HK1099649B - Pesticidal 5-substituted-oxyalkylamino-1-arylpyrazole derivatives - Google Patents
Pesticidal 5-substituted-oxyalkylamino-1-arylpyrazole derivatives Download PDFInfo
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Description
Pesticidal compounds
The present invention relates to novel 5-substituted-alkoxyaminopyrazole derivatives, processes for their preparation, compositions thereof and their use for controlling pests (including arthropods and helminths).
The use of 1-arylpyrazole compounds for controlling insects, arachnids and helminths has been described, for example, in patent publications WO87/03781, EP0295117, US 5556873, US 4771066 and WO 02/066423.
However, since modern pesticides have to meet the requirements in all respects, for example with regard to content, duration and range of action, range of use, toxicity, combination with other active substances, combination with formulation auxiliaries or synthetic methods, and because of the possible development of resistance, the development of such substances has never been considered to have to be stopped in this connection, and there has been a great need for new compounds which have superior properties over the known compounds, at least in some of the aspects mentioned.
It is an object of the present invention to provide a novel pesticide which can be used in domesticated companion animals.
It is advantageous to administer pesticides to animals in oral form to prevent possible contamination of humans or the surrounding environment.
It is another object of the present invention to provide a new pesticide which can be used at a lower dosage than existing pesticides.
It is another object of the present invention to provide a novel pesticide which is substantially non-emetic
It is another object of the present invention to provide a novel pesticide which is safe to both the user and the environment.
These objects are achieved in whole or in part by the present invention.
The present invention provides a compound which is a 5-substituted-alkoxyaminopyrazole derivative of the general formula (I):
wherein:
R1is CN, CSNH2Or C (═ N-Z) -S (O)r-Q；
Z is H, (C)1-C6) Alkyl radicals, (C)1-C6) -haloalkyl, (C)3-C6) -alkenyl, (C)3-C6) -alkynyl, - (CH)2)qR7、COR8、CO2-(C1-C6) Alkyl or S (O)pR8；
Q is (C)1-C6) -alkyl or CH2R7；
W is C-halogen, C-CH3Or N;
R2is hydrogen, halogen or CH3；
R3Is (C)1-C3) -haloalkyl, (C)1-C3) Haloalkoxy or SF5；
R4Is hydrogen, (C)2-C6) -alkenyl, (C)2-C6) -haloalkenyl, (C)2-C6) -alkynyl, (C)2-C6) -haloalkynyl, (C)3-C7) -cycloalkyl, (C)3-C7) -cycloalkyl- (C)1-C6) Alkyl, CO2-(C1-C6) Alkyl, CO2-(C3-C6) Alkenyl, CO2-(C3-C6) -alkynyl, CO2-(CH2)mR7Or SO2R8(ii) a Or by one or more substituents selected from halogen, (C)1-C6) -alkoxy, (C)1-C6) -haloalkoxy, (C)3-C6) -alkenyloxy, (C)3-C6) -haloalkenyloxy, (C)3-C6) -alkynyloxy, (C)3-C6) -haloalkynyloxy, (C)3-C7) Cycloalkyl, S (O)pR8、CN、NO2、OH、COR9、NR9R10、S(O)pR7、OR7And CO2R9Substituted or unsubstituted (C)1-C6) -an alkyl group;
a is (C)1-C6) Alkylene or (C)1-C6) -a haloalkylene group;
x is C (═ O), C (═ S), or SO2；
Y is O, NR11Or a covalent bond;
R5is (C)3-C6) -alkenyl, (C)3-C6) -haloalkenyl, (C)3-C6) -alkynyl, (C)3-C6) -haloalkynyl, (C)3-C7) -cycloalkyl, (C)3-C7) -cycloalkyl- (C)1-C6) -alkyl, - (CH)2)qR7Or- (CH)2)qR12(ii) a Or by one or more substituents selected from halogen, (C)1-C6) -alkoxy, (C)1-C6) -haloalkoxy, (C)3-C6) -alkenyloxy, (C)3-C6) -haloalkenyloxy, (C)3-C6) -alkynyloxy, (C)3-C6) -haloalkynyloxy, (C)3-C7) Cycloalkyl, S (O)pR8、CN、NO2、OH、COR9、NR9R10、S(O)pR7、OR7And CO2R9Substituted or unsubstituted (C)1-C6) -an alkyl group;
R6is (C)1-C6) Alkyl radicals, (C)1-C6) -haloalkyl, (C)2-C6) -alkenyl, (C)2-C6) -haloalkenyl, (C)2-C6) -alkynyl, (C)2-C6) -haloalkynyl;
R7is substituted by one or more groups selected from halogen, (C)1-C6) Alkyl radicals, (C)1-C6) -haloalkyl、(C1-C6) -alkoxy, (C)1-C6) Haloalkoxy, CN, NO2、S(O)pR8、COR10、COR13、CONR9R10、SO2NR9R10、NR9R10And OH, optionally substituted phenyl;
R8is (C)1-C6) -alkyl or (C)1-C6) -a haloalkyl group;
R9and R10Each independently is H, (C)1-C6) Alkyl radicals, (C)1-C6) -haloalkyl, (C)3-C6) -alkenyl, (C)3-C6) -haloalkenyl, (C)3-C6) -alkynyl, (C)3-C6) -cycloalkyl or (C)1-C6) -alkyl- (C)3-C6) -a cycloalkyl group; or
R9And R10Together with the N atom, form a five-or six-membered saturated ring optionally containing a further heteroatom selected from O, S and N, unsubstituted or substituted by one or more groups selected from halogen, (C)1-C6) -alkyl and (C)1-C6) -alkyl substitution of haloalkyl;
R11is H, (C)1-C6) Alkyl radicals, (C)1-C6) -haloalkyl, (C)3-C6) -alkenyl or (C)3-C6) -an alkynyl group;
R12is substituted by one or more groups selected from halogen, (C)1-C4) Alkyl radicals, (C)1-C4) -haloalkyl, (C)1-C4) -alkoxy, (C)1-C4) Haloalkoxy, NO2、CN、CO2(C1-C6) Alkyl, S (O)pR8An optionally substituted heterocyclic group with OH and oxygen;
R13is selected from one or moreHalogen, (C)1-C6) Alkyl radicals, (C)1-C6) -haloalkyl, (C)1-C6) -alkoxy, (C)1-C6) Haloalkoxy, CN, NO2、S(O)pR8And NR9R10Phenyl substituted or unsubstituted with the group of (a);
n, p and r are each independently 0, 1 or 2;
m and q are each independently 0 or 1; and each of the above heterocyclic groups is independently a heterocyclic group having 3 to 7 ring atoms and 1, 2 or 3 heteroatoms selected from N, O and S in the ring.
These compounds have valuable pesticidal properties.
The present invention also includes any stereoisomer, enantiomer or geometric isomer and mixtures thereof.
The term "pesticidally acceptable salt" refers to a salt in which the anion or cation is known and acceptable in the art, used to form a salt having pesticidal action. Suitable salts with bases, for example salts formed with compounds of formula (I) containing carboxylic acid groups, include salts of alkali metals (e.g. sodium and potassium), alkaline earth metals (e.g. calcium and magnesium), ammonium and amines (e.g. diethanolamine, triethanolamine, octylamine, morpholine and dioctylmethylamine). Suitable acid addition salts, for example the salts formed by the compounds of formula (I) containing an amino group, include salts of inorganic acids, for example hydrochloric, sulphuric, phosphoric and nitric acid, and salts of organic acids, for example acetic acid.
In the present description, including the appended claims, the above-mentioned substituents have the following meanings:
halogen atom means fluorine, chlorine, bromine or iodine.
The term "halo" before the radical name means that the radical is partially or fully halogenated, i.e. substituted by F, Cl, Br or I in any combination, preferably by F or Cl.
Alkyl groups and a portion thereof (unless otherwise specified) may be straight or branched chain.
Term "(C)1-C6) Alkyl "is understood to mean an unbranched or branched hydrocarbon radical having 1, 2, 3, 4, 5 or 6 carbon atoms, such as, for example, methyl, ethyl, propyl, isopropyl, 1-butyl, 2-methylpropyl or tert-butyl.
Unless otherwise specified, alkyl groups, and in complex groups, preferably have 1 to 4 carbon atoms.
“(C1-C6) Haloalkyl "refers to the term" (C)1-C6) Alkyl radicals mentioned under "in which one or more hydrogen atoms are replaced by the same number of identical or different halogen atoms, such as monohaloalkyl, perhaloalkyl, CF3、CHF2、CH2F、CHFCH3、CF3CH2、CF3CF2、CHF2CF2、CH2FCHCl、CH2Cl、CCl3、CHCl2Or CH2CH2Cl。
Term "(C)1-C6) Alkylene is understood to mean unbranched or branched alkanediyl having from 1 to 6 carbon atoms, according to the IUPAC Nomenclature of Organic Chemistry 1979, such as-CH2-、-CH2CH2-、-CH2CH2CH2-or-CH2CH(CH3)-。
Term "(C)1-C6) Haloalkylene "is understood to mean the term" (C)1-C6) -alkylene "wherein one or more hydrogen atoms are replaced by the same number of identical or different halogen atoms.
“(C1-C6) Alkoxy "means an alkoxy group whose carbon chain conforms to the term" (C)1-C6) -alkyl "as given. For example,"Haloalkoxy" is OCF3、OCHF2、OCH2F、CF3CF2O、OCH2CF3Or OCH2CH2Cl。
“(C2-C6) Alkenyl "refers to an unbranched or branched acyclic carbon chain having a number of carbon atoms falling within the recited ranges, which contains at least one double bond, which may be located anywhere in each unsaturated group. Thus, "(C)2-C6) Alkenyl "denotes, for example, vinyl, allyl, 2-methyl-2-propenyl, 2-butenyl, pentenyl, 2-methylpentene-yl or hexenyl.
“(C2-C6) Alkynyl "refers to an unbranched or branched acyclic carbon chain having a number of carbon atoms falling within the recited ranges, which contains a triple bond, which may be located anywhere within each unsaturated group. Thus, "(C)2-C6) Alkynyl "means, for example, propargyl, 1-methyl-2-propynyl, 2-butynyl or 3-butynyl.
Cycloalkyl groups preferably have 3 to 7 carbon atoms in the ring and are optionally substituted by halogen or alkyl.
In the compounds of formula (I), the following examples of radicals are provided: examples of alkyl substituted by cycloalkyl are cyclopropylmethyl; an example of an alkyl group substituted by an alkoxy group is methoxymethyl (CH)3OCH2-) according to the formula (I); and examples of alkyl substituted by alkylthio are methylmercapto (CH)3SCH2-)。
The "heterocyclyl" group may be a saturated, unsaturated or heterocyclic aromatic hydrocarbon; preferably containing one or more, in particular 1, 2 or 3, heteroatoms in the heterocycle, which are preferably selected from N, O and S; preferred are aliphatic heterocyclic groups having 3 to 7 ring atoms or aromatic heterocyclic groups having 5 to 7 ring atoms. The heterocyclyl group may be, for example, an aromatic heterocyclyl group or a cyclic (heteroaryl) group, such as a monocyclic, bicyclic or polycyclic aromatic system in which at least one ring contains one or more heteroatoms, such as pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinylThienyl, thiazolyl, thiadiazolyl,Azolyl radical, isoOxazolyl, furyl, pyrrolyl, pyrazolyl, imidazolyl or triazolyl, or which are partially or fully hydrogenated, such as epoxy (oxiranyl), oxetanyl, oxolanyl (oxolanyl) (═ tetrahydrofuryl); and (meth) acrylic acid esters,Alkyl, pyrrolidinyl, piperidinyl, piperazinyl, dioxolyl (dioxolanyl),Azolinyl, isoAn azolinyl group,Oxazolidinyl, isoOxazolidinyl and morpholinyl. "heterocyclyl" groups may be unsubstituted or substituted, preferably by one or more groups (preferably 1, 2 or 3 groups) selected from halogen, alkoxy, haloalkoxy, alkylthio, hydroxy, amino, nitro, carboxy, cyano, alkoxycarbonyl, alkylcarbonyl, formyl, carbamoyl, mono-and dialkylaminocarbonyl, substituted amino groups such as amido, mono-and dialkylamino and alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyl, haloalkylsulfonyl, alkyl and haloalkyl, and oxygen. The oxy group may also be at a heterocyclic atom of different oxygenated members, such as N and S.
