DE19520936A1 - Ectoparasiticides means - Google Patents

Abstract

The present invention relates to the use of compounds of formula (I) in which B is possibly substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, A is aryl, aryloxy, heteroaryl, heteroaryloxy which may be substituted and may be bonded to the oxazoline ring via a divalent radical Z, R is hydrogen or, together with A and the adjacent C atom, a spirocyclic 3 to 6-member ring which may contain one or more heteroatoms of the O, S, N group and may be condensed on a further ring, where the system may be substituted, for combatting insects and monoxenous ticks on humans and animals.

Description

The present invention relates to the use of oxazolines Be ectoparasites and ectoparasiticides containing oxazolines.

Oxazoline and their preparation and their use as insecticides and Acaricides in crop protection and against certain mites on animals are already known. About their use against ectoparasites and especially against insects and one-headed ticks, however, has not been disclosed.

The present invention relates to the use of compounds of the formula (I)

in which
B is optionally substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl,
A is aryl, aryloxy, heteroaryl, heteroaryloxy which are optionally substituted and which are optionally bonded via a divalent radical Z to the oxazoline ring,
R is hydrogen or together with A and the adjacent C atom for a spiro-cyclic 3- to 6-membered ring which may optionally contain one or more heteroatoms of the group O, S, N and to which optionally a further ring is fused, wherein the system is optionally substituted,
for controlling parasitic insects and human and animal ticks.

The compounds of formula (I) are z. B. Subject of the following patent applications:
WO 93/21 165, WO 93/24470, JP-OS H4 89 484, JP-OS H6 145 155, JP-OS H6 145 169, JP-OS H6 48 907, JP-OS H6 100 546; JP-OS H6 100 560, JP-OS H6 73 030, EP-OS 345 775, EP-OS 432 601, EP-OS 553 623, WO 93/22 297, WO 93/25 077, WO 93/25 079.

On the preferred compound groups and individual compounds and Her In this publication is hereby particularly reference taken.

Preference is given to compounds of the general formula (I) in which the definitions for the substituents have the following meanings:
Optionally substituted alkyl, alone or as part of a radical in the general formulas, denotes straight-chain or branched alkyl having preferably 1 to 20, in particular 1 to 18, carbon atoms. Examples which may be mentioned are preferably substituted methyl, ethyl, n- and i-propyl, n-, i- and t-butyl, neo-pentyl, undecyl, dodecyl, pentadecyl and octadecyl.

Optionally substituted alkenyl and the alkenyl moiety of a radical such as. B. optionally substituted alkenyloxy and alkenylthio in the general Formulas denote straight-chain or branched alkenyl preferably having 2 to 6, in particular 2 to 4 carbon atoms. By way of example and preferably optionally substituted ethenyl, propenyl- (1), propenyl- (2) and butenyl- (3) called.

Optionally substituted alkynyl and the alkynyl moiety of a radical such as. B. optionally substituted alkynyloxy and alkynylthio in the general Formulas denote straight-chain or branched alkynyl with preferably 2 to 6, in particular 2 to 4 carbon atoms. By way of example and preferably  optionally substituted ethynyl, propynyl (1), propynyl (2) and butynyl (3) called.

Optionally substituted cycloalkyl alone or as part of a radical in the general formulas means mono-, bi- and tricyclic cycloalkyl with preferably 3 to 10, in particular 3, 5 or 6 carbon atoms. example wisely and preferably be optionally substituted cyclopropyl, cyclo butyl, cyclopentyl, cyclohexyl.

Optionally substituted alkoxy alone or as part of a radical in the general formulas means straight-chain or branched alkoxy with preferably 1 to 6, in particular 1 to 4 carbon atoms. Exemplary and preferably substituted or unsubstituted methoxy, ethoxy, n- and i-propoxy and n-, o- and t-butoxy called.

Optionally substituted alkylthio alone or as part of a radical in the general formulas means straight-chain or branched alkylthio with preferably 1 to 6, in particular 1 to 4 carbon atoms. Exemplary and optionally substituted methylthio, ethylthio, n- and i-Propylthio, n-, o- and t-butylthio called.

Optionally substituted carbalkoxy alone or as part of a radical in the general formulas is straight-chain or branched carbalkoxy with preferably 2 to 7, in particular 2 to 5 carbon atoms. exemplary and preferably optionally substituted carbomethoxy, carboethoxy, Carbo-n- and i-propyloxy and carbo-n-, i- and t-butyloxy called.

Haloalkyl alone or as part of a radical such. B. haloalkoxy or Halogenoalkylthio in the general formulas contains 1 to 4, in particular 1 or 2 carbon atoms and preferably 1 to 5, in particular 1 to 3, the same or different halogen atoms, wherein as the halogen atoms preferably fluorine, chlorine and bromine, especially fluorine and chlorine. Exemplary are trifluoromethyl, Chloro-di-fluoromethyl, bromomethyl, 2,2,2-trifluoroethyl and pentafluoroethyl called.

Optionally substituted aryl alone or as part of a radical such. B. Aryloxy, arylthio, arylalkyl in the general formulas is preferably optionally substituted phenyl or naphthyl, in particular phenyl.  

Optionally substituted aralkyl in the general formulas optionally substituted in the aryl part and / or alkyl part aralkyl preferably 6 or 10, in particular 6 carbon atoms in the aryl part (preferably phenyl or naphthyl, in particular phenyl) and preferably 1 to 4, in particular 1 or 2 carbon atoms in the alkyl moiety, wherein the alkyl moiety may be straight or branched. By way of example and preferably optionally substituted benzyl and phenylethyl called.

Optionally substituted heteroaryl alone or as part of a radical such as heteroaryloxy, heteroarylthio, heteroaralkyl means in the general Formulas 5- to 7-membered rings with preferably 1 to 3, in particular 1 or 2 identical or different heteroatoms which satisfy the aromatic principle of Follow Hückel rule. Heteroatoms are oxygen, sulfur or nitrogen. Exemplary and preferably are optionally substituted thienyl, ge Nannt.

