ZA200403851B

ZA200403851B - Amidoacetonitrile derivatives.

Info

Publication number: ZA200403851B
Application number: ZA200403851A
Authority: ZA
Inventors: Pierre Ducray; Thomas Goebel; Joerg Fruechtel; Jacques Bouvier; Gabriela Flum
Original assignee: Novartis Ag
Priority date: 2002-01-21
Filing date: 2004-05-19
Publication date: 2005-08-10
Also published as: ATE395327T1

Description

H-32268A

AMIDOACETONITRILE DERIVATIVES

Srgenio-compounds-

The present invention relates to new amidoacetonitrile compounds of the formula

R R, PR, Re R

Nd Ww IN - a WT b I,

Ar— CN 0 R, R, (Rel in which

R1 is hydrogen, C;-Csalkyl, halo-Cs-Cealkyl, cyano-C4-Cealkyl, Ci-Cealkoxymethy! or benzyl;

Rg, Rs, Rs, Rs and Rg are either, independently of one another, hydrogen, halogen, unsubstituted or mono- or polyhalogenated C1-Cealkyl, unsubstituted or mono- or poly- halogenated C,-Cealkenyl, unsubstituted or mono- or polyhalogenated C,-Cgalkynyl; unsubstituted or mono- or polysubstituted C1-Cgalkoxy, unsubstituted or mono- or poly- substituted halo-C;-Csalkoxy, unsubstituted or mono- or polysubstituted C3-Cecycloalkyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen and C;-Cealkyl; or unsubstituted or mono- or poly- substituted phenyl, in which the substituents can be independent of one another and are chosen from the group consisting of-halogen, nitro, cyano, C;-Csalkyl, halo-C,-Cealkyl,

C1-Csalkoxy, halo-C-Cgalkoxy, C-Cealkylthio, halo-C-Cealkylthio, C;-Cealkylsulfinyl, halo-C,-Cealkyisulfinyl, C,-Csalkylsulfonyl, halo-C,-Cealkylsulfonyl, C:-Csalkylamino or di-C,-Cealkylamino; or Rz and R; are together C,-Cgalkylene; either :

Ry is unsubstituted or mono- or polysubstituted Cs-Cecycloalkoxy, unsubstituted or mono- or polysubstituted C;-Cecycloalkylthio, unsubstituted or mono- or polysubstituted (Ca-Cecyclo- alkyl)(Ro)N, in which the substituents in each case are chosen from the group consisting of halogen and C;-Cgalkyl; hetaryl or hetaryloxy; and

Rs is halogen, nitro, cyano, Cs-Cealkyl, halo-C4-Cealkyl, C,-Cealkoxy, halo-C4-Cealkoxy,

C2-Cealkenyl, halo-C.-Cgalkenyl, C2-Cealkynyl, Cs-Cecycloalkyl, C2-Cealkenyloxy, halo-C,-Ce- alkenyloxy, C¢-Cealkylthio, halo-C,-Cgalkylthio, C,-Cealkylsulfonyloxy,

. | H-32268A halo-C;-Cealkylsulfonyloxy, C-Cealkylsulfinyl, halo-C,-Cgalkylsulfinyl, Cs-Csalkylsulfonyl, halo-C,-Cealkylsulfonyl, C,-Cealkenylthio, halo-C,-Cgalkenylthio, C»-Cealkenylsulfinyl, halo-C,-Cgalkenylsulfinyl, C,-Cealkenylsulfonyl, halo-C-Cealkenylsulfonyl, C-Csalkylamino, di-C,-Cgalkylamino, C4-Csalkylsulfonylamino, halo-C;-Csalkylsulfonylamino, C;-Csalkyl- carbonyl, halo-C;-Cealkylcarbonyl, C-Cgalkoxycarbonyl, C+-Cealkylaminocarbonyl, di-C+-Cealkylaminocarbonyl, unsubstituted or mono- or polysubstituted phenylamino, unsubstituted or mono- or polysubstituted phenylcarbonyl; unsubstituted or mono- or polysubstituted phenylmethoxyimino; unsubstituted or mono- or polysubstituted phenyl- hydroxymethyl; unsubstituted or mono- or polysubstituted 1-phenyl-1-hydroxyethyl; unsubstituted or mono- or polysubstituted phenyichioromethyl; unsubstituted or mono- or polysubstituted phenylcyanomethyl; unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C;-Cealkyl, halo-C4-Cgalkyl, Cs-Cgsalkoxy, halo-C4-Cealkoxy, Cs-Cealkylthio, halo-Cs-Cealkylthio, C;-Csalkylsulfinyl, halo-C;-Cealkyl- sulfinyl, C4-Cealkylsulfony! and halo-C,-Cealkylsulfonyl; unsubstituted or mono- or polysubstituted phenoxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C;-Csalkyl, halo-C4-Csalkyl,

Ci-Cealkoxy, halo-C;-Cgalkoxy, C,-Cealkylthio, halo-C4-Cealkylthio, C,-Csalkylsulfinyl, halo-C4-Cealkylsulfinyl, C4-Cealkylsulfonyl and halo-C4-Cealkylsulfonyl; unsubstituted or mono- or polysubstituted phenylacetylenyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C4-Cealkyl, halo-C4-Cealkyl, C4-Cealkoxy, halo-Cy-Cealkoxy, Ci-Csalkylthio, halo-C;-Cealkylthio,

C,-Cealkylsulfinyl, halo-C-Csalkylsulfinyl, C4-Cealkylsulfonyl and halo-C-Csalkylsulfonyl; or unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C¢-Cealkyl, halo-C4-Csalkyl, C1-Cealkoxy, halo-C;-Cgalkoxy, C-Csalkyithio, halo-C+-Cealkylthio, C;-Cealkylsulfinyl, halo-C;-Cealkylsulfinyl, C;-Cealkylsulfonyl and halo-C1-Cgalkylsulfonyl; or R; and Rg are together C3-Csalkylene;

Ar is unsubstituted or mono- or polysubstituted phenyl, unsubstituted or mono- or poly- substituted hetaryl, unsubstituted or mono- or polysubstituted naphthy! or unsubstituted or mono- or polysubstituted quinolyl, in which in each case the substituents can be independent of one another and are chosen from the group consisting of R; and Rg;

Re is hydrogen, C,-Cealkyl, halo-C4-Csalkyl, allyl, C-Cealkoxymethyl or -C(O)Rg;

Rio is C4-Cealkyl, halo-C;-Cealkyl or C,-Cealkoxymethyl;

Wis O, S, S(O) or N(Ry);

Ry1 is hydrogen or C,-Cealkyl; ais1,2,3o0r4; bis0, 1, 2,3 or4,; and nis0,1 or2, in which, if R; is hetaryloxy, the hetaryl group in R; is other than pyridyl; to their preparation and use in the control of endo- and ectoparasites, especially helminths, in and on warm-blooded productive livestock, domestic animals and plants, and also to pesticides which comprise at least one of these compounds.

Substituted amidoacetonitrile compounds with pesticidal action are disclosed in

EP-0 953 565 A2, for example. The active ingredients specifically revealed therein may not, however, always meet the requirements concerning strength and activity spectrum. There consequently exists a need for active ingredients with improved pesticidal properties. It has now been found that the amidoacetonitrile compounds of the formula | have outstanding pesticidal properties, in particular against endo- and ectoparasites in and on productive livestock, domestic animals and plants.

Alkyl - as group per se and as structural component of other groups and compounds, for example of haloalkyl, alkoxy, alkylthio, alkyisulfinyl and alkylsulfonyl, - is, in each case giving due consideration to the number of carbon atoms which the relevant group or compound has in each individual case, either straight-chain, i.e. methyl, ethyl, propyl, butyl, pentyl or hexyl, or branched, e.g. isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl or isohexyl.

Alkenyl - as group per se and as structural component of other groups and compounds - is, in each case giving due consideration to the number of carbon atoms and conjugated or isolated double bonds which the relevant group or compound has in each individual case, either straight-chain, e.g. allyl, 2-butenyl, 3-pentenyl, 1-hexenyl or 1,3-hexadienyl, or branched, e.g. isopropenyl, isobutenyl, isoprenyl, tert-pentenyl or isohexenyl.

Alkynyl - as group per se and as structural component of other groups and compounds - is,

H-32268A in each case giving due consideration to the number of carbon atoms and conjugated or isolated double bonds which the relevant group or compound has in each individual case, either straight-chain, e.g. propargyl, 2-butynyl, 3-pentynyl, 1-hexynyl, 1-heptyny! or 3-hexen- 1-ynyl, or branched, e.g. 3-methylbut-1-ynyl, 4-ethyipent-1-ynyl or 4-methylhex-2-ynyl.

Cycloalkyl - as group per se and as structural component of other groups and compounds, for example of halocycloalkyl, cycloalkoxy or cycloalkylthio, - is, in each case giving due consideration to the number of carbon atoms which the relevant group or compound has in each individual case, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

Hetaryl is pyridyl, pyrimidyl, s-triazinyl, 1,2,4-triazinyl, thienyl, furanyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, triazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, benzothienyl, benzofuranyl, benzothiazolyl, indolyl or indazolyl, preferably pyridyl, pyrimidyl, s-triaziny! or 1,2,4-triazinyl, in particular pyridyl or pyrimidy|.

Halogen - as group per se and as structural component of other groups and compounds, such as of haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulfinyl and haloalkylsulfonyl, - is fluorine, chlorine, bromine or iodine, in particular fluorine, chlorine or bromine, especially fluorine or chlorine.

Halogen-substituted carbon-comprising groups and compounds, such as haloalkyl, halo- alkoxy, haloalkylthio, haloalkylsulfinyl and haloalkyisulfonyl, can be partially halogenated or perhalogenated, it being possible, in the case of polyhalogenation, for the halogen substituents to be identical or different. Examples of haloalkyl - as group per se and as structural component of other groups and compounds, such as of haloalkoxy or halo- alkylthio, - are methyl substituted up to three times by fluorine, chlorine and/or bromine, such as CHF; or CF3; ethyl substituted up to five times by fluorine, chlorine and/or bromine, such as CH,CF3, CF,CF3;, CF,CCls, CF,CHCI,, CF,CHF,, CF,CFCl,, CF,CHBr,, CF,CHCIF,

CF,CHBrF or CCIFCHCIF; propyl or isopropyl substituted up to seven times by fluorine, chlorine and/or bromine, such as CH,CHBrCH,Br, CF,CHFCF;, CH,CF.CF;, or CH(CF,)y; butyl or one of its isomers substituted up to nine times by fluorine, chlorine and/or bromine, such as CF(CF3)CHFCF; or CH,(CF.),CF3; pentyl or one of its isomers substituted up to eleven times by fluorine, chlorine and/or bromine, such as CF(CF3)(CHF),CF; or

CH»(CF2)sCFs; and hexyl or one of its isomers substituted up to thirteen times by fluorine, chlorine and/or bromine, such as (CH,)sCHBrCH,Br, CF,(CHF),CFs, CH,(CF,)4CF; or

C(CF3)2(CHF).CF3.

