WO1996041534A1 - Use of oxazolines for combatting ectoparasites - 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

 USE OF OXAZOLINES FOR CONTROLLING EKTOPARASITES

The present invention relates to the use of oxazolines for controlling ectoparasites and to ectoparasiticidal compositions which contain oxazolines.

Oxazolines and their production and use as insecticides and acaricides in crop protection and against certain mites on animals are already known. However, nothing is known about their use against ectoparasites and, above all, against insects and host ticks.

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

in welcher

in which

B represents optionally substituted alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl,

A represents aryl, aryloxy, heteroaryl, heteroaryloxy which are optionally substituted and which are optionally bonded to the oxazoline ring via a divalent radical Z,

R stands for hydrogen or together with A and the adjacent C atom for a spirocyclic 3- to 6-membered ring which may optionally contain one or more heteroatoms of the group O, S, N and to which another ring may be fused, where the system is optionally substituted,

for controlling parasitic insects and single-ticks on humans and animals.

The compounds of the formula (I) are, for example, the 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 100 546; JP-OS H6 100 560, JP-OS H6 73 030, EP-OS 345 775, EP-OS 432 661, EP-OS 553 623, WO 93/22 297, WO 93/25 079.

Special reference is hereby made to the preferred connecting groups as well as individual compounds and production processes in these publications.

Compounds of the general formula (I) in which the definitions of the substituents have the following meanings are preferred:

Optionally substituted alkyl alone or as part of a radical in the general formulas means straight-chain or branched alkyl having preferably 1 to 20, in particular 1 to 18, carbon atoms. Exemplified and preferred are optionally substituted methyl, ethyl, n- and i-propyl, n-, i- and t-butyl, neopentyl, undecyl, dodecyl, pentadecyl, octadecyl.

Optionally substituted alkenyl and the alkenyl portion of a residue such as e.g. optionally substituted alkenyloxy and alkenylthio in general

Formulas mean straight-chain or branched alkenyl with preferably 2 to 6, in particular 2 to 4, carbon atoms. Exemplarily and preferably, optionally substituted ethenyl, propenyl (1), propenyl (2) and butenyl (3) may be mentioned.

Optionally substituted alkynyl and the alkynyl portion of a residue such as e.g. optionally substituted alkynyloxy and alkynylthio in the general formulas mean straight-chain or branched alkynyl having preferably 2 to 6, in particular 2 to 4, carbon atoms. Substituted ethynyl, propynyl (1), propynyl (2) and butynyl (3) may be mentioned by way of example and in preference.

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. Examples and preferably, optionally substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl may be mentioned. 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. Exemplified and preferred are optionally substituted methoxy, ethoxy, n- and i-propoxy and n-, o- and t-butoxy.

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. Exemplarily and preferably, optionally substituted methylthio, ethylthio, n- and i-propylthio, n-, o- and t-butylthio may be mentioned.

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

Haloalkyl alone or as part of a residue such as e.g. Haloalkoxy or haloalkylthio 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 identical or different halogen atoms, fluorine, chlorine and bromine, in particular fluorine and chlorine, preferably being halogen atoms. Examples include trifluoromethyl, chlorodifluoromethyl, bromomethyl, 2,2,2-trifluoroethyl and pentafluoroethyl.

Optionally substituted aryl alone or as part of a residue such as e.g. Aryloxy, arylthio, arylalkyl in the general formulas preferably means optionally substituted phenyl or naphthyl, in particular phenyl.

Optionally substituted aralkyl in the general formulas means optionally substituted aralkyl in the aryl part and / or alkyl part with 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 part , wherein the alkyl part can be straight-chain or branched. Substituted benzyl and phenylethyl may be mentioned as examples and preferably. 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 follow the aromatic principle of the Hückel rule . The heteroatoms are oxygen, sulfur or nitrogen. Exemplified and preferably, optionally substituted thienyl may be mentioned.

The optionally substituted radicals of the general formula (I) can carry one or more, preferably 1 to 3, in particular 1 to 2 identical or different substituents. The following are examples of preferred substituents:

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, neopentyl, hexadecyl, octadecyl; Alkoxy preferably having 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 with 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; Haloalkyl having preferably 1 to 4, in particular 1 or 2, carbon atoms and preferably 1 to 5, in particular 1 to 3, halogen atoms, the halogen atoms being identical or different and being halogen atoms, preferably fluorine, chlorine or bromine, in particular fluorine, such as difluoromethyl,

Trifluoromethyl; Hydroxy; Halogen, preferably fluorine, chlorine, bromine, especially fluorine, chlorine; Cyano; Nitro; Amino; Monoalkyl- and dialkylamino with 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 formyl, alkyl carbonyl such as acetyl, arylcarbonyl such as benzoyl; Carboxyl; Carboxy with preferably 2 to 4, in particular 2 or 3, carbon atoms, such as carbomethoxy and carboethoxy; Alkylsulfinyl with 1 to 4, in particular 1 to 2, carbon atoms, haloalkylsulfinyl with 1 to 4, in particular 1 to 2, carbon atoms and 1 to 5 halogen atoms, such as trifluoromethylsulfinyl; Sulfonyl (-SO ₃ H); Alkylsulfonyl preferably having 1 to 4, in particular 1 or 2, carbon atoms, such as methyl sulfonyl and ethylsulfonyl; Haloalkyl sulfonyl having 1 to 4, in particular 1 to 2, carbon atoms and 1 to 5 halogen atoms, such as trifloromethylsulfonyl, perfluoro-t, n, s-butylsulfonyl; Arylsulfonyl preferably having 6 or 10 aryl carbon atoms, such as phenylsulfonyl; Acyl; Aryl; Aryloxy; Heteroaryl; Heteroaryloxy; which in turn is one of the above

