SK140693A3 - Application cn-substituted benzimidazols - Google Patents

Abstract

The invention relates to the use of CN-substituted benzimidazoles of the general formula (I) <IMAGE> in which X<1>, X<2>, X<3> and X<4> independently of one another in each case represent hydrogen, halogen, cyano or nitro, or represent in each case optionally substituted alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl or cycloalkyl, or represent dioxyalkylene which is fused and optionally substituted, or represent hydroxycarbonyl, alkylcarbonyl, alkoxycarbonyl, cycloalkyloxycarbonyl, or represent in each case optionally substituted amino or aminocarbonyl, or in each case optionally substituted aryl, aryloxy, arylthio, arylsulphinyl, arylsulphonyl, arylsulphonyloxy, arylcarbonyl, aryloxycarbonyl, arylazo or arylthiomethylsulphonyl, but where at least one of the substituents X<1>, X<2>, X<3> and X<4> is other than hydrogen and halogen and where R<1> represents hydrogen, alkyl or optionally substituted aryl, R<2> represents hydroxy, cyano or in each case optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, amino, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, dialkoxyphosphoryl, (hetero)aryl, (hetero)arylcarbonyl, (hetero)aryloxycarbonyl, (hetero)arylcarbonyloxy or (hetero)arylaminocarbonylaminocarbonyloxy, as agents for controlling parasitic protozoans and, in particular, Coccidia.

Description

Use of CN-substituted benzimidazoles

Technical field

The invention relates to the use of CN-substituted benzimidazoles as agents for controlling parasitic protozoa and in particular coccidia as well as parasites in fish and insects.

BACKGROUND OF THE INVENTION

Substituted benzimidazoles and their use as insecticides, fungicides and herbicides are already known (EP-OS 87 375, 152 360, US-P 3,472,865, 3,576,818, 3,418,318, EP-OS 260 744, 266 984, 181 826 and 239,508.

Also known are polyhalogenated benzimidazoles and their effect as antelmics, coccidiostats and pesticides (DE-OS 2 047 369). Nevertheless, their effect is in any case not satisfactory.

SUMMARY OF THE INVENTION

It is an object of the present invention to use

CN-substituted benzimidazoles of formula I i

in which ·>

X ^1, X ^2, X ³ and X ⁴ independently of one another represent hydrogen, halogen, cyano, nitro, in each case optionally substituted alkyl group, alkoxy group, alkylthio group, alkylsulfonyl group, alkylsulfinyl group or a cycloalkyl group, an optionally substituted, fused dioxyalkylene group , hydroxycarbonyl, alkoxycarbonyl, cycloalkyloxycarbonyl, in each case optionally substituted amino or aminocarbonyl, or in each case optionally substituted aryl, aryloxy, arylthio, arylsulfinyl, aryl, arylsulfonyloxy, arylsulfonyloxy, arylsulfonyloxy, one of X 1 -, X ² , X ³ and X ^{4 is} not a hydrogen atom or a halogen atom,

R ¹ represents a hydrogen atom, an alkyl group, a cycloalkyl group or an optionally substituted aryl group, and

R ² is hydroxyl, cyano or in each case optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, amino, aminocarbonyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, dialkoxyphosphoryl group, a (hetero) aryl, ( hetero) arylcarbonyl, (hetero) aryloxycarbonyl (hetero) arylcarbonyloxy, but (heteroaryl) aminocarbonylaminocarbonyloxy, as a means for destroying parasitic protozoa and in particular coccidia.

The compounds of the formula I can optionally exist, depending on the type and number of substituents, as geometric and / or optical isomers, or regioisomers or mixtures of these isomers of different compositions. The present invention claims the use of both pure isomers and isomeric mixtures.

Substituted benzimidazoles useful in the present invention are generally defined by Formula I. Preferred are compounds of Formula I wherein X ³ and X ^{4 are} each independently hydrogen, fluoro, chloro, bromo or iodo, cyano, nitro, in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, straight or branched haloalkyl, haloalkyl, haloalkyl, haloalkyl, haloalkyl, haloalkyl, haloalkyl, haloalkyl, haloalkyl, From 1 to 6 carbon atoms of up to 13 identical or different halogen atoms or, optionally, one or more times, equally or differently halogen and / or straight or branched (C1-C4) alkyl and / or straight or branched alkyl a C 1 -C 4 -halogenoalkyl group having from 1 to 9 identical or different halogen atoms, a double-bonded dioxyalkylene group having from 1 to 5 carbon atoms, in addition being a hydroxycarbonyl group, in each case a straight or branched alkylcarbonyl group or an alkoxycarbonyl group having in each case C 6 -C 6 -alkyl, cycloalkyloxycarbonyl having 3 to 8 carbon atoms in the cycloalkyl portion, or alternatively optionally one or more times the same or differently substituted amino or aminocarbonyl group, the following being in each case possible as amino substituents:

in each case straight-chain or branched alkyl having 1 to 6 carbon atoms, haloalkyl having 1 to 6 carbon atoms of up to 13 halogen atoms, alkoxyalkyl or alkylcarbonyl having 1 to 6 carbon atoms in each alkyl moiety or in the aryl moiety optionally once or polysubstituted in an identical or different substituted arylcarbonyl, arylsulfonyl, arylaminocarbonyl or arylmetylsulfonylová each having 6 to 10 carbon atoms in the aryl moiety, wherein the substituents of aryl are, each account of the groups stated under R ¹ furthermore represents in each case optionally in the aryl parts one or more times, as well or differently substituted aryl, aryloxy, arylthio, arylsulfinyl, arylsulfonyl, arylsulfonyloxy, arylcarbonyl, aryloxycarbonyl, arylthiomethylsulfonyl or arylalkyl having from 6 to 10 carbon atoms in the aryl moiety, the aryl substituents being those mentioned under R ¹ , but at least one of X ¹ , X ² , X ³ and X ^{4 being} not hydrogen or halogen,

R ¹ represents hydrogen, straight-chain or branched alkyl having 1 to 8 carbon atoms or optionally mono- or polysubstituted in an identical or different substituted phenyl, wherein the substituents are:

a halogen atom, a cyano group, a nitro group, a straight or branched alkyl group, an alkoxy group, an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group having from 1 to 6 carbon atoms, a straight or branched haloalkyl group, a haloalkoxy group, up to 6 carbon atoms and 1 to 13 identical or different halogen atoms, in each case straight or branched alkoxyalkyl, alkoxyalkoxy, alkanoyl, alkoxycarbonyl or alkoxyiminoalkyl of 1 to 6 carbon atoms in each alkyl moiety, optionally once or several times, likewise or various halogen and / or straight or branched (C 1 -C 6) alkyl and / or straight or branched (C 1 -C 6) haloalkyl of 1 to 13 identical i or a different halogen atom substituted, double bonded dioxyalkylene group having 1 to 5 carbon atoms or optionally one or more times the same or different halogen and / or straight or branched alkyl group having 1 to 6 carbon atoms and / or straight or branched haloalkyl group having 1 phenyl substituted with from 1 to 13 carbon atoms and 1 to 13 identical or different halogen atoms;

R ² is hydroxyl, cyano or in each case optionally mono- or polysubstituted in an identical or different, halogen substituted alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkyloxyfosforylovú each having up to 8 carbon atoms in the individual alkyl, alkenyl or alkynyl moieties, the substituents always being:

halogen, straight or branched alkoxy group having 1 to 8 carbon atoms or mono- or polysubstituted by identical or different substituents consisting of aryl of 6 to 10 carbon atoms, wherein the substituents of aryl are, for each group mentioned in R ¹ except that R ² each optionally one or more times, as well as a differently substituted amino or aminocarbonyl group, the substituents here being:

straight or branched (C 1 -C 8) alkyl, straight or branched (C 2 -C 8) alkenyl, (C 3 -C 8) cycloalkyl, alkoxycarbonyl, alkylthiocarbonyl, alkoxythiocarbonyl or alkylthio-thiocarbonyl in each case 8 carbon atoms in each straight or branched alkyl moiety, a double-bonded, ring-closed, 2-6C alkanediyloxycarbonyl group, or alternatively optionally one or more times, the same or differently substituted arylalkyl or aryl group having 6 to 10 carbon atoms in each of the aryl moiety and optionally of 1 to 6 carbon atoms in the straight or branched alkyl moiety, the aryl substituents being in each case the groups mentioned under R ¹ , in addition R ^{2 being} optionally once or several times, the same the or different, substituted aryl, arylcarbonyl, aryloxycarbonyl, arylcarbonyloxy or arylaminokarbonylaminokarbonyloxyskupinu each case having 6 to 10 carbon atoms in the aryl moiety, wherein the substituents of aryl are, each account of the groups stated under R ^1, and also repeatedly, heteroaryl, R ² in each case optionally one or the same or differently substituted, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylcarbonyloxy having 2 to 9 carbon atoms and 1 to 5 identical or different heteroatoms, in particular nitrogen, oxygen and / or sulfur in the heteroaryl moiety, being heteroaryl substituents They are, for the groups stated under R ^first

