempel 2) i form af et farveløst, fast stof. Ved omkrystallisation fra en blanding af toluen og hexan fås der 390 mg af sulfoxidet i 5 form af et farveløst pulver med smp. 152-154,5°C.B1 600 mg (48%) 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4-trifluoromethylsulfinylpyrrole (Example 2) as a colorless solid. Recrystallization from a mixture of toluene and hexane gives 390 mg of the sulfoxide in the form of a colorless powder with m.p. 152 to 154.5 ° C.

Eksempel 3a oa 3bExamples 3a and 3b

Eksempel 1 og 2 gentages med 1-(2,6-dichlor-4-tri-10 f luormethylphenyl) -2-chlor-3-cyano-4-trifluormethylthio-5-brompyrrol som udgangsmateriale, fremstillet ved fremgangsmåden ifølge eksempel 5. Forbindelsen fra eksempel 3a er 1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-3-cyano-4-tri-fluormethylsulfinyl-5-brompyrrol. Denne forbindelse, der 15 fremstilles ved anvendelse af en fremgangsmåde svarende til den i eksempel 2 beskrevne, har et smeltepunkt på ca. 123°C. Forbindelsen fra eksempel 3b er l-(2,6-dichlor-4-trifluormethylphenyl ) -2 - chlor-3-cyano-4-trif luormethylsulf onyl-5-brompyrrol. Denne forbindelse, der fremstilles under anven-20 delse af en fremgangsmåde svarende til den i eksempel 1 beskrevne, har et smeltepunkt på ca. 113°C.Examples 1 and 2 are repeated using 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4-trifluoromethylthio-5-bromopyrrole as starting material prepared by the method of Example 5. The compound from Example 3a is 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4-trifluoromethylsulfinyl-5-bromopyrrole. This compound, prepared using a method similar to that described in Example 2, has a melting point of approx. 123 ° C. The compound of Example 3b is 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4-trifluoromethylsulfonyl-5-bromopyrrole. This compound, prepared using a process similar to that described in Example 1, has a melting point of approx. 113 ° C.

Eksempel 4 25 En opløsning af 3 g (6,6 mmol) 1-(2,6-dichlor-4-tri- f luormethylphenyl) -2-amino-3-trifluormethylthio-4-cyano-5-chlorpyrrol (fremstillet ved den i eksempel 8 beskrevne fremgangsmåde) i 50 ml tør tetrahydrofuran omrøres under en nitrogenatmosfære, og der tilsættes 3,9 ml (3,4 g eller 30 33 mmol) tert.butylnitrit. Efter 30 minutters forløb opvarmes reaktionsblandingen til tilbagesvaling i ca. 1 time, hvorefter den koncentreres under formindsket tryk, hvorved der fås 3,69 g af en fast remanens. Denne fremgangsmnåde gentages, således at der i alt fås 4,07 g fast remanens, som 35 chromatograferes på silicagel med et elueringsmiddel bestående af en blanding af dichlormethan og hexan i rumfangsfor- I DK 175618 B1 I 102 I holdet 1:1, hvorved der fås 2,9 g (91%) 1-(2,6-dichlor-4- trifluormethylphenyl)-2-chlor-3-cyano-4-trifluormethylthio- I pyrrol (eksempel 4) i form af et farveløst, fast stof. Ved I omkrystallisation fra en blanding af hexan og ethylacetat I 5 fås der 1,87 g af produktet i form af et farveløst pulver I med smp. ca. 137°C.Example 4 A solution of 3 g (6.6 mmol) of 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3-trifluoromethylthio-4-cyano-5-chloropyrrole (prepared by the in 50 ml of dry tetrahydrofuran is stirred under a nitrogen atmosphere and 3.9 ml (3.4 g or 33 mmol) of tert.butyl nitrite is added. After 30 minutes, the reaction mixture is heated to reflux for approx. 1 hour, then concentrated under reduced pressure to give 3.69 g of a solid residue. This procedure is repeated so as to obtain a total of 4.07 g of solid residue which is chromatographed on silica gel with an eluent consisting of a mixture of dichloromethane and hexane in a 1: 1 volume ratio, whereby: 2.9 g (91%) of 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4-trifluoromethylthio-1-pyrrole (Example 4) are obtained as a colorless solid. Recrystallization from a mixture of hexane and ethyl acetate I gives 1.87 g of the product as a colorless powder I with m.p. ca. 137 ° C.

I Eksempel 5 10 Til en heterogen blanding af 2,4 g (5,28 mmol) 1-(2,6- dichlor-4-trifluormethylphenyl)-2-amino-3-trifluormethylthio- I 4-cyano-5-chlorpyrrol (fremstillet ved den i eksempel 8 beskrevne fremgangsmåde) i 40 ml bromoform under en indif- I ferent atmosfære sættes der 0,94 ml (820 mg eller 7,92 mmol)In Example 5 To a heterogeneous mixture of 2.4 g (5.28 mmol) of 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3-trifluoromethylthio-4-cyano-5-chloropyrrole ( prepared in the procedure described in Example 8) in 40 ml of bromoform under an inert atmosphere 0.94 ml (820 mg or 7.92 mmol) is added.

I 15 tert.butylnitrit. Efter 15 minutters omrøring ved omgivelser- IIn tert.butyl nitrite. After 15 minutes of stirring at ambient- I

I nes temperatur koncentreres reaktionsblandingen under for-At its temperature, the reaction mixture is concentrated under

I mindsket tryk, hvorved der fås 3,9 g remanens. Denne kom- IAt reduced pressure to give 3.9 g of residue. This one

bineres med produktet fra en tidligere omsætning af 300 mg Ibinder with the product from a previous reaction of 300 mg I

af det samme pyrrol-udgangsmateriale. Det rå produkt chroma- Iof the same pyrrole starting material. The crude product chroma- I

I 20 tograferes på silicagel under eluering med en blanding af IFor 20, trace on silica gel eluting with a mixture of I

I hexan og dichlormethan i rumfangsforholdet 4:1. Herved ud- IIn hexane and dichloromethane in a 4: 1 volume ratio. Hereby, I

I skilles der 1,72 g (56%) 1-(2,6-dichlor-4-trifluormethyl-. I1.72 g (56%) of 1- (2,6-dichloro-4-trifluoromethyl) are separated.

I phenyl)-2-brom-3-trifluormethylthio-4-cyano-5-chlorpyrrol IIn phenyl) -2-bromo-3-trifluoromethylthio-4-cyano-5-chloropyrrole I

I (eksempel 5), der omkrystalliseres fra hexan, hvorved der II (Example 5) which is recrystallized from hexane to give I

25 fås 780 mg af produktet i form af et farveløst, fast stof I25, 780 mg of the product is obtained in the form of a colorless solid I

I med smp. ca. 92 °C. II with m.p. ca. 92 ° C. IN

I Eksempel 6 IIn Example 6 I

I 30 En opløsning af 1,91 g (4,21 mmol) 1-(2,6-dichlor-4- IA solution of 1.91 g (4.21 mmol) of 1- (2,6-dichloro-4-I)

trifluormethylphenyl)-2-amino-3-trifluormethylthio-4-cyano- Itrifluoromethylphenyl) -2-amino-3-trifluoromethylthio-4-cyano-1

I 5-chlorpyrrol (fremstillet ved den i eksempel 8 beskrevne IIn 5-chloropyrrole (prepared by the I described in Example 8

fremgangsmåde), 77 mg (0,63 mmol) 4-dimethylaminopyridin og Imethod), 77 mg (0.63 mmol) of 4-dimethylaminopyridine and I

I 20 ml pyridin under en indifferent atmosfære afkøles til IIn 20 ml of pyridine under an inert atmosphere, cool to 1

I 35 0°C, og der tilsættes 1,01 ml (1,50 g eller 7,14 mmol) tri- IAt 35 ° C, add 1.01 ml (1.50 g or 7.14 mmol) of tri-I

I fluoreddikesyreanhydrid. Reaktionsblandingen omrøres ved IIn fluoroacetic anhydride. The reaction mixture is stirred at 1

DK 175618 B1 1,03 0°C i 1 time og ved 20°C i 4 timer, hvorefter der tilsættes yderligere 0,30 ml (2,1 mmol) trifluoreddikesyreanhydrid.B1 1.03 0 ° C for 1 hour and at 20 ° C for 4 hours, then an additional 0.30 ml (2.1 mmol) of trifluoroacetic anhydride is added.

Efter en samlet reaktionstid på 24 timer fortyndes reaktionsblandingen med dichlormethan og koncentreres. Remanensen 5 vaskes med vandig saltsyre, efterfulgt af vand, og der omkrystalliseres fra en blanding af hexan og ethylacetat, hvorved der fås 860 mg (37%) 1-(2,6-dichlor-4-trifluormethylphenyl) - 2- [ (trif luormethyl) -carbonylamino] -3-trifluormethylthio-4-cyano-5-chlorpyrrol (eksempel 6) som et svagt grønt, fast 10 stof med smp. ca. 190°C.After a total reaction time of 24 hours, the reaction mixture is diluted with dichloromethane and concentrated. The residue 5 is washed with aqueous hydrochloric acid, followed by water and recrystallized from a mixture of hexane and ethyl acetate to give 860 mg (37%) of 1- (2,6-dichloro-4-trifluoromethylphenyl) - 2- [(trif. (fluoromethyl) carbonylamino] -3-trifluoromethylthio-4-cyano-5-chloropyrrole (Example 6) as a pale green solid, m.p. ca. 190 ° C.

Eksempel 7Example 7

En blanding af 1,50 g (3,3 mmol) 1-(2,6-dichlor-4-15 trifluormethylphenyl)-2-amino-3-trifluormethylthio-4-cyano- 5-chlorpyrrol (fremstillet ved den i eksempel 8 beskrevne fremgangsmåde), 0,10 g 4-dimethylaminopyridin, 0,33 ml (0,32 g eller 4,1 mmol) pyridin, 0,31 ml (0,34 g eller 4,3 mmol) acetylchlorid og 10 ml acetonitril omrores i 4 dage 20 ved 20°C og 1 dag under tilbagesvaling. Der tilsættes derpå yderligere 0,03 ml acetylchlorid, og tilbagesvalingen fort^ sættes i yderligere 1 dag, hvorefter reaktionsblandingen afkøles, fortyndes med dichlormethan og fordeles successivt med vandig 1 N saltsyre og en mættet vandig natriumbicar-25 bonatopløsning. Det organiske lag tørres med vandfrit magnesiumsulfat og inddampes, hvorved der fås 1,42 g af et beigefarvet, fast stof. Ved chromatografi på silicagel under eluering med en blanding af hexan og ethylacetat i rumfangs-forholdet 4:1, efterfulgt af omkrystallisation fra en blan-30 ding af ethanol og vand, fås der 480 mg (29%) 1-(2,6-dichlor-4 - trif luormethylphenyl) -2-methylcarbonylamino-3 -trif luor-methylthio-4-cyano-5-chlorpyrrol (eksempel 7) i form af farveløse nåle med smp. ca. 216°C.A mixture of 1.50 g (3.3 mmol) of 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3-trifluoromethylthio-4-cyano-5-chloropyrrole (prepared by the example of Example 8) described procedure), 0.10 g of 4-dimethylaminopyridine, 0.33 ml (0.32 g or 4.1 mmol) of pyridine, 0.31 ml (0.34 g or 4.3 mmol) of acetyl chloride and 10 ml of acetonitrile are stirred. for 4 days 20 at 20 ° C and 1 day at reflux. An additional 0.03 ml of acetyl chloride is then added and the reflux is continued for a further 1 day, after which the reaction mixture is cooled, diluted with dichloromethane and partitioned successively with aqueous 1N hydrochloric acid and a saturated aqueous sodium bicarbonate solution. The organic layer is dried over anhydrous magnesium sulfate and evaporated to give 1.42 g of a beige solid. By chromatography on silica gel eluting with a mixture of hexane and ethyl acetate in a 4: 1 volume ratio, followed by recrystallization from a mixture of ethanol and water, 480 mg (29%) of 1- (2.6%) is obtained. dichloro-4 - trifluoromethylphenyl) -2-methylcarbonylamino-3-trifluoromethylthio-4-cyano-5-chloropyrrole (Example 7) in the form of colorless needles, m.p. ca. 216 ° C.

DK 175618 B1 104DK 175618 B1 104

Eksempel 8Example 8

En omrørt opløsning af 1,50 g (3,57 mmol) 1-(2,6-dichlor-4-trifl uorme t hyl phenyl )-2- amino - 3 -1 r i f luorme thyl thio -I 5 4-cyanopyrrol (fremstillet ved den i eksempel 13 beskrevne I fremgangsmåde) i 15 ml ethylether afkøles til -20°C under en indifferent atmosfære, og der tilsættes dråbevis en opløs- I ning af 0,29 ml (0,48 g eller 3,6 mmol) sulfurylchlorid i 15 ml vandfri ethylether. Reaktionsblandingen får dernæst I 10 lov at varme op til 20°C og omrøres i 2% dag, hvorefter der I tilsættes yderligere 0,03 ml (0,4 mmol) sulfurylchlorid, og I omrøringen fortsættes i yderligere 1 dag. Der tilsættes yderligere 0,03 ml sulfurylchlorid, og efter yderligere 1 I dags forløb standses reaktionen med 28 ml 10%'s vandig kali- I 15 umcarbonatopløsning. Faserne adskilles, og det vandige lag I ekstraheres med ether. Etherlagene kombineres derefter, H vaskes med vand, tørres med vandfrit magnesiumsulfat og I koncentreres, hvorved der fås 1,56 g af et gulbrunt, fast stof. Det rå produkt chromatograferes på silicagel med et 20 elueringsmiddel bestående af en blanding af dichlormethan og hexan i rumfangsforholdet 2:1, hvorved der fås 1,30 g (80%) l-(2,6-dichlor-4-trifluormethylphenyl)-2-amino-3-tri- fluormethylthio-4-cyano-5-chlorpyrrol (eksempel 8) i form af. et svagt rosafarvet, fast stof. Ved omkrystallisation 25 fra cyclohexan fås der 810 mg af produktet i form af grå- ligt-hvide nåle med smp. ca. 176°C.A stirred solution of 1.50 g (3.57 mmol) of 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3-1-rifluoromethyl thio-1-4-cyanopyrrole ( prepared in the procedure described in Example 13 in 15 ml of ethyl ether is cooled to -20 ° C under an inert atmosphere and a solution of 0.29 ml (0.48 g or 3.6 mmol) is added dropwise. sulfuryl chloride in 15 ml of anhydrous ethyl ether. The reaction mixture is then allowed to warm to 20 ° C and stirred for 2% a day, then an additional 0.03 ml (0.4 mmol) of sulfuryl chloride is added and stirring is continued for a further 1 day. An additional 0.03 ml of sulfuryl chloride is added and after a further 1 day the reaction is quenched with 28 ml of 10% aqueous potassium carbonate solution. The phases are separated and the aqueous layer I is extracted with ether. The ether layers are then combined, H washed with water, dried over anhydrous magnesium sulfate and concentrated to give 1.56 g of a tan solid. The crude product is chromatographed on silica gel with an eluent consisting of a mixture of dichloromethane and hexane in the 2: 1 volume to give 1.30 g (80%) of 1- (2,6-dichloro-4-trifluoromethylphenyl) -2 -amino-3-trifluoromethylthio-4-cyano-5-chloropyrrole (Example 8) in the form of. a pale pink, solid. Recrystallization from cyclohexane 25 gives 810 mg of the product in the form of greyish-white needles, m.p. ca. 176 ° C.

Eksempel 9 IExample 9 I

30 Der anvendes en fremgangsmåde svarende til den i I30 A method similar to that of I is used

eksempel 8 beskrevne, idet der dog anvendes 1-(2-chlor-4- IExample 8, however, using 1- (2-chloro-4- I)

trifluormethylphenyl) - 2 -amino-3 -tri fluormethylthio-4-cyano- Itrifluoromethylphenyl) -2-amino-3-tri-fluoromethylthio-4-cyano-1

I pyrrol (smp. 169°C) som reaktant, der fremstilles ved en IIn pyrrole (mp 169 ° C) as a reactant produced by an I

I fremgangsmåde svarende til den i eksempel 13 beskrevne. IIn a procedure similar to that described in Example 13. IN

35 Slutproduktet er 1-(2-chlor-4-trifluormethylphenyl)-2-amino- IThe final product is 1- (2-chloro-4-trifluoromethylphenyl) -2-amino-I

105 DK 175618 B1 3- trifluormethylthio-4-cyano-5-chlorpyrrol (eksempel 9) med smp. ca. 148°C.B1 3- trifluoromethylthio-4-cyano-5-chloropyrrole (Example 9), m.p. ca. 148 ° C.

Eksempel 10 5Example 10 5

Der anvendes en fremgangsmåde svarende til den i eksempel 8 beskrevne, idet der dog anvendes 1-(2,6-dichlor- 4- trifluormethylphenyl)-2-amino-3-dichlorfluormethylthio-4-cyanopyrrol (smp. 202°C) som reaktant, der fremstilles ved 10 en fremgangsmåde svarende til den i eksempel 13 beskrevne. Slutproduktet er 1-(2,6-dichlor-4-trifluormethylphenyl)-2-amino-3-dichlorfluormethylthio-4-cyano-5-chlorpyrrol (eksempel 10) med smp. 207°C.A procedure similar to that described in Example 8 is used, however, using 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3-dichlorofluoromethylthio-4-cyanopyrrole (mp 202 ° C) as reactant which is prepared by a process similar to that described in Example 13. The final product is 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3-dichlorofluoromethylthio-4-cyano-5-chloropyrrole (Example 10), m.p. 207 ° C.

15 Eksempel 11Example 11

Forbindelsen 1-(2,6-dichlor-4-trifluormethylphenyl)- 2,4-bis-(trifluormethylthio)-3-cyano-5-aminopyrrol (eksempel 11) har et smeltepunkt på 161°C og fremstilles ved den 20 i eksempel 13 beskrevne fremgangsmåde (første forbindelse) under anvendelse af et overskud af trifluormethansulfenyl-chlorid.The compound 1- (2,6-dichloro-4-trifluoromethylphenyl) -2,4-bis- (trifluoromethylthio) -3-cyano-5-aminopyrrole (Example 11) has a melting point of 161 ° C and is prepared at the 13 (first compound) using an excess of trifluoromethanesulphenyl chloride.

Eksempel 12 25Example 12 25

Til en kold (0°C) opløsning af 1,53 g (3,60 mmol) 1-(2,6-dichlor-4-trif luormethylphenyl) -2-amino-3-trifluor-methylthio-4-cyanopyrrol (fremstillet ved den i eksempel 13 beskrevne fremgangsmåde, smp. ca. 182°C) i 15 ml pyridin 30 sættes der under en indifferent atmosfære en opløsning af 1,46 g (3,6 mmol) 80%'s pyridiniumbromidperbromid i 15 ml pyridin. Efter 30 minutters forløb udhældes reaktionsblandingen i kold (0°C) ethylether, og der dannes en fældning, som fjernes ved filtrering. Filtratet vaskes med vandig 35 saltsyre, vandig natriumhydroxidopløsning og vand. Det organiske lag tørres med vandfrit magnesiumsulfat og inddampes,To a cold (0 ° C) solution of 1.53 g (3.60 mmol) of 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3-trifluoro-methylthio-4-cyanopyrrole (prepared in the procedure described in Example 13, mp about 182 ° C) in 15 ml of pyridine 30, a solution of 1.46 g (3.6 mmol) of 80% pyridinium bromide perbromide in 15 ml of pyridine is added under an inert atmosphere. After 30 minutes, the reaction mixture is poured into cold ether (0 ° C) ethyl ether and a precipitate is formed which is removed by filtration. The filtrate is washed with aqueous hydrochloric acid, aqueous sodium hydroxide solution and water. The organic layer is dried over anhydrous magnesium sulfate and evaporated,

I DK 175618 B1 II DK 175618 B1 I

I 106 I hvorved der fås 1,34 g af et brunt, fast stof. Dette kom- bineres med 230 mg produkt fra en tidligere omsætning af I 300 mg (0,7 mmol) 1-(2,6-dichlor-4-trifluormethylphenyl)-2- I amino-3-trifluormethylthio-4-cyanopyrrol og 0,2,9 g 80%'s I 5 pyridiniumbromidperbromid. De samlede produkter chromatogra-I 106 I yields 1.34 g of a brown solid. This is combined with 230 mg of product from a previous reaction of I 300 mg (0.7 mmol) of 1- (2,6-dichloro-4-trifluoromethylphenyl) -2- I amino-3-trifluoromethylthio-4-cyanopyrrole and 0 , 2.9 g 80% in pyridinium bromide perbromide. The total chromatographic products

feres på silicagel, idet der elueres med en blanding af Ion silica gel, eluting with a mixture of I

I hexan og ethylacetat i rumfangsforholdet 4:1, hvorved der IIn hexane and ethyl acetate in a 4: 1 volume ratio, whereby I

I fås 1,31 g (73%) 1-(2,6-dichlor-4-trifluormethylphenyl)-2- I1.31 g (73%) of 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-1

I amino-3-trifluormethylthio-4-cyano-5-brompyrrol (eksempel 12) IIn amino-3-trifluoromethylthio-4-cyano-5-bromopyrrole (Example 12) I

I 10 i form af et hvidt, fast stof. Ved omkrystallisation fra en IIn 10 in the form of a white solid. Upon recrystallization from an I

I blanding af hexan og ethylacetat fås der 910 mg af dette IIn a mixture of hexane and ethyl acetate, 910 mg of this is obtained

I produkt i form af farveløse nåle med smp. ca. 160°C. IIn product in the form of colorless needles with m.p. ca. 160 ° C. IN

I Eksempel 13 IIn Example 13 I

I 15 II 15 I

I En omrørt opløsning af 2,00 g (6,25 mmol) 1-(2,6- IIn a stirred solution of 2.00 g (6.25 mmol) of 1- (2.6-I)

I dichlor-4 - trif luormethylphenyl)-2-amino-4-cyanopyrrol i IIn dichloro-4-trifluoromethylphenyl) -2-amino-4-cyanopyrrole in I

60 ml dichlormethan, fremstillet som angivet i det følgende, I60 ml of dichloromethane, prepared as follows, I

afkøles ved hjælp af et isbad, og der tilsættes i en langsom Icool using an ice bath and add in a slow I

20 strøm 10 ml af en kold (-78QC) dichlormethanopløsning inde- I20 stream 10 ml of a cold (-78 ° C) dichloromethane solution contained i

I holdende 0,55 ml (0,85 g eller 6,2 mmol) trifluormethansul- IContaining 0.55 ml (0.85 g or 6.2 mmol) of trifluoromethane sulfur

I fenylchlorid. Efter omrøring ved 0°C i 2 timer ledes der en IIn phenyl chloride. After stirring at 0 ° C for 2 hours, an I is conducted

I strøm af nitrogen gennem reaktionsblandingen i 1 time. Ved IIn stream of nitrogen through the reaction mixture for 1 hour. Do you know

I fordeling med mættet vandig natriumbicarbonatopløsning og IIn distribution with saturated aqueous sodium bicarbonate solution and I

I 25 vand, tørring med vandfrit magnesiumsulfat og koncentrering IIn 25 water, drying with anhydrous magnesium sulfate and concentration I

I i vakuum fås der 3,14 g af et lysebrunt, fast stof. Dette IIn vacuo there is obtained 3.14 g of a light brown solid. This I

I stof chromatograferes på silicagel under anvendelse af et IIn substance, chromatographed on silica gel using an I

I elueringsmiddel bestående af en blanding af dichlormethan IIn eluent consisting of a mixture of dichloromethane I

I og hexan i rumfangsforholdet 3:2, hvorved der fås to farve- II and hexane in the 3: 2 volume ratio to give two color I

I 30 løse, faste prøver, der vejer 900 mg og 950 mg. Disse omkry- IIn 30 solid samples weighing 900 mg and 950 mg. These surround- I

I stalliseres fra chloroform, hvorved der fås henholdsvis 680 IYou are stalled from chloroform to give 680 I, respectively

I og 630 mg 1-(2,6-dichlor-4-trifluormethylphenyl)-2-amino-3- II and 630 mg of 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3- I

I trifluormethylthio-4-cyanopyrrol (eksempel 13) med smp. IIn trifluoromethylthio-4-cyanopyrrole (Example 13), m.p. IN

I ca. 182°C. IFor approx. 182 ° C. IN

I 35 Den reaktant, der anvendes ved denne fremgangsmåde, IThe reactant used in this process,

I fremstilles på følgende måde: En opløsning af 4,64 g II is prepared as follows: A solution of 4.64 g of I

107 DK 175618 B1 (14,5 mmol) 1-[ (2,6-dichlor-4-trifluormethylphenyl)-amino]- 2,3-dicyanopropen og 2,02 ml (1,47 g eller 14,5 mmol) tri-ethylamin i 30 ml benzen opvarmes til tilbagesvaling natten over og koncentreres derefter i vakuum. Remanensen fordeles 5 mellem ethylether og vand, og etherlaget tørres med vandfrit magnesiumsulfat og koncentreres, hvorved der fås 3,79 g af et lysebrunt, fast stof. Ved omkrystallisation fra en blanding af ethanol og vand fås der 2,79 g (60%) 1-(2,6-dichlor-4 -1 r i f 1 uorme t hyl phenyl )-2- amino - 4 -cyanopyrrol med smp.B1 (14.5 mmol) 1- [(2,6-dichloro-4-trifluoromethylphenyl) amino] -2,3-dicyanopropene and 2.02 ml (1.47 g or 14.5 mmol) tri -ethylamine in 30 ml of benzene is heated to reflux overnight and then concentrated in vacuo. The residue is partitioned between ethyl ether and water and the ether layer is dried over anhydrous magnesium sulfate and concentrated to give 3.79 g of a light brown solid. Recrystallization from a mixture of ethanol and water afforded 2.79 g (60%) of 1- (2,6-dichloro-4-1 in 1-dimethylphenyl) -2-amino-4-cyanopyrrole, m.p.

10 ca. 176°C.10 approx. 176 ° C.

Udgangsmaterialet 1-arylamino-2,3-dicyano-propen fremstilles på følgende måde: En prøve på 20,5 g (0,140 mol) af kaliumsaltet af formylsuccinonitril opløses i ca. 30 ml vand, og opløsningen gøres sur med koncentreret saltsyre.The starting material 1-arylamino-2,3-dicyano-propene is prepared as follows: A sample of 20.5 g (0.140 mol) of the potassium salt of formylsuccinonitrile is dissolved in ca. 30 ml of water and the solution is acidified with concentrated hydrochloric acid.

15 Opløsningen ekstraheres med ethylether, og etherekstrakten tørres med vandfrit magnesiumsulfat og inddampes, hvorved der fås 3,87 g af en brun væske. Denne sættes til en opløsning indeholdende 5,04 g (22 mmol) 2,6-dichlor-4-trifluor-methylanilin og 40 mg p-toluensulfonsyre-monohydrat i 50 ml 20 benzen. Den heterogene reaktionsblanding opvarmes til tilbagesvaling natten over under fraskillelse af vand. Reaktionsblandingen afkøles derefter og koncentreres, hvorved der fås 7,66 g af en gul væske. Ved tri turering med hexan udfældes der 6,68 g (95%) 1-[(2,6-dichlor-4-trifluormethyl-25 phenyl)-amino]-2,3-dicyanopropen i form af et gult, fast stof. Ved omkrystallisation fra en blanding af ethanol og vand fås der en prøve med smeltepunkt ca. 101°c.The solution is extracted with ethyl ether and the ether extract is dried over anhydrous magnesium sulfate and evaporated to give 3.87 g of a brown liquid. This is added to a solution containing 5.04 g (22 mmol) of 2,6-dichloro-4-trifluoro-methylaniline and 40 mg of p-toluenesulfonic acid monohydrate in 50 ml of benzene. The heterogeneous reaction mixture is heated to reflux overnight with water separation. The reaction mixture is then cooled and concentrated to give 7.66 g of a yellow liquid. When triturated with hexane, 6.68 g (95%) of 1 - [(2,6-dichloro-4-trifluoromethyl-phenyl) -amino] -2,3-dicyanopropene is precipitated as a yellow solid. By recrystallization from a mixture of ethanol and water, a sample having a melting point of approx. 101 ° C.