The term pest refers to arthropods (including insects and arachnids) and helminths (including nematodes).
In the following preferred definitions, it is generally understood that the symbol (symbol) not specifically defined is as previously defined in the specification.
Preferably R1Is CN, CSNH2Or C (═ N-Z) -S (O)r-Q; wherein Z is H, (C)1-C3) -alkyl, - (CH)2)qR7、COR8、CO2-(C1-C3) Alkyl or S (O)pR8Wherein R is7Is substituted by one or more groups selected from halogen, (C)1-C3) Alkyl radicals, (C)1-C3) -haloalkyl, (C)1-C3) Alkoxy, CN and NO2Substituted and unsubstituted phenyl, each R8Is (C)1-C3) -alkyl or (C)1-C3) -a haloalkyl group; q is (C)1-C3) -alkyl, and r is 0.
More preferably R1Is CN or CSNH2。
Preferably, W is C-Cl or N (more preferably W is C-Cl).
Preferably R2Is Cl.
Preferably R3Is CF3Or OCF3(more preferably R)3Is CF3)。
Preferably R4Is hydrogen, (C)2-C4) -alkenyl, (C)2-C4) -haloalkenyl, (C)2-C4) -alkynyl, (C)2-C4) -haloalkynyl, (C)3-C7) -cycloalkyl, CO2-(C1-C4) Alkyl, CO2-(C3-C4) Alkenyl, CO2-(C3-C4) -alkynyl, CO2-(CH2)mR7Or SO2R8(ii) a Or by one or more substituents selected from halogen, (C)1-C3) -alkoxy, (C)1-C4) -haloalkoxy, (C)3-C7) Cycloalkyl and S (O)pR8Substituted or unsubstituted (C)1-C4) -an alkyl group; wherein R is7Is substituted by one or more groups selected from halogen, (C)1-C3) Alkyl radicals, (C)1-C3) -haloalkyl, (C)1-C3) -alkoxy, (C)1-C3) Haloalkoxy, CN, NO2And S (O)pR8Phenyl substituted or unsubstituted with the group of (a); each R8Is (C)1-C3) -alkyl or (C)1-C3) -haloalkyl. More preferably R4Is CO2-(C1-C3) -alkyl or SO2R8(ii) a Or by one or more substituents selected from halogen, (C)1-C3) Alkoxy, S (O)pR8And CO2-(C1-C3) Alkyl substituted or unsubstituted (C)1-C3) -alkyl, R8Is (C)1-C3) -alkyl or (C)1-C3) -haloalkyl. Most preferred is R4Is (C)1-C3) -an alkyl group.
Preferably A is (C)1-C4) -an alkylene group.
More preferably, A is-CH2CH2-or-CH2CH2CH2-。
Preferably R5Is (C)3-C4) -alkenyl, (C)3-C4) -alkynyl, (C)3-C7) -cycloalkyl or- (CH)2)qR7(ii) a Or by one or more substituents selected from halogen, (C)1-C4) -alkoxy, (C)1-C4) -haloalkoxy, (C)3-C4) -alkenyloxy, (C)3-C4) -haloalkenyloxy, (C)3-C4) -alkynyloxy, (C)3-C4) -haloalkynyloxy, (C)3-C7) Cycloalkyl, S (O)pR8、CN、NO2、OH、COR9And CO2R9Substituted or unsubstituted (C)1-C4) -alkyl, wherein R7Is substituted by one or more groups selected from halogen, (C)1-C3) Alkyl radicals, (C)1-C3) -haloalkyl, (C)1-C3) -alkoxy, (C)1-C3) Haloalkoxy, CN, NO2And S (O)pR8Phenyl substituted or unsubstituted with the group of (a); each R8Is (C)1-C3) -alkyl or (C)1-C3) -a haloalkyl group; r9Is H or (C)1-C3) -an alkyl group.
More preferably R5Is (C)3-C4) -alkenyl, (C)3-C4) -alkynyl, - (CH)2)qR7、(C1-C3) -alkyl or (C)1-C3) -haloalkyl, wherein R7Is substituted by one or more groups selected from halogen, (C)1-C3) Alkyl radicals, (C)1-C3) -haloalkyl, (C)1-C3) -alkoxy, (C)1-C3) Haloalkoxy, CN, NO2And S (O)pR8Phenyl substituted or unsubstituted with the group of (a); each R8Is (C)1-C3) -alkyl or (C)1-C3) -haloalkyl.
Preferably R6Is (C)1-C3) Haloalkyl (more preferably R)6Is CF3)。
A preferred class of compounds of formula (I) for use in the present invention are those which meet the following characteristics:
R1is CN, CSNH2Or C (═ N-Z) -S-Q (more preferably R)1Is CN or CSNH2)；
Z is H, (C)1-C3) -alkyl, - (CH)2)qR7、COR8、CO2-(C1-C3) Alkyl or S (O)pR8；
Q is (C)1-C3) -an alkyl group;
w is C-Cl or N;
R2is Cl;
R3is CF3Or OCF3(more preferably R)3Is CF3)；
R4Is hydrogen, (C)2-C4) -alkenyl, (C)2-C4) -haloalkenyl, (C)2-C4) -alkynyl, (C)2-C4) -haloalkynyl, (C)3-C7) -cycloalkyl, CO2-(C1-C4) Alkyl, CO2-(C3-C4) Alkenyl, CO2-(C3-C4) -alkynyl, CO2-(CH2)mR7Or SO2R8(ii) a Or by one or more substituents selected from halogen, (C)1-C3) -alkoxy, (C)1-C3) -haloalkoxy, (C)3-C7) Cycloalkyl and S (O)pR8Substituted or unsubstituted (C)1-C4) -alkyl (more preferably R)4Is CO2-(C1-C3) -alkyl or SO2R8(ii) a Or by one or more substituents selected from halogen, (C)1-C3) Alkoxy, S (O)pR8And CO2-(C1-C3) Alkyl substituted or unsubstituted (C)1-C3) -an alkyl group);
a is (C)1-C4) Alkylene (more preferably A is-CH)2CH2-or-CH2CH2CH2-)；
X is C (═ O), C (═ S), or SO2；
Y is O, NH or a covalent bond;
R5is (C)3-C4) -alkenyl, (C)3-C4) -alkynyl, (C)3-C7) -cycloalkyl or- (CH)2)qR7(ii) a Or by one or more substituents selected from halogen, (C)1-C4) -alkoxy, (C)1-C4)-Haloalkoxy, (C)3-C4) -alkenyloxy, (C)3-C4) -haloalkenyloxy, (C)3-C4) -alkynyloxy, (C)3-C4) -haloalkynyloxy, (C)3-C7) Cycloalkyl, S (O)pR8、CN、NO2、OH、COR9And CO2R9Substituted or unsubstituted (C)1-C4) -alkyl (more preferably R)5Is (C)3-C4) -alkenyl, (C)3-C4) -alkynyl, - (CH)2)qR7、(C1-C3) -alkoxy, (C)1-C3) -alkyl or (C)1-C3) -haloalkyl);
R6is (C)1-C3) Haloalkyl (more preferably R)6Is CF3)；
Each R7Independently by one or more groups selected from halogen, (C)1-C3) Alkyl radicals, (C)1-C3) -haloalkyl, (C)1-C3) -alkoxy, (C)1-C3) Haloalkoxy, CN, NO2And S (O)pR8Phenyl substituted or unsubstituted with the group of (a); each R8Independently is (C)1-C3) -alkyl or (C)1-C3) -a haloalkyl group; r9Is H or (C)1-C3) -an alkyl group.
A more preferred class of compounds of formula (I) are those which meet the following characteristics:
R1is CN, CSNH2Or C (═ N-Z) -S-Q;
z is H, (C)1-C3) -alkyl, - (CH)2)qR7、COR8、CO2-(C1-C3) Alkyl or S (O)pR8；
Q is (C)1-C3) -an alkyl group;
w is C-Cl;
R2is Cl;
R3is CF3；
R4Is hydrogen, (C)2-C4) -alkenyl, (C)2-C4) -alkynyl, (C)3-C7) -cycloalkyl, CO2-(C1-C4) Alkyl, CO2-(C3-C4) Alkenyl, CO2-(C3-C4) -alkynyl, CO2-(CH2)mR7Or SO2R8(ii) a Or by one or more substituents selected from halogen, (C)1-C3) Alkoxy, S (O)pR8And CO2-(C1-C3) Alkyl substituted or unsubstituted (C)1-C3) -an alkyl group;
a is-CH2CH2-or-CH2CH2CH2-；
X is C (═ O) or SO2；
Y is O, NH or a covalent bond;
R5is (C)3-C4) -alkenyl, (C)3-C4) -alkynyl, - (CH)2)qR7、(C1-C3) -alkyl or (C)1-C3) -a haloalkyl group;
R6is CF3；
Each R7Independently by one or more groups selected from halogen, (C)1-C3) Alkyl radicals, (C)1-C3) -haloalkyl, (C)1-C3) -alkoxy, (C)1-C3) Haloalkoxy, CN, NO2And S (O)pR8Phenyl substituted or unsubstituted with the group of (a); each R8Independently is (C)1-C3) -alkyl or (C)1-C3) -haloalkyl.
A more preferred class of compounds of formula (I) are those which meet the following characteristics:
R1is CN or CSNH2；
W is C-Cl;
R2is Cl;
R3is CF3；
R4Is (C)1-C3) -an alkyl group;
a is-CH2CH2-or-CH2CH2CH2-；
X is C (═ O);
y is O, NH or a covalent bond;
R5is (C)3-C4) -alkenyl, (C)3-C4) -alkynyl, - (CH)2)qR7、(C1-C3) -alkyl or (C)1-C3) -a haloalkyl group;
R6is CF3；
R7Is substituted by one or more groups selected from halogen, (C)1-C3) Alkyl radicals, (C)1-C3) -haloalkyl, (C)1-C3) -alkoxy, (C)1-C3) Haloalkoxy, CN, NO2And S (O)pR8Phenyl substituted or unsubstituted with the group of (a);
R8is (C)1-C3) -alkyl or (C)1-C3) -haloalkyl.
A more preferred class of compounds of formula (I) are those which meet the following characteristics:
R1is CN;
w is C-Cl;
R2is Cl;
R3is CF3；
R4Is methyl;
a is-CH2CH2-；
X is C (═ O) or SO2；
Y is O, NH or a covalent bond;
R5is (C)3-C4) -alkenyl, (C)3-C6) -cycloalkyl or- (CH)2)qR7(ii) a Or by one or more substituents selected from halogen and (C)1-C6) (C) substituted or unsubstituted with an alkoxy radical1-C3) -an alkyl group;
R6is CF3；
R7Is substituted by one or more groups selected from halogen, (C)1-C3) Alkyl radicals, (C)1-C3) -haloalkyl, (C)1-C3) -alkoxy, (C)1-C3) Haloalkoxy and NO2Substituted or unsubstituted phenyl.
The compounds of the general formula (I) can be prepared by applying or modifying known methods, i.e. methods used hitherto or described in the chemical literature.
In the following description of the process, when the symbols appearing in the general formulae are not specifically defined, they are to be understood as being "as defined above" in accordance with the first definition of the respective symbol in the description.