Ί

Particularly preferred are compounds of formula I in which

X ^2, X ^2, X ³ and X ⁴ independently of one another denote hydrogen, fluorine, chlorine, bromine, cyano, nitro, in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl having in each case 1 to 6 C 3 -C 7 cycloalkyl, straight or branched haloalkyl, haloalkoxy, haloalkylthio, haloalkylsulphinyl or haloalkylsulphonyl, in each case having up to 4 carbon atoms or one or more times of the same or a number of 1 to 9 various halogen and / or straight or branched (C 1 -C 4) alkyl and / or straight or branched (C 1 -C 4) haloalkyl and (C 1 -C 9) halogen-substituted or dioxyalkylene substituted double-bonded dioxyalkylene group In addition, it is understood that, in addition, it is a straight-chain or branched hydroxycarbonyl group. alkylcarbonyl or alkoxycarbonyl having 1 to 4 carbon atoms in the alkyl moiety, cycloalkyloxycarbonyl having 3 to 7 carbon atoms in the cycloalkyl moiety, or alternatively optionally one or two times the same or differently substituted amino or aminocarbonyl group, in each case as amino substituents:

in each case straight-chain or branched alkyl having 1 to 4 carbon atoms, haloalkyl having 1 to 4 carbon atoms and having 1 to 9 halogen atoms, alkoxyalkyl or alkylcarbonyl having 1 to 4 carbon atoms in each alkyl moiety or in the aryl moiety respectively one to five times, the same or differently substituted arylcarbonyl δ

, arylsulfonyl, arylaminocarbonyl or arylmetylsulfonylová each having 6 to 10 carbon atoms in the aryl moiety, wherein the substituents of aryl are, each account of the groups stated under R ¹ furthermore represents in each case optionally in the aryl moiety one to five identical or different substituted aryl, aryloxy, arylthio, arylsulfinyl, arylsulfonyl, arylsulfonyloxy, arylcarbonyl, aryloxycarbonyl, aryltiometylsulfonylovú group or arylazo having in each case 6 to 10 carbon atoms in the aryl moiety, wherein the substituents of aryl are, for the groups stated under R ³ · provided, however, that at least one of X ¹ , X ² , X ³ and X ^{4 is} not a hydrogen atom or a halogen atom,

R ¹ represents a hydrogen atom, a straight or branched alkyl group having 1 to 6 carbon atoms or, optionally, one to three times, as well as a differently substituted phenyl group, with the following substituents being suitable:

a halogen atom, a cyano group, a nitro group, a straight or branched alkyl group, an alkoxy group, an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group having from 1 to 4 carbon atoms, a straight or branched haloalkyl group, a haloalkoxy group, haloalkylthio up to 4 carbon atoms and 1 to 9 identical or different halogen atoms, in each case straight or branched alkoxyalkyl, alkoxyalkoxy, alkanoyl, alkoxycarbonyl or alkoxyiminoalkyl of 1 to 4 carbon atoms in each alkyl moiety, optionally once to six times, the same or various halogen and / or straight or branched (C 1 -C 4) -alkyl and / or straight or branched (C 1 -C 4) -haloalkyl of up to about 9 or the same; a halogen-substituted, double-bonded, dioxyalkylene group having 1 to 4 carbon atoms or optionally one or more times as well or different halogen and / or a straight or branched alkyl group having 1 to 4 carbon atoms and / or a straight or branched haloalkyl group having 1 to 4 phenyl substituted with 1 to 9 identical or different halogen atoms;

R @ ² is cyano, cyano or in each case one to five times, as well as different halogen-substituted alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl or alkoxycarbonyl, alkylcarbonyl or alkoxycarbonyl groups; atoms in the individual alkyl, alkenyl or alkynyl moieties or in each case optionally one to three times, as well as a differently substituted alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl or 6-alkylcarbonyl, alkylcarbonyl alkoxy carbon atoms in the individual alkyl, alkenyl or alkynyl moieties, whereby in each case:

straight or branched alkoxy group having 1 to 6 carbon atoms or optionally mono- to trisubstituted by identical or different substituted aryl of 6 to 10 carbon atoms, wherein the substituents of aryl are, for each group mentioned in R ¹ except that R ² in each case optionally singly or twice, the same or differently substituted amino or aminocarbonyl group, the substituents here being:

straight or branched (C 1 -C 6) alkyl, straight or branched (C 2 -C 6) alkenyl, (C 3 -C 7) cycloalkyl, alkoxycarbonyl, alkylthiocarbonyl, alkoxythiocarbonyl or alkylthio-thiocarbonyl; 6 carbon atoms in each straight or branched alkyl moiety, a double-bonded, ring-closed, 2 to 5 carbon alkanediyloxycarbonyl group, or alternatively optionally one to three times, the same or differently substituted arylalkyl or aryl group having 6 to 10 carbon atoms in each of aryl and optionally 1 to 6 carbon atoms in a straight or branched alkyl moiety, the aryl substituents being in each case the groups mentioned under R ¹ , in addition R ^{2 being in} each case one to three times, the same or different substituted aryl, arylcarbonyl, aryloxycarbonyl, arylcarbonyloxy, or arylaminokarbonylaminokarbonyloxy group each having 6 to 10 carbon atoms in the aryl moiety, wherein the substituents of aryl are, each account of the groups stated under R ¹ except that R ² in each case optionally mono- to five times , likewise or differently substituted heteroaryl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylcarbonyloxy or heteroarylaminocarbonylaminocarbonyloxy having in each case 6 to 9 carbon atoms and having 1 to 4 identical or different heteroatoms, in particular with heteroatoms, with nitrogen, oxygen and / or the groups mentioned under R ^{@ 1 are in each case possible} .

Aryl radicals include phenyl or naphthyl, and heteroaryl radicals include pyridyl.

Most preferred are compounds of Formula I wherein:

X ^1, X ^2, X ³ and X ⁴ independently of one another represent hydrogen, chlorine, bromine, cyano, nitro, in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl having in each case 1 to 4 carbon atoms a cycloalkyl group having 3, 5 or 6 carbon atoms, a straight or branched haloalkyl group, a haloalkoxy group, a haloalkylthio group, a haloalkylsulfinyl group or a haloalkylsulfonyl group having in each case 1 to 3 carbon atoms and optionally 1 to 7 identical or different; or a different halogen and / or straight or branched alkyl group having 1 to 3 carbon atoms and / or a straight or branched haloalkyl group having 1 to 3 carbon atoms and having from 1 to 7 identical or different halogen atoms a substituted, double bonded dioxyalkylene group having In addition, it is a hydroxycarbonyl group, in each case a straight or branched alkylcarbonyl group or an alkoxycarbonyl group having in each case 1 to 3 carbon atoms in the alkyl moiety, a cycloalkyloxycarbonyl group having 3, 5 or 6 carbon atoms in the cycloalkyl moiety or in each case optionally once or the same or differently substituted amino or aminocarbonyl group, in each case identical or different, in each case the following may be used as amino substituents:

in each case straight-chain or branched alkyl having 1 to 3 carbon atoms, haloalkyl having 1 to 3 carbon atoms and having 1 to 7 halogen atoms, alkoxyalkyl or alkylcarbonyl having 1 to 3 carbon atoms in each alkyl moiety or in the phenyl moiety respectively one to three times, the same or differently substituted phenylcarbonyl, phenylsulfonyl, phenylaminocarbonyl or phenylmethylsulfonyl groups, in which case the groups mentioned under R &lt; ³ &^gt; in each case may also be used as phenyl substituents; substituted phenyl, phenyloxy, phenylthio, phenylsulfinyl, phenylsulfonyl, phenylsulfonyloxy, phenylcarbonyl, phenyloxycarbonyl, phenylthiomethylsulfonyl or phenylazo, wherein as phenyl substituents u is suitable for the groups mentioned under R ³ , but at least one of X ¹ , X ² , X ³ and X ^{4 is} not a hydrogen atom or a halogen atom,