Eksempel 14a og 14b 30Examples 14a and 14b 30

Til en suspension af 1,17 g (3,30 mmol) 2-(4-trifluor-methylphenyl)-2-amino-3-trifluormethylthio-4-cyanopyrrol og 0,46 ml (0,34 g eller 3,3 mmol) triethylamin i 20 ml chloroform, afkølet til -20°C, sættes der en opløsning af 0,19 ml 35 (0,59 g eller 3,7 mmol) brom i 5 ml chloroform. Reaktions blandingen omrøres ved -20°C i 1 time og tillades derpå atTo a suspension of 1.17 g (3.30 mmol) of 2- (4-trifluoro-methylphenyl) -2-amino-3-trifluoromethylthio-4-cyanopyrrole and 0.46 ml (0.34 g or 3.3 mmol) ) triethylamine in 20 ml of chloroform, cooled to -20 ° C, a solution of 0.19 ml of 35 (0.59 g or 3.7 mmol) of bromine in 5 ml of chloroform is added. The reaction mixture is stirred at -20 ° C for 1 hour and then allowed to

I DK 175618 B1 II DK 175618 B1 I

I 108 II 108 I

I varme op til 0°C. Der tilsættes dernæst yderligere 0,04 ml IIn heat up to 0 ° C. Then an additional 0.04 ml of I is added

I (0,13 g eller 0,8 mmol) brom, og efter yderligere 15 minut- IBromine (0.13 g or 0.8 mmol) and after a further 15 minutes I

I ters omrøring fortyndes reaktionsblandingen med dichlormethan IWith stirring, the reaction mixture is diluted with dichloromethane I

I og fordeles mellem vand og en mættet vandig natriumbicar- IAnd distributed between water and a saturated aqueous sodium bicarbonate

I 5 bonatopløsning. Det organiske lag tørres med vandfrit mag- IIn 5 bonate solution. The organic layer is dried with anhydrous mag

I nesiumsulfat og koncentreres, hvorved der fås 1,11 g af et IIn nesium sulfate and concentrated to give 1.11 g of an I

I brunt, fast stof. Dette materiale kombineres med materialet IIn brown, solid. This material is combined with the material I

I fra en tidligere omsætning af 1,00 g (2,8 mmol) l-(4-tri- IIn a previous reaction of 1.00 g (2.8 mmol) of 1- (4-tri-I)

I f luormethylphenyl) -2-amino-3-trif luormethylthio-4-cyanopyrrol I(Fluoromethylphenyl) -2-amino-3-trifluoromethylthio-4-cyanopyrrole I

I 10 og 0,15 ml brom. Ved chromatografi på silicagel under elue- IIn bromine and 0.15 ml. By chromatography on silica gel under elu- I

ring med en blanding af dichlormethan og hexan i rumfangs- Iring with a mixture of dichloromethane and hexane in volume I

I forholdet 3:1 fås der 1,40 g (51%) 1-(4-trifluormethylphe- IIn the 3: 1 ratio, 1.40 g (51%) of 1- (4-trifluoromethylphenyl) is obtained.

I nyl)-2-amino-3-trifluormethylthio-4-cyano-5-brompyrrol (ek- I(Nyl) -2-amino-3-trifluoromethylthio-4-cyano-5-bromopyrrole (e.g.

I sempel 14a) i form af et gult, fast stof. Ved omkrystalli- IIn Example 14a) in the form of a yellow solid. By recrystalli- I

I 15 sation fra en blanding af hexan og ethylacetat fås produktet IIn 15 sation from a mixture of hexane and ethyl acetate, product I is obtained

I i form af lysegule småplader med smp, ca, 175°C. IIn the form of light yellow small plates with m.p., about 175 ° C. IN

I Forbindelsen 1-(4-trif luorme thylphenyl) -2-amino-3- IIn Compound 1- (4-Trifluoromethylphenyl) -2-amino-3- I

I trifluormethylthio-4-cyanopyrrol (eksempel 14b) med smp. IIn trifluoromethylthio-4-cyanopyrrole (Example 14b), m.p. IN

I ca. 152°C kan fremstilles ud fra 1-[ (4-trifluormethylphenyl) - IFor approx. 152 ° C can be prepared from 1- [(4-trifluoromethylphenyl) - I

I 20 amino)-2,3-dicyanopropen ved en fremgangsmåde, der svarer IIn 20 amino) -2,3-dicyanopropene by a method similar to I

I til den i eksempel 13 beskrevne. II to the one described in Example 13. IN

I Eksempel 15a og 15b IIn Examples 15a and 15b I

I 25 1-[(2-Chlor-4-trifluormethylphenyl)-amino]-2,3-dicy- I1 - [(2-Chloro-4-trifluoromethylphenyl) amino] -2,3-dicylic acid

I anopropen fremstilles ved en fremgangsmåde svarende til den IThe anoprop is prepared by a method similar to that of I

I i eksempel 13 beskrevne. Denne dicyanopropen anvendes til IIn Example 13 described. This dicyanopropene is used for I

I fremstilling af 1-(2-chlor-4-trifluormethylphenyl)-2-amino- IIn the preparation of 1- (2-chloro-4-trifluoromethylphenyl) -2-amino-I

I 3-trifluormethylthio-4-cyanopyrrol (eksempel 15a) med smp. IIn 3-trifluoromethylthio-4-cyanopyrrole (Example 15a), m.p. IN

I 30 ca. 169°C, der fremstilles ved en fremgangsmåde svarende IFor approx. 169 ° C, prepared by a process similar to I

I til den i eksempel 13 beskrevne. Denne pyrrol anvendes til II to the one described in Example 13. This pyrrole is used for I

I 3 - trif luormethylthio-4-cyano-5-brompyrrol (eksempel 15b) II 3- trifluoromethylthio-4-cyano-5-bromopyrrole (Example 15b) I

I med smp. ca. 157°C under anvendelse af fremgangsmåden ifølge II with m.p. ca. 157 ° C using the method of I

I 35 eksempel 14. IIn Example 14. I

DK 175618 B1 IDK 175618 B1 I

Ϊ09 IΪ09 I

Eksempel 16a og 16b IExamples 16a and 16b I

1-(2,6-dichlor-4-trifluormethylphenyl)-2-amino-4- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-amino-4- I

cyanopyrrol, fremstillet ifølge eksempel 13, behandles med Icyanopyrrole, prepared according to Example 13, is treated with I

5 CFCl2-SCl i overensstemmelse med fremgangsmåden fra eksem- I5 CFC12-SC1 according to the method of Example I

pel 13 (hvor der anvendes CF3SCI) til fremstilling af 1-(2,6- Icolumn 13 (using CF3 SCI) to prepare 1- (2.6-1)

dichlor-4-trifluormethylphenyl) -2-amino-3-dichlorfluorméthyl- Idichloro-4-trifluoromethylphenyl) -2-amino-3-dichlorofluoromethyl-1

thio-4-cyanopyrrol (eksempel 16a) med smp. ca. 202°C. Ithio-4-cyanopyrrole (Example 16a), m.p. ca. 202 ° C. IN

Denne forbindelse behandles med tert.butylnitrit ved IThis compound is treated with tert-butyl nitrite at I

10 fremgangsmåden ifølge eksempel 4, hvorved der fås 1-(2,6- I10 the procedure of Example 4 to give 1- (2.6-1)

dichlpr-4-trifluormethylphenyl)-2-chlor-3-cyano-4-(dichlor- Idichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (dichloro-1

fluormethylthio)-pyrrol (eksempel 16b) med smp. ca. 158°C. Ifluoromethylthio) pyrrole (Example 16b), m.p. ca. 158 ° C. IN

Eksempel 17 IExample 17 I

1515

Den sidste forbindelse i eksempel 16 omsættes ved en IThe last compound of Example 16 is reacted by an I

fremgangsmåde, der svarer til fremgangsmåden fra eksempel 1 Ia procedure similar to that of Example 1 I

og 2, under anvendelse af hydrogenperoxid i trifluormethyl- Iand 2, using hydrogen peroxide in trifluoromethyl-I

pereddikesyre (i stedet for m-chlor-peroxybenzoesyre), hvor-20 ved der fås 1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-peracetic acid (instead of m-chloro-peroxybenzoic acid) to give 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro

3-cyano-4-(dichlorfluormethylsulfinyl)-pyrrol (eksempel 17) I3-cyano-4- (dichlorofluoromethylsulfinyl) pyrrole (Example 17) I

med smp. Ga. 119°C.with m.p. Go. 119 ° C.

Eksempel 18 25Example 18 25

Ved anvendelse af fremgangsmåden fra eksempel 17 under anvendelse af den dobbelte mængde hydrogenperoxid omdannes den sidste forbindelse i eksempel 16 til 1-(2,6-dichlor-4-trifluormethylphenyl)-2-chlor-3-cyano-4-(dichlor-30 f luorme thyl sul fonyl) -pyrrol (eksempel 18) med smp. ca. 179°C.Using the procedure of Example 17 using the double amount of hydrogen peroxide, the last compound of Example 16 is converted to 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (dichloro-30 f luorme thyl sulphonyl) pyrrole (Example 18) m.p. ca. 179 ° C.

Eksempel 19Example 19

Den første forbindelse i eksempel 16 behandles med 35 tert.butylnitrit ifølge fremgangsmåden fra eksempel 4, hvorved der fås 1-(2,6-dichlor-4-trifluormethylphenyl)-3-cyano-The first compound of Example 16 is treated with 35 tert-butyl nitrite according to the procedure of Example 4 to give 1- (2,6-dichloro-4-trifluoromethylphenyl) -3-cyano-4

110 I110 I

DK 175618 B1 IDK 175618 B1 I

4- (dichlorfluormethylthio)-pyrrol (eksempel 19) med smp. I4- (dichlorofluoromethylthio) pyrrole (Example 19), m.p. IN

ca. 120°C. Ica. 120 ° C. IN

Eksempel 20 IExample 20 I

Forbindelsen fra eksempel 19 oxideres i overensstem-The compound of Example 19 is oxidized accordingly.

melse med fremgangsmåden fra eksempel 17, hvorved der fås Iin accordance with the method of Example 17, which gives I

1-(2,6-dichlor-4-trifluormethylphenyl)-3-cyano-4-(dichlor- I1- (2,6-Dichloro-4-trifluoromethylphenyl) -3-cyano-4- (dichloro-1

f luormethylsulfinyl) -pyrrol (eksempel 20) med smp. 150-152°C. I(fluoromethylsulfinyl) pyrrole (Example 20), m.p. 150-152 ° C. IN

10 I10 I

Eksempel 21a, 21b og 21c IExamples 21a, 21b and 21c I

1-[ (2,6-dichlor-4-trifluormethoxyphenyl)-amino]-2,3- I1- [(2,6-dichloro-4-trifluoromethoxyphenyl) amino] -2,3-I

dicyanopropen fremstilles, ifølge fremgangsmåden til fremstil- Idicyanopropene is prepared according to the method of preparation I

15 ling af den sidste forbindelse i eksempel 13, idet der anven- I15 of the last compound of Example 13, using I

des 2,6-dichlor-4-trif 1 uormethoxyanilin i stedet for 2,6-dichlor-4-trifluormethylanilin.des 2,6-dichloro-4-trifluoromethoxyaniline instead of 2,6-dichloro-4-trifluoromethylaniline.

Denne forbindelse omdannes til 1-(2,6-dichlor-4-tri- IThis compound is converted to 1- (2,6-dichloro-4-tri-I)

fluormethoxyphenyl)-2-amino-4-cyanopyrrol i overensstemmelse Hfluoromethoxyphenyl) -2-amino-4-cyanopyrrole according to H

20 med fremgangsmåden til fremstilling af den anden forbindelse I20 with the method of preparing the second compound I

i eksempel 13. min Example 13. m

Denne forbindelse omdannes til 1-(2,6-dichlor-4-tri-· fluormethoxyphenyl) -2-amino-3-trifluormethylthio-4-cyanopyr-This compound is converted to 1- (2,6-dichloro-4-trifluoromethoxyphenyl) -2-amino-3-trifluoromethylthio-4-cyanopyridine.

rol under anvendelse af fremgangsmåden til fremstilling af Irole using the method of preparing I

25 den første forbindelse i eksempel 13. I25 the first compound of Example 13. I

fluormethoxyphenyl)-2-amino-3-(trifluormethylthio)-4-cyano- Ifluoromethoxyphenyl) -2-amino-3- (trifluoromethylthio) -4-cyano-I

5- chlorpyrrol (eksempel 21a) med smp. 196-197°C under anven- I5-chloropyrrole (Example 21a), m.p. 196-197 ° C under use

delse af fremgangsmåden fra eksempel 8. IThe method of Example 8. I

30 Denne forbindelse omdannes til 1-(2,6-dichlor-4-tri- IThis compound is converted to 1- (2,6-dichloro-4-tri-I)

fluormethoxyphenyl) -2-chlor-3-cyano-4-trifluormethylthio- Ifluoromethoxyphenyl) -2-chloro-3-cyano-4-trifluoromethylthio-I

pyrrol (eksempel 21b) med smp. 172°C ved anvendelse af frem- Ipyrrole (Example 21b), m.p. 172 ° C using forward I

gangsmåden fra eksempel 4. Denne forbindelse omdannes til IThe procedure of Example 4. This compound is converted to I

1- (2,6-dichlor-4-trifluormethoxyphenyl)-2-chlor-3-cyano-4- I1- (2,6-Dichloro-4-trifluoromethoxyphenyl) -2-chloro-3-cyano-4- I

35 trifluormethylsulfonylpyrrol (eksempel 21c) med smp. 187°C ITrifluoromethylsulfonylpyrrole (Example 21c), m.p. 187 ° C

ved anvendelse af fremgangsmåden fra eksempel 18. Iusing the method of Example 18. I

111 DK 175618 B1111 DK 175618 B1

Eksempel 22a. 22b og 22cExample 22a. 22b and 22c

En blanding af 2-chlor-4-chlorsulfenyl-3-cyano-l- ! (2',6'-dichlor-41-trifluormethyl-phenyl)-pyrrol og 2-chlor-5 3- cyano-4-dichlorfluor-methylsulfenyl-1- (2 ' , 6' -dichlor-4 1 - trifluormethylphenyl)-pyrrol (47,77 g, 0,101 mol eller 1,0 ækv.) opløses i 190 ml trifluoreddikesyre ved 0°C, og der tilsættes dråbevis 10,8 ml (0,106 mol eller 1,05 ækv.) 30%'s hydrogenperoxid. Reaktionsblandingen omrøres ved 0°C 10 i 7 timer og 15 minutter og anbringes derpå i køleskab (10°C) natten over. Der tilsættes yderligere 10,8 ml (0,106 mol eller 1,05 ækv.) 30%'s hydrogenperoxid ved 0°C den følgende morgen. Reaktionsblandingen omrøres ved 0°C i 9 timer og anbringes derefter i køleskab natten over. Den følgende 15 morgen tilsættes der ved 0°C yderligere 10,8 ml (0,106 mol eller 1,05 ækv.) 30%'s hydrogenperoxid. Efter 3¾ times forløb udhældes reaktionsblandingen i 2 liter af en blanding af is og vand, hvorefter der omrøres kraftigt og filtreres.A mixture of 2-chloro-4-chlorosulphenyl-3-cyano-1- (2 ', 6'-dichloro-41-trifluoromethyl-phenyl) -pyrrole and 2-chloro-5-cyano-4-dichlorofluoromethylsulphenyl-1- (2', 6'-dichloro-4'-trifluoromethyl-phenyl) - pyrrole (47.77 g, 0.101 mole or 1.0 eq.) is dissolved in 190 ml of trifluoroacetic acid at 0 ° C and 10.8 ml (0.106 mole or 1.05 eq.) of 30% hydrogen peroxide are added dropwise. The reaction mixture is stirred at 0 ° C for 7 hours and 15 minutes and then refrigerated (10 ° C) overnight. An additional 10.8 ml (0.106 mol or 1.05 eq) of 30% hydrogen peroxide is added at 0 ° C the following morning. The reaction mixture is stirred at 0 ° C for 9 hours and then refrigerated overnight. The following 15 mornings, an additional 10.8 ml (0.106 mol or 1.05 eq) of 30% hydrogen peroxide is added at 0 ° C. After 3 hours, the reaction mixture is poured into a mixture of ice and water in 2 liters, then vigorously stirred and filtered.

På tilsvarende måde opløses en blanding af 2-chlor-20 4-chlorsulfenyl-3-cyano-l-(2',6'-dichlor-4'-trifluormethyl-phenyl)-pyrrol og 2-chlor-3-cyano-4-dichlorfluormethylsul-fenyl- 1 - (2',6'-dichlor-4 *-trifluormethylphenyl)-pyrrol (40,77 g, 0,0848 mol eller 1,0 ækv.) i 188 ml trifluoreddikesyre ved 0°C. Der tilsættes dråbevis 17,7 ml (0,173 mol 25 eller 2,05 ækv.) 30%'s hydrogenperoxid. Reaktionsblandingen omrøres ved 0°C i 2 timer og 45 min. og anbringes derpå natten over i et køleskab ved 10°C. Efter omrøring i 8 timer ved 0°C anbringes reaktionsblandingen igen i køleskab natten over. Blandingen får dernæst lov at varme op til stuetempe-30 ratur og omrøres natten over ved stuetemperatur. Der tilsættes ved 0°C den følgende morgen yderligere 9,05 ml (0,0886 mol eller 1,05 ækv.) 30%'s hydrogenperoxid, og reaktionsblandingen holdes ved 0°C i 6 timer og 40 min., hvorefter den får lov at varme op til stuetemperatur og omrøres 35 weekenden over. Blandingen udhældes i 2 liter af en blanding af is og vand, omrøres kraftigt og filtreres derefter.Similarly, a mixture of 2-chloro-4-chlorosulphenyl-3-cyano-1- (2 ', 6'-dichloro-4'-trifluoromethyl-phenyl) -pyrrole and 2-chloro-3-cyano-4 is dissolved. -dichlorofluoromethylsul-phenyl-1- (2 ', 6'-dichloro-4 * -trifluoromethylphenyl) -pyrrole (40.77 g, 0.0848 mol or 1.0 equiv) in 188 ml of trifluoroacetic acid at 0 ° C. 17.7 ml (0.173 mol 25 or 2.05 eq) of 30% hydrogen peroxide are added dropwise. The reaction mixture is stirred at 0 ° C for 2 hours and 45 minutes. and then placed overnight in a refrigerator at 10 ° C. After stirring for 8 hours at 0 ° C, the reaction mixture is again refrigerated overnight. The mixture is then allowed to warm to room temperature and stirred overnight at room temperature. The following morning an additional 9.05 ml (0.0886 mol or 1.05 eq) of 30% hydrogen peroxide is added at 0 ° C and the reaction mixture is kept at 0 ° C for 6 hours and 40 minutes, then allowed allowed to warm to room temperature and stirred over the weekend. The mixture is poured into 2 liters of a mixture of ice and water, stirred vigorously and then filtered.

I DK 175618 B1 II DK 175618 B1 I

I 112 II 112 I

I Fældningerne fra begge reaktioner kombineres og oplø- IThe precipitates from both reactions are combined and dissolved

I ses i 500 ml dichlormethan og vaskes med 500 ml vand, 500 ml IDissolve in 500 ml of dichloromethane and wash with 500 ml of water, 500 ml of I

I 10%'s vandig natriumhydrogensulfitopløsniong og 500 ml mættet IIn 10% aqueous sodium hydrogen sulfite solution and 500 ml of saturated I

I natriumchloridopløsning. Den organiske fase tørres med natri- IIn sodium chloride solution. The organic phase is dried with sodium I

I 5 umsulfat og filtreres, og opløsningsmidlet fordampes, hvorved IIn 5 sulfurate and filter, the solvent is evaporated to give I.

I der fås 74,96 g (79,9%'s udbytte) af et fast stof. Dette I74.96 g (79.9% yield) of solid are obtained. This I

I omkrystalliseres fra 690 ml af en blanding af hexan og di- IRecrystallize from 690 ml of a mixture of hexane and di-I

I chlormethan i forholdet 2:1, hvortil der sættes 20 ml di- IIn chloromethane in a 2: 1 ratio, to which 20 ml of di-I is added

I chlormethan, hvorved der fås 6,98 g af et fast stof, der IIn chloromethane to give 6.98 g of a solid which I

I 10 identificeres som 2'-chlor-4-chlorsulfonyl-3-cyano-l-(2 1,6 ' - II is identified as 2'-chloro-4-chlorosulfonyl-3-cyano-1- (2,6 '- 1

I dichlor-4 '-trifluormethylphenyl)-pyrrol (eksempel 22a). IIn dichloro-4 '-trifluoromethylphenyl) -pyrrole (Example 22a). IN

I Denne forbindelse omkrystalliseres derefter fra 103 ml iso- IIn this compound is then recrystallized from 103 ml of iso-I

I propanol, hvorved der fås 3,97 g med smp. 187-188,5°C. IIn propanol to give 3.97 g of m.p. 187-188.5 ° C. IN

I 3,97 g (9,06 mmol eller 1,0 ækv.) 2-chlor-4-chlorsul- IIn 3.97 g (9.06 mmol or 1.0 eq) of 2-chloro-4-chlorosulphuric acid

I 15 fonyl-3-cyano-1 - (2 6 1 -dichlor-4 ’-trifluormethylphenyl) - IIn phonyl-3-cyano-1- (2,6-dichloro-4'-trifluoromethylphenyl) - I

I pyrrol opløses i 15,8 ml tetrahydrofuran ved 0°C. Der til- IIn pyrrole, dissolve in 15.8 ml of tetrahydrofuran at 0 ° C. There- I

I sættes 2,41 g (1,0 ækv.) triphenylphosphin i form af et I2.41 g (1.0 eq) of triphenylphosphine is added as an I

I fast stof. Opløsningen bliver herved gul. Efter 2¾ times IIn solid. The solution becomes yellow. After 2¾ hours I

I forløb fjernes isbadet, og reaktionsblandingen omrøres natten IGradually, the ice bath is removed and the reaction mixture is stirred overnight

I 20 over ved stuetemperatur. Der tilsættes yderligere 2,55 g IAt 20 over at room temperature. An additional 2.55 g of I is added

I (9,72 mmol eller 1,06 ækv.) triphenylphosphin, og reaktions- II (9.72 mmol or 1.06 eq) triphenylphosphine, and reaction I

I blandingen omrøres ved stuetemperatur natten over. Der dannes IIn the mixture, stir at room temperature overnight. It forms

I en fældning, der tilsættes 3 ml tetrahydrofuran, og reak- IIn a precipitate, add 3 ml of tetrahydrofuran, and react I

I tionsbiåndingen vaskes to gange med mættet natriumchloridop- IIn the reaction mixture, wash twice with saturated sodium chloride solution

I 25 løsning og tilbageekstraheres. Den organiske fase tørres IIn 25 solution and back extracted. The organic phase is dried

I med magnesiumsulfat og filtreres, og opløsningsmidlet for- IWith magnesium sulfate and filtered and the solvent evaporated

I dampes i vakuum, hvorved der fås et voksagtigt, fast stof.i IYou evaporate in vacuo to give a waxy solid

I en mængde på 9,44 g. Dette stof chromatograferes på silica- IIn an amount of 9.44 g. This substance is chromatographed on silica-I

I gel, hvorved der fås 3,39 g af et voksagtigt, fast stof. IIn gel to give 3.39 g of a waxy solid. IN

I 30 Dette stof omkrystalliseres derefter fra 140 ml isopropanol, IThis substance is then recrystallized from 140 ml of isopropanol, I

I hvorved der fås 2,54 g (74,9%) bis- [2-chlor-3-cyano-l- (21,6’ - ITo give 2.54 g (74.9%) of bis- [2-chloro-3-cyano-1- (21,6 '- 1)

I dichlor-4'-trifluormethylphenyl)-pyrrol-4-yl]-disulfid (ek- IIn dichloro-4'-trifluoromethylphenyl) -pyrrol-4-yl] disulfide (e.g.

I sempel 22b) med smp. 218,8-220,3°C. IIn Example 22b), m.p. 218.8 to 220.3 ° C. IN

I 0,80 g (1,08 mmol eller 1,0 ækv.) bis-[2-chlor-3- IIn 0.80 g (1.08 mmol or 1.0 eq) of bis- [2-chloro-3- I

I 35 cyano-1 - (2', 6 ’-dichlor-4 ’-trifluormethylphenyl)-pyrrol-4 - IIn cyano-1- (2 ', 6' -dichloro-4 '-trifluoromethylphenyl) -pyrrole-4-I

I yl]-disulfid opløses i 10 ml dimethylformamid og afkøles HIn yl] disulfide is dissolved in 10 ml of dimethylformamide and cooled H

DK 175618 Β· 113 til 0°C. 0,46 g (3,24 mmol eller 3,0 ækv.) Na2HP04 opløses i 5 ml vand, hvorefter dette sættes til DMF-opløsningen.DK 175618 113 · 113 to 0 ° C. Dissolve 0.46 g (3.24 mmol or 3.0 eq) of Na2HPO4 in 5 ml of water and add to the DMF solution.

Der dannes en fældning, og der tilsættes dernæst 15 ml DMF og 10 ml vand. Der tilsættes herefter 0,564 g (3,24 mmol 5 eller 3,0 ækv.) fast Na2S204. Reaktionsblandingen antager en bleggul farve. Der sættes 0,65 g (3,1 mmol eller 2,87 ækv.) dibromdifluormethan til en kold, aftareret ampul, hvorpå dette stof overføres til reaktionsblandingen. Reaktionsblandingen bliver farveløs under dannelse af en hvid 10 fældning. Efter 1 time og 50 minutters forløb tilsættes der 10 ml DMF, efterfulgt af yderligere 0,93 g CBr2F2, og reaktionsbeholderen tillukkes og omrøres ved stuetemperatur natten over. Efter afkøling til 0°C sættes reaktionsblandingen til 200 ml vand og ekstraheres fire gange med 150 ml 15 ethylether. Den organiske fase vaskes to gange med 150 ml 5%'s saltsyre, to gange med 100 ml mættet natriumhydrogen-carbonatopløsning og med 100 ml mættet natriumchloridopløs-ning. Den organiske fase tørres med magnesiumsulfat og filtreres, og opløsningsmidlet fordampes i vakuum, hvorved der 20 fås 80,7 mg af et hvidt, fast stof. Den første vandige fase filtreres derefter, hvorved der opsamles et hvidt, fast stof, der udfældes natten over. Dette stof opløses i dichlor-methan, opløsningsmidlet fordampes i vakuum, og der tørres, hvorved der fås 0,348 g af et hvidt, fast stof (totalt ud-25 bytte 0,429 g eller 40%). Dette stof kombineres med prøven på 80,7 mg og chromatograferes på silicagel, hvorved der fås 0,362 g af et hvidt, fast stof, der identificeres som 4-bromdifluormethylsulfenyl-2-chlor-3-cyano-l- (2 ', 6 ' -dichlor-4'-trifluormethylphenyl)-pyrrol (eksempel 22c) med smp.A precipitate is formed and then 15 ml of DMF and 10 ml of water are added. 0.564 g (3.24 mmol of 5 or 3.0 eq) of solid Na 2 S 2 O 4 is then added. The reaction mixture assumes a pale yellow color. 0.65 g (3.1 mmol or 2.87 eq) of dibromodifluoromethane is added to a cold, de-vaporized ampoule and then this substance is transferred to the reaction mixture. The reaction mixture becomes colorless to form a white precipitate. After 1 hour and 50 minutes, 10 ml of DMF is added, followed by an additional 0.93 g of CBr2F2 and the reaction vessel is sealed and stirred at room temperature overnight. After cooling to 0 ° C, the reaction mixture is added to 200 ml of water and extracted four times with 150 ml of 15 ethyl ether. The organic phase is washed twice with 150 ml of 5% hydrochloric acid, twice with 100 ml of saturated sodium hydrogen carbonate solution and with 100 ml of saturated sodium chloride solution. The organic phase is dried over magnesium sulfate and filtered and the solvent is evaporated in vacuo to give 80.7 mg of a white solid. The first aqueous phase is then filtered to collect a white solid which precipitates overnight. This substance is dissolved in dichloromethane, the solvent is evaporated in vacuo and dried to give 0.348 g of a white solid (total yield 0.429 g or 40%). This substance is combined with the 80.7 mg sample and chromatographed on silica gel to give 0.362 g of a white solid identified as 4-bromodifluoromethylsulfenyl-2-chloro-3-cyano-1- (2 ', 6'). -dichloro-4'-trifluoromethylphenyl) -pyrrole (Example 22c), m.p.