H _ l can carry substituents as well as the formimino radical C = N-O-alkyl

Compounds of the formula (I) in which the substituents have the following meanings are preferred:

B is C _j -CG-alkyl which is optionally monosubstituted or polysubstituted by identical or different substituents from halogen, cyano, C ₁ -C ₄ alkoxy such as so¬ through each case optionally mono- to trisubstituted by identical or different halogen , C _r C ₄ alkyl, C _] -C ₄ haloalkyl, C ₁ -C ₄ alkoxy, C _r C ₄ haloalkoxy, C ₁ -C ₄ alkylthio and / or C _j -C ₄ haloalkylthio substituted phenyl , Phenoxy, benzyloxy, phenylthio and benzylthio;

for optionally mono- or polysubstituted, identically or differently, C ₂ -C ₈ -alkenyl substituted by halogen;

for C ₃ -C ₈ cycloalkyl which is optionally mono- or polysubstituted, identically or differently, by halogen, C _r C ₄ alkyl, C ₂ -C ₄ alkenyl, C _r C ₄ haloalkyl or C ₂ -C ₄ -

Haloalkenyl;

for C ₅ -C ₇ cycloalkenyl which is optionally mono- or polysubstituted, identical or different, by halogen, C _j -C ₄ alkyl or C _j - ^ haloalkyl;

optionally monosubstituted, suitable substituents being up to tetrasubstituted by identical or different substi¬ tuiertes phenyl are halogen, C _r C ₄ alkyl, C _j -C ₄ - alkoxy-C -C ₄ alkyl, C _j -C ₄ -haloalkoxy ,

C _j - haloalkyl,

C _j -C ₄ alkoxy, which is optionally interrupted by a further 1-3 oxygen atoms, C _r C ₄ - alkylthio, C _] -C haloalkylthio.

A represents phenyl, benzyl, pheneth-1-yl, pheneth-2-yl, phenoxymethyl, which is optionally monosubstituted to tetrasubstituted or substituted differently,

Phenylthiomethyl, phenoxyeth-1-yl, phenylthioeth-1-yl, phenoxyeth-2-yl and styryl, each of which may be mentioned as a phenyl substituent

Halogen,

C _r C ₁₈ alkyl,

C _r C ₈ alkoxy-C _r C ₈ alkyl,

C _j -C ₈ haloalkoxy, C _r C ₄ haloalkyl,

C _j -C _j g alkoxy, which is optionally interrupted by a further 1-3 oxygen atoms,

C _r C ₁₈ alkylthio,

C _j -C ₈ haloalkylthio, 3, 4-difluoromethylene dioxo,

3,4-tetrafluoroethylene dioxo, optionally substituted by C ₁ -C ₄ alkyl, C ₃ -C ₆ cycloalkyl and / or halogen benzyliminooxymethyl, each optionally substituted by C _r C ₆ alkyl, CC ₆ - alkoxy, cyclohexyl or phenyl cyclohexyl and cyclohexyloxy; if necessary, single or double, identical or different

Halogen,

C _] -C ₄ alkyl or C _] -C ₄ .haloalkyl substituted pyridyloxy; each optionally single to triple, identical or different, by C _r C _{] 2} -alkyl, halogen, C _r C ₄ -haloalkyl, C _r C ₆ -alkoxy, -C ₈ -haloalkalkoxy, C ₁ -C ₆ -alkoxy- C ₁ -C ₆ alkyl, C _r C ₆ alkoxy-ethyleneoxy, C _r C ₆ -

Alkylthio and / or C ₁ -C ₆ haloalkylthio substituted phenyl, benzyl, phenoxy, phenylthio, benzyloxy and benzylthio.

R preferably represents hydrogen.

Compounds of the formula (I) in which the substituents have the following meanings are particularly preferred: B stands for C _j -Cg alkyl, which is optionally mono- or polysubstituted by identical or different substituents

Fluorine, chlorine, bromine, cyano, C ₁ -C ₂ alkoxy and, if appropriate, once or twice, identically or differently, by fluorine, chlorine, C _r C ₄ alkyl, C _r C ₂ haloalkyl, C _r C ₂ -alkoxy, C _r C ₂ -haloalkoxy,

C _j -C ^ alkylthio and / or C _] -C ₂ haloalkylthio substituted phenyl, phenoxy, benzyloxy, phenylthio and benzylthio;

for C ₂ -C ₆ alkenyl optionally substituted one or more times, identically or differently, by fluorine, chlorine and / or bromine;

for C ₃ -C ₈ cycloalkyl, which is optionally mono- or polysubstituted, identical or different, by

Fluorine, chlorine, C _r C ₄ alkyl, C ₂ -C ₄ alkenyl, C _r C ₂ haloalkyl with fluorine and / or chlorine as halogen atoms and C ₂ -C ₄ haloalkenyl with fluorine and / or chlorine as halogen atoms;

for C ₅ -C ₇ cycloalkenyl, which is optionally mono- or polysubstituted, identical or differently substituted by

Fluorine, chlorine, C _j -C ₄ - alkyl and C _j -C ₂ haloalkyl having fluorine and / or chlorine as halogen atoms;

for phenyl which is optionally monosubstituted to tetrasubstituted, identically or differently, where mentioned as substituents

F, Cl, Br, C _r C ₄ alkyl, one to six times, by identical or different F and / or Cl substi¬ tuiertes C _j - _j -alkoxy which is monosubstituted to pentasubstituted by identical or different F and / or Cl substi ¬ tuiert C _j -C ₂ alkyl.

