WO2001036372A1 - Organic compounds and their use in the control of ectoparasites - Google Patents

Abstract

New compounds of formula (I) are described, wherein R is the group (A). R1 and R2, independently of one another, are hydrogen, halogen, cyano, nitro, C1-4-alkyl; C1-4-haloalkyl, C1-4-alkoxy, C1-4-haloalkoxy or benzyl; A is oxygen, sulphur or -N(R6)-, whereby R6 is C1-4-alkyl, phenylthio or tolylthio; p is a whole number from 1 to 10; R3, R4 and R5 independently of one another, are hydrogen, halogen, cyano, nitro, C1-4-alkyl, C1-4-haloalkyl, C1-4-alkoxy or C1-4-haloalkocy; or R3 and R4 are in neighbouring positions and, together with the phenyl ring to which they are bonded, form a naphthyl group; n is 1, 2 or 3; m is 1, 2 or 3; and Z is C1-6-alkyl, phenyl or halogen; in free form or in the form of physiologically acceptable salts. In addition, the preparation and usage of these substances in the control of ectroparasites on domestic animals, livestock or pets, is described, as well as ectoparasitic compositions for usage on these animals.

Description

ORGANIC COMPOUNDS AND THEIR USE IN THE CONTROL OF ECTOPARASITES

The present invention relates to the new compounds of formula I, their preparation and their usage in the control of ectoparasites on domestic animals, productive livestock and pets, also ectoparasitic compositions for usage on these animals, whereby the compositions contain at least one of these compounds as the active ingredient, and to the usage of these substances in the preparation of said compositions.

The substances according to the invention are compounds of formula I

wherein R is the group

R_t and R₂, independently of one another, are hydrogen, halogen, cyano, nitro, C_1- alkyl,

Cι- -haloalkyl, d.₄-alkoxy, Cι- -haloalkoxy or benzyl;

A is oxygen, sulphur or -N(R₆)-, whereby R₆ is C_1-4-alkyl, phenylthio or tolylthio p is an integer from 1 to 10;

R₃, R and R₅, independently of one another, are hydrogen, halogen, cyano, nitro, C^alkyl,

Cι- -haioalkyl,

or Cι_-4-haloalkoxy; or R₃ and R₄ are in neighbouring positions and, together with the phenyl ring to which they are bonded, form a naphthyl group; n is 1 , 2 or 3; m is 1 , 2 or 3; and Z is C_1-6-alkyl, phenyl or halogen; in free form or in the form of physiologically acceptable salts. Preference is given here to compounds in which R_T and R₂ signifies hydrogen; A is oxygen; n is 1 ; m is 2; p is 3; and Z is CH₃ or F. Alkyl on its own, or as a constituent of a haloalkyl, alkoxy or haloalkoxy radical, is understood to be a saturated, unbranched or branched hydrocarbon radical with one to four carbon atoms, e.g. substituents such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec- butyl, isobutyl, tert.-butyl. The prefix halo indicates that the corresponding substituent is partially or wholly halogenated. Examples of haloalkyl - as a group perse and as structural element of other groups and compounds such as haloalkoxy - are methyl which is mono- to trisubstituted by fluorine, chlorine and/or bromine, such as CHF₂ or CF₃; ethyl which is mono- to pentasubstituted by fluorine, chlorine and/or bromine, such as CH₂CF₃, CF CF₃, CF₂CCI₃, CF₂CHCI₂, CF₂CHF₂, CF₂CFCI₂, CF₂CHBr₂, CF₂CHCIF, CF₂CHBrF or CCIFCHCIF; propyl or isopropyl, mono- to heptasubstituted by fluorine, chlorine and/or bromine, such as CH₂CHBrCH₂Br, CF₂CHFCF₃, CH₂CF₂CF₃ or CH(CF₃)₂; and butyl or one of its isomers, mono- to nonasubstituted by fluorine, chlorine and/or bromine, such as CF(CF₃)CHFCF₃ or CH₂(CF₂)₂CF₃. The terms halo and halogen denote halogen atoms and, as a rule, signify fluorine, chlorine, bromine or iodine, preferably fluorine or chlorine, as the substituent of an alkyl group especially fluorine and as the substituent of a phenyl ring especially chlorine.

Owing to their especially marked activity, there are particularly preferred sub-groups in the context of formula I, e.g. the group of compounds of formula la

wherein Ri and R₂, independently of one another, signify hydrogen, halogen or

A is oxygen, sulphur or -N(R₆)-, whereby R₆ is C_1-4-alkyl; R₃, R₄ and R₅ independently of one another are hydrogen, halogen, cyano, nitro, C_1-4-alkyl or Cι_-4-alkoxy; and Z is

phenyl or halogen, in free form or in the form of physiologically acceptable salts. The compounds which are notable within the context of formula la, are the following compounds, in which R and R₂, independently of one another, are hydrogen, fluorine, chlorine or methyl; A is oxygen, R₃, R₄ and R₅, independently of one other, are hydrogen, fluorine, chlorine, CF₃, cyano or nitro; and Z is CH₃, phenyl, fluorine or chlorine; in free form or in the form of the physiologically acceptable salts. The compounds in which Z is CH₃ are most particularly preferred.

Especially preferred individual compounds within the context of the present invention are: 4-methyl-5,5-difluoropent-4-enoic acid-{2-[4-(benzyloxy)-phenoxy]ethyl}ester; 4-methyl-5,5-difluoropent-4-enoic acid-{2-[4-(2-nitrobenzyloxy)-phenoxy]ethyl}ester; 4-methyl-5,5-difluoropent-4-enoic acid-{2-[4-(4-methylbenzyloxy)-phenoxy]ethyl}ester; 4-methyl-5,5-difluoropent-4-enoic acid-{2-[4-(4-trifluoromethylbenzyioxy)- phenoxy]ethyl}ester;

4-methyl-5,5-difluoropent-4-enoic acid-{2-[4-(3-nitrobenzyloxy)-phenoxy]ethyl}ester; 4-methyl-5,5-difluoropent-4-enoic acid-{2-[4-(4-tert.-butylbenzyloxy)-phenoxy]ethyl}ester; 4-methyl-5,5-difluoropent-4-enoic acid-{2-[4-(2-phenylbenzyloxy)-phenoxy]ethyl}ester; and 4-methyl-5,5-difluoropent-4-enoic acid-{2-[4-(α-naphthylmethoxy-benzyloxy)- phenoxy]ethyl}ester.

Compounds having the structural type of formula I are embraced in EP-0,577,555, but are not disclosed therein. The substances described therein are presented as active ingredients in the field of pest control, especially for usage against insects and arachnids, such as those present on crop plants and ornamentals in agriculture and horticulture, in particular in rice, cotton, vegetable and fruit plantations, and in forestry. Further fields of application are usage in the hygiene sector, the protection of material, as well as the protection of domestic animals and productive livestock, but these are not described.

The present invention also relates to the production of compounds of formula I, whereby a compound of formula II,

wherein R, Ri, R₂, A and m are defined as under formula I, is reacted with a compound of formula III, if necessary in the presence of an inert solvent or solvent mixture,

wherein Q is hydroxy or halogen and p is defined as under formula I, preferably chlorine or bromine; and Z and p are defined as under formula I; whereby when Q is hydroxy, the reaction is preferably carried out in the presence of a hydrophilic agent or a catalyst, and when Q is halogen, it is preferably carried out in the presence of an acid-binding agent.

The reaction of II with a compound of formula III, wherein Q is halogen, is preferably effected in an inert, hydroxy-group-free solvent in the presence of an organic base, for example pyridine, 4-dimethylaminopyridine, lutidine, collidine, trialkylamine, N,N-dialkyl- amine, or a bicyclic, non-nucleophilic base, such as 1 ,4- diazabicyclo[2.2.2]octane (DABCO), 1 ,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1 ,8-diazabicyclo[5.4.0]undec-7-ene (1 ,5-5) (DBU). The reaction is generally carried out at temperatures of -30°C to +70°C, preferably -10°C to +50°C. The process is suitably carried out in the presence of an inert solvent or solvent mixture. Suitable solvents for this purpose are for example aliphatic and aromatic hydrocarbons, such as benzene, toluene, xylenes, petroleum ether, hexane; halogenated hydrocarbons, such as chlorobenzene, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, ethylene tetrachloride; ethers and ether-like compounds, such as dialkyl ether (diethyl ether, diisopropyl ether, tert.-butylmethyl ether, etc.), anisole, dioxane, tetrahydrofuran; nitriles such as acetonitrile, propionitrile; esters such as ethyl acetate (acetic acid ethyl ester), propyl acetate or butyl acetate; ketones such as acetone, diethyl ketone, methyl ethyl ketone; and mixtures of such solvents with one another. The reaction is usually carried out at atmospheric pressure, although it may also be carried out at elevated or reduced pressure.