The optionally substituted radicals of the general formula (I) may carry one or more, preferably 1 to 3, in particular 1 to 2 identical or different substituents ver. As substituents are given by way of example and preferably before:
Alkyl having preferably 1 to 20, in particular 1 to 18 carbon atoms, such as methyl, ethyl, n- and i-propyl and n-, i- and t-butyl, neo-pentyl, hexadecyl, octadecyl; Alkoxy having preferably 1 to 14, in particular 1 to 4 carbon atoms, such as methoxy, ethoxy, n- and i-propyloxy and n-, i- and t-butyloxy; Alkylthio having preferably 1 to 4, in particular 1 or 2 carbon atoms, such as methylthio, ethylthio, n- and i-propylthio and n-, i- and t-butylthio; Halogenoalkyl having preferably 1 to 4, in particular 1 or 2 carbon atoms and preferably 1 to 5, in particular 1 to 3 halogen atoms, wherein the halogen atoms are identical or different and are halogen atoms, preferably fluorine, chlorine or bromine, in particular fluorine, such as difluoromethyl, trifluoromethyl ; hydroxy; Halogen, preferably fluorine, chlorine, bromine, in particular fluorine, chlorine, cyano; nitro; amino; Monoalkyl and dialkylamino having preferably 1 to 4, in particular 1 or 2, carbon atoms per alkyl group, such as methylamino, methylethylamino, n- and i-propylamino and methyl-n-butylamino; Acyl radicals such as Formayl, alkylcarbonyl such. For example, acetyl, arylcarbonyl such as. Benzoyl; carboxyl; Carboxy preferably having 2 to 4, especially 2 or 3 carbon atoms, such as carbomethoxy and carboethoxy; Alkylsulfinyl having 1 to 4, in particular 1 to 2 carbon atoms, haloalkylsulfinyl having 1 to 4, in particular 1 to 2 carbon atoms and 1 to 5 halogen atoms such as trifluoromethylsulfinyl having 1 to 4, in particular 1 to 2 carbon atoms having 1 to 5 halogen atoms such as trifluoromethylsulfinyl; Sulfonyl (-SO₃H); Alkylsulfonyl having preferably 1 to 4, in particular 1 or 2 carbon atoms, such as methylsulfonyl and ethylsulfonyl; Haloalkylsulfonyl having 1 to 4, in particular 1 to 2 carbon atoms and 1 to 5 halogen atoms such as trifluoromethylsulfonyl, perfluoro-t, n, s-butylsulfonyl; Arylsulfonyl having preferably 6 or 10 aryl carbon atoms, such as phenylsulfonyl; acyl; aryl; aryloxy; heteroaryl; heteroaryloxy; which in turn can carry one of the abovementioned substituents as well as the formiminoride

Preference is given to compounds of the formula (I) in which the Substituents have the following meaning:

B is C₁-C₈-alkyl which is optionally monosubstituted or polysubstituted, identically or differently, by halogen, cyano, C₁-C₄-alkoxy and by in each case optionally monosubstituted to trisubstituted by identical or different halogens, C₁-C₄-alkyl, C₁-C₄ haloalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, C₁-C₄ alkylthio and / or C₁-C₄ haloalkylthio substituted phenyl, phenoxy, benzyloxy, phenylthio and benzylthio;
for optionally mono- or polysubstituted by identical or different halogen-substituted C₂-C₅-alkenyl;
for C₃-C₈-cycloalkyl which is optionally monosubstituted or polysubstituted, identically or differently, by halogen, C₁-C₄alkyl, C₂-C₄alkenyl, C₁-C₄-haloalkyl or C₂-C₄haloalkenyl;
for C₅-C₇-cycloalkenyl which is optionally mono- or polysubstituted by identical or different substituents by halogen, C₁-C₄-alkyl or C₁-C₄-haloalkyl;
for optionally monosubstituted to trisubstituted by identical or different substituents phenyl, wherein as substituents may be mentioned halogen,
C₁-C₄-alkyl,
C₁-C₄-alkoxy-C₁-C₄-alkyl,
C₁-C₄-haloalkoxy,
C₁-C₄-haloalkyl,
C₁-C₄-alkoxy, which is optionally interrupted by another 1-3 oxygen atoms,
C₁-C₄ alkylthio,
C₁-C₄-haloalkylthio.

A is optionally monosubstituted to trisubstituted by identical or different substituents phenyl, benzyl, pheneth-1-yl, pheneth-2-yl, phenoxymethyl, phenylthiomethyl, phenoxyeth-1-yl, phenylthioeth-1-yl, phenoxyeth-2-yl and Styryl, where in each case as phenyl substituents may be mentioned halogen,
C₁-C₁₈-alkyl,
C₁-C₈-alkoxy-C₁-C₈-alkyl,
C₁-C₈-haloalkoxy,
C₁-C₄-haloalkyl,
C₁-C₁₈-alkoxy optionally interrupted by another 1-3 oxygen atoms,
C₁-C₁₈ alkylthio,
C₁-C₈ haloalkylthio,
3,4-difluoromethylenedioxo,
3,4-Tetrafluorethylendioxo,
optionally substituted by C₁-C₄-alkyl, C₃-C₆-cycloalkyl and / or halogen-substituted benzyliminooxymethyl,
each optionally substituted by C₁-C₆ alkyl, C₁-C₆ alkoxy, cyclohexyl or phenyl substituted cyclohexyl and cyclohexyloxy;
optionally mono- or disubstituted, identical or different, by halogen,
C₁-C₄ alkyl or C₁-C₄ haloalkyl-substituted pyridyloxy; in each case optionally mono- to trisubstituted by C₁-C₁₂-alkyl, halogen, C₁-C₄-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-halo genalkoxy, C₁-C₆-alkoxy-C₁-C₆-alkyl, C₁ -C₆-alkoxy-ethyleneoxy, C₁-C₆-alkylthio and / or C₁-C₆-haloalkylthio
substituted phenyl, benzyl, phenoxy, phenylthio, benzyloxy and benzylthio.

R is preferably hydrogen.

Particular preference may be given to compounds of the formula (I) in which the substituents have the following meaning:
B is C₁-C₆-alkyl which is optionally mono- or polysubstituted by identical or different substituents
Fluorine, chlorine, bromine, cyano, C₁-C₂-alkoxy and by any given case single or double, the same or different by fluorine, chlorine, C₁-C₄-alkyl, C₁-C₂-haloalkyl, C₁-C₂-alkoxy, C₁- C₂-haloalkoxy, C₁-C₂-alkylthio and / or C₁-C₂-haloalkylthio substituted phenyl, phenoxy, benzyloxy, phenylthio and benzylthio;
for optionally mono- or polysubstituted by identical or different fluorine, chlorine and / or bromine C₂-C₆-alkenyl;
for C₃-C₈-cycloalkyl which is optionally mono- or polysubstituted, identically or differently, by fluorine, chlorine, C₁-C₄-alkyl, C₂-C₄-alkenyl, C₁-C₂-haloalkyl with fluorine and / or chlorine as the halogen atoms and C₂ C₄-haloalkenyl with fluorine and / or chlorine as halogen atoms;
for C₅-C₇-cycloalkenyl which is optionally mono- or polysubstituted by identical or different substituents
Fluorine, chlorine, C₁-C₄-alkyl and C₁-C₂-haloalkyl with fluorine and / or chlorine as the halogen atoms;
for optionally monosubstituted to trisubstituted, identically or differently substituted phenyl, where the substituents mentioned are F, Cl, Br,
C₁-C₄-alkyl,
monosubstituted to disubstituted by identical or different substituents C 1 -C 4 -alkoxy substituted by F and / or Cl,
simply to five times, identically or differently by F and / or Cl substituted C₁-C₂-alkyl.