A particularly preferably represents phenyl, benzyl, pheneth-1-yl, pheneth-2-yl, phenoxymethyl, phenylthiomethyl, phenoxyeth-1-yl, phenoxyeth-2-yl, phenylthioeth, each optionally monosubstituted to tetrasubstituted by identical or different substituents -1-yl and styryl, each of which may be mentioned as a phenyl substituent F, Cl, Br, C _r C ₁₈ alkyl, C, -C ₆ alkoxy-C _r C ₈ alkyl which is monosubstituted to hexasubstituted by identical or different F and / or Cl substi¬ tuiertes C _j -C ₈ -alkoxy which is monosubstituted to pentasubstituted by by identical or different F and / or Cl substi¬ tuiertes C _j -C ₂ alkyl,

C _r C ₁₈ alkoxy and - (OC ₂ H ₄ ) ₁ . ₃ -OC _r C ₆ alkyl, C _r C ₁₂ alkylthio, single to six-fold, identical or different C _r C ₈ alkylthio substituted by F and / or Cl,

3,4-difluoromethylene dioxo, 3, 4-tetrafluoroethyl endioxo, the groupings

each optionally by CC ₄ alkyl, C _r C ₄ alkoxy, cyclohexyl or

Phenyl substituted cyclohexyl and cyclohexyloxy; pyridyloxy optionally substituted once or twice, identically or differently by F, Cl or CF ₃ ; in each case optionally up to three times, identically or differently, by C _r C ₁₂ alkyl, F, Cl, Br, CF ₃ , C _r C ₄ alkoxy, simply up to six times, identically or differently, CC ₄ - substituted by F and / or Cl Alkoxy, CC ₄ -

Alkoxy-C _r C ₄ -alkyl, C _j -C ₄ -alkoxy-ethyleneoxy, C _r C ₄ -alkylthio, simple to sixfold, identical or differently substituted by F and / or Cl

C _r C ₄ alkylthio substituted phenyl, benzyl, phenoxy, phenylthio, benzyloxy and benzylthio.

is particularly preferably hydrogen. A and R of the general formula (I) can preferably together form the following spirocyclic rings, which in turn can be substituted, for example, by radicals A:

wobei A die zuvor angegebenen Bedeutungen haben kann und

where A can have the meanings given above and

R represents hydrogen or one of the substituents specified for A.

Compounds of the formula (I) in which the radical A is characterized by the following formula may be mentioned with particular preference, it being possible for it to be bonded to the oxazoline ring either directly or via a bridge member Z:

R ^] stands for residues according to the following Table 1

(R ² ) stands for residues according to the following Table 2 Table 1

Tabelle 2

Table 2

(R ² ) _m (R ² ) _m

H 2 -CH ₃

2-C1 2-OCH ₃

2-F 2,3-Cl ₂

3-C1 2,6- (OC ₂ H ₅ ) ₂

2,6-Cl ₂ 3-CH ₃

3,5-Cl ₂ 3,5- (OCH ₃ ) ₂

3,5-F ₂ 3-OC ₆ H ₅

2,5-Cl ₂

3,5-Cl ₂ ; 2-F together with R ¹ for

2,3-F ₂ 3,4- (OCF ₂ O-)

2.5-F ₂ 3.4- (OCF ₂ CF ₂ O)

2,3,5,6-Cl ₄ 2-C1; 3-CF ₃

3-CF ₃ 2-C1; 5-CF ₃

The following radicals, which are bonded to the oxazoline ring either directly or via a bridge member Z, may be mentioned as examples:

(Continued table la)

(Fortsetzung Tabelle la)

(Continued table la)

(Fortsetzung Tabelle la)

(Continued table la)

(Fortsetzung Tabelle la)

(Continued table la)

(Fortsetzung Tabelle la)

(Continued table la)

(Fortsetzung Tabelle la)

(Continued table la)

(Fortsetzung Tabelle la)

(Continued table la)

(Fortsetzung Tabelle la)

(Continued table la)

(Continued table la)

(Fortsetzung Tabelle la)

(Continued table la)

(Fortsetzung Tabelle la)

(Continued table la)

Furthermore, A can stand for residues of the following formula al97

in which

represents optionally substituted alkanediyl and

X represents hydrogen or halogen. The following alkanediyl radicals E are preferred:

El -CF ₂ - E2 -CF (CC1 ₂ CF ₃ ) -

E3 -CFC1- E4 -CF ₂ -CF ₂ -

E5 -CF (CH ₃₎ - E6 -CF ₂ -CFC1-

E7 -C (CH ₃ ) (CH ₂ F E8 -CF ₂ -CF (CH ₃ ) -

E9 -C (CH ₃ ) (CH ₂ C1) - E10 -CF ₂ -C (CH ₃ ) ₂ -

Ei l -C (CF ₃ ) (CHC1CF ₃ ) E12 -CFC1-CFC1-

E13 -CH (CH ₂ CF ₃ ) - E14 -CF ₂ -CH (CH ₃ )

E15 -CH (CHC1CF ₃ ) - E16 -CF ₂ -CH (CF ₃ ) -

The following radicals may be mentioned as examples of the substituent B:

Beispielhaft seien für den Substituenten B folgende Reste genannt:

The following radicals may be mentioned as examples of the substituent B:

b17 b21 b25 b29 b33

b18 b22 b26 b30 b34 b37

b20 b24 b28 b32 b36 b39

b20 b24 b28 b32 b36 b39

The following meanings may be mentioned as examples of the divalent radical Z:

-CH ₂ -, -CH (CH ₃ ) -, -CH ₂ CH ₂ -, -CH = CH-, -CH ₂ O-, -CH ₂ S-, -CH (CH ₃ ) S-, -CH ( CH ₃ ) O-, -CH ₂ CH ₂ O-, -CH ₂ S (O) -, -CH ₂ -SO ₂ -.