R ^{@ 1} represents a hydrogen atom, a straight or branched alkyl group having 1 to 4 carbon atoms or, optionally, once or twice, the same or differently substituted phenyl group, the substituents being:

a halogen atom, a cyano group, a nitro group, a straight or branched alkyl group, an alkoxy group, an alkylthio group, an alkylsulfinyl group or an alkylsulfonyl group having from 1 to 3 carbon atoms, a straight or branched haloalkyl group, a haloalkoxy group, Straight or branched alkoxyalkyl, alkoxyalkoxy, alkanoyl, alkoxycarbonyl or alkoxyiminoalkyl of 1 to 3 carbon atoms in each alkyl moiety, optionally one to four times, the same or different halogen and / or a straight or branched alkyl group having 1 to 3 carbon atoms and / or a straight or branched haloalkyl group having 1 to 3 carbon atoms and having 1 to 7 identical or a halogen-substituted, double-bonded, dioxyalkylene group having 1 to 3 carbon atoms or optionally one to three times the same or different halogen and / or a straight or branched alkyl group having 1 to 3 carbon atoms and / or a straight or branched haloalkyl group having 1 to 3 phenyl substituted with 1 to 7 identical or different halogen atoms and

^R2 is kydroxyskupinu, cyano or in each case optionally mono- to trisubstituted by identical or different halogen substituted alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkyloxyfosforylovú radical having up to 4 carbon atoms in the individual alkyl, alkenyl or alkynyl moieties or in each case optionally once or twice, as well as differently substituted alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, dialkyloxy or alkylcarbonyloxy groups carbon atoms in the individual alkyl, alkenyl or alkynyl moieties, whereby in each case:

straight or branched alkoxy having 1 to 3 carbon atoms or optionally once or twice, as well as or differently substituted phenyl, the substituents phenyl being in each case R ¹ , in addition R ^{2 being} optionally once or twice, as well or a differently substituted amino or aminocarbonyl group, with the following substituents being suitable here:

straight or branched (C 1 -C 4) alkyl, straight or branched (C 2 -C 4) alkenyl, (C 3 -C 6) cycloalkyl, alkoxycarbonyl, alkylthiocarbonyl, alkoxythiocarbonyl or alkylthio-thiocarbonyl in each case 4 carbon atoms in each straight or branched alkyl moiety, a double-bonded, ring-closed, alkanediyloxycarbonyl group having 2 to 4 carbon atoms in the alkanediyl moiety or in each case optionally once or twice, as well as different phenylalkyl or phenyl groups, up to 3 carbon atoms in straight or branched alkyl moieties, wherein the substituents of phenyl are in each case the groups mentioned under R ¹ , optionally substituted with 1, in addition R ^{2 in} each case optionally one to three times, as well as differently substituted phenyl, phenylcarbonyl, fen yloxycarbonyl, phenylcarbonyloxy or phenylaminocarbonylaminocarbonyloxy, wherein the substituents of phenyl are in each case the groups mentioned under R ³ , in addition R ^{2 being in} each case optionally one to three times, the same or differently substituted heteroaryl,

- heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylcarbonyloxy or heteroarylaminocarbonylaminocarbonyloxy having from 2 to 9 carbon atoms and from 1 to 3 identical or different heteroatoms, in particular with nitrogen, oxygen and / or sulfur in the heteroaryl moiety; under R ¹ .

A heteroaryl radical is a pyridyl group.

In addition, the substituted benzimidazoles of general formula (I) shown in the following table may be mentioned in addition to the compounds of the Examples:

CN

(D

X

2 '

χΐ X2 X3 χ4 A br H cf ₃ -s- H .N -CH3 -COOC3H3 br H cf ₃ -s- H -CHO-O-C2H5 br H C1FCH-CF ₂ -S- H - .N -CH 3 COC 6 H 4 br H C1FCH-CF2-S- H -CH 2 -OC ₂ H ₅ br H F3C-CHF-CF2-S- H <ΡΗ. 1 N -CH3 -COOC3H3 br H f ₃ c-chf-cf ₂ -s- H -CH2-O-C2H5 br H f ₃ c- H -CH2-O-C2H5 br H f ₃ č-o- H CA .N -CH 3 COOC 3 H 3 br H f ₃ co- H -CH2-O-C2H5 br H no ₂ H CA —CHj COOCjHí br H no ₂ H -CH2-O-C2H5 and H CF3-S- H .N -CH 3 COOC 3 H 3 and H cf ₃ -s- H -CH2-O-C2H5 and H C1FCH-CF2-S- H -CHj TOOCjHj cr H C1FCH-CF ₂ -S- H -CH9-O-C9H5 and H f ₃ c-chf-cf ₂ -s- H 9Λ

—Αζ ^ cooCjHj xi α

ci

Xi

H

H

X ³

F3C-CHF-CF2-SF ₃ CX4

H

H

-CH 2 -O-C 2 H 5 O ₃ F ₃ C-O-CH ₃ COOC 3

-CH2-O-C2H5

CA

F3C-0no ₂

-CH3C4Cj-Hj

-CH2-O-C2H5

CA α

ca ₃ no ₂

CF 3 -S-Olf 4 COOC 4

-CH ₂ -OC ₂ H ₅

CA ca ₃ ca ₃

CF3-CF2-SC1FCH S ^ αζ cooCjHj -CH ₂ -OC ₂ hours _{5 watts CF3 CF3}

C1FCH-CF2-CHF-SF3C CF 2 S

WITH

-CH 2 COOC 4 H 3

-CH2-O-C2H5

CA

COOC2 H3 cf ₃ cf ₃

F3C-CHF-CF2-S

F 3 C-ch ₂ -oc ₂ h ₅

CA f ₃ c —σζζζooCjHj -CH 2 -O-C2H5

χΐ Χ2 Χ3 x ⁴ Α cf ₃ Η f ₃ co- Η <jA .Ν -CHj XOOCjHj cf ₃ Η F3C-0- Η -ch ₂ -oc ₂ h ₅ cf ₃ Η Ν0 ₂ Η CA .N —CH3 ^ COOC3H3 cf ₃ Η νο ₂ Η -CH2-O-C2H5 COOCH3 Η CF3-S- Η CA .N -CHj COOCft COOCH3 Η CF3-S- Η -CH2-O-C2H5 COOCH3 Η C1FCH-CF2-S- Η CA - ^N - CH 3 COOC 3 H 3 COOCH3 Η C1FCH-CF2-S- Η -CH2-O-C2H5 COOCH3 Η F3C-CHF-CF2-S- Η CA .N -CH 3 COOC 3 H 3 COGCH3 Η F3C-CHF-CF2-S- Η -ch ₂ -oc ₂ h ₅ COOCH3 Η 3 C- Η CA - ^N 1 -CH 2 COOC 3 H 4 COOCH3 Η 3 C- Η -CH2-O-C2H5 COOCH3 Η F3C-0- Η CA -CH 3 COOC 3 H 3 COOCH3 Η F3C-0- Η -CH2-O-C2H5

X ¹ X2 X3 χ4 A COOCH3 H no ₂ H CA .N -CH 3 COOC 3 H 3 COOCH3 H no ₂ H -CH ₂ -OC ₂ H ₅ COO-n-C3H7 H CF3-S- H CA - ^N \ —A COOCH 11-COO-C3H7 H CF3-S- H -CH ₂ -OC ₂ H 5 11-COO-C3H7 H C1FCH-CF ₂ -S- H CA - ^N \ -CHj COOCÉHj COO-C ₃ H ₇ H cifch-cf ₂ -s- H -CH ₂ -OC ₂ H 5 COO-C ₃ H ₇ H C ₃ CHF-CF ₂ -S- H ' ^N \ —A cooca COO-C ₃ H ₇ H C ₃ CHF-CF ₂ -S- H CH ₂ OC ₂ H '; COO-C ₃ H ₇ H F ₃ C- H CA A. —A COOCjHj 11-COO-C3H7 H f ₃ c- H -CH ₂ -OC ₂ H ₅ COO-C ₃ H ₇ H f ₃ co- H CA —A cooca COO-C ₃ H ₇ H F3C-0- H -CH ₂ -OC ₂ H 5 11-COO-C3H7 H no ₂ H CA 1 CO 6 - C ₃ H 7 -A 2 COOC 3 H 3 H no ₂ H -CH ₂ -OC ₂ H ₅

Substituted benzimidazoles of the formula I are known in part (see for example DE 20 47 369; DE 20 14 293; EP 448 206 and J. Chem. SOC. C, 1967, 2536-2540).