' H-32268A

Alkoxy groups preferably have a chain length of 1 to 6 carbon atoms. For example, alkoxy is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy, and also the pentyloxy and hexyloxy isomers; preferably methoxy and ethoxy. Haloalkoxy groups preferably have a chain length of 1 to 6 carbon atoms. Haloalkoxy is, e.g., fluoro- methoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy and 2,2,2-trichloroethoxy; preferably difluoromethoxy, 2-chloroethoxy and trifluoromethoxy.

Preferred embodiments within the context of the invention are: (1) A compound of the formula 1, in which R; is hydrogen, C;-Caalkyl or halo-C;-Caalkyl; particularly hydrogen or C,-C,alkyi; very particularly hydrogen; (2) A compound of the formula I, in which R;, Rj, Rs, Rs and Rg are, independently of one another, hydrogen, unsubstituted or mono- or polyhalogenated C;-Cealkyl, unsubstituted or mono- or polyhalogenated C»-Csalkenyl or unsubstituted or mono- or polyhalogenated

C,-Cealkynyl; particularly, independently of one another, hydrogen or unsubstituted or mono- or polyhalogenated C;-Cgalkyl; very particularly, independently of one another, hydrogen or unsubstituted C;-C,alkyl; (3) A compound of the formula 1, in which R; is unsubstituted C3-Cscycloalkoxy, unsubstituted Cs-Cecycloalkylthio or unsubstituted (Cs-Cscycloalkyl)(Rg)N; particularly unsubstituted C;-Cscycloalkoxy or unsubstituted (C;-Cscycloalkyl)(Rg)N; very particularly unsubstituted C;-C,cycloalkoxy; (4) A compound of the formula |, in which Rs is halogen, nitro, cyano, C4-C,alkyl, halo-C4-Calkyl, C4-Csalkoxy, halo-C;-Cjalkoxy, C»-Csalkenyl, halo-C.-Cialkenyl,

C2-Caalkynyl, C5-Cscycloalkyl, C,-Caalkenyloxy, halo-C,-Csalkenyloxy, C,-Cjalkylthio, halo-C;-Cjalkylthio, C,-C,alkenylthio, halo-C.-Calkenylthio, C4-Cqalkylamino, di-C,-Calkyl- amino, C¢-Calkyicarbonyl, halo-C;-C,alkylcarbonyl, C-Csalkoxycarbonyl, unsubstituted or mono- or polysubstituted phenylamino, unsubstituted or mono- or polysubstituted phenyl- carbonyl; unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of oo H-32268A halogen, nitro, cyano, C,-C,alkyl, halo-C4-Caalkyl, C;-Csalkoxy, halo-C,-Caalkoxy, C,-Caalkyl- thio and halo-C-C,alkylthio; unsubstituted or mono- or polysubstituted phenoxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C-C,alkyl, halo-C-C,alkyl, C-C,alkoxy, halo-C;-Cjalkoxy, C;-Csalkylthio and halo-C4-C,alkylthio; or unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C,-C4alkyl, halo-C;-C,alkyl,

C+-Caalkoxy, halo-C4-C,alkoxy, C;-Caalkylthio and halo-C4-C,alkylthio; particularly halogen, nitro, cyano, C,-C,alkyl, halo-C;-C,alkyl, Cs-Cjalkoxy, halo-C;-C,alkoxy,

Cs-Cscycloalkyl, C,-Caalkyicarbonyl, C;-C,alkoxycarbonyl, unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C;-C,alkyl, halo-C;-Caalkyl, C4-Caalkoxy and halo-Cs-C,alkoxy; or unsubstituted or mono- or poly- substituted phenoxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C,-C,alkyl, halo-C;-Calkyl,

C4-Caalkoxy, halo-C;-Caalkoxy, Cy-Cialkylthio and halo-C,-Cgalkylthio; very particularly halogen, nitro, cyano, C4-Czalkyl, halo-C;-Czalkyl, C;-C,alkoxy, halo-C;-Czalkoxy, Cs-C4cycloalkyl, Ci-C.alkylcarbony! or C;-C alkoxycarbonyl; (5) A compound of the formula |, in which Ar is unsubstituted or mono- or polysubstituted phenyl or unsubstituted or mono- or polysubstituted hetaryl, in which in each case the substituents can be independent of one another and are chosen from the group consisting of R; and Reg; particularly unsubstituted or mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from Rg; very particularly mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from Rg; (6) A compound of the formula |, in which Rg is hydrogen, C;-Cealkyl or halo-C,-Cgalky; particularly hydrogen or C,-C,alkyl; very particularly hydrogen or C;-Coalkyl; (7) A compound of the formula I, in which W is O, S or N(R); particularly O or S;

H-32268A very particularly O; (8) A compound of the formula I, in which Ry, is hydrogen or C,-C,alkyl; particularly hydrogen or C4-Caalkyl; very particularly methyi; (9) A compound of the formula |, in which ais 1, 2 or 3; particularly 1 or 2; very particularly 1; (10) A compound of the formula [, in which bis 0, 1,2 or 3; particularly O or 1; very particularly 0; (11) A compound of the formula |, in whichb is 0, 1 or2 particularly nis 1 or 2; very particularly 2; (12) A compound of the formula |, in which

R: is hydrogen, C,-C,alkyl or halo-C,-C,alkyl;

Raz, Rs, Rs, Rs and Rs are, independently of one another, hydrogen, unsubstituted or mono- or polyhalogenated C4-Cealkyl, unsubstituted or mono- or polyhalogenated C,-Csalkenyl or unsubstituted or mono- or polyhalogenated C,-Cgalkynyl;

Ry is unsubstituted Cs-Cgcycloalkoxy, unsubstituted Cs-Cscycloalkylthio or unsubstituted (C3-Cecycloalkyl)(Rg)N;

Rg is halogen, nitro, cyano, C4-Calkyl, halo-C4-Csalkyl, Cs-Caalkoxy, halo-C,-Caalkoxy,

C.-Caalkenyl, halo-C,-C,alkenyl, C,-Cialkynyl, Cs-Cscycloalkyl, C»-Cjalkenyloxy, halo-C,-C,alkenyloxy, C4-Csalkyithio, halo-C4-C,alkylthio, C,-Csalkenyithio, halo-C,-Caalkenylthio, C-C,alkylamino, di-C;-Caalkylamino, C;-C,alkylcarbonyl, halo-C+-Csalkylcarbonyl, Cs-Cjalkoxycarbonyl, unsubstituted or mono- or polysubstituted phenylamino, unsubstituted or mono- or polysubstituted phenylcarbonyl; unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano,

" H-32268A

Ci-Caalkyl, halo-Cs-Caalkyl, C4-Caalkoxy, halo-C4-Csalkoxy, C,-Cialkyithio and halo-C,-Cjalkylthio; unsubstituted or mono- or polysubstituted phenoxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C4-C,alkyl, halo-C,-Caalkyl, C-C,alkoxy, halo-C;-Csalkoxy,

Ci-Caalkylthio and halo-C;-C,alkylthio; or unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C;-Caalkyl, halo-C4-Caalkyl, C4-C,alkoxy, halo-C4-Cjalkoxy, C;-Csalkylthio and halo-C4-Cjalkyithio;

Ar is unsubstituted or mono- or polysubstituted phenyl or unsubstituted or mono- or polysubstituted hetaryl, in which in each case the substituents can be independent of one another and are chosen from the group consisting of R; and Rg;

Rs is hydrogen, C;-Cgalkyl or halo-C4-Cgalkyl;

Wis O, S or N(R);

R11 is hydrogen or C4-C,alkyl; ais1,2o0r3; bis0,1,2o0r3; and nis 0, 1or2; (13) A compound of the formula |, in which : R, is hydrogen or C;-C,alkyl;

Ra, Ra, Rs, Rs and Rg are, independently of one another, hydrogen or unsubstituted or mono- or polyhalogenated C,-Cgalkyl;

Ry is unsubstituted C3-Cscycloalkoxy or unsubstituted (Cs-Cscycloalkyl)(Rg)N;

Rs is halogen, nitro, cyano, C4-Cajalkyl, halo-C:-Cjalkyl, C,-Caalkoxy, halo-C4-C,alkoxy,

Cs-Cscycloalkyl, Cy-Caalkylcarbonyl, C4-Csalkoxycarbonyl, unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, Ci-Caalkyl, halo-Ci-Caalkyl, Ci-Csalkoxy and halo-C,-Caalkoxy; or unsubstituted or mono- or polysubstituted phenoxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C;-C,alkyl, halo-C+-C,alkyl,

Ci-Caalkoxy, halo-C4-Cjalkoxy, C4-Caalkylthio and halo-C;-Cqalkyithio;

H-32268A

Ar is unsubstituted or mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from R, and Rg;

Rs is hydrogen or C4-C,alkyl;

Wis OorS; ais1or2; bisOor 1; and nis 1or2; (14) A compound of the formula I, in which

R: is hydrogen;

Ra, Rs, Ra, Rs and Rg are, independently of one another, hydrogen or unsubstituted

Ci-Caalkyl;

Ry is unsubstituted Cs-Cycycloalkoxy or unsubstituted (C;-Cycycloalkyl)(Rg)N;

Rs is halogen, nitro, cyano, C,-Cqalkyl, halo-C,-Cpalkyl, C-Cjalkoxy, halo-C;-C,alkoxy,

Cs-Cycycloalkyl, C4-Coalkylcarbonyl or C,-Cjalkoxycarbonyl;

Ar is mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from Rg;

Rg is hydrogen or C,-Coalkyl;

Wis O;

Ry is methyl; ais 1; b is 0; and nis 2.

The compounds of the formula I listed in Table 1 are particularly preferred within the context of the invention and the compounds of the formula | mentioned in the synthetic examples are very particularly preferred.