According to one aspect of the invention, the compounds of formula (I) can be prepared by acylation or sulfonylation of a compound of formula (II) with a compound of formula (III), wherein R in formula (I)2、R3、R4、R5、R6W, A and n are as defined above, R1Is CN, Y and X are as defined above, but
With the exception of compounds in which-Y-X is-NH-CO-or-NH-CS-; the general formula (II) is:
wherein R is2、R3、R4、R6W, A and n are as defined above; the general formula (III) is:
R5-Y-X-L (III)
wherein Y and X are as defined above, with the exception of compounds wherein-Y-X is-NH-CO-or-NH-CS-, and L is a leaving group. For acylation reactions where X is CO or CS and Y is O or a covalent bond, formula (III) is preferably an acid halide and L is preferably chlorine or bromine (more preferably chlorine). The base is optionally present in a reaction which is generally carried out in an inert solvent, for example tetrahydrofuran, bis (tetrahydrofuran), at a temperature of from 0 ℃ to 150 ℃, preferably from 20 ℃ to 100 ℃Alkane, acetonitrile, toluene, diethyl ether, dichloromethane, dimethyl sulfoxide or N, N-dimethylformamidinium. The base is typically an alkali metal hydroxide such as potassium hydroxide, an alkali metal hydride such as sodium hydride, an alkali metal carbonate such as potassium carbonate or sodium carbonate, an alkali metal alkoxide such as sodium methoxide, an alkaline earth metal carbonate such as calcium carbonate, or an organic base such as a tertiary amine, e.g. triethylamine or ethyldiisopropylamine, or pyridine, or 1, 8-diazabicyclo [5.4.0 ]]Undec-7-ene (DBU).
For X is SO2The sulfonylation reaction in (2) is preferably carried out using a sulfonyl halide in the general formula (III), and L is preferably chlorine or bromine (more preferably chlorine). A base is optionally present in the reaction, which generally employs a base, solvent and temperature similar to the acylation reaction.
According to another aspect of the invention, the compound of formula (I) may be prepared by reacting a compound of formula (II) with an isocyanate or isothiocyanate compound of formula (IV) or (V), wherein R in formula (I)1Is CN, -Y-X is-NH-CO-or-NH-CS-, R2、R3、R4、R5、R6W, A and n are as defined above; r in the general formula (II)1、R2、R3、R6W, A and n are as defined above; formula (IV) and formula (V) are each:
R5-N＝C＝O (IV) R5-N＝C＝S (V)
wherein R is5As defined above. The reaction is optionally carried out in the presence of a base, for example an alkali metal hydride such as sodium hydride, in an inert solvent, for example acetonitrile or tetrahydrofuran, at a temperature of from 0 ℃ to 100 ℃.
According to another aspect of the present invention, wherein R1Is CN, n is 1 or 2, R2、R3、R4、R5、R6Compounds of formula (I) wherein, W, A, X and Y are as defined above may be prepared by oxidation of the corresponding compound wherein n is 0 or 1. The oxidation reaction is generally carried out using a peracid such as 3-chloroperbenzoic acid in a solvent such as dichloromethane or 1, 2-dichloroethane at a temperature of from 0 ℃ to the reflux temperature of the solvent.
According to one aspect of the present invention, wherein R1Is CSNH2，R2、R3、R4、R5、R6The compounds of formula (I) wherein R, W, A, X, Y and n are as defined above may be prepared by reacting the corresponding compounds of formula (I) wherein R is1Is CN, in an inert solvent at a temperature of-35 ℃ to 50 ℃, preferably 0 ℃ to 30 ℃, wherein the alkali metal or alkaline earth metal hydrosulfide is exemplified by lithium, potassium, calcium or preferably sodium hydrosulfide, and the inert solvent is exemplified by N, N-dimethylAcyl ammonium, pyridine, diAlkane, tetrahydrofuran, sulfolane, dimethyl sulfoxide, methanol or ethanol. Optionally, with H2S is treated in situ in the presence of an organic base, such as a metal alkoxide or trialkylamine, or an inorganic base, such as an alkali or alkaline earth metal hydroxide or carbonate, such as sodium carbonate, potassium carbonate or ammonium carbonate, to produce the hydrosulfide. The reaction can be accelerated effectively by using a metal complex reagent such as crown ether. The reaction of the hydrosulfide salt with the compound of formula (II) can also be carried out in a two-phase system of water/organic solvent using a phase transfer catalyst, examples of which are crown ethers or tetraalkylammonium salts, such as tetra-n-butylammonium bromide or benzyltrimethylammonium chloride. Organic solvents suitable for use with water in a two-phase system include benzene, toluene, methylene chloride, 1-chlorobutane and methyl tert-butyl ether.
Or, wherein R1Is CSNH2The compounds of the formula (I) can also be prepared by reaction of2PS2Treating in which R1Compounds of general formula (I) which is CN, as described in tet.lett., 24(20), 2059 (1983).
According to another aspect of the present invention, wherein R1Is CSNH2，R2、R3、R4、R5、R6The compounds of formula (I) wherein R, W, A, X, Y and n are as defined above may be prepared by reacting the corresponding compounds of formula (I) wherein R is1Is CN, is reacted with a bis (trialkylsilyl) sulfide, preferably bis (trimethylsilyl) sulfide, in the presence of a base, typically an alkali metal alkoxide such as sodium methoxide, in a solvent, for example N, N-dimethylformamide, at a temperature of 0 ℃ to 60 ℃. This method is generally described by Lin, Ku and Shiao in Synthesis 1219 (1992).
According to another aspect of the present invention, wherein R1Is C (═ N-H) -S-Q, Q, R2、R3、R4、R5、R6Compounds of formula (I) wherein R, W, A, X, Y and n are as defined above may be prepared by reacting the corresponding compounds of formula (I) wherein R is1Is CSNH2With an alkylating agent of the general formula (VI) or (VII), wherein the general formula (VI) and the general formula (VII) are respectively:
Q-L1 (VI) Q3O+BF4 - (VII)
wherein Q is as defined above, L1Is a leaving group, typically halogen, preferably chlorine, bromine or iodine. The reaction is generally carried out in an inert solvent such as tetrahydrofuran at a temperature of from 0 ℃ to 60 ℃ in the presence of a base, such as an alkali metal hydride such as sodium hydride or an alkali metal alkoxide such as potassium tert-butoxide. Alternatively, it is possible to use an alkali metal carbonate such as potassium carbonate, or an organic base such as trialkylamine, for example triethylamine or N, N-diisopropylethylamine, in an inert solvent such as acetone at a temperature of from 0 ℃ to the reflux temperature of the solvent. When a compound of formula (VII) such as trimethyloxytetrafluoroborate is used as the alkylating agent, the base is preferably an alkali metal bicarbonate such as sodium bicarbonate, in a solvent such as dichloromethane at a temperature of from 0 ℃ to the reflux temperature of the solvent.
According to another aspect of the present invention, wherein R1Compounds of formula (I) wherein Z is H, other values are as defined in formula (I) may be prepared by alkylation, acylation or sulphonylation of a corresponding compound of formula (I) wherein Z is H, with a compound of formula (VIII) wherein formula (VIII) is:
Z-L2 (VIII)
wherein Z is as defined above (except for H), L2Is a leaving group. For the alkylation reaction, Z is (C)1-C6) Alkyl radicals, (C)1-C6) -haloalkyl, (C)3-C6) -alkenyl, (C)3-C6) -alkynyl or- (CH)2)qR7，L2Preferably halogen, alkylsulfonyloxy or arylsulfonyloxy (more preferably chlorine, bromine, iodine, methylsulfonyloxy or p-toluenesulfonyloxy). The base is optionally present in a reaction which is generally carried out in an inert solvent, for example tetrahydrofuran, bis (tetrahydrofuran), at a temperature of from-30 ℃ to 200 ℃, preferably from 20 ℃ to 100 ℃Alkane, acetonitrile, toluene, diethyl ether, dichloromethane, dimethyl sulfoxide or N, N-dimethylformamidinium. The base is typically an alkali metal hydroxide such as potassium hydroxide, an alkali metal hydride such as sodium hydride, an alkali metal carbonate such as potassium carbonate or sodium carbonate, an alkali metal alkoxide such as sodium methoxide, an alkaline earth metal carbonate such as calcium carbonate, or an organic base such as a tertiary amine, e.g. triethylamine or ethyldiisopropylamine, or pyridine, or 1, 8-diazabicyclo [5.4.0 ]]Undec-7-ene (DBU). For Z is COR8Or CO2-(C1-C6) Acylation with alkyl, the formula (VIII) is preferably an acid chloride halide, L2Preferably chlorine or bromine (more preferably chlorine). The base is optionally present in a reaction which is generally carried out under base, solvent and temperature conditions similar to those of the alkylation reaction. For Z being S (O)pR8The sulfonylation reaction is preferably carried out in the presence of a compound of the formula (VIII) which is a sulfonyl halide, L2Preferably chlorine or bromine (more preferably chlorine). A base is optionally present in the reaction, which is generally carried out under base, solvent and temperature conditions similar to those of the alkylation reaction.
The intermediate compounds of the formula (II) can be prepared simply by reacting compounds of the formula (IX) in which A is-CH with ethylene oxide2CH2-，R2、R3、R4、R6W and n are as defined above; formula (IX) is:
the reaction is generally carried out in an inert solvent in the presence of a catalyst, which may be a base or an acid, at a temperature of from 0 ℃ to reflux temperature.
Wherein A is-CH2CH2-，R2、R3、R6W and n are as defined above, R4The intermediate compounds of the formula (II) as defined above (with the exception of H) may consist of the corresponding compounds in which R is4The compounds of formula (II) which are H are prepared by alkylation, acylation or sulfonylation according to known conditions. In some cases, it is desirable to use suitable protecting groups to avoid reaction at the hydroxyl group, followed by introduction of the appropriate R4After the partial removal of the protecting group. Suitable protection methods are well known in the art.
The intermediate compound of formula (II) can be prepared by reacting a compound of formula (X) with a compound of formula (XI) wherein n in formula (II) is 2 and R is2、R3、R4、R6W and A are as defined above; the general formula (X) is:
wherein R is2、R3、R4、R6W and A are as defined above, n is 2, L3Is a leaving group, typically halogen, preferably bromine; formula (XI) is:
HO-A-NHR4 (XI)
wherein R is4As defined above. The reaction is carried out in the presence of a base in an inert solvent at a temperature of from 0 ℃ to 100 ℃, examples of inert solvents being tetrahydrofuran, bisAlkane, acetonitrile, toluene, diethyl ether, dichloromethane, dimethyl sulfoxide or N, N-dimethylformamidinium. The base is typically an alkali metal hydride such as sodium hydride, an alkali metal carbonate such as potassium carbonate or sodium carbonate, an alkali metal alkoxide such as sodium methoxide, an alkaline earth metal carbonate such as calcium carbonate.
Wherein R is2、R3、R4、R6Intermediates of formula (II) wherein W, A and n are as defined above can additionally be prepared by other known methods.
The collection (collection) of compounds of formula (I) which can be synthesized by the above-described method can also be prepared in a parallel (parallel) manner, which can be carried out manually or in a semi-automated or fully automated manner. In this case, for example, the reaction process, work-up or purification of the product or intermediate can be automated. In general, it is understood to mean, for example, the annual newspaper of combined chemistry and molecular diversity in s.h. dewitt: automated Synthesis (Automated Synthesis), Vol.1, Verlag Escom 1997.
A series of commercial equipment is available from Stem Corporation, Woodorlffe Road, Tollesbury, Essex, CM 98 SE, British or H + P Labortechnik GmbH, Bruckmann ring28, 85764 Oberschlei β heim, Germany or Radleys, Shirehill, Saffron Walden, Essex, British for carrying out parallel reaction processes and work-up processes. For parallel purification of the compounds of formula (I) or intermediates obtained in the preparation, chromatography and the like equipment may be used, such as those provided by ISCO, Inc., 4700Superior Street, Lincoln, NE 68504, USA.
The apparatus mentioned is used to carry out modular reaction processes in which the individual process steps are automated, but manual operations must be carried out between the individual process steps. This can be avoided by using a semi-integrated or fully integrated automation system, wherein the automation module in question can be operated by, for example, a robot. Such automated systems are commercially available from Zymark Corporation, Zymark Center, Hopkinton, MA 01748, USA.