Until now unknown, the subject of the earlier application of the same Applicant is substituted benzimidazoles of the general formula Ia

1-1

in which

X ^1-1, X ^{2 '1,} X ^3-3 and X ⁴ · ^"1 independently of one another represent hydrogen, halogen, cyano, an optionally substituted alkyl group, alkoxy group, alkylthio group, alkylsulfonyl group, alkylsulfinyl group or a cycloalkyl group , optionally substituted fused dioxyalkylene, hydroxycarbonyl, alkoxycarbonyl, cycloalkyloxycarbonyl, in each case optionally substituted amino or aminocarbonyl, or in each case optionally substituted aryl, aryloxy, arylthio, arylthio, arylsulfinyl, arylsulfinyl, arylsulfinyl, arylsulfinyl group or arylthiomethylsulfonyl, however, at least one of ^X1-1 , ^X2-1 , ^X3-1 and ^X4-1 is nitro, haloalkyl, haloalkylthio, haloalkylsulfinyl, haloalkylsulfonyl; a phenyl group and an alkylsulfonyl group, an optionally substituted fused dioxyalkylene group, a hydroxycarbonyl group, an alkylcarbonyl group, an alkoxycarbonyl group or a cycloalkyloxycarbonyl group, in each case an optionally substituted amino group or an aminocarbonyl group, or an optionally substituted aryl group, an aryl group, an aryl group, arylazo or arylthiomethylsulfonyl,

R ¹ represents a hydrogen atom, an alkyl group, a cycloalkyl group or an optionally substituted aryl group, and

R ² represents hydroxy: yskupinu, cyano or in each case optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, alkylthio, amino, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, dialkoxyphosphoryl group, a (hetero) aryl, (hetero arylcarbonyl, (hetero) aryloxycarbonyl, (hetero) arylcarbonyloxy, or (hetero) arylaminocarbonylaminocarbonyloxy.

; The known and still unknown substituted benzimidazoles of the formula I or Ia are obtained by reacting also the ΙΗ-benzimidazoles of the formula II

(Π) in which X ¹ , X ² , X ³ and X ^{4 are} as defined above, with alkylating agents of formula III

R ¹

I

E - CH (III), ₁₂

R ² in which

E represents a suitable leaving group and

R ¹ and R ² are as defined above, if appropriate in the presence of a diluent and if appropriate in the presence of a reaction auxiliary.

When 5-nitro-2-cyanobenzimidazole and chloromethyl ethyl ether are used as starting materials, the reaction of the production process can be illustrated by the following reaction scheme:

Ο, Ν — CN + 2 Cl — CH3-O — C1 H3

H

- HCl

----

base

The 1H-benzimidazoles required as starting materials for carrying out the production process are generally defined by Formula II. In this formula, the substituents X ¹ , X ² , X ³ and X ^{4 have} the same meanings as those mentioned above with respect to the description of the compounds of formula I useful according to the present invention as preferred.

The 1 H -benzimidazoles of formula II are known or can be obtained analogously to known methods (see, for example, J. Amer. Chem. Soc. 75, 2192 (1953); US 3,576,818).

The alkylating agents required below as starting products for carrying out the production process are generally defined by the formula

III. In this formula III, the substituents R ¹ and R ² have the preferred meanings indicated as being advantageous in connection with the description of the compounds of the general formula I which can be used according to the invention.

Substituent E represents a leaving group customary for alkylating agents, preferably a halogen atom, in particular chlorine, bromine or iodine or in each case an optionally substituted alkylsulfonyloxy, alkoxysulfonyloxy or arylsulfonyloxy group, in particular methanesulfonyloxy group, trifluoromethanone, trifluoromethanone.

In addition, substituent E is also an alcohol, alkanoyloxy or alkoxy group, such as, for example, hydroxy, acetoxy or methoxy, in particular when they are to be prepared by the above process of a compound of formula I in which R ^{@ 1 is} not hydrogen.

The compounds of the formula III are generally known and can be obtained analogously to known methods (see, for example, DE 20 40 175; DE 21 19 518; Synthesis 1973. 703).

Possible diluents which are inert include particularly aliphatic organic solvents for the production process. To these, alicyclic or aromatic, optionally halogenated hydrocarbons such as benzene, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform or carbon tetrachloride; such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran, ethylene glycol dimethyl ether or ethylene glycol trimethyl ether; ketones such as acetone, butanone or methyl isobutyl ketone; nitriles such as acetonitrile, propionitrile or benzonitrile; amides such as

N, N, -dimethylformamide, Ν, Ν-dimethylacetamide, N-methylformanilide,

N-methylpyrrolidone or hexamethylphosphoric triamide; esters such as ethyl acetate, bases such as formic acid or acetic acid.

Said process is preferably carried out in the presence of a suitable auxiliary reagent. As such, all conventional inorganic or organic bases are suitable. These include, for example, alkali metal or alkaline earth metal hydroxides, hydrides, amides, alcoholates, acetates, carbonates or bicarbonates such as sodium hydride, sodium amide, lithium diethylamide, sodium methylate, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate , ammonium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or ammonium carbonate, organolithium compounds such as n-butyllithium, and tertiary amines such as trimethylamine, triethylamine, tributylamine, diisopropylethylamine, tetramethylguanide , N, N-dimethylamine, pyridine, piperidine, N-methylpiperidine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclo-cyclononene (DBN) or diazabicycloundecene (DBU).

Alternatively, organic or inorganic acids such as, for example, sulfuric acid, hydrochloric acid, p-toluenesulfonic acid, perfluorobutanesulfonic acid or strongly acidic ion exchangers are particularly suitable as auxiliary reagents, in particular when, in the alkylating agents of the formula II used, E is hydroxy, acyloxy or alkoxy. .

Said process may optionally also be carried out in a two-phase system, such as water / toluene or water / dichloromethane, optionally in the presence of a suitable phase transfer catalyst. Examples of such catalysts include: tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, tributylmetylfosfóniumbromid, trimethylcyclohexoxy / cis-alkylammonium ammonium methyl sulphate, _dimethyl-C12 / _C14 -alkyl-benzylammonium chloride, _dimethyl-C12 / _C14 -alkyl-benzylamóniumbromid, tetrabutylammonium hydroxide , triethylbenzylammonium chloride, methyltrioctylammonium chloride, trimethylbenzylammonium chloride, 15-krone-5, 18-krone-6 or tris- [2- (2-methoxyethoxyJetyl) amine.

The reaction temperatures can be varied within a wide range when carrying out the production process. In general, temperatures of -70 ° C to 200 ° C, preferably between 0 ° C and 130 ° C, are employed.

The production process is generally carried out at normal pressure, but it is also difficult to work at elevated or reduced pressure.

In carrying out the production process, one-mol of ΙΗ-benzimidazole of the formula II is generally used in the range of 1.0 to 5.0 mol, preferably 1.0 to 2.5 mol, of the alkylating agent of the formula III and optionally 0.01 to 5.0 mol, preferably 0 to 3.0 moles of auxiliary reagent.

In a particular embodiment, the ΙΗ-benzimidazole of formula (II) can also be silylated using a conventional silylation procedure, for example with hexamethyldisilazane or trimethylsilyl chloride, optionally in the presence of a suitable catalyst such as sulfuric acid, trifluoroacetic acid, ammonium sulfate or imidazole. saccharin, at a temperature in the range of -20 ° C to 150 ° C, and the 1-trimethylsilylbenzimidazoles thus obtained are reacted with alkylating agents of formula II in the next second step. In this case, it is preferred to add tin tetrachloride as the catalyst for the alkylation reaction (see, e.g., Chem. Heterocycl. Comp. USSR 24 514 (1981)).

Conducting the reaction, working up and isolating the reaction product are carried out by known methods (see, for example, also the production examples).

The purification of the end products of the formula I is carried out by customary methods, for example by column chromatography or crystallization.

The characterization of the melting or the products is carried out by means of the temperature of the non-crystallising compounds, in particular

- 27 for regioisomers, by proton nuclear resonance spectroscopy (1 H-NMR).

The active substances are suitable for good toxicity in warm-blooded animals for the control of parasitic protozoa, which occur in the cultivation and breeding of livestock, breeding animals, zoo animals, laboratory animals, experimental animals and animals reared for pleasure. They are effective against all or individual developmental stages of pests, as well as against resistant and normally sensitive species. The destruction of parasitic protocols is intended to reduce disease, mortality and performance degradation (for example, in the production of meat, milk, wool, skins, eggs, honey and the like), so that the use of the active ingredients makes animal breeding more economical and easier.

Parasitic protozoa include:

Mastigophora (Flagellata), such as Trypanosomatidae, e.g. Trypanosoma b. brucei, T.b. gamniense, T.b. rhodesiense, T. congolense, T. cruzi, T. evansi, T. equinum, T. lewisi, T. percae, T. simiae, T. vivax, Leishmania brasiliensis,

L. donovani, L. tropica such as Trichomonadidade, e.g. Giardia lamblia, G. canis.

Sarcomastigophora (Rhizopoda) such as Entamoebidade, for example Entamoeba histolytica, Harmanellidae, for example Acanthamoeba sp., Hartmanella sp.