A further subject-matter of the invention is the process for the preparation of the compounds of the formula |, in each case in the free form or in the salt form, e.g. which comprises the reaction of a compound of the formula

H-32268A

R, \ R, i ea

N + (C),—W—(C); I,

H oN L \ (Ry), which is known or can be prepared by analogy to relevant known compounds and in which

Ri, Ra, Rs, Rs, Rs, Re, Ry, Rg, X, W, a, b and n are as defined above in the formula |, with a compound of the formula

Q

A—

Oo which is known or can be prepared by analogy to relevant known compounds and in which

Ar is as defined above in the formula | and Q is a leaving group, if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula | obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula |, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula | obtainable according to the process to a salt or the conversion of a salt of a compound of the formula | obtainable according to the process to the free compound of the formula | or to another salt.

That which has been said above for salts of compounds | applies analogously to starting materials mentioned hereinabove and hereinafter with regard to the salts thereof.

The reactants can be reacted with one another as such, i.e. without addition of a solvent or diluent, e.g. in the molten form. For the most part, however, it is advantageous to add an inert solvent or diluent or a mixture thereof. Mention may be made, as examples of such solvents or diluents, of: aromatic, aliphatic and alicyclic hydrocarbons and halogenated hydrocarbons, such as benzene, toluene, xylene, mesitylene, tetralin, chlorobenzene, dichlorobenzene, bromobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, trichloromethane, tetrachloromethane, dichloroethane, trichloroethene or tetrachioroethene; ethers, such as diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, tert-butyl methyl ether, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol dimethyl ether, dimethoxydiethyl ether, tetrahydrofuran or dioxane; ketones, such as acetone, methyl ethyl ketone or methyl isobutyl ketone; amides, such as N,N-dimethyi- formamide, N,N-diethyiformamide, N,N-dimethylacetamide, N-methylpyrrolidone or hexamethylphosphoramide; nitriles, such as acetonitrile or propionitrile; and sulfoxides,

Preferred leaving groups Q are OH, halogens, tosylates, mesylates and triflates, particularly preferably halogens, especially chlorine.

Suitable bases for facilitating the reaction are, e.g., alkali metal or alkaline earth metal hydroxides, hydrides, amides, alkoxides, acetates, carbonates, dialkylamides or alkyl- silylamides, alkylamines, alkylenediamines, if desired N-alkylated and saturated or unsaturated, cycloalkylamines, basic heterocycles, ammonium hydroxides and carbocyclic amines. Mention may be made, by way of examples, of sodium hydroxide, sodium hydride, sodamide, sodium methoxide, sodium acetate, sodium carbonate, potassium tert-butoxide, potassium hydroxide, potassium carbonate, potassium hydride, lithium diisopropylamide, potassium bis(trimethyisilyl)amide, calcium hydride, triethylamine, diisopropylethylamine, triethylenediamine, cyclohexylamine, N-Cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine, 4-(N,N-dimethylamino)pyridine, quinuclidine, N-methyimorpholine, benzyitrimethylammonium hydroxide and 1,5-diazabicyclo[5.4.0]Jundec-5-ene (DBU).

The reaction is advantageously carried out at a temperature from approximately 0°C to approximately +150°C, preferably from approximately 20°C to approximately +100°C.

Salts of compounds | can be prepared in a way known per se. Thus, for example, acid addition salts of compound | are obtained by treatment with a suitable acid or a suitable ion- exchange reagent and salts with bases are obtained by treatment with a suitable base or a suitable ion-exchange reagent.

Salts of compounds | can be converted in the usual way to the free compounds |, acid addition salts, e.g. by treatment with a suitable basic agent or a suitable ion exchange reagent, and salts with bases, e.g. by treatment with a suitable acid or a suitable ion- exchange reagent.

Salts of compounds | can be changed in a way known per se to other salts of compounds |, acid addition salts for example to other acid addition salts, e.g. by treatment of a salt of an inorganic acid, such as a hydrochloride, with a suitable metal salt, such as a sodium, barium or silver salt, of an acid, e.g. with silver acetate, in a suitable solvent, in which an inorganic salt, e.g. silver chloride, being formed is insoluble and for this reason precipitates from the reaction mixture.

According to the method or reaction conditions, the compounds | with salt-forming

H-32268A properties can be obtained in the free form or in the form of salts.

The compounds | can also be obtained in the form of their hydrates and/or can incorporate other solvents, which might, for example, be used in the crystallization of compounds existing in the solid form.

The compounds | can exist in the form of one of the possible isomers or as a mixture of the same, e.g., according to the number, absolute and relative configuration of the asymmetric carbon atoms, as pure isomers, for example optical isomers and/or diastereoisomers, or as mixtures of isomers, such as mixtures of enantiomers, e.g. racemates, mixtures of diastereoisomers or racemate mixtures; the invention relates both to the pure isomers and to all possible mixtures of isomers and is to be correspondingly understood in each case heretofore and hereinafter, even if stereochemical details are not specifically referred to in every case.

Mixtures of diastereoisomers and mixtures of racemates of compounds | obtainable according to the process - depending on the choice of the starting materials and operating methods - or otherwise obtainable can be separated in a known way into the pure diastereoisomers or racemates on the basis of the physicochemical differences of the components, for example by fractional crystallization, distillation and/or chromatography.

Correspondingly obtainable mixtures of enantiomers, such as racemates, can be resolved into the optical isomers by known methods, for example by recrystaliization from an optically active solvent, by chromatography on chiral adsorbents, e.g. high performance liquid chromatography (HPLC) on acetyicellulose, with the help of suitable microorganisms, by cleavage with specific immobilized enzymes, via the formation of inclusion complexes, e.g. by using chiral crown ethers, in which only one enantiomer is complexed.

In addition to through separation of the corresponding mixtures of isomers, pure diastereoisomers or enantiomers according to the invention can also be obtained through generally known methods of diastereoselective or enantioselective synthesis, e.g. by carrying out the process according to the invention with educts with correspondingly suitable stereochemistry.

Advantageously, the biologically more effective isomer, e.g. enantiomer, or mixture of isomers, e.g. mixture of enantiomers, is isolated or synthesized each time, provided that the individual components have different biological activity.

H-32268A

In the process of the present invention, use is preferably made of such starting materials and intermediates which result in the compounds | described at the beginning as particularly valuable.

The invention relates in particular to the preparation process described in the example.

Starting materials and intermediates used according to the invention for the preparation of the compounds | which are novel, their use and processes for their preparation likewise form a subject-matter of the invention.

The compounds | according to the invention are characterized by a particularly broad activity spectrum and are valuable active ingredients in the field of pest control which are well tolerated by warm-blooded species, fish and plants, including in particular for controlling endo- and ectoparasites which parasitize animals.

In the context of the present invention, the term “ectoparasites” is understood to mean, in particular, insects, mites and ticks. This includes insects of the orders: Lepidoptera,

Coleoptera, Homoptera, Heteroptera, Diptera, Thysanoptera, Orthoptera, Anoplura,

Siphonaptera, Mallophaga, Thysanura, Isoptera, Psocoptera and Hymenoptera. However, reference may in particular be made to ectoparasites which are a nuisance to man or animals and which transmit pathogens, for example flies, such as Musca domestica, Musca vetustissima, Musca autumnalis, Fannia canicularis, Sarcophaga carnaria, Lucilia cuprina,

Hypoderma bovis, Hypoderma lineatum, Chrysomyia chloropyga, Dermatobia hominis,

Cochliomyia hominivorax, Gasterophilus intestinalis, Oestrus ovis, Stomoxys calcitrans,

Haematobia irritans, and mosquitoes (Nematocera), such as Culicidae, Simuliidae,

Psychodidae, but also bloodsucking 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, stable flies and horse flies (Tabanidae), Haematopota spp., such as Haematopota pluvialis, Tabanidea spp., such as Tabanus nigrovittatus, Chrysopsinae spp., such as Chrysops caecutiens, tsetse flies, such as Glossinia species, biting insects, in particular 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, e.g.,

Boophilus, Amblyomma, Anocentor, Dermacentor, Haemaphysalis, Hyalomma, Ixodes,

Rhipicentor, Margaropus, Rhipicephalus, Argas, Otobius and Ornithodoros and the like,

H-32268A which preferably infest warm-blooded animals, including farm animals, such as cows, pigs, sheep and goats, poultry, such as chickens, turkeys and geese, fur-bearing animals, such as mink, foxes, chinchillas, rabbits and the like, and pets, such as cats and dogs, but also man.

The compounds | according to the invention are also effective against all or individual development stages of normally sensitive but also of resistant animal pests, such as insects and representatives of the order Acarina. The insecticidal, ovicidal and/or acaricidal action of the active ingredients according to the invention may in the process be displayed directly, i.e. in killing the pests, which occurs immediately or only after some time, for example during moulting, or their eggs, or indirectly, e.g. in reduced egg laying and/or in a reduced hatching rate, in which the good action corresponds to a kill rate (mortality) of at least 50 to 60%.

The compounds | can also be used against hygiene pests, in particular of the order Diptera with the families Sarcophagidae, Anophilidae and Culicidae; of the orders Orthoptera,

Dictyoptera (e.g. the family Blattidae) and Hymenoptera (e.g. the family Formicidae).

The compounds | also have lasting activity in the case of phytoparasitic mites and insects.

In the case of spider mites of the order Acarina, they are active against eggs, nymphs and adults of Tetranychidae (Tetranychus spp. and Panonychus spp.).

They are highly active in the case of the sucking insects of the order Homoptera, in particular against pests of the families Aphididae, Delphacidae, Cicadellidae, Psyllidae,

Loccidae, Diaspididae and Eriophydidae (e.g. citrus rust mite); of the orders Hemiptera,

Heteroptera and Thysanoptera, and in the case of the phytophagous insects of the orders

Lepidoptera, Coleoptera, Diptera and Orthoptera.

They are also suitable as soil insecticides against pests in the soil.

The compounds of the formula | are accordingly active against all development stages of sucking and feeding insects on crops such as cereals, cotton, rice, maize, soya beans, potatoes, vegetables, fruit, tobacco, hops, citrus fruit, avocados and others.

The compounds of the formula [ are also active against plant nematodes of the genera

Meloidogyne, Heterodera, Pratylenchus, Ditylenchus, Radopholus, Rizoglyphus and others.