In addition to the methods already described herein, the compounds of the general formula (I) can be prepared partially or completely by the solid-phase-supported method. For this purpose, the synthesis suitable for the process in question or each or all of the intermediate steps in a synthesis are combined in one synthetic resin. Solid phase support synthesis methods are described in large numbers in The technical literature, for example, Barry A. Bunin, in "The Combinatorial Index", Academic Press, 1998.
The use of solid phase support synthesis methods enables a series of protocols known in the literature to be implemented, either manually or in an automated manner. For example, the "tea bag (tea-bag) method" (Houghten, US 4,631, 211; Houghten et al, Proc. Natl. Acad. Sci, 1985, 82, 5131-. The automation of parallel synthesis of solid supports is successfully carried out, for example, by means of apparatus (Argonaut Technologies, Inc., 887 Industrial road, San Carlos, CA 94070, USA or MultiSynTech GmbH, Wullener Feld4, 58454 Witten, Germany).
The preparation of the methods described herein results in compounds of formula (I) that exist in the manner of collections of materials called libraries. The invention also relates to a library comprising at least two compounds of formula (I).
The compounds of the formulae (III), (IV), (V), (VI), (VII), (VIII), (IX), (X) and (XI) are known or can be prepared by known methods.
The following non-limiting examples illustrate the preparation of compounds of formula (I)
Chemical examples
Unless otherwise stated, NMR spectroscopic measurements were performed in deuterated chloroform.
In the examples below, the values (and percentages) are by weight unless otherwise indicated. The proportion of solvent is by volume.
Example 1
1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-5- { N-methyl-N- [2- (4-toluenesulfonyloxy) ethyl ] amino } -4-trifluoromethylsulfonylpyrazole
A solution of 1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-5- [ N- (2-hydroxyethyl) -N-methylamino ] -4-trifluoromethylsulfonyl pyrazole (0.100 g, 0.2 mmol) and sodium hydride (0.016 g, 0.4 mmol) in dry tetrahydrofuran was stirred vigorously under a nitrogen atmosphere at 20 ℃ for 1 hour. 4-Toluenesulfonylchloride (0.056 g, 0.3 mmol) was then added and stirring was continued at 20 ℃ for 1 hour. Then the mixture was added to a saturated ammonium chloride solution and ethyl acetate; the organic layer was washed with water and brine, dried (sodium sulfate), and evaporated. The residue was purified by flash column chromatography eluting with heptane/ethyl acetate (4: 1) to give the title compound (0.074 g, compound 93, 55% yield) as a white fine powder, 19F-NMR: -64.2, -79.2.
Example 2
1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-5- { N-methyl-N- [2- (4-trifluoromethyl-benzyloxy) ethyl ] amino } -4-trifluoromethylsulfonylpyrazole
Sodium hydride (0.012 g, 0.3 mmol) was added to a solution of 1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-5- [ N- (2-hydroxyethyl) -N-methylamino ] -4-trifluoromethylsulfonyl pyrazole (0.100 g, 0.2 mmol) in dry tetrahydrofuran, and the mixture was stirred vigorously under a nitrogen atmosphere at 20 ℃ for 1 hour. 4-Trifluoromethylbenzoyl chloride (0.053 g, 0.3 mmol) was then added and the resulting mixture was stirred for an additional 2 hours at 20 ℃. The mixture was then poured into saturated ammonium chloride solution and ethyl acetate, and the organic layer was washed with water and brine, dried (sodium sulfate), and evaporated. The residue was purified by flash column chromatography eluting with heptane/ethyl acetate (4: 1) to give the title compound as an off-white oil (0.085 g, compound 54, 61% yield), 19F-NMR: -63.7, -63.8, -78.6.
Example 3
1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-5- { N-methyl-N- [2- (4-ethoxyphenylaminocarbonyloxy) ethyl ] amino } -4-trifluoromethylsulfonylpyrazole
Sodium hydride (0.012 g, 0.3 mmol) was added to a solution of 1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-5- [ N- (2-hydroxyethyl) -N-methylamino ] -4-trifluoromethylsulfonyl pyrazole (0.100 g, 0.2 mmol) in dry tetrahydrofuran, and the mixture was stirred vigorously under a nitrogen atmosphere at 20 ℃ for 1 hour. 4-ethoxyphenyl isocyanate (0.041 g, 0.3 mmol) was then added and the resulting mixture was stirred for an additional 2 hours at 20 ℃. The mixture was then poured into saturated ammonium chloride solution and ethyl acetate, and the organic layer was washed with water and brine, dried (sodium sulfate), and evaporated. The residue was purified by flash column chromatography eluting with heptane/ethyl acetate (4: 1 to 2: 1) to give the title compound (0.041 g, compound 69, 30% yield) as a white powder,
19F-NMR：-63.7、-78.5。
example 4
1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-5- { N-methyl-N- [2- (4-ethoxycarbonyloxy) ethyl ] amino } -4-trifluoromethylsulfonylpyrazole
Sodium hydride (0.012 g, 0.3 mmol) was added to a solution of 1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-5- [ N- (2-hydroxyethyl) -N-methylamino ] -4-trifluoromethylsulfonyl pyrazole (0.100 g, 0.2 mmol) in dry tetrahydrofuran, and the mixture was vigorously stirred at 20 ℃ for 2 hours under a nitrogen atmosphere. Ethyl chloroformate (0.029 g, 0.3 mmol) was then added and the resulting mixture was stirred at 20 ℃ for an additional 1 hour. The mixture was then added to a saturated solution of ammonium chloride and ethyl acetate, and the organic layer was washed with water and brine, dried (sodium sulfate), and evaporated. The residue was purified by flash column chromatography eluting with heptane/ethyl acetate (4: 1) to give the title compound (0.098 g, compound 6, 81% yield) as a white powder, 19F-NMR: 63.8 and 78.6.
The following intermediate examples illustrate the preparation of the intermediates used in the synthesis of the above examples.
Intermediate example 1
Potassium carbonate (7.29 g, 52.2 mmol) in fine powder form was added to a solution of 5-bromo-1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylsulfonyl pyrazole (10.00 g, 19.3 mmol) in dry N, N-dimethylformamide (85 ml) and stirred at 20 ℃ for 1 hour. 2- (methylamino) ethanol (3.11 ml, 38.7 mmol) was then added and stirring continued for 2 hours at 20 ℃. The resulting mixture was poured into saturated ammonium chloride solution, extracted with ethyl acetate, the organic layer washed with water and brine, dried (sodium sulfate), evaporated and purified by chromatography column eluting with hexane and ethyl acetate (2: 1) to give 1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-5- [ N- (2-hydroxyethyl) -N-methylamino ] -4-trifluoromethylsulfonyl pyrazole (5.65 g, 57% yield) as a white powder, 19F-NMR: 63.7 and 78.4.
Intermediate example 2
Tert-butyl nitrite (84 ml, 0.662 mmol) was added to a suspension of 5-amino-1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylsulfonylpyrazole (100 g, 0.221 mol) in bromoform (320 ml). The resulting mixture was heated to 60-70 ℃ over 3 hours. Another batch of tert-butyl nitrite (84 ml, 0.662 mol) was added and the mixture was stirred at 60-70 ℃ for an additional 2.5 hours. Then cooled, washed with hexane, hexane-toluene, and then filtered. The solid was washed with pentane and dried in vacuo to give 5-bromo-1- (2, 6-dichloro-4-trifluoromethylphenyl) -3-cyano-4-trifluoromethylsulfonylpyrazole (96.69 g, 79% yield) as a yellow solid with a melting point of 142 ℃.
The following preferred compounds listed in Table 1 also form part of the present invention and these compounds are or can be prepared according to the methods described above in examples 1-4 or the general methods described above, or analogously thereto.
In the tables, Me represents a methyl group, Et represents an ethyl group, Pr represents an n-propyl group, i-Pr represents an isopropyl group, cPr represents a cyclopropyl group, OMe represents a methoxy group, OEt represents an ethoxy group, Ph represents a phenyl group, CH2(2-FPh) represents a 2-fluorobenzyl group.
The 19F-NMR spectral shift values are given in ppm.
Compound numbers are given for reference purposes only.
Table 1: compounds of general formula (I) wherein the substituents have the following meanings:
R1＝CN，R4is Me, R6Is CF3A is-CH2CH2-，W＝C-Cl，R2＝Cl，R3＝CF3。
| Compound number | X | Y | R5 | n | Melting Point C | 19F-NMR |
| 1 | CO | O | Me | 0 | ||
| 2 | CO | O | Me | 1 | ||
| 3 | CO | O | Me | 2 |
| 4 | CO | O | Et | 0 | ||
| 5 | CO | O | Et | 1 | ||
| 6 | CO | O | Et | 2 | -63.8，-78.6 | |
| 7 | CO | O | Pr | 0 | ||
| 8 | CO | O | Pr | 1 | ||
| 9 | CO | O | Pr | 2 | ||
| 10 | CO | O | iPr | 0 | ||
| 11 | CO | O | iPr | 1 | ||
| 12 | CO | O | iPr | 2 | -63.7，-78.5 | |
| 13 | CO | O | CH2CH＝CH2 | 0 | ||
| 14 | CO | O | CH2CH＝CH2 | 1 | ||
| 15 | CO | O | CH2CH＝CH2 | 2 | ||
| 16 | CO | O | cPr | 0 | ||
| 17 | CO | O | cPr | 1 | ||
| 18 | CO | O | cPr | 2 | ||
| 19 | CO | O | Ph | 0 | ||
| 20 | CO | O | Ph | 1 | ||
| 21 | CO | O | Ph | 2 | ||
| 22 | CO | O | 4-CF3Ph | 0 | ||
| 23 | CO | O | 4-CF3Ph | 1 | ||
| 24 | CO | O | 4-CF3Ph | 2 | ||
| 25 | CO | O | 4-MePh | 0 | ||
| 26 | CO | O | 4-MePh | 1 | ||
| 27 | CO | O | 4-MePh | 2 | ||
| 28 | CO | O | 4-NO2Ph | 0 | ||
| 29 | CO | O | 4-NO2Ph | 1 | ||
| 30 | CO | O | 4-NO2Ph | 2 |
| Compound number | X | Y | R5 | n | Melting Point C | 19F-NMR |
| 31 | CO | O | 4-OMePh | 0 | ||
| 32 | CO | O | 4-OMePh | 1 | ||
| 33 | CO | O | 4-OMePh | 2 | ||
| 34 | CO | O | 4-OEtPh | 0 | ||
| 35 | CO | O | 4-OEtPh | 1 | ||
| 36 | CO | O | 4-OEtPh | 2 | ||
| 37 | CO | Covalent bond | Me | 0 | ||
| 38 | CO | Covalent bond | Me | 1 | ||
| 39 | CO | Covalent bond | Me | 2 | -63.8，-78.6 | |
| 40 | CO | Covalent bond | Et | 0 | ||
| 41 | CO | Covalent bond | Et | 1 | ||
| 42 | CO | Covalent bond | Et | 2 | ||
| 43 | CO | Covalent bond | Et | 0 | ||
| 44 | CO | Covalent bond | Et | 1 | ||
| 45 | CO | Covalent bond | Et | 2 | ||
| 46 | CO | Covalent bond | Pr | 0 | ||
| 47 | CO | Covalent bond | Pr | 1 | ||
| 48 | CO | Covalent bond | Pr | 2 | ||
| 49 | CO | Covalent bond | CH2OMe | 0 | ||
| 50 | CO | Covalent bond | CH2OMe | 1 | ||
| 51 | CO | Covalent bond | CH2OMe | 2 | -64.2，-79.1 | |
| 52 | CO | Covalent bond | 4-CF3Ph | 0 | ||
| 53 | CO | Covalent bond | 4-CF3Ph | 1 | ||
| 54 | CO | Covalent bond | 4-CF3Ph | 2 | -63.7，-36.8，-78.6 | |
| 55 | CO | Covalent bond | 2，6-F2Ph | 0 | ||
| 56 | CO | Covalent bond | 2，6-F2Ph | 1 | ||
| 57 | CO | Covalent bond | 2，6-F2Ph | 2 | -63.7，-78.7，-110.2 | |
| 58 | CO | Covalent bond | Ph | 0 | ||
| 59 | CO | Covalent bond | Ph | 1 |
| Compound number | X | Y | R5 | n | Melting Point C | 19F-NMR |
| 60 | CO | Covalent bond | Ph | 2 | ||
| 61 | CO | Covalent bond | 2-FPh | 0 | ||
| 62 | CO | Covalent bond | 2-FPh | 1 | ||
| 63 | CO | Covalent bond | 2-FPh | 2 | -63.8，-78.7 | |
| 64 | CO | NH | 4-MeOPh | 0 | ||
| 65 | CO | NH | 4-MeOPh | 1 | ||
| 66 | CO | NH | 4-MeOPh | 2 | ||
| 67 | CO | NH | 4-EtOPh | 0 | ||
| 68 | CO | NH | 4-EtOPh | 1 | ||
| 69 | CO | NH | 4-EtOPh | 2 | -63.7，-78.5 | |
| 70 | CO | NH | 4-CF3OPh | 0 | ||
| 71 | CO | NH | 4-CF3OPh | 1 | ||
| 72 | CO | NH | 4-CF3OPh | 2 | -58.7，-63.7，-78.5，-78.9 | |