Apicomplexa (Sporozoa), acervulina, E. adenoides, E. arloingi, E. ashata, E. canis, E. chinchillae, E.

crandalis, E falciformis, hagans, E. labbeana, E. meleagridis, debliecki, E. faurei, intestinalis leucarti,

E. mitis such as Eimeridae, for example Eimeria E. alabahmensis, E. anatis, E. anseris, auburnesis, E. bovis, E. brunetti, E. clupearum, E. columbae, E. contorta, E.

E. dispersa, E. allipsoidales, E. E. flavescens, E., gallopavonis, E., E. iroquolina, E. irresidua, E. E. magna, E. maxima, E. media, E. E. necatrix, E. ninakohlyakimovae, E.

ovis, E. parva, E. pavonis, E. perforans, phasani, E.

piriformis, E. praecox, E. residua, E. scarba, E. spec., E.

stiedai, E. suis, tenella, E. truncata, E. truttae, E. zuernii, Globidium spec., Isospora belli, I. canis, I. felis, I. ohioensis, I. rivolta, I. spec., I. suis, Cystisospora spec., Cryptosporidium spec., Toxoplasmadidae, for example Toxoplasma gondii, such as Sarcocystidae, for example Sarcocystis bovicanis, S. bovihominis, S. ovicanis, S. ovifelis, S. spec., S. suihominis, such as Leucozytoidae, e.g. simondi such as Plasmodiidae, for example Plasmodium berghei, P. Falciparum, P. malariae, P. ovale, P. vivax, P. spec., e.g. Babesia argentina, B. bovis, B.

such as Phiroplasmea, canis, B. spec.,

Theileria parva, Theileria spec. Such as Hepatozoon canis, H. spec.

Adeleina, for example

Further, Myxospora and Microspora, for example, Glugea spec., Wear spec.

Furthermore, Pneumocystis carinii as well as Ciliophora (Ciliata) such as Balantidium coli, Ichtiophthirinus spec., Trichodina spec., Epistylis spec.

The compounds of the present invention are also active against protozoa, which occur as parasites on insects. As such, parasites of the genus Microspodia, in particular of the genus Nosema, can be mentioned. Particular mention should be made of Nosema apis in honey bees.

Utility and breeding animals include mammals such as cows, horses, sheep, pigs, goats, camels, buffaloes, donkeys, rabbits, fallow deer, reindeer, fur animals such as mink, chinchilla and raccoon, birds such as chickens , geese, turkeys, ducks, pigeons, birds for the household and zoo. It also includes commercial and ornamental fish.

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

The animals kept for pleasure include dogs and cats.

The fish include commercial, breeding, aquarium and decorative fish of all ages, freshwater and saltwater. Commercial and breeding fish include, for example, carp, eel, trout, whitefish, salmon, bream, rhinoceros, red penguin, turbot, flounder, halibut, Seriola quinqueradiata, Anquilla japonica, Pagurus major, Dicentrarchus labrax, mugilus cephalus, Pompano, auratus, Tilapia spp., Chichlida species, such as, for example, Plagioscion Channel catfisch. Particularly suitable are the compositions according to the invention for the treatment of fish larvae, for example carp of 2-4 cm. These compositions are also very suitable for eel feed.

Application can be carried out both prophylactically and therapeutically.

The use of the active compounds takes place directly in the form of suitable preparations enterally, parenterally, dermally or nasally.

Enteral administration of the active ingredients takes place, for example, orally in the form of powder, suppositories, tablets, capsules, pastes, beverages, granules, drains, medicated feed or drinking water. The dermal application is carried out, for example, by dipping, spraying, bathing, washing, watering and powdering. Parenteral administration takes the form of injections (intramuscular, subcutaneous, intravenous, intraperitoneal) or implants.

Preferred formulations include:

Solutions such as injectable solutions, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, glazing preparations and jellies;

emulsions and suspensions for oral or dermal administration as well as for injection; semi-solid preparations;

preparations in which the active substance is incorporated in an ointment base or in oil-in-water or water-in-oil emulsion bases;

Solid formulations such as powders, premixes or concentrates, granules, pellets, tablets, and capsules; aerosols and inhalants, moldings containing the active substance.

Injectable solutions may be administered intravenously, intramuscularly and subcutaneously.

Injectable solutions are prepared by dissolving the active compound in a suitable solvent and adding optional ingredients such as solubilizers, acids, bases, buffer salts, anitioxidants, preservatives and the like. These solutions are sterile filtered and filled.

Suitable solvents include physiologically acceptable solvents such as water, alcohols such as ethyl alcohol, butyl alcohol, benzyl alcohol and glycerol, hydrocarbons, propylene glycol, polyethylene glycols, N-methylpyrrolidone, and mixtures thereof.

Alternatively, the active compounds may also be dissolved in physiologically acceptable vegetable or synthetic oils which are suitable for injection.

Dissolution agents are understood to be solvents which promote the dissolution of the active substance in the principal solvent or prevent its precipitation. Examples include polyvinylpyrrolidone, polyoxyethyl castor oil and polyoxyethyl sorbitan ester.

Preservatives include benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester or n-butyl alcohol.

Oral solutions are applied directly. Concentrates are applied orally after previous dilution to the desired concentration. Oral solutions and concentrates are prepared as described for injectable solutions, but sterile work may be dispensed with.

Solutions for use on the skin are poured, dropped, spread, sprayed, sprayed, sprayed or applied by dipping, bathing or washing. These solutions are prepared as described for injection solutions.

It may be advantageous to add thickeners during manufacture. These thickeners include inorganic thickeners such as bentonites, colloidal silicic acid or magnesium stearate or organic thickeners such as cellulose derivatives, polyvinyl alcohols and copolymers thereof, acrylates and methacrylates.

The jellies are applied or coated onto the skin or introduced into the body cavities. This jelly is prepared by mixing the solutions prepared as described for injectable solutions with an amount of thickening agent until a clear, oily consistency is obtained. The thickeners mentioned above are used as thickeners.

The pouring means is poured or sprayed onto the delimited areas of the skin, whereby the active substance either penetrates the skin and systematically acts or disperses on the body surface.

The pour-on compositions are prepared by dissolving, suspending or emulsifying the active ingredient in a suitable skin-acceptable solvent or solvent mixture. Optionally, additional excipients such as colorants, resorption enhancers, antioxidants, light preservatives, tackifiers and the like are added.

Solvents include water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenylethanol or phenoxyethanol, esters such as ethyl acetate, butyl acetate or benzyl benzoate, ethers such as alkylene glycol alkyl ethers, for example dipropylene glycol monomethyl ether or diethylene glycol monobutyl ether, ketones such as acetone or methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, dimethylformamide, dimethylacetamide, N-methylpyrrolidone and 4-methylpyrrolidone and 2-dimethyl-pyrrolidone.

All dyes applicable to animals which can be dissolved or suspended can be used as dyes.

As dimethyl sulfoxide enhancers, expandable dipropylene glycol pelargonate, resorption is oils, such as silicone, for example, isopropyl myristate, oils, fatty acid esters, triglycerides, and fatty alcohols.

Antioxidants are sulfites or meta-hydrogen sulfites, such as potassium metabisulfite, ascorbic acid, butylhydroxytoluene, butylhydroxyanisole or tocopherol.

Light-protective agents are, for example, substances from the group of benzophenone or novantisolic acid.

Adhesion agents include, for example, cellulose derivatives, starch derivatives, polyacrylates or natural polymers such as alginates or gelatin.

The emulsions may be administered orally, dermally or as injections.

They are prepared by dissolving the active substance either in the hydrophilic or hydrophobic phase and using suitable emulsifiers and, if appropriate, other auxiliaries such as colorants, resorption agents, preservatives, antioxidants, light-protective agents and viscosity enhancers. , homogenizes with the second phase solvent.

As the hydrophobic phase, mention may be made of paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil and castor oil, synthetic triglycerides, caprylic and capric biglyceride, mixtures of triglycerides with vegetable fatty acids with a chain length of ^c 8 ^_c 12 ^and l ^e k ° ^with other specially selected natural fatty acids, mixtures of partial or unsaturated partial glycerides, possibly also hydroxyl groups containing fatty acids and monoglycerides with diglycerides of fatty acids ^c 8 / ^c 10 *

Further, there may be mentioned fatty acid esters, such as ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene glycol pelargonate, esters of a branched fatty acid of medium chain saturated fatty alcohols of chain length ^C 18 ^-C i6 'isopropyl myristate , an ester of caprylic acid and capric acid with a saturated fatty alcohol having a chain length of ^C 12 to ^C 18 isopropyl stearate, oleic acid oleic ester, oleic acid ethyl ester, ethyl oleate, lactic acid ethyl ester, waxy fatty acid esters such as dibutyl phthalate and diisopropyl ester related ester mixtures, among other fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetyl stearate alcohol and oleyl alcohol.

