AU663631B2 - Use of CN-substituted benzimidazoles - Google Patents

Description

A N AI 1 1 Our Ref: 489060 P/00/011 Regulation 3:2

AUSTRALIA

Patents Act 1990 j"6

ORIGINAL

COMPLETE SPECIFICATION STANDARD PATENT A04 The prese substitute parasiticA Kfish and i Substitute( I' fungicides (EP-OS (Eu: 152 360, US EP-OS 260 Polyhalogen elmintics, closed (DE- 4 .Hwv cases.

The present parasitic p or to a hab 1 CN-substitu- 3 A A 14 4 A 4 A A A A c i~ (ft I A

(C

H,

4,' Applicant(s): Bayer Aktiengesellschaft D-51368 LEVERKUSEN

GERMANY

Address for Service: DAVIES COLLISON CAVE Patent Trade Mark Attorneys Level 10, 10 Barrack Street SYDNEY N'SW 2000 Use of CN-substituted benzimidazoles Invention Title: The following statement is a full description of best method of performing it known to me:this invention, including the 5020 ii

I

r I a r.

f' ii The present invention relates to the use of CNsubstituted benzimidazoles as agents for combating parasitic protozoa and in particular coccidia, as well as fish and insect parasites.

Substituted benzimidazoles and their use as insecticides, fungicides and herbicides have already been disclosed (EP-OS (European Published Specification) 87 375 and 152 360, US-P 3 472 865 and 3 576 818, US-P 3 418 318 and EP-OS 260 744, 266 984, 181 826 and 239 508) in which xl, x 2

X

case repr 5 alko cyc1 fuse carb alky 10 opti repr aryl aryl aryl 15 but o. 0 wher R' repr sent 20 R 2 repr case alko amin carb (het (het 0i 0 I I loot ii 0 i~00 0 0 0 0015 I I CI 0 0 Polyhalogenated benzimidazoles and their action as anthelmintics, coccidiostatics and pesticides have been disclosed (DE-OS (German Published Specification) 2 047 36- 9) However, their action is not satisfactory in all cases.

The present invention relates to a method of combating parasitic protozoa which comprises applying thereto, or to a habitat thereof, an effective amount of a CN-stbstituted benzimidazole of the formula (I)

-~CN

14 k I x

CH-R

Le A 29

-I-

2 tT~ ;'i n p r:- 9i~ r b~ !1 rr~-rT d i: ~1 in which i ijcarbo Where appr 5 substituen as geometr isomer mixl use of the are claimne( .e a or o 15 ar ooaa a a or a ro a co a rc o

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, alkylsuiphinyl, alkylsuiphonyl or cycloalkyl, or represent optionally substituted, fused-on dioxyalkylene, or represent hydroxycarbonyl, alkylcarbonyl, alkoxycarbonyl or cycloalkyloxycarbonyl, or represent in each case optionally substituted amino or aminocarbonyl, or represent in each case optionally substituted aryl, aryloxy, arylthio, arylsulphinyl, arylsuiphonyl, arylsuiphonyloxy, arylcarbonyl, aryloxycarbonyl, arylazo or arylthiomethylsulphonyl, but wherein at least one of the substituents X 1

X

2

X

3 and X 4 is other than hydrogen and halogen, and wherein.

R

1 represents hydrogen, alkyl or cycloalkyl, or represents optionally substituted aryl, and

R

2 represents hydroxyl or cyano, or represents in each case optionally substituted alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, amino, aminocarbonyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, dialkoxyphosphoryl, (hetero) aryl, (hetero)arylcarbonyl, (hetero)aryloxycarbonyl, (hetero) arylcarbonyloxy or (hetero) arytamino- 10 00 .0 0* 0 0o 25r Formula (I stituted b the inventi those in w xl, x 2 x 3 case bromir each c al kylt in ea( cycloa in E haloge haloge having identi civale ~,014~ a

O

0 1(111( a 0, 25 0 0r Le A 29 484 Le A 29 484 -2

.'N

~i 'r I '4 l i:

I;:

i 1 *01

I,

a

F,

44j i;F 5 carbonylainocarbonyloxy..

Where appropriate, depending on the nature and number of substituents, the compounds of the formula can exist as geometric and/or optical isomers or regioisomers or isomer mixtures thereof in varying compositions. Both the use of the pure isomers and that of the isomer mixtures are claimed according to the invention.

1* r ie 15 F p4. 00 44 0 0 a :i 20 I 0* Formula provides a general definition of the substituted benzimidazoles which can be used according to the invention. Preferred compounds of the formula are those in which

X

2

X

3 and X- independently of one another in each case represent hydrogen, fluorine, chlorine, bromine, iodine, cyano or nitro, or represent in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsuiphonyl having in each case 1 to 8 carbon atoms, or represent cycloalkyl having 3 to 8 carbon atoms, or represent in each case straight-chain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsulphinyl, halogenoalkylsulphonyl having in each case 1 to 6 carbon atoms and 1 to 13 identical or diff-rent halogen atoms, or represent divalent dioxyaDlyiene having L to 5 carbon atoms 09 which identi compri alkyl chain :oms atoms, repreE alkyic 1 to repreatoms or ami polyst stitu each c in eac 1 to carbor or al atoms carbor arylme carbor optior mo iet possil those Le A 29 481 25 0,6'.4 i

I

8 Le A 29 484 -3r- 1

I

1 o1 i, aa r- Saaryls comprising halogen and/or straight-chain or branched aryl i 1+ alkyl having 1 to 4 carbon atoms and/or straight- arylt S5 case( chain or branched halogenoalkyl having 1 to 4 carbon Satoms, or furthermore represent hydroxycarbonyl, or aryl represent in each case straight-chain or branched possil alkylcarbonyl or alkoxycarbonyl having in each case those 1 to 6 carbon atoms in the alkyl moiety, or but w represent cycloalkyloxycarbonyl having 3 to 8 carbon 3X anc atoms in the cycloalkyl moiety, or represent amino or aminocarbonyl, in each case optionally mono- or polysubstituted by identical or different substituents, possible substituents on the amino in repres brancl each case being: I 15 sents S* stitut in each case straight-chain or branched alkyl having ti o possi 1 to 6 carbon atoms, halogenoalkyl having 1 to 6 possi' on °s 20° carbon atoms and 1 to 13 halogen atoms, alkoxyalkyl a hog or alkylcarbonyl having in each case 1 to 6 carbon atoms in the individual alkyl moieties, or aryl- or bra i 2 0 or alk carbonyl, arylsulphonyl, arylaminocarbonyl or S I atoms, arylmethylsulphonyl having in each case 6 to 10 o haloge carbon atoms in the aryl moiety and in each case haloge 25 optionally mono- or polysubstituted in the aryl having .moiety by identical or different substituents, 5 in °r 25 identi S. straig those mentioned for alk alkoxy i SLe A 29 484 Le A 29 484 4 -afI .1 aa i +5 I L- 6 ii 'r a" 4J '4 4 i: l 1: ii i' C i' i 4' 1 I

I

L

I

;rl; /4 ii

I

ia

I

a is or furthermore represent aryl, aryloxy, aryithio, arylsuiphinyl, arylsuiphonyl, arylsuiphonyloxy, arylcarbonyl, aryloxycarbonyl, aryithiomethylsuiphonyl or arylazo having in each case 6 to 10 carbon atoms in the aryl moiety and in each case optionally mono- or polysubstituted in the aryl moiety by identical or different substituents, possible substituents on the aryl in each case being those mentioned for R 1 but wherein at least one of the substituents X 1

X

2

X

3 and X 4 is other than hydrogen and halogen, and wherein

R

1 represents hydrogen, or represents straight-chain or branched alkyl having 1 to 8 carbon atoms, or represents phenyl which is optionally mono- or polysubstituted by identical or different substituents, possible substituents being: halogen, cyano, nitro, in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl having in each case 1 to 6 carbon atoms, in each case straight-chain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsulphinyl or halogenoalkylsulphonyl having in each case 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms, in each case straight-chain or branched alkoxyalkyl, alkoxyalkoxy, alkanoyl, alkoxycarbonyl or alkoximinoalkyl r o r, o noo oo* o~ o o 20 ,.t25 having individ having or poly stituen straigh carbon halogen identic which identic compris alkyl Ii chain o atoms a atoms,

R

2 represe alkenyl alkylth carbony case up alkenyl optiona differe each ca halogen to 8 c atoms A by ide Le A 29 484 ~a oo oo rrr Irr ru*a o uurrrrr err r bYI OI OI

OI

D

pa a~ a Le A 29 484 i 1

K

;f'

J~

I

-u, i

I

i :I i~ c I,t; ;i f. i.

u 1 I' -i ill i r: -t 1~* r ;r :i rr r r ;lu 1 r, f;: a di r it. i, Ii" t ,II i i 1 Y 'f r r -1 I;' r:: :i

J

i: r: i I

I''

t I i I

I-

i.

:T i I~ i" r ii r ii 1 11: 'p

-I-~I

V 5

I;:

having in each case 1 to 6 carbon atoms in the individual alkyl moieties, divalent dioxyalkylene having 1 to 5 carbon atoms which is optionally monoor polysubstituted by identical or different substituents from the group comprising halogen and/or straight-chain or branched alkyl having 1 to 6 carbon atoms and/or straight-chain or branched halogenoalkyl having 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms, or phenyl which is optionally mono- or polysubstituted by identical or different substituents from the group comprising halogen and/or straight-chain or branched alkyl having 1 to 6 carbon atoms and/or straightchain or branched halogenoalkyl having 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms, R 2 represents hydroxyl or cyano, or represents alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkoxyphosphoryl having in each case up to 8 carbon atoms in the individual alkyl or alkenyl or alkinyl moieties and in each case optionally mono- or polysubstituted by identical or different substituents, possible substituents in each case being: halogen, straight-chain or branched alkoxy having 1 to 8 carbon atoms or aryl having 6 to 10 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents, possible substit Rlf rr rrr r re r ri; rrr rrri r t 20 a a r o or rr 1 roar cc ,25 rorir

F

rO11 *0* a 1) DI *O P4 r 10 15 a a 2 20

R

2 furthex each c identic stituer straigI carbon having 8 carbc alkoxyt in eac] straigI cyclic atoms i having moiety in the in eacl identic substil mentioi

R

2 furthe carbon] carbon] in the or po 6a.* a0 a tr a a o 25 a a at a a a Le A 29 484 -6 Le A 29 484 LZZ721 i i_)

I;

li:: i:_ r.