The compounds are particularly active against helminths, among which the endoparasitic nematodes and trematodes can be the cause of serious diseases in mammals and poultry, e.g. in sheep, pigs, goats, cattle, horses, donkeys, dogs, cats, guinea pigs and ornamental

* H-32268A birds. Typical nematodes of this indication are: Haemonchus, Trichostrongylus, Ostertagia,

Nematodirus, Cooperia, Ascaris, Bunostonum, Oesophagostonum, Chabertia, Trichuris,

Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris,

Ancylostoma, Uncinaria, Toxascaris and Parascaris. Mention may specifically be made, among the trematodes, of the family of the Fasciolideae, in particular Fasciola hepatica.

The particular advantage of the compounds of the formula | is their activity against such parasites, which are resistant to benzimidazole-based active ingredients.

Certain species of the genera Nematodirus, Cooperia and Oesophagostonum attack the intestinal tract of the host animal, while others of the genera Haemonchus and Ostertagia parasitize in the stomach and others of the genus Dictyocaulus parasitize in lung tissue.

Parasites of the families Filariidae and Setariidae are found in internal cell tissue and in organs, e.g. the heart, blood vessels, lymph vessels and subcutaneous tissue. Mention may particularly be made here of the dog heartworm, Dirofilaria immitis. The compounds of the formula | are highly effective against these parasites.

The pests which can be controlled with the compounds of the formula | also include, from the class Cestoda (tapeworms), the families Mesocestoidae, in particular the genus

Mesocestoides, especially M. lineatus; Dilepididae, in particular Dipylidium caninum,

Joyeuxiella spp., especially Joyeuxiella pasquali, and Diplopylidium spp.; and Taeniidae, in particular Taenia pisiformis, Taenia cervi, Taenia ovis, Taenia hydatigena, Taenia multiceps, Taenia taeniaeformis, Taenia serialis and Echinocuccus spp., particularly preferably Taenia hydatigena, Taenia ovis, Taenia multiceps, Taenia serialis; Echinocuccus granulosus and Echinococcus granulosus and Echinococcus multilocularis, and Multiceps multiceps.

In a very particularly preferred way, Taenia hydatigena, T. pisiformis, T. ovis, T. taeniae- formis, Multiceps multiceps, Joyeuxiella pasquali, Dipylidium caninum, Mesocestoides spp.,

Echinococcus granulosus and E. multilocularis are controlled simultaneously with Dirofilaria immitis, Ancylostoma spp., Toxocara spp. and/or Trichuris vulpis on or in dogs and cats.

Also in a preferred way, Ctenocephalides felis and/or C.canis are controlled simultaneously with the abovementioned nematodes and cestodes.

The compounds of the formula | are also suitable for controlling parasites which are pathogenic to man, among which may be mentioned, as typical representatives occurring in the digestive tract, those of the genera Ancylostoma, Necator, Ascaris, Strongyloides,

Trichinella, Capillaria, Trichuris and Enterobius. The compounds of the present invention are also active against parasites of the genera Wuchereria, Brugia, Onchocerca and Loa from the family of the Filariidae, which occur in the blood, in tissue and in various organs, and also against Dracunculus and parasites of the genera Strongyloides and Trichinella, which specifically infect the gastrointestinal tract.

In addition, the compounds of the formula i are also active against harmful fungi which cause disease in plants and in man and animals.

The good pesticidal action of the compounds of the formula | according to the invention corresponds to a kill rate (mortality) of at least 50-60% of the pests mentioned. In particular, the compounds of the formula | are characterized by an extraordinarily long duration of action.

The compounds of the formula | are used as such or preferably together with the auxiliaries conventional in formulation technology and can accordingly be processed in a known way, for example to emulsifiable concentrates, directly dilutable solutions, dilute emulsions, soluble powders, granules and also encapsulations in polymer substances. The application methods as well as the compositions are chosen in accordance with the intended aims and the prevailing circumstances.

The formulation, i.e. the compositions, preparations or combinations comprising the active ingredient of the formula |, or combinations of these active ingredients with other active ingredients, and, if desired, a solid or liquid additive, is prepared in a known way, for example by intimately mixing and/or grinding the active ingredients with extenders, for example with solvents, solid carriers and, if desired, surface-active compounds (surfactants).

The following are possible as solvents: alcohols, such as ethanol, propanol or butanol, and glycols, and their ethers and esters, such as propylene glycol, dipropylene glycol ether, ethylene glycol, ethylene glycol monomethy! ether or ethylene glycol monoethy! ether, ketones, such as cyclohexanone, isophorone or diacetone alcohol, strongly polar solvents, such as N-methyl-2-pyrrolidone, dimethyl sulfoxide, dimethylformamide or water, vegetable oils, such as rapeseed oil, castor oil, coconut oil or soybean oil; and, if desired, silicone oils.

Preferred application forms for use in warm-blooded animals for controlling helminths include solutions, emulsions, suspensions (drenches), feed additives, powders, tablets, including effervescent tablets, boluses, capsules, microencapsulations and pour-on

Suitable binders for tablets and boluses are chemically modified polymeric natural products which are soluble in water or alcohol, such as starch, cellulose or protein derivatives (e.g., methylcellulose, carboxymethyicellulose, ethylhydroxyethylcellulose, proteins, such as zein, gelatin, and the like), and synthetic polymers, for example polyvinyl alcohol, polyvinylpyrrolidone, and the like. Tablets also comprise fillers (e.g., starch, microcrystalline cellulose, sugar, lactose, and the like), lubricants and disintegrating agents.

If the anthelmintic compositions are present in the form of feed concentrates, then high- performance feed, feed cereals or protein concentrates, for example, are used as carriers.

Such feed concentrates or compositions can, in addition to the active ingredients, also comprise additives, vitamins, antibiotics, chemotherapeutics, or other pesticides, mainly bacteriostats, fungistats, coccidiostats, or also hormone preparations, anabolics or substances which promote growth, influence the quality of meat from animals for slaughter or are useful to the organism in another way. If the compositions or the active ingredients of the formula | present therein are added directly to the feed or to the drinking water for the animals, the finished feed or the finished drinking water comprises the active ingredients preferably in a concentration from approximately 0.0005 to 0.02% by weight (5-200 ppm).

The compounds of the formula | according to the invention can be used alone or in combination with other biocides. They can, e.g., be combined with pesticides possessing the same direction of action, in order to enhance the action, or can be combined with substances possessing another direction of action, in order to broaden the activity spectrum. it may also make sense to add substances which repel, known as repellents. If it is desired to expand the activity spectrum with regard to endoparasites, for example worms, the compounds of the formula | are appropriately combined with substances having endoparasiticidal properties. They can also, naturally, be used in combination with antibacterial compositions. Since the compounds of the formula | represent adulticides, i.e. since they are effective in particular against the adult stages of the target parasites, the addition of pesticides which are more likely to attack the juvenile stages of parasites can be highly advantageous. In this way, most of those parasites causing great economic damage are namely included. In addition, a substantial contribution is also made as well to avoiding the formation of resistance. Some combinations can also lead to synergistic effects, i.e. that the total amount of active substance consumed can be reduced, which is desirable from an

© H-32268A ecological viewpoint. Preferred groups of combination participants and particularly preferred combination participants are mentioned subsequently, which combinations can, in addition to a compound of the formula |, comprise one or more of these participants.

Suitable participants in the mixture include biocides, for example the insecticides and acaricides with different mechanisms of action mentioned subsequently and sufficiently known to a person skilled in the art, for example chitin synthesis inhibitors, growth regulators; active ingredients which act as juvenile hormones; active ingredients which act as adulticides; broad spectrum insecticides, broad spectrum acaricides and nematicides; but also the sufficiently known anthelmintics and substances which repel insects and/or members of the Acarina, known as repellents or detachers.

Nonlimiting examples of suitable insecticides and acaricides are:

~H-32268A

Nonlimiting examples of suitable anthelmintics are mentioned subsequently, in which some representatives, in addition to the anthelmintic activity, also have an insecticidal and acaricidal activity and are already included in the above list: (A1) Praziguantel = 2-Cyclohexylcarbonyi-4-oxo-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1- ajisoquinoline (A2) Closantel = 3,5-Diiodo-N-[5-chloro-2-methyl-4-(a-cyano-4-chlorobenzyl)phenyl]- salicylamide (A) Triclabendazole = 5-Chloro-6-(2,3-dichlorophenoxy)-2-methyithio-1H-benzimidazole (A4) Levamisole = L-(-)-2,3,5,6-Tetrahydro-6-phenylimidazo[2,1-b]thiazole (A5) Mebendazole = Methyl! 5-benzoyl-1H-benzimidazol-2-ylcarbamate (A6) Omphalotin = a macrocyclic fermentation product from the fungus Omphalotus olearius disclosed 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 Ala (A11) Milbemectin = Mixture of Milbemycin A3 and Milbemycin A4 (A12) Milbemycin oxime = 5-Oxime of Milbemectin

Nonlimiting examples of suitable repelling substances (repellents or detachers) are: (R1) DEET (N,N-Diethyl-m-toluamide)

H-32268A (R2) KBR 3023 N-Butyl-2-oxycarbonyl-2-(2-hydroxyethyl)piperidine (R3) Cymiazole = N-2,3-Dihydro-3-methyl-1,3-thiazol-2-ylidene-2,4-xylidine

The participants in the mixture which are mentioned are very well known to a person skilled in the art. Most are described in the various editions of The Pesticide Manual, The British

Crop Protection Council, London, others in the various editions of The Merck Index, Merck & Co. Inc., Rahway, New Jersey, USA, or in the patent literature. The following listing is accordingly restricted to a few references by way of examples. (I) 2-Methyl-2-(methyithio)propionaldehyde O-methylcarbamoyloxime (Aldicarb), from The

Pesticide Manual, 11" Ed. (1997), The British Crop Protection Council, London, page 26; (Il) S-(3,4-Dihydro-4-oxobenzo[d][1,2,3]triazin-3-yimethyl) O,0-dimethyl phosphorodithioate (Azinphos-methyl), from The Pesticide Manual, 11"Ed. (1997), The British Crop

Protection Council, London, page 67; (lll) Ethyl N-[2,3-dihydro-2,2-dimethylbenzofuran-7-yloxycarbonyl(methyl)aminothio}-N- isopropyl-B-alaninate (Benfuracarb), from The Pesticide Manual, 11"Ed. (1997), The