Oleic acids and mixtures thereof may also be used.

The hydrophilic phase includes water, alcohols such as propylene glycol, glycerol and sorbitol and mixtures thereof.

Emulsifiers include:

nonionic surfactants such as polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate and alkylphenol polyglycol ether;

ampholytic surfactants such as di-N, N-lauryl-βiminodipropionate or lecithin;

anionic surfactants such as Na-lauryl sulfate, fatty alcohol ether sulfates or monoethanolamine salt of mono / dialkyl polyglycol ether orthophosphoric ester;

cationic surfactants such as cetyltrimethylammonium chloride.

Other excipients include:

Viscosity-increasing and emulsion-stabilizing agents such as carboxymethylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, acacia, polyvinylpyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols or mixtures of the aforementioned colloids, waxes, colloids .

Suspensions may be administered orally, dermally or as injections. They are prepared by suspending the active substance in a carrier liquid, optionally with the addition of further excipients, such as wetting agents, colorants, resorption agents, preservatives, antioxidants and light-protective agents.

All homogeneous solvents and solvent mixtures can be used as carrier liquids.

Wetting agents (dispersing agents) which may be mentioned are the surfactants mentioned above.

The other excipients used are those mentioned above.

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

For the preparation of solid preparations, the active ingredient is mixed with a suitable carrier, if desired with the addition of excipients, and converted to the desired form.

Carriers which may be mentioned are all physiologically acceptable solid inert substances, both inorganic and organic. Inorganic carriers are, for example, sodium chloride, carbonates such as calcium carbonate, bicarbonates, alumina, silicas, aluminates, precipitated or colloidal silicon dioxide, and phosphates. Organic carriers include, for example, sugar, cellulose, food and feed, such as milk powder, animal meal and cereal flour, and scrap or starches.

Excipients are preservatives, antioxidants or colorants which have already been mentioned above.

Other excipients include lubricants and glidants such as magnesium stearate, stearic acid, talc, bentonite, disintegrants such as starch or cross-linked polyvinylpyrrolidone, binders such as starches, gelatin or linear polyvinylpyrrolidone, as well as dry binders such as microcrystalline cellulose.

The active substances may be present in the formulations in admixture with synergists or other active substances.

Formulations suitable for use contain the active ingredient in a concentration of 10 ppm to 20% by weight, preferably 0.1 to 10% by weight.

Formulations which are diluted before use contain the active ingredient in a concentration of 0.5 to 90% by weight, preferably 1 to 50% by weight.

In general, it has proven advantageous to achieve effective results when an amount of about 0.5 to about 50 mg, preferably 1 to 20 mg, of active ingredient per kilogram of body weight per day is applied.

The active substances may also be administered to the animals together with feed or drinking water.

Feed and food contain 0.01 to 250 ppm, preferably 0.5 to 100 ppm of the substance in combination with a suitable edible material.

Said feed and foodstuffs may be used for both medical and prophylactic purposes.

The production of said feed and foodstuffs is carried out by mixing a concentrate or premix containing 0.5 to 30% by weight, preferably 1 to 20% by weight, of the active ingredient in admixture with an edible organic or inorganic carrier with conventional feedstuffs. Edible carriers include, for example, corn flour, soybean flour and corn flour or mineral salt, which preferably contain a small amount of an anti-dusting oil such as corn oil or soybean oil. The premix thus obtained can then be added to the complete feed prior to feeding the animals.

For example, the use of active ingredients in coccidiosis may be mentioned:

For the treatment and prophylaxis of coccidiosis in poultry, in particular chickens, geese, ducks and turkeys, 0.1 to 100 ppm, preferably 0.5 to 100 ppm, of the active compound are mixed with a suitable edible material, for example a nutritious feed. If necessary, this amount can be increased, especially when the active ingredient is well tolerated by the recipient. Drinking water application is carried out accordingly.

For the treatment of individual animals, for example in the treatment of coccidiosis in mammals or toxoplasmosis, the active ingredient is preferably applied daily in an amount of 0.5 to 100 mg / kg body weight, in order to achieve the desired results. Nevertheless, it may often be necessary to dispense with the amounts indicated, in particular depending on the body weight of the animal to be treated or the type of application method, but also on the type of animal and its individual response to the active substance or preparation. was applied. In some cases, it is sufficient to start from less than the above, while in other cases the upper limit must be exceeded. If larger amounts are administered, it may be useful to divide these into multiple individual doses over the day.

In addition, the compounds of the present invention are active against fish parasites, counted to helminths (worms).

Fish parasites are of the subclass Protozoa species of the Ciliata strain, for example, Ichtthyophthiritus multifiliis, Chilodonella cyprini, Trichodina spp., Glossatella spp., Epistylis spp. Myxosporidia strains, for example Myxosoma cerebralis, Myxidium Heneguya spp.

Thelohania spp., Pleistophora spp., Trematodes; Monogenea, for example spp., Myxobolus spp., For example Glugea spp., From the strain Plathelminthen:

Dactylogyrus spp., Gyrodactylus spp., Pseudodactylogyrus spp. Diplozoon spp., Cestoden, for example from the groups Caryphyllidea (for example Caryophyllaeus laticeps), Pseudophyllidea (for example Diphyllobothrium spp.), Tetraphyllidea (for example Phyllobothrium spp.) And Protocephalida (for example species of Proteocephalus) and Arthropoda, Branchiura and Copepoda, as well as the Isopoda and Amphipoda series.

The treatment of the fish is carried out either orally, for example by feeding or short-term treatment in a medicinal bath into which the fish is placed and in which they are kept for a certain time (minutes to several hours), for example when moving from one tank to another.

The treatment may also be carried out by transient or permanent treatment of the fish environment (for example, the entire fishpond, aquarium, tank or pool) in which the fish is left.

The active substance is applied in formulations adapted for use.

The concentration of the active ingredient in the preparations is in the range of 1 ppm to 10% by weight.

Preferred formulations for short-term treatment by use as a medicinal bath, for example in fish transfer or environmental treatment (pond treatment) are solutions of the active ingredient in one or more polar solvents which are alkaline when diluted with water.

For the preparation of these solutions, the active ingredient is dissolved in a polar, water-soluble solvent which either reacts with an alkali or adds an alkaline, water-soluble substance. This is preferably also soluble in the solvent, but can also be suspended in the solvent and only dissolved in water. In this case, the water should have a pH of 7 to 10, preferably 8 to 10, after addition of the active compound solution.

The concentration of active ingredient may be in the range of 0.5 to 50%, preferably in the range of 1 to 25 t

Suitable solvents are all water-soluble solvents in which the active substance is soluble in sufficient concentration and which are physiologically harmless.

Such solvents include ethyl alcohol, isopropyl alcohol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycols, poly (oxyethylene) -poly (oxypropylene) -polymers, basic alcohols such as monoethanolamine, diethanolamine and triethanolamine, e.g. esters such as ethyl lactic acid ester, N-methylpyrrolidone, dimethylacetamide, dimethylformamide and dispersing and emulsifying agents such as polyoxyethyl castor oil, polyethylene glycol sorbitan monooleate, polyethylene glycol stearate or polyethylene glycol ethers and polyethylene glycol ethers and polyethylene glycol ethers.

Bases for adjusting the alkaline pH include organic bases such as basic amino acids such as L- or D, L-arginine, L- or D, L-lysine, methylglucosoamine, 2-amino-2-hydroxymethylpropanediol- (1,3) followed by Ν, Ν, Ν ', N'-tetrakis- (2-hydroxypropyl) -ethylenediamine or ethylenediamine-based polyether-tetrol (MG 480-420) or an inorganic base such as ammonia or sodium carbonate, optionally with the addition of water.

The formulations may also contain 0.1 to 20% by weight, preferably 0.1 to 10% by weight, of excipients such as antioxidants, surfactants, suspension and thickening stabilizers, such as methylcellulose, alginates, polysaccharides, gphalactomananes and colloidal silicic acid. Addition of coloring, flavoring and building materials for animal nutrition is also possible. It is also possible to mention acids which together with the bases used form a buffer system or reduce the pH of the solution.

The concentration of the active ingredient in use depends on the type and duration of treatment as well as the age and condition of the fish to be treated. It is, for example, in the case of a short-term treatment of 2 to 50 mg of active ingredient per liter of water, preferably of 5 to 10 mg per liter of water for a treatment period of 3 to 4 hours. In the treatment of young carp, for example, a concentration of 5 to 10 mg / l is employed at a treatment time of 1 to 4 hours.

The eels are treated for about 4 hours at a concentration of about 5 mg / L.

A correspondingly lower concentration may be selected for longer treatment periods or continuous treatment.