I

i r i i :2iil i; 1)~ i,

I':

i

I:.

-i r L i r. I"

'I

'I

i' r Ir r -I i 1; ii i", i I' I' .r i "i' i i i 'i 1 t i i r r :cO ir i trr~ substituents on the aryl being those mentioned for a,.

St oaa a a a o &l a*

R

2 furthermore represents amino or aminocarbonyl, in each case optionally mono- or disubstituted by identical or different substituents, possible substituents being: straight-chain or branched alkyl having 1 to 8 carbon atoms, straight-chain or branched alkenyl having 2 to 8 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, alkoxycarbonyl, alkylthio-carbonyl, alkoxythiocarbonyl or alkylthio-thiocarbonyl having in each case 1 to 8 carbon atoms in the individual straight-chain or branched alkyl moieties, divalent, cyclic alkanediyloxycarbonyl having 2 to 6 carbon atoms in the alkanediyl moiety, or arylalkyl or aryl having in each case 6 to 10 carbon atoms in the aryl moiety and, where appropriate, 1 to 6 carbon atoms in the straight-chain or branched alkyl moiety and in each case optionally mono- or polysubstituted by identical or different substituents, possible substituents on the aryl in each case being those mentioned for R',

R

2 furthermore represents aryl, arylcarbonyl, aryloxycarbonyl, arylcarbonyloxy or aryl aminoc arbonyl aminocarbonyloxy having in each case 6 to 10 carbon atoms in the aryl moiety and in each case optionally monoor polysubstitited by identical or different Particularly I those in whic- 15 X 1 x 2

X

3 and case re, bromine, straightalkylsulp 20 1 to 6 ca 3 to 7 straightalkoxy, he halogenoa 25 carbon al halogen a having 11 substitu each cas(

R

2 furtherm( carbonyl 5 oxy or having ii identica: nitrogen, moiety a: 10 substitul possible being the Le A 29 484 -7 Le A 29 484

A

t~l jj ~1 ii Irau substituents, possible substituents on the aryl in each case being those mentioned for R,

S!|

R

2 furthermore represents heteroaryl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylcarbonyloxy or heteroarylaminocarbonylaminocarbonyloxy having in each case 2 to 9 carbon atoms and 1 to identical or different hetero atoms in particular nitrogen, oxygen and/or sulphur in the heteroaryl moiety and in each case optionally mono- or polysubstituted by identical or different substituents, possible substituents on the heteroaryl in each case being the substituents on the aryl mentioned for R'.

Particularly preferred compounds of the formula are those in which X1, X 2

X

3 and X' independently of one another in each case represent hydrogen, fluorine, chlorine, bromine, cyano or nitro, or represent in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl having in each case 1 to 6 carbon atoms, or represent cycloalkyl having 3 to 7 carbon atoms, or represent in each case straight-chain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsulphinyl or halogenoalkylsulphonyl having in each case 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms, or represent divalent dioxyalkylene having 1 to 4 carbon atoms which is optionally mono- SA 2 having in each case 2 to 9 carbon atoms and 1 to VS M t 1 S 042334

I'

~s i to hexasubstituted by identical or different substituents fromt the group comprising halogen and/or straight-chain or branched alkyl having 1 to 4 carbon atoms and/or straight-chain or branched halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms, or further represent hydroxycarbonyl, or represent in each case sti iight-chain or branched alkylcarbonyl or alkoxycarbonyl having in each case 1 to 4 carbon atoms in the alkyl moiety, or represent cycloalkyloxycarbonyl having 3 t.o 7 carbon atoms in the cycloalkyl moiety, or represent amino or aminocarbonyl, in each case optionally mono- or disubstituted by identical or different substituents, possible substituents on the amino in each case being: in each case straight-chain or branched alkyl having 1 to 4 carbon atoms, halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 halogen atoms, alkoxyalkyl or alkylcarbonyl having in each case 1 to 4 carbon 2toms in the individual alkyl moieties, or arylcarbonyl, arylsulphonyl, arylaminocarbonyl or arylmethylsuiphonyl having in each case 6 or 10 carbon atoms in the aryl moiety and in each case optionally mono- to pentasubstituted in the aryl moiety by identical or different substituents, possible substituents on the aryl in each case being those mentioned for R1; 31 o 44 0 04t 044 40 4 0 06 4 0 000s 0004 4 0r 0.4 4 4 O 0 0b44 0 0ru 44 o 0o or furthermore represent aryl, aryloxy, aryithio, Le A Le A 29 484 f! A member of tl DAVIES

COLI

for and on beha S 042334 301193 5010

A

arylsuiphinyl, arylsuiphonyl, arylsuiphonyloxy, arylcarbonyl, aryloxycarbonyl, arylthiomethylsuiphonyl or arylazo having in each case 6 or carbon atoms in the aryl moiety and in each case optionally mono- to pentasubstituted in the aryl moiety by identical or different substituents, possible substituents on the aryl in each case being those mentioned for R1, but wherein at least one of the substituents X 1 3 2

X

3 and X 4 is other than hydrogen and halogen, and wherein R1 represents hydrogen, or represents straight-chain or branched alkyl having 1 to 6 carbon atoms, or represents phenyl which is optionally mono- to trisubstituted by identical or different substituents, possible substituents being: halogen, cyano, nitro, in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsulphonyl having in each case I to 4 carbon atoms, in each case straight-chain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsulphinyl or halogenoalkylsulphonyl having in each case 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms, in each case straight-chain or branched alkoxyalkyl, alkoxyalkoxy, alkanoyl, alkoxycarbonyl or alkoximinoalkyl having in each case 1 to 4 carbon atoms in the

A

15 0* talc 000t 0091, 20 04 1 0s 0 0 0e 0 00) 00 0 a a a c c a e a c 540440 0 4 Le A 2 Le A 29 484 10 71lr L, 3

IE

s

I

A member of the firm of DAVIES COLLISON CAVE for and on behalf of the applicant.

I

I

PAWPDOCS\NH\48WO.MNH 1 3 J I, individual alkyl moieties, divalent dioxyalkylene having 1 to 4 carbon atoms which is optionally monoto hexasubstituted by identical or different substituents from the group comprising halogen and/or straight-chain or branched alkyl having 1 to 4 carbons atoms and/or straight-chain or branched halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 identir- 1l or different halogen atoms, or phenyl which is optionally mono- to pentasubstituted by identical or different substituents from the group comprising halogen and/or straight-chain or branched alkyl having 1 to 4 carbon atoms and/or straightchain or branched halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms, 9 4 201 4 4* 9 R 2 represents hydroxyl or cyano, or represents alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkoxyphosphoryl having in each case up to 6 carbon atoms in the individual alkyl or alkenyl or alkinyl moieties and in each case optionally mono- to pentasubstituted by identical or different halogen atoms, or represents alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkoxyphosphoryl having in each case up to 6 carbon atoms in the individual alkyl or alkenyl or alkinyl moieties and in each case optionally mono- to trisubstituted by identical

IJ

.t44 *00 9.42 4r 4 9 *r 9 94 9 4r 4 944404 44194 4 4 9494 04 04 49 9 4r Le A; Le A 29 484 11 I t En which

I

I

i X1, X 2 X, and X' independently of one another in each case represent hydrogen, halogen, Cyano or nitro, or represent in each case optionally /2

V-

id i i i;

I:

i:! .at 4 It a at 15 at 'a 4 2 aaaI I.

or I a -a a a, a a #4 Ca *L a a or different substituents, possible substituents in each case being: straight-chain or branched alkoxy having 1 to 6 carbon atoms, or aryl having 6 or 10 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents, possible substituents on the aryl being those mentioned for R1,

R

2 furthermore represents amino or aminocarbonyl, in each case optionally mono- or disubstituted by identical or different substituents, possible substituents being: straight-chain or branched alkyl having 1 to 6 carbon atoms, straight-chain or branched alkenyl having 2 to 6 carbon atoms, cycloalkyt he'r-ing 3 to 7 carbon atoms, alkoxycarbonyl, alkylthio-carbonyl, alkoxythiocarbonyl or alkylthio-thiocarbonyl having in each case 1 to 6 carbon atoms in the individual straight-chain or branched alkyl moieties, divalent, cyclic alkanediyloxycarbony'l having 2 to 5 carbon atoms in the alkanediyl moiety, or aryaalkyl or aryl having in each case 6 or 10 carbon atoms in the aryl moiety and, where appropriate, 1 to 6 carbon atoms in the straight-chain or branched alkyl moiety and in each case optionally mono- to trisubstituted by identical or different substituents, possible substituents on the aryl in each case being those mentioned for R 1

R

2 fu ca ca ir tc st

R

2 ft ca 0 I he ni mc st bp a. I It too 4 0400 0 a 04 a 6.44 aa a 1 a a a.