The reaction of II with a compound of formula III, wherein Q is hydroxy, is advantageously carried out in the presence of water-cleaving reagents that are conventional for esterification, for example in the presence of a carbodiimide [dicyclohexylcarbodiimide (DCC)] or a 1-alkyl-2-halogen-pyridinium salt such as 1-methyl-2-chloropyridinium iodide. The reaction is suitably carried out in the presence of an inert solvent or solvent mixture, at temperatures of -30°C to +70°C, preferably -10°C to +50°C. The process is preferably effected in the presence of a base, for example in the presence of an organic amine, such as a trialkylamine (trimethylamine, triethylamine, tripropylamine or diisopropylethylamine), a pyridine (pyridine itself, 4-dimethylaminopyridine or 4-pyrrolidinopyridine), a morpholine (N- methylmorpholine) or a N,N-dialkylaniline (N,N-dimethylaniline or N-methyl-N-ethylaniline). Suitable solvents for this purpose are for example aliphatic and aromatic hydrocarbons, such as benzene, toluene, xylenes, petroleum ether, hexane; halogenated hydrocarbons, such as chlorobenzene, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, ethylene tetrachloride; ethers and ether-like compounds, such as dialkyl ether (diethyl ether, diisopropyl ether, tert.-butylmethyl ether, etc.), anisole, dioxane, tetrahydrofuran; nitrites such as acetonitrile, propionitrile; esters such as ethyl acetate (acetic acid ethyl ester), propyl acetate or butyl acetate; and mixtures of such solvents with one another.

Conversion of free compounds I into salts and of salts into free compounds I or into other salts is effected in conventional manner, e.g. by treating a free compound I with an acid or treating a salt with a base.

Compounds of the type of formulae II and III and their preparation are known from literature or may be prepared analogously to known representatives. The compounds III may also be prepared by the processes described in US-4,950,666 and EP-A-0,432,861. Moreover, the procedure described in EP-0,577,555 pages 5-8 may also be followed.

Preparation examples

Example 1 : Preparation of 4-methyl-5,5-difluoropent-4-enoic acid-(2-r4(4-trifluoromethyl- benzyloxy)-phenoxy]ethyllester of formula C

3.7 g of 5,5-difluoropent-4-enoic acid chloride are added in portions, whilst cooling with ice, to a solution of 6.3 g of 2-{4-(4-trifluoromethylbenzoylphenoxy)}ethanol and 2.5 ml of pyridine in 60 ml of dichloroethene. The mixture is stirred for 12 hours at normal pressure and at room temperature. Then, the mixture is concentrated in a vacuum and the residue taken up in ethylether/HCI 2M. The organic phase is separated, then washed once with 2M HCI, twice with aqueous sodium hydrogen carbonate solution and once with sodium chloride solution, dried over sodium sulphate, filtered and concentrated in a vacuum. 8.7 g of a viscous oil are obtained. This is purified by chromatography on silica gel (1 :2 ethyl- ether/n-hexane). After removing the solvent, 7.4 g of title substance are obtained in the form of white crystals which have a melting point of 40-43°C.

In a modified embodiment, the procedure starts with 5,5-difluoropent-4-enoic acid in diethyl- ether/4-pyrrolidinopyridine and the reagent used is again 4-(4-trifluoromethyl- benzoylphenoxy)ethanol, whereby the reaction is carried out at ca. 0°C. Then, at temperatures of ca. 0°C to ca. +5°C, a total of g of N,N'-dicyclohexylcarbodiimide is added in portions, the ice cooling is removed and the reaction mixture is heated to room temperature whilst stirring over the course of 16 hours. The N,N'-dicyclohexylurea which precipitates as a deposit is separated and discarded. The solvent is removed in a vacuum and the residue purified by column chromatography on silica gel (eluant: hexane/ethyl acetate, 9:1 ). The pure title compound with the above-mentioned properties is obtained.

The representatives of formula I named in the following may also be prepared in analogous manner. The compound of formula I are usually obtained as very viscous colourless to yellowish oils of a waxy consistency. Ph denotes phenyl.