For the treatment of the pond, a concentration of 0.1-5 mg of active ingredient per liter of water may be used.

Formulations for use as a feed additive have, for example, the following composition:

(a) Active substance of the formula I: soybean protein

b) Active ingredient of the formula I benzyl alcohol hydroxypropylmethylcellulose water

1-10 parts by weight 49 - 90 parts by weight.

0.5-10 parts by weight 0.08-1.4%. parts 0-3.5 parts by weight rest up to 100 parts.

Preparations for use in medicinal baths and for pond treatment have, for example, the following composition:

(c) 2.5 g of the active compound of the formula I are dissolved in 100 ml of triethylamine with heating.

(d) 2.5 g of the active compound of the formula I and 12.5 g of lactic acid are dissolved in 100 ml of triethanolamine with heating and stirring.

e) 10.0 g of the active compound of the formula I are dissolved in 100 ml of monoethanolamine.

f) Active ingredient of the formula I 5.0 g propylene glycol 50.0 g sodium carbonate 5.0 g water to 100 ml.

g) the active compound of the formula I monoethanolamine N-methylpyrrolidone

(h) the active substance of the formula I, sodium carbonate propylene glycol 200

5.0 g 10.0 g to 100 ml.

2.5 g

5.0 g to 100 ml.

The active substance is dissolved in propylene glycol with heating and sodium carbonate is suspended in this solution.

DETAILED DESCRIPTION OF THE INVENTION

Example A

Coccidiosis in chickens up to 11 days old were infected with 40,000 sporulated oocysts of strongly virulent strains of Eimeria acervuline, E. maxime and E. tenella, causative agents of intestinal coccidiosis.

days before infection and 8 days after infection (end of the experiment), the animals were treated with the active compound at the indicated concentration, admixed with the feed.

The number of oocysts in the faeces was determined by McMaster-Kammer (see Engelbrecht et al. Parasitologische Arbeitsmethoden in Medizin und Veterinärmedizin, p. 172, Akademie-Verlag, Berlin (1965)).

The following Table 1 shows the drug doses and oocyst excretion in% for each agent. 100% means no effect and 0% is complete effect, i.e. no excretion of oocysts.

Table 1

Coccidiosis in chickens

Example dose ppm E. acervulina oocyst clearance in% compared to untreated infected control E. maximum oocyst elimination in% compared to untreated infected control tenella nespr. infects. controls. 0 100 100 100 37 250 0.5 0 0 100 28 26 32 45 250 0.1 0 0 100 11 8 5 57 250 0.01 0 0 100 38 5.3 93

Production examples

Example 1

br

COOCHj

43 A mixture of 9.0 g (0.03 mol) of 4-bromo-2-cyano-6-trifluoromethyl-1H-benzimidazole (see for example EP 239 508), 8.3 g (0.06 mol) of potassium carbonate, 4.2 g (0.03 mol) of N-chloromethyl-N-methylcarbamic acid methyl ester and 105 ml of ethyl acetate were heated at reflux for 4 hours. After work-up, the cooled reaction mixture is filtered, the filtrate is washed with water, dried over anhydrous sodium sulphate and concentrated in vacuo. The residue obtained is recrystallized from a mixture of diethyl ether and petroleum ether (1:10) and finally purified by column chromatography (eluent: dichloromethane).

6.0 g (51% of theory) of N- (4-bromo-2-cyano-6-trifluoromethyl-1H-benzimidazol-1-ylmethyl) -N-methylcarbamic acid methyl ester of melting point 138-141 are obtained. ° C

The following substituted benzimidazoles of formula I are obtained in an analogous manner and according to the general production data:

χΐ X ² X3 X ⁴ A const 2 H no ₂ (H) H (NO ₂ ) H CA —CHj COOCHj mp 120-121 ° C 3 H no ₂ (H) H (NO ₂ ) H η-Ο, Η, ^N \ - CH COOCH ₃ mp 99-102 ° C 4 H no ₂ (H) ..H (NO ₂ ) H 1 · -N _x —CH 2 COOC 3 H, mp 92-96 ° C 5 H no ₂ (H) H (NO ₂₎ H <jA —CHj COOC.H, mp 65-70 ° C 6 H no ₂ (H) H (NO ₂ ) H —CHj COOCjHj * H NMR); 6.0; 6.05 (72:28) 7 H no ₂ (H) H (NO ₂ ) H CHU-C.H. —CHj COOCjK, t.t.78-82 C 8 br H cf ₃ H CA mp 107-110 ° C

—CHj COOCH ₃

χΐ X2 X3 X ⁴ A phys. Const. 9 br H CF3 H n-QH, H-NMR * \ 6.03 —CH, COOCH3 10 Η CF3 H br CA t .t. 163-168 ° C • —CHj COOCH, 11 br H CF3 H ľ ¹ · t.t.llO-113 DEG C. —CH3 XOOC, H, 12 br H CF3 H mp 84-87 ° C —CHj COOCjH, 13 br H CF3 H N-CH H NMR ^ * 6.02 —CHj COOCjHj 14 H NO ₂ H H ABOUT*, mp 127-131 ° C (H) (NO ₂ ) 1 —CHj COOCHj (65:31) 15 br H CF3 H CH2-COOCH3 mp 160-163 ° C 16 br H CF3 H -CH 9 -COOC 2 H _S t.t.113-117 C 17 br H CF3 H z ® CH mp 105-108 ° C ^x cooch ₃ 18 br H CF3 H • NH-CH2-COOCH3 mp 205-208 ° C 19 br H CF3 H -ch ₂ -cn mp 157-160 ° C 20 H NO ₂ H H mp 87-91 ° C (H) (NO2) / CH (57:43) ^ COOCHj 21 H NO ₂ H H CH2-COOC2H5 mp 96-100 ° C (H) (NO ₂ ) (1: 1): 22 H NO ₂ H H CH2-COOCH3 mp 141-143 ° C . (H) (NO2) (1: 1)

Pr.

X ¹ X ² X ³ X ⁴ Phys. const.

23 br H cf ₃ H t.t.l54-157 C (H) (CF ₃ ) (H) (Br) -ovnJ (63:37) 24 br H cf ₃ H 0 in mt 212-217 ^e C -ψο 25 br H cf ₃ H -CH ₂ -CH = CH ₂ mp 95-99 ° C (H) (CF ₃ ) (H) (Br) (78:22) 26 H cf ₃ H br -ch ₂ -cn t.tJ70-172 C 27 br (H) H (CF ₃ ) ca ₃ (H) H (Br) mp 147-150 ° C 28 br H cf ₃ H -CH ₂ -C ₆ H ₅ mp 140-143 ° C (H) (CF ₃ ) (H) (Br) (95: 5) 29 br H cf ₃ H -ch ₂ -cooh mp > 195 ° C (cut 30 br H cf ₃ H mp 83-86 ° C —CH, COOCH3 31 br H cf ₃ H CN mp 90-93 ° C —CH, COOiC, H, 32 br H cf ₃ H mp, 97-101 ° C —CH2CCO + C.H, 33 br H cf ₃ H -OL-N ⁷ ^ \ ^ N mp 120-123 ° C (H) (CF ₃ ) (H) (Br) (84:16) 34 br • H cf ₃ H P mp 101-105 ° C —CH, COO-o-C.H, 35 br H cf ₃ H - at-N 1 mp, 160-163 ° C (H) (CF ₃ ) (H) (Br) (75:25) \ ^ N 36 ' br H cf ₃ H —CH, X00C, H, * H NMR); 6.11

χΐ X ² X3 X ⁴ A phys. Const. 37 br H cf ₃ H n-C.H. 1 * H NMR); —CH, COOCH3 5.94 38 br H CF3 H (CHjJj-CH 1 H-NMR *); 1 6.06 —CH, COOCH3 39 br H cf ₃ H mp 86-90 ° C —CH, COOCH3 40 br H cf ₃ H mp 137-140 ° C —CH2 CO-H 41 br H cf ₃ H -OnC ₃ H7 mp 105-109 ° C (H) (CF ₃ ) (H) (Br) (86:14) 42 br H cf ₃ H -OiC ₃ H ₇ (H) (CF ₃ ) (H) (Br) 5.98; 6.06 (53:47) 43 br H cf ₃ H -o ~ ch ₂ -c = ch t t.73-76 C (H) (CF ₃ ) (H) (Br) (53:47) 44 br (H) H (CF ₃ ) ca ₃ (H) H (Br) -a mp ₇ 5-78 ° C (36:64) 45 br H cf ₃ H - ' CH 2 -O-CO-tC ₄ H ₉ ΐΗ-ΝΜίνΛ (H) (CF ₃ ) (H) (Br) 6.49 (66:34) 46 br H cf ₃ 1 H -CH 2 -O- (CH ₂ ) ₃ -C ₆ H ₅ 1 H-NMR (H) (CF ₃ ) (H) (Br) 5.96; 6.05 47 br H CF ₃ H 0 0 mp 175-180 ° C

II II —O — C-NH-C-NH <S //

Cl

Pr.