A particularly preferably represents phenyl which is optionally monosubstituted to monosubstituted by identical or different substituents, benzyl, pheneth-1-yl, phenethyl-2-yl, phenoxymethyl, phenylthiomethyl, phenoxyeth-1-yl, phenoxyeth-2-yl, phenylthioeth-1 -yl and styryl,
where each may be mentioned as phenyl substituents
F, Cl, Br,
C₁-C₁₈-alkyl,
C₁-C₆-alkoxy-C₁-C₈-alkyl,
monosubstituted to trisubstituted, identically or differently by F and / or Cl substituted C₁-C₈-alkoxy,
mono- or trisubstituted by identical or different substituents C₁-C₂-alkyl substituted by F and / or Cl,
C₁-C₁₈-alkoxy and - (OC₂H₄) _1-3 -O-C₁-C₆-alkyl, C₁-C₁₂-alkylthio,
monosubstituted to disubstituted, identically or differently substituted by F and / or Cl substituted C₁-C₈-alkylthio,
3,4-difluoromethylenedioxo,
3,4-tetrafluoroethylene dioxo, the groupings

each optionally substituted by C₁-C₄alkyl, C₁-C₄alkoxy, cyclohexyl or phenyl substituted cyclohexyl and cyclohexyloxy;
optionally mono- or disubstituted, identically or differently by F, Cl or CF₃-substituted pyridyloxy;
in each case optionally monosubstituted to trisubstituted, identical or differently, by C₁-C₁₂-alkyl, F, Cl, Br, CF₃, C₁-C₄-alkoxy, C₁-C₄-alkoxy, monosubstituted or disubstituted by identical or different substituents F and / or Cl, C₁-C₄-alkoxy-C₁-C₄-alkyl, C₁-C₄-alkoxy-ethyleneoxy, C₁-C₄-alkylthio, mono- or hexane, C₁-C₄-alkylthio monosubstituted or disubstituted by F and / or Cl
substituted phenyl, benzyl, phenoxy, phenylthio, benzyloxy and benzylthio.

R is particularly preferably hydrogen.

A and R of the general formula (I) may together preferably have the following spiro form cyclic rings, which in turn z. B. be substituted by radicals A. can:

where A can have the meanings given above, and
R² is hydrogen or one of the substituents indicated at A.

Very particular preference is given to compounds of the formula (1) in which the radical A is characterized by the following formula, either directly or via a bridge member Z may be bound to the oxazoline ring:

R¹ represents radicals according to the following Table 1
(R 2) _m is radicals according to the following Table 2

Table 1

Table 2

By way of example, the following radicals may be mentioned for the substituent A, either are bonded to the oxazoline ring directly or via a bridge member Z:

Furthermore, A can be radicals of the following formula a197

in which
E is optionally substituted alkanediyl and
X is hydrogen or halogen.

The following alkanediyl radicals E are preferably mentioned:

E1 -CF₂- E2 CF (CCl₂CF₃) - E3 -CFCl- E4 -CF₂-CF₂- E5 CF (CH₃) - E6 -CF₂-CFCl- E7 -C (CH₃) (CH₂F) - E8 -CF₂-CF (CH₃) - E9 -C (CH₃) (CH₂Cl) - E10 -CF₂-C (CH₃) ₂- E11 -C (CF₃) (CHClCF₃) E12 -CFCl-CFCl- E13 -CH (CH₂CF₃) - E14 -CF₂-CH (CH₃) - E15 -CH (CHClCF₃) - E16 -CF₂-CH (CF₃) -

By way of example, the following radicals may be mentioned for the substituent B:

By way of example, the following radicals may be mentioned for the substituent B:

By way of example, the following meanings are given for the divalent radical Z:

-CH₂-, -CH (CH₃) -, -CH₂CH₂-, -CH = CH-, -CH₂O-, -CH₂S-, -CH (CH₃) S-, -CH (CH₃) O-, -CH₂CH₂O-, -CH₂S (O) -, -CH₂-SO₂-.

The preparation of the oxazolines of the formula (I) is known in principle. she can done by

• a) amino alcohols of the formula (II) in which
  A and R have the meanings given above,
  with a carboxylic acid of the formula (III) B-COOH (III) in which
  B has the meaning given above,
  with a dehydrating agent and optionally in the presence of a diluent;
  or
• b) amide alcohols of the formula (IV) in which
  A, B and R have the meanings given above,
  with a dehydrating agent, optionally in the presence of a diluent;
• c) Amide derivatives of the formula (V) in which
  A, B and R have the meanings given above; and
  X is a leaving group such as halogen, alkylsulfonyloxy or aryl-sulfonyloxy,
  with a base, if appropriate in the presence of a diluent.

The in the process (a) for the preparation of the compounds of formula (I) as Aus Catalysts to be used amino alcohols are known and / or can after known methods by reduction of the corresponding amino acids (Heterocycles 9 (1978), 1277-1285; J. Org. Chem. 43 (1978), 2539-2541; Liebigs Ann Chem. 1980, 122-139; Tetrahedron Lett. 26 (1985), 4971-4974).

Those in process (a) for the preparation of the compounds of formula (I) further than Starting materials to be used carboxylic acids of the formula (III) are known organic synthesis chemicals, or in a known manner available.

The processes (a) and (b) are carried out using a water-withdrawing Performed by means. It can be the usual water in organic chemistry withdrawing funds are used. Preferably usable are sulfur acid, polyphosphoric acid (PPS), phosphorus (V) oxide, dicyclohexylcarbodiimide (DCC), phosphorus (V) sulfide and the triphenylphosphine / triethylamine / tetra system chloromethane.

As a diluent for carrying out the processes (a) to (c) the usual organic solvents are suitable. Preferably  usable are aliphatic, alicyclic or aromatic, optionally halo hydrogenated hydrocarbons, such as, for example, benzene, benzene, toluene, xylene, Chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, Chloroform, carbon tetrachloride; Ethers, such as diethyl ether, diisopropyl ether, dioxane, Tetrahydrofuran or ethylene glycol dimethyl or diethyl ether; Ketones, like Acetone, butanone or methyl isobutyl ketone; Nitriles, such as acetonitrile, propionitrile or benzonitrile; Amides, such as N, N-dimethylformamide and N, N-dimethylacetamide, N-methylpyrrolidone or hexamethylphosphoric triamide; Esters such as acetic acid methyl ester or ethyl acetate, as well as sulfoxides, such as dimethyl sulfoxide, optionally also alcohols such as methanol or ethanol.