30 128,3-133,7°C.128.3-133.7 ° C.

Yderligere svnteseeksemplerFurther synthesis examples

Under anvendelse af de metoder, der er angivet i 35 enkeltheder i det foregående til syntese af forbindelserne ifølge eksempel 1-22, eller de øvrige fremgangsmåder tilUsing the methods set forth in the foregoing details for the synthesis of the compounds of Examples 1-22, or the other methods of

I DK 175618 B1 II DK 175618 B1 I

I 114 II 114 I

I syntese, der generelt er beskrevet i nærværende beskrivelse, IIn synthesis generally described herein, I

I fremstilles der et antal yderligere synteseprodukter (ASE) IA number of additional synthesis products (ASE) I are prepared

I af pyrrolforbindelser med den almene formel I. Strukturerne II of pyrrole compounds of general formula I. The structures I

I for disse forbindelser og deres tilsvarende smeltepunkter II for these compounds and their corresponding melting points

I 5 fremgår af den følgende tabel III (ASE-nr. 1-91: forbindelser II 5 is shown in the following Table III (ASE No 1-91: Compounds I

I med formlen I, hvor X2 og X2 er hydrogen, og de øvrige sub- II of formula I wherein X 2 and X 2 are hydrogen and the other sub-I

I stituenter er som angivet i det foregående) og tabel IV IIn stituents are as given above) and Table IV I

I (ASE-nr. 92-195: forbindelser med formlen I, i hvilken X2 II (ASE Nos. 92-195: compounds of formula I in which X2 I

I og X3 betyder hydrogen, X1 og X4 betyder chlor, Y betyder II and X3 are hydrogen, X1 and X4 are chlorine, Y is I

I 10 trifluormethyl, og de øvrige substituenter har den ovenfor IIn trifluoromethyl, and the other substituents have it above I

I angivne betydning). IIn the sense given). IN

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I Tabel IV IIn Table IV I

I Yderligere eksempler på syntese af pyrrolforbindelser IFurther Examples of Synthesis of Pyrrole Compounds I

I med formlen I, hvor IYou have the formula I wherein I

I X2 & X3=H; x1 & X4=cif og Y=CF3 . IIn X2 & X3 = H; x1 & X4 = cif and Y = CF3. IN

I SUBSTITUENTER IIN SUBSTITUENTS

I ASE R1 X R2 R3 Skid. (° C) II ASE R1 X R2 R3 Skid. (° C) I

I nr.I no.

I 92. NH2 CF2CIS CN H 160.5-175 II 92. NH2 CF2CIS CN H 160.5-175 I

I 93. H CF3SO2 CN H 199.5-201 II 93. H CF3SO2 CN H 199.5-201 I

I 94. H CF2CIS CN H 104.9-106.8 II 94. H CF2CIS CN H 104.9-106.8 I

I 95. H CF2CIS CN CF2CIS 114.5-117 II 95. H CF2CIS CN CF2CIS 114.5-117 I

I 96. NH2 CF2CIS CN Cl 178-181 II 96. NH2 CF2CIS CN Cl 178-181 I

I 97. H CF2CISO2 CN H 199.8-202 II 97. H CF2CISO2 CN H 199.8-202 I

I 98. H CF2CISO2 CN Cl 193.1-195.8 II 98. H CF2CISO2 CN Cl 193.1-195.8 I

I 99. H CF2C1SO CN Cl 145.2-147.5 II 99. H CF2C1SO CN Cl 145.2-147.5 I

I 100. H CF2CIS CN Cl 139.0-143.1 II 100. H CF2CIS CN Cl 139.0-143.1 I

I 101. H CF3S CN Br 137-138 II 101. H CF3S CN Br 137-138 I

I 102. H CF3SO CN Br 164-165.5 II 102. H CF3SO CN Br 164-165.5 I

I 103. H CF3SO2 CN Br 197-198 II 103. H CF3SO2 CN Br 197-198 I

I 104. H CF2C1S0 CN H 126.8-129.6 · II 104. H CF2C1S0 CN H 126.8-129.6 · I

I 105. H CF3S CN H 152-153 II 105. H CF3S CN H 152-153 I

I 106. NH2 CFCI2CF2S CN H 183-190 II 106. NH2 CFCI2CF2S CN H 183-190 I

I 107. NH2 CCI3S CN H 189-193 II 107. NH2 CCI3S CN H 189-193 I

I 108. H CFCI2CF2S CN H 118.8-123.8I 108. H CFCI2CF2S CN H 118.8-123.8

I 109. H CFCI2CF2SO2 CN H 157.5-161.9 II 109. H CFCI2CF2SO2 CN H 157.5-161.9 I

I 110. H CFCI2CF2SO CN H 182.5-183.9 II 110. H CFCI2CF2SO CN H 182.5-183.9 I

I 111. NH2 CFCI2CF2S CN Cl 186.5-188 II 111. NH2 CFCI2CF2S CN Cl 186.5-188 I

Yderligere eksempler på syntese af pyrrolforbindelser med formlen I, hvor X2 & X3=H; X1 & X4=C1; og Y=CF3Further examples of the synthesis of pyrrole compounds of formula I wherein X2 & X3 = H; X1 & X4 = C1; and Y = CF 3

Tabel IVTable IV

DK 175618 B1 123DK 175618 B1 123

SUBSTITUENTERSUBSTITUENTS

ASE R1 X R2 R3 Smo. (° C) nr._ 112. H CFCI2CF2SO CN Cl 149.5-151 113. Br CF3S CN H. 163-164 114. H CFCI2CF2S CN Cl 113.5-116.5 115. H CCI3S CN Cl 177-182 116. H CFCI2CF2SO2 CN Cl 147-150.5 117. H CCI3SO2 CN Cl 200-202 118. H CCI3SO CN Cl 152.2-153.5 119. Cl CF3SO CN H 161.5-162.5 120. NH2 CH3S CN H 150-151 121. H CFCI2S CN Br 117-142 122. NH2 CFCI2S CN Br 195.5-197 123. . Br CF3SO CN H 170-172 124. H CFCI2SO2 CN Br 176-178.5 125. H CFCI2SO . CN Br 116.5-135.5 126. H SCN CN H 173rl73.5 127. Br CF3SO2 CN H 179-180.5 128. H CK3S CN H 107-108.5 129. NH2 CF2C1S CN Br 174.5-178 130. Br CF2CIS CN Cl 129.5-133.5 131. H CF2C1S CN Br 133.5-137.1ASE R1 X R2 R3 Smo. (° C) No. 112. H CFCI2CF2SO CN Cl 149.5-151 113. Br CF3S CN H. 163-164 114. H CFCI2CF2S CN Cl 113.5-116.5 115. H CCI3S CN Cl 177-182 116. H CFCI2CF2SO2 CN Cl 147-150.5 117. H CCI3SO2 CN Cl 200-202 118. H CCI3SO CN Cl 152.2-153.5 119. Cl CF3SO CN H 161.5-162.5 120. NH2 CH3S CN H 150-151 121. H CFCI2S CN Br 117-142 122. NH2 CFCI2S CN Br 195.5-197 123.. Br CF3SO CN H 170-172 124. H CFCI2SO2 CN Br 176-178.5 125. H CFCI2SO. CN Br 116.5-135.5 126. H SCN CN H 173rl73.5 127. Br CF3SO2 CN H 179-180.5 128. H CK3S CN H 107-108.5 129. NH2 CF2C1S CN Br 174.5-178 130. Br CF2CIS CN Cl 129.5-133.5 131. H CF2C1S CN Br 133.5-137.1

I DK 175618 B1 II DK 175618 B1 I

I 124 II 124 I

I Tabel IV : IIn Table IV: I

I med formlen I, hvor IYou have the formula I wherein I

I X2 & X3=H; X1· & X4=C1; og Y=CF3 IIn X2 & X3 = H; X1 · & X4 = C1; and Y = CF3 I

I SUBSTITUENTER IIN SUBSTITUENTS

I ASE r1 X R2 R3 Smp. (° C) II ASE r1 X R2 R3 Mp. (° C) I

I ΓιΧ · HIn ΓιΧ · H

I 132: NH2 Cl CN H 159.5-160 II 132: NH2 Cl CN H 159.5-160 I

I 133. NH2 CF3S CN SCN 169-171 II 133. NH2 CF3S CN SCN 169-171 I

I 134. H CF3S CN SCN 105-106.5 II 134. H CF3S CN SCN 105-106.5 I

I 135. Br CF2CISO CN Cl 157.5-159 II 135. Br CF2CISO CN Cl 157.5-159 I

I 138· H Cl CN H 105.5-106.5 II 138 · H Cl CN H 105.5-106.5 I

I 137. H CH3SO CN H 144.5-145.5 II 137. H CH3SO CN H 144.5-145.5 I

I 138 H CH3SO2 CN H 173-173.5 II 138 H CH3SO2 CN H 173-173.5 I

I 139. NH2 CF3S CN SCH3 14 6-14 8 II 139. NH2 CF3S CN SCH3 14 6-14 8 I

I 140. H CF3S CN SOCH3 143-145 II 140. H CF3S CN SOCH3 143-145 I

I 141. H CF2CISO CN Br 143-146.5 II 141. H CF2CISO CN Br 143-146.5 I

I 142. Br CFCI2SO2 CN Cl 117.8-122.5 II 142th Br CFCI2SO2 CN Cl 117.8-122.5 I

I .143. CF3CONH CF3S CN H 187-188.5 II .143. CF3CONH CF3S CN H 187-188.5 I

I 144. H CF2CISO2 CN Br 182-185 II 144. H CF2CISO2 CN Br 182-185 I

I 143· H CF3S CN CH3S 89-91 II 143 · H CF3S CN CH3S 89-91 I

I 146 · H CF3S CN CH3SO2 136-138 II 146 · H CF3S CN CH3SO2 136-138 I

I 147 - H CF3SO CN CH3SO2 161-163 II 147 - H CF3SO CN CH3SO2 161-163 I

I 148. NH2 CF3CCI2S CN H 200-220 II 148. NH2 CF3CCI2S CN H 200-220 I

I 149. NH2 CF3CCI2S CN Cl 223.5-232.5 II 149. NH2 CF3CCI2S CN Cl 223.5-232.5 I

I 150. H CF3CCI2S CN Cl 170-172.5 II 150. H CF3CCI2S CN Cl 170-172.5 I

I 151. H CF3CCI2SO2 CN Cl 195.6-197.2 II 151. H CF3CCI2SO2 CN Cl 195.6-197.2 I

Yderligere eksempler på syntese af pyrrolforbindelser med formlen I, hvor x2 & X3=H; X1 & X4=C1; og Y=CF3 125Further examples of the synthesis of pyrrole compounds of formula I wherein x2 & X3 = H; X1 & X4 = C1; and Y = CF3 125

Tabel IVTable IV

DK 175618 B1DK 175618 B1

SUBSTITUENTERSUBSTITUENTS

ASE R1 X R2 R3 - Smp.(° C) nr._ 152. H CF3CCI2SO CN Cl 161-161.5 153. H CF3S CN CF3S 95-96 154. NH2 CH3SO CN H 130-132 155. NH2 CH3SO2 CN H 248-248.5 15j6 . H CF3SO CN CF3S 145-148 157. H CH3S CN Cl 128-129 158. NH2 CF3S CN SOCH3 139-141 159. CH3S CF3S CN Cl 73-74 160. NH2 CFCI2SO CN H 156.4-195 161. H CF3SO2 CN CF3S 156-157 162. H CH3SO CN Cl 130-131 163. NH2 CF3S CN F 164-164.5 164. H Cl CN Cl 129-129.5 165. CH3SO CF3S CN Cl 133-135 166. CH3S CFC12S CN Cl 112.2-124.8 167. NH2 CFC12SO CN Cl 163-169.5 168. CF3CONH CF3SO CN H 195-197.5 169. H CF3S CN F 116-117 170. CH3SO2 CFC12S CN Cl 164.5-170.5 171. CH3SO CFC12S CN Cl 193-195.7ASE R1 X R2 R3 - Mp (° C) No_152. H CF3CCl2SO CN Cl 161-161.5 153. H CF3S CN CF3S 95-96 154. NH2 CH3SO CN H 130-132 155. NH2 CH3SO2 CN H 248 248.5 15j6. H CF3SO CN CF3S 145-148 157. H CH3S CN Cl 128-129 158. NH2 CF3S CN SOCH3 139-141 159. CH3S CF3S CN Cl 73-74 160. NH2 CFCI2SO CN H 156.4-195 161. H CF3SO2 CN CF3S 156 -157 162. H CH3SO CN Cl 130-131 163. NH2 CF3S CN F 164-164.5 164. H Cl CN Cl 129-129.5 165. CH3SO CF3S CN Cl 133-135 166. CH3S CFC12S CN Cl 112.2-124.8 167. NH2 CFC12SO CN Cl 163-169.5 168. CF3CONH CF3SO CN H 195-197.5 169. H CF3S CN F 116-117 170. CH3SO2 CFC12S CN Cl 164.5-170.5 171. CH3SO CFC12S CN Cl 193-195.7

I DK 175618 B1 II DK 175618 B1 I

I 126 II 126 I

I Tabel IV IIn Table IV I

I med formlen I, hvor IYou have the formula I wherein I

I SUBSTITUENTER IIN SUBSTITUENTS

I ASE Ri X r2 r3 Smp. (O c) II ASE Ri X r2 r3 Mp. (O c) I

nr._ "_no._ "_

I 172. N«2 CF3SO CN H sønderd. over 175 ^ IIn 172. N «2 CF3SO CN H disintegrated. over 175 ^ I

I 173. H CF3S CF2H H 54-56 II 173. H CF3S CF2H H 54-56 I

I 174. H CH3SO2 CN Cl 165-166· II 174. H CH3SO2 CN Cl 165-166 · I

I 175. H Br CN Br 127.5-128 II 175. H Br CN Br 127.5-128 I

I 176. H Br CN H 120-121 II 176. H Br CN H 120-121 I

I 177. NK2 CFCI2SO2 CN Cl 203-214.5 II 177. NK2 CFCI2SO2 CN Cl 203-214.5 I

I 17 B . H CF3SO CN F 129-130 II 17 B. H CF3SO CN F 129-130 I

I 179. Br Cl CN H 121-123 II 179. Br Cl CN H 121-123 I

I 18 0. . NH2 CF3SO2 CN H 258-260 II 18 0.. NH2 CF3SO2 CN H 258-260 I

I 181. CH3SO CF3SO CN Cl 238-239 II 181. CH3SO CF3SO CN Cl 238-239 I

I 182. H CF2BrS CN Cl 128.3-133.7 II 182. H CF2BrS CN Cl 128.3-133.7 I

I 183. H CF2BrS0 CN Cl 117-119 , II 183. H CF2BrS0 CN Cl 117-119, I

I 184. H CF23rS02 CN Cl 172-181 II 184. H CF23rS02 CN Cl 172-181 I

I 185. H CF3S CH3 H olie II 185. H CF3S CH3 H oil I

I 186. H CF3SO CH3 Br 106-107 II 186. H CF3SO CH3 Br 106-107 I

I 187. H CF3SO2 CH3 Br 7 6-77 II 187. H CF3SO2 CH3 Br 7 6-77 I

I 188. NH2 CF3S CN CH(SCH3)2 159-161 : II 188. NH2 CF3S CN CH (SCH3) 2 159-161: I

I 189. CH3SCH=N CF3S CN CH(SCH3)2124.5-125.5 ; II 189. CH3SCH = N CF3S CN CH (SCH3) 2124.5-125.5; IN

I II I

I 190. H CF3S (CH3) 3COCONH Br 113-114 II 190. H CF3S (CH3) 3COCONH Br 113-114 I

191. H CF3S Br Br olie 1 I191. H CF3S Br Br oil 1 I

Tabel IVTable IV

Yderligere eksempler på syntese af pyrrolforbindelser med formlen I, hvor X2 & X3=H; X1· & X4=C1; og Y=CF3 DK 175618 B1 127Further examples of the synthesis of pyrrole compounds of formula I wherein X2 & X3 = H; X1 · & X4 = C1; and Y = CF3 DK 175618 B1 127

SUBSTITUENTERSUBSTITUENTS

ASE R1 X R2 R3 Smp. (O C) nr ._é .ASE R1 X R2 R3 Mp. (O C) no.

.192. H CF3SO CH3 OH* 149-151 *kan.eksistere som den keto-tautomere 193. Br CF3S CH3 Br olie 194. Br Br H CF3S olie 195. H CF3S CN I 107-109 I DK 175618 B10.192. H CF3SO CH3 OH * 149-151 * may exist as the keto-tautomer 193. Br CF3S CH3 Br oil 194. Br Br H CF3S oil 195. H CF3S CN I 107-109 I DK 175618 B1

I 128 II 128 I

I Pesticide anvendelsesmetoder og præparater IPesticidal Methods and Preparations I

I Ifølge opfindelsen tilvejebringes der en fremgangsmåde IIn accordance with the invention there is provided a method I

I til bekæmpelse af arthropoder, især insekter og acarider, II for the control of arthropods, especially insects and acarides,

I 5 plantenematoder samt helmintiske eller protozo-skadelige IIn 5 plant nematodes as well as helminthic or protozoal damages I

organismer på et sted, der omfatter behandling af stedet, Iorganisms at a site comprising site treatment,

I f.eks. ved påføring eller indgivelse, under anvendelse af IIn e.g. by application or administration, using I

I en virksom mængde af en forbindelse med den almene formel I, IIn an effective amount of a compound of general formula I, I

i hvilken de forskellige symboler har den ovenfor angivne Iin which the various symbols have the above I

I 10 betydning. Forbindelserne med den almene formel I kan i IIn 10 meaning. The compounds of the general formula I can in I

I særdeleshed anvendes inden for det veterinærmedicinske område IIn particular, in the field of veterinary medicine I

samt husdyrbesætninger og ved opretholdelsen af den offent- Ias well as livestock herds and in maintaining the public I

lige sundhed over for arthropoder, helminter eller protozoer, Iequal health to arthropods, helminths or protozoa;

I der er parasitiske internt eller eksternt i forbindelse med IIn which there are parasitic internally or externally associated with I

I 15 vertebrater, navnlig varmblodede vertebrater, f.eks. menne- IIn 15 vertebrates, especially warm-blooded vertebrates, e.g. men- I

I sker og husdyr, f.eks. kvæg, får, geder, heste, svin, fjer- IIn happenings and pets, e.g. cattle, sheep, goats, horses, pigs, feather- I

I kræ, hunde og katte, f.eks. Acarina, herunder blodmider, IIn cats, dogs and cats, e.g. Acarina, including blood mites, I

I (f.eks. Ixodes spp.), Boophilus spp., f.eks. Boophilus micro- II (e.g. Ixodes spp.), Boophilus spp., E.g. Boophilus micro- I

plus, Amblyomma spp., Hyalomma spp., Rhipicephalus spp., Iplus, Amblyomma spp., Hyalomma spp., Rhipicephalus spp., I

20 f.eks. Rhipicephalus appendiculatus, Haemaphysalis spp., I20 e.g. Rhipicephalus appendiculatus, Haemaphysalis spp., I

I Dermacentor spp., Ornithodorus spp. (f.eks. Ornithodorus IIn Dermacentor spp., Ornithodorus spp. (e.g. Ornithodorus I

I moubata) og mider, (f.eks. Damalinia spp., Dermahyssus gal- IIn moubata) and mites, (e.g. Damalinia spp., Dermahyssus gal- I

I linae, Sarcoptes spp., f.eks. Sarcoptes scabiei, Psoroptes IIn lineages, Sarcoptes spp., E.g. Sarcoptes scabiei, Psoroptes I

I spp., Chorioptes spp., Demodex spp., Eutrombicula spp.), IIn spp., Chorioptes spp., Demodex spp., Eutrombicula spp.), I

I 25 Diptera (f.eks. Aedes spp., Anopheles spp., Musca spp., IIn Diptera (e.g., Aedes spp., Anopheles spp., Musca spp., I

I Hypoderma spp., Gasterophilus spp., Simulium spp.), Hemiptera IIn Hypoderma spp., Gasterophilus spp., Simulium spp.), Hemiptera I

I (f.eks. Triatoma spp.), Phthirapter (f.eks. Damalinia spp., II (e.g., Triatoma spp.), Phthirapter (e.g., Damalinia spp., I

I Linognathus spp.), Siphonaptera (f.eks. Ctenocephalides IIn Linognathus spp.), Siphonaptera (e.g., Ctenocephalides I

I spp.), Dictyoptera (f.eks. Periplaneta spp., Blatella spp.), IIn spp.), Dictyoptera (e.g., Periplaneta spp., Blatella spp.), In

I 30 Hymenoptera (f.eks. Monomorium pharaonis); f.eks. mod infek- IIn 30 Hymenoptera (eg Monomorium pharaonis); eg. against infect- I

I tioner i fordøjelseskanalen forårsaget af parasitiske nema- IIn tions in the digestive tract caused by parasitic nema- I

I todeorme, f.eks. medlemmer af familien Trichostrongylidae, IIn toworms, e.g. members of the family Trichostrongylidae, I

I Nippostrongylus brasiliensis, Trichinella spiralis, Haemon- IIn Nippostrongylus brasiliensis, Trichinella spiralis, Haemon- I

I chus contortus, Trichostrongylus colubriformis, Nematodirus IIn chus contortus, Trichostrongylus colubriformis, Nematodirus I

I 35 battus, Ostertagia circumcincta, Trichostrongylus axei, II 35 battus, Ostertagia circumcincta, Trichostrongylus axei, I

I Cooperia spp. og Hymenolepis nana; ved bekæmpelse og behand- IIn Cooperia spp. and Hymenolepis nana; by combating and treating I

129 DK 175618 B1 ling af protozo-lidelser forårsaget af f.eks. Eimeria spp., f.eks. Eimeria tenella, Eimeria acervulina, Eimeria brunetti,129 DK 175618 B1 of protozoal disorders caused by e.g. Eimeria spp., E.g. Eimeria tenella, Eimeria acervulina, Eimeria brunetti,

Eimeria maxima og Eimeria necatrix, Trypanosoma cruzi, Lei-shamania spp., Plasmodium spp., Babesia spp., Trichomonadidae 5 spp., Histomonas spp., Giardia spp., Toxoplasma spp., Entamoeba histolytica og Theileria spp.; ved beskyttelse af oplagrede produkter, f.eks. kornsorter, herunder kerner og mel, jordnødder, animalsk foder, tømmer og husholdningsmaterialer, f.eks. tæpper og tekstiler, mod angreb af arthropo-10 der, navnlig biller, herunder snudebiller, møl og mider, f.eks. Ephestia spp. (melmøl); Anthrenus spp. (tæppebiller); Tribolium spp. (melbiller); Sitophilus spp. (komsnudebiller) og Acarus spp. (mider) ; ved bekæmpelse af kakerlakker, myrer og termitter og lignende arthropode-skadedyr på inficerede 15 hus- og industriområder, og ved bekæmpelse af moskitolarver i vandledninger, brønde, reservoirer eller andet strømmende eller stillestående vand, til behandling af fundamenter, struktur og jord ved hindring af angreb på bygninger af termitter, f.eks. Reticulitermes spp., Heterotermes spp., 20 Coptotermes spp.; i landbrug mod voksne larver og æg af Lepidoptera (sommerfugle og møl), f.eks. Heliothis spp. såsom Heliothis virescens (tobaksknoporm) , Heliothis armigera og Heliothis zea., Spodoptera spp., f.eks. S. exempta, S. Littoralis (ægyptisk bomuldsorm), S. eridania (sydlig "hær-25 orm"), Mamestra configurata (bertha-"hærorm"); Earias spp., f.eks. E. insulana (ægyptisk frøkapselorm), Pectinophora spp., f.eks. Pectinophora gossypiella (lyserød frøkapselorm), Ostrinia spp., f.eks. 0. nubilalis (europæisk majsborer), Trichoplusiani (kålmålerlarve), Pieris spp. (kålorme), La-30 phygma spp. ("hærorme"), Agrotis og Amathes spp. (skæreorme),Eimeria maxima and Eimeria necatrix, Trypanosoma cruzi, Lei-shamania spp., Plasmodium spp., Babesia spp., Trichomonadidae 5 spp., Histomonas spp., Giardia spp., Toxoplasma spp., Entamoeba histolytica and Theileria spp .; for the protection of stored products, e.g. cereals, including grains and flour, peanuts, animal feed, timber and household materials, e.g. carpets and textiles, against arthropod-10 attacks, in particular beetles, including beetles, moths and mites, e.g. Ephestia spp. (Flour moths); Anthrenus spp. (Carpet beetles); Tribolium spp. (Flour beetles); Sitophilus spp. (ginger beetles) and Acarus spp. (mites); for the control of cockroaches, ants and termites and similar arthropod pests in infected 15 domestic and industrial areas, and for the control of mosquito larvae in water pipes, wells, reservoirs or other flowing or stagnant water, for the treatment of foundations, structure and soil by obstruction of attacks on buildings of termites, e.g. Reticulitermes spp., Heterothermes spp., 20 Coptotermes spp .; in agriculture against adult larvae and eggs of Lepidoptera (butterflies and moths), e.g. Heliothis spp. such as Heliothis virescens (tobacco budworm), Heliothis armigera and Heliothis zea., Spodoptera spp., e.g. S. exempta, S. Littoralis (Egyptian cotton worm), S. eridania (southern "army-25 worm"), Mamestra configurata (bertha- "army worm"); Earias spp., E.g. E. insulana (Egyptian seed capsule worm), Pectinophora spp., E.g. Pectinophora gossypiella (pink seed capworm), Ostrinia spp., E.g. 0. nubilalis (European corn borer), Trichoplusiani (cabbage measuring larvae), Pieris spp. (cabbage worms), La-30 phygma spp. ("armyworms"), Agrotis and Amathes spp. (Cut worms),

Wiseana spp. (porinamøl) , Chilo spp. (risstængelborer), Tryporyza spp. og Diatraea spp. (sukkerrørborere og ris-borere), Sparganothis pilleriana (druebærmøl), Cydia pomo-nella (æbleviklermøl), Archips spp. (frugttræviklermøl), 35 Plutella xylostella (kålmøl); mod voksne og larver af Cole-optera (biller), f.eks. Hypothenemus hampei (kaffebærborer),Wiseana spp. (porin moth), Chilo spp. (rice stalk borer), Tryporyza spp. and Diatraea spp. (sugar cane and rice borers), Sparganothis pilleriana (grape moth), Cydia pomo-nella (apple wrap moth), Archips spp. (fruit tree moth), 35 Plutella xylostella (cabbage moth); against adults and larvae of Cole-optera (beetles), e.g. Hypothenemus hampei (coffee berry drill),

I DK 175618 B1 II DK 175618 B1 I

I 130 II 130 I

I Hylesinus spp. (barkbiller) , Anthonomus grandis (bomuldsfrø- IIn Hylesinus spp. (bark beetle), Anthonomus grandis (cotton seed- I

I kapselsnudebille), Acalymma spp. (agurkebiller), Lema spp., IIn capsule beetle), Acalymma spp. (cucumber), Lema spp., i

I Psylliodes spp., Leptinotarsa decemlineata (coloradokartof- IIn Psylliodes spp., Leptinotarsa decemlineata (colorado

I felbille), Diabrotica sp. (majsrodorme), Gonocephalum spp. IIn the beetle), Diabrotica sp. (corn rootworms), Gonocephalum spp. IN

I 5 (falske trådorme), Agriotes spp. (trådorme), Dermolepida og IIn 5 (false wireworms), Agriotes spp. (worms), Dermolepida and I