Table 1 : Preferred sub-group of compounds of formula la

No. R₃ R₄ Rs Z Ri R₂ A physical constant

1.01 H H H CH₃ H H O waxy

1.02 H H 2-CI CH₃ H H O 1.03 6-CI H 2-CI CH₃ H H O

1.04 H H 2-F CH₃ H H O

1.05 2-NO₂ H H CH₃ H H O waxy

1.06 5-CI H 3-CI CH₃ H H O

1.07 6-CI 4-CI 2-CI CH₃ H H O

1.08 H H H CH₃ H 3-CI O

1.09 H H 2-CI CH₃ H 3-CI O

1.10 6-CI H 2-CI CH₃ 5-CI 3-CI O

1.11 H H 2-F CH₃ H 3-F O

1.12 H H 2-F CH₃ 5-F 3-F O

1.13 5-CI H 3-CI CH₃ 6-CI 3-CI O

1.14 6-CI 4-CI 2-CI CH₃ 6-CI 2-CI O

1.15 H 4-CH3 H CH₃ H H O vitreous solid

1.16 H 4-CF3 H CH₃ H H O m.p: 43°C

1.17 H 3-NO₂ H CH₃ H H O n_D ²³= 1.521

1.18 4-CH3 3-CH3 H CH₃ H H O

1.21 H 4-CN H CH₃ H H O

1.22 H 4-F H CH₃ H H O

1.23 H 4-t.-Butyl H CH₃ H H O waxy

1.27 4-CH3 3-CH3 H CH₃ H 2-CI O

1.29 H 4-OCH3 H CH₃ H 2-CH3 O

1.30 H 4-CN H CH₃ 6-CI 2-CI O

1.31 H 4-F H CH₃ 5-F 2-F O

1.32 H 4-t.-Butyl H CH₃ H 3-CH3 O

1.33 H H H C₂H₅ H H O

1.34 H H 2-CI C₃H₇-n H H O

1.37 H H 2-F C₃H₇-i H H O

1.38 5-CI H 3-CI C₄H₉-n H H O

1.39 6-CI 4-CI 2-CI C₄H₉-s H H O

1.41 H H 2-CI C₃H₇-n H 3-CI O

1.42 6-CI H 2-CI CsHio-n 5-CI 3-CI O

1.43 H H 2-F C₆H₁ n H 3-F O

1.45 5-CI H 3-CI C₄H₉-n 6-CI 3-CI O

1.46 6-CI 4-CI 2-CI CeHn-n 6-CI 2-CI O

1.50 4-CH₃ 3-CH3 H C-2H5 H H O

1.51 H 2-NO₂ H C₃H₇-i H H O

1.52 H 4-OCH3 H C₃H₇-n H H O 1 .53 H 4-CN H C₄H₉-n H H O

1 .55 H 4-t.-Butyl H C-βHn-n H H 0

1 .56 H 4-CH₃ H C2H5 H 3-CI O

1.58 H 3-NO₂ H CsHio-n 5-F 3F O

1.59 4-CH₃ 3-CH3 H C₃H₇-n H 2-CI O

1.60 H 2-NO₂ H C₄H₉-n H 2-F O

1.61 H 4-OCH₃ H C2H5 H 2-CH₃ O

1.62 H 4-CN H C₄Hg-t 6-CI 2-CI O

1.63 H 4-F H C₄Hg-S 5-F 2-F O

1.64 H 4-t.-Butyl H C₃H₇-i H 3-CH₃ O

1.66 H H 2-CI C₃H₇-n H H S

1.69 H H 2-F C₃H₇-i H H S

1.70 5-CI H 3-CI C₄H₉-n H H S

1.71 H H H C₂H₅ H 3-CI S

1.72 H H 2-CI C₃H₇-n H 3-CI S

1.73 6-CI H 2-CI CsHio-n 5-CI 3-CI S

1.76 5-CI H 3-CI C₄Hg-n 6-CI 3-CI s

1.77 6-CI 4-CI 2-CI C₆H_ι n 6-CI 2-CI s 1.78 H 4-CH₃ H C₃H₇-n H H S

1.81 4-CH₃ 3-CH3 H C₂H₅ H H S

1.82 H 2-NO₂ H C₃H₇-i H H S

1.83 H 4-OCH3 H C₃H₇-n H H S

1.84 H 4-CN H C₄H₉-n H H S

1.86 H 4-t.-Butyl H C₆H_ι n H H S

1.87 H 4-CH3 H C₂H₅ H 3-CI S

1.89 H 3-NO₂ H C₅H₁₀-n 5-F 3F S

1.90 4-CH3 3-CH3 H C₃H₇-n H 2-CI S

1.91 H 2-NO2 H C₄H₉-n H 2-F S

1.92 H 4-OCH₃ H C₂H₅ H 2-CH3 S

1.93 H 4-CN H C₄Hg-t 6-CI 2-CI S

1.94 H 4-F H C₄Hg-S 5-F 2-F S

1.95 H 4-t.-Butyl H C₃H₇-i H 3-CH3 S

1.96 H H H CH₃ H H S

1.97 H H 2-CI CH₃ H H S

1.98 6-CI H 2-CI CH₃ H H S

1.99 H H 2-F CH₃ H H s

1.100 H H 2-F CH₃ H H s

1.101 5-CI H 3-CI CH₃ H H s

1.102 6-CI 4-CI 2-CI CH₃ H H s 1.103 H H H CH₃ H 3-CI S

1.104 H H 2-CI CH₃ H 3-CI S

1.105 6-CI H 2-CI CH₃ 5-CI 3-CI S

1.106 H H 2-F CH₃ H 3-F S

1.107 H H 2-F CH₃ 5-F 3-F S

1.108 5-CI H 3-CI CH₃ 6-CI 3-CI S

1.109 6-CI 4-CI 2-CI CH₃ 6-CI 2-CI S

1.113 4-CH₃ 3-CH3 H CH₃ H H S

1.114 H 2-NO₂ H CH₃ H H S

1.116 H 4-CN H CH₃ H H S

1.117 H 4-F H CH₃ H H S

1.1 18 H 4-t.-Butyl H CH₃ H H S

1.1 19 H 4-CH3 H CH₃ H 3-CI S

1.121 H 3-NO2 H CH₃ 5-F 3F S

1.122 4-CH3 3-CH3 H CH₃ H 2-CI S

1.124 H 4-OCH3 H CH₃ H 2-CH3 S

1.125 H 4-CN H CH₃ 6-CI 2-CI S

1.126 H 4-F H CH₃ 5-F 2-F S

1.127 H 4-t.-Butyl H CH₃ H 3-CH3 S 1.128 H H H F H H O

1.129 H H 2-CI F H H O

1.130 6-CI H 2-CI F H H O

1.131 H H 2-F F H H O

1.132 H H 2-F F H H O

1.133 5-CI H 3-CI F H H O

1.134 6-CI 4-CI 2-CI F H H O

1.135 H H H F H 3-CI O

1.136 H H 2-CI F H 3-CI O

1.137 6-CI H 2-CI F 5-CI 3-CI O

1.138 H H 2-F F H 3-F O

1.139 H H 2-F F 5-F 3-F O

1.140 5-CI H 3-CI F 6-CI 3-CI O

1.141 6-CI 4-CI 2-CI F 6-CI 2-CI O

1.148 H 4-CN H F H H O

1.148 H 4-F H F H H O

1.150 H 4-t.-Butyl H F H H O

1.154 4-CH₃ 3-CH3 H F H 2-CI O

1.155 H 2-NO₂ H F H 2-F O

1.156 H 4-OCH3 H F H 2-CH3 O

1.157 H 4-CN H F 6-CI 2-CI O

1.158 H 4-F H F 5-F 2-F O

1.159 H 4-t.-Butyl H F H 3-CH3 O

1.160 H H H Cl H H O

1.161 H H 2-CI Cl H H O

1.162 6-CI H 2-CI Cl H H O

1.163 H H 2-F Br H H O

1.164 H H 2-F Cl H H O

1.165 5-CI H 3-CI Br H H O

1.166 6-CI 4-CI 2-CI Cl H H O

1.167 H H H Cl H 3-CI S

1.168 H H 2-CI Cl H 3-CI S

1.169 6-CI H 2-CI Cl 5-CI 3-CI S

1.170 H H 2-F Br H 3-F S

1.171 H H 2-F Cl 5-F 3-F S

1.172 5-CI H 3-CI Br 6-CI 3-CI S

1.173 6-CI 4-CI 2-CI Cl 6-CI 2-CI S

1.174 H H H F H H NH

1.175 H H 2-CI F H H NCH₃

1.176 6-CI H 2-CI F H H NC2H5

1.177 H H 2-F F H H NH 1.178 H H 2-F Cl H H NC₆H₁₃-n

1.179 5-CI H 3-CI Cl H H NH

1.180 6-CI 4-CI 2-CI Cl H H NH

1.181 H H 2-F Cl 5-F 3-F NCH₃

1.182 5-CI H 3-CI F 6-CI 3-CI NC₂H₅

1.183 6-CI 4-CI 2-CI F 6-CI 2-CI NC2H5

1.185 H 4-CF3 H F H H NC₄H₉-n

1.187 4-CH₃ 3-CH3 H Cl H H NH

1.188 H 2-NO₂ H Cl H H NH

1.189 H 4-OCH3 H Br H H NCH₃

1.190 H 4-CN H Cl H H NCH₃

1.192 H 4-t.-Butyl H Cl H H NH

1.193 H 4-CH3 H Cl H 3-CI NCH₃

1.195 H 3-NO₂ H F 5-F 3F NCH₃

1.196 4-CH3 3-CH3 H F H 2-CI NH

1.197 H 2-NO2 H Ph H 2-F NC2H5

1.198 H 4-OCH3 H Ph H 2-CH3 NC₃H₇-n

1.199 H 4-CN H Ph 6-CI 2-CI NCH₃

1.200 H 4-F H Ph 5-F 2-F NCH₃

1.201 H 4-t.-Butyl H Ph H 3-CH3 NH

1.202 2-Ph H H CH₃ H H O n_D ²³= 1.527 1.203 2-Ph H H CH₃ H H S

1.204 3-CI 5-CI H CH₃ H H O

1.205 3-CI 5-CI H CH₃ H H S

1.206 H 4-C₄H₉-t H CH₃ H H O

1.207 H 4-C₄H₉-t H CH₃ H H S

1.208 H H H Br H 3-CI NCH₃

1.209 H H 2-CI Cl H 3-CI NC₂H₅

1.210 6-CI H 2-CI Br 5-CI 3-CI NH

Table 2: Compounds of formula lb:

No. R₅ m Ri R₂ physical constant

2.01 H CH₃ 1 2 H H O waxy

2.02 2-CI CH₃ 1 2 H H O

2.03 2-CI CH₃ 2 1 H H O

2.04 2-F CH₃ 1 2 H H O

2.05 2-F CH₃ 3 2 H H O

2.06 3-CI CH₃ 1 2 H H O

2.07 2-CI CH₃ 2 2 H H O

2.08 H CH₃ 2 1 H 3-CI O

2.09 2-CI CH₃ 3 1 H 3-CI O

2.10 2-CI CH₃ 3 3 5-CI 3-CI O 2.1 1 2-F CH₃ 2 H 3-F O

2.12 2-F CH₃ 2 5-F 3-F O

2.13 3-CI CH₃ 2 6-CI 3-CI O

2.14 2-CI CH₃ 2 6-CI 2-CI O

2.17 H CH₃ 2 H H NCH₃

2.18 H CH₃ 2 H 3-CI NH

2.19 H CH₃ 2 2 H 3-F S

2.20 H CH₃ 2 2 5-F 3F S

In the interim, the excellent insecticidal and acaricidal activity of the substances disclosed in EP-0,577,555 in in vitro tests and also in vivo in the field of plant protection could be confirmed. In contrast to this, the usage of the substances disclosed in EP-0.577.555 and indicated therein as speculative, for protecting domestic animals and productive livestock, proved to be substantially inapt, since the compounds release intolerable side effects when applied to productive livestock or domestic animals. These range from serious skin irritation, necrosis, to death of the treated animals. This means that this class of substance is completely unsuitable for usage in the field of animal health.