15 Aryl r naphth3 20 are pyx Very pa are the xl, x 2 25 ni

LA

Le A 29 Le k 29 484 12 Vt' best method of pe.

i S1 4 i j:t ;i i I p .oo04~~~4~

A

all at( 4ca:

R

2 furthermore represents aryl, arylcarbonyl, aryloxycarbonyl, arylcarbonyloxy or arylaminocarbonylaminocarbonyloxy having in each case 6 or 10 carbon atoms in the aryl moiety and in each case optionally monoto pentasubstituted by identical or different substituents, possible substituents on the aryl in each case being those mentioned for R',

R

2 furthermore represents heteroaryl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylcarbonyloxy or heteroarylaminocarbonylaminocarbonyloxy having in each case 2 to 9 carbon atoms and 1 to 4 identical or different hetero atoms in particular nitrogen, oxygen and/or sulphur in the heteroaryl moiety and in each case optionally mono- to penta- 15 substituted by identical or different substituents, possible substituents on the heteroaryl in each case being the substituents on the aryl mentioned for R'.

Aryl radicals which may be mentioned are phenyl or naphthyl, and heteroaryl radicals which may be mentioned 20 are pyridyl.

i 04~r *0 44 *o 0 4404 Ott' tos 40 4 o 4* 04 4 0 4 15 0 *so a 4 4 t sort O 40 4 4 440 chz hal gel at( atc to tet sti stx cai hal ide rep sty car the hay moi cas or the in 1 t car.

or atoi 04 4 4 O 4 4 *4 *4 4 444404 4 Very particularly preferred compounds of the formula (I) are those in which x 1 x 2

X

3 and X 4 independently of one another in each case represent hydrogen, chlorine, bromine, cyano or nitro, or represent in each case straight-chain or branched alkyl, alkoxy, alkylthio, a.lkylsulphinyl or 4 4 25 *4.44 0 4 0444 *r 0 04 9 Le A 29 484 13 Le A 29 4, p

I

J L.uwing statement is a full description of this invention, including the best method of performing it known to me:- 5020

F

i i 41* t alkylsuiphonyl having in each case 1 to 4 carbon atoms, or represent cycloalkyl having 3, 5 or 6 carbon atoms, or represent in each case straightchain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsulphinyl or halogenoalkylsuiphonyl having in each case 1 to 3 carbon atoms and 1 to 7 identical or different halogen atoms, or represent divalent dioxyalkylene having 1 to 3 carbon atoms which is optionally mono- to tetrasubstituted by identical or different substituents from the group comprising halogen and/or straight-chain or branched alkyl having 1 to 3 carbon atoms and/or straight-chain or branched halogenoalkyl having 1 to 3 carbon atoms and 1 to 7 identical or different halogen atoms, or furthermore represent hydroxycarbonyl, or represent in each case straight-chain or branched alkylcarbonyl or alkoxycarbonyl having in each case 1 to 3 carbon atoms in the alkyl moiety, or represent cycloalkyloxycarbonyl having 3, 5 or 6 carbon atoms in the cycloalkyl moiety, or represent amino or aminocarbonyl, in each case optionally mono- or disubstituted by identical or different substituents, possible substituents on the amino in each case being: in each case straight-chain or branched alkyl having 1 to 3 carbon atoms, halogenoalkyl having 1 to 3 carbon atoms and 1 to 7 halogen atoms, alkoxyalkyl or alkylcarbonyl having in each case 1 to 3 carbon atoms in the individual alkyl moieties, or phe or mon iide 5 sub: men or phei 0 iii1oxy 10 met optj moiE sib] tho 15 but x 3 whex R' rep bran 20 repy disu stit Ci halo or b.

25 ora atom 0* 00

S

5

I

04,r

S

I C Le A,29 4 Le A 29 484 -14 *b Fa~ h i

I

t Le A 29 4 phenylcarbonyl, phenylsuiphonyl, phenylaminocarbonyl or phenylmethylsulphonyl, in each case optionally mono- to trisubstituted in the phenyl moiety by identical or different substituents, possible substituents on the phenyl in each case being those mentioned for R 1 or furthermore for phenyl, phenyloxy, phenylthio, phenylsulphinyl, phenylsulphonyl, phenylsuiphonyloxy, phenylcarbonyl, phenyloxycarbonyl, phenylthiomethylsulphonyl or phenylazo, in each case optionally mono- to trisubstituted in the phenyl moiety by identical or different substituents, possible substituents on the phenyl in each case being those mentioned for R 1 but wherein at least one of the substituents X 1

X

2 X3 or X 4 is other than hydrogen and halogen, and wherein RI represents hydrogen, or represents straight-chain or branched alkyl having 1 to 4 carbon atoms, or represents phenyl which is optionally mono- or disubstituted by identical or different substituents, possible substituents being: halogen, cyano, nitro, in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsulphinyl or alkylsuiphonyl having in each case 1 to 3 carbon atoms, in each case straight-chain or branched halo( halo( havii iden stra.

alko havi indi havi.

to subs and! 3 cE halo iden whic iden comp alky chai ato ato ft t afa 15 gala ft it i ct r Cr i~: ii I ii a *.aa S ft.

ft f

R

2 repl alkE alk3 cark cas( alke opt: c C L a It C, *C V ft Le A 29 484 15

I

I

L

Le A 29 Ah i''>t Le A 29 484 Le A 29 484 -2

K

K'

I tM -n j _i ii i i!

I

i..

7 i:ii I £rr 15 4- 0 4 halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsulphinyl or halogenoalkylsulphoyl having in each case 1 to 3 carbon atoms and 1 to 7 identical or different halogen atoms, in each case straight-chain or branched alkoxyalkyl, alkoxyalkoxy, alkanoyl, alkoxycarbonyl or alkoximinoalkyl having in each case 1 to 3 carbon atoms in the individual alkyl moieties, divalent dioxyalkylene having 1 to 3 carbon atoms which is optionally monoto tetrasubstituted by identical or different substituents from the group comprising halogen and/or straight-chain or branched alkyl having 1 to 3 carbo.: atoms and/or straight-chain or branched halogenoalkyl having 1 to 3 carbon atoms and 1 to 7 identical or different halogen atoms, or phenyl which is optionally mono- to trisubstituted by identical or different substituents from the group comprising halogen and/or straight-chain or branched alkyl having 1 to 3 carbon atoms and/or straightchain or branched halogenoalkyl having 1 to 3 carbon atoms and 1 to 7 identical or different halogen atoms,

R

2 represents hydroxyl or cyano, or represents alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkoxyphosphoryl having in each case up to 4 carbon atoms in the individual alkyl or alkenyl or alkinyl moieties and in each case optionally mono- to trisubstituted by identical or diff r alker alky alky each alky* case or d: each stra carb disu stit thoE ,r r r: rr crr~ fior r r rrrt rr G C I (t

LE'

I

B

O I OD1D 15 R 2 furt eacl idei sub- 4, *45444 4- 44 *4 S20 4- .4.4-c stri car] hay 6 calk in str cyc atc Le A 29 484 -16 Le A 29 1-* Le A 29 484 i Le A 29 484

K

t ii i 1~ '4 1t .044 *4k different halogen atoms, or represents alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkoxyphosphoryl having in each case up to 4 carbon atcms in the individual alkyl or alkenyl or alkinyl moieties and in each case optionally mono- or disubstituted by identical or different substituents, possible substituents in each case being: straight-chain or branched alkoxy having 1 to 3 carbon atoms or phenyl which is optionally mono- or disubstituted by identical or different substituents, possible substituents on the phenyl being those mentioned for R 1 R' furthermore represents amino or aminocarbonyl in each case optionally mono- or disubstituted by identical or different substituents, possible substituents being: straight-chain or branched alkyl having 1 to 4 carbon atoms, straight-chain or branched alkenyl having 2 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, alkoxycarbonyl, alkylthio-carbonyl, alkoxythio-carbonyl or alkylthio-thiocarbonyl having in each case 1 to 4 carbon atoms in the individual straight-chain or branched alkyl moieties, divalent, cyclic alkanediyloxycarbonyl having 2 to 4 carbon atoms in the alkanediyl moiety, or phenylalky or i i i

'Y

I

18 r i r i phenyl atoms and in by id substi mentio C 4 44 4 *c C 004444 4 **4 0* C

S

R 2 furthe phenyl carbon to t substi each c

R

2 furthe carbon oxy having identi nitrog moiet substj possi being R11 Heteroaryl The followformula

(I)

Le A 29 484 17 Le A 29 48.

PhE~I~ r i i I Le A 29 484 -4 Le AZ9 484

)I

~i

II

p phenyl having, where appropriate, 1 to 3 carbon atoms in the straight-chain or branched alkyl moiety and in each case optionally mono- or disubstituted by identical or different substituents, possible substituents on the phenyl in each case being those mentioned for R',

R

2 furthermore represents phenyl, phenylcarbonyl, phenyloxycarbonyl, phenylcarbonyloxy or phenylaminocarbonylaminocarbonyloxy, in each case optionally monoto trisubstituted by identical or different substituents, possible substituents on the phenyl in each case being those mentioned for R',

R

2 furthermore represents heteroaryl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylcarbonyloxy or heteroarylaminocarbonylaminocarbonyloxy having in each case 2 to 9 carbon atoms and 1 to 3 identical or different hetero atoms in particular nitrogen, oxygen and/or sulphur in the heteroaryl moiety and in each case optionally mono- to trisubstituted by identical or different substituents, possible substituents on the heteroaryl in each case being the substituents on the phenyl mentioned for R11 Heteroaryl which may be mentioned is pyridyl.