I Heteronychus spp. (hvide larver), Phaedon cochleariae (sen- IIn Heteronychus spp. (white larvae), Phaedon cochleariae (late- I

I nepsbiller), Lissorhoptrus oryzophilus (risvandssnudebille), ILissorhoptrus oryzophilus (rice water snuff beetle), I

I Meligethes spp. (pollenbiller), Ceutorhynchus spp., Rhyncho- IIn Meligethes spp. (pollen beetles), Ceutorhynchus spp., Rhyncho- I

I phorus og Cosmopolites spp. (rodsnudebiller); mod Hemiptera, IIn the phorus and Cosmopolites spp. (Root weevils); v. Hemiptera, I

I 10 f.eks. Psylla spp., Bemisia spp., Trialeurodes spp.. Aphis IIn 10 e.g. Psylla spp., Bemisia spp., Trialeurodes spp .. Aphis I

I spp., Myzus spp., Megoura viviae, Phylloxera spp., Adelges IIn spp., Myzus spp., Megoura viviae, Phylloxera spp., Adelges I

I spp., Phorodon humuli (humlebladlus), Aeneolamia spp., Nepho- IIn spp., Phorodon humuli (hop aphid), Aeneolamia spp., Nepho-I

I tettix spp. (risbladhoppere), Empoasca spp., Nilaparvata IIn tettix spp. (rice leaf hoppers), Empoasca spp., Nilaparvata I

I spp., Perkinsiella spp., Pyrilla spp., Aonidiella spp. (rød- IIn spp., Perkinsiella spp., Pyrilla spp., Aonidiella spp. (red- I

I 15 skjoldlus), Coccus spp., Pseucoccus spp., Helopeltis spp. IIn 15 shields), Coccus spp., Pseucoccus spp., Helopeltis spp. IN

I (moskitoinsekter), Lygus spp., Dysdercus spp., Oxycarenus II (mosquito insects), Lygus spp., Dysdercus spp., Oxycarenus I

I spp., Nezara spp., Hymenoptera, f.eks. Athalia spp. og Cephus IIn spp., Nezara spp., Hymenoptera, e.g. Athalia spp. and Cephus I

I spp. (savfluer), Atta spp. (bladbidende myrer); Diptera, IIn spp. (saw flies), Atta spp. (leaf-biting ants); Diptera, I

I f.eks. Hylemyia spp. (rodfluer), Atherigona spp. og Chlorops IIn e.g. Hylemyia spp. (root flies), Atherigona spp. and Chlorops I

I 20 spp. (skudfluer), Phytomyza spp. (bladminerer), Ceratitis IIn 20 spp. (shoot flies), Phytomyza spp. (leafminer), Ceratitis I

I spp. (frugtfluer), Thysanoptera, f.eks. Thrips tabaci, Or- IIn spp. (fruit flies), Thysanoptera, e.g. Thrips tabaci, Or- I

I thoptera, f.eks. Locusta og Schistocerca spp. (græshopper) IIn thoptera, e.g. Locusta and Schistocerca spp. (grasshopper) I

I og fårekyllinger, f.eks. Gryllus spp. og Acheta spp., Collem- IIn and sheep chickens, e.g. Gryllus spp. and Acheta spp., Collem- I

I bola, f.eks. Sminthurus spp. og Onychiurus spp. (springha- IIn bola, e.g. Sminthurus spp. and Onychiurus spp. (springha- I

I 25 ler), Isoptera, f.eks. Odontotermes spp (termitter), Dermap- IIn 25 clays), Isoptera, e.g. Odontotermes spp (termites), Dermap- I

I tera, f.eks. Forficula spp. (ørentvister) og også andre IIn tera, e.g. Forficula spp. (ear disputes) and others

I arthropoder af landbrugsmæssig betydning, f.eks. Acari IIn arthropods of agricultural importance, e.g. Acari I

I (mider), f.eks. Tetranychus spp., Panonychus spp. og Bryobia IIn (mites), e.g. Tetranychus spp., Panonychus spp. and Bryobia I

I spp. (spindemider), Eriophyes spp. {gallemider), Polyphago- IIn spp. (spider mites), Eriophyes spp. {bile mites), Polyphago- I

I 30 tarsonemus spp., Blaniulus spp. (millipeder), Scutigerella IIn 30 tarsonemus spp., Blaniulus spp. (millipeds), Scutigerella I

I spp. (symphilider) , Oniscus spp. (trælus) og Triops spp. IIn spp. (symphilids), Oniscus spp. (tree lice) and Triops spp. IN

I (crustacea), nematoder, der angriber planter og træer af II (crustacea), nematodes that attack plants and trees of I

I betydning for landbrug, skovbrug og havebrug, enten direkte IImportant for agriculture, forestry and horticulture, either directly I

I eller ved spredning af bakterie-, virus-, myoplasma- eller IIn or by the spread of bacterial, viral, myoplasmic or I

I 35 svampesygdomme i planterne, rodknoldenematoder, f.eks. IIn 35 fungal diseases of the plants, root tuber nematodes, e.g. IN

I Meloidogyne spp. (f.eks. M. incognita), cystenematoder, IIn Meloidogyne spp. (e.g., M. incognita), cyst nematodes, I

i 131 DK 175618 B1 f.eks. Globodera spp., f.eks. G. rostochiensis), Heterodera spp. (f.eks. H. avenae) , Radopholus spp. (f.eks. R. similis), læsionsnematoder, f.eks. Pratylenchus spp. (f.eks. P. praten-sis), Belonolaimus spp. (f.eks. B. gracilis), Tylenchulus 5 spp. (f.eks. T. semipenetrans), Rotylenchulus spp. (f.eks.in 131 DK 175618 B1 e.g. Globodera spp., E.g. G. rostochiensis), Heterodera spp. (e.g., H. avenae), Radopholus spp. (e.g., R. similis), lesion nematodes, e.g. Pratylenchus spp. (e.g. P. praten-sis), Belonolaimus spp. (e.g. B. gracilis), Tylenchulus 5 spp. (e.g., T. semipenetrans), Rotylenchulus spp. (eg.

R. reniformis), Rotylenchus spp. (f.eks. R. robustus), Heli-cotylenchus spp. (f.eks. H. multicinctus), Hemicycliophora spp. (f.eks. H. gracilis), Criconemoides spp. (f.eks. C. similis), Trichodorus spp. (f.eks. T. primitivus), stiknema-10 toder, f.eks. Xiphinema spp. (f.eks. X. diversicaudatum) ,R. reniformis), Rotylenchus spp. (e.g., R. robustus), Heli-cotylenchus spp. (e.g., H. multicinctus), Hemicycliophora spp. (e.g. H. gracilis), Criconemoides spp. (e.g., C. similis), Trichodorus spp. (e.g., T. primitivus), sampling methods, e.g. Xiphinema spp. (e.g., X. diversicaudatum),

Longidorus spp (f.eks. L. elongatus), Hoplolaimus spp.Longidorus spp. (E.g. L. elongatus), Hoplolaimus spp.

(f.eks. H. coronatus), Aphelenchoides spp. (f.eks. A. rit-zema-bosi, A. besseyi) , stik- og knoldålorme, f.eks. Ditylen-chus spp. (f.eks. D. dipsaci).(e.g., H. coronatus), Aphelenchoides spp. (e.g., A. rit-zema-bosi, A. besseyi), plug and tuber worms, e.g. Ditylen-chus spp. (e.g., D. dipsaci).

15 Yderligere skadelige organismer, der kan bekæmpes med forbindelserne ifølge opfindelsen, omfatter: fra ordenen Isopoda f.eks. Oniseus asellus, Armadillidium vulgare og Porcellio scaber, fra ordenen Diplopoda f.eks. Blaniulus guttulatus, fra ordenen Chilopoda f.eks. Geophilus carpo-20 phagus og Scutigera spex, fra ordenen Symphyla f.eks. Scuti-gerella immaculata, fra ordenen Thysanura f.eks. Lepisma saccharian, fra ordenen Collembola f.eks. Onychiurus armatus, fra ordenen Orthoptera f.eks. Blatta orientalis, Periplaneta americana, Leucophae maderae, Blatella germanica, Acheta 25 domesticus, Gryllotalpa spp., Locusta migratoria migratori-oides, Melanoplus differentialis og Schistocerca gregaria, fra ordenen Dermaptera f.eks. Forficula auricularia, fra ordenen Isoptera f.eks. Reticulitermes spp., fra ordenen Anoplura f.eks. Phylloxera vastatrix, Pemphigus spp., Pedi-30 culus humanus corporis, Haematopinus spp. og Linognathus spp., fra ordenen Mallophaga f.eks. Trichodectes spp. og Damalinea spp., fra ordenen Thysanoptera f.eks. Hercinothrips femoralis og Thrips tabaci, fra ordenen Heteroptera f.eks.Further harmful organisms which can be combated with the compounds of the invention include: from the order Isopoda e.g. Oniseus asellus, Armadillidium vulgare and Porcellio scaber, from the order Diplopoda e.g. Blaniulus guttulatus, from the order Chilopoda e.g. Geophilus carpo-20 phagus and Scutigera spex, from the order Symphyla e.g. Scutigerella immaculata, from the order Thysanura e.g. Lepisma saccharian, from the order Collembola e.g. Onychiurus armatus, from the order Orthoptera e.g. Blatta orientalis, Periplaneta americana, Leucophae maderae, Blatella germanica, Acheta 25 domesticus, Gryllotalpa spp., Locusta migratoria migratori-oides, Melanoplus differentialis and Schistocerca gregaria, of the order Dermaptera e.g. Forficula auricularia, from the order Isoptera e.g. Reticulitermes spp., From the order Anoplura e.g. Phylloxera vastatrix, Pemphigus spp., Pediculus humanus corporis, Haematopinus spp. and Linognathus spp., from the order Mallophaga e.g. Trichodectes spp. and Damalinea spp., from the order Thysanoptera e.g. Hercinothrips femoralis and Thrips tabaci, from the order Heteroptera e.g.

Eurygaster spp., Dysdercus intermedius, Piesma quadrata, : 35 Cimex lectularius, Rhodnius prolixus og Triatoma spp., fra ordenen Coleoptera f.eks. Anobium punctatum, RhizoperthaEurygaster spp., Dysdercus intermedius, Piesma quadrata,: 35 Cimex lectularius, Rhodnius prolixus and Triatoma spp., From the order Coleoptera e.g. Anobium punctatum, Rhizopertha

I DK 175618 B1 II DK 175618 B1 I

I 132 II 132 I

I dominica, Bruchidius obtectus, Acanthoscelides obtectus, II dominica, Bruchidius obtectus, Acanthoscelides obtectus, I

I Hylotrupes baj ulus, Agelastica alni, Leptinotarsa decern- IIn Hylotrupes baj ulus, Agelastica alni, Leptinotarsa decern- I

I lineata, Phaedon cochleariae, Diabrotica spp., Psylliodes IIn lineata, Phaedon cochleariae, Diabrotica spp., Psylliodes I

I chrysocephala, Epilachna varivestis, Atomaria spp., Oryzae- IIn chrysocephala, Epilachna varivestis, Atomaria spp., Oryzae- I

I 5 philus surinamensis, Anthonomus spp., Sitophilus spp., Otior- II 5 philus surinamensis, Anthonomus spp., Sitophilus spp., Otior- I

I rhynchus sulcatus, Cosmoplites sordidus, Ceuthorrhynchus II rhynchus sulcatus, Cosmoplites sordidus, Ceuthorrhynchus I

I assimilis, Hypera postica, Dermestes spp., Trogoderma spp., II assimilis, Hypera postica, Dermestes spp., Trogoderma spp., I

I Anthrenus spp., Attagenus spp., Lyctus spp., Maligethes IIn Anthrenus spp., Attagenus spp., Lyctus spp., Maligethes I

I aeneus, Ptinus spp., Niptus hololeucrus, Gibbium psylloides, II aeneus, Ptinus spp., Niptus hololeucrus, Gibbium psylloides, I

I 10 Tribolium spp.,Tenebrio molitor, Agriotes spp., Conoderus IIn 10 Tribolium spp., Tenebrio molitor, Agriotes spp., Conoderus I

I spp., Melolontha melolontha, Amphimallon solstitialis og ' IIn spp., Melolontha melolontha, Amphimallon solstitialis and 'I

Costelytra zealandica, fra ordenen Hymenoptera, f.eks. ICostelytra zealandica, from the order Hymenoptera, e.g. IN

I Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pha- IIn Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pha- I

I raonis og Vespa spp., fra ordenen Diptera, f.eks. Aedes IIn raonis and Vespa spp., From the order Diptera, e.g. Aedes I

I 15 spp., Anopheles spp., Culex spp., Drosophila melanogaster, IIn 15 spp., Anopheles spp., Culex spp., Drosophila melanogaster, I

I Musca spp., Fannia spp., Calliphora erythrocephala, Luculia IIn Musca spp., Fannia spp., Calliphora erythrocephala, Luculia I

I spp., Chrysomyia spp., Cuterebra spp., Gastrophilus spp., II spp., Chrysomyia spp., Cuterebra spp., Gastrophilus spp., I

I Hyppobosca spp., Stomoxys spp., Oestrus spp., Hypoderma IIn Hyppobosca spp., Stomoxys spp., Oestrus spp., Hypoderma I

I spp., Tabanus spp., Tannia spp., Bibio hortulanus, Oscinella IIn spp., Tabanus spp., Tannia spp., Bibio hortulanus, Oscinella I

I 20t frit, Phorbia spp., Pegomyia hyoscyani, Ceratitis capitata, IFor 20h freely, Phorbia spp., Pegomyia hyoscyani, Ceratitis capitata, I

I Dacus oleae og Tipula paludosa, fra ordenen Siphonaptera, IIn Dacus oleae and Tipula paludosa, from the order Siphonaptera, I

I f.eks. Xenopsylla cheopis og Ceratophyllus spp., fra ordenen' IIn e.g. Xenopsylla cheopis and Ceratophyllus spp., From the order 'I

I Arachnida, f.eks. Scorpio tnaurus og Latrodectus mactans, IIn Arachnida, e.g. Scorpio tnaurus and Latrodectus mactans, I

I fra ordenen Homoptera, f.eks. Aleurodes brassicae, Bemisia IIn the order Homoptera, e.g. Aleurodes brassicae, Bemisia I

I 25 tabaci, Trialeurodes vaporariorum, Aphis gossypii, Brevico- IIn 25 tabaci, Trialeurodes vaporariorum, Aphis gossypii, Brevico- I

I ryne brassicae, Cryptomyzus ribis, Doralis fabae, Doralis II ryne brassicae, Cryptomyzus ribis, Doralis fabae, Doralis I

I pomi, Eriosoma lanigerum Hyalopterus arundinis, Macrosiphum IIn pomi, Eriosoma lanigerum Hyalopterus arundinis, Macrosiphum I

I avenae, Myzus spp., Phorodon humuli, Rhopalosiphum padi, IIn avenae, Myzus spp., Phorodon humuli, Rhopalosiphum padi, I

I Empoasca spp., Euscelis bilobatus, Nephotettix cincticeps, IIn Empoasca spp., Euscelis bilobatus, Nephotettix cincticeps, I

I 30 Lecanium corni, Saissetia oleae, Laodelphax striatellus, II 30 Lecanium corni, Saissetia oleae, Laodelphax striatellus, I

I Nilaparvata lugens, Aonidiella aurantii, Aspidiotus hederae, IIn the Nilaparvata lugens, Aonidiella aurantii, Aspidiotus hederae, I

I Pseudococcus spp. og Psylla spp., fra ordenen Lepidoptera, IIn Pseudococcus spp. and Psylla spp., from the order Lepidoptera, I

I f.eks. Pectinophora gossypiella, Bupalus piniarius, Cheima- IIn e.g. Pectinophora gossypiella, Bupalus piniarius, Cheima- I

I tobia brumata, Lithocolletis blancardella, Hyponomeuta IIn tobia brumata, Lithocolletis blancardella, Hyponomeuta I

I 35 padella, Plutella maculipennis, Malacosoma neustria, Euproc- IIn 35 padella, Plutella maculipennis, Malacosoma neustria, Euproc- I

I tis chrysorrhoea, Lymantria spp., Bucculatrix thurberiella, II tis chrysorrhoea, Lymantria spp., Bucculatrix thurberiella, I

133 DK 175618 B1133 DK 175618 B1

Phyllocnistis citrella, Agrotis spp., Euxoa spp., Feltia spp., Earias insulana, Heliothis spp., Laphygma exigua,Phyllocnistis citrella, Agrotis spp., Euxoa spp., Feltia spp., Earias insulana, Heliothis spp., Laphygma exigua,

Mamestra brassicae, Panolis flammea, Prodenia litura, Spodop-tera spp., Trichoplusiani, Carpocapsa pomonella, Pieris 5 spp., Chilo spp., Pyrausta nubialis, Ephestiakuehniella,Mamestra brassicae, Panolis flammea, Prodenia litura, Spodoptera spp., Trichoplusiani, Carpocapsa pomonella, Pieris 5 spp., Chilo spp., Pyrausta nubialis, Ephestiakuehniella,

Galleria mellonella, Tineola bisselliella, Tinea pellionella, !Galleria mellonella, Tineola bisselliella, Tinea pellionella ,!

Hofmannophila pseudospretella, Cacoecia podana, Capua reti- IHofmannophila pseudospretella, Cacoecia podana, Capua reti- I

culana, Choristoneura fumiferana, Clysia ambiguelis, Homona magnanime og Tortix viridana.culana, Choristoneura fumiferana, Clysia ambiguelis, Homona magnanime and Tortix viridana.

10 Opfindelsen angår også en fremgangsmåde til bekæmpelse af arthropoder eller nematoder, der er skadelige organismer i forbindelse med planter, og denne fremgangsmåde omfatter påføring på planterne eller det medium, hvori de vokser, af en virksom mængde af en forbindelse med den almene formel I.The invention also relates to a method for controlling arthropods or nematodes which are harmful to plant organisms, and this method comprises applying to the plants or medium in which they grow an effective amount of a compound of the general formula I.

15 Til bekæmpelse af arthropoder og nematoder påføres den aktive forbindelse i almindelighed det sted, hvor infektionen med arthropoder eller nematoder skal bekæmpes, i en mængde på fra ca. 0,005 kg til ca. 15 kg aktiv forbindelse pr. hektar behandlet areal, fortrinsvis fra 0,02 til 2 kg/ha.For the control of arthropods and nematodes, the active compound is generally applied to the site where the infection with arthropods or nematodes is to be fought, in an amount of from about. 0.005 kg to approx. 15 kg of active compound per per hectare of treated area, preferably from 0.02 to 2 kg / ha.

20 Under ideelle betingelser, afhængigt af den skadelige organisme, der skal bekæmpes, kan en lavere anvendelsesmængde give tilstrækkelig beskyttelse. På den anden side kan dårlige vejrforhold, resistens hos de skadelige organismer og andre faktorer kræve, at den aktive bestanddel anvendes i større 25 mængder. Ved anvendelse til påføring på blade kan der benyttes en mængde på fra 0,01 til 1 kg/ha. Den optimalt anvendte mængde afhænger i almindelighed af den type skadelig organisme, der skal bekæmpes, samt typen og vækststadiet for den inficerede plante, afstanden mellem planterækkerne samt 30 påføringsmetoden.20 Under ideal conditions, depending on the harmful organism to be controlled, a lower amount of use can provide adequate protection. On the other hand, poor weather conditions, resistance of the harmful organisms and other factors may require the active ingredient to be used in greater quantities. When used for application to leaves, an amount of from 0.01 to 1 kg / ha can be used. The optimum amount used generally depends on the type of harmful organism to be controlled, as well as the type and stage of growth of the infected plant, the distance between the plant rows and the method of application.

Når den skadelige organisme findes i jorden, fordeles præparatet indeholdende den aktive forbindelse ensartet over det areal, der skal behandles, på enhver bekvem måde.When the harmful organism is present in the soil, the composition containing the active compound is evenly distributed over the area to be treated in any convenient manner.

Påføringen kan omønsket ske på marken eller på afgrødedyrk- i 35 ningsarealet i almindelighed eller i tæt nærhed af de frø eller planter, der skal beskyttes mod angreb. Den aktiveThe application may, if desired, be carried out on the field or on the crop cultivation area in general or in close proximity to the seeds or plants to be protected from attack. The active

134 I134 I

DK 175618 B1 IDK 175618 B1 I

bestanddel kan vaskes ned i jorden ved sprøjtning med vandIngredients can be washed into the soil by spraying with water

over arealet eller kan efterlades til naturlig påvirkning Iabove the area or may be left to natural impact

af regn. Under eller efter påføringen kan præparatet om Iof rain. During or after application, the composition of I

ønsket fordeles mekanisk i jorden, f.eks. ved pløjning eller Ithe desired mechanical distribution in the soil, e.g. by plowing or I

5 harvning. Påføringen kan ske før udplantningen, ved udplant- I5 harrowing. Application can be done before transplanting, at transplant I

ningen, efter udplantningen, men inden kimdannelsen har Iafter planting, but before germination you have

fundet sted, eller efter spiringen. Ioccurred, or after germination. IN

Forbindelserne med den almene formel I kan påføres i IThe compounds of general formula I may be applied in I

faste eller flydende præparater, der anvendes i forbindelse Isolid or liquid preparations used in compound I

10 med jorden, i hovedsagen til bekæmpelse af de nematoder, I10 with the soil, mainly for the control of the nematodes, I

der opholder sig i jorden, men også til blade, principielt Ithat resides in the ground, but also to leaves, in principle I

til bekæmpelse af de nematoder, der angriber de i luften Ito combat the nematodes that attack them in the air I

værende dele af planterne, f.eks. Aphelenchoides spp. og Ibeing parts of the plants, e.g. Aphelenchoides spp. and in

Ditylenchus spp., der er angivet ovenfor. HDitylenchus spp. Listed above. H

15 Forbindelserne med den almene formel I kan være af IThe compounds of general formula I may be of I

værdi til bekæmpelse af skadelige organismer, der indtager Ivalue to control harmful organisms consuming

deres næring på dele af planten, der befinder sig fjernt Htheir nourishment on parts of the plant that are distant H

frå påføringsstedet, idet f.eks. bladædende insekter dræbes Hfrom the site of application, e.g. leaf-eating insects are killed H

af de her omhandlede forbindelser, når disse påføres på Iof the compounds of this invention when applied to I

20 rødderne. Desuden kan forbindelserne formindske angreb på I20 the roots. In addition, the compounds can reduce attacks on I

planterne gennem virkninger, der bevirker, at organismerne Ithe plants through effects that cause the organisms

ikke æder af planterne, eller at organismerne frastødes fra Ido not eat the plants or the organisms are repelled by I

planterne. Iplants. IN

Forbindelserne med den almene formel I er af særlig HThe compounds of general formula I are of particular H

25 værdi ved beskyttelse af afgrøder i marken, foderafgrøder, I25 value in the protection of crops in the field, fodder crops, I

.plantageafgrøder, drivhusafgrøder, afgrøder i frugthaver og H.plant crops, greenhouse crops, orchard crops and H

vingårde, prydtræer og plantage- og skovtræer, f.eks. korn- Ivineyards, ornamental trees and plantation and forest trees, e.g. grain- I

sorter, såsom majs, hvede, ris og sorghum, bomuld, tobak, Ivarieties such as maize, wheat, rice and sorghum, cotton, tobacco, I

grøntsager og salater, f.eks. bønner, rapsafgrøder, curcur- Ivegetables and salads, e.g. beans, rapeseed, curcur- I

30 bits, salat, løg,· tomater og peber, markafgrøder, f.eks. I30 bits, lettuce, onions, tomatoes and pepper, field crops, e.g. IN

kartofler, sukkerroer, jordnødder, sojabønner og oliefrøraps, Ipotatoes, sugar beets, peanuts, soybeans and oilseed rape, I

sukkerrør, græsarealer og foderafgrøder, f.eks. majs, Isugar cane, grassland and forage crops, e.g. corn, i

sorghum eller lucerne, plantager, f.eks. med te, kaffe,sorghum or alfalfa, plantations, e.g. with tea, coffee,

kakao, bananer, oliepalmer, kokosnødder, gummi og krydderier, Icocoa, bananas, palm trees, coconuts, rubber and spices, I

35 frugthaver og frugtplantager, f.eks. med sten- og kernefrugt, I35 orchards and orchards, e.g. with stone and kernel fruit, I

citrusfrugter, kiwifrugter, avocado, mangofrugter, oliven Hcitrus fruits, kiwifruit, avocado, mango fruits, olives H

135 DK 175618 B1 og valnødder, vingårde, prydplanter, blomster og grøntsager og buske under glas og i haver og parker, skovtræer, såvel løvfældende som stedsegrønne i skovplantninger, plantager og planteskoler.135 DK 175618 B1 and walnuts, vineyards, ornamental plants, flowers and vegetables and shrubs under glass and in gardens and parks, forest trees, deciduous as well as evergreen in forest plantations, plantations and nurseries.

5 Forbindelserne er også værdifulde til beskyttelse af tømmer (stående, fældet, omdannet, opbevaret eller konstruktionstømmer) mod angreb af savfluer, f.eks. Urocerus, eller biller, f.eks. scolytider, platypodider, lyctider, bostry-chider, cerambycider eller anobiider, eler termitter, f.eks.5 The compounds are also valuable for protecting timber (standing, felled, converted, stored or structural timber) against attacks by saw flies, e.g. Urocerus, or beetles, e.g. scolytids, platypodids, lyctides, bostrychids, cerambycides or anobiids, or termites, e.g.

10 Reticulitermes spp. , Heterotermes spp. eller Coptotermes spp.10 Reticulitermes spp. , Heterothermes spp. or Coptotermes spp.

Forbindelserne kan anvendes ved beskyttelse af opbevarede produkter såsom korn eller kerner, frugter, nødder, krydderier og tobak, hvad enten der er tale om hele, formalede eller sammensatte produkter, mod angreb af møl, bil-15 ler, mider og kornsnudebiller (Sitophilus granarius). Man kan også beskytte opbevarede animalske produkter, f.eks. huder, hår, uld og læder på naturlig eller omdannet form, f.eks. som tæpper eller tekstiler, mod angreb af møl og biller, og endvidere kan man beskytte opbevaret kød og fisk 20 mod angreb af biller, mider og fluer.The compounds can be used to protect stored products such as grains or grains, fruits, nuts, spices and tobacco, whether whole, ground or composite, against attacks of moths, beetles, mites and cereal beetles (Sitophilus granarius ). It is also possible to protect stored animal products, e.g. hides, hair, wool and leather in natural or transformed form, e.g. such as carpets or textiles, against moth and beetle attacks, and furthermore, protected meat and fish 20 can be protected from attacks by beetles, mites and flies.

Forbindelserne med den almene formel I kan være af særlig værdi ved bekæmpelsen af arthropoder, helminter eller protozoer, der er skadelige for eller spreder eller virker som vektorer for sygdomme hos mennesker og hos-dyr, f.eks.The compounds of general formula I may be of particular value in the control of arthropods, helminths or protozoa which are harmful to or spread or act as vectors for human and animal diseases, e.g.

25 de i det foregående nævnte, og i særlig grad ved bekæmpelsen af blodmider, mider, lus, lopper, myg samt bidende, generende og myiasis-fluer. Forbindelserne med den almene formel I er særligt anvendelige til bekæmpelse af arthropoder, helminter eller protozoer, der er til stede i det indre af værtshusdyr, 30 eller som indtager deres næring i eller på huden eller udsuger blodet af dyrene, til hvilket formål forbindelserne kan indgives oralt, parenteralt, percutant eller topisk. Coc-cidiosis, der er en lidelse, der forårsages af infektioner med protozo-parasitter af slægten Eimeria, er en betydnings-35 fuld potentiel årsag til økonomisk tab i forbindelse med husdyr og fjerkræ, navnlig sådanne, som opdrættes eller25, and especially in the fight against blood mites, mites, lice, fleas, mosquitoes, and biting, bothersome and myiasis flies. The compounds of general formula I are particularly useful for controlling arthropods, helminths or protozoa present in the interior of host animals, or feeding on or on the skin or extracting the blood of the animals for which purpose the compounds may be administered. orally, parenterally, percutaneously or topically. Coccidiosis, a disease caused by infections with protozoal parasites of the genus Eimeria, is a significant potential cause of economic loss in livestock and poultry, especially those raised or farmed.