| 73 | CO | NH | 4-CF3Ph | 0 | ||
| 74 | CO | NH | 4-CF3Ph | 1 | ||
| 75 | CO | NH | 4-CF3Ph | 2 | ||
| 76 | CO | Covalent bond | Me | 0 | ||
| 77 | SO2 | Covalent bond | Me | 1 | ||
| 78 | SO2 | Covalent bond | Me | 2 | -63.8，-78.6 | |
| 79 | SO2 | Covalent bond | Et | 0 | ||
| 80 | SO2 | Covalent bond | Et | 1 | ||
| 81 | SO2 | Covalent bond | Et | 2 | ||
| 82 | SO2 | Covalent bond | Pr | 0 | ||
| 83 | SO2 | Covalent bond | Pr | 1 | ||
| 84 | SO2 | Covalent bond | Pr | 2 | -64.3，-79.1 | |
| 85 | SO2 | Covalent bond | CH2Ph | 0 | ||
| 86 | SO2 | Covalent bond | CH2Ph | 1 | ||
| 87 | SO2 | Covalent bond | CH2Ph | 2 | -64.2，-79.1 | |
| 88 | SO2 | Covalent bond | 4-ClPh | 0 |
| Compound number | X | Y | R5 | n | Melting Point C | 19F-NMR |
| 89 | SO2 | Covalent bond | 4-ClPh | 1 | ||
| 90 | SO2 | Covalent bond | 4-ClPh | 2 | -64.2，-79.2 | |
| 91 | SO2 | Covalent bond | 4-MePh | 0 | ||
| 92 | SO2 | Covalent bond | 4-MePh | 1 | ||
| 93 | SO2 | Covalent bond | 4-MePh | 2 | -64.2，-79.2 | |
| 94 | SO2 | Covalent bond | CH2(2-FPh) | 0 | ||
| 95 | SO2 | Covalent bond | CH2(2-FPh) | 1 | ||
| 96 | SO2 | Covalent bond | CH2(2-FPh) | 2 | ||
| 97 | SO2 | Covalent bond | CH2(4-ClPh) | 2 | ||
| 98 | SO2 | Covalent bond | CH2(4-MePh) | 0 | ||
| 99 | SO2 | Covalent bond | CH2(4-MePh) | 1 | ||
| 100 | SO2 | Covalent bond | CH2(4-MePh) | 2 | ||
| 101 | SO2 | Covalent bond | CH2(4-ClPh) | 0 | ||
| 102 | SO2 | Covalent bond | CH2(4-ClPh) | 1 | ||
| 103 | SO2 | Covalent bond | CH2(4-ClPh) | 2 |
According to another aspect of the present invention, there is provided a method for controlling pests at a locus by applying thereto an effective amount of a compound of formula (I) or a salt thereof. For this purpose, the compounds are generally used in the form of pesticidal compositions (i.e., in combination with compatible diluents or carriers and/or surfactants suitable for use in pesticidal compositions), as described below.
The term "compounds of the invention" used hereinafter includes 5-substituted-alkylaminopyrazoles of the general formula (I) described above and the agrochemically acceptable salts thereof.
One aspect of the invention described above is a method of controlling pests at a locus. These sites include, for example, the pests themselves, the places where the pests reside or feed (plants, fields, forests, orchards, waterways, soil, plant products, etc.), or are susceptible to infestation by the pests. Thus, the compounds of the present invention may be applied directly to the pests, to the locus where the pests reside or feed, or to a locus susceptible to infestation by the pests.
As is evident from the foregoing pesticidal uses, the present invention provides pesticidally active compounds, and methods of using the compounds to control a number of pest species, including: arthropods, in particular insects or acarids, or plant nematodes. The compounds of the invention can therefore advantageously be used in practical applications, for example in agricultural or horticultural crops, in forestry, veterinary or animal husbandry, or in public health.
For example, the compounds of the present invention may be used in the following applications and act on the following pests:
for controlling soil insects such as corn rootworm, termites (especially for protecting buildings), root maggots, nematodes, root weevils, spodoptera exigua, cutworms, root aphids or maggots. They may also be used to provide activity against phytopathogenic nematodes, such as root nodules, cysts, flag (flag), lesions, or stem or bulb nematodes, or against mites. For controlling soil pests such as corn rootworm, the compounds are advantageously applied or incorporated in effective proportions to the growing crop or soil to be planted, or to the seed or growing plant roots.
In the field of public health, the compounds are particularly useful for controlling a variety of pests, particularly foul flies or other pests of the order diptera, such as house flies, stable flies, soldier flies, horn flies, deer flies, horse flies, midges, mosquitos or mosquitoes.
In the protection of stored products, for example in the protection of cereals, including cereals or flour, groundnuts, animal feed, wood or household goods such as carpets and textiles, the compounds of the invention are useful against arthropod attacks, in particular against beetles, including weevils, moths or mites, for example pink bollworm (Ephestia spp.) (moth), bark capsule (Anthrenus spp.) (carpet beetle), pseudograzing (tribour spp.) (pink beetle), elephant (Sitophilus spp.) (cereal weevil) or mite (acarus spp.) (mite).
For controlling cockroaches, ants or termites or similar arthropod pests in infested domestic or industrial sites, or for controlling mosquito larvae in waterways, wells, reservoirs or other flowing or ponding waters.
For treating foundations, buildings or soils to protect the buildings from attack by termites, examples of which are Reticulitermes spp, Heterotermites spp, and Coptotermes spp.
In agriculture, lepidopteran (butterfly and moth) resistant adults, larvae and eggs, for example, the cotton bollworm (Heliothis spp.), such as the green bollworm (Heliothis virescens), the cotton bollworm (Heliothis armigera) and the corn armyworm (Heliothis zea). Coleoptera (beetle) -resistant adults and larvae, for example Anthonomus spp, such as, for example, Strongylostoma tapetum (boll weevil), Solanum tuberosum (Leptinotarsa decemlineata) (Colorado potato beetle), Diabrotica spp (corn rootworm). Against insects of the sub-order Heteroptera (Hemiptera and Homoptera), such as leaf lice (Psylla spp.), Bemisia (Bemisia spp.), whitefly (Trialeurodes spp.), Aphis (Aphis spp.), Oncorhynchus septempus (Myzus spp.), Neurospora nidulans (Megouriae), Rhizopus vitis (Phylloxata spp.), Nephotettix cincticus (Nephotettix oryzae), and plant hopper (Nilaparvata spp.).
Against diptera, for example flies (Musca spp.). Against the order of the Thysanoptera (Thysanoptera), for example, Thrips tabaci (Thrips tabaci).
Against orthoptera, such as Locusta migratoria (Locusta) and Locusta (schistoserca spp.) (locusts and crickets), for example, oil hyacinth (Gryllus spp.) and crickets (Acheta spp.), for example, cockroaches (blatta orientalis), Periplaneta americana (Periplaneta americana), german cockroach (Blatella manerica), tropical Locusta migratoria (Locusta migratoria) and desert Locusta (schistoserca gregaria). Against the order of the Collelmola, such as Blatta Periplaneta (Periplaneta spp.) and Blatta Seu Periplaneta (Blatellasp).
Against arthropods which have a major impact on agriculture, such as mites (mites), for example tetranychus (tetranychuspp.) and Panonychus (Panonychus spp.).
Against nematodes attacking plants or trees of agricultural, forestry or horticultural importance, either directly or by transmitting bacterial, viral, mycoplasma or fungal diseases of plants. For example, root knot nematodes, such as Meloidogyne spp (e.g., Meloidogyne incognita).
In the veterinary or animal husbandry field or maintenance public health, against arthropods, in particular warm-blooded vertebrates, which are parasitic inside or outside vertebrates, such as domestic animals, for example cattle, sheep, goats, horses, pigs, poultry, dogs or cats, for example Acarina (Acarina), including ticks (e.g. mollusks, including Rhynchophthys reevesii (Argaidae spp)), such as Argass spp and Ornithodoros spp (e.g. Ornithodoros moubata)), hard ticks, including Ixodidae spp, such as cattle ticks (Boophilus spp.), such as Boophilus microplus (Boophilus spp.), Rhipicephalus spp), such as Rhipicephalus fasciatus (Rhynchophus fasciatus (Rhynchophagus spp.) and Ctenocephalides (Ctenocephalides fasciatus, Ctenocephalides fasciatus (Ctenoides fasciata), such as Ctenocephalides fasciola hepatica (Ctenophilus spp.), for example, avian lice (Menopon spp.); diptera (e.g., irises spp.), plottes spp, flies (Musca spp), subcutaneous flies (Hypoderma spp)); hemiptera; dictyoptera (Dictyoptera) (e.g., cockroach (Periplaneta spp.)), cockroach (Blatella spp.); hymenoptera (Hymenoptera); for example against gastrointestinal infections caused by parasitic nematodes, such as members of the Trichostrongylidae superfamily (Trichostrongylidae).
In a preferred aspect of the invention, the compounds of the general formula (I) are used for controlling parasites in animals. Preferably the animal to be treated is a companion animal of domestic origin such as a dog or cat.
In another aspect of the invention, a compound of formula (I) or a salt thereof or a composition thereof is used to prepare veterinary drugs.
Accordingly, another aspect of the present invention is directed to the use of a compound of formula (I) or a salt thereof, or a composition thereof, for controlling pests.
In practical use for controlling arthropods (particularly insects or mites) or helminths (particularly plant nematodes), for example, one method comprises applying to the plant or the medium in which the plant is growing an effective amount of a compound of the present invention. For this method, the compounds of the invention are generally applied to the locus where control of arthropod or nematode infestation is desired in an effective ratio of from about 2g to about 1 kg of active compound per hectare of the area to be treated. Ideally, a lower proportion provides adequate protection depending on the pest to be controlled. On the other hand, adverse climatic conditions, resistance to pests or other factors may lead to the need to use the active ingredients in higher proportions. The optimum ratio generally depends on a number of factors, for example on the type of pest to be controlled, the type or growth stage of the infested plant, the spacing between rows or the method of application. Preferably, the effective ratio of active compound ranges from about 10 g/ha to about 400 g/ha, more preferably from about 50 g/ha to about 200 g/ha.
When the pest is soil-borne, the active substance is generally formulated in the composition so that it is evenly distributed to the area to be treated by any convenient means (i.e. for example, broadcast treatment or tape treatment) and applied at a rate of from about 10 to about 400, preferably from about 50 to about 200, grams per hectare. When applied to seedlings in root dip (root dip) mode or applied to plants as drip irrigation, the liquid solution or suspension contains about 0.075 to 1000 milligrams active ingredient per liter, preferably about 25 to 200 milligrams active ingredient per liter. If desired, it can generally be applied to the field or to the area where the crop is growing, or in close proximity to the seed or plant to be protected from attack. The compounds of the invention may be washed into the soil by spraying with water over the area, or left to the natural action of rainfall. During or after application, the formulated compound may be mechanically distributed into the soil, if desired, for example, by plowing, raking or using a tow chain. Application can be carried out before, at or after planting, but before or after germination.