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

a) amino alcohols of the formula (II)

in which

A and R have the meanings given above,

with a carboxylic acid of formula (III)

B-COOH (in)

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

Converts diluent;

or c) amide derivatives of the formula (V)

in which

A, B and R have the meanings given above; and

X represents a leaving group, such as halogen, alkylsulfonyloxy or arylsulfonyloxy,

with a base, optionally in the presence of a diluent.

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

The carboxylic acids of the formula (III) to be used further as starting materials in process (a) for the preparation of the compounds of the formula (I) are known organic synthesis chemicals or can be obtained in a known manner.

Processes (a) and (b) are carried out using a dehydrating agent. The dehydrating agents common in organic chemistry can be used. Sulfuric acid, polyphosphoric acid (PPS), phosphorus (V) oxide, dicyclohexylcarbodiimide (DCC), phosphorus (V) sulfide and the system triphenylphosphine / triethylamine / tetrachloromethane can preferably be used.

The usual organic solvents are suitable as diluents for carrying out processes (a) to (c) according to the invention. Preferably Aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, gasoline, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform, carbon tetrachloride, can be used; Ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl or diethyl ether; Ketones, such as acetone, butanone or methyl isobutyl ketone; Nitriles such as acetonitrile, propionitrile or benzonitrile; Amides such as N, N-dimethylformamide and N, N-dimethylacetamide, N-methyl-pyrrolidone or hexamethylphosphoric triamide; Esters such as methyl acetate or ethyl acetate, as well as sulfoxides such as dimethyl sulfoxide, optionally also alcohols such as methanol or ethanol.

The reaction temperatures can be varied within a substantial range when carrying out process (a) according to the invention. In general, temperatures between 0 ° C and 150 ° C, preferably at temperatures between 10 ° C and 100 ° C.

Process (a) according to the invention is generally carried out under normal pressure. However, it is also possible to work under increased or reduced pressure - generally between 0.1 bar and 10 bar.

To carry out process (a) according to the invention, the starting materials required in each case are generally used in approximately equimolar amounts. However, it is also possible to use one of the two components used in each case in a larger excess. The reactions are generally carried out in a suitable diluent in the presence of a dehydrating agent, and the reaction mixture is stirred for several hours at the temperature required in each case. The processing takes place according to usual methods.

In a special embodiment of process (a) according to the invention, corresponding nitriles can also be used instead of the carboxylic acids of the formula (III), in which case a catalyst, such as e.g. Zinc (II) chloride is used.

The amide alcohols to be used as starting materials in process (b) for the preparation of the compounds of the formula (I) are known and / or can be prepared by processes known per se. The amide alcohols of the formula (IV) are obtained, for example, by acid chlorides derived from the carboxylic acids of the formula (III) with amino alcohols of the formula (II) in the presence of an acid binder, such as triethylamine, pyridine, potassium carbonate, sodium hydroxide or potassium t-butoxide , and in the presence of a diluent such as toluene, chlorobenzene, acetone or acetonitrile, at temperatures between 0 ° C and 100 ° C.

The acid chlorides derived from the carboxylic acids of the formula (III) are largely known and / or can be prepared by processes known per se, 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.

For example, α-fluoro-β, β-dichloro-acrylic acid chloride of the formula (VI) can be obtained by hydrolyzing 2-fluoro-1,3,3,3-pentachloropropene, optionally in the presence of a catalyst. Lewis acids, inorganic acids and their acid salts, such as FeCl ₃ , BF ₃ , H ₂ SO ₄ ,

HC1, KHSO ₄ , NaHSO ₄ and others in question.

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

The reaction temperatures can be varied within a substantial range when carrying out process (b). In general, temperatures between -20 ° C and + 150 ° C, preferably at temperatures between

0 ° C and 100 ° C.

Process (b) according to the invention is generally carried out under normal pressure. However, it is also possible to work under increased or reduced pressure - generally between 0.1 bar and 10 bar. To carry out process (b) for the preparation of the compounds of the formula (I), 1 to 20 mol, preferably 1 to 5 mol, of dehydrating agent are generally employed per mole of amide alcohol of the formula (IV).

In a preferred embodiment of process (b) according to the invention, the amide alcohol of the formula (IV) is placed in a diluent and the water-removing agent is then metered in. The reaction mixture is stirred at the required temperature until the end of the reaction and then worked up in the customary manner.

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

The amide derivatives of the formula (V) are obtained if corresponding amide alcohols of the formula (IV) are used with chlorinating agents, e.g. Thionyl chloride or phosphorus (V) chloride, or with sulfonylating agents, e.g. Methanesulfonic acid chloride or p-toluenesulfonic acid chloride in the usual manner, if appropriate in

In the presence of a base and optionally in the presence of a diluent.

Process (c) is carried out in the presence of a base. All customary inorganic or organic bases can be used. Alkaline earth metal or alkali metal hydrides, hydroxides, amides, alcoholates,

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 hydrogen carbonate , Sodium hydrogen carbonate or ammonium carbonate and also tertiary amines such as trimethylamine, triethylamine, tributylamine, N, N-dimethylaniline, pyridine, N-methylpiperidine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclonones (DBN) or diazabicycloundec.

The reaction temperatures can be varied within a substantial range when carrying out process (c). In general, 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 to work under increased or reduced pressure - generally between 0.1 bar and 10 bar.

To carry out process (c) for the preparation of the compounds of the formula (I), 1 to 3 mol, preferably 1.0 to 1.5 mol, of a base are generally employed per mol of amide derivative of the formula (V).

In a preferred embodiment of process (c), the amide derivative of the formula (V) and a base are mixed in a suitable diluent; the mixture is stirred at the required temperature until the reaction has ended and then worked up in the customary manner.