Surprisingly, a smaller specific group of structurally related new compounds, namely the compounds of formula I defined at the beginning, was discovered within this giant substance class. This group does not cause these negative side effects, but in contrast is tolerated extremely well by productive livestock and domestic animals even in larger quantities, and has excellent activity against insects and members of the family of acarids (arachnids, and especially mites and ticks). These unexpected favourable effects on warmblooded animals were totally unforeseeable and may be used with excellent results in the field of animal health for the control of ectoparasites. This favourable activity is evidently linked with the specific chemical structure. ln the context of the present invention, ectoparasites are understood to be in particular insects, mites and ticks. These include insects of the order: Lepidoptera, Coleoptera, Homoptera, Heteroptera, Diptera, Thysanoptera, Orthoptera, Psoroptes, Anoplura, Siphonaptera, Mallophaga, Thysanura, Isoptera, Psocoptera and Hymenoptera. However, the ectoparasites which may be mentioned in particular are those which trouble humans or animals and carry pathogens, for example flies such as Musca domestica, Musca vetustissima, Musca autumnalis, Fannia canicularis, Sarcophaga carnaria, Lucilia cuprina, Hypoderma bovis, Hypoderma lineatυm, Chrysomyia chloropyga, Dermatobia hominis, Cochliomyia hominivorax, Gasterophilus intestinalis, Oestrus ovis, Stomoxys calcitrans, Haematobia irritans and midges (Nematocera), such as Culicidae, Simuliidae, Psychodidae, but also blood-sucking parasites, for example fleas, such as Ctenocephalides felis and Ctenocephalides canis (cat and dog fleas), Xenopsylla cheopis, Pulex irritans, Dermatophilus penetrans, lice, such as Damalina ovis, Pediculus humanis, biting flies and horse-flies (Tabanidae), Haematopota spp. such as Haematopota pluvialis, Tabanidea spp. such as Tabanus nigrovittatus, Chrysopsinae spp. such as Ch ysops caecutiens, tsetse flies, such as species of Glossinia, biting insects, particularly cockroaches, such as Blatella germanica, Blatta orientalis, Periplaneta americana, mites, such as Dermanyssus gallinae, Sarcoptes scabiei, Psoroptes ovis and Psorergates spp. and last but not least ticks. The latter belong to the order Acarina. Known representatives of ticks are, for example, Boophilus, Amblyomma, Anocentor, Dermacentor, Haemaphysalis, Hyalomma, Ixodes, Rhipicentor, Margaropus, Rhipicephalus, Argas, Otobius and Ornithodoros and the like, which preferably infest warm-blooded animals including farm animals, such as cattle, pigs, sheep and goats, poultry such as chickens, turkeys and geese, fur-bearing animals such as mink, foxes, chinchillas, rabbits and the like, as well as domestic animals such as cats and dogs, but also humans.

Ticks may be divided into hard and soft ticks, and are characterised by infesting one, two or three host animals. They attach themselves to a passing host animal and suck the blood or body fluids. Fully engorged female ticks drop from the host animal and lay large amounts of eggs (2000 to 3000) in a suitable crack in the floor or in any other protected site where the larvae hatch. These in turn seek a host animal, in order to suck blood from it. Larvae of ticks which only infest one host animal moult twice and thus become nymphs and finally adult ticks without leaving the host they have selected. Larvae of ticks which infest two or three host animals leave the animal after feeding on the blood, moult in the local environment and seek a second or third host as nymphs or as adult ticks, in order to suck its blood.

Ticks are responsible world-wide for the transmission and spread of many human and animal diseases. Because of their economic influence, the most important ticks are Boophi- lus, Rhipicephalus, Ixodes, Hyalomma, Amblyomma and Dermacentor. They are carriers of bacterial, viral, rickettsial and protozoal diseases and cause tick-paralysis and tick-toxicosis. Even a single tick can cause paralysis whereby its saliva penetrates into the host animal during ingestion. Diseases caused by ticks are usually transmitted by ticks which infest several host animals. Such diseases, for example babesiosis, anaplasmosis, theileriasis and heart water disease, are responsible for the death or impairment of a large number of domestic and farm animals in the entire world. In many countries of temperate climate, ixodide ticks transmit the agent of the chronically harmful Lyme's disease from wild animals to humans. Apart from the transmission of disease, the ticks are responsible for great economic losses in livestock production. Losses are not confined to the death of the host animals, but also include damage to the coats, loss of growth, a reduction in milk production and reduced value of the meat. Although the harmful effects of a tick infestation on animals have been known for years, and enormous progress has been made using tick-control programmes, until now no completely satisfactory methods of controlling or eliminating these parasites have been found, and in addition, ticks have often developed resistance to chemical active ingredients.

The infestation of fleas on domestic animals and pets likewise still represents for the owner a problem which has not been satisfactorily resolved or can only be resolved at considerable expense. As with ticks, fleas are not only troublesome, but are carriers of disease, and transmit various fungal diseases from host animal to host animal and to the animal keeper, particularly in moist, warm climatic areas, for example in the Mediterranean, in the southern part of USA, etc. Those at risk in particular are people with a weakened immune system or children whose immune system has not yet fully developed. Owing to their complex life cycle, none of the known methods for the control of fleas is completely satisfactory, especially as most known methods are basically directed towards the control of adult fleas in the coat, and leave completely untouched the different juvenile stages of the fleas, which exist not only in the coat of the animal, but also on the floor, in carpets, in the bedding of the animal, on chairs, in the garden and all other places with which the infested animal comes into contact. Flea treatment is usually expensive and has to be continued over long periods of time. Success usually depends on treating not only the infested animal, e.g. the dog or cat, but at the same time all the locations which the infested animal frequents. The compounds of formula I are suitable both for the direct treatment of the animal, and also to disinfect its surroundings, and, because of its good tolerability, also for treating bedding.

A further preferred object of the present invention is thus a method for the control of parasites on domestic animals, livestock and pets, whereby a composition which contains at least one compound of formula I, or a physiologically acceptable salt thereof, is administered for curative usage to the warm-blooded animal preferably topically in an effective dose or is administered preventatively to the parasite-free warm-blooded animal.

As topical forms of application, pour-on and spot-on formulations are preferred in particular. However, administration in the form of sprays, ointments, solutions, baths or powders, may also be useful.

In the usage according to the invention, the compound of formula I according to the invention is normally not applied in pure form, but preferably in the form of a composition which contains, in addition to the active ingredient, application-enhancing constituents, whereby such constituents are beneficial to the host animal. The control according to the invention includes both the adult parasites and the juvenile stages of the parasites. Of course, further active substances may be added to broaden the spectrum of activity.

Such compositions to be used according to the invention usually contain 0.1 to 99 % by weight, especially 0.1 to 95 % by weight, of a compound of formula I according to the invention and 99.9 to 1 % by weight, especially 99.9 to 5 % by weight, of a solid or liquid, physiologically acceptable carrier, including 0 to 25 % by weight, especially 0.1 to 25 % by weight, or a non-toxic dispersant. Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations. Such compositions may also contain further additives, such as stabilisers, anti-foaming agents, viscosity regulators, binding agents or tackifiers, as well as other active ingredients, in order to achieve special effects.

The formulation excipients which may be used are the physiologically acceptable carriers which are known from veterinary medicine for oral, percutaneous and topical administration. A few examples are mentioned hereinafter.

Suitable carriers are in particular fillers, such as sugars, e.g. lactose, saccharose, mannitol or sorbitol, cellulose preparations and/or calcium phosphates, e.g. tricalcium phosphate or calcium hydrogen phosphate, in a broader sense also binders, such as starch pastes using e.g. corn, wheat, rice or potato starch, gelatin, tragacanth, methyl cellulose and/or, if desired, disintegrants, such as the above-mentioned starches, in a broader sense also carboxymethyl starch, cross-linked polyvinylpyrrolidone, agar, alginic acid or a salt thereof, such as sodium alginate. Excipients are especially flow conditioners and lubricants, for example silicic acid, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and/or polyethylene glycol. Tablet cores may be provided with suitable, where appropriate enteric, coatings, using inter alia concentrated sugar solutions which may comprise gum arabic, talc, polyvinylpyrrolidone, polyethylene glycol and/or titanium dioxide, or coating solutions in suitable organic solvents or solvent mixtures, or, for the preparation of enteric coatings, solutions of suitable cellulose preparations, such as acetylcellulose phthalate or hydroxypropylmethylcellulose phthalate. Dyes, flavours or pigments may be added to the tablets or tablet coatings, for example for identification purposes or to indicate different doses of active ingredient.

The preferred pour-on or spot-on method consists in applying the compound of formula I to a specific location of the skin or coat, advantageously to the neck or backbone of the animal. This takes place e.g. by applying a swab or spray of the pour-on or spot-on formulation to a relatively small area of the coat, from where the active substance is dispersed almost automatically over wide areas of the coat owing to the spreading nature of the components in the formulation and assisted by the animal's movements.