Thus, the compounds and methods of controlling pests of the present invention are particularly valuable in protecting field crops, forage crops, farm crops, greenhouse crops, orchard or vineyard crops, ornamentals or planted or forest trees, such as: cereals (such as wheat or rice), cotton, vegetables (such as pepper), field crops (such as sugar beet, soybean or oilseed rape), turf or forage crops (such as corn or sorghum), orchard or small tree crops (such as stone or stone-free (pitfruit) or citrus), ornamentals in greenhouses or in gardens or parks, flowers or vegetables or bushes, or forest trees (fallen leaves and evergreen) in forests, plantations or nurseries.
They are also valuable in protecting wood (uncut, cut, modified, stored or constructed) from attack by, for example, saw flies or beetles or termites.
Whether whole, ground or mixed into a product, they are used to protect stored products, such as grains, fruits, nuts, spices or tobacco, from moth, beetle, mite or cereal weevil attacks. Stored animal products such as skin, hair, wool or feathers are also protected in natural or transformed form against moths or beetles, and stored meat, fish or cereals are also protected against beetles, mites or flies.
In addition, the compounds of the present invention and methods of using them are particularly valuable in controlling arthropods or helminths that can harm livestock animals by transmission or as vectors of disease, such as those mentioned above, and more particularly, ticks, mites, lice, fleas, midges or stinging flies (biting flies), nuisance flies (flies), or myiasis flies (myiasis flies). The compounds of the invention are particularly useful for controlling arthropods or helminths present in domestic host animals or parasitic in or on the skin of animals or on the surface of the skin or in the blood of animals, and for this purpose can be administered orally, parenterally, transdermally or topically.
The compositions described hereinafter for application to growing crops or crop growth or as seed dressings may alternatively be used in general for the protection of stored products, household items, items and areas of the general environment. Suitable methods of administering the compounds of the present invention include: as a foliar spray (e.g., an in-furrow spray), a powder (dust), a granule, a fog or a foam, or as a finely divided suspension or encapsulated composition applied to a growing crop as a soil or root treatment by liquid drench, powder, granule, smoke or foam; by seed applied as a seed dressing to the crop, for example, by a liquid slurry or powder;
applying a composition to an animal infested by or exposed to arthropods or worms by parenteral, oral or topical administration, in which composition the active component exhibits immediate and/or sustained action against the arthropods or worms for a period of time, e.g. by incorporation into feed or suitable oral pharmaceutical preparations, edible baits, saline and alkaline land, dietary supplements, spot-on formulations (sprays), baths, dips (dips), showers (shovers), sprays (jets), powders, oils, shampoos, emulsions, wax paints (wax paints) or self-treatment systems of livestock;
the compositions are applied as a spray, mist, powder, smoke, wax spread, paint, granule or bait to the general environment or to a specific location where pests may be dormant, including stored products, wood, household items or domestic or industrial sites, or in trickle feed (tricoklefeses) to waterways, wells, reservoirs or other running or standing waters.
When administered orally, the compounds of formula (I) are particularly useful for controlling parasites in animals, and in another preferred aspect of the invention, the compounds of formula (I) are administered orally to control parasites in animals. The compound of formula (I) or a salt thereof may be administered before, at or after a meal. The compound of formula (I) or a salt thereof may be admixed with a carrier and/or a food product.
The compounds of formula (I) and salts thereof are administered orally to animals in a dosage range of: generally corresponding to 0.1-500 mg/kg of a compound of formula (I) or a salt thereof per kg of animal body weight (mg/kg).
The frequency of treatment of animals is such that generally domestic animals are preferably treated with the compound of the formula (I) or a salt thereof about once per week to about once per year, preferably about once per two weeks to about once per three months.
The compounds of the invention are preferably administered together with other parasiticidally effective materials, such as parasiticides and/or ectoparasiticides and/or parasiticides in and/or out of the body. For example, such compounds include macrocyclic lactones such as avermectins or milbemycins, for example ivermectin, pyratel, or insect growth regulators such as lufenuron or methoprene.
The compounds of the general formula (I) can also be used for controlling harmful organisms in known genetically engineered plants or in crops of genetically engineered plants to be developed. Generally, transgenic plants are known for their particularly advantageous properties, for example resistance to certain specific crop protection agents, resistance to plant diseases or pathogens of plant diseases, for example specific insects or microorganisms such as fungi, bacteria or viruses. Other specific properties relate to, for example, the quantity, quality, storage properties, composition and specific composition of the harvested material. Thus, transgenic plants are known in which the starch content is increased, or the starch quality is altered, or the harvested material has a different fatty acid composition.
Transgenic crops using economically important useful and ornamental plants are preferred, for example cereals, such as wheat, barley, rye, oats, millet, rice, cassava and maize, or other sugar beet, cotton, soybean, oilseed rape, potato, tomato, pea or other types of vegetable crops.
When used in transgenic crops, in particular those which are resistant to insects, effects can often be observed, for example a change or a specific widening of the range of pests which can be controlled, or a change in the applicable ratio, in addition to the effects on harmful organisms observed in other crops, which applies in particular in the transgenic crop in question.
The invention therefore also relates to the use of compounds of the general formula (I) for controlling harmful organisms in transgenic crops.
According to another aspect of the present invention there is provided a pesticidal composition comprising one or more compounds as defined above, preferably uniformly dispersed in, and used in combination with, one or more compatible pesticidally acceptable diluents or carriers and/or surfactants [ i.e. diluents or carriers and/or surfactants generally acceptable in the art, suitable for use in pesticidal compositions, and which are compatible with the compounds of the present invention ].
Indeed, the compounds of the present invention most typically form part of a composition. These compositions are useful for controlling arthropods, especially insects or plant nematodes or mites. The composition may be any type of composition known in the art suitable for application to a target pest at any locus (indoor or outdoor). These compositions contain at least one compound of the invention as an active ingredient in combination or association with one or more other compatible ingredients, such as solid or liquid carriers or diluents, adjuvants, surfactants and the like suitable for the intended use and which are agriculturally or pharmaceutically acceptable. These compositions, which may be prepared by any method known in the art, also form part of the present invention.
The compounds according to the invention, in their commercial formulations and in the use forms prepared from these formulations, can be used in admixture with other active substances, such as insecticides, attractants, sterilants, acaricides, nematicides, fungicides, growth-regulating substances or herbicides.
Pesticides include, for example, phosphates, carbamates, carboxylates, formamidines, tin compounds, and substances produced by microorganisms.
Preferred components in the mixture are:
1. a phosphorus-containing compound selected from the group consisting of:
acephate, fenzophos, ethoprophos, methyl oryphos, bromophos, ethylbromophos, cadusafos (F-67825), phos-phoxim, chlorfenvinphos, chlormephos, chlorpyrifos-methyl, systemic phophos, methyl systemic phophorus, SULFOROPHON, CHLOPHOSPHAS, diazinon, dichlorvos, chlorothalofos, dimethoate, disulfoton, EPN, ethion, fenamiphos, oxypyrimidine, phosmet, clorophos, fenitrothion, fenthion, pyrafluphos, disulfoton, dichlofenthion, heptenophos, isazophos, isoprophos, isofenthion, fenamiphos, fenthion, fenthioTriazophos, malathion, chlorfenvinphos, methamidophos, methidathion, chlorfenapyr, fenaminophos, monocrotophos, naled, omethoate, sufenthion, parathion, methyl parathion, phenthoate, phorate, vophos, cotton ANFO, EPP-P-methyl-P-carb (BAS-301), phosmet, phosphamidon, fencloxim, chlorfenap, ethoprofen, methyl chlorfenap, profenofos, propaphos, proetams, prothiofos, pyrazofos, thiofenthion, thiofos, terbufos, pyrifos, chlorfenphos, methamphos, triazophos, trichlorfon, and aphicide;
2. a carbamate selected from:
cotton boll-carbofuran (OK-135), aldicarb, methyl 2-sec-butylbenzene carbamate (BPMC), carbaryl, carbofuran, carbosulfan, carbofuran, benfuracarb, HCN-801, isoprocarb, methomyl, 5-methyl-m-cumylbutyryl (methyl) carbamate, oxamyl-carbofuran, pirimicarb, propoxur, thiodicarb, tetramethocarb, 1-methylthio (ethyleneamino) -N-methyl-N- (morpholinothio) carbamate (UC 51717), triazamate;
3. a carboxylic acid ester selected from:
bifenthrin, allethrin, alphamethrin, 5-benzyl-3-furylmethyl (E) - (1R) -cis-2, 2-dimethyl-3- (2-oxothiolan-3-yliden) methyl cyclopropanecarboxylate, beta-cyfluthrin, alpha-cypermethrin, beta-cypermethrin, bioallethrin ((S) -cyclopentyl isomer), tetramethrin, bifenthrin, (RS) -1-cyano-1- (6-phenoxy-2-pyridyl) methyl (1RS) -trans-3- (4-tert-butylphenyl) -2, 2-dimethylcyclopropane carboxylate (NCI 85193), acetonitrile pyrethrin, cythrin, cythithrin, cypermethrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, pentafluoro-pyrethrin, fenpropathrin, flucythrinate, flumethrin, cyfluthrin (D isomer), imiprothrin (S-41311), lambda-cyhalothrin, permethrin, phenothrin (S-41311)Isomers), prallethrin, pyrethrin (natural product), resmethrin, tefluthrin, tetramethrin, theta-cypermethrin, tralomethrin, transfluthrin, delta-cypermethrin (F-56701);
4. an amidine selected from:
chlorfenapyr, chlordimeform;
5. a tin compound selected from the group consisting of:
cyhexatin, fenbutatin oxide;
6. others
Abamectin, ABG-9008, acetamiprid, chlorfenapyr, Anagrex falcate, AKD-1022, AKD-3059, ANS-118, Melanin (azadirachtin), Bacillus thuringiensis, Beauveria bassiana (Beauveria bassiana), bensulam, bifenazate, binapacryl, BJL-932, bromopropylate, BTG-504, BTG-505, buprofezin, toxaphene, pyraclorac, dicofol, flufenpyr, chlorfluazuron, 2- (4-chlorophenyl) -4, 5-diphenylthiobenzene (UBI-T930), chrofenzine, chlorhexyn, chromafenozide (chromafenozide), clothianidin (clothidinine), 2-naphthylmethylcyclopropanecarboxylate (Ro12-0470), thiamethoxam (thiamethoxam), thiamethoxam (DBI-3204-D-3, dicofoam), dicofol-4- (3-D-5-D-E), 1, 2, 3, 3, 3-hexafluoro-1-propoxy) phenyl) carbamoyl) -2-carboximidic acid (carboximidate) ethyl ester, DDT, clotrimazole, diflubenzuron, N- (2, 3-dihydro-3-methyl-1, 3-thiazol-2-yl ethylene) -2, 4-xylidine, dihydroxymethyl dihydroxypyrrolidine, dinocap, diphenylpropyl ether, emamectin benzoate (emamectin benzoate), endosulfan (endosulfan), ethiprole (ethiprole) (thifenpyr), ethofenprox, etoxazole (etoxazole), fenazaquin, fenoxycarb, fipronil, flonicamid (flonicamid) (i-220), fluazuron, flufenzine (flufenzine), SZI-121), 2-fluoro-5- (4- (4-ethoxyphenyl) -4-methyl-1-pentyl) diphenylbenzene Basal ethers (MTI 800), granuloma proliferatum and nucleopolyhedrovirus, fenpyroximate, fenthiocarb, fluacrypyrim (fluacrypyrim), thiazole mite, brofluthrin (flucythrinate), flufenoxuron, flutenzine, trifluorethofenprox, benmesifen (fluproxyfen), lindane, chlorfenapyr (halofenozide), haloethrin, hexaflumuron (DE _473), hexythiazox, HOI-9004, mirex (AC 217300), indoxacarb, ivermectin, L-14165, imidacloprid, indoxacarb (DPX-MP062), fenaminoquinone (AKD-2023), octaflubenzuron, M-020, methoxyfenozide, milbemectin, neemgard, dinotefuran (nifedidinotefuran), nitenpyran, 2-nitromethoprene, 2-nitromethyl-4, H-355-2-dihydrothiazole (D-52618-2-dihydrothiazole (DS-35651, 2-2, 3) and dihydrothiazole (D-3, 2-3, thiabendazole), 2-Nitromethylene-1, 2-thiazinan-3-ylcarbamide (WL 108477), novaluron, pirydryl, propargite, pyrethrin (procifenbute), pymetrozine, pyridaben, pyriminostrobin, NC-196, NC-1111, NNI-9768, novaluron (MCW-275), OK-9701, OK-9601, OK-9602, OK-9802, R-195, RH-0345, RH-2485, RYI-210, S-1283, S-1833, SI-8601, silatran, silodine (CG-177), Ikefir 105, spirodiclofen (spirodiclofen), SU-9118, diphenhydrazide, imidacloprid, thifluazuron, thifenpyr (thifenpyr), thifenpyr (fenpyr), thifenpyr (fenpyrad), thifenpyr-ethyl (fenpyr-3), thifenpyr-9602, thifluzine (fenpyr-177), thifenpyr-ethyl (pyrifos), thifenpyr-1, thifenpyr-ethyl (fenpyr-3), thifenpyr-ethyl (thifenpyr-ethyl), thifenpyr, Tolfenpyrad (tolfenpyrd), triazamate, triethoxyspinosyn A, chlorfluazuron, verastin (verbutin), mecoball (rotalec) (mykotal), YI-5301.