- χΐ X2 X3 X ⁴ A phys. Const. 48 br H cf ₃ H H-NMR * \ (H) (CF ₃ ) (H) (Br) 1 6.03 —CH, ^ COOCH, (76:24) 49 br H cf ₃ H c-QHN mp 90-93 ° C —CH, COOCH3 50 br H cf ₃ H mp 105-108 ° C —CH, COOCH3 51 br H cf ₃ H ICH, mp 86-90 ° C (H) (CF ₃ ) (H) (Br) 1 (81:19) —CH, COOCH3 52 br H cf ₃ H N-CH H-NMR *): (H) (CF ₃ ) (H) (Br) 1 N 5.95; 6.35 —CH, X00C, H, (80:20) 53 br H cf ₃ H * H NMR); —CH, XOOClH, 6.05 54 br H cf ₃ H n -CH " H-NMR *): (H) (CF ₃ ) (H) (Br) I —CH, XOOClH, 5.95 (76:24) 55 br H CF3 H ⁿ orH ₁₇ 1 H-NMR *): (H) (CF ₃ ) (H) (Br) and 5.95; 6.35 —CH, COOClH, (72:28) 56 br H cf ₃ H KpH. mp 115-120 ° C —CH, ΧΟΟ + Ο, Η, 57 br H cf ₃ H mp, 112-116 ° C —CH, COC2H3, 58 br H cf ₃ H H, C-CH mp 135-140 ° C '' -CH AľOOCH, 59 H H cf ₃ H -O-C2H5 mp 173-176 ° C

χΐ X2 X3 χ4 A fyz. Const. 60 H HF ₂ CH-CF ₂ -O- H -O-C7H5 m.p. 35-4 ° C 61 H CF3-O- H -OC ₂ H ₅ 1 H-NMR'A 5.91 62 H c ₆ h ₅ h H -OC ₂ H ₅ 1 H-NMR * - ': (H) (C ₆ H ₅ ) 5.87; 5.92 63 H -O- (CH ₂ ) ₂ -O- H -OC ₂ H 5 mp 150-151 ° C 64 H -O- (CH ₂ ) 2 -O- H o *, m.p. 162-164 ° C ' ^N ' —CH, XOOCH, 65 H -o-cf- _2- cfci-o- H ch, m.p. 127-13O C _(-O-CF2-cfc1 -O-) 1 —CH, XOOCH, 66 H -o-cf- _2- cfci-o- H -OC ₂ H ₅ mp 96-100 ° C _(-O-CF2-cfc1 -O-) (1: 1) 67 H -o-cf- _2- cfci-o- H _(-O-CF2-cfc1 -O-) 5.91 —CH, COOCH3 68 H -O-CF ₂ -CFC 1 -O- H mp 130-133 ° C _(-O-CF2-cfc1 -O-) 1 —Ch, ^ coocp-ς 69 H -o-cf- _2- cfci-o- H * 5> H, m.p. 62-66 ° C _(-O-CF2-cfc1 -O-) —CH, COOCH3 70 H -o-cf ₂ -cf ₂ -o H -OC ₂ H ₅ mp 90-93 ° C 71 H -o-cf ₂ -cf ₂ -o H ch, m.p. 140-144 ° C —CH, ^ COOCH, 72 H -O-CF ₂ -CF ₂ -O- H -CH 2 -CH 2 -OCH 3 mp 60-64 ° C 73 H -o-cf ₂ -cf ₂ -o H (pH, mp 53-57 ° C) —CH, ^ COOCJE, 74 H -O-CF ₂ -CF ₂ -O- H ch. mp? 23-125 ° C

—CH, COOCH, Phys. konŠ't

Pr.

χΐ X ² χ3 χ4

75 H -O-CF 2 CF 2 -O- H —CH, COOClH, mp 7O-73 ° C 76 H -O-CF2-CHF-O- H -oc ₂ H ₅ m.p., 75-80 ° C 77 H -O-CF 2 -O- H -O-C2H5 mp, 110-103 ° C 78 H -0-CF2-0- H T mp 147-150 ° C —CH, COOCH3

*) 'H-NMR spectra were determined in deuterochloroform (CDC1 ₃₎ or hexadeuterio-dimethylsulphoxide (DMSO-d) with tetramethylsilane (TMS) as an internal standard. The chemical shift of the N-Cl-N-group as δ-value in ppm is reported.

T

Production of starting compounds

Example II -1

A solution of 120 g (0.3 mol) of 4-bromo-2-trichloromethyl-6-trifluoromethyl-1H-benzimidazole is added dropwise and stirred with stirring to 900 ml of saturated aqueous ammonia solution at 15 ° C to 25 ° C (see for example EP 239 508) in 300 ml of ethyl alcohol and after the addition is complete, the mixture is stirred for one hour at room temperature. After working up, the reaction mixture was acidified to pH1 with 4000 ml of 20% hydrochloric acid and extracted three times with 300 ml of dichloromethane each time. The combined organic phases are dried over anhydrous sodium sulphate, concentrated in vacuo and the oily liquid obtained is purified by chromatography on silica gel (mobile phase: cyclohexane / ethyl acetate 2: 1) and crystallized from petroleum ether.

49.1 g (55% of theory) of 4-bromo-2-cyano-6-trifluoromethyl-1H-benzimidazole of melting point 130 134 DEG C. are obtained.

Accordingly, the following substituted 1H-benzimidazoles of formula II are obtained:

I

Pr. χΐ Χ2 Χ3 X ⁴ phys. Const. ΙΙ-2 Η νο ₂ Η Η 1.1. > 240 ° C (Η) (Ν0 ₂ ) Π-3 Η -O-CF ₂ -CFC 1 -O- Η mp . > 230 ° C

(-0-cfc1-CF2-0-)

IM H -O-CF ₂ -CF ₂ -O- H mp, > 230 ° C II-5 H H (CF ₃ ) ca ₃ (H) H mp 173-176 ° C II-6 H H (C ₂ H ₅ -O-) C ₂ H ₅ -O- (H) H mp 86-90 ° C II-7 H H (F ₂ CH-CF ₂ -O-) F ₂ CH-CF ₂ -O- (H) H mp 130-132 ° C II-8 H CF ₃ _O- cf ₃ .o- H mp 194-198 ° C II-9 H H (c ₆ h ₅ ) C6H5 (H) H mp > 230 ° C Π-10 H -O- (CH ₂ ) ₃ -O- H mp > 230 ° C

ΡΓ. x ¹ x ² x ³ x ⁴ phyx. const

II-II H -O-CF2-CHF-0-H m.p. 5O-60 ° C (-O-CHF-CF2-O-)

11-12 H -O-CF2-O- H 1.1. > 220 ° C

Claims (5)

PATENT CLAIMS Use of CN-substituted benzimidazoles of the formula I (I) in which X ³ and X ⁴ independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an optionally substituted alkyl group, an alkoxy group, an alkylthio group, an alkylsulfonyl group, an alkylsulfinyl group. or cycloalkyl, optionally substituted, fused dioxyalkylene, hydroxycarbonyl, alkoxycarbonyl, cycloalkyloxycarbonyl, in each case optionally substituted amino or aminocarbonyl, or in each case optionally substituted aryl, aryloxy, aryl, aryl, aryl, aryl, aryl, aryl, aryl, , aryloxycarbonyl, arylazo or arylthiomethylsulfonyl, wherein at least one of the substituents and X is not a hydrogen atom or a halogen atom, is a hydrogen atom, an alkyl group or cycloalkyl or optionally substituted aryl; and R ² is hydroxyl, cyano or in each case optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, t · t -K t alkynyloxy, aminocarbonyl alkoxycarbonyl dialkoxyphosphoryl alkylthio, amino, group, alkylcarbonyl, group, alkylcarbonyloxy, group, (hetero) aryl, (hetero) arylcarbonyl, (hetero) aryloxycarbonylamino (aryloxycarbonylamino) parasitic protozoa and especially coccidia. A parasitic protozoa composition comprising at least one substituted benzimidazole of formula I according to claim 1. Process for the control of parasitic protozoa, characterized in that these and / or their environment are treated with the substituted benzimidazoles of the formula I according to claim 1. IN • 4. A process for the preparation of an anti-parasitic protozoa composition, which comprises mixing the substituted benzimidazoles of the formula I as claimed in claim 1 with fillers and / or surfactants. Use of the substituted benzimidazoles of the formula I according to claim 1 for the production of compositions against parasitic protozoa.