British Crop Protection Council, London, page 96; (IV) 2-Methylbiphenyi-3-yimethyl (2)-(1RS)-cis-3-(2-chloro-3,3,3-triflucroprop-1-enyl)-2,2- dimethylcyclopropanecarboxylate (Bifenthrin), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 118; (V) 2-tert-Butylimino-3-isopropyl-5-phenyl-1,3,5-thiadiazinan-4-one (Buprofezin), from The

Pesticide Manual, 11"Ed. (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™Ed. (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"Ed. (1997), The British Crop Protection

Council, London, page 188; (VIII) S,S-(2-Dimethylaminotrimethylene) bis(thiocarbamate) (Cartap), from The Pesticide

Manual, 11"Ed. (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- difluorobenzoyl)-urea (Chlorfluazuron), from The Pesticide Manual, 11"Ed. (1997), The

British Crop Protection Council, London, page 213;

Pesticide Manual, 11™Ed. (1997), The British Crop Protection Council, London, page 235; (XI) (RS)-a~-Cyano-4-fluoro-3-phenoxybenzyl (1RS,3RS;1 RS,3RS)-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropanecarboxylate (Cyfluthrin), from The Pesticide Manual, 11™Ed. (1997), The British Crop Protection Council, London, page 293; (XI) Mixture of (S)-o-cyano-3-phenoxybenzyl (2)-(1R,3R)-3-(2-chloro-3,3,3-trifluoro- propenyl)-2,2-dimethyicyclopropanecarboxylate and (R)-o-cyano-3-phenoxybenzyl (2)- (15,35)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate (Lambda-Cyhalothrin), from The Pesticide Manual, 11"Ed. (1997), The British Crop

Protection Council, London, page 300; (Xlit) Racemate consisting of (S)-a-cyano-3-phenoxybenzyl (1R,3R)-3-(2,2-dichlorovinyl)- 2,2-dimethylcyclopropanecarboxylate and (R)-o-cyano-3-phenoxybenzyl (18,35)-3-(2,2- dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (Alpha-cypermethrin), from The

Pesticide Manual, 11™Ed. (1997), The British Crop Protection Council, London, page 308; (XIV) A mixture of the stereoisomers of (S)-a-cyano-3-phenoxybenzyl (1RS,3RS,1RS,3RS)- 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate (zeta-Cypermethrin), from The

Pesticide Manual, 11™Ed. (1997), The British Crop Protection Council, London, page 314; (XV) (8)-a-Cyano-3-phenoxybenzyl (1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylicyclopropane- carboxylate (Deltamethrin), from The Pesticide Manual, 11"Ed. (1997), The British Crop

Protection Council, London, page 344; (XVI) 1-(4-Chlorophenyl)-3-(2,6-difluorobenzoyl)urea (Diflubenzuron), from The Pesticide

Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 395; (XV) (1,4,5,6,7,7-Hexachloro-8,9,10-trinorborn-5-en-2,3-ylenebismethylene) sulfite (Endosulfan), from The Pesticide Manual, 11™Ed. (1997), The British Crop Protection

Council, London, page 459; (XVIII) a-Ethylthio-o-tolyl methylcarbamate (Ethiofencarb), from The Pesticide Manual, 11"™Ed. (1997), The British Crop Protection Council, London, page 479; (XIX) O,0-Dimethy! O-4-nitro-m-tolyl phosphorothioate (Fenitrothion), from The Pesticide

Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 514;

© H-32268A (XX) 2-sec-Butylphenyl methylcarbamate (Fenobucarb), from The Pesticide Manual, 11" Ed. (1997), The British Crop Protection Council, London, page 516; (XXI) (RS)-0-Cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate (Fenvalerate), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection

Council, London, page 539; (XXII) S-[Formyl(methyl)carbamoylmethyl] O,O-dimethyl phosphorodithioate (Formothion), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 625; (XXIH) 4-Methylthio-3,5-xylyl methylcarbamate (Methiocarb), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 813; (XXIV) 7-Chlorobicyclo[3.2.0]hepta-2,6-dien-6-yl dimethyl phosphate (Heptenophos), from

The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 670; (XXV) 1-(6-Chloro-3-pyridylmethyl)- N-nitroimidazolidin-2-ylideneamine (Imidacloprid), from

The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 706; (XXVI) 2-Isopropylphenyl methylcarbamate (Isoprocarb), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 729; (XXVII) O, S-Dimethyl phosphoramidothioate (Methamidophos), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 808; (XXVIII) S-Methyl N-(methylcarbamoyloxy)thioacetimidate (Methomyl), from The Pesticide

Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 815; (XXIX) Methyl 3-(dimethoxyphosphinoyloxy)but-2-enoate (Mevinphos), from The Pesticide

Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 844; (XXX) O,0O-Diethyl O-4-nitrophenyl phosphorothioate (Parathion), from The Pesticide

Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 926; (XXXI) O,O-Dimethyl O-4-nitrophenyl phosphorothioate (Parathion-methyl), from The

Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 928; (XXXIt) S-6-Chloro-2,3-dihydro-2-oxo-1,3-benzoxazol-3-ylmethyl O,O-diethyl phosphoro- dithioate (Phosalone), from The Pesticide Manual, 11"Ed. (1997), The British Crop

Protection Council, London, page 963;

' H-32268A (XXXII) 2-Dimethylamino-5,6-dimethylpyrimidin-4-yl dimethylcarbamate (Pirimicarb), from

The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 985; (XXXIV) 2-Isopropoxyphenyl methylcarbamate (Propoxur), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 1036; (XXXV) 1-(3,5-Dichioro-2,4-difluorophenyl)-3-(2,6-difluorobenzoyl)urea (Teflubenzuron), from The Pesticide Manual, 11"™Ed. (1997), The British Crop Protection Council, London, page 1158; (XXXVI) S-tert-Butylthiomethyl O,O-diethyl phosphorodithioate (Terbufos), from The

Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 1165; (XXXVI) Ethyl (3-tert-butyl-1-dimethyicarbamoyl-1H-1,2,4-triazol-5-ylthio)acetate, (Triazamate), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection

Council, London, page 1224; (XXXVIIl) Abamectin, from The Pesticide Manual, 11"Ed. (1997), The British Crop

Protection Council, London, page 3; (XXXIX) 2-sec-Butylphenyl methyicarbamate (Fenobucarb), from The Pesticide Manual, 11™Ed. (1997), The British Crop Protection Council, London, page 516; (XL) N-tert-Butyl-N-(4-ethylbenzoyl)-3,5-dimethylbenzohydrazide (Tebufenozide), from The

Pesticide Manual, 11™Ed. (1997), The British Crop Protection Council, London, page 1147, (XL1) (x)-6-Amino-1-(2,6-dichloro-a, a, o-trifluoro-p-tolyl)-4-trifluoromethylsulfinylpyrazole- 3-carbonitrile (Fipronil), from The Pesticide Manual, 11"Ed. (1997), The British Crop

Protection Council, London, page 545; (XLII) (RS)-a-Cyano-4-fluoro-3-phenoxybenzyl (1RS,3RS;1RS,3SR)-3-(2,2-dichlorovinyl)- 2,2-dimethylcyclopropanecarboxylate (beta-Cyfluthrin), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 295; (XLIN) (4-Ethoxyphenyl)[3-(4-fluoro-3-phenoxyphenyl)propyl](dimethyl)silane (Silafluofen), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 1105; (XLIV) tert-Butyl (E)-0-(1,3-dimethyl-5-phenoxypyrazol-4-ylmethyleneamino-oxy)-p-toluate (Fenpyroximate), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection

Council, London, page 530;

'H-32268A (XLV) 2-tert-Butyl-5-(4-tert-butylbenzyithio)-4-chloropyridazin-3(2H)-one (Pyridaben), from

The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 1161; (XLVI) 4-[[4-(1,1-Dimethylethyl)phenyllethoxy]quinazoline (Fenazaquin), from The Pesticide

Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 507; (XLVI) 4-Phenoxyphenyl (RS)-2-(2-pyridyloxy)propy! ether (Pyriproxyfen), from The

Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 1073; (XLVII1) 5-Chloro-N-{2-[4-(2-ethoxyethyl)-2,3-dimethylphenoxy]ethyl}-6-ethylpyrimidin-4- amine (Pyrimidifen), from The Pesticide Manual, 11"Ed. (1997), The British Crop

Protection Council, London, page 1070; (XLIX) (E)-N-(6-Chloro-3-pyridylmethyl)-N-ethyl-N-methyl-2-nitrovinylidenediamine (Nitenpyram), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection

Council, London, page 880; (L) (E)-N'-[(6-Chloro-3-pyridyl)methyl]-N?-cyano-N'-methylacetamidine (NI-25, Acetamiprid), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 9; (LI) Avermectin By, from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection

Council, London, page 3; (LI) An insect-active extract from a plant, in particular (2R,6aS5,12aS)-1,2,6,6a,12,12a- hexahydro-2-isopropenyl-8,9-dimethoxychromeno[3,4-b]furo[2,3-hjchromen-6-one (Rotenone), from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection

Council, London, page 1097; and an extract from Azadirachta indica, in particular azadirachtin, from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection

Council, London, page 58; (LIN) A preparation comprising insect-active nematodes, preferably Heterorhabditis bacteriophora and Heterorhabditis megidis, from The Pesticide Manual, 11"Ed. (1997),

The British Crop Protection Council, London, page 671; Steinernema feltiae, from The

Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 1115, and Steinemema scapterisci, from The Pesticide Manual, 11"Ed. (1997),

The British Crop Protection Council, London, page 1116; (LIV) A preparation obtainable from Bacillus subtilis, from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 72; or from a Bacillus

H-32268A thuringiensis strain except for compounds isolated from GC91 or from NCTC11821; The

Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 73; (LV) A preparation comprising insect-active fungi, preferably Verticillium lecanii, from The

Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 1266; Beauveria brogniartii, from The Pesticide Manual, 11"Ed. (1997), The British

Crop Protection Council, London, page 85; and Beauveria bassiana, from The Pesticide

Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 83; (LVI) A preparation comprising insect-active viruses, preferably Neodipridon Sertifer NPV, from The Pesticide Manual, 11"Ed. (1997), The British Crop Protection Council, London, page 1342; Mamestra brassicae NPV, from The Pesticide Manual, 11"Ed. (1997), The

British Crop Protection Council, London, page 759; and Cydia pomonella granulosis virus, from The Pesticide Manual, 11™Ed. (1997), The British Crop Protection Council,

London, page 291; (CLXXXI) N-tert-Butyl-N*-(3,5-dimethylbenzoyl)-3-methoxy-2-methylbenzohydrazide (RH- 2485, Methoxyfenozide), from The Pesticide Manual, 11"Ed. (1997), The British Crop

Protection Council, London, page 1094; (CLXXXH) Isopropyl N*-[4-methoxybiphenyl-3-yllhydrazinecarboxylate (D 2341), from

Brighton Crop Protection Conference, 1996, 487- 493; and (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.