Pour-on or spot-on formulations suitably contain carriers, which promote rapid dispersement over the skin surface or in the coat of the host animal, and are generally regarded as spreading oils. Suitable carriers are e.g. oily solutions; alcoholic and isopropanoiic solutions such as solutions of 2-octyldodecanol or oleyl alcohol; solutions in esters of monocarboxylic acids, such as isopropyl myristate, isopropyl palmitate, lauric acid oxalate, oleic acid oleyl ester, oleic acid decyl ester, hexyl laurate, oleyl oleate, decyl oleate, capric acid esters of saturated fat alcohols of chain length Cι₂-Cι₈; solutions of esters of dicarboxylic acids, such as dibutyl phthalate, diisopropyl isophthalate, adipic acid diisopropyl ester, di-n-butyl adipate or also solutions of esters of aliphatic acids, e.g. glycols. It may be advantageous for a dispersing agent to be additionally present, such as one known from the pharmaceutical or cosmetic industry. Examples are pyrrolidin-2-one, N-alkylpyrrolidin-2-one, acetone, polyethylene glycol and the ethers and esters thereof, propylene glycol or synthetic triglycerides.

The oily solutions include e.g. vegetable oils such as olive oil, groundnut oil, sesame oil, pine oil, linseed oil or castor oil. The vegetable oils may also be present in epoxidised form. Paraffins and silicone oils may also be used.

A pour-on or spot-on formulation generally contains 1 to 20 % by weight of a compound of formula (I), 0.1 to 50 % by weight of dispersing agent and 45 to 98.9 % by weight of solvent.

The pour-on or spot-on method is especially advantageous for use on herd animals such as cattle, horses, sheep or pigs, in which it is difficult or time-consuming to treat all the animals orally or by injection. Because of its simplicity, this method can of course also be used for all other animals, including individual domestic animals or pets, and is greatly favoured by the keepers of the animals, as it can often be carried out without the specialist presence of the veterinarian.

The preparations of the present invention may be produced in known manner, e.g. by conventional processes. The following examples and patent claims illustrate the above- described invention, but in no way limit its scope. The temperatures are given in degrees Celsius. In the following formulation examples, the term compound of formula I represents a compound from the tables, preferably benzoic acid-4-methyl-5,5-difluoropent-4-enoic acid- 2-{[4-(4-trifluoromethylbenzyloxy)-phenoxy}ethylester. Formulation examples

Example: Pour on

A. compound of formula I 10% epoxidised soybean oil 5% oleyl alcohol 85%

B compound of formula 20% pyrrolidin-2-one 15% isopropyl myristate 65%

compound of formula I 5 g isopropyl myristate 10 g isopropanol ad 100 ml

D. compound of formula I 2 g hexyl laurat 5 g medium-chained triglycerides 15 g ethanol ad 100 ml

E. compound of formula I 2 g oleyl oleate 5 g

N-methyl-pyrrolidone 40 g isopropanol ad 100 ml

Spravable powder 25 parts by weight compound of formula I 1 part by weight sodium lauryl sulphate, 3 parts by weight colloidal silica gel, and 71 parts by weight urea. The constituents are mixed and ground together until homogeneous.

Suspension concentrates: compound of formula I 5 to 75 %, preferably 10 to 50 % water: 94 to 24 %, preferably 88 to 30 % surfactant: 1 to 40 %, preferably 2 to 30 %

Further biologically active substances or additives, which are neutral towards the compounds of formula I and do not have a harmful effect on the host animal to be treated, as well as mineral salts or vitamins, may be added to the described compositions.

The compositions may also contain further additives, such as stabilisers, e.g. where appropriate epoxidised vegetable oils (epoxidised coconut oil, rapeseed oil, or soybean oil); antifoams, typically silicone oil, preservatives, viscosity regulators, binders, and tackifiers, as well as fertilisers or other chemical agents to achieve special effects.

Further preparations with active substances of formula I may also be prepared analogously to the described formulations.

The compounds of formula I according to the invention may be used alone or in combination with other biocides. They may be combined with pesticides having the same sphere of activity e.g. to increase activity, or with substances having another sphere of activity e.g. to broaden the range of activity. It can also be sensible to add so-called repellents. If the range of activity is to be extended to endoparasites, e.g. wormers, the compounds of formula I are suitably combined with substances having endoparasitic properties. Of course, they can also be used in combination with antibacterial compositions. Since the compounds of formula I are adulticides, i.e. since they are effective in particular against the adult stage of the target parasites, the addition of pesticides which instead attack the juvenile stages of the parasites may be very advantageous. In this way, the greatest part of those parasites that produce great economic damage will be covered. Moreover, this action will contribute substantially to avoiding the formation of resistance. Many combinations may also lead to synergistic effects, i.e. the total amount of active ingredient can be reduced, which is desirable from an ecological point of view. Preferred groups of combination partners and especially preferred combination partners are named in the following, whereby combinations may contain one or more of these partners in addition to a compound of formula I.

Suitable partners in the mixture may be biocides, e.g. the insecticides and acaricides with a varying mechanism of activity, which are named in the following and have been known to the person skilled in the art for a long time, e.g. chitin synthesis inhibitors, growth regulators; active ingredients which act as juvenile hormones; active ingredients which act as adulticides; broad-band insecticides, broad-band acaricides and nematicides; and also the well known anthelminthics and insect- and/or acarid-deterring substances, said repellents or detachers.

Non-limitative examples of suitable insecticides and acaricides are:

(I) Aldicarb; (XVII) Endosulfan; (XXXV) Teflubenzuron;

(") Azinphos-methyl; (XVIII) Ethiofencarb; (XXXVI) Terbufos;

(III) Benfuracarb; (XIX) Fenitrothion; (XXXVII) Triazamate;

(IV) Bifenthrin; (XX) Fenobucarb; (XXXVIII) Abamectin;

(V) Buprofezin; (XXI) Fenvalerate; (XXXIX) Fenobucarb;

(VI) Carbofuran; (XXII) Formothion; (XL) Tebufenozide;

(VII) Dibutylaminothio (XXIII) Methiocarb; (XLI) Fipronil;

(VIM) Cartap; (XXIV) Heptenophos; (XLII) beta-Cyfluthrin;

(IX) Chlorfluazuron; (XXV) Imidacloprid; (XLIII) Silafluofen;

(X) Chlorpyrifos; (XXVI) Isoprocarb; (XLIV) Fenpyroximate;

(XI) Cyfluthrin; (XXVII) Methamidophos; (XLV) Pyridaben;

(XII) Lambda-Cy- (XXVIII) Methomyl; (XLVI) Fenazaquin; halothrin; (XXIX) Mevinphos; (XLVII) Pyriproxyfen;

(XIII) Alpha- (XXX) Parathion; (XLVIII) Pyrimidifen; cypermethrin; (XXXI) Parathion- (XLIX) Nitenpyram;

(XIV) zeta- m ethyl; (L) NI-25,

Cypermethrin; (XXXII) Phosalone; Acetamiprid;

(XV) Deltamethrin; (XXXIII) Pirimicarb;

(XVI) Diflubenzuron; (XXXIV) Propoxur;

(LI) Avermectin Bi;

(Lll) an insect-active extract from a plant;

(Llll) a preparation containing insect-active nematodes;

(LIV) a preparation obtainable from Bacillus subtilis;

(LV) a preparation containing insect-active fungi; (LVI) a pn eparation containir ig insect-active ! viruses;

(LVII) AC 303 630; (XCI) Dichlofenthion; (CXXVI) Malathion;

(LVIII) Acephat; (XCII) Dicliphos; (CXXVII) Mecarbam;

(LIX) Acrinathrin; (XCIII) Diethion; (CXXVIII) Mesulfenphos;

(LX) Alanycarb; (XCIV) Dimethoat; (CXXIX) Metaldehyd;

(LXI) Alphamethrin; (XCV) Dimethyl- (CXXX) Metolcarb;

(LXII) Amitraz; vinphos; (CXXXI) Milbemectin;

(LXIII) AZ 60541 ; (XCVI) Dioxathion; (CXXXII) Moxidectin;

(LXIV) Azinphos A; (XCVII) Edifenphos; (CXXXI II) Naled;

(LXV) Azinphos M; (XCVIII) Emamectin; (CXXXIV) NC 184;

(LXVI) Azocyclotin; (XCIX) Esfenvalerat; (CXXXV) Omethoat;

(LXVII) Bendiocarb; (C) Ethion; (CXXXVI) Oxamyl;

(LXVIII) Bensultap; (Cl) Ethofenprox; (CXXXVII) Oxydeme-

(LXIX) Betacyfluthrin; (Cll) Ethoprophos; thon M;

(LXX) BPMC; (Clll) Etrimphos; (CXXXVIII) Oxydeprofos;

(LXXI) Brofenprox; (CIV) Fenamiphos; (CXXXIX) Permethrin;

(LXXII) Bromophos A; (CV) Fenbutatinoxid; (CXL) Phenthoat;

(LXXIII) Bufencarb; (CVI) Fenothiocarb; (CXLI) Phorat;