136 I136 I

DK 175618 B1 IDK 175618 B1 I

holdes under intensive betingelser. Eksempelvis kan kvæg, Ikept under intense conditions. For example, cattle, I

får, grise og kaniner påvirkes, men sygdommen er af særlig Isheep, pigs and rabbits are affected, but the disease is of particular concern

betydning hos fjerkræ, navnlig kyllinger. Himportance in poultry, especially chickens. H

Fjerkræsygdommen spredes i almindelighed ved, at IThe poultry disease is generally spread by:

5 fuglene optager den infektionsfremkaldende organisme fra I5 the birds occupy the infectious organism of I

materialet på forurenet affald eller jord eller ved indta- Ithe material on contaminated waste or soil or upon ingestion

gelse af næring eller drikkevand. Sygdommen viser sig ved Inourishment or drinking water. The disease appears in I

blødning, akkumulering af blod i coecum, passage af blod Ibleeding, accumulation of blood in the coecum, passage of blood I

til hønsegødningen, svaghed og fordøjelsesvanskeligheder. Ifor the chicken manure, weakness and digestive difficulties. IN

10 Sygdommen ender ofte med dyrets død, men de dyr, der over- I10 The disease often ends with the death of the animal, but the animals that transmit it

lever alvorlige infektioner, har som et resultat af infek- Ihave serious infections, have as a result of infection

tionen en i væsentlig grad formindsket markedsværdi. Ition, a significantly diminished market value. IN

Indgivelse af en ringe mængde af en forbindelse med IAdministration of a small amount of a compound with I

den almene formel I, fortrinsvis i kombination med fjerkræ- Hthe general formula I, preferably in combination with poultry H

15 foder, kan være effektiv til hindring eller kraftig for- H15 feed, can be effective in obstruction or heavy for- H

mindskelse af forekomsten af coccidiosiss. Forbindelsernedecrease in the incidence of coccidiosis. The compounds

er virksomme både mod coecum-formen, der forårsages af Iare effective both against the coecum form caused by I

E. tenella, og de intestinale former, der hovedsageligt IE. tenella, and the intestinal forms which mainly I

foråsages af E. acervulina, E. brunetti, E. maxima og Iis caused by E. acervulina, E. brunetti, E. maxima and I

20 E. necatrix. IE. necatrix. IN

Forbindelserne med den almene formel I kan Også udøve IThe compounds of general formula I may also be exercised

en inhiberende virkning på oocyster, idet forbindelserne i Ian inhibitory effect on oocysts, the compounds of I

stort omfang formindsker antallet og/eller sporuleringen afgreatly reduces the number and / or sporulation of

de oocyster, der frembringes. Ithe oocysts produced. IN

25 De i det følgende beskrevne præparater til topisk I25 The topical I compositions described below

anvendelse til mennesker og dyr og ved beskyttelsen af opbe- Iuse in humans and animals and in the protection of housing

varede produkter, husholdningsmaterialer, ejendom og arealer Igoods, household materials, property and land I

i det generelle miljø, kan i almindelighed, alternativt Iin the general environment, generally, alternatively I

anvendes til påføring på voksende afgrøder eller steder, Iused for application to growing crops or places, I

30 hvor sådanne afgrøder vokser, og som et præparat til behand- I30 where such crops grow and as a preparation for treatment

ling af frø. Egnede metoder til anvendelse af forbindelserne Iling of seeds. Suitable methods for using the compounds I

med den almene formel I omfatter følgende: til personer Ithe general formula I includes the following: to persons I

eller dyr, der er inficeret med eller udsat for infektion Ior animals infected or exposed to infection I

fra arthropoder, helminter eller protozoer ved parenteral, Ifrom arthropods, helminths or protozoa at parenteral, I

35 oral eller topisk anvendelse af præparaterne, i hvilke den IOral or topical use of the compositions in which it I

aktive bestanddel udøver en umiddelbar og/eller forlænget Iactive ingredient exerts an immediate and / or prolonged I

137 DK 175618 B1 virkning over et tidsrum mod arthropoderne, helminterne eller protozoerne, f.eks. ved inkorporering i foderet eller egnede oralt indgivelige farmaceutiske præparater, spiselig lokkemad, saltslikkesten, fodersupplement, påhældnings-5 præparater, spraypræparater, bade, dyppepræparater, sprøjtepræparater, spraypræparater af forskellig art, støvpræparater, smørepræparater, shampoopræparater, cremer, vokssmøre-præparater, og systemer til selvbehandling af husdyr. Endvidere kan man behandle omgivelserne i almindelighed eller 10 de specifikke steder, hvor de skadelige organismer kan opholde sig, herunder opbevarede produkter, tømmer, husholdningsmaterialer og bolig- og industriområder, idet præparaterne anvendes som spraypræparater, tågepræparater, støvpræparater, røgpræparater, vokssmørepræparater, lakpræpara-15 ter, granulater og lokkemad, og præparaterne kan endvidere anvendes i form af strømmende foder til tilsætning til vandveje, brønde, reservoirer og andet strømmende eller stillestående vand. Præparaterne kan endvidere anvendes til husdyr i foderet til bekæmpelse af fluelarver, der indtager deres 20 næring i dyrenes ekskrementer. Præparaterne kan endvidere anvendes til voksende afgrøder i form af bladspraypræparater, støvpræparater, granulater, tågepræparater og skum. Præparaterne kan endvidere anvendes som suspensioner af findelte og indkapslede forbindelser med den almene formel I ved 25 jord- og rodbehandlinger med flydende præparater, støvpræparater, granulater, røgpræparater og skum, og præparaterne kan endvidere anvendes som frøbehandlingspræparater i form af væskeformige opslæmninger og støvpræparater.B1 activity over a period of time against the arthropods, helminths or protozoa, e.g. by incorporating into the feed or suitable orally administered pharmaceutical compositions, edible baits, salt licks, feed supplements, pouring preparations, spray preparations, baths, dips, spray preparations, spray preparations of various kinds, for the self-care of livestock. Furthermore, the environment can be treated in general or the specific places where the harmful organisms may reside, including stored products, timber, household materials and residential and industrial areas, the compositions being used as spray preparations, fog preparations, dust preparations, smoke preparations, wax lubricants, wax lubricants, 15, granules and baits, and the compositions can also be used in the form of flowing feed for addition to waterways, wells, reservoirs and other flowing or stagnant water. Furthermore, the compositions can be used for livestock in the feed to control fluvial larvae that take their nourishment in the animals' excrement. The compositions can also be used for growing crops in the form of foliar sprays, dust preparations, granules, mist preparations and foams. The compositions can furthermore be used as suspensions of finely divided and encapsulated compounds of the general formula I in soil and root treatments with liquid preparations, dust preparations, granules, smoke preparations and foams, and the preparations can also be used as seed treatment preparations in the form of liquid preparations and molds.

Forbindelserne med den almene formel I kan anvendes 30 til bekæmpelse af arthropoder, helminter eller protozoer i præparater af enhver type, der er kendt i teknikken og egnet til intern eller ekstern indgivelse til vertebrater eller anvendelse til bekæmpelse af arthropoder på alle indendørs og udendørs arealer, indeholdende som aktiv bestanddel i ' 35 det mindste én forbindelse med den almene formel I i forbindelse med et eller flere kompatible fortyndingsmidler ellerThe compounds of general formula I can be used to control arthropods, helminths or protozoa in preparations of any type known in the art and suitable for internal or external administration to vertebrates or use for controlling arthropods in all indoor and outdoor areas, containing as active ingredient in at least one compound of the general formula I in association with one or more compatible diluents or

138 I138 I

DK 175618 B1 IDK 175618 B1 I

tilsætningsstoffer, der er egnede til den tilsigtede anven-additives suitable for the intended use

delse. Alle sådanne præparater kan fremstilles på enhver i Icompound. All such preparations may be prepared on any of the following

teknikken kendt måde. Hthe technique known way. H

Præparater, der er egnede til indgivelse til vertebra- ICompositions suitable for administration to vertebrate I

5 ter eller mennesker, omfatter præparater, der er egnede H5 or human, include compositions suitable H

til oral, parenteral, percutan, f.eks. påhældnings-anven- Ifor oral, parenteral, percutaneous, e.g. pouring application I

delse, eller topisk indgivelse. Ior topical administration. IN

Præparater til oral indgivelse indeholder en ellerCompositions for oral administration contain one or

flere af forbindelserne med den almene formel I i forbindelse Iseveral of the compounds of general formula I in compound I

10 med farmaceutisk acceptable bærestoffer eller overtræk og I10 with pharmaceutically acceptable carriers or coatings and I

omfatter f.eks. tabletter, piller, kapsler, pastaer, geler, Iincludes e.g. tablets, pills, capsules, pastes, gels, I

makrodoser, medikerede fodermidler, medikeret drikkevand, Imacro doses, medicated feed, medicated drinking water, I

medikeret næringsmiddelsupplement, boluspræparater med lang- Imedicated food supplement, bolus preparations with long- I

som frigivelse eller andre præparater med langsom frigivelse, Ias release or other slow release preparations, I

15 der skal bibeholdes i fordøjelseskanalen. Ethvert af disse I15 to be retained in the digestive tract. Any of these I

præparater kan indeholde aktiv bestanddel indesluttet i Ipreparations may contain active ingredient contained in I

mikrokapsler eller overtrukket med syre-labile eller alkali- Imicrocapsules or coated with acid-labile or alkali-I

-labile eller andre farmaceutisk acceptable, enteriske over-labile or other pharmaceutically acceptable enteric agents

træk. Foder-forblandinger og -koncentrater indeholdende de Irow. Feed premixes and concentrates containing the I

20 omhandlede forbindelser til anvendelse ved fremstilling af I20 compounds for use in the preparation of I

medikerede fodermaterialer, drikkevand eller andre materialer Imedicated feed materials, drinking water or other materials

til indtagelse af dyr, kan også anvendes. Ifor ingestion of animals may also be used. IN

Præparater til parenteral indgivelse omfatter opløs- IPreparations for parenteral administration include solution I

ninger, emulsioner eller suspensioner i ethvert egnet, far-solutions, emulsions or suspensions in any suitable paint.

25 maceutisk acceptabelt bærestof eller faste eller halvfaste I25 pharmaceutically acceptable carrier or solid or semi-solid I

subkutane implantationspræparater eller pellets, der er Isubcutaneous implant preparations or pellets which are I

beregnet til frigivelse af aktiv bestanddel over et udstrakt Iintended for release of active ingredient over an extended I

tidsrum, og de kan fremstilles og gøres sterile på enhver Itime, and they can be made and sterile on any I

egnet måde, der er kendt i teknikken. Isuitable way known in the art. IN

30 Præparater til perkutan og topisk indgivelse omfatter I30 Percutaneous and topical administration compositions include I

spraypræparater, støvpræparater, bade, dyppepræparater, Ispray preparations, dust preparations, baths, dipping preparations, I

strålepræparater, jetpræparater, smørepræparater, shampoo-. Ijet preparations, jet preparations, lubricants, shampoos. IN

-præparater, cremer, vokssmørepræparater eller påhældnings- Ipreparations, creams, wax lubricants or pouring I

præparater samt anordninger, f.eks. øremærker, der fastgøres Ipreparations and devices, e.g. ear tags to be attached

35 på det ydre af dyrene på en sådan måde, at der tilvejebringes I35 on the exterior of the animals in such a way as to provide I

lokal eller systemisk bekæmpelse af arthropoder. Ilocal or systemic control of arthropods. IN

139 DK 175618 B1139 DK 175618 B1

Faste eller flydende lokkemadspræparater, der er egnede til bekæmpelse af arthropoder, indeholder en eller flere forbindelser med den almene formel I og et bærestof eller fortyndingsmiddel, der kan omfatte et næringsmiddelstof 5 eller et andet stof, der inducerer indtagelse af arthropoden.Solid or liquid bait preparations suitable for the control of arthropods contain one or more compounds of general formula I and a carrier or diluent which may comprise a nutrient or other substance which induces ingestion of the arthropod.

Når forbindelserne i praksis anvendes i landbruget, anvendes de sjældent alene. Disse forbindelser udgør for det meste dele af præparater. Disse præparater, der kan anvendes som insecticide midler, indeholder en forbindelse ifølge opfin-10 delsen som tidligere beskrevet som den aktive bestanddel i kombination med i landbruget acceptable.faste eller flydende bærestoffer og overfladeaktive midler, der ligeledes er landbrugsmæssigt acceptable. De indifferente og gængse bærestoffer og de gængse overfladeaktive midler kan i særdeleshed 15 anvendes. Disse præparater omfattes også af den foreliggende opfindelse. -When used in agriculture, the compounds are rarely used alone. These compounds form mostly parts of preparations. These compositions which can be used as insecticidal agents contain a compound of the invention as previously described as the active ingredient in combination with agriculturally acceptable solid or liquid carriers and surfactants which are also agriculturally acceptable. The inert and conventional carriers and the usual surfactants may in particular be used. These compositions are also encompassed by the present invention. -

Disse præparater kan også indeholde alle typer af øvrige bestanddele, f.eks. beskyttelseskolloider, adhæsiver, fortykkelsesmidler, tixotrope midler, gennemtrængningsmidler, 20 sprayolier, navnlig til acaricide anvendelser, stabilisatorer, konserveringsmidler, især konserveringsmidler mod svampe, sekvestreringsmidler eller lignende, samt andre kendte aktive bestanddele med pesticide egenskaber, især insec-ticider eller fungicider, eller med egenskaber, der tjener 25 til regulering af plantevæksten. Mere generelt kan forbindelserne, der anvendes ifølge opfindelsen, kombineres med alle de flydende eller faste additiver, der svarer til de sædvanlige præparatsammensætningsmetoder.These compositions may also contain all types of other ingredients, e.g. protective colloids, adhesives, thickeners, thixotropic agents, penetrating agents, spray oils, especially for acaricidal uses, stabilizers, preservatives, especially fungicides, sequestrants or the like, and other known active ingredients having pesticidal properties, especially insecticides or properties that serve 25 to regulate plant growth. More generally, the compounds used according to the invention can be combined with all the liquid or solid additives corresponding to the usual preparation composition methods.

De anvendte doser af de her omhandlede forbindelser 30 kan variere inden for vide grænser, især afhængigt af naturen af den skadelige organisme, der skal elimineres, og den sædvanlige grad af angreb på afgrøderne med disse organismer.The doses used for the compounds of this invention may vary widely, especially depending on the nature of the harmful organism to be eliminated and the usual degree of crop attack with these organisms.

I almindelighed indeholder præparaterne ifølge opfindelsen sædvanligvis fra ca. 0,05 til ca. 95 vægt-% af et 35 eller flere aktive stoffer ifølge opfindelsen, fra ca. 1 til ca. 95 vægt-% af et eller flere, faste eller flydendeIn general, the compositions of the invention usually contain from 0.05 to approx. 95% by weight of a 35 or more active substances according to the invention, from approx. 1 to approx. 95% by weight of one or more solid or liquid

140 I140 I

DK 175618 B1 IDK 175618 B1 I

bærestoffer samt eventuelt fra ca. 0,1 til ca. 50 vægt-% af Icarriers and possibly from approx. 0.1 to approx. 50% by weight of I

et eller flere overfladeaktive midler. Ione or more surfactants. IN

I overensstemmelse med det allerede anførte kombineres IIn accordance with the above, I

de ifølge opfindelsen anvendte forbindelser i almindelighed Ithe compounds of the invention generally used I

5 med bærestoffer og eventuelt også overfladeaktive midler. I5 with carriers and optionally also surfactants. IN

I den foreliggende sammenhæng betegner udtrykket IIn the present context, the term I means

"bærestof" en organisk eller uorganisk bestanddel, der er I"carrier" means an organic or inorganic component which is I

naturlig eller syntetisk, med hvilken den aktive bestanddel Inatural or synthetic with which the active ingredient I

kombineres til lettelse af påføringen på planten, på frøene Icombined to facilitate application on the plant, on the seeds I

10 eller på jorden. Dette bærestof er derfor i almindelighed I10 or on earth. This carrier is therefore generally I

indifferent, og det skal være landbrugsmæssigt acceptabelt, Iindifferent and it must be agricultural acceptable, I

navnlig over for den behandlede plante. Bærestoffet kan Iespecially towards the treated plant. You can use the carrier

være fast (lerarter, naturlige eller syntetiske silicater, Ibe solid (clays, natural or synthetic silicates, I

siliciumdioxid, harpikser, voksarter, faste gødningsstoffer, Isilica, resins, waxes, solid fertilizers, I

15 f.eks. ammoniumsalte og formalede naturlige mineraler, f.eks. I15 e.g. ammonium salts and ground natural minerals, e.g. IN

kaoliner, lerarter, talk, kalk, kvarts, attapulgit, mont- Ikaolin, clay, talc, lime, quartz, attapulgite, mont- I

morillonit, bentonit eller diatoméjord, og formalede syn- Imorillonite, bentonite or diatomaceous earth, and ground syn- I

tetiske mineraler, f.eks. siliciumdioxid, aluminiumoxid, Itetical minerals, e.g. silica, alumina, I

silicater, navnlig aluminium- eller magnesiumsilicater. Som Isilicates, in particular aluminum or magnesium silicates. As in

20 faste bærestoffer for granulater egner sig f.eks. knuste og I20 solid carriers for granules are suitable e.g. shattered and I

fraktionerede, naturlige mineraler, f.eks. calcit, marmor, Ifractionated natural minerals, e.g. calcite, marble, I

pimpsten, sepiolit og dolomit, samt syntetiske granulater Ipumice, sepiolite and dolomite, and synthetic granules I

af uorganiske og organiske mel, og granulater af organisk Iof inorganic and organic flour, and granules of organic I

materiale, f.eks. savsmuld, kokosnøddeskaller, majskolber Imaterial, e.g. sawdust, coconut shells, corn cobs I

25 og tobaksstængler, endvidere kiselgur, majskolber, trical- I25 and tobacco stalks, also diatomaceous earth, corn cobs, trical- I

ciumphosphat, pulveriseret kork, absorberende carbon black Icium phosphate, powdered cork, absorbent carbon black I

og vandopløselige polymere, harpikser, voksarter, faste Iand water-soluble polymers, resins, waxes, solids I

gødningsstoffer, og sådanne faste præparater kan om ønsket Ifertilizers and such solid preparations may, if desired, I

indeholde et eller flere forenelige fugtemidler, disperge- Icontain one or more compatible wetting agents, dispersants

30 ringsmidler, emulgeringsmidler eller farvende midler, der, I30, emulsifying or coloring agents which, I

når de er faste, også kan tjene som fortyndingsmidler. Bære- Iwhen solid, can also serve as diluents. Carry I

stoffet kan også være flydende, f.eks. alkoholer, især buta- Ithe substance may also be liquid, e.g. alcohols, especially buta- I

nol eller glycol, samt deres ethere eller estere, navnlig Inol or glycol, and their ethers or esters, in particular I

methylglycolacetat, ketoner, især acetone, cyclohexanon, Imethylglycol acetate, ketones, especially acetone, cyclohexanone, I

35 methylethylketon, methylisobutylketon og isophoron, jord- I35 methyl ethyl ketone, methyl isobutyl ketone and isophorone, soil I

oliefraktioner, paraffiniske eller aromatiske carbonhydrider, Ioil fractions, paraffinic or aromatic hydrocarbons, I

141 DK 175618 B1 | især xylener eller alkylnaphthalener, jordoliefraktioner, mineralske og vegetabilske olier, aliphatiske chlorerede carbonhydrider, især trichlormethan eller methylenchlorid, eller aromatiske chlorerede carbonhydrider, især chlorben- ] 5 . zener, vandopløselige eller stærkt polære opløsningsmidler, ! f.eks. dimethylformamid, dimethylsulfoxid eller N-methylpyr- | rolidon, samt vand, fordråbede gasser og lignende samt blandinger deraf.141 DK 175618 B1 | in particular xylenes or alkyl naphthalenes, petroleum fractions, mineral and vegetable oils, aliphatic chlorinated hydrocarbons, especially trichloromethane or methylene chloride, or aromatic chlorinated hydrocarbons, especially chlorobenzene. zenes, water-soluble or highly polar solvents,! eg. dimethylformamide, dimethylsulfoxide or N-methylpyr- | rolidone, as well as water, liquefied gases and the like, and mixtures thereof.

Det overfladeaktive middel kan være et emulgeringsr 10 middel, dispergeringsmiddel eller fugtemiddel af den ioniske eller ikke-ioniske type eller en blanding af sådanne overfladeaktive midler. Der kan som eksempler nævnes salte af polyacrylsyrer, salte af lignosulfonsyrer, salte af phenol-sulfonsyrer eller naphthalensulfonsyrer, polykondensater af 15 ethylenoxid med 'fedtalkoholer eller fedtsyrer eller fedtestere eller fedtaminer, substituerede phenoler, især alkyl-phenoler eller arylphenoler, salte af sulforavsyreestere, taurinderivater, især alkyltaurater, phosphorsyreestere af alkoholer eller af polykondensater af ethylenoxid med pheno-20 ler, estere af fedtsyrer med polyoler, og sulfat-, sulfonat-og phosphat-funktionelle derivater af de ovennævnte forbindelser. Tilstedeværelsen af mindst ét overfladeaktivt middel er i almindelighed essentiel, når den aktive bestanddel og/eller det indifferente bærestof kun er svagt vandopløse-25 lige eller ikke er vandopløselige, og bærestoffet, der anvendes, er vand.The surfactant may be an emulsifier, dispersant, or wetting agent of the ionic or nonionic type or a mixture of such surfactants. Examples include salts of polyacrylic acids, salts of lignosulfonic acids, salts of phenolic sulfonic acids or naphthalene sulfonic acids, polycondensates of ethylene oxide with fatty alcohols or fatty acids or fatty esters or fatty amines, substituted phenols, especially alkyl phenols, sulfate acids, arylphenols, , in particular alkyl taurates, phosphoric acid esters of alcohols or of polyethylene oxide polycondensates with phenols, esters of fatty acids with polyols, and sulfate, sulfonate and phosphate functional derivatives of the above compounds. The presence of at least one surfactant is generally essential when the active ingredient and / or inert carrier is only slightly water-soluble or not water-soluble and the carrier used is water.

Præparater ifølge opfindelsen kan indeholde yderligere forskellige additiver, f.eks. adhæsiver og farvende midler.Compositions of the invention may contain further various additives, e.g. adhesives and staining agents.

Adhæsiver såsom carboxymethylcellulose og naturlige og syn-30 tetiske polymere i form af pulvere, granulater eller latexer, f.eks. gummi-arabicum, polyvinylalkohol og polyvinylacetat, samt naturlige phospholipider, f.eks. kephaliner og lecithi-ner, samt syntetiske phospholipider, kan anvendes i præparaterne. Yderligere additiver kan være mineralske og vegeta-35 bilske olier. Det er muligt at anvende farvende midler, f.eks. uorganiske pigmenter, såsom jernoxid, titanoxid ellerAdhesives such as carboxymethyl cellulose and natural and synthetic polymers in the form of powders, granules or latexes, e.g. rubber arabic, polyvinyl alcohol and polyvinyl acetate, as well as natural phospholipids, e.g. Cephalins and lecithins, as well as synthetic phospholipids, may be used in the compositions. Additional additives may be mineral and vegetable oils. It is possible to use coloring agents, e.g. inorganic pigments such as iron oxide, titanium oxide or

I DK 175618 B1 II DK 175618 B1 I

I 142 II 142 I

preussisk blåt, og organiske farvestoffer, f.eks. alizarin- IPrussian blue, and organic dyes, e.g. alizarin- I

I farvestoffer, azofarvestoffer og metalphthalocyaninfarve- IIn dyes, azo dyes and metal phthalocyanine dyes- I

stoffer, samt sporelementer, f.eks. salte af jern, mangan, Isubstances, as well as trace elements, e.g. salts of iron, manganese, I

I bor, kobber, cobalt, molybden og zink. IIn boron, copper, cobalt, molybdenum and zinc. IN

5 Præparater indeholdende forbindelser med den almene I5 Compositions containing Compounds with the General I

I formel I, der kan anvendes til bekæmpelse af arthropoder, IIn Formula I, which can be used to combat arthropods, I

I plantenematoder, helminter og protozo-skadedyr, kan også IIn plant nematodes, helminths and protozoa pests, you can also

I indeholde synergister, f.eks. pipéronylbutoxid eller sesamex, IYou contain synergists, e.g. piperonylbutoxide or sesamex, I

I stabiliserende stoffer, andre insecticider, acaricider, IIn stabilizers, other insecticides, acaricides, I

I 10 plante-nematodicider, anthelmintica eller anticoccodiose- IIn 10 plant nematodicides, anthelmintics or anticoccodiosis- I

I -midler, fungicider (til anvendelse i landbruget eller til II - agents, fungicides (for use in agriculture or for I

I veterinær anvendelse, f.eks. benomyl eller iprodion), bac- IIn veterinary use, e.g. benomyl or iprodione), bac- I

I tericider, midler, der tiltrækker eller frastøder arthropoder IIn tericides, agents that attract or repel arthropods I

I eller vertebrater, eller pheromoner, reodoranter, smags- II or vertebrates, or pheromones, reodorants, taste I

I 15 givende midler, farvestoffer og terapeutiske hjælpemidler, IIn 15 giving agents, dyes and therapeutic aids, I

I f.eks. sporelementer. Disse præparater kan udformes til IIn e.g. trace elements. These compositions may be formed into I

I forbedring af styrken, den varige virkning, sikkerheden, IIn improving strength, lasting impact, safety,

optagelsen, når dette ønskes, det spektrum af skadelige Irecording, when desired, the spectrum of harmful I

organismer, der skal bekæmpes, eller til at bevirke, at Iorganisms to be controlled or to cause:

20 præparatet kan udøve andre nyttige funktioner hos det samme j IThe composition may perform other useful functions of the same

dyr eller det areal, der behandles. Ianimal or the area being treated. IN

Eksempler på andre pesticidt aktive forbindelser, IExamples of other pesticide-active compounds, I

der kan inkluderes i eller anvendes i forbindelse med præ- Iwhich may be included in or used in connection with pre-I

paraterne ifølge den foreliggende opfindelse er acephat, Ithe preparations of the present invention are acephate, I

25 chlorpyrifos, demeton-S-methyl, disulfoton, ethoprofos, IChloropyrifos, demeton-S-methyl, disulfoton, ethoprophos, I

fenitrothion, malathion, monocrotophos, parathion, phosalon, Ifenitrothione, malathion, monocrotophos, parathion, phosalon, I

pirimiphos-methyl, triazophos, cyfluthrin, cypermethrin, Ipirimiphos-methyl, triazophos, cyfluthrin, cypermethrin, I

deltamethrin, fenpropathrin, fenvalerat, permethrin, aldi- Ideltamethrin, fenpropathrin, fenvalerate, permethrin, aldi- I

carb, carbosulfan, methomyl, oxamyl, pirimicarb, bendiocarb, Icarb, carbosulfan, methomyl, oxamyl, pirimicarb, bendiocarb, I

30 teflubenzuron, dicofol, endosulfan, linden, benzoximat, I30 teflubenzuron, dicofol, endosulfan, linden, benzoximate, I

cartap, cyhexatin, tetradifon, avermectiner, ivermectin, . Icartap, cyhexatin, tetradifone, avermectins, ivermectin ,. IN

milbemyciner, thiophanat, trichlorfon, dichlorvos, diaveridin Imilbemycins, thiophanate, trichlorphon, dichlorvos, diaveridine I

og dimetriadazol. Iand dimetriadazole. IN

Til deres anvendelse i landbruget er forbindelserneFor their use in agriculture are the compounds

35 med formlen I derfor i almindelighed benyttet i form af I35 of formula I is therefore generally used in the form of I

præparater, der befinder sig på forskellige faste eller Ipreparations located on different solids or I

143 DK 175618 B1 flydende former. Flydende præparater kan anvendes til behandling af substrater eller steder, der inficeres eller er udsat for infektion med arthropoder, herunder omgivelser, udendørs eller indendørs opbevarings- eller behandlingsare-5 aler, beholdere eller udstyr eller stillestående eller strømmende vand.143 DK 175618 B1 liquid forms. Liquid preparations can be used to treat substrates or sites that are infected or exposed to infection with arthropods, including environment, outdoor or indoor storage or treatment areas, containers or equipment, or stagnant or flowing water.