According to what has been said above, a further essential aspect of the present invention relates to combination preparations for the control of parasites in warm-blooded animals, which comprise, in addition to a compound of the formula |, at least one further active ingredient with an identical or different direction of action and at least one physiologically compatible carrier. The present invention is not restricted to combinations of two.

The anthelmintic compositions according to the invention generally comprise 0.1 to 99% by weight, in particular 0.1 to 95% by weight, of active ingredient of the formula | or mixtures thereof, and 99.9 to 1% by weight, in particular 99.8 to 5% by weight, of a solid or liquid additive, including 0 to 25% by weight, in particular 0.1 to 25% by weight, of a surfactant.

The compositions according to the invention can be applied topically, perorally, parenterally or subcutaneously to the animals to be treated, the compositions being present in the form

H-32268A of solutions, emulsions, suspensions (drenches), powders, tablets, boluses, capsules and as pour-on formulations.

The pour-on or spot-on method consists in applying the compound of the formula | to a locally restricted part of the skin or fur, advantageously on the neck or back of the animal.

This is carried out, e.g., by applying a spot or dash of the pour-on or spot-on formulation to a relatively small area of the fur, from where the active substance spreads out virtually unaided over wide regions of the fur because of the spreading components of the formulation and supported by the movements of the animal.

It is advantageous for pour-on or spot-on formulations to comprise carriers which promote speedy distribution on the surface of the skin or in the fur of the host animal and which are generally described as spreading oils. Suitable carriers are, e.g., oily solutions; alcoholic and isopropanolic solutions, for example solutions of 2-octyldodecanol or oleyl alcohol; solutions in esters of monocarboxylic acids, such as isopropyl myristate, isopropy! palmitate, lauric acid oxal ester, oleyl oleate, decyl oleate, hexyl laurate, capric acid esters of saturated fatty alcohols with a chain length of Cy»-Css; solutions of esters of dicarboxylic acids, such as dibutyl phthalate, diisopropyl! isophthalate, diisopropyl adipate or di(n-butyl) adipate, or also solutions of esters of aliphatic acids, e.g. glycols. It can be advantageous if a dispersant known from the pharmaceutical or cosmetics industry is additionally present.

Examples are 2-pyrrolidone, 2-(N-alkyl)pyrrolidone, acetone, polyethylene glycol and 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 can also be present in epoxidized form.

Paraffin oils and silicone oils can also be used.

In general, a pour-on or spot-on formulation comprises 1 to 20% by weight of a compound of the formula [, 0.1 to 50% by weight of dispersant and 45 to 98.9% by weight of solvent.

The pour-on or spot-on method can be used particularly advantageously with gregarious animals, such as cattle, horses, sheep or pigs, where it is difficult or time-consuming to treat all the animals orally or via injection. Because of its simplicity, this method can naturally also be used with all other animals, including individual domestic animals or pets, and is very popular with animal owners because it can often be implemented without the expert assistance of a veterinary surgeon.

While concentrated compositions are more preferred as commercially available products,

H-32268A the end user generally uses dilute compositions.

Such compositions can comprise vet further additives, such as stabilizers, antifoaming agents, viscosity regulators, binders, deposit builders and other active ingredients to obtain specific effects.

Such anthelmintic compositions used by the end user likewise form part of the present invention.

In each of the methods according to the invention for controlling pests or of the pesticides according to the invention, the active ingredients of the formula | can be used in all their steric configurations or mixtures thereof.

The invention also includes a method for the prophylactic protection of warm-blooded animals, in particular of productive livestock, domestic animals and pets, against parasitic helminths, which comprises applying the active ingredients of the formula | or the active ingredient formulations prepared therefrom as a feed additive or drinking water additive or also in the solid or liquid form, orally, by injection or parenterally, to the animals. The invention also includes the compounds of the formula | according to the invention for use in one of the methods mentioned.

The following examples serve merely to illustrate the invention, without limiting it, the term “active ingredient” representing a substance listed in Table 1.

Preferred formulations are in particular composed in the following way: (% = per cent by weight)

Formulation examples 1. Granules a) b)

Active ingredient 5% 10%

Kaolin 94% -

Highly dispersed silica 1% -

Attapulgite - 90%

The active ingredient is dissolved in methylene chloride and sprayed onto the carrier, and the solvent is subsequently evaporated under reduced pressure. Such granules can be added to the animal feed. 2. Granules

Active ingredient 3%

H-32268A

Polyethylene glycol (MW 200) 3%

Kaolin 94% (MW = molecular weight)

The finely milied active ingredient is applied evenly in a mixer to the kaolin, which has been moistened with polyethylene glycol. In this way, dust-free coated granules are obtained. 3. Tablets or Boluses

I Active ingredient 33.00%

Methylcellulose 0.80%

Highly dispersed silica 0.80%

Maize starch 8.40%

Il Cryst. lactose 22.50%

Maize starch 17.00%

Microcryst. cellulose 16.50%

Magnesium stearate 1.00%

I Methyicellulose is stirred into water. After the material has swollen, silica is stirred in and the mixture is homogeneously suspended. Active ingredient and maize starch are mixed. The aqueous suspension is incorporated in this mixture and kneaded to a dough. The substance thus obtained is granulated through a 12 M sieve and dried.

II All 4 auxiliaries are intimately mixed. lll The premixes obtained according to | and I! are mixed and pressed to give tablets or boluses. 4, Injectables

A. Oily vehicle (slow release) 1. Active ingredient 0.1-1.0g

Groundnut oil ad 100 ml 2. Active ingredient 0.1-1.0g

Sesame oil ad 100 ml

Preparation: The active ingredient is dissolved in a portion of the oil with stirring and, if desired, gentle heating, made up to the required volume after cooling and sterilely filtered through a suitable membrane filter with a size of 0.22 um.

B. Water-miscible solvent (medium release rate)

'H-32268A 1. Active ingredient 0.1-1.0g 4-Hydroxymethyl-1,3-dioxolane (glycerol formal) 40g 1,2-Propanediol ad 100 ml 2. Active ingredient 0.1-10g

Glycerol dimethyl acetal 40g 1,2-Propanediol ad 100 ml

Preparation: The active ingredient is dissolved in a portion of the solvent with stirring, made up to the required volume and sterilely filtered through a suitable membrane filter with a size of 0.22 pm.

C. Aqueous solubilisate (rapid release) 1. Active ingredient 0.1-10g

Polyethoxylated castor oil (40 ethylene oxide units) 10g 1,2-Propanediol 20g

Benzyl alcohol 1g

Water for injections ad 100 mi 2. Active ingredient 0.1-10g

Polyethoxylated sorbitan monooleate (20 ethylene oxide units) 8g 4-Hydroxymethyl-1,3-dioxolane (glycerol formal) 20g

Benzyl alcohol 1g

Water for injections ad 100 mi

Preparation: The active ingredient is dissolved in the solvents and the surfactant and made up to the required volume with water. Sterile filtration is carried out through a suitable membrane filter with a pore diameter of 0.22 um. 5. Pour-on

A.

Active ingredient 59

Isopropyl myristate 10g

Isopropanol ad 100 mi

B.

Active ingredient 29

Hexyl laurate 5g

Triglycerides of medium chain length 15g

Ethanol ad 100 ml

C.

Active ingredient 24

Oleyl oleate 59g

N-Methylpyrrolidone 40g isopropanol ad 100 ml

The aqueous systems can preferably also be used for oral and/or intraruminal administration.

The compositions can also comprise further additives, such as stabilizers, e.g. epoxidized or nonepoxidized vegetable oils (epoxidized coconut oil, rapeseed oil or soybean oil), antifoaming agents, e.g. silicone oil, preservatives, viscosity regulators, binders, deposit builders and fertilizers or other active ingredients to obtain specific effects.

Further biologically active substances or additives which are neutral towards the compounds of the formula | and have no adverse effect on the host animal to be treated, and mineral salts or vitamins, can also be added to the compositions described.

The following examples serve to clarify the invention. They do not limit the invention. The symbol 'h' denotes hour.

Preparation examples

Example 1: N-[2-[2-Cyano-1-[2-(cyclopropylmethylamino)-4,5-difluorophenoxylpropyl]-4- trifluoromethoxybenzamide a) 19 g of 2-bromo-4,5-difluoroanisole, 9.44 ml of cyclopropylamine, 0.39 g of tris(dibenzylideneacetone)dipalladium, 0.8 g of 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl and 11.46 g of sodium tert-butoxide in 800 ml of toluene degassed with argon are stirred at 80°C for 24 h under a nitrogen atmosphere. The mixture is then concentrated under vacuum, the residue is diluted with diethyl ether and the organic phase is washed four times with water and dried with magnesium sulfate. After evaporating, the crude product is purified by flash chromatography, giving cyclopropy!(4,5-difluoro-2-anisyl)amine as a yellow oil. b) 2 g of cyclopropyl(4,5-difiuoro-2-anisyl)amine and 0.48 g of sodium hydride are stirred in ml of dimethylformamide for 20 min at ambient temperature, 1.25 mi of methyl iodide are

'H-32268A subsequently added and the mixture is additionally stirred for 20 h at 40°C.

After filtering and evaporating, the reaction mixture is taken up in diethyl ether and the organic phase is washed with water, dried with magnesium sulfate and evaporated to dryness.

Cyclopropyl- (4,5-difluoro-2-anisyl)methylamine is thus obtained as a yellow oil. c) 1 g of cyclopropy}(4,5-difiuoro-2-anisyl)methylamine is dissolved in 7 ml of methylene chloride and cooled under a nitrogen atmosphere to -70°C, 7.03 ml of a 1M solution of boron tribromide in methylene chloride are then added and the mixture is stirred at -70°C for a further 30 min.

The cooling is then removed and the mixture is allowed to warm up to ambient temperature over 3.5 h with constant stirring. 20 ml of water are subsequently added and the organic phase is separated, dried with magnesium sulfate and evaporated to dryness.