The following substituted benzimidazoles of the general formula may be mentioned specifically, addition to Wi -il the compaunl fi t

;Q

is i i i i i? i X1 Br Br Br i 4t 44 4I o .4, #4 44r 4* 0 4 Br Br Br Le A 29 484 Le A 29 484 18

L~

eA2944Le A 29 484 -5- Le A 29 484

I

the compounds mentioned in the Preparation Examples X1 Cl 4 1 x 2' HR

R

a a, a

I

*aGaa t

C

a. sa

CF

3

-S-

CF3-S- ClFCH-CF 2

-S-

ClFCH-CF 2

-S-

F

3 C-CHF -CF 2 -S

F

3 C-CHF -CF 2 -S

F

3

C-

F

3

C-O-

F

3

C-O-

N0 2 N02 H CH H -CH 2

-O-C

2

H

H CH -i 2 N 'OOC 2 H-4 H -CH 2

-O-C

2

HS

H C 2 H5 H -CH 2

-O-C

2

H

H -CH 2 -o-C 2

HS

H CH

CH

2

COOC

2 H-3 H -CH 2

-O-C

2

H

5 H

C

2

H

H -CH 2 -o-C 2

H

5 aoa.15 Cl Cl Cl

CF

3

CF

3

CF

3

CF

3 Le A 29 484 19 Le A 29 484 eA2944- -Le A 29 484 Le A 29 484

K

X1 K CF 3

CF

3

CF

3

CF

3

-S-

CF

3

-S-

ClFCH-CF 2

-S-

ClFCH-CF 2

-S-

F

3

C-CHF-CF

2

-S-

F

3

C-CHF-CF

2

F

3

C-

F

3

C-O-

F

3

C-O-

N0 2

NO

2

CF

3

-S-

C

2 H5 1

COOC

2 1-1

-CH

2

-O-C

2

H

5

-CH

2

COOC

2 H

-CH

2

-O--C

2

HS

CAH

-cH2 COOC 2

-CH

2

-O-C

2

H

CH

2 cCo 2 Hl- -cH- COOCAH

-CH

2

-O-C

2

H

Mc 2

COOC

2

-CH

2

-O-C

2

H

-CH

2

-O-C

2 H.9

CA

2

H

-cH' 2

COOC

2 Hs

-CH

2

-O-C

2

H

CF

3

CF

3

CF

3

COOCH

3

COOCH

3

COOCH

3 S. SQ 0C#t S S 555.5.

Cl Cl Cl

CF

3 C S SI I IISt~ SIGh

S'S.

'15

CF

3

CF

3 115

CF

3

-S-

ClFCH-CF 2 -S

COOCH

3

COOCH

3 COOCH3

COOCH

3

COOCH

3 H C1FCH-CF 2

-S-

Le A 29 484 20 Le A 29 484 tan *1 -~22 eA2944- -Le A 29 484 Le A 29 484 SIr- X1X 2 x4 A

CF

3

CF

3

CF

3 H F 3

C-CHF-CF

2

-S-

CF

3

CF

3 *0 00 0490

CF

3

COOCH

3

COOCH

3

COOCH

3

COOCH

3

COOCH

3 COOCH3

COOCH

3

COOCH

3

F

3

C-CHF-CF

2

-S-

F

3

C-

F

3

C-

F

3

C-O-

F

3

C-O-

NO

2

NO

2

CF

3

-S-

CF

3

-S-

ClFCH-CF 2

-S-

C1FCH-CF 2

-S-

F

3

C-CHF-CF

2

-S-

F

3

C-CHF-CF

2

-S-

F

3

C-

F

3

C-

C

2

HS

-cH 2

COOC

2 14

-CH

2

-O-C

2

H

5

CAH

"N

-CH

2

-O-C

2

H

-cH 2

COOCAH

-CH

2

O-C

2

H

5 g q 2 45 -cH 2

COOC

2

HS

-CH

2

-O-C

2

H

5

C

2 1-4 -cH 2

COOC-

2 14

-CH

2

-O-C

2

H

5

CAH

-CH

2

-O-C

2

H

5

C

2

H

5

-CI

2

COOC

2

H-

-CH

2

-O-C

2

H

4~ 9000 000! 044 10 U 04 00 0 *0 0*4004 0 0004 04 04 0 0 1~ 0 X1-

COOCH

3

COOCH

3

COOCH

3

COOCH

3 COO-n-C 3

H

7 COO-n-C 3

H

7 COO-n-CH 7 COO-n-C 3

H

7 COO-n-C 3

H

7 COO-n-C 3

H

7 COO-n-C 3

H.,

COO-n-CH 7 COO-n-CH 7 COO-n-C 3

H

7 COO-n-C 3

H

7 44015 Le A 29 484 21 Le A 29 484 Le A 29 484- 8

K

K~ mm-

COOCH

3 C00CH 3

COOCH

3

FC-O-

F

3

C-O-

N0 2

COOCH

3 COO -n-C 3

H

7

NO

2

CF

3

-S-

COO-n-C 3

H

7 COO-n-CH 7

CF

3

-S-

ClFICH-CF 2 -S Stit Set.

t St.' 10 ,t COO-n-C 3

H

7 COO-n-C 3

H

7 C1FCH-CF 2

S--

F

3

C-CHF-CF

2

-S-

CAH

CH

2 z COOC21H

-CH

2

-O-C

2

HS

-CH

2

-O-C

2

H

-CH2

-CH

2

-O-C

2

H

C~H

0 2 COOC2H4

-CH

2

-O-C

2

H

Z COOC2ZH

-CH

2 -o-C 2

H

q 2

HS

N CooclH,

CH

2

H

-CHi 2 -o-C 2

H

-CU2 COOC 2 85 0 0 0 00 S

I

COO-n-C 3

H.,

COO-n-C 3

H-,

F

3

C-.CHF-CF

2 -S

F

3

C-

COO-n-C 3

H.,

COO-n-C 3

H

7

F

3

C-

F

3

C-O-

COO-n-C 3

H

7 COO-n-C 3 11 7

F

3

C-O-

NO

2 Le A 29 484 22 Le A 29 484 -9 jLe 'el i iI f :i i i:E ia ii i i-

I

COO-n-C 3 H7 NO 2

-CH

2

-O-C

2

H

Some of the substituted benzimidazoles of the formula (I) are known (compare, for example, DE 20 47 369; DE 20 14 293; EP 448 206; J. Chem. Soc. C, 1967, 2536- 2540).

Substituted benzimidazoles which are not yet known but are the subject-matter of a previous Application which has been filed by the Applicant Company are those of the formula (Ia)

I-I

X

2-1 X

N

I -CN (Ia) 3-11 3.11 N X 1 4-1 CH-R X 2

R

in which 00 0 0:2 000 0 X2- 1

X

3 and X 4 -1 independently of one another in each case represent hydrogen, halogen, cyano or nitro, or represent in each case optionally substituted alkyl, alkoxy, alkylthio, alkylsulphinyl, alkylsulphunyl or cycloalkyl, or represent optionally substituted, fused-on dioxyalkylene, or represent hydroxycarbonyl, alkylcarbonyl, alkoxycarbonyl or cycloalkyloxycarbonyl, or represent in each case optionally r so r D a rrr r o oi 00 44 4 0,004 00 0 0 0 Le A 29 484 23 Le A I qP-- Ilw :s d ILe A 2 S Le A 29 484 -1 10 substituted amino or axinocarbonyl, or represent in each case optionally substituted aryl, aryloxy, arylthio, arylsuiphinyl, arylsulphonyl, arylsuiphonyloxy, arylcarbonyl, aryloxycarbonyl, arylazo or aryi-thiomethylsuiphonyl, but wherein at least one of the substituents X 1 1 x 2 1

X'-

1 and X 4 1 represents nitro, halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsuiphinyl, halogenoalkylsulphonyl or alkcylsulphonyl, or represents optionally substituted, fused-on dioxyalkylene, or represents hydroxycarbonyl, alkylcarbonyl, alkoxycarbonyl or cyc]Loalkyloxycarbonyl, or represents in each case optionally substituted amino or aminocarbonyl, or represents in each case optionally substituted aryl, arylthio, arylsulphinyl, arylsulphonyl, arylsulphonyloxy, arylcarbonyl, aryloxycarbonyl, arylazo or arylthiomethylsulphonyl, and wherein

R

1 represents hydrogen or alkyl, or represents optionally substituted aryl, R 2 represents hydroxyl or cyano, or represents in each case optionally substituted alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, amino, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, dialkoxyphosphoryl, (hetero) aryl, (hetero) arylcarbonyl, (hetero) The (Ia) 5 by a osoc 0t 0 0 #000 00 0 00 Sc 0000 *00 S are 0 0 o 0000 o 00 00 0 0,0*90 o 004000 0 S *00000 00 00 00 0 0 0 0 0 0,00 0 0* 0 0 0 0 Le A 29 484 24 _1 i 1 4 I 1i~

'S.

im__- Le k 2 Le A 29 484 11 lii aryloxycarbonyl, (hetero) arylcarbonyloxy or (hetero) arylaminocarbonylaininocarbonylo~xy.

The substituted benzimidazoles of the formulae and (Ia) which are known and are. not yet known are obtained by a process in whicii a) lH-benzimidazoles of the formula (II)

I

x 2 X3 N x in which

X

1

X

2

X

3 and X 4 have the abovementioned meaning, are reacted with alkylating agents of the formula (III) if, chlox thec 5 be r a'S:

G@

00 0 t *00 0 02

I~

at 0tat taco a a.

0 a

R

E-CH

\-2

(III)

00 0 a a 00 0 044400 0 .04040 0 0 S ova.

*0 0J 00 0 0 i n whi.c h E represents a suitah~e- leaving group and

R

1 and R 2 have the abovementioned meaning, if appropriate in the presence of a diluent and if 00 00 0 0000 a a* 00 5 10 0 0 *000 o 0 0000 00 04 o a 0 a 0 carryi

(II),I

which substi compou to the Le A 29 484 Le A 25 'I' E7 Lie A 29 Lie A 29 484 12

I,

appropriate in the if, for example, chioromethyl ethyl the course of the re be represented by t] ~0 presence of a reaction auxiliary.