Faste, homogene eller heterogene præparater indeholdende en eller flere forbindelser med den almene formel I, f.eks. granulater, pellets, briketter eller kapsler, kan 10 anvendes til behandling af stillestående eller strømmende vand over et vist tidsrum. En lignende virkning kan opnås ved anvendelse af strømmende eller intermitterende tilsætninger af i vand dispergerbare koncentrater som her beskrevet .Solid, homogeneous or heterogeneous compositions containing one or more compounds of general formula I, e.g. granules, pellets, briquettes or capsules can be used to treat stagnant or flowing water over a certain period of time. A similar effect can be obtained by using flowing or intermittent additions of water dispersible concentrates as described herein.

15 Præparater i form af aerosoler og vandige eller ikke- -vandige opløsninger eller suspensioner, der er egnede til spraybehandling, tågebehandling eller low- eller ultra-low--volume-spraybehandling, kan også anvendes.Preparations in the form of aerosols and aqueous or non-aqueous solutions or suspensions suitable for spray treatment, mist treatment, or low or ultra-low volume spray treatment may also be used.

Faste præparatformer, der kan nævnes, er støvpulvere 20 (med et indhold af forbindelsen med formlen I, der kan gå op til 80%) eller fugtelige pulvere eller granulater, navnlig sådanne, der fås ved ekstrudering, kompaktbehandling, imprægnering af et granuleret bærestof eller granulering startende ud fra et pulver (idet indholdet af forbindelsen med form-25 len I i disse fugtelige pulvere eller granulater ligger mellem 0,5 og 80%).Solid formulations which may be mentioned are dust powders 20 (containing a compound of the formula I which can go up to 80%) or moist powders or granules, in particular those obtained by extrusion, compacting, impregnating a granulated carrier or granulation starting from a powder (the content of the compound of formula I in these moist powders or granules being between 0.5 and 80%).

Opløsninger, især emulgerbare koncentrater, emulsioner, strømmedygtige midler, aerosoler, fugtelige pulvere (eller pulvere til spraybehandling), tørre, strømmedygtige 30 materialer og pastaer, kan nævnes som præparatformer, der er flydende, eller som skal danne flydende præparater, når de påføres.Solutions, especially emulsifiable concentrates, emulsions, flowing agents, aerosols, wettable powders (or powders for spray treatment), dry, flowable materials and pastes, may be mentioned as liquid formulations or liquid formulations when applied.

De emulgerbare eller opløselige koncentrater omfatter også som oftest 5 til 80% aktiv bestanddel, medens emul-35 sionerne eller opløsningerne, der er klar til anvendelse, i dette tilfælde indeholder fra 0,01 til 20% aktiv bestanddel.The emulsifiable or soluble concentrates also usually comprise 5 to 80% active ingredient, while the emulsions or solutions ready for use contain in this case from 0.01 to 20% active ingredient.

I DK 175618 B1 II DK 175618 B1 I

I 144 II 144 I

I Ud over opløsningsmidlet kan de emulgerbare koncentrater om IIn addition to the solvent, the emulsifiable concentrates on I

I ønsket indeholde fra 2 til 50% egnede additiver, f.eks. IIf desired, contain from 2 to 50% suitable additives, e.g. IN

I stabilisatorer, overfladeaktive midler, gennemtrængningsmid- IIn stabilizers, surfactants, penetrating agents

I ler, korrosionsinhibitorer, farvende midler eller adhæsiver. IIn clay, corrosion inhibitors, staining agents or adhesives. IN

I 5 Emulsioner med enhver ønsket koncentration, der er II 5 Emulsions with any desired concentration that is I

I særligt egnede til påføring på planter, kan fås ud fra disse IParticularly suitable for application to plants can be obtained from these I

I koncentrater ved fortynding med vand. IIn concentrates by dilution with water. IN

I De koncentrerede suspensioner, der kan påføres ved IThe concentrated suspensions that can be applied at I

I spraybehandling, fremstilles således, at der fås et stabilt, IIn spray treatment, is prepared so as to obtain a stable, I

I 10 flydende produkt, der ikke afsættes (fin formaling) og almin- IIn 10 liquid product that is not marketed (fine grinding) and generally- I

I deligvis indeholder fra 10 til 75% aktiv bestanddel, fra II partially contains from 10 to 75% of active ingredient, from I

I 0,5 til 30% overfladeaktive midler, fra 0,1 til 10% thixo- IIn 0.5 to 30% of surfactants, from 0.1 to 10% of thixo-I

I trope midler, fra 0 til 30% egnede additiver, f.eks. anti- IIn tropical agents, from 0 to 30% suitable additives, e.g. anti- I

I skummidler, korrosionsinhibitorer, stabiliseringsmidler, IIn foaming agents, corrosion inhibitors, stabilizers, I

I 15 gennemtrængningsmidler, adhæsiver og, som bærestof, vandIn 15 penetrants, adhesives and, as a carrier, water

I eller en organisk væske, i hvilken den aktive bestanddel er II or an organic liquid in which the active ingredient is I

I dårligt opløselig eller uopløselig. Nogle organiske, faste IIn poorly soluble or insoluble. Some organic, solid I

I stoffer eller uorganiske salte kan opløses i bærestoffet IIn substances or inorganic salts can be dissolved in the carrier I

I til hjælp ved hindring af afsætning eller som ant i frysemidler II to aid in the prevention of marketing or as ant in freezers I

I 20 for vand.In 20 for water.

I De fugtelige pulvere eller pulvere til spraybehandling IThe damp powders or sprays for spraying

I fremstilles almindeligvis således, at de indeholder fra 10 IGenerally, you are prepared to contain from 10 I

I til 80% aktiv bestanddel, og de indeholder i almindelighed II to 80% active ingredient and generally contain I

I ud over det faste bærestof fra 0 til 5% af et fugtemiddel, IIn addition to the solid carrier from 0 to 5% of a wetting agent, I

I 2 5 fra 3 til 10% af et dispergeringsmiddel og om nødvendigt II from 3 to 10% of a dispersant and if necessary I

I fra 0 til 80% af en eller flere stabilisatorer og/eller II from 0 to 80% of one or more stabilizers and / or I

I andre additiver, f.eks. gennemtrængningsmidler, adhæsiver IIn other additives, e.g. penetrating agents, adhesives I

I eller antisammenbagningsmidler, farvende midler eller lig- II or anti-caking agents, coloring agents or the like

I nende. II nende. IN

I 30 Til opnåelse af disse fugtelige pulvere blandes den ITo obtain these moist powders, it is mixed

I aktive bestanddel eller de aktive bestanddele grundigt i IIn active ingredient or active ingredients thoroughly in I

I egnede blandeapparater med yderligere stoffer, der kan im- IIn suitable mixers with additional substances which can be im-

I prægneres på det porøse fyldstof og er eller bliver formalet IYou are embossed on the porous filler and are or are being ground I

I under anvendelse af møller eller andre egnede formalingsap- IUsing mills or other suitable milling apparatus

I 35 parater. Der fås herved fugtelige pulvere, hvis fugtbarhed IIn 35 pieces. There are thus obtained moist powders whose wettability I

I og suspenderbarhed er fordelagtig. De kan suspenderes i IIn and suspendability is advantageous. They can be suspended in I

145 DK 175618 B1 vand til opnåelse af enhver ønsket koncentration, og disse suspensioner kan anvendes med stor fordel, navnlig til påføring på planternes blade.B1 water to achieve any desired concentration and these suspensions can be used with great advantage, especially for application to the leaves of plants.

De "i vand dispergerbare granuler (WG)", dvs. granu-5 ler, der er let dispergerbare i vand, har en sammensætning, der i det væsentlige kommer nær til sammensætningen af de fugtelige pulvere. De kan fremstilles ved granulering af præparater, der er beskrevet for de fugtelige pulvere, enten ad en våd vej (ved kontakt mellem findelt aktiv bestanddel 10 og det indifferente fyldstof og en ringe mængde vand, f.eks. fra 1 til 2 0%, eller med en vandig opløsning af disperge-ringsmiddel eller bindemiddel, efterfulgt af tørring og sigtning) eller ad en tør vej (ved kontaktbehandling efterfulgt af formaling og sigtning).The "water dispersible granules (WG)", i.e. granules which are readily dispersible in water have a composition substantially close to the composition of the moist powders. They can be prepared by granulating compositions described for the moist powders either by a wet path (by contact between finely divided active ingredient 10 and the inert filler and a small amount of water, for example from 1 to 20%, or with an aqueous solution of dispersant or binder, followed by drying and sieving) or by a dry route (by contact treatment followed by grinding and sieving).

15 Som allerede angivet omfattes de vandige dispersioner og emulsioner, f.eks. præparater opnået ved fortynding med vand, et fugtigt pulver eller et emulgerbart koncentrat ifølge opfindelsen, af det generelle omfang af de præparater, der skal anvendes ifølge opfindelsen. Emulsionerne kan være 20 af vand-i-olie- eller af olie-i-vand-typen, og de kan have en tyk konsistens.As already stated, the aqueous dispersions and emulsions, e.g. compositions obtained by dilution with water, a moist powder or an emulsifiable concentrate according to the invention, of the general scope of the compositions to be used according to the invention. The emulsions may be water-in-oil or oil-in-water type and may have a thick consistency.

Alle disse vandige dispersioner eller emulsioner eller sprayblandinger kan påføres på afgrøder ved hjælp af vilkårlige egnede metoder, hovedsageligt ved spraybehandling, 25 i mængder, der i almindelighed ligger i størrelsesordenen fra 100 til 1200 liter sprayblanding pr. hektar.All of these aqueous dispersions or emulsions or spray mixtures can be applied to crops by any suitable methods, mainly by spray treatment, in amounts generally in the range of 100 to 1200 liters spray mixture per day. acres.

Produkterne og præparaterne ifølge opfindelsen påføres bekvemt på vegetation og især på rødder eller blade med skadelige organismer, der skal udryddes.The products and compositions of the invention are conveniently applied to vegetation and especially to roots or leaves with harmful organisms to be eradicated.

30 En anden fremgangsmåde til anvendelse af forbindel serne eller præparaterne ifølge opfindelsen består i tilsætning af et præparat indeholdende den aktive bestanddel til overrislingsvand. Overrislingen kan være sprinkler-overrisling i forbindelse med pesticider, der skal anvendes til 35 behandling af blade, eller overrislingen kan være overrisling af jorden eller undergrunden ved anvendelse af systemiskeAnother method for using the compounds or compositions of the invention consists in the addition of a composition containing the active ingredient to irrigation water. The irrigation may be sprinkler irrigation in connection with pesticides to be used for the treatment of leaves, or the irrigation may be irrigation of the soil or subsoil using systemic

I DK 175618 B1 II DK 175618 B1 I

I 146 II 146 I

I pesticider. Den anvendte dosis af aktiv bestanddel ligger i IIn pesticides. The dose of active ingredient used is in I

almindelighed mellem 0,1 og 10 kg/ha, fortrinsvis mellem Igenerally between 0.1 and 10 kg / ha, preferably between 1

I 0,5 og 4 kg/ha. De anvendte mængder og koncentrationer kan IAt 0.5 and 4 kg / ha. The quantities and concentrations used may be I

I nærmere bestemt variere i overensstemmelse med anvendelses- ISpecifically, vary according to the application I

I 5 metoden og naturen af de anvendte præparater. IIn the method and nature of the compositions used. IN

I I almindelighed indeholder præparaterne til anvendelse IGenerally, the compositions for use contain I

I til bekæmpelse af arthropoder, plantenematoder, helminter II for the control of arthropods, plant nematodes, helminths

I eller protozo-skadelige organismer, i almindelighed fra IIn or protozoal harmful organisms, generally from I

I 0,00001 til 95 vægt-%, især fra 0,0005 til 50 vægt-% af en IIn 0.00001 to 95 wt%, especially from 0.0005 to 50 wt% of an I

I 10 eller flere forbindelser med den almene formel I eller af IIn 10 or more compounds of general formula I or of I

I totale aktive bestanddele, dvs. en eller flere forbindelser IIn total active ingredients, ie. one or more compounds I

I med den almene formel I sammen med andre stoffer, der er IYou have the general formula I together with other substances that you are

I toksiske over for arthropoder og plantenematoder, anthelmin- IIn Toxic to Arthropods and Plant Nematodes, Anthelmin- I

I tica, anticoccodiosemidler, synergister, sporelementer eller IIn tica, anticoccodiosis agents, synergists, trace elements or I

I 15 stabilisatorer. De faktisk anvendte præparater og deres IIn 15 stabilizers. The preparations actually used and their I

I anvendelsesmængde vælges til opnåelse af den eller de ønskede IIn amount of application is selected to obtain the desired I or I

I virkninger af landmanden, kvægopdrættere, lægen eller vete- IIn the effects of the farmer, cattle breeders, the doctor or wheat

rinæren eller den operatør, der udøver bekæmpelsen af de Ithe veterinarian or the operator engaged in the fight against the I

I skadelige organismer, .eller en anden på området erfaren IIn harmful organisms, or another in the field, you experienced

I 20 person. Faste og flydende præparater til topisk anvendelse IIn 20 person. Solid and liquid preparations for topical use

I til dyr, tømmer, opbevarede produkter eller husholdnings- IFor animals, timber, stored products or household

I materialer indeholder i almindelighed fra 0,00005 til IIn materials generally contain from 0.00005 to 1

I 90 vægt-%, især fra 0,001 til 10 vægt-% af en eller flere IIn 90% by weight, especially from 0.001 to 10% by weight of one or more I

I forbindelser med den almene formel I. Til indgivelse oralt IIn compounds of the general formula I. For oral administration

I 25 eller parenteralt til dyr, herunder ved anvendelse af per- I25 or parenterally to animals, including the use of per- I

I kutane, faste eller flydende præparater, indeholder disse IIn cutaneous, solid or liquid preparations, these contain I

I normalt fra 0,1 til 90 vægt-% af en eller flere forbindelser IUsually from 0.1 to 90% by weight of one or more compounds I

I med den almene formel I. Medicinsk behandlede foderstoffer II of the general formula I. Medicated feedingstuffs I

indeholder normalt fra 0,001 til 3 vægt-% af en eller flere Iusually contains from 0.001 to 3% by weight of one or more I

I 30 forbindelser med den almene formel I. Koncentrater og sup- IIn compounds of the general formula I. Concentrates and sup- I

I piementer til blanding med foderstoffer indeholder normalt IIn feed mixes with feed usually I

I fra 5 til 90 vægt-% og fortrinsvis fra 5 til 50 vægt-% af II from 5 to 90% by weight and preferably from 5 to 50% by weight of I

I en eller flere forbindelser med den almene formel I. Mine- IIn one or more compounds of general formula I. Mine- I

I ralsalt-slikkesten indeholder normalt fra 0,1 til 10 vægt-% IIn the salt salt candy box usually contains from 0.1 to 10% by weight of I

35 af en eller flere forbindelser med den almene formel I. I35 of one or more compounds of general formula I.

I Støvpræparater og flydende præparater til anvendelse IDust preparations and liquid preparations for use

j DK 175618 B1 147 til kvæg, personer, materialer, forskellige arealer eller udendørs områder kan indeholde fra 0,0001 til 15 vægt-%, især fra 0,005 til 2,0 vægt-% af en eller flere forbindelser med den almene formel I. Egnede koncentrationer i behandlede 5 vandmængder ligger mellem 0,0001 dpm og 20 dpm, især fra 0,001 dpm til 5,0 dpm af en eller flere forbindelser med den almene formel I og kan også anvendes terapeutisk i fiskebrug med passende tidsrum, i hvilke fiskene udsættes for de aktive forbindelser. Spiselig lokkemad kan indeholde fra 10 0,01 til 5 vægt-%, fortrinsvis fra 0,01 til 1,0 vægt-% af en eller flere forbindelser med den almene formel I.for cattle, persons, materials, various areas or outdoor areas may contain from 0.0001 to 15% by weight, in particular from 0.005 to 2.0% by weight of one or more compounds of the general formula I. Suitable concentrations in treated amounts of water range from 0.0001 ppm to 20 ppm, in particular from 0.001 ppm to 5.0 ppm of one or more compounds of general formula I, and may also be used therapeutically in fish farms with appropriate periods of time in which the fish are exposed. for the active compounds. Edible bait may contain from 0.01 to 5% by weight, preferably from 0.01 to 1.0% by weight of one or more compounds of the general formula I.

Ved indgivelse til vertebrater ad parenteral, oral eller perkutan vej eller på anden måde vil den anvendte dosis af forbindelser med den almene formel I afhænge af j 15 arten, alderen og helbredstilstanden hos den pågældende vertebrat samt af naturen og graden af den faktiske eller potentielle infektion med arthropoder, helminter eller protozoer. En enkelt dosis på fra 0,1 til 100 mg, fortrinsvis fra 2,0 til 20,0 mg pr. kg kropsvægt af dyret, eller doser 20 på fra 0,01 til 20,0 mg, fortrinsvis fra 0,1 til 5,0 mg pr. kg kropsvægt af dyret pr. dag til langvarig medicinsk behandling er i almindelighed passende ved oral eller parenteral indgivelse. Ved anvendelse af præparater eller materialer med forhalet frigivelse kan de daglige doser, der kræves 25 over en periode på måneder, kombineres og indgives til dyrene ved én enkelt lejlighed.When administered to vertebrates by parenteral, oral or percutaneous route or otherwise, the dose of compounds of general formula I used will depend on the nature, age and state of health of the vertebrate in question, and the nature and degree of actual or potential infection. with arthropods, helminths or protozoa. A single dose of from 0.1 to 100 mg, preferably from 2.0 to 20.0 mg per day. or doses 20 of from 0.01 to 20.0 mg, preferably from 0.1 to 5.0 mg per kilogram. kg body weight of the animal per day to long-term medical treatment is generally appropriate by oral or parenteral administration. Using delayed release preparations or materials, the daily doses required over a period of months can be combined and administered to the animals on a single occasion.

De følgende udførelseseksempler illustrerer landbrugskemiske præparater indeholdende de her omhandlede forbindelser, hvorefter der følger eksempler på de insecticide og 30 acaricide anvendelser og egenskaber i forbindelse med nogle af de her omhandlede forbindelser.The following embodiments illustrate agricultural chemical compositions containing the compounds of the present invention, followed by examples of the insecticidal and acaricidal uses and properties of some of the compounds of the present invention.

Præparatanvendelseseksempler 35 De følgende præparateksempler 23-28 illustrerer præ parater til anvendelse mod arthropoder, især insekter ogPreparation Examples 35 The following Preparation Examples 23-28 illustrate preparations for use against arthropods, especially insects and

I DK 175618 B1 II DK 175618 B1 I

I 148 II 148 I

I acarider, plantenematoder samt skadelige organismer hørende IIn acarides, plant nematodes and harmful organisms

I til helminter eller protozoer, hvilke præparater som aktiv II for helminths or protozoa which preparations as active

I bestanddel indeholder forbindelser med den almene formel I, IIn constituent compounds of general formula I, I

I især forbindelser såsom de, der er beskrevet i fremstil- IIn particular, compounds such as those described in the preparation I

I 5 lingseksemplerne 1-22 samt i tabel III og IV. De præparater, IIn Examples 1-22 and in Tables III and IV. The preparations I

I der er beskrevet i præparateksemplerne 23-28, kan hver for- IAs described in Preparation Examples 23-28, each formulation may be used

I tyndes i vand til dannelse af et sprøjteligt præparat i IYou are diluted in water to form a sprayable composition in I

I koncentrationer, der er egnede til anvendelse i marken. IAt concentrations suitable for use in the field. IN

I Generiske kemiske beskrivelser af bestanddelene (for hvilke IGeneric chemical descriptions of the constituents (for which I

I 10 alle de følgende procentmængder er angivet i vægt-%), der IIn 10 all the following percentages are given in% by weight that I

I anvendes i præparateksemplerne 23-28, er som følger: II used in Preparation Examples 23-28 are as follows:

I Ethylan BCP: nonylphenol-ethylenoxid-kondensat IIn Ethylan BCP: nonylphenol-ethylene oxide condensate I

I Soprophor BSU: kondensat af tristyrylphenol og ethylenoxid IIn Soprophor BSU: condensate of tristyryl phenol and ethylene oxide I

I 15 Arylan CA: 70% w/v opløsning af calciumdodecylbenzen- IIn Arylan CA: 70% w / v solution of calcium dodecylbenzene-I

I sulfonat IIn sulfonate I

I Solvesso 150 let C10-aromatisk opløsningsmiddel IIn Solvesso 150 light C10 aromatic solvent I

I Arylan S: Na-dodecylbenzensulfonat IIn Arylan S: Na-dodecylbenzenesulfonate I

I Darvan Na-lignosulfonat IIn Darvan Na lignosulfonate I

I 20 Celite PF syntetisk magnesiumsilicat-bærer IIn 20 Celite PF synthetic magnesium silicate carrier I

I Sopropon T36 Na-salt af polycarboxylsyre IIn Sopropon T36 Na salt of polycarboxylic acid I

I Rhodigel 23 polysaccharid-xanthangummi IIn Rhodigel 23 polysaccharide xanthan gum I

I Bentone 38: organisk derivat af magnesiummontmorillonit IIn Bentone 38: Magnesium Montmorillonite Organic Derivative I

I Aerosil siliciumdioxid med mikrofin partikelstør- IIn Aerosil silica with microfine particle size I

I 25 relse IIn room I

I Eksempel 23 IIn Example 23 I

I Et vandopløseligt koncentrat fremstilles ud fra føl- IA water-soluble concentrate is prepared from foil I

I 30 gende bestanddele: IIngredients:

I Aktiv bestanddel 7% IActive ingredient 7% I

I ETHYLAN BCP 10% II ETHYLAN BCP 10% I

I N-methylpyrrolidon 83% IIn N-methylpyrrolidone 83% I

I 35 II 35 I

I ved opløsning af ETHYLAN BCP i en portion N-methylpyrrolidon, II by dissolving ETHYLAN BCP in a portion of N-methylpyrrolidone, I

149 DK 175618 B1 hvorefter man tilsætter den aktive bestanddel under opvarmning og omrøring, indtil den er opløst. Den fremkomne opløsning fyldes op til det ønskede rumfang ved tilsætning af resten af opløsningsmidlet.149 DK 175618 B1 and then the active ingredient is added with heating and stirring until dissolved. The resulting solution is made up to the desired volume by adding the rest of the solvent.

55

Eksempel 24Example 24

Et emulgerbart koncentrat fremstilles ud fra følgende bestanddele: 10An emulsifiable concentrate is prepared from the following ingredients: 10

Aktiv bestanddel 7%Active ingredient 7%

Soprophor BSU 4%Soprophor BSU 4%

Arylan CA 4% N-methylpyrrolidon 50% 15 Solvesso 150 35% ved opløsning af Soprophor BSU, Arylan CA og den aktive bestanddel i N-methylpyrrolidon, hvorefter der tilsættes Solvesso 150 til det ønskede rumfang.Arylan CA 4% N-methylpyrrolidone 50% 15 Solvesso 150 35% by dissolving Soprophor BSU, Arylan CA and the active ingredient in N-methylpyrrolidone, then adding Solvesso 150 to the desired volume.

2020

Eksempel 25Example 25

Et fugteligt pulver fremstilles ud fra følgende. bestanddele: 25A moist powder is prepared from the following. Ingredients: 25

Aktiv bestanddel 40% ARYLAN S 2%Active ingredient 40% ARYLAN S 2%

Darvan No. 2 5%Darvan No. 2 5%

Celite PF 53% 30 ved sammenblanding af bestanddelene og formaling af blandingen i en hammermølle til en partikelstørrelse på mindre end 50 μ.Celite PF 53% 30 by mixing the ingredients and grinding the mixture in a hammer mill to a particle size of less than 50 µ.

I DK 175618 B1 II DK 175618 B1 I

I 150 II 150 I

I Eksempel 26 IIn Example 26 I

I Et vandigt, strømmedygtigt præparat fremstilles ud IAn aqueous, flowable preparation is prepared I

I fra følgende bestanddele: IFrom the following components:

I 5 II 5 I

I Aktiv bestanddel 40,00% IActive ingredient 40.00% I

I Ethylan BCP 1,00% IIn Ethylan BCP 1.00% I

I Sopropon T36 0,20% II Sopropon T36 0.20% I

I Ethylenglycol 5,00% IIn Ethylene Glycol 5.00% I

I 10 Rhodigel 23 0,15% II 10 Rhodigel 23 0.15% I

I Vand 53,65% IIn Water 53.65% I

I ved grundig sammenblanding af bestanddelene og formaling i IBy thoroughly mixing the ingredients and grinding in

I en kuglemølle, indtil middelpartikelstørrelsen er mindre IIn a ball mill until the average particle size is smaller

I 15 end 3 μ. 'IIn 15 than 3 µ. 'IN

I Eksempel 27 IIn Example 27 I

I Et emulgerbart suspensionskoncentrat fremstilles ud IAn emulsifiable suspension concentrate is prepared from I

I 20 fra følgende bestanddele: I20 from the following constituents:

I Aktiv bestanddel 30,0% IActive ingredient 30.0% I

I Ethylan BCP 10,0% IIn Ethylan BCP 10.0% I

I Bentone 38 0,5% IIn Bentone 38 0.5% I

I 25 Solvesso 150 59,5% II 25 Solvesso 150 59.5% I

I ved grundig blanding af bestanddelene og formaling i en IYou thoroughly mix the ingredients and grind in a

I kuglemølle, indtil middelpartikelstørrelsen er mindre end IIn a ball mill until the mean particle size is less than I

I 3 μ. IIn 3 μ. IN

I 30 II 30 I

IIN

DK 175618 B1 j i i 151 i jDK 175618 B1 j i i 151 i j

Eksempel 28 j i i I vand dispergerbare granuler fremstilles ud fra j følgende bestanddele: i 5 · i jExample 28 µl in water dispersible granules are prepared from the following ingredients: i 5 · i j

Aktiv bestanddel 30%Active ingredient 30%

Darvan No. 2 15%Darvan No. 2 15%

Arylan S 8%Arylan S 8%

Celite PF 47% i 10 ved blanding af bestanddelene, mikronisering i en væskeener-gimølle og dernæst granulering i en roterende pelletmaskine ved påsprøjtning af en tilstrækkelig mængde vand (op til 10% efter vægt pr. rumfang). De fremkomne granuler tørres i 15 et tørreapparat med fluidiseret lag til fjernelse af overskud af vand.Celite PF 47% in 10 by mixing the ingredients, micronizing in a liquid energy germ mill and then granulating in a rotary pellet machine by spraying a sufficient amount of water (up to 10% by weight per volume). The resulting granules are dried in a fluidized bed dryer to remove excess water.

Eksempel 29 20 Et støvpulver kan fremstilles ved grundig sammenblan ding af følgende bestanddele: iExample 29 A dusting powder can be prepared by thoroughly mixing the following ingredients: i

Aktiv bestanddel 1-10%Active ingredient 1-10%

Superfin talk 99-90% 25Super Fine Talk 99-90% 25

Dette pulver kan påføres på stedet for en arthropode--infektion, f.eks. affaldspladser eller dumpningsarealer, opbevarede produkter eller husholdningsmaterialer eller dyr, der er inficeret med eller udsat for infektion med 30 arthropoder til bekæmpelse af arthropoder ved oral indgivelse. Egnede midler til fordeling af støvpulveret til det sted, hvor infektionen med arthropoder finder sted, omfatter mekaniske blæsere, håndrystere og selvbehandlingsapparater til kvæg.This powder can be applied at the site of an arthropod infection, e.g. waste disposal sites or dumping areas, stored products or household materials or animals infected with or susceptible to infection by 30 arthropods for the control of arthropods by oral administration. Suitable means for distributing the dust powder to the site where the infection with arthropods takes place include mechanical blowers, hand shakers and cattle self-handling devices.