(LXXIV) Butocarboxin; (CVII) Fenpropathrin; (CXLII) Phosmet;

(LXXV) Butylpyridaben; (CVIII) Fenpyrad; (CXLIII) Phoxim;

(LXXVI) Cadusafos; (CIX) Fenthion; (CXLIV) Pirimiphos M;

(LXXVII) Carbaryl; (CX) Fluazinam; (CXLV) Pirimiphos A;

(LXXVIII) Carbopheno- (CXI) Flucycloxuron; (CXLVI) Promecarb; thion; (CXII) Flucythrinat; (CXLVII) Propaphos;

(LXXIX) Chloethocarb; (CXI II) Flufenoxuron; (CXLVIII) Prothiofos;

(LXXX) Chlorethoxyfos; (CXIV) Flufenprox; (CXLIX) Prothoat;

(LXXXI) Chlormephos; (CXV) Fonophos; (CL) Pyrachlophos;

(LXXXII) Cis-Res- (CXVI) Fosthiazat; (CLI) Pyrada- methrin; (CXVII) Fubfenprox; phenthion;

(LXXXIII) Clocythrin; (CXVIII) HCH; (CLII) Pyresmethrin;

(LXXXIV) Clofentezin; (CXIX) Hexaflumuron; (CLIII) Pyrethrum;

(LXXXV) Cyanophos; (CXX) Hexythiazox; (CLIV) RH 5992;

(LXXXVI) Cycloprothrin; (CXXI) Iprobenfos; (CLV) Salithion;

(LXXXVII) Cyhexatin; (CXXII) Isofenphos; (CLVI) Sebufos;

(LXXXVIII) Demeton M; (CXXIII) Isoxathion; (CLVII) Sulfotep;

(LXXXIX) Demeton S; (CXXIV) Ivermectin; (CLVIII) Sulprofos;

(XC) Demeton-S- (CXXV) Lambda- (CLIX) Tebufenpyrad; methyl; cyhalothrin; (CLX) Tebupirimphos; (CLXI) Tefluthrin;

(CLXII) Temephos;

(CLXIII) Terbam;

(CLXIV) Tetrachlor- vinphos;

(CLXV) Thiafenox;

(CLXVI) Thiodicarb;

(CLXVII) Thiofanox;

(CLXVIII) Thionazin;

(CLXIX) Thuringiensin;

(CLXX) Tralomethrin;

(CLXXI) Triarthen;

(CLXXII) Triazophos;

(CLXXIII) Triazuron;

(CLXXIV) Trichlorfon;

(CLXXV) Triflumuron;

(CLXXVI) Trimethacarb;

(CLXXVI 1) Vamidothion;

(CLXXVIII) Xylylcarb;

(CLXXIX) Yl 5301/5302;

(CLXXX) Zetamethrin;

(CLXXXI) DPX-MP062;

(CLXXXII) RH-2485;

(CLXXXIII) D 2341 ;

(CLXXXIV) XMC (3,5-Xy- lylMethyl- carbamat),

(CLXXXV) Lufenuron

(CLXXXVI) Fluazuron

(CLXXXVII) Methoprene

(CLXXXVIII) Hydro- prene

(CLXXXIX) Fenoxycarb

(CXC) Chlorfenapyr or

(CXCI) Spinosad

(CXCII) Thiamethoxam Non-limitative examples of suitable anthelminthics are named in the following, a few representatives have insecticidal and acaricidal activity in addition to the anthelminthic activity, and are partly already in the above list.

(A1) Praziquantel = 2-cyclohexylcarbonyl-4-oxo-1 ,2,3,6,7,1 1 b-hexahydro-4H-pyrazino[2,1- αjisoquinoline (A2) Closantel = 3,5-diiodo-N-[5-chloro-2-methyl-4-(a-cyano-4-chlorobenzyl)phenyl]- salicylamide (A3) Triclabendazole = 5-chloro-6-(2,3-dichlorophenoxy)-2-methylthio-1 H-benzimidazole (A4) Levamisol = L-(-)-2,3,5,6-tetrahydro-6-phenylimidazo[2,1 b]thiazole (A5) Mebendazole = (5-benzoyl-1 H-benzimidazol-2-yl)carbaminic acid methylester (A6) Omphalotin = a macrocyclic fermentation product of the fungus Omphalotus olearius described in WO 97/20857 (A7) Abamectin = avermectin B1 (A8) Ivermectin = 22,23-dihydroavermectin B1 (A9) Moxidectin = 5-O-demethyl-28-deoxy-25-(1 ,3-dimethyl-1 -butenyl)-6,28- epoxy-23-

(methoxyimino)-milbemycin B (A10) Doramectin = 25-cyclohexyl-5-O-demethyl-25-de(1 -methylpropyl)-avermectin A1a (A11 ) Milbemectin = mixture of milbemycin A3 and milbemycin A4 (A12) Milbemvcinoxim = 5-oxime of milbemectin

Non-limitative examples of suitable repellents and detachers are:

(RP DEET (N, N-diethyl-m-toluamide)

(R2) KBR 3023 N-butyl-2-oxycarbonyl-(2-hydroxy)-piperidine

(R3) Cvmiazole = N,-2,3-dihydro-3-methyl-1 ,3-thiazol-2-ylidene-2,4-xylidene

The said partners in the mixture are best known to specialists in this field. Most are described in various editions of the Pesticide Manual, The British Crop Protection Council, London, and others in the various editions of The Merck Index, Merck & Co., Inc., Rahway, New Jersy, USA or in patent literature. Therefore, the following listing is restricted to a few places where they may be found by way of example.

(I) 2-Methyl-2-(methylthio)propionaldehyde-0-methylcarbamoyloxime (Aldicarb), from The Pesticide Manual, 11^th Ed. (1997), The British Crop Protection Council, London, page 26; (II) S-(3,4-dihydro-4-oxobenzo[o -[1 ,2,3]-triazin-3-ylmethyl)O,O-dimethyl-phosphoro- dithioate (Azinphos-methyl), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 67;

(III) Ethyl-N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl-(methyl)aminothio]-N- isopropyl-β-alaninate (Benfuracarb), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 96;

(IV) 2-Methylbiphenyl-3-ylmethyl-(Z)-(1 ftS)-c/s-3-(2-chloro-3,3,3-trifluorprop-1 -enyl)-2,2- dimethylcyclopropanecarboxylate (Bifenthrin), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 118;

(V) 2-tert-butylimino-3-isopropyl-5-phenyl-1 ,3,5-thiadiazian-4-one (Buprofezin), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 157;

(VI) 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl-methylcarbamate (Carbofuran), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 186;

(VII) 2,3-Dihydro-2,2-dimethylbenzofuran-7-yl-(dibutylaminothio)methylcarbamate (Carbosulfan), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 188;

(VIII) S,S'-(2-dimethylaminotrimethylene)-bis(thiocarbamate) (Cartap), from The Pesticide Manual, 1 1^lhEd. (1997), The British Crop Protection Council, London, page 193;

(IX) 1 -[3,5-Dichloro-4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenyl]-3-(2,6-difluoro- benzoyl)-urea (Chlorfluazuron), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 213;

(X) 0,C liethyl-C^3,5₎6-trichloro-2-pyridyl-phosphorothioate (Chlorpyrifos), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 235;

(XI) (flS)-α-cyano-4-fluoro-3-phenoxybenzyl-(1 RS,3RS;X flS,3RS)-3-(2,2-dichlorovinyl)- 2,2-di-methylcyclopropanecarboxylate (Cyfluthrin), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 293;

(XII) Mixture of (S)-α-cyano-3-phenoxybenzyl-(Z)-(1 fl,3F?)-3-(2-chloro-3,3,3-trifluoro- propenyl)-2,2-dimethylcyclopropanecarboxylate and (f?)-α-cyano-3-phenoxybenzyl-(Z)- (1 f?,3 ^:?)-3-(2-chloro-3₎3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate (Lambda-Cyhalothrin), from The Pesticide Manual, 1 1^,hEd. (1997), The British Crop Protection Council, London, page 300;

(XIII) Racemate consisting of (S)-α-cyano-3-phenoxybenzyl-(Z)-(1 f?,3H)-3-(2,2- dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate and (fi)-α-cyano-3-phenoxybenzyl- (1 S,3S)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (Alpha-cypermethrin), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 308;

(XIV) a mixture of the stereoisomers of (S)-α-cyano-3-phenoxybenzyl (1 RS,3RS,X RS,3RS)- 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (zeta-Cypermethrin), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 314;

(XV) (S)- -cyano-3-phenoxybenzyl-(1 R,3f?)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane- carboxylate (Deltamethrin), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 344;