The reaction temperatures can in carrying out the inventive Method (a) can be varied over a wider range. In general works at temperatures between 0 ° C and 150 ° C, preferably at temperatures between 10 ° C and 100 ° C.

The process (a) according to the invention is generally carried out under atmospheric pressure carried out. However, it is also possible under increased or decreased Pressure - generally between 0.1 bar and 10 bar - to work.

For carrying out the process (a) according to the invention, the respective be required starting materials in general in approximately equimolar amounts puts. However, it is also possible, one of the two Kom used in each case components in a larger excess. The reactions are in the general in a suitable diluent in the presence of a water carried out, and the reaction mixture is several hours stirred at the required temperature. The workup is done according to usual methods.

In a particular embodiment of the process (a) according to the invention instead of the carboxylic acids of the formula (III), corresponding nitriles can also be used be set, in which case preferably in place of a water-withdrawing By means of a catalyst, such as. As zinc (II) chloride is used.

The in process (b) for the preparation of the compounds of formula (I) as Aus Catalysts to be used amide alcohols are known and / or can after be prepared per se known methods.  

The amide alcohols of the formula (IV) are obtained, for example, if one of the Carboxylic acids of the formula (III) derived acid chlorides with amino alcohols of Formula (II) in the presence of an acid binder, such as. Triethylamine, pyridine, Potassium carbonate, sodium hydroxide or potassium t-butylate, and in the presence of a Diluent, such as. As toluene, chlorobenzene, acetone or acetonitrile, at Temperatures between 0 ° C and 100 ° C converts.

The acid chlorides derived from the carboxylic acids of formula (III) are widely known and / or can according to known methods, for example, by reacting the carboxylic acids of the formula (III) with a Halogenating agent such as thionyl chloride, optionally in the presence of a Diluent can be prepared.

For example, α-fluoro-βg, β-dichloro-acrylic acid chloride of the formula (VI) can be obtained by adding 2-fluoro-1,1,3,3,3-pentachloropropene optionally in Presence of a catalyst hydrolyzed. The catalysts used are Lewis Acids, inorganic acids and their acid salts, such as. B. FeCl₃, BF₃, H₂SO₄, HCl, KHSO₄, NaHSO₄ u. a. in question.

Depending on the reaction conditions (such as the residence time of the acid chloride in the reaction mixture) and of the added water amount of the primary α-fluoro-β, β-dichloro-acrylic acid chloride is given partially hydrolyzed to the corresponding acrylic acid, which subsequently for example, by reaction with thionyl chloride back into the acid chloride can be transferred.

The reaction temperatures may be in carrying out the process (b) in be varied over a larger area. Generally you work at Tem temperatures between -20 ° C and + 150 ° C, preferably at temperatures between 0 ° C and 100 ° C.

The process (b) according to the invention is generally carried out under atmospheric pressure carried out. However, it is also possible under increased or decreased Pressure - generally between 0.1 bar and 10 bar - to work.  

For carrying out the process (b) for the preparation of the compounds of Formula (I) is in general 1 per mole of amide alcohol of the formula (IV) to 20 moles, preferably 1 to 5 moles of dehydrating agent.

In a preferred embodiment of the process (b) according to the invention presented the amide alcohol of the formula (IV) in a diluent and the Dehydrating agent is then metered. The reaction mixture is added the required temperature until the end of the reaction and stirred closing worked up in the usual way.

The in process (c) for the preparation of the compounds of formula (I) as Aus The starting materials to be used amide derivatives are known and / or can according to be prepared per se known methods.

The amide derivatives of the formula (V) are obtained if appropriate amide alcohols of the formula (IV) with chlorinating agents, such as. B. thionyl chloride or Phosphorus (V) chloride, or with sulfonylating agents, such as. For example, methanesulfone acid chloride or p-toluenesulfonyl chloride in the usual way, optionally in Presence of a base and optionally in the presence of a diluent implements.

Process (c) is carried out in the presence of a base. Everyone comes here customary inorganic or organic bases into consideration. Preferably ver reversible are alkaline earth or alkali metal hydrides, hydroxides, amides, alkoxides, acetates, carbonates or bicarbonates, such as sodium hydride, Sodium amide, sodium methylate, sodium ethylate, potassium tert-butoxide, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, Calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium hydrogencarbonate, sodium bicarbonate or ammonium carbonate and ter tiary amines, such as trimethylamine, triethylamine, tributylamine, N, N-dimethylaniline, Pyridine, N-methylpiperidine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU).

The reaction temperatures may be in carrying out the process (c) in be varied over a larger area. Generally you work at Tem temperatures between -20 ° C and + 150 ° C, preferably at temperatures between 0 ° C and 100 ° C.  

Process (c) is generally carried out under normal pressure. However, it is also possible, under increased or reduced pressure - in general between 0.1 bar and 10 bar - to work.

For carrying out the process (c) for the preparation of the compounds of Formula (I) is used per mole of amide derivative of the formula (V) in general 1 to 3 mol, preferably 1.0 to 1.5 mol of a base.

In a preferred embodiment of process (c), the amide Derivative of the formula (V) and a base in a suitable diluent ver mixed; the mixture is at the required temperature until the end of Reaction stirred and then worked up in the usual way.

The active substances are suitable for combating warm-blooded toxicity animal pests such as insects, common ticks used in animal husbandry and animal breeding in livestock, breeding, zoo, laboratory, experimental and hobby animals occurrence. They are against all or individual stages of development of the Pests and against resistant and normally sensitive species of pests effective.

By controlling the animal pests diseases and their Transmission, death and reduced performance (eg in the production of Meat, milk, wool, hides, eggs) are prevented, so that by the use the active ingredients a more economical and easier animal husbandry is possible or becomes possible in certain areas.

The pests include:
From the order of Anoplura z. Haematopinus spp., Linognathus spp., Soleno potes spp., Pediculus spp., Pthims spp .;
from the order of Mallophaga z. Trimenopon spp., Menopon spp., Eomenacanthus spp., Menacanthus spp., Trichodectes spp., Felicola spp., Damalinea spp., Bobiola spp., Trinoton spp., Werneckiella spp., Lepikeutron spp .;
from the order of Diptera z. Chrysops spp., Tabanus spp., Musca spp., Hydrotaea spp., Muscina spp., Haematobosca spp., Haematobia spp., Stomoxys spp., Fannia spp., Glossina spp., Lucilia spp., Calliphora spp. Auchmeromyia spp., Cardylobia spp., Cochiomyia spp., Chrysomyia spp., Sarcophaga spp., Wohlfartia spp., Gaserophilus spp., Oesteromyia spp., Oedemagena sp., Hypoderma spp., Oestms spp., Rhinoestrus spp., Melophagus spp ., Hippobosca spp.