3535

DK 175618 B1 IDK 175618 B1 I

152 I152 I

Eksempel 30 IExample 30 I

En spiselig lokkemad kan fremstilles ved grundig IAn edible bait can be prepared by thorough I

sammenblanding af følgende bestanddele: Imixing the following components:

5 ’ I5 'I

Aktiv bestanddel 0,1-1,0% IActive ingredient 0.1-1.0% I

Hvedemel 80,0% IWheat flour 80.0% I

Melasse 19,9-19,0% IMolasses 19.9-19.0% I

10 Denne spiselige lokkemad kan fordeles på et sted, I10 This edible bait can be distributed in a location, I

f.eks. i beboelseshuse eller industriejendomme, f.eks. køk- Ieg. in residential or industrial properties, e.g. kitchen- I

kener, hospitaler eller opbevaringsrum, eller udendørs are- Ikings, hospitals or storage rooms, or outdoor areas- I

aler, der er inficeret med arthropoder, f.eks. myrer, græs- Ispecies infected with arthropods, e.g. ants, grass- I

hopper, kakerlakker og fluer, til bekæmpelse af arthropoderne Imares, cockroaches and flies, to combat the arthropods I

15 ved oral indgivelse. I15 by oral administration. IN

Eksempel 31 IExample 31 I

En opløsning kan fremstilles indeholdende følgende IA solution may be prepared containing the following I

20 bestanddele: I20 constituents: I

Aktiv bestanddel 15% IActive ingredient 15% I

Dimethylsulfoxid 85% IDimethylsulfoxide 85% I

25 ved opløsning af pyrrolderivatet i en portion af dimethyl- I25 by dissolving the pyrrole derivative in a portion of dimethyl-I

sulfoxidet og derefter tilsætning af mere dimethylsulfoxid Ithe sulfoxide and then the addition of more dimethyl sulfoxide I

til opnåelse af det ønskede rumfang. Denne opløsning kan Ito obtain the desired volume. You can use this solution

anvendes i forbindelse med husdyr, der er inficeret med Iis used in connection with domestic animals infected with I

arthropoder, perkutant ved anvendelse ved påhældning eller, Iarthropods, percutaneous when used in pouring or, I

30 efter sterilisation ved filtrering gennem en polytetrafluor- I30 after sterilization by filtration through a polytetrafluoro-I

ethylen-membran (0,22 mikrometers porestørrelse) ved par- Iethylene membrane (0.22 micron pore size) at par I

enteral injektion i en mængde på fra 1,2 til 12 ml opløsning Ienteral injection in an amount of 1.2 to 12 ml of solution I

pr. 100 kg dyrevægt. Iper. 100 kg animal weight. IN

153 DK 175618 B1153 DK 175618 B1

Eksempel 32Example 32

Et fugteligt pulver kan fremstilles ud fra følgende bestanddele: 5A moist powder can be prepared from the following ingredients: 5

Aktiv bestanddel 50%Active ingredient 50%

Ethylan BCP (9 mol oxid pr. mol phenol) 5%Ethylan BCP (9 moles of oxide per mole of phenol) 5%

Aerosil 5%Aerosil 5%

Celite PF 40% 10 ved absorption af Ethylan BCP på Aerosil, blanding med de øvrige bestanddele og formaling af blandingen i en hammermølle til dannelse af et fugteligt pulver, der kan fortyndes med vand til en koncentration på fra 0,001 til 2% (vægt pr.Celite PF 40% 10 by absorption of Ethylan BCP on Aerosil, mixing with the other ingredients and grinding the mixture in a hammer mill to form a moist powder which can be diluted with water to a concentration of 0.001 to 2% (wt.

15 rumfangsenhed) af den aktive forbindelse og påføres på stedet for infektion med arthropoder, f.eks. larver af diptere, eller plantenematoder ved spraybehandling, eller husdyr, der er inficeret med eller udsat for infektion med arthropoder, helminter eller protozoer, ved sprøjtning eller dyp-20 ning, eller ved oral indgivelse i drikkevand, til bekæmpelse af arthropoderne, helminterne eller protozoerne.15 volumes) of the active compound and applied at the site of infection with arthropods, e.g. larvae of dippers, or plant nematodes by spray treatment, or domestic animals infected with or susceptible to infection by arthropods, helminths or protozoa, by spraying or dipping, or by oral administration in drinking water, to control the arthropods, helminths or protozoa .

Eksempel 33 25 En bolus med langsom frigivelse kan fremstilles ud fra granuler indeholdende et densitetsmiddel, bindemiddel, et middel til forhalet frigivelse og den aktive bestanddel, fremstillet ifølge eksempel 27 med varierende procentmængder af bestanddelene. Ved komprimering af blandingen kan der 30 dannes en bolus med en massefylde på 2 eller mere, og denne kan indgives oralt til drøvtyggerhusdyr til retention i reticulo-rumen til frembringelse af en kontinuerlig langsom frigivelse af pyrrolforbindelse over et udstrakt tidsrum til bekæmpelse af infektion af drøvtyggerhusdyrene med 35 arthropoder, helminter eller protozoer.Example 33 A slow release bolus can be prepared from granules containing a density agent, binder, a delayed release agent and the active ingredient prepared according to Example 27 with varying percentages of the ingredients. By compressing the mixture, a bolus having a density of 2 or more may be formed and may be administered orally to ruminant livestock for retention in the reticulo space to produce a continuous slow release of pyrrole compound over a prolonged period of time to control infestation of ruminant livestock. with 35 arthropods, helminths or protozoa.

I DK 175618 B1 II DK 175618 B1 I

I 154 II 154 I

I Eksempel 34 IIn Example 34 I

I Et præparat med langsom frigivelse kan fremstilles IA slow release preparation may be prepared

I ud fra følgende bestanddele: IBased on the following components:

I 5 II 5 I

I Aktiv bestanddel 0,5-25% IActive ingredient 0.5-25% I

I Polyvinylchlorid-basis 75-99,5% IIn Polyvinyl Chloride Base 75-99.5% I

I ved blanding af polyvinylchlorid-basismaterialet med den II by mixing the polyvinyl chloride base material with the I

I 10 aktive forbindelse og et egnet blødgøringsmiddel, f.eks. IIn active compound and a suitable plasticizer, e.g. IN

I dioctylphthalat, og smelteekstrudering eller -formning af IIn dioctyl phthalate, and melt extrusion or molding of I

I det homogene præparat til egnede former, f.eks. granuler, IIn the homogeneous composition for suitable forms, e.g. granules, I

I pellets, briketter eller strimler, der f.eks. er egnet til IIn pellets, briquettes or strips, e.g. is suitable for I

I tilsætning til stillestående vand eller, i tilfælde af strim- IIn addition to stagnant water or, in the case of strip I

I 15 ler, fremstilling af kraver eller øremærker til påsætning IIn 15 clays, manufacture of collars or ear tags for application I

I på husdyr til bekæmpelse af skadelige insekter ved langsom IIn domestic animals for the control of harmful insects by slow

I frigivelse af den aktive forbindelse. IIn releasing the active compound. IN

I Lignende præparater kan fremstilles med erstatning ISimilar preparations can be made with substitute I

I af den aktive bestanddel i præparateksemplerne med en pas- II of the active ingredient in the composition examples with a pass

I 20 sende mængde af enhver anden forbindelse med den almene II send quantity of any other connection with the general I

I formel I. IIn Formula I.

I Eksempler på pesticide anvendelsesmetoder IExamples of pesticide application methods

I 25 I de følgende anvendelseseksempler nr. 35-47 anvendes II In the following application examples Nos. 35-47, I is used

I der forbindelser ifølge opfindelsen i forskellige koncentra- IIn compounds of the invention in different concentrations

I tioner. Anvendelsen af en 1 dpm (koncentration af forbindel- IIn tions. The use of a 1 ppm (concentration of compound I)

I sen i dele pr. million af den påførte forsøgsopløsning) ILate in parts per million of the applied test solution) I

I opløsning eller suspension eller emulsion til påføring på IIn solution or suspension or emulsion for application to I

I 30 blade svarer omtrentlig til anvendelse af 1 g aktiv bestand- IIn 30 leaves approximately corresponds to the use of 1 g of active ingredient

I del pr. hektar, beregnet på et omtrentligt sprøjterumfang IIn part pr. per hectare, calculated on an approximate spray volume I

I på 1000 1/ha (tilstrækkeligt til afløb) . Ved de følgende IIn 1000 l / ha (sufficient for drainage). By the following I

I anvendelser vil bladspraypræparater med fra ca. 6,25 til IIn applications, foliar spray compositions with from about 6.25 to 1

I ca. 500 dpm således svare til fra ca. 6 til ca. 500 g/ha.For approx. 500 ppm thus corresponds to approx. 6 to approx. 500 g / ha.

I 35 Til anvendelser til jorden svarer en jordkoncentration på 1 II 35 For soil applications, a soil concentration of 1 I is equivalent

I dpm, beregnet på basis af en jorddybde på 7,5 cm, til om- IIn ppm, calculated on the basis of a soil depth of 7.5 cm, to about I

155 DK 175618 B1 trentlig 100 g/ha til anvendelse ved udspredning på marken.155 DK 175618 B1 approximately 100 g / ha for use in field application.

Eksempel 35 5 Aktivitet mod bladlus .........Example 35 Activity against aphids .........

Der fremstilles en blanding med følgende bestanddele: 0,01 g aktiv bestanddel 10 0,16 g dimethylformamid 0,838 g acetone 0,002 g overfladeaktiv blanding indeholdende både en alkylarylpolyetheralkohol og en alkylaryl-polyetheralkohol med sulfonsyregrupper på 15 aryldelen 98,99 g vand.A mixture is prepared with the following ingredients: 0.01 g of active ingredient 10 0.16 g of dimethylformamide 0.838 g of acetone 0.002 g of surfactant mixture containing both an alkylaryl polyether alcohol and an alkylaryl polyether alcohol with sulfonic acid groups of 15 aryl part 98.99 g of water.

Denne fortyndede vandige blanding sprøjtes på i potter anbragte dværg-nasturtiumplanter, hvorpå der befinder sig 20 voksne og nymfestadier af vrietorn-bladlusen (Aphis nastur-tii) . Antallet af bladlus pr. potte er. 100-150. Rumfanget af påsprøjtet vandig blanding er tilstrækkeligt til befugt- ! ning af planterne til afløb. Efter sprøjtebehandlingen opbevares potterne ved 20°C i ét døgn, hvorefter de levende 25 bladlus optælles. Mortalitetsprocenten er 100% for forbindelserne ifølge eksemplerne 1, 2, 3a, 4, 5, 16c, 17, 18, 19 og 20, samt ASE-numrene 12, 24, 33, 34, 38, 39, 42, 44, 45, .This dilute aqueous mixture is sprayed onto dwarf nasturtium plants housed in pots, on which are 20 adults and nymph stages of the vrietorn aphid (Aphis nastur-tii). The number of aphids per pot is. 100-150. The volume of sprayed aqueous mixture is sufficient for humidity! planting for drainage. After spraying, the pots are stored at 20 ° C for one day, after which the live 25 aphids are counted. The mortality rate is 100% for the compounds of Examples 1, 2, 3a, 4, 5, 16c, 17, 18, 19 and 20, as well as ASE numbers 12, 24, 33, 34, 38, 39, 42, 44, 45, .

54, 57, 60, 62, 98-100, 102-104, 125, 128, 130, 131, 135, ! i 137, 141, 142, 144, 157, 158, 162, 165, 166 og 174 ved en 30 koncentration på 100 dpm.54, 57, 60, 62, 98-100, 102-104, 125, 128, 130, 131, 135 ,! at 137, 141, 142, 144, 157, 158, 162, 165, 166 and 174 at a concentration of 100 ppm.

iin

I DK 175618 B1 II DK 175618 B1 I

I 156 II 156 I

I Eksempel 36 IIn Example 36 I

I Aktivitet mod mider IIn Activity Against Mites

I 5 Den samme præparatfremstillingsmetode som beskrevet I5 The same preparation method as described in I

I i eksempel 35 anvendes. I dette tilfælde anbringes der imid- II of Example 35 is used. In this case, however, I

I lertid 150-200 toplettede mider (Tetranychus urticae) på IIn the clay period 150-200 toplet mites (Tetranychus urticae) on I

I "tendergreen"-bønner. Efter sprøjtebehandling holdes plan- IIn "tender green" beans. After spraying, plan I is kept

I terne ved 30°C i 5 dage. Mortalitetsprocenten for miderne IIn the terns at 30 ° C for 5 days. Mortality rate for mites I

I 10 er 100% for forbindelserne fra eksempel 2, 3a, 16c, 17 og II 10 is 100% for the compounds of Examples 2, 3a, 16c, 17 and I

I 18 samt ASE-numrene 9, 20, 25, 41, 44, 46, 52, 53, 58, 59, II 18 and ASE numbers 9, 20, 25, 41, 44, 46, 52, 53, 58, 59, I

I 63, 64, 70, 74, 77-81, 83, 90, 98, 99, 102, 124 og 141 ved IIn 63, 64, 70, 74, 77-81, 83, 90, 98, 99, 102, 124 and 141, I

I en koncentration på 100 dpm. IAt a concentration of 100 ppm. IN

I 15 Eksempel 37-39 IIn Examples 37-39 I

I Aktivitet på "sydlig hærorm11 IIn Activity on "Southern Army Worms11 I

I 37: Der anvendes samme præparat som i eksempel 35. I II 37: The same preparation is used as in Example 35. I

I 20 dette tilfælde anbringes larver af andet stadium af "sydlig IIn this case, larvae of the second stage are placed by "southern I

I hærorm" (Spodoptera eridania) på Sieva-bønner med en højde IIn armyworm "(Spodoptera eridania) on Sieva beans with a height I

I på ca. 15 cm. Der iagttages følgende mortalitetsprocenter II in approx. 15 cm. The following mortality percentages are observed

I eifter 5 dages forløb: der fås 100%'s mortalitet med forbin- IIn spite of 5 days: 100% mortality with compound I is obtained

I delserne fra eksempel 3a, 3b, 5,6, 7, 8, 9, 11, 12, 15b, IIn the sentences of Examples 3a, 3b, 5.6, 7, 8, 9, 11, 12, 15b, I

I 25 16c, 17, 18, 20, 21b og 21c samt ASE-numrene 42, 44, 60, IIn 16c, 17, 18, 20, 21b and 21c as well as ASE numbers 42, 44, 60, I

I 62, 64, 98-100, 102, 103, 121, 124, 125, 131, 141, 142, II 62, 64, 98-100, 102, 103, 121, 124, 125, 131, 141, 142, I

I 144, 162, 166 og 174 ved en koncentration på 100 dpm, og II 144, 162, 166 and 174 at a concentration of 100 ppm, and I

I der opnås en mortalitet på 80% med forbindelsen fra eksem- IIn 80% mortality is obtained with the compound of Example I

I pel 13 i en mængde på 500 dpm. IIn column 13 at a rate of 500 ppm. IN

I 30 38: Der anvendes samme præparatfremstillingsmetode II 30 38: The same preparation method I is used

I som i eksempel 35, bortset fra, at præparatet i dette til- II as in Example 35, except that the composition of this invention

I fælde indeholder følgende bestanddele: IIn the case, the following constituents contain:

157 DK 175618 B1 2.5 mg aktiv bestanddel 0,05 g dimethyl formamid 9,9228 g acetone 0,0247 g overfladeaktivt middel {som i eksempel 35) 5 90 g vand157 DK 175618 B1 2.5 mg of active ingredient 0.05 g of dimethyl formamide 9.9228 g of acetone 0.0247 g of surfactant (as in Example 35) 5 90 g of water

Forbindelsen fra eksempel 4 giver 100%'s mortalitet over for "sydlig hærorm" ved 25 dpm.The compound of Example 4 gives 100% mortality to "southern armyworm" at 25 ppm.

39: Der anvendes samme præparatfremstillingsmetode 10 som i eksempel 38, bortset fra, at præparatet i dette tilfælde indeholder følgende bestanddele: 0,625 mg aktiv bestanddel 12.5 mg dimethylformamid 15 9,9621 g acetone 0,0247 g overfladeaktivt middel (som i eksempel 35) 90 g vand39: The same preparation method 10 is used as in Example 38 except that in this case the composition contains the following ingredients: 0.625 mg of active ingredient 12.5 mg of dimethylformamide 9.9621 g of acetone 0.0247 g of surfactant (as in Example 35) 90 g of water

Forbindelserne fra eksempel 1 og 2 giver 100%'s mor-20 talitet over for "sydlig hærorm" ved 6,25 dpm.The compounds of Examples 1 and 2 give 100% mortality to "Southern Army Worm" at 6.25 ppm.

Eksempel 40-43Examples 40-43

Aktivitet over for mexikansk bønnebille 25 40: Der anvendes samme præparatfremstillingsmetode som i eksempel 37, bortset fra, at der i dette tilfælde anvendes følgende bestanddele: 30 12,5 mg aktiv bestanddel 0,25 g dimethylformamid 9,726 g acetone 24,1 mg overfladeaktivt middel {som i eksempel 35) 89,988 g vand 35Activity on Mexican bean beet 25 40: The same preparation method is used as in Example 37 except that in this case the following ingredients are used: 12.5 mg of active ingredient 0.25 g of dimethylformamide 9.726 g of acetone 24.1 mg of surfactant (as in Example 35) 89.988 g of water 35

Larver på andet stadium af den mexikanske bønnebille I DK 175618 B1Larvae on the second stage of the Mexican bean beetle I DK 175618 B1

I 158 II 158 I

I (Epilachna varivestis, muls) anbringes på Sieva-bønner tned II (Epilachna varivestis, muls) are placed on Sieva beans on I

I en højde på ca. 15 cm. Der fås følgende procentmortalitet IAt an altitude of approx. 15 cm. The following percent mortality is obtained

I efter 5 dage: 100%'s mortalitet opnås med forbindelsen fra IAfter 5 days: 100% mortality is achieved with the compound of I

I eksempel 13 ved 125 dpm. IIn Example 13 at 125 ppm. IN

I 5 -41: Under anvendelse af præparatfremstillingsmetoden II 5 -41: Using the Preparation Method I

I fra eksempel 38, men under anvendelse af forbindelsen fra II of Example 38, but using the compound of I

I eksempel- 8 som aktiv bestanddel, fås der 100%'s mortalitet IIn Example 8 as active ingredient, 100% mortality I is obtained

I for mexikansk bønnebille ved 25 dpm. IIn for Mexican bean beetle at 25 ppm. IN

I 42: Under anvendelse af den i eksempel 35 beskrevne II 42: Using the I described in Example 35

I 10 præparat fremstillingsmetode, men med indhold af den ikke-bro- IIn 10 preparation method of preparation, but containing the non-bridge I

I merede forbindelse fra eksempel 15a som aktiv bestanddel, IIn compound of Example 15a as active ingredient, I

opnås der en 100%'s mortalitet for mexikansk bønnebillé ved Ia 100% mortality rate for Mexican bean beet is obtained at I

I 100 dpm. IAt 100 ppm. IN

43: Der anvendes samme præparatfremstillingsmetode I43: The same preparation method I is used

I 15 som i eksempel 40, bortset fra, at præparatet i dette til- II, as in Example 40, except that the composition of the present invention

I 10 mg aktiv bestanddel IIn 10 mg of active ingredient I

I 0,2 g dimethylformamid IIn 0.2 g of dimethylformamide I

I 20 9,7657 g acetone I9.7657 g of acetone I

I 0,0243 g overfladeaktivt middel (som i eksempel 35) IIn 0.0243 g of surfactant (as in Example 35) I

I 90 g vand IIn 90 g of water I

I Der opnås følgende mortalitetsprocenter for mexikansk IThe following mortality rates are obtained for Mexican I

25 bønnebille: 80%’s mortalitet med forbindelserne fra eksem- I25 bean beetle: 80% mortality with the compounds of Example I

pel 15a og 15b ved 100 dpm og 100%‘s mortalitet med forbin- Icolumns 15a and 15b at 100 ppm and 100% compound mortality

I delserne fra eksempel 1, 2, 9, 17, 18 samt ASE-numrene 42, IIn the sentences of Examples 1, 2, 9, 17, 18 and ASE numbers 42, I

I 44, 60, 62, 64, 98, 99, 124, 125, 141, 142 og 144 ved ‘ IIn 44, 60, 62, 64, 98, 99, 124, 125, 141, 142 and 144 at 'I

I 100 dpm. IAt 100 ppm. IN

I 30 II 30 I

I Eksempel 44-46 IIn Examples 44-46 I

I Aktivitet på husfluer II Activity on house flies I

I 35 Det toksiske middel i form af en 10 ml vandig suk- II The toxic agent in the form of a 10 ml aqueous sugar

keropløsning indeholdende 10% sukker efter vægt pr. vægtenhed Icuring solution containing 10% sugar by weight per weight unit I

159 DK 175618 B1 samt 100 dpm af det kemiske, toksiske stof, anvendes i et præparat, der fremstilles på samme måde som i eksempel 35.159 DK 175618 B1 and 100 ppm of the chemical toxic substance are used in a preparation prepared in the same manner as in Example 35.

Efter behov foretages der yderligere seriefortyndinger. Der fremstilles de tre følgende forskellige præparater til af-5 prøvning:Further serial dilutions are made as needed. The following three different preparations are prepared for testing:

Eksempel nr.Example No.

44 45 46 i 10 Aktiv bestanddel, mg 10 10 1,25 |44 45 46 i 10 Active ingredient, mg 10 10 1.25 |

Dimethylformamid, mg 160 200 25Dimethylformamide, mg 160 200 25

Overfladeaktivt middel (som i eksempel 35), mg 2,15 24,3 14,25Surfactant (as in Example 35), mg 2.15 24.3 14.25

Acetone, g 8,42 9,766 5,73 15 Vand, g 88,99 81 84,38Acetone, g 8.42 9.766 5.73 Water, g 88.99 81 84.38

Sukker, g 10 9 9,84 25 Voksne fluer (Musca domestica) anæstetiseres med carbondioxid og overføres derefter til en lokkemiddelskål 20 indeholdende det toksiske præparat. Efter én dag ved 27°C er den målte procentvise mortalitet for fluerne som følger:Sugar, g 10 9 9.84 25 Adult flies (Musca domestica) are anesthetized with carbon dioxide and then transferred to a bait bowl 20 containing the toxic preparation. After one day at 27 ° C, the measured percent mortality of the flies is as follows:

For eksempel 44: 100% mortalitet med forbindelserne fra eksempel 1, 2, 3b, 4-6, 8, 9, 16c, 17-20, 25 21b og 21c samt ASE-nr. 42, 44, 60, 62, 64, 98, 99, 100, 102, 103, 121, 124, 125, 131, 141, 142, 144, 162, 166 og 174 ved 100 dpm.For example, 44: 100% mortality with the compounds of Examples 1, 2, 3b, 4-6, 8, 9, 16c, 17-20, 25 21b and 21c and ASE no. 42, 44, 60, 62, 64, 98, 99, 100, 102, 103, 121, 124, 125, 131, 141, 142, 144, 162, 166 and 174 at 100 ppm.

For eksempel 45: 100% mortalitet med forbindelserne fra 30 eksempel 12 ved 100 dpm.For example, 45: 100% mortality with the compounds of Example 12 at 100 ppm.

For eksempel 46: 100% mortalitet med forbindelserne fra eksempel 1, 2 og 5 ved 12,5 dpm.For example, 46: 100% mortality with the compounds of Examples 1, 2 and 5 at 12.5 ppm.

I DK 175618 B1 II DK 175618 B1 I

I 160 II 160 I

I Eksempel 47 IIn Example 47 I

I Aktivitet over for "sydlig maisrodorm" IActivity Against "Southern Maize Worm" I

I 5 Der fremstilles et præparat på lignende måde som i II A preparation is prepared in a similar manner as in I

I eksempel 35, bortset fra, at der i dette tilfælde kun anven- IIn Example 35, except that in this case only I-

I des 48,99 g vand, hvorved der tilvejebringes en begyndelses- IIn des, 48.99 g of water, thereby providing an initial I

I koncentration af forsøgsforbindelsen på 200 dpm. Aliquoter IIn concentration of the test compound at 200 ppm. Aliquots I

I af dette præparat anvendes derefter direkte i overensstem- II of this preparation is then used directly in accordance with I

I 10 melse med den påkrævede forsøgskoncentration i dpm (dele IIn accordance with the required test concentration in ppm (Part I

I pr. million) efter vægt, i overensstemmelse med følgende II per million) by weight, in accordance with the following I

I forsøgsmetodik: ! IIn experimental methodology:! IN

I II I

Til en krukke indeholdende 60 g sandholdig lerjord jFor a jar containing 60 g of sandy clay soil j

I sættes der en aliquot af 200 dpm-forsøgsforbindelsespræpa- j IAn aliquot of 200 ppm test compound preparation is added

I 15 ratet (som passende for den endelige jordkoncentration af IIn the rat (as appropriate for the final soil concentration of I

I forsøgsforbindelsen), 3,2 ml vand og fem forspirede majsfrø- IIn the test compound), 3.2 ml of water and five germinated corn seeds

I planter. Krukken rystes grundigt til opnåelse af en jævn IIn plants. Shake the jar thoroughly to obtain an even I

I fordeling af forsøgspræparatet. Herefter anbringes der 20 IIn distribution of the test preparation. Then place 20 I

I "sydlige majsrodorm"-æg i en hulhed, der frembringes i jor- IIn "southern corn rootworm" eggs in a cavity produced in the soil

I 20 den. Til denne hulhed sættes der 1 ml vermiculit og 1,7 ml IIn the 20 den. To this cavity is added 1 ml of vermiculite and 1.7 ml of I

I vand. På tilsvarende måde fremstilles der en ubehandlet IIn water. Similarly, an untreated I is prepared

I kontrol ved anvendelse af samme størrelse aliquot af en IIn control using the same size aliquot of an I

I vand-acetone-dimethylformamid-emulgeringsmiddelopløsning, IIn water-acetone-dimethylformamide emulsifier solution, I

I der ikke indeholder nogen forsøgsforbindelse. Desuden anven- IIn which contains no test compound. In addition, I

I 25 des der en behandlet kontrol med en kommerciel teknisk for- IOn December 25, a commercial check was conducted with a commercial technical I

I bindelse, der er sammensat på samme måde, som forsøgsstan- IIn a compound composed in the same manner as the test standard

I dard. Efter 7 dages forløb optælles de levende rodormelarver II dard. After 7 days, the living rootworm larvae I are counted

I under anvendelse af en velkendt "Berlese"-tragtekstraktions- ' IUsing a well-known "Berlese" funnel extraction method

I metode. IIn method. IN

I 30 De følgende forbindelser giver alle 100%’s bekæmpelse IThe following compounds give all 100% control I

I ved anvendelse af jordkoncentrationer på 1,45, 0,72 og 0,36 II using soil concentrations of 1.45, 0.72 and 0.36 L

I dpm. Forbindelserne fra eksempel 3b, 4 og 17-19 samt ASE- II ppm. The compounds of Examples 3b, 4 and 17-19 and ASE-I

I -numre 98, 99, 101, 105, 113, 119, 121, 124, 125, 130 og 173. II numbers 98, 99, 101, 105, 113, 119, 121, 124, 125, 130 and 173. I