The above-mentioned components for The combination are known active substances, many of which are described in ch.rworthing, s.b.walker, The handbook of pesticides (The Pesticide Manual), 12 th edition, british crop Protection Council, Farnham 2000.
The effective application doses of the compounds for use in the invention can vary within wide limits, in particular depending on the kind of pests to be removed or, for example, the extent to which crops are infested with these pests. In general, the compositions of the present invention will generally contain from about 0.05 to about 95% by weight of one or more active ingredients of the invention, from about 1 to about 95% of one or more solid or liquid carriers, and optionally from about 0.1 to about 50% of one or more other compatible ingredients, such as surfactants and the like.
In the present invention, the term "carrier" refers to a natural or synthetic organic or inorganic component, combined with an active ingredient, to facilitate application to, for example, plants, seeds or soil. Thus, the carrier is generally inert and must be acceptable (e.g., agronomically acceptable, particularly for the plant to be treated).
The carrier may be a solid, for example, clay, natural or synthetic silicate, silica, resin, wax, solid fertiliser (e.g. ammonium salts), ground natural minerals (such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite, bentonite or diatomaceous earth), or ground synthetic minerals (such as silica, alumina or silicates, especially ammonium or magnesium silicates). As solid carriers for the particles, the following are suitable: crushed or graded natural rocks such as calcite, marble, pumice, sepiolite and dolomite; synthetic inorganic or organic coarse powder particles: particles of organic matter, such as wood chips, coconut shells, corn cobs, corn husks or tobacco stalks (talk); diatomaceous earth, tricalcium phosphate, powdered cork or adsorbent carbon black; water-soluble polymers, resins, waxes; or a solid fertilizer. Such solid compositions may, if desired, contain one or more compatible wetting, dispersing, emulsifying or coloring agents, which when solid, may also be employed as diluents.
The carrier may also be a liquid, for example: water; alcohols, in particular butanol or ethylene glycol, and their esters or ethers, in particular ethylene glycol monomethyl ether acetate; ketones, in particular acetone, cyclohexanone, methyl ethyl ketone, methyl isobutyl ketone or isophorone; petroleum fractions such as paraffinic or aromatic hydrocarbons, in particular xylenes or alkyl naphthalenes; mineral or vegetable oils; aliphatic chlorinated hydrocarbons, in particular trichloroethane or dichloromethane; aromatic chlorinated hydrocarbons, in particular chlorobenzene; water-soluble or strongly polar solvents such as dimethylformamide, dimethyl sulfoxide or N-methylpyrrolidone; liquefied gas, etc., or mixtures thereof.
The surfactant may be an emulsifier, dispersant or wetting agent, of ionic or non-ionic type, or a mixture of such surfactants.
Among them are, for example, salts of polyacrylic acids, salts of lignosulfonic acids, salts of phenolsulfonic or naphthalenesulfonic acids, polycondensates of ethylene oxide with fatty alcohols or fatty acids or fatty esters or fatty amines, substituted phenols (in particular alkylphenols or arylphenols), salts of sulfosuccinic esters, taurine derivatives (in particular alkyl taurates), phosphoric esters of alcohols or polycondensates of ethylene oxide with phenols, esters of fatty acids with polyhydric alcohols, or functional derivatives of sulfuric, sulfonic or phosphoric esters of the above compounds. The presence of at least one surfactant is generally important when the active ingredient and/or inert carrier is only sparingly soluble or insoluble in water and the carrier agent of the administered composition is water.
The composition of the present invention may further contain other additives such as a sizing agent or a coloring agent. Examples of adhesives which can be used in the formulation are carboxymethylcellulose or natural or synthetic polymers, such as gum arabic, polyvinyl alcohol or polyvinyl acetate, in powder, granule or grid form; natural phospholipids, such as cephalins or lecithins, or synthetic phospholipids. Examples of colorants that can be used are inorganic pigments, such as: iron oxide, titanium oxide, or prussian blue; organic dyes such as alizarin dyes, azo dyes, or metal phthalocyanine dyes; or trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum or zinc.
Thus, for agricultural use, the compounds of the present invention are generally used in the form of compositions which are in various solid or liquid forms. Solid forms of the compositions which may be used are dusting powders (up to 80% of the compound of the invention), wettable powders or granules (including water-dispersible granules), especially those obtained by extrusion, pressing, impregnation of a particulate support or by granulation of a powder (the content of the compound of the invention in these wettable powders or granules is from about 0.5% to about 80%). Solid homogeneous or heterogeneous compositions, e.g., granules, pellets, briquettes, or capsules, containing one or more compounds of the invention can be used to treat standing or running water over a period of time. Similar effects can be obtained using trickle or intermittent feeding of the above-described water-dispersed concentrate. Liquid compositions, for example, include aqueous or non-aqueous solutions or suspensions (such as emulsifiable concentrates, emulsions, flowables, dispersions, or solutions) or aerosols. In particular, liquid compositions also include emulsifiable concentrates, dispersions, emulsions, flowables, aerosols, wettable powders (or powders for spraying), dry flowables or pastes, as liquid compositions or to be formed upon application, for example, as water sprays (including low and ultra-low volumes) or as sprays or aerosols.
Liquid compositions, for example, in the form of emulsifiable or soluble concentrates, most often contain from about 5% to 80% by weight of the active ingredient, while emulsions or solutions to be applied contain from about 0.01% to about 20% of the active ingredient. The emulsifiable or soluble concentrate may contain, if desired, in addition to the solvent, from about 2% to about 50% of suitable additives, such as stabilizers, surfactants, penetrants, corrosion inhibitors, colorants, or adhesives. For example, emulsions of any desired concentration, particularly suitable for application to such plants, can be obtained by diluting such concentrates with water. Such compositions are included within the scope of the present invention and may be used in the present invention. The emulsions may be in the form of water-in-oil or oil-in-water, and they may have a thicker consistency.
In addition to normal agricultural use, the liquid compositions of the present invention may be used, for example, to treat materials or locus infested or susceptible to infestation by arthropods (or other pests which can be controlled by the compounds of the present invention), including houses, outdoor or indoor storage or operating areas, containers or equipment, or standing or running water.
All of these aqueous dispersions or emulsions or spray mixtures can be applied to, for example, crops using any suitable method, primarily by spraying, typically at a rate of from about 100 to 1200 liters per hectare, but this rate can also be higher or lower (e.g., low or ultra-low volume) depending on the need or technique of application. The compounds or compositions of the invention can be conveniently applied to plants, in particular to the roots or foliage of the pests to be removed. Another method of applying the compounds or compositions of the present invention is by chemigation, i.e., adding a formulation containing the active ingredient to irrigation water. The irrigation can be leaf pesticide spray irrigation or systemic pesticide ground irrigation or underground irrigation of the soil.
Concentrated suspensions, which can be applied by spraying, are prepared to produce stable liquid products which do not undergo sedimentation (finely ground), and generally contain from about 10% to about 75% by weight of the active component, from about 0.5% to about 30% of a surfactant, from about 0.1% to about 10% of a thixotropic agent, from about 0% to about 30% of a suitable additive, such as an antifoam, corrosion inhibitor, stabilizer, penetrant, adhesive, and water or organic liquid as carriers in which the active component is poorly soluble or insoluble. Some organic solids or inorganic salts may be dissolved in the carrier to prevent sedimentation or to act as antifreeze for water.
Wettable powders (or powders for spraying) are typically prepared to contain from about 10% to about 80% by weight of the active ingredient, from about 20% to about 90% of a solid carrier, from about 0% to about 5% of a wetting agent, from about 3% to about 10% of a dispersing agent, from about 0% to about 80% of one or more stabilizers and/or other additives such as penetrants, adhesives, anti-caking agents, colorants, and the like. To obtain these wettable powders, the active ingredient is thoroughly mixed with other substances which may be impregnated onto the porous filler in a suitable blender using a mill or other suitable grinding machine. This operation produces a wettable powder, which is very excellent in wettability and suspensibility. They can be suspended in water to give any desired concentration and the suspension is advantageously applied in particular to the leaves of plants.
"Water dispersible particles (WGs)" (particles that readily disperse in water) have a composition that is substantially completely similar to that of the wettable powder. They can be prepared by granulating a preparation of the wettable powders described above, either by the wet route (contacting the finely divided active component with an inert filler and a small amount of water (e.g. 1 to 20% by weight) or with an aqueous solution of a dispersant or binder, followed by drying and sieving) or by the dry route (compacting, followed by grinding and sieving).
The proportion and concentration of the formulated compositions may vary depending on the method of administration, the nature of the compositions, or their use.
In general, compositions for controlling arthropod or plant nematodes contain from about 0.00001% to about 95%, more preferably from about 0.0005% to about 50%, by weight of one or more compounds of the invention, based on the total active ingredient (i.e. the compounds of the invention and other substances, synergists, trace elements or stabilizers, which are toxic to arthropod or plant nematodes). The actual compositions employed and the proportions in which they are applied are selected by the farmer, livestock farmer, doctor or veterinarian, pest control operator or other skilled person in the art to achieve the desired effect or effects.
Solid or liquid compositions for topical application to animals, wood, stored products, or household items generally contain from about 0.00005% to about 90%, preferably from about 0.001% to about 10%, by weight of one or more compounds of the present invention. For oral or parenteral administration to an animal, including transdermal administration of solid or liquid compositions, these compositions typically contain from about 0.1% to about 90% by weight of one or more compounds of the invention. The pharmaceutical feed typically contains from about 0.001% to about 3% by weight of one or more compounds of the invention. Concentrates or supplements for mixing with feed generally contain from about 5% to about 90%, preferably from about 5% to about 50%, by weight of one or more compounds of the invention. Mineral saline-alkali lands typically contain from about 0.1% to about 10% by weight of one or more compounds of formula (I) or a pesticidally acceptable salt thereof.
The powder or liquid composition for application to livestock, goods, houses or outdoor areas may contain from about 0.0001% to about 15%, more preferably from about 0.005% to about 2.0%, by weight of one or more compounds of the invention.