From the order of Siphonaptera z. Ctenocephalides spp., Echidnophaga spp., Ceratophyllus spp., Pulex spp.

Of the parasitic ticks, the following genera and species are Hyalomma spp., Rhipicephalus evertsi, Boophilus spp., Amblyomma spp., Dermacentor spp., Ixodes ricinus, Argas spp., Ornithodorus spp., Otobius spp .;
from the order of the Mesastigmata Dermanyssus spp., Pneumonyssus spp.

From the order of the Prostigmata z. Cheyletiella spp., Psorergates spp., Myobia spp., Demdex spp., Neotrombicula spp .; from the order of the astigmata z. Acarus spp., Myocoptes spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Neoknemidodoptex spp., Lytodites spp., Laminosioptes spp.

Particularly emphasized is the effect of the compounds of formula (I) against one-prized ticks. These include Boophilus spp., Hyalomma spp.

The domestic and farm animals include mammals such. Cattle, sheep, goats, Horses, pigs, dogs, cats, camels, water buffalo, donkey, rabbit, Fallow deer, reindeer, fur animals such as Mink, chinchilla, raccoon, birds like z. Chickens, turkeys, pheasants, geese, ducks.

Laboratory and experimental animals include mice, rats, guinea pigs, gold hamsters, dogs and cats.

Hobby animals include dogs and cats.

The application can be both prophylactic and therapeutic.

The application of the active ingredients is carried out directly or in the form of suitable Zube Preparations enteral, parenteral, dermal, nasal, by treatment of the environment or with the aid of active ingredient shaped body such. As strips, plates, bands, neck ribbons, ear tags, limb bands, marking devices.  

The enteral application of the active ingredients happens z. As orally in the form of powder, Suppositories, tablets, capsules, fasting, potions, granules, drenches, boluses, medicated feed or drinking water. The dermal application happens z. In Form of diving (dipping), spraying, bathing, washing, infusion (pour-on and spot-on) and powdering. The parenteral application happens z. In the form of injection (intramuscular, subcutaneous, intravenous, intraperitoneal) or by implants.

Suitable preparations are:
Solutions such as injectable solutions, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, infusion formulations, gels;
Emulsions and suspensions for oral or dermal application and for injection; Semi-solid preparations;

Formulations in which the active ingredient in an ointment base or in an oil is processed in water or water in oil emulsion base;

Solid preparations such as powders, premixes or concentrates, granules, pellets, Tablets, boluses, capsules; Aerosols and inhalants, active substance-containing moldings.

Injection solutions are administered intravenously, intramuscularly and subcutaneously.

Injection solutions are prepared by placing the active ingredient in a suitable Solvent is dissolved and possibly additives such as solubilizers, acids, Bases, buffer salts, antioxidants, preservatives are added. The Solutions are sterile filtered and bottled.

The following may be mentioned as solvents: Physiologically acceptable solvents such as Water, alcohols such as ethanol, butanol, benzyl alcohol, glycerine, carbon hydrogens, propylene glycol, polyethylene glycols, N-methylpyrrolidone, as well as Mixtures thereof.

The active ingredients can be optionally also in physiologically compatible vegetable or synthetic oils suitable for injection.  

As solubilizers may be mentioned: solvents which are the solution of the Wirk promote material in the main solvent or prevent its precipitation. Examples are polyvinylpyrrolidone, polyoxyethylated castor oil, polyoxyethylated Sorbitan.

Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol.

Oral solutions are applied directly. Concentrates are after previous Dilution to the application concentration applied orally. Oral solutions and concentrates are prepared as described above for the injection solutions provided that sterile work can be dispensed with.

Solutions for use on the skin are dribbled, brushed on rubbed, sprayed on, sprayed on or by dipping (dipping, bathing or Wa applied. These solutions are as above for the injection solutions described prepared.

It may be advantageous to add thickening agents in the preparation. Thickeners are: Inorganic thickeners such as bentonites, colloidal Silica, aluminum monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and methacrylates.

Gels are applied or painted on the skin or in body cavities brought in. Gels are made by using solutions similar to the Injek tion solutions have been prepared, with so much thickener be added that a clear mass with ointment-like consistency arises. When Thickeners are the thickeners given above set.

Pour-on formulations are infused on limited areas of the skin or injected, wherein the active ingredient either penetrates the skin and systemic or distributed on the body surface.

Pour-on formulations are prepared by mixing the active ingredient in suitable skin-compatible solvents or solvent mixtures dissolved, suspended  or emulsified. Optionally, other auxiliaries such as dyes, Absorption-promoting substances, antioxidants, light stabilizers, adhesives added.

The following may be mentioned as solvents: water, alkanols, glycols, polyethylene glycols, Polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenyl ethanol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, benzyl benzoate, ethers such as alkylene glycol alkyl ethers such as dipropylene glycol monomethyl ether, diethylene glycol mono-butyl ether, ketones such as acetone, methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, Dimethylacetamide, N-methylpyrrolidone, 2-dimethyl-4-oxy-methylene-1,3-dioxolane.

Dyes are all dyes approved for animal use that have been dissolved or suspended.

Absorption promoting substances are z. B. DMSO, spreading oils such as Isopro pylmyristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, Fatty alcohols.

Antioxidants are sulfites or metabisulfites such as potassium metabisulfate, Ascor binsäure, Butylhydroxytoluol, Butylhydroxyanisol, Tocopherol.

Light stabilizers are z. B. substances from the class of benzophenones or Novan tisolsäure.

Adhesives are z. As cellulose derivatives, starch derivatives, polyacrylates, natural Polymers such as alginates, gelatin.

Emulsions can be administered orally, dermally or as an injection.

Emulsions are either water-in-oil type or oil-in-water type.

They are made by adding the active ingredient either in the hydrophobic or dissolved in the hydrophilic phase and this with the aid of suitable Emulsifiers and optionally other auxiliaries such as dyes, resorp promoting substances, preservatives, antioxidants, light stabilizers, viscosity-increasing substances homo with the solvent of the other phase genisiert.  

As hydrophobic phase (oils) may be mentioned: paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic / capric acid biglycerid, triglyceride mixture with vegetable fatty acid Ket tenlänge C _8-12 or other specially selected natural fatty acids, partial glyceride mixtures saturated or unsaturated, possibly hydroxyl-containing fatty acids, mono- and diglycerides of C₈ / C₁₀ fatty acids.

Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, lauric acid hexyl ester, dipro pyleneglycol pelargonate, esters of a medium-chain branched fatty acid with saturated fatty alcohols of chain length C₁₆-C₁₈, isopropyl myristate, isopro pylpalmitate, Cypryl / capric acid esters of saturated fatty alcohols of chain length C₁₂-C₁₈, isopropyl stearate, oleyl oleate, oleic acid decyl ester, ethyl oleate, milk acid ethyl esters, waxy fatty acid esters, such as artificial duckbill glands fat, Dibutyl phthalate, diisopropyl adipate, the latter related ester mixtures u. a.

Fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol, oleyl alcohol.

Fatty acids such. As oleic acid and its mixtures.

As hydrophilic phase may be mentioned:
Water, alcohols such. As propylene glycol, glycerol, sorbitol and their mixtures.

As emulsifiers may be mentioned: nonionic surfactants, for. Polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ethers;
ampholytic surfactants such as di-Na-N-lauryl-β-iminodipropionate or lecithin;
anionic surfactants such as Na lauryl sulfate, fatty alcohol ether sulfates, mono / dialkyl polyglycol ether orthophosphoric acid ester monoethanolamine salt;
cationic surfactants such as cetyltrimethylammonium chloride.

Other auxiliaries which may be mentioned are: viscosity-increasing and the emulsion sta bilisierende substances such as carboxymethylcellulose, methylcellulose and others  Cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, Polyvinyl pyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and Maleic anhydride, polyethylene glycols, waxes, colloidal silica or Mixtures of the listed substances.

Suspensions may be administered orally, dermally or as an injection. you are prepared by gege the active ingredient in a carrier liquid if appropriate, with the addition of further auxiliaries, such as wetting agents, dyes, resorp promoting substances, preservatives, antioxidants light stabilizer sus pendiert.

As carrier liquids are all homogeneous solvents and Lösungsge called mixed.

As wetting agents (dispersants), the surfactants mentioned above ge Nannt.

As further auxiliaries mentioned above.

Semi-solid preparations may be administered orally or dermally. You under differ from the suspensions and emulsions described above only by their higher viscosity.

For the preparation of solid preparations, the active ingredient with suitable carrier optionally mixed with the addition of excipients and in the desired shape brought.

Suitable carriers are all physiologically compatible solid inert substances. All such are inorganic and organic substances. Inorganic substances are z. For example, common salt, carbonates such as calcium carbonate, bicarbonates, aluminum oxides, silicas, clays, fumed or colloidal silica, Phos phosphates.

Organic substances are z. As sugar, cellulose, food and feed such Milk powder, animal meal, cereal flours and meals, starches.  

Excipients are preservatives, antioxidants, dyes that are already further have been listed above.

Other suitable auxiliaries are lubricants and lubricants such. B. Magne sium stearate, stearic acid, talc, bentonites, decay promoting substances such as Starch or crosslinked polyvinylpyrrolidone, binders such. As starch, Gela tine or linear polyvinylpyrrolidone and dry binders such as mikrokri stalline cellulose.

The active substances can also be mixed with synergists in the preparations or with other active ingredients.

Ready-to-use preparations contain the active substance in concentrations of 10 ppm to 20 wt .-%, preferably from 0.1 to 10 wt .-%.

Preparations that are diluted before use contain the active substance in Concentrations of 0.5 to 90 wt .-%, preferably from 5 to 50 wt .-%.

In general, it has proven to be advantageous to use amounts of about 1 to 100 mg of active ingredient per kg of body weight per day to achieve effective results to administer.

As active ingredient (1) is used in the following examples, the compound of Formula:

2- (2,6-difluorophenyl) -4- [4- (4-difluoromethoxyphenyl) phenyl] -2-oxazol-in.  

example 1

SC (suspension concentrate) formulation:

368 g of active ingredient 1
35 g block polymer of emulsifier ethylene oxide and propylene oxide
12 g of ditolyl ether sulfonate-formaldehyde condensate (emulsifier)
3.5 g of water-soluble polyvinyl alcohol
58.0 g NH₄Cl
116.0 g urea
1.2 g (37% aqueous hydrochloric acid)
4.6 g of xanthan gum
560.5 g of distilled water

Example 2

WP (dispersible powder) formulation:

25.0 g of active ingredient 1
1.0 g of diisobutylnaphthalene-Na-sulfonate
10.0 g of n-dodecylbenzylsulfonic acid calcium
12.0 g of highly dispersed silicic acid-containing alkylaryl polyglycol ether
3.0 g of ditolyl ether sulfonate-formaldehyde condensate (emulsifier)
2.0 g of ®Baysilon-E, a silicone defoamer from Bayer AG
2.0 g of finely divided silica and
45.0 g of kaolin

Example 3

SL (water soluble concentrate) formulation:

18.3 g of active ingredient 1
2.5 g of neutral emulsifier based on alkylaryl polyglycol ether
3.5 g of sodium sulfosuccinic diisooctyl ester
38.4 g of dimethyl sulfoxide and
37.5 g of 2-propanol

Example 4

SL (water soluble concentrate) formulation:

185, g active ingredient 1
5.0 g of diisooctyl sodium sulfonosuccinate and
76.5 g of dimethyl sulfoxide

are made up of a 100g shampoo formulation

44.4% by weight of Marlon AT 50, a triethanolamine salt of alkylbenzenesulfonic acids from Huls AG
11.1% by weight of Marlon A 350, sodium salt of alkylbenzenesulfonic acids from Huls AG
3.0% by weight of condensation product of oleic acids and diethanolamine from Huls AG and
41.5% by weight of polyethylene glycol

added.

Example 5

Spray formulation consisting of:

2.0 g of active ingredient 1
10.0 g of dimethyl sulfoxide
35.0 g of 2-propanol and
53.0 g of acetone

Preparation Examples example 1

To 1 g (6 mmol) of 4-t-butylthiophenol in 50 ml of methanol is added 0.3 while stirring g (6 mmol) of sodium methylate (slightly exothermic). Dripping to this solution 2.1 g (6 mmol) of 2- (2,6-difluorophenyl) -4- (p-tolylsulfonyloxymethyl) at 40 ° C 1,3-oxazoline in 30 ml of methanol. The reaction mixture is allowed to stand for 2 hours 40 ° C and then stirred for 16 hours under reflux. After that it will be Distilled solvent, the residue taken up in 100 ml of ethyl acetate and washed three times with 50 ml of water. The solvent is removed and the residue on silica gel column chromatography with toluene / toluene, ethyl acetate 10: 1 as the eluent chromatographed.

This gives 0.9 g (41.6% of theory) of 2- (2,6-difluorophenyl) -4- (4-t-butylphenylthio methyl) -1,3-oxazoline with a distribution coefficient log P (octanol / water) of 4.64 and a refractive index n = 1.5660.  