Claims

1. Pyrrole derivatives, characterized in that they have the general formula 5 in 10 Χ24ί *] - χ3 Y in which X means a halogen atom, cyano, haloalkyl, alkoxy, haloalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, haloalkyrthio, haloalkylsulfinyl or haloalkylsulfonyl wherein the alkyl, haloalkyl, alkoxy and haloalkoxy groups have linear or branched chain and less than 10 carbon atoms, and the halogen substitution in each of these groups consists of one or more halogen atoms which are the same or different, from mono up to complete polysubstitution, R 1, R 2 and R 3 are each selected from the same set of substituents as described for X, a hydrogen atom, an alkyl group and a substituent wherein no more than one of them (R 1, R 2 and R 3 ) is selected from the group consisting of formyl, amino, alkylamino and dialkylamino wherein the alkyl groups are linear or branched and have 30 less than 10 carbon atoms, Y represents a halogen atom or cyano, alkyl, halogenal alkyl, haloalkyl, alkoxy and haloalkoxy groups are linear or branched and have less than 10 carbon atoms, and the halogen substitution in all of these groups consists of one or more halogen atoms which are the same or in DK 175618 B1 In 162 II different, from mono- and up to complete polysubstitution, or IIY represents a hydrogen atom when IIX means a halogen atom or a group R5S (0) n, II5 where n means 0, 1 or 2, and R5 means alkyl II or haloalkyl, and the alkyl carbon chains and halogen I substitution are as defined above, II R 1 and R 2 each represent a hydrogen atom and I R 3 means cyano, II X 1, X 3, X 2 and X 4 are each selected from the same set sub-I substituents as described for Y and a hydrogen atom, II with the following provisos: II at least one of the substituents in tuents R1, R3 and R2 is selected I from the same set of substituents as described for X, II if X4 and X1 are hydrogen, and X is halo or cyano, R3 is different from X, and II is X4 and is hydrogen and Y is methyl, X is different from bromine, II except for the compound in which II is X4 = X1 = Y = R1 = X = R3 = R2 = C1 and at the same time X3 = X2 = H. IN

2 N ^ χΙ-Α-χ * (HD

A compound of formula (I) according to claim 1, ke η-II characterized in that I 25. is a halogen atom or cyano, haloalkyl, alkoxy, II haloalkoxy, alkylthio, alkylsulfinyl, alkylsulphonyl, haloalkylthio, haloalkylsulphinyl or II haloalkylsulfonyl wherein the alkyl, haloalkyl, II alkoxy and haloalkoxy groups are linear or II branched and have less than 10 carbon atoms and the halogen II substitution in all these groups is monosubstitution or up to complete polysubstitution, II R1, R 3 and R 2 are each selected from the same substituent group and a substituent wherein no more than one of I 3 I's as described for X, a hydrogen atom, an alkyl I 4 I thereof (R1, R3 , R2) is selected from the group consisting of I DK 175618 B1 | ! Formyl, amino, alkylamino and dialkylamino, wherein the alkyl of the groups are linear or branched and have less than 10 carbon atoms, Y represents a halogen atom or cyano, alkyl, haloalkyl, alkoxy or haloalkoxy, wherein alkyl, halo- the gene alkyl, alkoxy and haloalkoxy groups are linear or branched and have less than 10 carbon atoms and the halogen substitution in all these groups is monosubstitution or up to complete polysubstitution, and X1, X2, χ3 and X4 are as defined in claim 1 .! i i

3. X2-Jis ^ i-X3 V 1 which χΐ, X2, X3, X4 and Y have the same meaning as in claim 1, wherein a dicyanopropene derivative of the formula I is NH-CH = C-CH 2 —CN II x, -irVx4 ** II x2-ILJ-x3 (iv) II 5 * II is reacted with a basic agent. IN

A compound of formula (I) according to claim 2, characterized in that 15 X means a halogen atom or a group R 2 S (O) n, i! which n means 0, 1 or 2, and R5 means alkyl or haloalkyl, R - * - means a hydrogen atom, a halogen atom or alkylthio, R 4 means cyano, a hydrogen atom or a halogen atom, Y means a hydrogen atom, a halogen atom, haloalkyl or haloalkoxy, with the exception that Y is a hydrogen atom as defined in claim 1 and X 1, X 2, χ 3 and X 4 are each selected from the group consisting of! of a hydrogen atom, a halogen atom, C 1 -C 3 alkyl, C 1 -C 3 alkoxy and C 1 -C 3 alkylthio. 30 35 I DK 175618 B1 I I 164 I

A compound according to claim 3, characterized in that it has the general formula. IIX - - I b'4kJLr> IIYII 10 in which IIX means R5S (0) n, in which n means 0, 1 or 2, II and R5 means CH3, CF3, CF2C1, CFC12, CF2Br, CHF2, II CHC12 or CHC1F , II R2 means cyano, II 15 means H, F, Cl or Br, II R3 means H, F, Cl or Br, II X1 means H or Cl, and IIY means CF3 or CF30. IN

5 X4 = X1 = Y = R1 = X = R2 = R3 = C1 and at the same time X3 = X2 = H. in

5 HO-IL JLr3. 1. (XXXII) x'-rS-x4 X2_I1 JLx3 y 10. which various symbols are as defined in claim 1, and X, cyano and R3 are optionally protected in known manner, according to A-II (a or b) above to forming a compound of formula (Ic) wherein I R1 is alkoxy or haloalkoxy followed by an optional deprotection step, or I (d) when X, R1, R3, X1, X2, X3, X4 and Y are the same meaning I as in claim 1, and R 2 is CHO, reacting a compound of formula (Ic) with a reducing agent in a I solvent to convert the group CN to a I group CHO and to form the compound in which In R2, CHO, which compound is optionally oxidized in known manner to form the corresponding compound I of formula (XXXV) EC73 * I s I 'x'-irV * 4 (xxxv) I * I 30 I (E) when X , R 1, R 3, X 1, X 2, X 3, X 4 and Y have the same meaning I as in claim 1, and R 2 is cyano, alkyl or haloalkyl, reacting a compound of formula (I) in which n R2 is CHO, if necessary, protecting X, R1 or R3 in known manner according to I A-III (a, b, c or d), A-II (a or b) or CI I DK 175618 B1 II 178 II above, if necessary followed by a deprotection II step, or II (F) when X, R1, R3, X1, X2, X3, X4 and Y have the same meaning II as in claim 1, and R2 are amino, alkylamino, dialkyl-amino, hydrogen, halogen, alkylthio, haloalkylthio, II alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, II haloalkylsulfonyl or trifluoromethyl, reaction II of a compound of formula (XXXV) above, after II if necessary protecting X, R1 or R3 II 10 in known manner, e.g. converting to an acid chloride, followed by reaction with an alkali metal azide, II or with diphenylphosphoryl azide in the presence of an II organic base in an alcoholic solvent to form a carbamate which can then be hydrolyzed II to form the corresponding compound, in which II R2 is amino which is then optionally reacted according to II claim 9 (A) below or CI (ac) above, and II thereafter when R2 is halogen, optionally reacted according to II BI (a) above, followed if necessary of an elimination step, or II (G) when X, R1, R3, X1, X2, X3, X4 and Y have the same meaning II as in claim 1, and R2 is alkoxy or haloalkoxy, II reacting an compound of formula II xttoh II χΙ-Α-χ «(XXXVI) II X2-IIYjJ-x3. IIII 30 II wherein the various symbols are as defined II in claim 1, after optionally protecting II of X, R1 or R3, according to B-III above, if necessary II followed by a deprotection step, or II 35 (H) when R 1, R 2, R 3, Y, X 1, X 2, X 3 and X 4 are as defined in II of claim 1, and X is a perhaloalkylthio group, if phrase (a) of a compound of formula {XXXVIII} X '- 10.ρχ4 (XXXVHI) x2Jy ^ x3 Y 10. which X is hydrogen and the other symbols are as defined in claim 1, with chlorosulfonic acid (CISO3H) at a temperature of 0 to 150 ° C and optionally in an organic solvent to prepare an compound of the formula 15 cl0jSirTR2 I ri_1! .nJLr3 I x'nrV-4 <XXXIX) I χ2-ϋΧχ3 I 20 YI wherein the various symbols are as defined in claim 1; In (b) reacting a compound of formula (XXXIX) with I a reducing agent at a temperature of 0 to 110 ° C in an organic solvent to form a I disulfide compound of formula (XLI) I '- p-s_ 21 I (xli) I x24J-x ^ L γ J2 in I 35 in which the various symbols are as defined I in claim 1; and (c) reacting the disulfide compound of formula (XLI) II with a perhaloalkane of formula (XLII), ZCFR7R8, II wherein Z is Cl, Br or I, R7 is F, Cl or Br, and II R8 is F, Cl, Br or a perfluoroacyl group, in the vicinity of a free radical promoting reducing agent, and optionally in the presence of a base, in an organic solvent at a temperature of 20 to II. 85 ° C and optionally under pressure, to produce a compound of formula (I) wherein X is a perhalogen-II 10 'alkylthio group and the other symbols are as defined II in claim 1, or II (I) converting a compound prepared as described in any of steps AH above to a compound II of formula (I) as defined in claim 1. II

A compound of formula (I) according to claim 1, 2 or II 3, characterized in that II R1 is a hydrogen atom or a halogen atom, II R2 is cyano, IIX is a haloalkyl-S (O) n group, wherein n is 0, 1 or II 2, II X 1 and X 4 are different from a hydrogen atom, I Y is a haloalkyl or haloalkoxy group, and II X 2 and X 3 are a hydrogen atom. I DK 175618 B1 165

Compound according to claim 2, characterized in that it has the formula (II) I (II) Y 10 wherein X means R 5 S (0) n, where n is 0, 1 or 2 and R 5 is CH 3, CF 3, CF 2 Cl or CFC12, R2 is cyano, R1 is H, F, Cl, Br or NH2,

A compound according to claim 1, characterized in that it is 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (trifluoromethylthio) pyrrole; 1- (2,6-dichloro-4-trifluoromethoxyphenyl) -2-chloro-3-cyano-4- (trifluoromethylsulfonyl) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (dichlorofluoromethylthio) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (dichlorofluoromethylsulfinyl) pyrrole; 1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-chloro-3-30 cyano-4- (dichlorofluoromethylsulfonyl) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (chlorodifluoromethylsulfonyl) pyrrole, 1- (2,6-dichloro-4-trifluoromethylphenyl) -2- chloro-3-cyano-4- (chlorodifluoromethylsulfinyl) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (chlorodifluoromethylthio) pyrrole; In DK 175618 B1 I 166 I I 1- (2,6-Dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-I 4- (trifluoromethylsulfinyl) pyrrole; I I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-I I 4- (trifluoromethylsulfonyl) pyrrole; 1- (1- (2,6-dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-1-4- (dichlorofluoromethylthio) pyrrole; I-1- (2,6-dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-1- (dichlorofluoromethylsulfonyl) pyrrole; 1- [1- (2,6-dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-4- [dichlorofluoromethylsulfinyl] pyrrole; I I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-I I 4- (chlorodifluoromethylthio) pyrrole; I I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-I I 4- (chlorodifluoromethylsulfinyl) pyrrole; 1- I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I cyano-4- (dichlorofluoromethylsulfonyl) -5-bromopyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-1- [4- (chlorodifluoromethylsulfonyl) pyrrole; I I 1- (2,6-dichloro-4-trifluoromethoxyphenyl) -2-chloro-3- I I in cyano-4- (dichlorofluoromethylsulfinyl) pyrrole; H 1 1- (2,6-Dichloro-4-trifluoromethoxyphenyl) -2-chloro-3- I H I cyano-4- (dichlorofluoromethylsulfonyl) pyrrole; . I I 1- (2-chloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-I I 4- (dichlorofluoromethylsulfonyl) pyrrole; 1- (2-chloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-1- (4- dichlorofluoromethylsulfinyl) pyrrole; I I 1- (2-chloro-4-trifluoromethylphenyl) -2-bromo-3-cyano-I I 4- (dichlorofluoromethylsulfonyl) pyrrole; I I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I I cyano-4- (dichlorofluoromethylthio) -5-methyl thiopyrrole; I I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I I cyano-4- (bromodifluoromethylthio) pyrrole; I I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I cyano-4- (bromodifluoromethylsulfinyl) pyrrole; 1- I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I cyano-4- (bromodifluoromethylsulfonyl) pyrrole; I (I) I (I) I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (methylsulfinyl) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (methylsulfonyl) pyrrole; 1- (4-bromo-2,6-di chloropheny 1) -3-cyano-4- (chlorodifluoromethylthio) pyrrole; 1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (trifluoromethylthio) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (chlorodifluoro-methylthio) pyrrole; in 1- (2,4,6-trichlorophenyl) -3-cyano-4- (chlorodifluoro-methylsulfinyl) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (dichlorofluoromethylthio) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (dichlorofluoromethylsulfinyl) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (dichlorofluoromethylsulfonyl) pyrrole; 1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (dichlorofluoromethylthio) pyrrole; 1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (dichlorofluoromethylsulfinyl) pyrrole; 1- (4-bromo-2,6-dichlorophenyl) -3- cyano-4- (dichlorofluoromethylsulfonyl) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (trifluoromethylthio) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (trifluoromethylsulfinyl) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (trifluoromethylsulfonyl) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (trichloromethyl-thio) pyrrole; 1- (2,4-dichlorophenyl) -3-cyano-4- (dichlorofluoromethyl-thio) pyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4-chloropyrrole; 1- (2,4,6-trichlorophenyl) -3-cyano-4- (chlorodifluoro-methylsulfonyl) pyrrole; I I 1- (2,6-dichlorophenyl) -3-cyano-4- (dichlorofluoromethyl-thio) pyrrole; I I 1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- {trifluoro-methylsulfinyl) pyrrole; I-1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (trifluoro-1-methylsulfonyl) pyrrole; I I 1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (chlorodifluoro-1 L methylsulfinyl) pyrrole; 1- (1- (4-bromo-2,6-dichlorophenyl) -3-cyano-4- (chlorodifluoro-methylsulfonyl) pyrrole; I I 1- (4-bromo-2,6-dimethylphenyl) -3-cyano-4- (trifluoro-I-methylsulfinyl) pyrrole; I I 1- (4-bromo-2,6-dimethylphenyl) -3-cyano-4- (trifluoro-methylsulfonyl) pyrrole; I I 1- (4-bromo-2,6-difluorophenyl) -3-cyano-4- (dichlorofluoro-methyl-thio) pyrrole; I I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- I I cyano-4- (trifluoromethylsulfonyl) pyrrole; In 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- In cyano-4- (trifluoromethylsulfinyl) pyrrole; 1- [1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-] cyano-4-trifluoromethylsulfinyl-5-bromopyrrole; In 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3- In cyano-4-trifluoromethylsulfonyl-5-bromopyrrole, II 1- (2,6-dichloro-4-trifluoromethylphenyl) -2 -chloro-3-cyano-4-trifluoromethylthio-pyrrole; I I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-bromo-3-tri-I I fluoromethylthio-4-cyano-5-chloropyrrole; 1- (2,6-Dichloro-4-trifluoromethylphenyl) -2 - [(trifluoro-1-methyl) carbonylamino] -3-trifluoromethylthio-4-cyano-5-chloro-. I I pyrrole; I I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2- (methylcaronylamino) -3-trifluoromethylthio-4-cyano-5-chloropyrrole; 1- I 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3- I-trifluoromethylthio-4-cyano-5-chloropyrrole; In DK 175618 B1 169 1- (2-chloro-4-trifluoromethylphenyl) -2-amino-3-tri-fluoromethylthio-4-cyano-5-chloropyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3-dichlorofluoromethylthio-4-cyano-5-chloropyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2,4-bis- (trifluoromethylthio-3-cyano-5-aminopyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2- amino-3-trifluoromethylthio-4-cyano-5-bromopyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-amino-3-trifluoromethylthio-4-cyanopyrrole; 1- (4-trifluoromethylphenyl) ) -2-amino-3-trifluoromethyl-thio-4-cyano-5-bromo-pyrrole; 1- (2-chloro-4-trifluoromethyl-phenyl) -2-amino-3-trifluoromethyl-thio-4 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (dichlorofluoromethylthio) pyrrole; 1- (2,6-dichloro-4-tri fluoromethylphenyl) -2-chloro-3-cyano-4- (dichlorofluoromethylsulfinyl) pyrrole; 1- (2,6-dichloro-4-trifluoromethylphenyl) -2-chloro-3-cyano-4- (dichlorofluoromethylsulfonyl) pyrrole; 1- (2,6-Dichloro-4-trifluoromethylphenyl) -3-cyano-4- (dichlorofluoromethylthio) pyrrole, * 1- (2,6-Dichloro-4-trifluoromethylphenyl) -3-cyano-4- (dichlorofluoromethylsulfinyl) -pyrrole or 1- (2,6-dichloro-4-trifluoromethoxyphenyl) -2-chloro-3- c Yano-4- (trifluoromethylsulfonyl) pyrrole.

Process for the preparation of compounds of formula (I) characterized in that 30 (A) when the compound has formula (Ia): xXTCN HjN-Jvn ^ (la) x'-lfV-x * 35 YI DK 175618 B11 I 170 In which X1, X2, X3, X4 and Y are as defined in claim 1, I1 and I (AI): X is halogen, trifluoromethyl, cyano, alkylthio, alkylsulfinyl, alkyl sulfony, haloalkylthio, (hal) alkylsulfinyl or haloalkylsulfonyl, reacting with a compound of formula I 10 x, -Ar ^ (iii) III in which the various symbols are as defined in claim I 15 and the amino group is optionally protected II (a) with a halogenating agent, optionally in the presence of a solvent to form a compound II of formula (Ia), wherein X is halogen and then this compound is optionally reacted with trifluoromethyl-II copper in known manner to form compounds II of formula (Ia) ) where X is trifluoromethyl; II (b) with a tris (alkylthio) methane or tris (arylthio) '- In methane in the presence of a Lewis acid, upon which the II formed the compound of formula (XI) II 25 II h ^ cn in χ, ν% Γ * 4 (xi) 11 in X2VX3 y I in which X is bis (alkylthio) methyl or bis (aryl-IIthio) methyl and the other symbols are as defined in I2 I of claim 1, optionally reacting with an alkyl nitrite after -! I 3 I 35 followed by hydrolysis to form the compound of I 4 I formula (XI) in which X is formyl, upon which this compound is contacted with hydroxylamine followed by dehydration in known manner to form the compound of formula (Ia) in which X is a cyano group; (C) having a compound of formula MSCN, wherein M is an alkali metal, in the presence of bromine in a solvent to form the compound of formula (Ia), in which X is a thiocyanate group upon which this compound is reacted with an alkyl halide or dialkyl -10 sulfate in the presence of a base in a solvent to form a compound of formula (Ia) wherein X is alkylthio; or (d) with a sulfenyl halide of the formula RSHal in which R is an alkyl, haloalkyl, phenyl or heteroaryl group, and Hal is a halogen atom, in an organic liquid reaction medium, optionally in the presence of an acid acceptor, to form a compound of formula (Ia) in which X is alkylthio or halo-alkylthio, whereupon the resulting compound is optionally oxidized in known manner to form a compound of formula (Ia) in which X is RS (0) n, where n is 1 or 2, or (A-II) when X is alkoxy or haloalkoxy, reacting a compound of the formula "" TTCN x1 2-rT'S-x4 (xxviii) 30 x'Afi * 3 Y which they various symbols are as defined in claim 2 and, if necessary, the amino and cyano groups are suitably protected. I (a) with an alkylating agent, optionally in the presence of I in a base, to form compounds of formula I I (Ia) in which X is alkoxy; or II (b) by haloalkylation in known manner to form II compounds of formula (Ia) wherein X is halo-II gene alkoxy, or II (A-III) when X is haloalkyl, reacting a compound II with formula II 10 I (VI> II 15 VII in which the various symbols are as defined in II claim 1 and, if necessary, amino and cyano are suitably protected, II 20 (a) with a fluorinating agent in known manner to form II of. the compound of formula (Ia), in which X is a II difluoromethyl group; II (b) with an oxidizing agent for converting the group II -CHO into a carboxylic acid group, to which the formed II compounds are exposed to a fluorinating agent in the known manner to form the compound of formula II (1a) in which X is trifluoromethyl; II (c) to convert to a compound in which group II -CHO is replaced by a methyl group to which the compound formed II is subjected to a halogenating agent-II part in a solvent to form a compound of formula (Ia) in which X is bromomethyl I or chloromethyl; or II (d) sequentially with a haloalkyl metal derivative or II trifluorotrimethylsilane to convert the group II -CHO to haloalkylcarbinol, upon which the compound, DK 175618 B1 173 wherein X is haloalkylcarbinol, is reacted with a halogenating agent to form compounds of formula (Ia) wherein X is α-haloalkyl-ar-halo-methyl, all of the preceding steps being followed, if necessary, by a deprotection step, or (B) when the compound of formula (I) has formula (Ib) (Ib) Y wherein X, X1, X2, X2, X4 and Y have the same meaning as in claim 1 and when (BI) R3 is halogen, formyl, haloalkyl, alkyl, alkylthio, haloalkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl or haloalkylsulfonyl, a compound of formula (Ia) wherein X, cyano and amino are optionally protected if necessary: (a) according to AI (a) above to form compounds of formula (Ib) in which R 3 is halogen, whereupon 25 for optionally, the bond is reacted according to A-I (a) above to form compounds of formula (Ib) wherein R 3 is trifluoromethyl; (b) according to AI (b) above to first form a compound of formula (Ib) wherein R 3 is a bis (alkylthio) methyl or bis (arylthio) methyl group and then a compound of formula (Ib) ) in which R 3 is formyl; or (c) according to AI (c, d) above to form compounds of formula (Ib) wherein R 3 is alkylthio or haloalkylthio, whereupon optionally oxidized according to AI (d) above to form compounds of formula I Wherein R3 is alkylsulfinyl, alkylsulphonyl, haloalkylsulphinyl or haloalkylsulphonyl, with the proviso that X is not an RS group II capable of undergoing undesired oxidation; and when X is halo optionally treated with an alkyl lithium in a known II manner followed by an aqueous reaction quenching and II sulfenylation according to AI (c, d) above to form II of compounds of formula (Ib) wherein X is II alkylthio or haloalkylthio, or II 10 II (B-II) when R 3 is cyano or alkyl, reacting a compound of formula II x'-Ay-x4 (xxix) II x2-4J-x3 II * II 20 in which R3 is formyl or alkylcarbonyl, the other II symbols are as defined in claim 1, and X, cyano and II amino are protected if necessary: II (a) by condensation with hydroxylamine or O-alkylhydroxylamine or their addition salts in a solvent II to form a compound of formula II (Ib) in which R3 is hydroxyiminoalkylidenyl or II alkoxyiminoalkylidenyl, and converting the group R3 II to cyano to form a compound of formula II (Ib) in which R3 is a cyano group; I (30) when R 3 is formyl, according to A-III (a, b, c or d) above I I to form a compound of formula (Ib), in which R 3 is a methyl or haloalkyl group; II or II (c) when R 3 is formyl, with a Grignard reagent derived from II 35 an alkyl halide or alkyl lithium to form II of a carbinol, followed by a dehydration step I to form a compound in which R 3 is alkenyl, followed by reduction to form compounds of formula (Ib) in which R 3 is alkyl, optionally followed by a deprotection step, or 5 (B-III) when R 3 is alkoxy or haloalkoxy, reacting a compound of formula

A process for the preparation of intermediate II compounds which can be used to prepare compounds of formula (I), characterized in that it II comprises: II 20 (A) a process for the preparation of compounds II of formula (I) XXXIV) II 25 x'-r - x4 (XXXIV) II XJ-tsJ-X3 II y II in which X, X1, X2, X3, X4 and Y are as defined in II of claim 1 and R3 is amino , alkylamino or dialkylamino, II wherein a compound of formula (XXX) II λκ '** (xxx) II 35 II χ2 ^ υΐχ3 II y I DK 175618 B1 181 in which the various symbols are as defined in claim 1, and the amino group is suitably protected, reduced to form compounds of formula (XXXIV) in which R 3 is amino which compounds are reacted: with an alkylating agent in an organic solvent to form a mono- or disubstituted amino group; or by converting the amino group to an alkoxyalkylideneimino group, succeeding t of 10 reduction to form compounds of formula (XXXIV) in which R3 is alkylamino or dialylamino, if necessary followed by a deprotection step, or (B) a process for preparing compounds of formula (XXVIII), (XXXI) ), (XXXII) and (XXXV) according to claim 8 (A-II), (B-III), (E) or (G), wherein the corresponding compound of claim 8 (AI) (a), (Β- Ϊ) (a), (C-1) (b) or (F), after protection of the amino group, if present, is converted into a Grignard reagent or lithium derivative, followed by reaction with a trialkylborate and oxidation on method, if necessary followed by a deprotection step, or (C) a process for preparing a compound of formula

An arthropodic, plant nematode, anthelmintic II or antiprotozoic composition containing a compound of the general formula (I) as defined in any II of claims 1-7 or the compound in which II X 4 = X * = Y = R1 = X = R2 = R3 = C1, and at the same time X3 = X2 = H, together with an II or more compatible diluents or carriers. I I 15 I

Wherein H is amino, cyano and X are optionally protected, according to A-II (a, b or c) above to form a compound of formula (Ib) wherein R 3 is alkoxy or haloalkoxy, or (c) when the compound of formula (I) has formula (Ic): 20 χΙ-Α-χί <IC> X2-25 γ in which X, R3, X1, X2, X3, X4 and Y have the claim 1 is hydrogen, halogen, alkylthio, haloalkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl, haloalkylsulfonyl, alkylamino, dialkylamino, formyl, haloalkyl or alkyl, reacting a compound of formula 35 176 I 4TJS I & φ: ϊ II y II in which the amino group is deprotected, after necessary protection of X, R3 or the cyano group: II {a) with a diazotizing agent in an inert solvent II to form a compound of formula II (Ic) in which R 1 is Η; I (b) with a diazotizing agent in the presence of a halogen donor to form a compound of formula I I (Ic) wherein R 1 is halogen; II (c) with a diazotizing agent in the presence of (SCN) 2 II or a disulfide in a solvent to form II of compounds of formula (Ic) in which X 1 is II 20 alkylthio or haloalkylthio, and then optionally II oxidation according to AI ( d) above to form a II. compound of formula (Ic) in which R 1 is alkyl-1-sulfinyl or alkyl-sulfonyl; I (d) according to claim 9 (A) below to form compounds of formula (Ic) wherein R 1 is alkylamino I 1 or dialkylamino; or II (e) with sodium nitrite and formaldexime, copper sulfate and II HCl in known manner to form compounds of II formula (Ic) in which R 1 is formyl, whereupon (i) II is optionally reacted according to B-II (a) above to form a compound of formula (Ic), in which I R1 is cyano, or (ii) is reacted according to A-III (ad) I above to form a compound of formula I (Ic) in which R 1 is haloalkyl or methyl, if necessary followed by a deprotection step; or in DK 175618 B1 177 (C-II) when R 1 is alkoxy or haloalkoxy, reacting a compound of formula XT "TCN

A composition for use in veterinary medicine II and animal husbandry or in the maintenance of public health, containing as active ingredient at least one compound according to II any one of claims 1-7 or the compound in which II 20 X4 = X1 = Y = R1 = X = R2 = R3 = C1 and at the same time X3 = X2 = H. IN

An insecticide, acaricide or nematodicide composition comprising an effective amount of a compound of II formula (I) according to any one of claims 1-7 or the compound, II wherein X4 = X1 = Y = R1 = X = R2 = R3 = C1 and at the same time X3 = X2 = H. IN

Composition according to claim 12, containing II between 0.05 and 95% by weight of one or more active ingredients, between 1 and 95% by weight of one or more agricultural acceptable carriers and between 0 , 1 and 50% by weight of HI one or more agriculturally acceptable surfactants II. IN

14. Method of use in veterinary medicine HI 35 and animal husbandry or in maintaining public health for II control of harmful arthropods, helminths or protozoa which are parasitic internally or externally in warm-blooded vertebrates, characterized in that the site is applied to an effective amount of a compound of formula (I) according to any one of claims 1-7 or the compound wherein

Method for controlling harmful arthropods and nematodes according to claim 14, characterized in that the compound is applied to the site where the attack of 10 arthropods or nematodes is to be controlled, in an amount from 0.005 to 15 kg of the compound per day. acres of the site occupied.

R3 is H, F, Cl, Br, CF3 or CN, X1 is H or Cl, and Y is CF3 or CF30.

A compound of formula (III), (XXVIII) to I 15 (XXXII), (XXXIV) to (XXXVI), (XXXVIII), (XXXIX) and (XLI), wherein the various substituents have the same meaning as in I the preceding claims, with the exception of compounds wherein I R1 = R2 = H, R3 = amino, X = cyano, X3 = X4 = H and X1 methyl, methoxy I or chloro, and X2 = Y = H, X2 = methyl , methoxy or chlorine, and I X = Y = H, Ysmethyl, methoxy or chlorine, and X3 = X2 = H. '