The active ingredients are suitable for combating animal pests such as insects and single ticks, which occur in animal husbandry and animal breeding in useful, breeding, zoo, laboratory, experimental and hobby animals with favorable warm-blooded toxicity. They are effective against all or individual stages of development of the pests and against resistant and normally sensitive types of pests.

The fight against animal pests is intended to prevent diseases and their transmission, deaths and reduced performance (for example in the production of meat, milk, wool, hides, eggs), so that the use of the active compounds enables more economical and simple animal husbandry or is only possible in certain areas.

The pests include:

From the order of the anoplura e.g. Haematopinus spp., Linognathus spp., Solenopotes spp., Pediculus spp., Pthirus spp .; from the order of the Mallophaga e.g. 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 the Diptera e.g. 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 spp., Hypoderma spp., Oestrus spp., Rhinoestrus spp., Melophagus spp., Hippobosca spp ..

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

The following genera and species of the parasitic ticks: 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 e.g. Cheyletiella spp., Psorergates spp., Myobia spp., Demdex spp., Neotrombicula spp .; from the order of the astigmata e.g. Acarus spp., Myocoptes spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Neoknemidodoptex spp., Lytodites spp., Laminosioptes spp ..

The action of the compounds of the formula (I) against ticks which comply with the law is particularly emphasized. These include Boophilus spp., Hyalomma spp ..

Domestic and farm animals include mammals such as Cattle, sheep, goats, horses, pigs, dogs, cats, camels, water buffalos, donkeys, rabbits, fallow deer, reindeer, fur animals such as Mink, chinchilla, raccoon, birds such as Chickens, turkeys, pheasants, geese, ducks.

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

The pets include dogs and cats.

The application can be prophylactic as well as therapeutic.

The active ingredients are used directly or in the form of suitable preparations enterally, parenterally, dermally, nasally, by treating the environment or with the aid of shaped articles containing active ingredients, such as, for example, strips, plates, bands, necklaces, ear tags, limb bands, marking devices. The enteral application of the active ingredients takes place, for example, orally in the form of powder, suppositories, tablets, capsules, pastes, drinkers, granules, drenches, boluses, medicated feed or drinking water. The dermal application takes place, for example, in the form of dipping (dipping), spraying (spraying), bathing, washing, pouring on (pour-on and spot-on) and powdering. Parenteral use is for example in the form of injection (intramuscular, subcutaneous, intravenous, intraperitoneal) or by implants.

Suitable preparations are:

Solutions such as injection 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 use and for injection; Semi-solid preparations;

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

Solid preparations such as powders, premixes or concentrates, granules, pellets, tablets, boluses, capsules; Aerosols and inhalants, molded articles containing active ingredients.

Solutions for injection are administered intravenously, intramuscularly and subcutaneously.

Injection solutions are prepared by dissolving the active ingredient in a suitable solvent and possibly additives such as solubilizers, acids,

Bases, buffer salts, antioxidants, preservatives can be added. The solutions are sterile filtered and filled.

The following may be mentioned as solvents: physiologically compatible solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol, hydrocarbons, propylene glycol, polyethylene glycols, N-methylpyrrolidone, and mixtures thereof.

If appropriate, the active compounds can also be dissolved in physiologically tolerable vegetable or synthetic oils which are suitable for injection. The following may be mentioned as solubilizers: solvents which promote the dissolution of the active ingredient in the main solvent or prevent its precipitation. Examples are polyvinyl pyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.

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

Oral solutions are applied directly. Concentrates are used orally after previous dilution to the application concentration. Oral solutions and concentrates are produced as described above for the injection solutions, whereby sterile work can be dispensed with.

Solutions for use on the skin are dripped on, spread on, rubbed in, sprayed on, sprayed on or applied by dipping (dipping, bathing or washing). These solutions are prepared as described above for the injection solutions.

It may be advantageous to add thickeners during manufacture.

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 to or spread on the skin or placed in body cavities. Gels are produced by adding enough thickening agent to solutions which have been prepared as described for the injection solutions to produce a clear mass with an ointment-like consistency. The thickeners specified above are used as thickeners.

Pour-on formulations are poured or sprayed onto limited areas of the skin, the active ingredient either penetrating the skin and acting systemically or being distributed over the surface of the body.

Pour-on formulations are prepared by suspending the active ingredient in suitable skin-compatible solvents or solvent mixtures or is emulsified. If necessary, other auxiliaries such as dyes, absorption-promoting substances, antioxidants, light stabilizers and adhesives are added.

The following may be mentioned as solvents: water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenylethanol, 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 and glycol monoethyl ether Acetone, methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide, N-methylpyrrolidone, 2,2-dimethyl-4-oxy-methylene-l, 3-dioxolane.

Dyes are all dyes approved for use on animals, which can be dissolved or suspended.

Absorbing substances are e.g. DMSO, spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.

Antioxidants are sulfites or metabisulfites such as potassium metabisulfite, ascorbic acid, butylated hydroxytoluene, butylated hydroxyanisole, tocopherol.

Light stabilizers are e.g. Substances from the class of benzophenones or novantisolic acid.

Adhesives are e.g. Cellulose derivatives, starch derivatives, polyacrylates, natural

Polymers such as alginates, gelatin.

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

Emulsions are either water in oil or oil in water.

They are produced by dissolving the active ingredient either in the hydrophobic or in the hydrophilic phase and using suitable ones

Emulsifiers and optionally other auxiliaries such as dyes, absorption-promoting substances, preservatives, antioxidants, light stabilizers, Viscosity-increasing substances, homogenized with the solvent of the other phase.

The following are mentioned as hydrophobic phase (oils): paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic / capric acid biglyceride, triglyceride mixtures with vegetable fatty acids of chain length C ₈ _ ₁₂ or other specially selected natural fatty acids, partial - Glyceride mixtures of saturated or unsaturated, possibly also hydroxyl-containing fatty acids, mono- and diglycerides of C ₈ / C _{] 0} fatty acids.

Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, lauric acid hexyl ester, dipropylene glycol pelargonate, esters of a branched fatty acid of medium chain length with saturated fatty alcohols of chain length C ₁₆ -C ₁₈ , isopropyl myristate, isopropyl palmitate, caprylic / capric alcohol esters of the saturated fatty acid Chain length C ₁₂ -C ₁₈ , isopropyl stearate, oleic acid oleyl ester, oleic acid decyl ester, ethyl oleate, lactic acid ethyl ester, waxy fatty acid esters such as artificial duck pancreas fat, dibutyl phthalate, adipic acid diisopropyl ester, the latter related ester mixtures and others

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

Fatty acids such as Oleic acid and its mixtures.

The following can be mentioned as the hydrophilic phase:

Water, alcohols such as e.g. Propylene glycol, glycerin, sorbitol and their mixtures.

The following may be mentioned as emulsifiers: nonionic surfactants, e.g. polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether;

ampholytic surfactants such as di-Na-N-lauryl-β-iminodipropionate or lecithin;

anionic surfactants, such as sodium lauryl sulfate, fatty alcohol ether sulfates, mono / dialkyl polyglycol ether orthophosphoric acid ester monoethanolamine salt;

cationic surfactants such as cetyltrimethylammonium chloride. The following may be mentioned as further auxiliaries: substances which increase viscosity and stabilize the emulsion, such as carboxymethyl cellulose, methyl cellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes , colloidal silica or mixtures of the listed substances.

Suspensions can be used orally, dermally or as an injection. They are produced by suspending the active ingredient in a carrier liquid, if appropriate with the addition of other auxiliaries such as wetting agents, dyes, absorption-promoting substances, preservatives, antioxidants and light stabilizers.

All homogeneous solvents and solvent mixtures may be mentioned as carrier liquids.

The surfactants specified above may be mentioned as wetting agents (dispersants).

Further additives mentioned are those mentioned above.

Semi-solid preparations can be administered orally or dermally. They differ from the suspensions and emulsions described above only in their higher viscosity.

To prepare solid preparations, the active ingredient is mixed with suitable carriers, if appropriate with the addition of auxiliaries, and brought into the desired shape.

All physiologically compatible solid inert substances may be mentioned as carriers. All of these serve inorganic and organic substances. Inorganic substances are e.g. Table salt, carbonates such as calcium carbonate, hydrogen carbonates, aluminum oxides, silicas, clays, precipitated or colloidal silicon dioxide, phosphates.

Organic substances are, for example, sugar, cellulose, food and feed such as milk powder, animal meal, cereal meal and meal, starches. Excipients are preservatives, antioxidants, dyes, which have already been listed above.

Other suitable auxiliaries are lubricants and lubricants such as Magnesium stearate, stearic acid, talc, bentonite, decay-promoting substances such as starch or cross-linked polyvinylpyrrolidone, binders such as e.g. Starch, gelatin or linear polyvinylpyrrolidone and dry binders such as microcrystalline cellulose.

The active substances can also be present in the preparations as a mixture with synergists or with other active substances.

Ready-to-use preparations contain the active substance in concentrations of

10 ppm to 20% by weight, preferably from 0.1 to 10% by weight.

Preparations which are diluted before use contain the active ingredient in concentrations of 0.5 to 90% by weight, preferably 5 to 50% by weight.

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

The active compound (1) used in the following examples is the compound of the formula:

2- (2,6-difluorophenyl) -4- [4- (4-trifluoromethoxyphenyl) phenyl] -2-oxazoline. example 1

SC- (suspension concentrate) formulation:

368 g of active ingredient 1 35 g of block polymer composed of emulsifier ethylene oxide and propylene oxide

12 g ditolyl ether sulfonate formaldehyde condensate (emulsifier)

3.5 g water-soluble polyvinyl alcohol 58.0 g NH ₄ C1

116.0 g urea 1.2 g (37% aqueous hydrochloric acid)

4.6 g xanthan gum 560.5 g distilled water

Example 2

WP (dispersible powder) formulation:

25.0 g of active ingredient 1

1.0 g diisobutyl naphthalene Na sulfonate

10.0 g of n-dodecylbenzenesulfonic acid calcium

12.0 g of highly disperse silicic acid-containing alkylaryl polyglycol ether

3.0 g ditolyl ether sulfonate-formaldehyde condensate (emulsifier) 2.0 g ^® Baysilon-E, a silicone-containing defoamer from Bayer AG, 2.0 g finely dispersed silicon dioxide and 45.0 g kaolin

Example 3

SL (water-soluble concentrate) formulation

18.3 g of active ingredient 1

2.5 g neutral emulsifier based on alkylaryl polyglycol ether 3.5 g diisooctyl sodium sulfosuccinate

38.4 g of dimethyl sulfoxide and

37.5 g 2-propanol Example 4

SL (water soluble concentrate) formulation

185 g active ingredient 1

5.0 g of diisooctyl sodium sulfonate and 76.5 g of dimethyl sulfoxide

100 g of a shampoo formulation consisting of

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

Manufacturing examples

example 1

0.3 g (6 mmol) of sodium methylate (slightly exothermic) are added to 1 g (6 mmol) of 4-t-butyl-thiophenol in 50 ml of methanol with stirring. 2.1 g (6 mmol) of 2- (2,6-difluorophenyl) -4- (p-tolylsulfonyloxymethyl) -1,3-oxazoline in 30 ml of methanol are added dropwise to this solution at 40.degree. The reaction mixture is allowed to stir at 40 ° C. for 2 hours and then under reflux for 16 hours. The solvent is then distilled off, the residue is taken up in 100 ml of ethyl acetate and washed three times with 50 ml of water each time. The solvent is stripped off and the residue is purified by chromatography on silica gel column chromatography with toluene / toluene, ethyl acetate 10: 1 as the eluent.