Preparation of the starting compound Example 1a

To 5.3 g (0.023 mol) of 2- (2,6-difluorophenyl) -4-hydroxymethyl-1,3-oxazoline in 100 ml of ethyl acetate are added 5.6 ml (0.069 mol) of pyridine and then added dropwise 4.4 g (0.023 mol) of p-toluenesulfonyl chloride in 50 ml of ethyl acetate. The rising Temperature at 50 ° C on. The mixture is stirred for 2.5 hours at 50 ° C and then 8 Hours under reflux. The organic phase is washed four times with 50 ml each Washed water and the solvent distilled off. The residue is over Silica gel column chromatography with eluent toluene under gradient with Eluent ethyl acetate chromatographed.

This gives 2.1 g (24.8% of theory) of 2- (2,6-difluorophenyl) -4- (p-tolylsulfonyloxy methyl) -1,3-oxazoline with a distribution coefficient log P (octanol / water) of ~ 2.68 and a refractive index n = 1.5491.

Example 1b

6.5 g (0.0168 mol) of N- [1-chloro-3- (4-t-butylbenzoyloxy) -2-propyl] -2,6-difluorobenzene amide are dissolved in 100 ml of methanol. 2 ml (0.033 mol) of 45% are added Sodium hydroxide solution and allowed to stir for 4 hours under reflux. After distilling off the Solvent, the residue is taken up in 100 ml of ethyl acetate, three times washed with 50 ml of water and distilled off the solvent.  

This gives 2.8 g (72% of theory) of 2- (2,6-difluorophenyl) -4-hydroxymethyl-1,3- oxazoline of melting point 82 ° C.

Example 1c

9 g (0.023 mol) of N- [1-hydroxy-3- (4-t-butylbenzoyloxy) -2-propyl] -2,6-difluorobenzene amide are suspended in 60 ml carbon tetrachloride, with 1.7 ml (0.023 mol) Thionyl chloride and heated for 1.5 hours under reflux. The solvent is distilled off.

This gives 9.3 g of N- [1-chloro-3- (4-t-butylbenzoyloxy) -2-propyl] -2,6-difluorobenz amide with a distribution coefficient log P (octanol / water) of 3.86.

Example 1d

To 21 g of 2-amino-3- (4-t-butylbenzoyloxy) -1-propanol hydrochloride in 400 ml of vinegar first 21.9 ml (0.158 mol) of triethylamine are added and ester then at 0 ° C 13.9 g of 2,6-Difluorbenzoesäurechlorid in 20 ml of ethyl acetate dropwise. The mixture is stirred for 1 hour at 20 ° C; the precipitation is going down sucks, the organic phase washed three times with 100 ml of water, the Lö Distilled off solvent and the residue is stirred with diisopropyl ether.

After drying, 14 g (48% of theory) of N- [1-hydroxy-3- (4-t butylbenzoyloxy) -2-propyl] -2,6-difluorobenzamide having a partition coefficient log P (octanol / water) of 2.82.  

Example 2

To 4.3 g (0.013 mol) of N- [2-chloro-1- (4-t-butylphenyl) ethyl] -2,2-bis (fluoromethyl) - propionic acid amide in 100 ml of methanol at reflux 1.6 ml (0.026 mol) 45% sodium hydroxide solution in 5 ml of water. The reaction mixture is allowed to reach 1 Stirring under reflux and then concentrated by distilling off the Solvent. The residue is stirred with water, the precipitate sucked and dried.

This gives 3.8 g (99% of theory) of 2- (1,3-difluoro-2-methyl-prop-2-yl) -4- (4-t butylphenyl) -1,3-oxazoline of melting point 62-63 ° C.

Preparation of the starting compounds for Example 2 Example 2a (Step 1)

To 3.9 g (0.02 mol) of 2-amino-2- (4-t-butylphenyl) -1-ethanol in 150 ml of ethyl acetate Are added 3.3 ml (0.024 mol) of triethylamine and then added at 0 ° C. 3.7 g (0.024 mol) of 2,2-bis (fluoromethyl) -propionic acid chloride dropwise. because After allowing to warm to room temperature and stirred overnight. Subsequently, the precipitate is filtered off, the filtrate several times with water washed, the organic phase separated, dried over sodium sulfate, filtered and concentrated.  

4.5 g (71.9% of theory) of N- [2-hydroxy-1- (4-t-butylphenyl) -ethyl] are obtained. 2,2-bis (fluoromethyl) -propionamide of melting point 141 ° C.

Example 2b (Level 2)

To 4.5 g (0.0144 mol) of N- [2-hydroxy-1- (4-t-butylphenyl) ethyl] -2,2-bis (fluor ethyl) -propionamide (see Step 1) in 100 ml of carbon tetrachloride Added 1.05 ml (0.0144 mol) of thionyl chloride. The reaction mixture is allowed react for 1 hour under reflux. After distilling off the solvent 4.3 g (90% of theory) of N- [2-chloro-1- (4-t-butylphenyl) ethyl] -2,2-bis- (fluoromethyl) -propionamide of melting point 98 ° C.

Example 3

To a solution of 2.0 g (5.2 m mol) of n- [1- (4-tert-butylphenyl) -2-chloroethyl] - 2,3,5,6-Tetrafluorbenzoesäureamid in 30 ml of tetrahydrofuran are added 0.75 g (6.7 m mol) of potassium tert-butoxide and stirred at 50 ° C. After 3 hours you pour that Reaction mixture on water and extracted with methylene chloride. The organic ones Extracts are washed with water, dried over magnesium sulfate and then concentrated in vacuo. The residue is purified by column chromatography graphie (eluent chloroform).

This gives 0.8 g (44.7% of theory) of 4- (4-tert-butylphenyl) -2- (2,3,5,6-tetra fluorophenyl) -1,3-oxazoline with a distribution efficiency log P (octanol / water) of 4.70 (pH 7.4).  

Preparation of the starting compounds for Example 3 Example 3a

2.1 g (5.7 m mol) of N- [1- (4-tert-butylphenyl) -2-hydroxyethyl] -2,3,5,6-tetrafluoro benzoic acid amide in 50 ml of toluene with 5 ml of thionyl chloride for 18 hours under Reflux heated. Subsequently, in the vacuum, excess thionyl chloride and the solvent removed.

This gives 2.2 g (100% of theory) of N- [1- (4-tert-butylphenyl) -2-chloroethyl] - 2,3,5,6-tetrafluorobenzoic acid amide which is reacted further directly.