5-nitro-.2-cyano-benzimidazole and ether are used as starting compounds, -action of the preparation process can the following equation: The I!Hare obt (compar [1953]; 5 ForMula alkylat product this fc radical, for thei of the 0 2

NN

)C N

H

2 2 Q-CH-Q-qH a accordi: Ha base ac 00 00~ .OOt 0 0000 00 00 0 00 0 00 00 0 000 0 00 00 00 0 004.

0 00 00 0 00040.

0 0 000000 0000 0 0 0000 00 00 00 0 0 0 N>c 0 2 N

N\

Formula (II) provides a general definition of the 1Hbenzimidazoles required as starting substances for carrying out the preparation process. In this formula (II) X 1

X

2

X

3 and X1 preferably represent those radicals 10 which have already been mentioned as preferred for these substituents in connection with the description of the compounds of the formula which can be used according to the invention.

0 0' 0 C, 00 0tC, 0t 0~ 0000 00 0 0 0 0 0 00 0 00 00 0 000 0 00 00 00 0 0 C 0000 00 00 0 E repre agents, 15 represe~ each c alkoxysi particu' sulphon, 20 p-toluei 0..:25 0000 0 0 0000 00 00 00 0 0 0 Sf urthE alkoxy or meth f ormula preparec invent ic lie-A 29

I

11I Lie A 29 484 26

I

Le A 29 4 Le A 29 484 13 ,i r! ;e The 1H-benzimidazoles of the formula (II) are known or are obtainable by processes analogous to known processes (compare, for example, J. Amer. Chem. Soc. 75, 2192 [1953]; US 3,576,818) Formula (III) provides a general definition of the alkylating agents furthermore required as starting products for carrying out the preparation process. In this formula (III), RI and R 2 preferably represent those radicals which have already been mentioned as prepared for theje substituents in connection with the description of the substances of the formula which can be used according to the invention.

E represents a leaving radical customary in alkylating agents, and preferably represents halogen, in particular represents chlorine, bromine or iodine, or represents in each case optionally substituted alkylsulphonyloxy, aI alkoxysulphonyloxy or arylsulphonyloxy, such as, in a particular, methanesulphonyloxy, trifluoromethanea sulphonyloxy, methoxysulphonyloxy, ethoxysulphonyloxy or p-toluenesulphonyloxy.

The compo are obtal (compare, I SynthesiE possible process particule halogena benzene, petroleup chlorofo diethyl furan or ketones, ketone; r benzoniti dimethyl pyrrolidc esters, 20 bases, st a acid or co o aaa.

a a.

Saa a a ass a6 9' furthermore also represents an alcohol, alkanoyloxy or alkoxy group, such as, for example, a hydroxyl, acetoxy or methoxy group, in particular if compounds of the formula in which R 1 is other than hydrogen are to be prepared with the aid of the process according to the invention.

a, ac asa, as c aaara, The preppresence reaction 25 organic I metal ox alcoholal such as, lithium at a Le A 29 Le A 29 484 27

LU-ID~

j tr i:, 1 p- Le A 29 484 14 Le A 29 4E p 4 _CIIIIII~-LI~CdL. ilLLY--_II__LIII~L---i rr 1 i j i:: f i I f The compounds of the formula (III) are generally known or are obtainable by processes analogous to known processes (compare, for example, DE 20 40 175; BE 21 19 518; Synthesis 1973, 703).

Possible diluents for carrying out the preparation process are inert organic solvents. These include, in particular, aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, benzine, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, methylene chloride, chloroform or carbon tetrachloride; ethers, such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl or ci.ethyl ether; ketones, such as acetone, butanone or methyl isobutyl ketone; nitriles, such as acetonitrile, propionitrile or benzonitrile; amides, such as N,N-dimethylformauide, N,Ndimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric acid triamide; esters, such as methyl acetate or ethyl acetate, or 20 bases, such as pyridine, or organic acids, such as formic acid or acetic acid.

The preparation process is preferably carried out in the presence of a suitable reaction auxiliary. Possible reaction auxiliaries are all customary inorganic or 25 organic bases. These include, for example, alkaline earth metal or alkali metal hydrides, hydroxides, amides, alcoholates, acetates, carbonates or hydrogencarbonates, such as, for example, sodium hydride, sodium amide, lithium diethylamide, sodium methylate, sodium ethylate, f J j.

6 ii 1 iJ i.

potassium hydroxide acetate, carbonat 5 hydrogenci carbonate butyllith.

trimethy diisoprop, 10 dimethylal piperidin (DABCO), c

(DBU).

Alternati' 15 organic sulphuric acid, per: exchanger.

the formu' 20 alkoxy ra( If approcarried o water!toli in the pr 25 Examples tetrabuty' tetrabuty.

bromide, Itr *0 C. *r C. 4 0eee

-C

i 0 A IC Le A 29 484 Le A-29 41 28 a491D cllrrrarrap

II

.i tt Le A 29 Le A 29 484 15 31I 1 1% 1potassium tert-butylate, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, potassium hydrogencarbonate, sodium hydrogencarbonate or ammonium carbonate, organolithium compounds, such as nbutyllithium, and tertiary amines, such as trimethylamine, triethylamine, tributylamine, diisopropylethylamine, tetramethylguanidine, NNdimethylaniline, pyridine, piperidine, N-methylpiperidine, 1 N-dimethylaminopyridine, diaz abicyc looctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene

(DBU).

ii i 1I-:6 f i i i:i i i;

I

;r i.j j j: i, ja i i i 'i ;i i 5 i- I trimethylammonium ammonium bromide, 5 ammonium trimethyib or tris-[2 The reacti stantial r.

10 The reacti between between OC The prepan normal pre 15 out the pr i: 'i i rB s i i- :I :i i;i si i i r;tr ir: i:l cii re; st cc, r~ 1 Alternatively, possible reaction auxiliaries are also 15 organic or inorganic acids, such as, for example, sulphuric acid, hydrochloric acid, p-toluenesulphonic acid, perfluorobutanesulphonic acid or strongly acid ion exchangers, especially if E in the alkylating agents of the formula (III) used represents a hydroxyl, acyloxy or alkoxy radical.

If appropriate, the preparation process can also be carried out in a two-phase system, such as, for example, water/toluene or water/methylene chloride, if appropriate in the presence of a suitable phase transter catalyst.

25 Examples of such catalysts which may be mentioned are: tetrabutylammonium iodide, tetrabutylammonium bromide, tetrabutylammonium chloride, tributylmethylphosphoniumu bromide, trimethyl-C 1 3

/C

1 5 -alkylammonium chloride, I 14 I C I CE C

CC

For carryi to 5.0 mol agent of t mol, p, 20 are employ

(II).

In a parti lH-benz im ted in a F 25 silylating disilazane CC t C C Le A 29 48 Le A 29 484 29 rnrnj::,q ip i Le A 29 484 -16 Le A 291 I j jtrimethyl-C 13 /C 1 5 -alkylammonium bromide, dibenzyldimethylammonium methyl sulphate, dimethyl-C 12

/C

14 -alkylbenzylammonium chloride, dimethyl-C 1 2

/C.

4 -alkylbenzylammonium bromide, tetrabutylammonium hydroxide, triethylbenzylammonium chloride, methyltrioctylammonium chloride, trimethylbenzylammonium chloride, 15-crown-5, 18-crbwn-6 or tris-[2-(2-methoxyethoxy)-ethyl]-amine.

The reaction temperatures can be varied within a substantial range when carrying out the preparation process.

The reaction is in general carried out at temperatures between -70C and +200C, preferably at temperatures between OC and 130C.

The preparation process is usually carried out under normal pressure. However, it is also possible to carry 15 out the preparation under increased or reduced pressure.

For carrying out the preparation process, in general 1.0 to 5.0 mol, preferably 1.0 to 2.5 mol, of alkylating agent of the formula (III) and if appropriate 0.01 to mol, preferably 1.0 to 3.0 mol, of reaction auxiliary 20 are employed per mole of lH-benzimidazole of the formula

(II).

In a particular embodiment, it is also possible for the 1H-benzimidazoles of the formula (II) first to be silylated in a prior reaction step with the aid of customary 25 silylating processes, for example with hexamethyldisilazane or trimethylsilyl chloride, if appropriate in the preser example, s sulphate, Ii -20C and +1 5 thus obtai stage witi accordance is advant alkylation 10 Chem. Hete i

I

a3

I

The reactic worked up context, cc i i i r

ECI

ii ly f i irr L-.i t 3 i~ -r ig trtic

II

c 4 t ;:3 1~ i 'j i :2 1 i s j8 f, r0 I:i i c c t cP cc C crc c The end pro 15 aid of cust tography oz The produc melting po compounds 20 mixtures resonance s The active protozoa wh and test an 25 rearing, an animals. Th ccrc Et c 4c,' t

C

44- 4 94cc @9 *4 44 4 t

^C

Cf I~ :1 c Le A 29 484 Le A 29 484 30 6apBp~aSp SIOB $9r"--91" p Le A 29 48, Le A 29 484 17 -444" the presence of a suitable catalyst, such as, for example, sulphuric acid, trifluoroacetic acid, ammonium sulphate, imidazole or saccharin, at temperatures between and +150C and for the l-trimethylsilylbenzimidazoles thus obtainable to be reacted in a subsequent second stage with alkylating agents of the formula (II) in accordance with the preparation process. In this case, it is advantageous to add tin tetrachloride to the alkylation reaction as a catalyst (compare, for example, Chem. Heterocycl. Comp. USSR 24, 514 [1988]).

The reaction is carried out and the reaction products are worked up and isolated by known processes (in this context, compare also the Preparation Examples).

The end products of the formula arg purified with the aid of customary processes, for example by column chromatography or by recrystallisation.

of develoi normally protozoa, (for exam 5 skins, egg that more possible b, s

IF

g: The parasil 0 C,

C

4 Cf 1(0 5 -4 4 44

SC

The products are characterised with the aid of the melting point or, in the case of non-crystallising compounds especially in the case of regioisomer 20 mixtures with the aid of proton nuclear magnetic resonance spectroscopy (H-NMR).