0.9 g (41.6% of theory) of 2- (2,6-difluorophenyl) -4- (4-t-butylphenylthio-methyl) -l, 3-oxazoline with a log P (octanol / water) distribution coefficient are obtained ) of -4.64 and a refractive index n ⁰ = 1.5660.

Preparation of the starting compound

Example la

5.6 ml (0.069 mol) of pyridine are added to 5.3 g (0.023 mol) of 2- (2,6-difluorophenyl) -4-hydroxymethyl-1,3-oxazoline in 100 ml of ethyl acetate, and 4.4 g are then added dropwise (0.023 mol) of p-toluenesulfonic acid chloride in 50 ml of ethyl acetate. The temperature rises to 50 ° C. 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 of water each time and the solvent is distilled off. The residue is purified by chromatography on silica gel column chromatography with eluent toluene under a gradient with eluent ethyl acetate.

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

Example lb

6.5 g (0.0168 mol) of N- [l-chloro-3- (4-t-butylbenzoyloxy) -2-propyl] -2,6-difluorobenzamide are dissolved in 100 ml of methanol. 2 ml (0.033 mol) of 45% sodium hydroxide solution are added and the mixture is stirred under reflux for 4 hours. After the solvent has been distilled off, the residue is taken up in 100 ml of ethyl acetate, washed three times with 50 ml of water each time and the solvent is distilled off. 2.8 g (72% of theory) of 2- (2,6-difluorophenyl) -4-hydroxymethyl-1,3-oxazoline with a melting point of 82 ° C. are obtained.

Example lc

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

9.3 g of N- [l-chloro-3- (4-t-butylbenzoyloxy) -2-propyl] -2,6-difluorobenzamide are obtained with a log P (octanol / water) distribution coefficient of -3.86 .

Example ld

21.9 ml (0.158 mol) of triethylamine are first added to 21 g of 2-amino-3- (4-t-butylbenzoyloxy) -l-propanol hydrochloride in 400 ml of ethyl acetate and then 13.9 g of 2. 6-Difluorobenzoic acid chloride added dropwise in 20 ml of ethyl acetate. The mixture is stirred at 20 ° C for 1 hour; the precipitate is filtered off with suction, the organic phase is washed three times with 100 ml of water each time, the solvent is distilled off and the residue is stirred with diisopropyl ether.

After drying, 14 g (48% of theory) of N- [l-hydroxy-3- (4-t-butylbenzoyloxy) -2-propyl] -2,6-difluorobenzamide with a distribution 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 are refluxed to 1.6 ml (0.026 mol) 45% sodium hydroxide solution is dropped into 5 ml of water. The reaction mixture is left 1

Stir under reflux for an hour and then concentrated by distilling off the solvent. The residue is stirred with water, the precipitate is filtered off with suction and dried.

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 are obtained -63 ° C.

Preparation of the starting compounds for Example 2

Example 2a

(Step 1)

3.3 ml (0.024 mol) of triethylamine are added to 3.9 g (0.02 mol) of 2-amino-2- (4-t-butylρhenyl) -1 -ethanol in 150 ml of ethyl acetate, followed by addition at 0 ° C dropwise with 3.7 g (0.024 mol) of 2,2-bis (fluoromethyl) propionic acid chloride. Thereafter, the mixture is allowed to warm to room temperature and stirred overnight. The precipitate is then filtered off with suction, the filtrate is washed several times with water, the organic phase is separated off, dried over sodium sulfate, filtered and concentrated. 4.5 g (71.9% of theory) of N- [2-hydroxy-1- (4-t-butylphenyl) ethyl] - 2,2-bis (fluoromethyl) propionic acid amide with a melting point of 141 ° C. are obtained.

Example 2b

Level 2)

To 4.5 g (0.0144 mol) of N- [2-hydroxy-1- (4-t-butylphenyl) ethyl] -2,2-bis (fluoromethyl) propionic acid amide (cf. stage 1) in 100 ml of carbon tetrachloride are added to 1.05 ml (0.0144 mol) of thionyl chloride. The reaction mixture is left to react under reflux for 1 hour. After distilling off the solvent, 4.3 g (90% of theory) of N- [2-chloro-1- (4-t-butylphenyl) ethyl] -2,2-bis-

(fluoromethyl) propionic acid amide, melting point 98 ° C.

Example 3

0 is added to a solution of 2.0 g (5.2 m mol) of N- [1- (4-tert-butylphenyl) -2-chloroethyl] - 2,3,5,6-tetrafluorobenzoic acid amide in 30 ml of tetrahydrofuran , 75 g (6.7 m mol) of potassium tert-butoxide and stirred at 50 ° C. After 3 hours, the reaction mixture is poured onto water and extracted with methylene chloride. The organic extracts are washed with water, dried over magnesium sulfate and then concentrated in vacuo. The residue is purified by means of column chromatography (eluent chloroform).

0.8 g (44.7% of theory) of 4- (4-tert-butylphenyl) -2- (2,3,5,6-tetra-fluorophenyl) -1, 3-oxazoline with a log distribution coefficient are obtained 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 are dissolved in 50 ml of toluene with 5 ml of thionyl chloride Heated under reflux for 18 hours. Excess thionyl chloride and the solvent are then removed in vacuo.

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

Example 3b

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 1.6 g (7.5 m mol) of 2,3,5,6-tetrafluorobenzoyl chloride, dissolved in 10 ml of methylene chloride, with stirring at 20 ° C. After boiling overnight, the mixture is diluted with methylene chloride, washed with water and the organic phase is concentrated in vacuo. The residue is stirred with a little n-pentane and suction filtered.