(XVI) (4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea (Diflubenzuron), from The Pesticide Manual, 1 1 ^hEd. (1997), The British Crop Protection Council, London, page 395;

(XVII) (1 ,4,5,6,7,7-Hexachloro-8,9,10-trinorborn-5-en-2,3-yienebismethylene)-sulphite (Endosulfan), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 459;

(XVIII) α-ethylthio-o-tolyl-methylcarbamate (Ethiofencarb), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 479;

(XIX) 0,0-dimethyl-0-4-nitro-/7>tolyl-phosphorothioate (Fenitrothion), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 514;

(XX) 2-sec-butylphenyl-methylcarbamate (Fenobucarb), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 516;

(XXI) (f?S)-α-cyano-3-phenoxybenzyl-(flS)-2-(4-chlorophenyl)-3-methylbutyrate (Fenvalerate), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 539;

(XXII) S-[formyl(methyl)carbamoylmethyl]-0,0-dimethyl-phosphorodithioate (Formothion), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 625;

(XXIII) 4-Methylthio-3,5-xylyl-methylcarbamate (Methiocarb), from The Pesticide Manual, H^Ed. (1997), The British Crop Protection Council, London, page 813; (XXIV) 7-Chlorobicyclo[3.2.0]hepta-2,6-dien-6-yl-dimethylphosphate (Heptenophos), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 670;

(XXV) 1 -(6-chloro-3-pyridylmethyl)-/V-nitroimidazolidin-2-ylidenamine (Imidacloprid), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 706;

(XXVI) 2-isopropylphenyl-methylcarbamate (Isoprocarb), from The Pesticide Manual, 1 1 ^hEd. (1997), The British Crop Protection Council, London, page 729;

(XXVII) O.S-dimethyl-phosphoramidothioate (Methamidophos), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 808;

(XXVIII) S-Methyl-/ -(methylcarbamoyloxy)thioacetimidate (Methomyl), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 815;

(XXIX) Methyl-3-(dimethoxyphosphinoyloxy)but-2-enoate (Mevinphos), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 844;

(XXX) 0,0-diethyl-0-4-nitrophenyl-phosphorothioate (Parathion), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 926;

(XXXI) 0,0-dimethyl-0-4-nitrophenyl-phosphorothioate (Parathion-methyl), from The Pesticide Manual, 11 ^hEd. (1997), The British Crop Protection Council, London, page 928;

(XXXII) S-6-chloro-2,3-dihydro-2-oxo-1 ,3-benzoxazol-3-ylmethyl-0,0-diethyl-phosphor- dithioate (Phosalone), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 963;

(XXXIII) 2-Dimethylamino-5,6-dimethylpyrimidin-4-yl-dimethylcarbamate (Pirimicarb), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 985;

(XXXIV) 2-isopropoxyphenyl-methylcarbamate (Propoxur), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 1036;

(XXXV) 1 -(3,5-dichloro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea (Teflubenzuron), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 1158; (XXXVI) S-tert-butylthiomethyl-O.O-dimethyl-phosphorodithioate (Terbufos), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1165;

(XXXVII) ethyl-(3-terf.-butyl-1 -dimethylcarbamoyl-1 H-1 ,2,4-triazol-5-yl-thio)-acetate, (Triazamate), from The Pesticide Manual, 1 1^,hEd. (1997), The British Crop Protection Council, London, page 1224;

(XXXVIII) Abamectin, from The Pesticide Manual, 1 1 ^thEd. (1997), The British Crop Protection Council, London, page 3;

(XXXIX) 2-sec-butylphenyl-methylcarbamate (Fenobucarb), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 516;

(XL) Λ/-te/t-butyl-N-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide (Tebufenozide), from

The Pesticide Manual, 1 1^lhEd. (1997), The British Crop Protection Council, London, page

1 147; (XLI) (±)-5-amino-1 -(2,6-dichloro-α,α,α-trifluoro-p-tolyl)-4-trifluoromethyl-sulphinylpyrazol-3- carbonitrile (Fipronil), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop

Protection Council, London, page 545; (XLII) (f?S)-α-cyano-4-fluoro-3-phenoxybenzyl(1 RS,3RS;X RS,3RS)-3-(2,2-dich\oτo- vinyl)-2,2-dimethylcyclopropanecarboxylate (beta-Cyfluthrin), from The Pesticide Manual,

1 1^thEd. (1997), The British Crop Protection Council, London, page 295; (XLIII) (4-ethoxyphenyl)-[3-(4-fluoro-3-phenoxyphenyl)propyl](dimethyl)silane

(Silafluofen), from The Pesticide Manual, 11 ^hEd. (1997), The British Crop Protection

Council, London, page 1105; (XLIV) terf.-butyl (E)-α-(1 ,3-dimethyl-5-phenoxypyrazol-4-yl-methylenamino-oxy)-p- toluate (Fenpyroximate), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop

Protection Council, London, page 530; (XLV) 2-terf.-butyl-5-(4-te/t-butylbenzylthio)-4-chloropyridazin-3(2H)-one (Pyridaben), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 1 161 ; (XLVI) 4-[[4-(1 ,1-dimethylphenyl)phenyl]ethoxy]-quinazoline (Fenazaquin), from The

Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page

507; (XLVII) 4-phenoxyphenyl-(RS)-2-(pyridyloxy)propyl-ether (Pyriproxyfen), from The Pesticide Manual, 11^t Ed. (1997), The British Crop Protection Council, London, page 1073;

(XLVIII) 5-chloro-Λ/-{2-[4-(2-ethoxyethyl)-2,3-dimethylphenoxy]ethyl}-6-ethylpyrimidine-4- amine (Pyrimidifen), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 1070;

(XLIX) (£)-/V-(6-chloro-3-pyridylmethyl)-W-ethyl-N-methyl-2-nitrovinylidenediamine (Nitenpyram), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 880;

(L) (^-^-[(e-chloro-S-pyridy methylj-Λ^-cyano-Λ/^methylacetamidine (NI-25,

Acetamiprid), from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 9;

(LI) Avermectin Bi , from The Pesticide Manual, 1 1^,hEd. (1997), The British Crop Protection Council, London, page 3;

(Lll) an insect-active extract from a plant, especially (2/^:?,6aS,12aS)-1 ,2,6,6a,12,12a- hexhydro-2-isopropenyl-8,9-dimethoxy-chromeno[3,4- 3]furo[2,3-/7]chromen-6-one (Rotenone), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 1097; and an extract from Azadirachta indica, especially azadirachtin, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 59; and

(Lll!) a preparation which contains insect-active nematodes, preferably Heterorhabditis bacteriophora and Heterorhabditis megidis, from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 671 ; Steinernema feltiae, from The Pesticide Manual, 11^,hEd. (1997), The British Crop Protection Council, London, page 1115 and Steinernema scapterisci, from The Pesticide Manual, 1 1^,hEd. (1997), The British Crop Protection Council, London, page 1 1 16;

(LIV) a preparation obtainable from Bacillus subtilis, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 72; or from a strain of Bacillus thuringiensis with the exception of compounds isolated from GC91 or from NCTC11821 ; The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 73;

(LV) a preparation which contains insect-active fungi, preferably Verticillium lecanii, from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 1266; Beauveria brogniartii, from The Pesticide Manual, 1 1 ^hEd. (1997), The British Crop Protection Council, London, page 85 and Beauveria bassiana, from The Pesticide Manual, 11 ^hEd. (1997), The British Crop Protection Council, London, page 83;

(LVI) a preparation which contains insect-active viruses, preferably Neodipridon Sertiter NPV, from The Pesticide Manual, 1 1^thEd. (1997), The British Crop Protection Council, London, page 1342; Mamestra brassicae NPV, from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 759 and Cydia pomonella αraπu/os/s virus, from The Pesticide Manual, 1 1^,hEd. (1997), The British Crop Protection Council, London, page 291 ;

(CLXXXI) 7-chloro-2,3,4a,5-tetrahydro-2-[methoxycarbonyl(4-trifluoromethoxyphenyl)- carbamoyl]indol[1 ,2e]oxazoline-4a-carboxylate (DPX-MP062, Indoxycarb), from The Pesticide Manual, 11 ^hEd. (1997), The British Crop Protection Council, London, page 453;

(CLXXXII) /V-tert.-butyl-/V-(3,5-dimethylbenzoyl)-3-methoxy-2-methylbenzohydrazide (RH- 2485, Methoxyfenozide), from The Pesticide Manual, 11^thEd. (1997), The British Crop Protection Council, London, page 1094; and

(CLXXXIII) (Λ/'-[4-methoxy-biphenyl-3-yl]-hydrazinecarboxylic acid isopropylester (D 2341 ), from Brighton Crop Protection Conference, 1996, 487- 493;

(R2) Book of Abstracts, 212th ACS National Meeting Orlando, FL, August 25-29 (1996), AGRO-020. Publisher: American Chemical Society, Washington, D.C. CONEN: 63BFAF.