The active compounds are suitable for combating parasitic protozoa which occur on stock, breeding, zoo, laboratory and test animals and pets in animal husbandry and animal rearing, and have a favourable toxicity to warm-blooded animals. They are active here against all or some stages 0a 9h4S St *00 S Mastigophoi 10 Trypanosonv gambiense, evansi, T.

vivax, Leis such as, Giardia lam Sarcomasti example E example Aca Apicomplexa 20 Emeria ac anatis, E.

auburnensis chinchillae crandalis, 25 E. falcif gallopavoni St t t.

K

S

4C 0 005 44 0 o 44$, 0 40 0 o0 3 i Le A 29 484 Le A 29 484 31 a MISS R 11 1 -Il -44~- Le A 29 484 Le A 29 484 18-

I

f 4 4 of development of the pests and against resistant and normally sensitive strains. By combating the parasitic protozoa, illness, fatalities and reductions in output (for example in the production of meat, milk, wool, skins, eggs, honey and the like) are to be reduced, so that more economical and easier animal husbandry is possible by using the active compouiids.

The parasitic protozoa include: Mastigophora (Flagellata), such as, for example, Trypanosomatidae, fo:c example Trypanosoma b. brucei, T.b.

gambiense, 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, for example, Trichomonadidae, for example Giardia lamblia, G. canis.

E. irresi maxima, E.

mitis, E.

parva, F.

5 piriforris E. stiedai E. zuernii felis,, I.

Cystisospo Toxoplasma Sarcocysti bovihomini suihominis Leucozytoz Plasmodium P. vivax, Babesia a Theileria example He a r a a ao err a ro a a o Sarcomastigophora (Rhizopoda), such as Entamoebidae, for example Entamoeba histolytica, Hartmanellidae, for example Acanthamoeba sp., Hartmanella sp.

0 00 00 4 000 1 0o 0 Os4* OdOJ 0* 0 00 0 Apicomplexa (Sporozoa), such as Eimeridae, for example 20 Eimeria acervulina, E. adenoides, E. alabahnensis, E.

anatis, E. anseris, E. arloingi, E. ashata, E.

auburnensis, E. bovis, E. brunetti, E. canis, E.

chinchillae, E. clupearum, E. columbae, E. contorta, E.

crandalis, E. debliecki, E. dispersa, E. ellipsoidales, 25 E. falciformis, E. faurei, E. flavescens, E.

gallopavonis, E. hagani, E. intestinalis, E. iroquoina, *0 Sr 040 0 t 04 40 0 4; 0000 0 0 Furthermor spec. Nose Furthermor (Ciliata), Ichthiopht The compou against p Such paras 0 0 0o 0 Le A 29 48 Le A 29 484 32 b I Le A 29 484 Le A 29 484 -19

I;

i II I-r~i

I

~i, E. irresidua, E. labbeana, E. leucarti, E. magna, E.

maxima, E. media, E. meleagridis, E. meleagrimitis, E.

mitis, E. necatrix, E. ninakohlyakimovae, E. ovis, E.

parva, F. pavonis, E. perforans, E. phasani, E.

piriformis, E. praecox, E. residua, E. scabra, E. spec., E. stiedai, E. suis, E. tenella, E. truncata, E. truttae, E. zuernii, Giobidium spec., Isospora belli, I. canis, I.

felis, I. ohioensis, I. rivolta, I. spec., I. suis, Cystisospora spec., Cryptosporidium spec., such as Toxoplasmadidae, for example Toxoplasma gondii, such as Sarcocystidae, for example Sarcocystis bovicanis, S.

bovihominis, S. ovicais, S. ovifelis, S. spec., S.

suihominis, such as Leucozoidae, for example Leucozytozoon simondi, such as Plasmodiidae, for example Plasmodium berghei, P. falciparum, P. malariae, P. ovale, P. vivax, P. spec., such as Piroplasmea, for example Babesia argentina, B. bovis, B. canis, B. spec., Theileria parva, Theileria spec., such as Adeleina, for example Hepatozoon canis, H. spec.

:j a ii t:I:I i

I'

f

.E

i: :Iz i i: j i i F1 I r! i- I:i 1i: phylum Micros 1 Nosema apis on The stock and for example, c 5 water buffalo, deer, fur-beai chinchillas a example, chic] species of bi:j 10 animals also i The laborator: guinea-pigs, g The pets inclu *4, op IP 25 Furthermore, Myxospora and Microspora, for example Glugea spec. Nosema spec.

Furthermore, Pneumocystis carinii, as well as Ciliophora (Ciliata), such as, for example, Balantidiuu coli, Ichthiophthirius spec., Trichodina spec., Epistylis spec.

The compounds according to the invention are also acti ve against protozoa which occur as parasites on insects.

Such parasites which may be mentioned are those of the The fish inclu 15 fish of all a water. The sto( carp, eel, trou sole, plaice, quinqueradiata 20 seabrear, (Paguz Grey mullet seabream (Spa] species, such catfish. The 25 particularly su carp of body 1E 4e*s i o 0 0 0 o P tCS (1 tO I I I 4 Le A 29 484 Le A 29 484 33 L a~clseDar~apausl~s~apia~ ~krsa~

_I

IC

C~?

i f Le A 29 484 Le A 29 484 20

J.

1 7 i phylum Microsporida, in particular of the genus Nosema.

Nosema apis on honey bees may be mentioned in particular.

The stock and breeding animals include mammals, such as, for example, cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer and reindeer, fur-bearing animals, such as, for example, mink, chinchillas and raccoons, and birds, such as, for example, chickens, geese, turkeys, ducks, pigeons and species of birds for keeping at home and in zoos. The animals also include stock and ornamental fish.

The laboratory and test animals include mice, rats, guinea-pigs, golden hamsters, dogs and cats.

suitable for They can be 1 cally.

The active c 5 dermally or r formulations.

Enteral use example, ora tablets, cap 10 boli, medica effected, fo.

spraying (spi and spot-on) for example, 15 subcutaneous, implants.

0* o Suitable fo Solutions, st concentrates 20 solutions fox on formulatic 9 i: 1 1i1i i" i' 1i i:1 t i ii j1 The pets include dogs and cats.

The fish include stock, breeding, aquarium and ornamental fish of all ages which live in fresh water and salt water. The stock and breeding fish include, for example, carp, eel, trout, white fish, salmon, bream, roach, chub, sole, plaice, halibut, Japanese yellowtail (Seriola quinqueradiata), Japanese eel (Anguilla japonica), Red seabrear. (Pagurus major), Seabass (Dicentrarchus labrax), Grey mullet (Mugilus cephalus), Pompano, Gilthread seabream (Sparus auratus), Tilapia spp., Chichlidae species, 8uch as, for example, Plagioscion, Channel catfish. The agents according to the invention are particularly suitable for treating fish fry, for example carp of body length 2 to 4 cm. The agents are also very Emulsions anc injection; s( 0s*000

S

00r0 00 0O Il S Le A 29 484 Le A 29 484 34 p.-p~d~P~l .r.gll~ d--s~iB~asBIBW B pt~sla t d r t s: j': Le A 29 484 -21 Le A 29 484 M-7-n suitable for eel fattening.

They can be used either prophylactically or therapeutically.

The active compounds are used enterally, parenterally, dermally or nasally, directly or in the form of suitable formulations.

Enteral use of the active compounds is effected, for example, orally in the form of powders, suppositories, tablets, capsules, pastes, drinks, granules, drenches, boli, medicated feed or drinking water. Dermal use is effected, for example, in the form of dipping (dips), spraying (sprays), bathing, washing, pouring on (pour-on and spot-on) and powdering. Parenteral use is effected, for example, in the form of injection (intramuscular, subcutaneous, intravenous or intraperitoneal) or by implants.

91 Formulatio-s ii an ointment ba emulsion base; Solid formulat trates, granul aerosols and.

the active coi Injection so] intramuscular 10 Injection solu compound in a such as solubi -3 antioxidants a jected to ster: ao *0

S

Suitable formulations are: 15 Solvents which tolerated solv ethanol, butan carbons, prop3 methylpyrrolidc 20 If appropriatE dissolved in synthetic oils so 0a 0 *5* 0*# 0.0 CC Solutions, such as injection solutions, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, pouron formulations and gels; Emulsions and suspension for oral or dermal use and for injection; semi-solid formulations; Solubilising ag which promote s t (I C C Le A 29 484 Le A 29 484 35 row IAZ i ii Le A 29 484 22 Formulations in which the active compound is processed in an ointment base or in an oil-in-water or water-in-oil emulsion base; Solid formulations, such as powders, premixes or concentrates, granules, pellets, tablets, boli or capsules; aerosols and inhalants, and shaped articles containing the active compound.

Injection solutions are administered intramuscularly and subcutaneously.

intravenously, ii ii i ~lS i ,i i:i i i i -:i i ii i o 10 Injection solutions are prepared by dissolving the active compound in a suitable solvent and adding any additives, such as solubilising agents, acids, bases, buffer salts, antioxidants and preservatives. The solutions are subjected to sterile filtration and bottled.

Solvents which may be mentioned are: physiologically tolerated solvents, such as water, alcohols, such as ethanol, butanol, benzyl alcohol or glycerol, hydrocarbons, propylene glycol, polyethylene glycols, Nmethylpyrrolidone and mixtures thereof.

20 If appropriate, the active compounds can also be dissolved in physiologically tolerated vegetable or synthetic oils which are suitable for injection.