Suitable concentrations of one or more compounds of the invention in the treated water range from about 0.0001ppm to about 20ppm, preferably from about 0.001ppm to about 5.0ppm, and can be therapeutically used in fish fields with a suitable exposure time. The edible bait comprises from about 0.01% to about 5%, preferably from about 0.01% to about 1.0% by weight of one or more compounds of the present invention.
When administered parenterally, orally or transdermally or otherwise to vegetables, the dosage of the compounds of the present invention will depend on the variety, age or health of the vegetable, and its actual or potential type and extent of infestation by arthropods or nematodes. A single dose of about 0.1 to 100 mg, preferably about 2.0 to 20.0 mg per kg of animal body weight, or for sustained administration a dose of about 0.01 to 20.0 mg, preferably about 0.1 to 5.0 mg per kg of animal body weight per day, is generally suitable for oral or parenteral administration. By using sustained release formulations or devices, the desired daily doses can be combined over several months and administered to the animal at once.
Examples 2A-2M below illustrate compositions for combating arthropods, in particular mites or insects, or plant nematodes, which compositions comprise as active ingredient a compound of the invention, such as those described in the preparation examples. The compositions described in examples 2A-2M can all be diluted to give sprayable compositions of a concentration suitable for field use. The general chemical description of the components used in the compositions exemplified in examples 2A-2M below (where all percentages are by weight) is as follows:
chemical description of trade name
Ethylan BCP based phenol ethylene oxide condensate
Soprophor BSU tristyrylphenol ethylene oxide condensate
Arylan CA 70% w/v calcium dodecylbenzenesulfonate solution
Solvesso150 light (light) C10Aromatic solvent
Arylan S sodium dodecyl benzene sulfonate
Darvan NO2Sodium lignosulfonate
Magnesium silicate carrier synthesized by Celite PF
Sodium salt of Sopropofol T36 polycarboxylic acid
Rhodigel 23 polysaccharide xanthan gum
Organic derivatives of Bentone 38 magnesium montmorillonite
Aerosil ultrafine silica
Example 2A
A water soluble concentrate was prepared with the following composition:
active component 7%
Ethylan BCP 10％
N-methylpyrrolidone 83%
To a solution of ethyl lan BCP dissolved in a portion of N-methyl pyrrolidone was added the active ingredient with heating and stirring until dissolved. The volume of the resulting solution was made up with the rest of the solvent.
Example 2B
An Emulsifiable Concentrate (EC) was prepared with the following composition:
active ingredient 25% (maximum)
Soprophor BSU 10％
Arylan CA 5％
N-methyl pyrrolidone 50%
Solvesso 150 10％
The first three ingredients were dissolved in N-methylpyrrolidone, to which Solvesso150 was then added to give the final volume.
Example 2C
Wettable Powders (WP) were prepared with the following composition:
active component 40%
Arylan S 2％
Darvan NO2 5％
Celite PF 53％
These components are mixed and ground in a hammer mill to a powder having a particle size of less than 50 microns.
Example 2D
A water-flowable (aquous-flowable) formulation was prepared with the following composition:
active component 40.00%
Ethylan BCP 1.00％
Sopropon T360 0.20％
Ethylene glycol 5.00%
Rhodigel 230 0.15％
53.65 percent of water
The components were thoroughly mixed and then milled in a sand mill until the average particle size was less than 3 microns.
Example 2E
An emulsifiable suspension concentrate was prepared with the following composition:
30.0 percent of active component
Ethylan BCP 10.0％
Bentone 38 0.5％
Solvesso 150 59.5％
The components were thoroughly mixed and then ground in a sand mill until the average particle size was less than 3 microns.
Example 2F
Water dispersible granules were prepared with the following composition:
30 percent of active component
Darvan No 2 15％
Arylan S 8％
Celite PF 47％
The components were mixed, micronised in a jet mill and then granulated in a rotary granulator by spraying water (up to 10%). The resulting granules were dried in a fluid bed dryer to remove the remaining water.
Example 2G
Dusting powder was prepared with the following composition:
1 to 10 percent of active component
99 to 90 percent of superfine talcum powder
These components were thoroughly mixed and then further ground as needed to give a fine powder. The powder can be applied to arthropod-infested sites, such as garbage dumps, stored products or household goods, or to arthropod-infested or at-risk animals for controlling arthropods by oral ingestion. Suitable means for dispersing the dusting into arthropod infested areas include mechanical blowers, hand shakers (handshakers) or livestock self-disposal devices (livestock self-disposal devices).
Example 2H
An edible bait was prepared with the following composition:
0.1 to 10 percent of active component
Wheat flour 80%
Molasses 19.9-19%
These components are thoroughly mixed to form a bait shape as desired. The edible bait may be dispersed to a place infested with arthropods such as ants, locusts, cockroaches or flies, for example, a home or industrial place such as a kitchen, hospital or store or an outdoor area, to control arthropods by oral ingestion.
Example 2I
A solution formulation was prepared with the following composition:
active component 15%
Dimethyl sulfoxide 85%
The active ingredient is dissolved in dimethyl sulfoxide, mixed and/or heated as required. The solution can be applied transdermally to arthropod-infested livestock by pour-on application or by injection after filtered sterilization through a polytetrafluoroethylene membrane (pore size 0.22 μm) at a rate of 1.2-12 ml per 100 kg of animal body weight.
Example 2J
Wettable powders were prepared with the following composition:
active component 50%
Ethylan BCP 5％
Aerosil 5％
Celite PF 40％
The ethan BCP is absorbed on Aerosil and then mixed with the other components and ground in a hammer mill to give a wettable powder which can be diluted with water to a concentration of 0.001 to 2% by weight of the active compound and applied by spraying to the locus infested by arthropods such as dipteran larvae or plant nematodes or by spraying or dipping or oral administration in drinking water to domestic animals infested by or at risk of being infested by arthropods.
Example 2K
The sustained release pellets were formed from granules containing the following ingredients in different percentages (similar to those in the aforementioned composition) as required:
active component
Densifier
Sustained release agent
Adhesive agent
The thoroughly mixed components are formed into granules which are compressed into pellets having a specific gravity of 2 or more. The pellets can be administered orally to domestic ruminants to remain in their reticulum (reticulum-rumen) and thereby release the active compound continuously and slowly over a prolonged period of time to prevent infestation of domestic ruminants by arthropods.
Example 2L
Sustained release compositions in the form of granules, pills, pellets and the like can be prepared according to the following composition:
active component 0.5-25%
75-99.5% of polyvinyl chloride
Dioctyl phthalate (plasticizer)
These components are blended and then formed into the appropriate shape by melt extrusion or molding. These compositions are useful, for example, for incorporation into still water, or for making collars or ear tags for attachment to livestock (earthags) to control pests by slow release.
Example 2M
Water dispersible granules were prepared with the following composition:
active component 85% (maximum)
Polyvinylpyrrolidone 5%
Palygorskite (Attapulgite clay) 6%
Sodium dodecyl sulfate 2%
2 percent of glycerin
These ingredients were mixed with water to form a 45% slurry, then wet milled to a particle size of 4 microns, and then spray dried to remove water.
Method for using pesticide
The following representative test procedures were performed using the compounds of the present invention to determine the parasiticidal activity of the compounds of the present invention.
The method A comprises the following steps: screening method for testing systemic properties of compounds against Ctenocephalides felis (cat fleas)
One test container was filled with 10 adults of Ctenocephalides felis. One end of a glass cylinder was closed with parafilm and placed on top of the test vessel. The test compound solution was then removed from the bovine blood and added to a glass cylinder. The treated Ctenocephalides felis was maintained in this artificial hemophagous test (blood, 37 deg.C, 40-60% relative humidity; Ctenocephalides felis, 20-22 deg.C, 40-60% relative humidity) and evaluated at 24 and 48 hours post-application. Compound nos. 6, 30, 39, 51, 54, 57, 63, 69, 72, 84, 90 and 93 showed control of ctenocephalides felis at least 80% at test concentrations less than or equal to 500 ppm.
Claims (8)
1. A compound of formula (I) or a pesticidally acceptable salt thereof,
wherein:
R1is CN;
w is C-halogen;
R2is halogen;
R3is (C)1-C6) -a haloalkyl group;
R4is (C)1-C6) -an alkyl group;
a is (C)1-C6) -an alkylene group;
x is C (═ O) or C (═ S);
y is O, NR11Or a covalent bond, wherein R11Is hydrogen;
R5is- (CH)2)qR7(ii) a Or quilt (C)1-C6) -alkoxy substituted or unsubstituted (C)1-C6) -an alkyl group; wherein q is 0 or 1, R7Is substituted by one or more groups selected from halogen and NO2Phenyl substituted or unsubstituted with the group of (a);
R6is (C)1-C6) -a haloalkyl group;
n is 0, 1 or 2.
2. A compound or pesticidally acceptable salt thereof according to claim 1, wherein R is6Is CF3。
3. The compound or pesticidally acceptable salt thereof according to claim 1,
w is C-Cl;
R2is Cl;
R3is CF3；
A is-CH2CH2-；
X is C (═ O);
R5is- (CH)2)qR7、(C1-C3) -an alkyl group;
R6is CF3；
R7Is selected from one or more of halogen, (C)1-C3) Alkyl radicals, (C)1-C3) -haloalkyl, (C)1-C3) Alkoxy and NO2Phenyl substituted or unsubstituted with the group (a)
q is 0 or 1.
4. A process for the preparation of a compound of general formula (I) or a pesticidally acceptable salt thereof as defined in any of claims 1 to 3, which process comprises:
a) when R is2、R3、R4、R5、R6W, A, X, Y and n are as defined in any one of claims 1 to 3, except that, with the exception of compounds in which-Y-X is-NH-CO-or-NH-CS-, compounds of formula (II) are subjected to an acylation or sulphonylation reaction with a compound of formula (III):
wherein R is2、R3、R4、R6W, A and n are as defined for formula (I), formula (III) being:
R5-Y-X-L (III)
wherein R is5Y and X are as defined for formula (I), with the exception of compounds in which-Y-X is-NH-CO-or-NH-CS-, L is a leaving group; or
b) When R is1、R2、R3、R4、R5、R6W, A and n are as defined in any of claims 1 to 3, reacting a compound of formula (II) with an isocyanate or isothiocyanate compound of formula (IV) or (V), R in formula (II)2、R3、R4、R6W, A and n are as defined in any one of claims 1 to 3, and-Y-X is-NH-CO-or-NH-CS-, and formula (IV) or formula (V) respectively:
R5-N＝C＝O (IV) R5-N＝C＝S (V)
wherein R is5As defined in formula (I); or
c) When n is 1 or 2, R1、R2、R3、R4、R5、R6W, A, X and Y are as defined in any one of claims 1 to 3, oxidizing the corresponding compound wherein n is 0 or 1;
d) if desired, the resulting compound of formula (I) is converted into a pesticidally acceptable salt thereof.
5. A pesticidal composition comprising a compound of formula (I) or a pesticidally acceptable salt thereof as defined in any one of claims 1 to 3, and a pesticidally acceptable diluent or carrier and/or surfactant.
6. Use of a compound of general formula (I) or a pesticidally acceptable salt thereof, as defined in any of claims 1 to 3, or of a composition as defined in claim 5, for the preparation of a veterinary medicament.
7. Use of a compound of general formula (I) according to any one of claims 1 to 3 or a pesticidally acceptable salt thereof or a composition according to claim 5 for pest control of non-therapeutic purposes.
8. A method of controlling pests at a locus not to be treated, which comprises applying to the locus an effective amount of a compound of formula (I) as claimed in any one of claims 1 to 3 or a pesticidally acceptable salt thereof or a composition as claimed in claim 5.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03019618.2 | 2003-09-04 | ||
| EP03019618 | 2003-09-04 | ||
| PCT/EP2004/009378 WO2005023776A1 (en) | 2003-09-04 | 2004-08-21 | Pesticidal 5-substituted-oxyalkylamino-1-arylpyrazole derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HK1099649A1 HK1099649A1 (en) | 2007-08-17 |
| HK1099649B true HK1099649B (en) | 2011-12-16 |
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