The residue is purified by flash chromatography. 2-(N-Cyclopropyl-N- methylamino)-4,5-difluorophenol is thus obtained as a mauve-coloured oil. d) 53 mg of 2-(N-cyclopropyl-N-methylamino)-4,5-difluorophenol, 44 mg of potassium carbonate, 6.4 mg of potassium iodide and 0.03 ml of chioroacetone are mixed in 1 mi of acetone and are heated at reflux for 20 h.

The mixture is then evaporated and the residue is taken up in diethyl ether and washed with water.

The organic phase is dried with magnesium sulfate and evaporated to dryness, and the residue is purified by flash chromatography. 1-[2-(N-Cyclopropyl-N-methylamino)-4,5-difluorophenoxy]propan-2-one is thus obtained as a yellow oil. e) 47 mg of 1-{2-(N-cyclopropyl-N-methylamino)-4,5-difluorophenoxy]propan-2-one, 10 mg of sodium cyanide and 14.7 mg of ammonium chloride are added to 1 ml of a 25% aqueous ammonia solution and the mixture is stirred at ambient temperature for 24 h.

The mixture is then evaporated, the residue is taken up in diethyl ether and washed with water, the organic phase is dried with magnesium sulfate and evaporated to dryness, and the residue is purified by flash chromatography. 1-Amino-1-[2-(N-cyclopropyl-N-methylamino)-4,5- difluorophenoxymethyl]propionitrile is thus obtained. f) 0.21 ml, 21.4 mg, of 4-dimethylaminopyridine and 237 mg of 4-trifluoromethoxybenzoyl chloride are added to a solution of 247 mg of 1-amino-1-[2-(N-cyclopropyl-N-methylamino)- 4,5-difluorophenoxymethyl]propionitrile in 3.5 ml of methylene chloride and the mixture is stirred at ambient temperature for 24 h under a nitrogen atmosphere.

The reaction mixture is subsequently washed, first with a saturated sodium bicarbonate solution and then with a saturated sodium chloride solution.

The organic phase is dried with magnesium sulfate and

' H-32268A evaporated to dryness, and the residue is purified by flash chromatography. The title compound is thus obtained, which compound has a melting point of 136-40°C.

The substances mentioned in the following table can also be prepared analogously to the procedure described above. The melting point values are given in °C.

Table 1

N | (Rg),

No. Ry; (Re)n R12 Phys. data 1.1 Cyclopropyloxy H H 1.2 Cyclopropyloxy H 4-F 1.3 Cyclopropyloxy H 4-Cl 1.4 Cyclopropyloxy H 4-CF3 1.5 Cyclopropyloxy H 4-OCF; 1.6 Cyclopropyloxy H 4-OC¢Hs 1.7 Cyclopropyloxy 4-F H 1.8 Cyclopropyloxy 4-F 4-F 1.9 Cyclopropyloxy 4-F 4-Cl 1.10 Cyclopropyloxy 4-F 4-CF; 1.11 Cyclopropyloxy 4-F 4-OCF; 1.12 Cyclopropyloxy 4-F 4-OCgHs 1.13 Cyclopropyloxy 5-F H 1.14 Cyclopropyloxy 5-F 4-F 1.15 Cyclopropyloxy 5-F 4-Cl 1.16 Cyclopropyloxy 5-F 4-CF; 1.17 Cyclopropyloxy 5-F 4-OCF; 1.18 Cyclopropyloxy 5-F 4-OCgHs 1.19 Cyclopropyloxy 45-F, H 1.20 Cyclopropyloxy 4,5-F, 4-F 1.21 Cyclopropyloxy 4,5-F, 4-Ci 1.22 Cyclopropyloxy 4,5-F, 4-CF; 1.23 Cyclopropyloxy 4,5-F, 4-OCF; 1.24 Cyclopropyloxy 4,5-F;, 4-OCgHs 1.25 Cyclopropylamino H H 1.26 Cyclopropylamino H 4-F 1.27 Cyclopropylamino H 4-Cl

'H-32268A

1.28 Cyclopropylamino H 4-CF3 1.29 Cyclopropylamino H 4-OCF; 1.30 Cyclopropylamino H 4-OCe¢Hs 1.31 Cyclopropylamino 4-F H

1.32 Cyclopropylamino 4-F 4-F

1.33 Cyclopropylamino 4-F 4-Cl 1.34 Cyclopropylamino 4-F 4-CF; 1.35 Cyclopropylamino 4-F 4-OCF; 1.36 Cyclopropylamino 4-F 4-OCgHs 1.37 Cyclopropylamino 5-F H

1.38 Cyclopropylamino 5-F 4-F

1.39 Cyclopropylamino 5-F 4-Cl 1.40 Cyclopropylamino 5-F 4-CF; 1.41 Cyclopropylamino 5-F 4-OCF; 1.42 Cyclopropylamino 5-F 4-OCgHs 1.43 Cyclopropylamino 45-F, H

1.44 Cyclopropylamino 4,5-F, 4-F

1.45 Cyclopropylamino 4,5-F, 4-Cl 1.46 Cyclopropylamino 45-F, 4-CF; 1.47 Cyclopropylamino 4,5-F, 4-OCF; 1.48 Cyclopropylamino 4,5-F, 4-OCgHs 1.49 Cyclobutyloxy H H

1.50 Cyclobutyloxy H 4-F

1.51 Cyclobutyloxy H 4-Cl 1.52 Cyclobutyloxy H 4-CF3 1.53 Cyclobutyloxy H 4-OCF; 1.54 Cyclobutyloxy H 4-OC¢Hs 1.55 Cyclobutyloxy 4-F H

1.56 Cyclobutyloxy 4-F 4-F

1.57 Cyclobutyloxy 4-F 4-Cl 1.58 Cyclobutyloxy 4-F 4-CF, 1.59 Cyclobutyloxy 4-F 4-OCF, 1.60 Cyclobutyloxy 4-F 4-OC¢Hs 1.61 Cyclobutyloxy 5-F H

H-32268A

1.62 Cyclobutyloxy 5-F 4-F 1.63 Cyclobutyloxy 5-F 4-Cl 1.64 Cyclobutyloxy 5-F 4-CF; 1.65 Cyclobutyloxy 5-F 4-OCF; 1.66 Cyclobutyloxy 5-F 4-OCgHs 1.67 Cyclobutyloxy 45-F, H 1.68 Cyclobutyloxy 4,5-F, 4-F 1.69 Cyclobutyloxy 4,5-F, 4-Cl 1.70 Cyclobutyioxy 4,5-F, 4-CF; 1.71 Cyclobutyloxy 4,5-F, 4-OCF; 1.72 Cyclobutyloxy 4,5-F, 4-OCgHs 1.73 Cyclobutylamino H H 1.74 Cyclobutylamino H 4-F 1.75 Cyclobutylamino H 4-Cl 1.76 Cyclobutylamino H 4-CF; 1.77 Cyclobutylamino H 4-OCF; 1.78 Cyclobutylamino H 4-OC¢Hs 1.79 Cyclobutylamino 4-F H 1.80 Cyclobutylamino 4-F 4-F 1.81 Cyclobutylamino 4-F 4-Cl 1.82 Cyclobutylamino 4-F 4-CF; 1.83 Cyclobutylamino 4-F 4-OCF; 1.84 Cyclobutylamino 4-F 4-OCgHs 1.85 Cyclobutylamino 5-F H 1.86 Cyclobutylamino 5-F 4-F 1.87 Cyclobutylamino 5-F 4-Cl 1.88 Cyclobutylamino 5-F 4-CF; 1.89 Cyclobutylamino 5-F 4-OCF; 1.90 Cyclobutylamino 5-F 4-OCgHs 1.91 Cyclobutylamino 45-F, H 1.92 Cyclobutylamino 45-F, 4-F 1.93 Cyclobutylamino 45-F, 4-Cl 1.94 Cyclobutylamino 4,5-F, 4-CF; 1.95 Cyclobutylamino 4,5-F, 4-OCF,3

Claims

1. A compound of the formula R R, R, Rs R AN | | ’ N Per l, Ar—{ CN o Ry Re (Rg), in which Ry is hydrogen, C4-Cealkyl, halo-C;-Cealkyl, cyano-Cs-Cealkyl, C1-Csalkoxymethyl or benzyl; Ra, Rs, Rs, Rs and Rg are either, independently of one another, hydrogen, halogen, unsubstituted or mono- or polyhalogenated C;-Cealkyl, unsubstituted or mono- or polyhalogenated C,-Csalkenyl, unsubstituted or mono- or polyhalogenated C,-Cealkynyl; unsubstituted or mono- or polysubstituted C;-Cgalkoxy, unsubstituted or mono- or polysubstituted halo-C+-Cgalkoxy, unsubstituted or mono- or polysubstituted C,-Cgcycloalkyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen and C;-Cgalkyl; or unsubstituted or mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C;-Cealkyl, halo-C,-Cgalkyl, C+-Cealkoxy, halo-C4-Cealkoxy, C1-Cealkylthio, halo-C;-Cgalkylthio, C-Cealkylsulfinyl, halo-C;-Csalkylsulfinyl, C,-Cealkylsulfonyl, halo-C,-Csalkylsulfonyl, C;-Cealkylamino or di-C¢-Cealkylamino; or R; and Rj are together C,-Csalkylene; either R- is unsubstituted or mono- or polysubstituted C;-Cecycloalkoxy, unsubstituted or mono- or polysubstituted Cs-Cgcycloalkylthio, unsubstituted or mono- or polysubstituted (Cs-Cecyclo- alkyl)(Re)N, in which the substituents in each case are chosen from the group consisting of halogen and C,-Cgalkyl; hetaryl or hetaryloxy; and Re is halogen, nitro, cyano, Cy-Cealkyl, halo-C,-Cealkyl, C1-Cgalkoxy, halo-C,-Cealkoxy, C2-Cealkenyl, halo-C,-Cealkenyl, C,-Cealkynyl, C3-Cecycloalkyl, Co-Csalkenyloxy, halo-C,-Cq- alkenyloxy, Cs-Cealkylthio, halo-C4-Cealkylthio, C;-Cgalkylsulfonyloxy, halo-C,-Cealkyl- sulfonyloxy, Cs-Cealkylsulfinyl, halo-C,-Cealkylsulfinyl, C;-Cealkylsulfonyl, halo-C;-Cgalkyl-