Solubilising agents which may be mentioned are: solvents which promote solution of the active compound in the main Lit C C

CCC'

CC CC C C

C

Le A 29 484 36 tib !j 1 Le A 2 Le A 29 484 23 was solvent or prevent its, precipitation. Examples are polyvinylpyrrolidone, polyoxyethylated castor oil and polyoxyethylated sorbitan esters.

Preservatives are: benzyl alcohol, trichlorobutanol, phydroxybenzoic acid esters and n-butanol.

Oral solutions are used directly. Concentrates are used orally after prior dilution to the use concentration.

Oral solutions and concentrates are prepared as described above for the injection solutions, but sterile working can be dispensed with.

Solutions for use on the skin are dripped on, brushed on, massages in, sprayed on, atomised on or applied by dipping, bathing or washing. These solutions are prepared as described above for the injection solutions.

It may be advantageous to add thickening agents during the preparation. Thickening agents are: inorganic thickening agents, such as bentonites, colloidal silicic acid and aluminium monostearate, and organic thickening agents, such as cellulose derivatives, polyvinyl alcohols and copolymers thereof, acrylates and metacrylates.

Gels are applied or brushed onto the or introduced into body cavities. Gels are prepared by adding to solutions, which have been prepared as described fQ~r the injection solutions, thickening agents in an amount such that a clear mass having an ointment-like consistency is formed.

Thick4 agent., Pourareas throu sprea Pour-( ding solve] IQ skin.

dyesti light o aGO a a Solve glycol 15 glycei pheny acetal as al glyco 20 ether, aromat sy thE methyJ dioxoJ oo oo re o o or a o o 25 Dyesti.

animal GO a a a LeA Le A 29 484 37 Ir la~lpeL-s~p b IP ~CI lli~- P- ~I~X~F pYY+- I J: Le A Le A 29 484 24 -aa~ti3birhq~

LI

-p- Thickening agents which are employed are the thickening agents mentioned above.

Pour-on formulations are poured or sprayed onto limited areas of the skin, the active compound either penetrating through the skin and having a systemic action or spreading over the body surface.

Pour-on formulations are prepared by dissolving, suspending or emulsifying the active compound in suitable solvents or solvent mixtures which are tolerated by the '0 skin. If appropriate, further auxiliaries, such as dyestuffs, absorption-promoting substances, antioxidants, light stabilisers and adhesion promoters, are added.

Solvents which may be mentioned are: water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols, such as benzyl alcohol, phenylethanol and phenoxyethanol, esters, such as ethyl acetate, butyl acetate and benzyl benzoate, ethers, such as alkylene glycol alkyl ethers, such as dipropyllene glycol monomethyl ether and diethylene glycol monobutyl 20 ether, ketones, such as acetone and methyl ethyl ketone, aromatic and/or aliphatic hydrocarbons, vegetable or synthetic oils, dimethylformamide, dimethylacetamide, Nmethylpyrrolidone or 2-dimethyl-4-oxymethylene-l ,3dioxolane.

Absorl sprea glycol trigl' 5 Atio pctass toluen Light class 10 Adhesi tives, occurr.

Emulsic o o or o

D

a*aa Daso os r a c o rr so s ar o 0 00, 15 0 00 :OO 20 0000 0000 009 00 00 Emulsic oil-in- They a either homoger phase priate promoti stabili As the paraffi 00r 4 0 0 000000 25 Dyestuffs are all the dyestuffs approved for use on animals and can be dissolved or suspended.

00 0 Le A 29 L l -a Le A 29 484 38 I I Io

I

I

II

Le A 29 484 25 :~a 172 Absorption-promoting substances are, for example, DMSO, spreading oils, such as isopropylmyristate, dipropylene glycol pelargonate and silicone oils, fatty acid esters, triglycerides and fatty alcohols.

An-tioxidants are sulphiter or metabisulphites, such as potassium metabisulphite, ascorbic acid, butyihydroxytoluene, butylhydroxyanisole and tocopherol.

Light stabilisers are, for example, substances from the class of benzophenones or novantisol acid.

Adhesion promoters are, for example, cellulose derivatives, starch derivatives, polyacrylates and naturally occurring polymers, such as alginates and gelatin.

Emulsions can be used orally, dermally or as injections.

Le A 2 vegeta oil, E acid b fatty 5 select glycer acids, and di Fatty 10 adipat esters with isopro acid e C1-C18 ethyl as di mixtux 00such 20 stea 4444 *0 Fatty mixtux As thE water, glyce3 Emuls: non-i 4044 40#4r 04 00 00 1 15 0040 4400

OQ

0 20 00 0 Emulsions are either of the water-in-oil type or of the oil-in-water type.

They are prepared by dissolving the active compound either in the hydrophobic or in the hydrophilic phase and homogenising this phase with the solvent of the other phase with the aid of suitable emulsifiers and if appropriate other auxiliaries, such as dyestuffs, absorptionpromoting substances, preservatives, antioxidants, light stabilisers and viscosity-increasing substances.

As the hydrophobic phase (oils) there may be mentioned: paraffin oils, silicone oils, naturally occurring 0 0*r 0r 0 Le A Le A 29 484 39 -~s~s ~72 -S I _1 Le A 29 484 26 Le.. A 2 9 Pla~ sPI-" -sRlllsaakllll~l*L m Vt.

u i i vegetable oils, such as sesame oil, almond oil and castor oil, synthetic triglycerides, such as caprylic/capric acid biglyceride, a triglyceride mixture with vegetable fatty acids of chain length C 8 12 or other specifically selected naturally occurring fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids, which may also contain hydroxyl groups, and monoand diglycerides of C 8 /Cj 0 -fatty acids.

Fatty acid esters, such as ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene glycol pelargonate, esters of a branched fatty acic of medium chain length with saturated fatty alcohols of chain length C 1 6

-C

18 isopropyl myristate, isopropyl palmitate, caprylic/capric acid esters of saturated fatty alcohols of chain length

C

12

-CI

8 isopropyl stearate, oleyl oleate, decyl oleate, ethyl oleate, ethyl lactate, waxy fatty acid esters, such as dibutyl phthalate, diisopropyl adipate and ester mixtures related to the latter, and also fatty alcohols, such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol and oleyl alcohol.

1 g

I

/a i g castor sorbita: polyoxy( ampholyl 5 dipropic anionic alcohol orthophc cationic 10 chloridE o 0 0000 00 000 15 a it

D

a o oo r r r orrr coii ar o o o o O ro o cc a a o r Other ai substanc emulsior and otl acrylate pyrrolid vinyl et waxes, stances Fatty acids, such as, for example oleic acid and its mixtures.

00 0r 000 00 0 As the hydrophilic phase there may be mentioned: water, alcohols, such as, for example, propylene glycol, glycerol, sorbitol and their mixtures.

Emulsifiers which may be mentioned are: non-ionic surfactants, for example polyoxyethylated 0 0u~ #04 0 00 00r 0 0 0 0 0 0 0O Suspensi tion. Th in a car other ai absorpti 25 oxidants I Le A 29 484 40 Le A 29 i h All- Le A 29 484 27 castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate and alkyiphenol polyglycol ether; ampholytic surf actants, such as di-Na N-lauryl--iminodipropionate or lecithin; anionic surf actants, such as Na lauryl sulphate, fatty alcohol ether sulphates, mono/dialkyl polyglycol ether orthophosphoric acid ester monoethanolamine salt; cationic surfactants, such as cetyltrimethylamoniuif chloride.

Other auxiliaries which may be mentioned are: substances which increase the viscosity and stabilise the emulsion, such as carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes, colloidal silicic acid or mixtures of the substances listed.

Suspensions can be used orally, dermally or as an injection. They are prepared by suspending the active compound *o in a carrier liquid, if appropriate with the addition of other auxiliaries, such as wetting agents, dyestuffs, absorption-promoting substances, preservatives, anti- 25 oxidants and 7ight stabilisers.

Le A 29

IF

Carrier homogene Wetting are the 5 Other at mentionec Semi-sob dermally describe To prepaj mixed wi addition the desir Excipient 15 cally tol inorganic are, for calcium cz silicic 20 silicon di

A

Organic si foodstuffs flours, ce Le A 29 48 6c 0 00 0 0 0 Le A 29 484 41 i ~g~llO*M ~i- 6!

"I

I

Le A 29 484 28 ~6~fM-PIM-FO. MlAWSWOM 10 AllB t i CS33 Carrier liquids which may be mentioned are homogeneous solvents and solvent mixtures.

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

Other auxiliaries which may be mentioned are those mentioned above.

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

Le A 29 4E Auxiliari i which hav Other su agents, si 5 acid, ta.

disintegr pyrrolido gelatin o: such as m 10 The activ< tions as compounds i Ready-to-1 Sconcentral i 15 preferabl.

Formulatic Sactive coi by weight In genera 20 amounts o i 20 mg, of in order 1 11

H

To prepare mixed with addition of the desired solid formulations, the active compound is suitable excipients, if appropriate with auxiliaries, and the mixture is brought into form.

Excipients which may be mentioned are all the physiologically tolerated solid inert substances. All such serve inorganic and organic substances. Inorganic substances are, for example, sodium chloride, carbonates, such as calcium carbonate, hydrogencarbonates, aluminium oxides, silicic acids, aluminas, precipitated or colloidal 20 silicon dioxide and phosphates.

Organic substances are, for example, sugars, cellulose, foodstuffs and feedstuffs, such as milk powder, animal flours, cereal flours and crushed cereal and starches.

The activ animals te Le A 29 4 Le A 29 484 42 <1 .17 Le A 29 484

I

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:1 Le A 29 484, 29 c~aa~* uc iIN I ININ~--apli~ IIIII NM Ilm 11- J a~L s;risFmsl *IL i~ Y~4 a44leasP~~ 1

I

I

Auxiliaries are preservatives, antioxidants and dyestuffs which have already been listed above.