Example 3b

To a solution of 1.45 g (7.5 m mol) of 2-amino-2- (4-tert-butylphenyl) ethanol and 0.75 g (7.5 m mol) of triethylamine in 20 ml of methylene chloride is added dropwise Stirring at 20 ° C. 1.6 g (7.5 m mol) of 2,3,5,6-tetrafluorobenzoyl chloride, dissolved in 10 ml of methylene chloride, too. After boiling overnight, dilute with methylene chloride, washed with water and concentrated the organic phase in vacuo. The The residue is stirred with a little n-pentane and filtered with suction.

This gives 2.3 g (83.1% of theory) of N- [1- (4-tert-butylphenyl) -2-hydroxyethyl] - 2,3,5,6-tetrafluorobenzoic acid amide of melting point 158-160 ° C.  

Example 4

3.4 g (8.7 mmol) of 2-phenyl-S- (2,6-dichlorobenzoylamino) -5-hydroxymethyl-1,3-dioxane are suspended in 50 ml of toluene and with 2 g of thionyl chloride for 24 hours 80 ° C stirred. Then excess thionyl chloride and toluene in the water distilled off jet vacuum.

The residue is taken up in 50 ml of toluene and 0.9 g of potassium t-butylate added. The reaction mixture is then subjected to thin-layer chromatography Control stirred at 50 ° C. After complete reaction, the Lö washed with water and then the organic phase in water concentrated vacuum. The residue is chromatographed on silica gel with cyclohexane / vinegar acid ethyl ester (vol. 2: 1) chromatographed.

This gives 1 g (31% of theory) of 8-phenyl-2- (2,6-dichloro-phenyl) -1-aza-3,7,9-tri oxa-spiro [4.5] dec-1-ene of melting point 158 ° C-160 ° C.

Preparation of the starting compounds for Example 4 Example 4a

104 g (0.35 mol) of 2- (4-t-butylphenyl) -5-hydroxymethyl-5-nitro-1,3-dioxane in 1 liter of ethanol with 10 ml of triethylamine and 10 g of palladium / carbon and added 3 Days hydrogenated at 20 ° C and 30 bar. Then it is filtered, the filtrate in a water jet  Concentrated vacuum, the residue digested with n-hexane and this crystalline product isolated by suction.

This gives 43 g (47% of theory) of 2- (4-t-butylphenyl) -5-hydroxymethyl-5-amino 1,3-dioxane of melting point 138 ° C-140 ° C.

Example 4b

5 g (20 mmol) of 2- (4-t-butyl-phenyl) -5-amino-5-hydroxymethyl-1,3-dioxane are dissolved in 80 ml of methylene chloride with 5 ml of triethylamine. Then at 0 ° C a Solution of 4.5 g (20 mmol) of 2,6-dichloro-benzoyl chloride in 5 ml of methylene chloride is added dropwise and the mixture is stirred for 15 hours at 20 ° C. Subsequently, will washed with 0.5 N sodium hydroxide solution, the organic phase with sodium sulfate ge dries and filtered. The filtrate is concentrated in a water-jet vacuum, the rear was crystallized by digestion with n-hexane and the product isolated by suction.

This gives 7.2 g (83% of theory) of 2- (4-t-butylphenyl) -5-hydroxymethyl-5- (2,6- dichloro-benzoyl-amino) -1,3-dioxane of melting point 178 ° C-180 ° C.

Example 5

0.67 g (2 mmol) of N- (2-hydroxy-1 (3,4-difluoromethylenedioxy-phenyl) -ethyl) -2,6-di fluoro-benzamide are placed in 15 ml of toluene and 0.27 ml (4 mmol) of thionyl  Chloride are added at 20 ° C to it. The reaction mixture is then 3 hours heated to reflux. After cooling, the residue is concentrated in 15 ml of tetra hydrofuran and after addition of 0.23 g (2 mmol) of potassium t-butylate The mixture is stirred for one hour at 50 ° C. Then it narrows, the return was shaken with methylene chloride / water, the organic phase over Dried magnesium sulfate and filtered. The filtrate is concentrated and the reverse was recrystallized from methylene chloride / petroleum ether.

This gives 0.13 g (20% of theory) of 2- (2,6-difluoro-benzoyl) -4- (3,4-difluoro methylenedioxy-phenyl) -2-oxazoline of melting point 86 ° C.  

Preparation of the starting materials for Example 5 Example 5a

2.31 g (10 mmol) of α-amino-α- (3,4-difluoromethylenedioxy-phenyl) -acetic acid are charged with 0.91 g (24 mmol) of sodium borohydride in 30 ml of tetrahydrofuran at 0 ° C and a solution of 3 Add 0.05 g (24 mmol) of iodine in 10 ml of tetrahydrofuran dropwise. After the evolution of gas has subsided, the mixture is heated under reflux for 16 hours. Then, after cooling with methanol ver thinned until a clear solution is formed. It is concentrated, the residue taken up in 20 ml of 20% 2N sodium hydroxide solution and extracted three times with 50 ml of methylene chloride. The combined organic phases are dried over magnesium sulfate and filtered. After evaporation of the filtrate, the crude product obtained as residue is reacted further without further purification.
Yield: 1.52 g (70% of theory),
Melting point: 70 ° C.

Example 5b

1.0 g (2 mmol) of N- [2- (2,6-difluorobenzoyloxy) -1- (3,4-difluoromethylenedioxy-phenyl) -ethyl] -2,6-difluorobenzamide are introduced into 2 ml of methanol, at 20 C., 2 ml of 1N sodium hydroxide solution are added and the mixture is heated to reflux for one hour with stirring. After cooling, it is shaken three times with 50 ml of methylene chloride each time. The combined organic phases are dried over magnesium sulfate and filtered. The filtrate is concentrated and the crude product obtained as residue is further reacted without further purification.
Yield: 0.67 g (93% of theory),
Melting point: 158 ° C.

Claims (4)

1. Use of compounds of the formula (I) in which
B is optionally substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl,
A is aryl, aryloxy, heteroaryl, heteroaryloxy which are optionally substituted and which are optionally bonded via a divalent radical Z to the oxazoline ring,
R is hydrogen or together with A and the adjacent C atom for a spiro-cyclic 3- to 6-membered ring which may optionally contain one or more heteroatoms of the group O, S, N and to which optionally a further ring is fused, wherein the system is optionally substituted,
for controlling parasitic insects and human and animal ticks. 2. Agents against parasitizing insects and ticks on humans and humans Animal characterized by a content of at least one compound of Formula (I) according to claim 1. 3. Process for the preparation of agents against parasitic insects and one-pronged ticks on humans and animals, characterized in that one Compounds of formula (I) according to claim 1 with extenders and / or mixed surface-active agents.   4. Use of compounds of the formula (I) according to claim 1 to Preparation of agents against parasitic insects and ticks in humans and animals.