'H-32268A sulfonyl, C,-Cgalkenylthio, halo-C,-Csalkenylthio, C,-Cealkenylsulfinyl, halo-C,-Csalkenylsulfinyl, C,-Csalkenylsulfonyl, halo-C,-Cealkenylsulfonyl, Ci-Cealkylamino, di-C4-Cealkylamino, C,-Csalkylsulfonylamino, halo-C;-Cesalkylsulfonylamino, C4-Cealkylcarbonyl, halo-C4-Cgalkyicarbonyl, C4-Cgalkoxycarbonyl, Cs-Cealkylaminocarbonyl, di-C4-Cealkylaminocarbonyl, unsubstituted or mono- or polysubstituted phenylamino, unsubstituted or mono- or polysubstituted phenylcarbonyl; unsubstituted or mono- or polysubstituted phenylmethoxyimino; unsubstituted or mono- or polysubstituted phenylhydroxymethyl; unsubstituted or mono- or polysubstituted 1-phenyl-1-hydroxyethyl; unsubstituted or mono- or polysubstituted phenylchloromethyl; unsubstituted or mono- or polysubstituted phenylcyanomethyl; unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C1-Csalkyl, halo-C;-Cealkyl, C-Csalkoxy, halo-C4-Cealkoxy, C1-Csalkylthio, halo-C;-Cealkylthio, C-Cealkylsulfinyl, halo-C-Cealkylsulfinyl, C4-Cealkyisulfonyl and halo-C4-Csalkylsulfonyl; unsubstituted or mono- or polysubstituted phenoxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C,-Cealkyl, halo-C;-Cealkyl, C4-Cealkoxy, halo-C;-Cealkoxy, C,-Cealkylthio, halo-C,-Cealkylthio, C1-Cealkylsulfinyl, halo-C+-Cealkylsulfinyl, Cs-Cealkylsulfonyl and halo-C4-Cealkylsulfonyl; unsubstituted or mono- or polysubstituted phenylacetylenyl, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C;-Cealkyl, halo-C4-Cealkyl, C4-Cealkoxy, halo-C,-Cealkoxy, C4-Cealkylthio, halo-C,-Csalkylthio, C1-Cealkyisulfinyl, halo-C;-Cealkylsulfinyl, C;-Cgalkylsulfonyl and halo-Cs-Cealkylsulfonyl; or unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C;-Cealkyl, halo-C;-Cealkyl, Ci-Cgalkoxy, halo-C,-Cealkoxy, C-Cealkylthio, halo-C4-Cealkylthio, C;-Cealkylsulfinyl, halo-C-Csalkylsulfinyl, C,-Cgalkylsulfonyl and halo-C,-Cealkylsulfonyl; or Ry and Rs are together C;-Csalkylene; Ar is unsubstituted or mono- or polysubstituted phenyl, unsubstituted or mono- or polysubstituted hetaryl, unsubstituted or mono- or polysubstituted naphthyl or unsubstituted or mono- or polysubstituted quinolyl, in which in each case the substituents can be independent of one another and are chosen from the group consisting of R; and Rg; Ry is hydrogen, C4-Cealkyl, halo-C;-Cealkyl, allyl, C;-Cealkoxymethyl or -C(O)Ryq;

* H-32268A Ryo is C4-Cealkyl, halo-C;-Cealkyl or C;-Cgalkoxymethyi; Wis O, S, S(O.) or N(Ry1); Ri1 is hydrogen or C-Cealkyl; ais 1,2,3o0r4; bis 0,1, 2, 3o0r4; and nis0,1or2, in which, if Ry is hetaryloxy, the hetaryl group in Ry is other than pyridyl.

2. A compound of the formula | according to claim 1, in which R; is unsubstituted or mono- or polysubstituted Cs-Cecycloalkoxy, unsubstituted or mono- or polysubstituted Cs-Cecycloalkylthio or unsubstituted or mono- or polysubstituted (Cs-Cecycloalkyl)(Rg)N, in which the substituents in each case are chosen from the group consisting of halogen and C,-Cgalkyl.

3. A compound of the formula | according to claim 1, in which Ri is hydrogen, Cs-C,alky! or halo-C;-Cjalkyl; Raz, Rs, Rs, Rs and Rg are, independently of one another, hydrogen, unsubstituted or mono- or polyhalogenated C4-Csalkyl, unsubstituted or mono- or polyhalogenated C,-Csalkenyl or unsubstituted or mono- or polyhalogenated C,-Cgalkynyl; Ry is unsubstituted C3-Cecycloalkoxy, unsubstituted C;-Cgeycloalkylthio or unsubstituted (Cs-Cecycloalkyl)(Rg)N; Rg is halogen, nitro, cyano, C4-Caalkyl, halo-C,-Caalkyl, C-Caalkoxy, halo-Cy-C,alkoxy,

C.-Caalkenyl, halo-C,-Caalkenyl, C,-Cialkynyl, Cs-Cscycloalkyl, C.-Cjalkenyloxy, halo-C,-Cjalkenyloxy, C4-Caalkylthio, halo-C,-C,alkylthio, C,-Cjalkenyithio, halo-C,-Caalkenyithio, C4-Caalkylamino, di-C;-C,alkylamino, C;-C,alkylcarbonyl, halo-C4-Calkylcarbonyl, C-C,alkoxycarbonyl, unsubstituted or mono- or polysubstituted phenylamino, unsubstituted or mono- or polysubstituted phenylcarbonyl; unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C:-Caalkyl, halo-C4-Cgalkyl, C4-Csalkoxy, halo-C,-Csalkoxy, C4-Caalkylthio and halo-C,-Caalkylthio; unsubstituted or mono- or polysubstituted phenoxy, in which the substituents can be independent of one another and are chosen from the group consisting

© 'H-32268A of halogen, nitro, cyano, C;-Csalkyl, halo-C,-C,alkyl, C4-C,alkoxy, halo-C;-C,alkoxy, Ci-Caalkylthio and halo-C,-C,alkylthio; or unsubstituted or mono- or polysubstituted pyridyloxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C,-C,alkyl, halo-C,-C,alkyl, C;-C,alkoxy, halo-C4-C,alkoxy, C+-C,alkylthio and halo-C4-C,alkylthio; Ar is unsubstituted or mono- or polysubstituted phenyl or unsubstituted or mono- or polysubstituted hetaryl, in which in each case the substituents can be independent of one another and are chosen from the group consisting of R; and Rg; Rg is hydrogen, C;-Cgalky! or halo-C,-Cealkyl; Wis O, S or N(Ry4); R11 is hydrogen or C4-Cjalkyl; ais1,2o0r3; bis0,1,2 or 3; and nis 0, 1or2.

4. A compound of the formula | according to claim 1, in which R, is hydrogen or C,-Calkyl;

R., Rs, Rs, Rs and Rs are, independently of one another, hydrogen or unsubstituted or mono- or polyhalogenated C,-Cgalkyl; R; is unsubstituted C3-Cscycloalkoxy or unsubstituted (Cs-Cscycloalkyl)(Rg)N; Rg is halogen, nitro, cyano, C4-Caalkyl, halo-C4-Caalkyl, C4-Csalkoxy, halo-C4-Cjhalkoxy, Cs-Cscycloalkyl, Cy-Caalkylcarbonyl, Cy-Cialkoxycarbonyl, unsubstituted or mono- or polysubstituted phenyl, in which the substituents in each case can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, C,-C,alkyl, halo-C4-Caalkyl, Cs-Csalkoxy and halo-C,-C,alkoxy; or unsubstituted or mono- or poly- substituted phenoxy, in which the substituents can be independent of one another and are chosen from the group consisting of halogen, nitro, cyano, Cs-Caalkyl, halo-C+-Caalkyl, C:-Caalkoxy, halo-C4-Csalkoxy, C4-C,alkylthio and halo-C4-Cgalkylthio; Ar is unsubstituted or mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from R; and Rg;

5. A compound of the formula I according to claim 1, in which R; is hydrogen; Ra, Rs, Rs, Rs and Rg are, independently of one another, hydrogen or unsubstituted C+-C,alkyl; Ry is unsubstituted C;-Cycycloalkoxy or unsubstituted (Cs-Cacycloalkyl)(Rg)N; Rg is halogen, nitro, cyano, C-Cpalkyl, halo-C;-Cpalkyl, C4-Cralkoxy, halo-C4-Calkoxy, C3-Cacycloalkyl, Cy-Coalkylcarbonyl or C,-Cjalkoxycarbonyl; Ar is mono- or polysubstituted phenyl, in which the substituents can be independent of one another and are chosen from Rg; Rs is hydrogen or Cy-C.alkyl; Wis O; Ri is methyl; ais 1, b is 0; and nis 2.

6. A compound of the formula | according to claim 1, with the name N-[2-[2-cyano-1-[2- (cyclopropyimethylamino)-4,5-difluorophenoxy]propyi]-4-trifluoromethoxybenzamide.

7. A process for the preparation of a compound of the formula |, in each case in the free form or in the salt form, according to claim 1, which comprises the reaction of a compound of the formula

© H-32268A R R, R, Rs X—R "\ | | ’ N es I, H oN Rl Re (Rg) which is known or can be prepared by analogy to relevant known compounds and in which Ri, Ra, Rs, Rs, Rs, Rg, Ry, Rg, X, W, a, b and n are as defined above in the formula |, with a compound of the formula Q A—{ It, O which is known or can be prepared by analogy to relevant known compounds and in which Ar is as defined above in the formula | and Q is a leaving group, if desired in the presence of a basic catalyst, and in each case, if desired, the conversion of a compound of the formula | obtainable according to the process or in another way, in each case in the free form or in the salt form, to another compound of the formula |, the separation of a mixture of isomers obtainable according to the process and the isolation of the desired isomer and/or the conversion of a free compound of the formula | obtainable according to the process to a salt or the conversion of a salt of a compound of the formula | obtainable according to the process to the free compound of the formula | or to another salt.

8. A composition for controlling parasites, which comprises, in addition to carriers and/or dispersants, at least one compound of the formula | according to claim 1 as active ingredient.

9. The use of a compound of the formula | according to claim 1 for controlling parasites.

10. A method for controlling parasites, which comprises the use, against the parasites, of an effective amount of at least one compound of the formula | according to claim 1.

11. The use of a compound of the formula | according to claim 1 in a method for controlling parasites in warm-blooded animals.

12. The use of a compound of the formula | according to claim 1 for preparing a pharmaceutical composition against parasites in warm-blooded animals.