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

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

The residue is taken up in 50 ml of toluene and mixed with 0.9 g of potassium t-butoxide. The reaction mixture is then stirred at 50 ° C. under thin-layer chromatographic control. After the reaction is complete, the solution obtained is washed with water and the organic phase is then concentrated in a water jet vacuum. The residue is chromatographed on silica gel using cyclohexane / ethyl acetate (vol. 2: 1).

1 g (31% of theory) of 8-phenyl-2- (2,6-dichlorophenyl) -l-aza-3,7,9-tri-oxa-spiro [4.5] dec-1-ene is obtained 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 are mixed with 10 ml of triethylamine and 10 g of palladium / carbon in 1 liter of ethanol and Hydrogenated for 3 days at 20 ° C and 30 bar. Then it is filtered, the filtrate in a water jet concentrated in vacuo, the residue digested with n-hexane and the product obtained in crystalline form isolated by suction.

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

Example 4b

5 g (20 mmol) of 2- (4-t-butylphenyl) -5-amino-5-hydroxymethyl-1,3-dioxane are mixed with 5 ml of triethylamine in 80 ml of methylene chloride. A solution of 4.5 g (20 mmol) of 2,6-dichlorobenzoyl chloride in 5 ml of methylene chloride is then added dropwise at 0 ° C. and the mixture is stirred at 20 ° C. for 15 hours. The mixture is then washed with 0.5 N sodium hydroxide solution, the organic phase is dried with sodium sulfate and filtered. The filtrate is concentrated in a water jet vacuum, the residue is crystallized by digestion with n-hexane and the product is isolated by suction.

7.2 g (83% of theory) of 2- (4-t-butylphenyl) -5-hydroxymethyl-5- (2,6-dichlorobenzoylamino) -1,3-dioxane with a melting point of 178 are obtained ° C - 180 ° C.

Example 5

0,67 g (2 mmol) N-(2-Hydroxy-l(3,4-difluormethylendioxy-phenyl)-ethyl)-2,6-di- fluor-benzamid werden in 15 ml Toluol vorgelegt und 0,27 ml (4 mmol) Thionyl¬ chlorid werden bei 20°C dazu gegeben. Das Reaktionsgemisch wird dann 3 Stunden zum Rückfluß erhitzt. Nach Abkühlen wird eingeengt der Rückstand in 15 ml Tetra- hydrofuran aufgenommen und nach Zugabe von 0,23 g (2 mmol) Kalium-t-butylat wird das Gemisch eine Stunde bei 50°C gerührt. Dann wird eingeengt, der Rück¬ stand mit Methylenchlorid/Wasser geschüttelt, die organische Phase über Magnesiumsulfat getrocknet und filtriert. Das Filtrat wird eingeengt und der Rück¬ stand aus Methylenchlorid Petrolether umkristallisiert.

0.67 g (2 mmol) of N- (2-hydroxy-l (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. The reaction mixture is then heated to reflux for 3 hours. After cooling, the residue is concentrated in 15 ml of tetrahydrofuran and, after adding 0.23 g (2 mmol) of potassium t-butoxide, the mixture is stirred at 50 ° C. for one hour. The mixture is then concentrated, the residue is shaken with methylene chloride / water, the organic phase is dried over magnesium sulfate and filtered. The filtrate is concentrated and the residue is recrystallized from methylene chloride petroleum ether.

0.13 g (20% of theory) of 2- (2,6-difluorobenzoyl) -4- (3,4-difluoromethylenedioxyphenyl) -2-oxazoline with a melting point of 86 ° C. is obtained.

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 introduced with 0.91 g (24 mmol) of sodium borohydride in 30 ml of tetrahydrofuran at 0 ° C and a solution of 3 , 05 g (24 mmol) iodine in 10 ml tetrahydrofuran is then added dropwise. After the evolution of gas has subsided, the mixture is heated under reflux for 16 hours. Then, after cooling, the mixture is diluted with methanol until a clear solution is obtained. It is concentrated, the residue is taken up in 20 ml of 20% 2N sodium hydroxide solution and extracted three times with 50 ml of methylene chloride each time. The combined organic phases are dried over magnesium sulfate and filtered. After evaporating the filtrate, the crude product obtained as a 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-difluoro-benzamide are placed in 2 ml of methanol, at 20 ° C become 2 ml IN sodium hydroxide solution is added and the mixture is heated under 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 a residue is reacted further without further purification.

Yield: 0.67 g (93% of theory),

Melting point: 158 ° C.

According to the preparation examples and according to the general information on the preparation, the following compounds of the general formula (I)

receive:

Claims

claims 1. Use of compounds of the formula (I)

in which B represents optionally substituted alkyl, alkenyl, cycloalkyl, Cycloalkenyl, aryl, A represents aryl, aryloxy, heteroaryl, heteroaryloxy which are optionally substituted and which are optionally bonded to the oxazoline ring via a divalent radical Z, R stands for hydrogen or together with A and the adjacent one See C atom for a spirocycli 3- to 6-membered ring which may optionally contain one or more heteroatoms of the group O, S, N and to which another ring may be fused, the system optionally being substituted, to control parasitic insects and single-host ticks Human and animal. 2. Agents against parasitic insects and single-host ticks in humans and animals, characterized by a content of at least one compound of the formula (I) according to claim 1. 3. A process for the preparation of agents against parasitic insects and single-host ticks on humans and animals, characterized in that compounds of the formula (I) according to Claim 1 are mixed with extenders and / or surface-active agents. 4. Use of compounds of formula (I) according to claim 1 for the preparation of agents against parasitic insects and single-ticks in humans and animals.