As a consequence of the above details, a further essential aspect of the present invention relates to combination preparations for the control of parasites on warm-blooded animals, characterised in that they contain, in addition to a compound of formula I, at least one further active ingredient having the same or different sphere of activity and at least one physiologically acceptable carrier. The present invention is not restricted to two-fold combinations.

Biological Examples:

Example 1 : Tolerabilitv study on sheep following pour-on application

Fully healthy females sheep aged from 4 to 5 months and weighing ca. 33 to 34 kg are shorn until bald on their backs, given a numbered ear tag for clear identification, and kept for the whole duration of the test in separate sheds with a slatted floor. One small group remains untreated and serves as a control. All the sheep are given standard fodder according to their age and water as desired. On day 0, 33 to 34 ml of a pour-on formulation according to example B (50 mg test substance/kg body weight) is applied to the back of each sheep. The sheep are continuously observed on the day of treatment, in order to establish unusual behaviour and local side effects. 6 hours after treatment and once each morning on the subsequent days, blood samples are taken and evaluated in respect of the following parameters.

blood values chemical values erythrocytes (RBC) aspartate aminotransferase (ASAT) haemoglobin (HB) alanine aminotransferase (ALAT) mean cell volume (HCT) creatine kinase (CK/NAC) mean cell haemoglobin (MCH) γ-glutamate transpeptidase (G-GT) mean cell haemoglobin concentration total bilirubin (TBILI)

(MCHC) leucocytes (WBC) creatinine (CREA) blood platelets (PLT) glucose (GLUC) blood platelets (PLT) glutamate dehydrogenase (GLDH) blood-urea-nitrogen (BUN) total protein (TOT. PROTEIN) albumin (ALB) globulin (GLOB) sodium (NA) potassium (K) calcium (CA) magnesium (MG)

It is shown that, following pour-on application, the test substances at no point lead to local side effects, and the measured blood and chemical values show absolutely the same range of fluctuation as in the untreated control animals. The compounds of formula I, e.g. compounds 1.01 , 1.02, 1.15, 1.16, 1.17, 1.23, 1.202 and 2.01 , proved to be well tolerated under the test conditions up to a dosage of 50 mg/kg. Example 2: In vivo efficacy on mange mites of sheep following pour-on application Healthy sheep of an average body weight of ca. 35 kg are artificially infected between the shoulder blades and in the groin area with mange (Psoroptes ovis) of all stages of development. After 3 weeks, about 90% of the sheep show infested skin areas of ca. 25- 50 cm². These infested sheep are selected for further studies and are given a numbered ear tag so that they can be clearly distinguished. During the whole duration of the test, the sheep are kept in individual sheds (0.9 x 1.2 m) with a slatted bottom. They are fed with ca. 0.7 kg maize and ca. 0.2 kg hay daily and have access to drinking water. 8 sheep are treated; 2 remain untreated and serve as a control group. Treatment is carried out using an aqueous emulsion with a final concentration of test substance of 500 ppm. Treatment is carried out by carefully wetting the infected places, taking care that the emulsion thoroughly moistens both the wool and the parts of skin below. Ca. 1 litre of emulsion is used per sheep. Efficacy of the test substances is determined at 14 day intervals based on the proportion of infested areas for a period of 6-8 weeks. The changes are determined in relation to the initial situation, whereby infestation directly before starting treatment represents the value 100%. In parallel with this, a record of the behaviour of the test animals is kept. Completely analogous tests are carried out with diluted test emulsions (100 ppm).

The evaluation shows that compounds of formula I from Tables 1 and 2 at a concentration of 500 ppm completely eliminate the infection after at most 48 hours, in that no more surviving mites can be found and the damaged parts of the skin show a progressing healing process. In the case of some compositions, e.g. compounds 1.01 , 1.02, 1.15, 1.16, 1.17, 1.23, 1.202 and 2.01 , this result is achieved even at a dilution of the test substance of 100 ppm. None of the animals treated shows undesired side effects; they behave perfectly normally during the whole duration of the test.

Example 3: In vivo effect of topical treatment on infestation with mouse fur mites

Mice infested with mites (Myocopetes musculinus and Myobia musculi) are anaesthetized, and the density of the mite population is examined under a stereomicroscope. The mice are divided into groups with the same infection index, i.e. with the same mite population in each case, the index consisting of a scale from 1 (no mites) to 30 (greatest mite density). For test purposes, only mice with an index of at least 25 on the said scale (high mite density) are used. The test substance is applied in the form of a pour-on solution, suspension or emulsion, i.e. applied topically to the coat. The dose is in the range 32 to 0.1 mg/kg bodyweight. Per mouse, 150 //I of solution, suspension or emulsion is applied along the backbone. Efficacy is evaluated 7, 28 and 56 days after application by comparing the infection index after treatment with that before treatment. The efficacy is expressed as a percentage reduction of the mite population. In this test, compounds of formula I from Tables 1 and 2, e.g. compounds 1.01 , 1.02, 1.15, 1.16, 1.17, 1.23, 1.202 and 2.01 , show a reduction of mite infestation of over 80% at a dilution of up to 10 mg/kg body weight, and even at the highest concentration of active substance show no negative side effects.

Claims

What we claim is:

1. Compounds of formula I

wherein R is the group

R_T and R₂, independently of one another, are hydrogen, halogen, cyano, nitro, d.₄alkyl,

C_1- -haloalkyl, C_1-4-alkoxy, C_1-4-haloalkoxy or benzyl;

A is oxygen, sulphur or -N(R₆)-, whereby R₆ is C_1-4-alkyl, phenylthio or tolylthio p is an integer from 1 to 10;

R₃, R₄ and R₅, independently of one another, are hydrogen, halogen, cyano, nitro, Cι_-4alkyl,

C_1- -haloalkyl, C_1-4-alkoxy or Cι-₄-haloalkoxy; or R₃ and R₄ are in neighbouring positions and, together with the phenyl ring to which they are bonded, form a naphthyl group; n is 1 , 2 or 3; m is 1 , 2 or 3; and Z is d-β-alkyl, phenyl or halogen; in free form or in the form of physiologically acceptable salts.

2. Compound of formula I according to claim 1 , in which Ri and R₂ signify hydrogen; A is oxygen; n is 1 ; m is 2; p is 3; and Z is CH₃ or F.

3. Compound of formula I according to claim 1 , which stems from the sub-group of formula la,

wherein R, and R₂, independently of one another, signify hydrogen, halogen or C_1-4-alkyl; A is oxygen, sulphur or -N(R₆)-, whereby R₆ is d.₄-alkyl; R₃, R₄ and R₅ independently of one another are hydrogen, halogen, cyano, nitro, Cι- -alkyl or C_1- -alkoxy; and Z is d.₄-alkyl, phenyl or halogen, in free form or in the form of physiologically acceptable salts.

4. Combination preparation for the control of parasites on warm-blooded animals, which contains, in addition to a compound of formula I, at least one further active ingredient having the same or other sphere of activity and at least one physiologically acceptable carrier.

5. Process for the preparation of compounds of formula I according to one of claims 1 to 4, whereby a compound of formula II,

wherein R, Ri, R , A and m are defined as under formula I, is reacted with a compound of formula III, if necessary in the presence of an inert solvent or solvent mixture,

wherein Q is hydroxy or halogen and p is defined as under formula I, preferably chlorine or bromine; and Z and p are defined as under formula I; whereby when Q is hydroxy, the reaction is preferably carried out in the presence of a hydrophiiic agent or a catalyst, and when Q is halogen, it is preferably carried out in the presence of an acid-binding agent.

6. Composition for the control of ectoparasites on a domestic animal, on livestock or on a pet, which contains as the active substance, in addition to inert excipients and carriers, at least one compound of formula I according to claim 1.

7. Method of producing a composition according to claim 6, whereby a compound of formula I according to claim 1 is intimately mixed with inert excipients and carriers.

8. A method of controlling ectoparasites on a domestic animal, on livestock or on a pet, whereby a compound according to one of claims 1 to 4 or a composition as in claim 6 is applied to the ectoparasites or to their locus.

9. Method according to claim 8, in which the compound of formula I according to one of claims 1 to 4 is applied as a pour-on formulation to the coat of a domestic animal, livestock or a pet.

10. Use of a compound of formula I according to one of claims 1 to 4, for producing an ectoparasitic composition for domestic animals, livestock or pets.