Other suitable auxiliaries are lubricants and slip agents, such as, for example, magnesium stearate, stearic acid, talc and bentonites, substances which promote disintegration, such as starch or crosslinked polyvinylpyrrolidone, binders, such as, for example, starch, gelatin or linear polyvinylpyrrolidone, and dry binders, such as microcrystalline cellulose.

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

Ready-to-use formulations comprise the active compound in concentrations of 10 ppm to 20 per cent by weight, preferably 0.1 to 10 per cent by weight.

Formulations which are diluted before use comprise the active compound in concentrations of 0.5 to 90 per cent by weight, preferably 1 to 50 per cent by weight.

In general, it has proved advantageous to administer amounts of about 0.5 to about 50 mg, preferably 1 to mg, of active compound per kg of body weight per day in order to achieve effective results.

Feedstuffs preferably combinatior Such a foo 5 healing pui Such a fee concentrat 1 to 20% b edible org feedstuffs, or maize which pref dust-prevei The premix to the co animals.

Use for coc i; For curing in poultry 20 turkeys, 0.

active coi material, I these amou3 compound ii itttct 25 tion can b( I (i( II II The active compounds can also be administered to animals together with the feed or drinking water.

the Le A 29 48 Le A 29 484 43 F p L.z2 I i

I

i Le A 29 484 30 Le A 29 484 gsiarrsl~lsnaPar~srr~

L-

Feedstuffs and foodstuffs comprise 0.01 to 250 ppm, preferably 0.5 to 100 ppm of the active compound in combination with a suitable edible material.

Such a foodstuff and feedstuff can be sent either for healing purposes or for prophylactic purposes.

Such a feedstuff or foodstuff is prepared by mixing a concentrate or a premix comprising 0.5 to 30%, nreferably 1 to 20% by weight of an active compound mixed with an edible organic or inorganic carrier, with customary feedstuffs. Edible carriers are, for example, maize flour or maize flour and soya bean flour or mineral salts, which preferably contain a small amount of an edible dust-preventing oil, for example maize oil or soya oil.

The premix obtained by this procedure can then be added to the complete feedstuff before this is fed to the animals.

LI

It Ii 1j '1 4 4 4 4 4 4 K4 For the tre the case of toxoplasmos 100 mg/kg c 5 daily in ori less, it ma amounts men body weight administrat 10 genus and i or the natu: at which t] cases it m abovementio 15 upper limit large amour divide thes of the day.

44r 4 It It 4 4r 4 Use for coccidiosis may be mentioned by way of example: For curing and prophylaxis, for example, of coccidiosis in poultry, in particular in chickens, ducks, geese and turkeys, 0.1 to 100 ppm, preferably 0.5 to 100 ppm, of an active compound are mixed with a suitable edible material, for example a nutritious feedstuff. If desired, these amounts can be increased, especially if the active compound is tolerated well by the recipient. Administra- 25 tion can be effected accordingly via the drinking water.

2 Si The compou effective a the helmint 4 l

I

444 .444 4 4( .4 4 Parasites protozoa, example 1 25 cyprini, T spp. of tJ Myxosoma c Heneguya Le A 29 484 Le A 29 484 44 _I I DC--LI ly m m Irsr~~c~ Oil

O

Le A 29 484 31 Le A 29 484 sbcaoa~ls~skoAl ~r~llaa~ ~a ii; rl n r

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"6 ii Ii CI~ Bs*~-CWULII~~~LP~~li--i t For the treatment of individual animals, for example in the case of the treatment of coccidiosis in mammals or of toxoplasmosis, amounts of active compound of 0.5 to 100 mg/kg of body weight are preferably administered daily in order to achieve the desired results. Nevertheless, it may sometimes be necessary to deviate from the amounts mentioned, in particular as a function of the body weight of the test animal or of the nature of the administration method, but also because of the animal genus and its individual reaction to the active compound or the nature of the formulation and the time or interval at which the latter is administered. Thus, in certain cases it may suffice to manage with less than the abovementioned minimum amount, while in other cases the upper limit mentioned must be exceeded. If relatively large amounts are administered, it may be expedient to divide these into several individual doses in the course of the day.

r i) i 1 is i: i a i: -r Microsporid Pleistophor Trematodes; Gyrodactylu 5 spp., Cestc Caryphyllidi Pseudophyll.

Tetraphylli4 Protocephal 10 Pro-teocepha' various pat subclasses (copepods) Amphipoda (i

I

f 44,r The compounds according to the invention moreover are effective against various fish parasites which belong to the helminths (worms).

44 t Itt a 6 I o 4 4n 6 Parasites on fish include, from the subkingdom of the protozoa, species from the phylum of the Ciliata, for example Ichthyophthirius multifiliis, Chilodonella 25 cyprini, Trichodina spp., Glossatella spp., Epistylis spp. of the phylum of the Myxosporidia, for example Myxosoma cerebralis, Myxidium spp., Myxobolus spp., Heneguya spp., Hoferellus spp., of the class of 15 Treatment o example via "medicinal which they several hou 6%*r 20 from one br( However, teri ment of th 0 C aquaria, tar also be car 444014 25 The active c are appropr: LA24 Le A 29 484 Le A 29 484 45 i~arr-~--~pl ~I 1

I

a, 0# a a a a a a Le A 29 48 Le A 29 484 32 Microsporidia, for example Glugea spp., Thelohania spp., V Pleistophora spp., from the phylum of the Plathelminths: Trematodes; Monogenea, for example Dactyloqyrus spp., Gyrodactylus spp., Pseudodactyloqyrus spp., Diplozoon spp., Cestodes, for example from the groups of the Caryphyllidea (for exampi'e Caryophyllaeus laticeps), Pseudophyllidea (for example Diphyllobothrium spp.), Tetraphyllidea (for example Phyllobothrium spp.) and Protocephalida (for example species of the genus Proteocephalus) and, from the phylum of the Arthropoda, various parasitic Crustacea, in particular from the subclasses of the Branchiura (fish lice) and Copepoda (copepods) and the orders of the Isopoda (isopods) and Amphipoda (amphipods).

Treatment of the fish is carried out either orally, for example via the feed, or by short-term treatment, a "medicinal bath", into which the fish are put and in *tit, which they are kept for a certain period (minutes up to several hours), for example when they are transferred a, 20 from one breeding tank to another.

However, temporary or permanent treatment of the environment of the fish (for example entire pond systems, a a c aquaria, tanks or troughs) in which the fish are kept can also be carried out.

a:aaa: 25 The active compound is administered in formul.ations which are appropriate for the applications.

taa ala, a. ae pI~L The concentr tions is 1 p Preferred f application treatment wh the environm tions of the vents which water.

10 To prepare dissolved in gives an alka soluble subsi likewise dis 15 suspended in After additic should have E The concentri range from 0, to Possible sol, which the ac concentratior C C

C,

at a These are e Le A 29 484 Le A 29 484 46 -4

'I

j1 1 I ,mldb mm II. LIY 411 BI~ ll~ l~ blllll~-d- 1 t os 0 Le A 29 484 Le A 29 484 33 a. L-as I, Is oar alll IN In Ilia' allB~ka~"B~~sD"P~ srl8li c. rz2 The concentration of the active compound in the formulations is 1 ppm to 10% by weight.

Preferred formulations for short-term treatment in application as a "medicinal bath", for example for treatment when transferring the fish or for treatment of the environment (pond treatment) of the fish, are solutions of the active compound in one or more polar solvents which give an alkaline reaction on dilution with water.

PB;-

alcohol, gl glycols, pol basic alcohol ketones, such 5 such as etl pyrrolidone, furthermore d polyoxyethyla monooleate, P glycol ether J iBases which alkaline pH a such as L- or glucosamine a and furthermo propyl)-ethylE ethylenediami bases, such a: priate with ad The formulatic preferably 0.' auxiliaries, s sion stabilisE example, meth 25 galactomannans of colour, fl nutrition is system togethe To prepare these solutions, the active compound is dissolved in a polar, water-soluble solvent, which either gives an alkaline reaction or to which an alkaline watersoluble substance is added. The latter is advantageously likewise dissolved in the solvent, but can also be suspended in the solvent and dissolves only in the water.

After addition of the active compound solution, the water should have a pH of 7 to 10, but preferably a pH of 8 to C c CC. 'C IL I 4 4 The concentration range from 0.5 to to 25%.

Possible solvents which the active concentration and 25 These are ethyl of the active compound can be in the 50%, but preferably in a range from 1 are all the water-soluble solvents in compound is soluble in a sufficient which are physiologically acceptable.

alcohol, isopropyl alcohol, benzyl Le-A 29 484 Le A 29 484 47 L" -4 It: INIMMIrl- ",b i,' 4 4~ 44 44 4 4 4 Le A 29 484 Le A 29 484 34 Hf alcohol, glycerol, propylene glycol, polyethylene glycols, poly( oxoethylene) -poly( oxypropylene) polymers, basic alcohols, such as mono-, di- and triethanolamine, ketones, such as acetone or methyl ethyl ketone, esters, such as ethyl lactate, and furthermore N-methylpyrrolidone, dimethylacetamide and dimethylformamide, and furthermore dispersing and emulsifying agents, such as polyoxyethylated castor oil, polyethylene glycol sorbitan monooleate, polyethylene glycol stearate or polyethylene glycol ether and polyethylene glycol alkylamines.

Bases which may be mentioned for establishing the alkaline pH are organic bases, such as basic amino acids, such as L- or D, L-arginine, L- or D, L-lysine, methylglucosamine and 2-amino-2-hydroxymethylpropane-1,3-diol, and furthermore such as N,NN',N'-tetrakis-(2-hydroxypropyl)-ethylenediamine, or polyether-tetrol based on ethylenediamine (molecular weight 480-420), and inorganic bases, such as ammonia or sodium carbonate if appropriate with addition of water.

The formulations can also comprise 0.1 to 20% by weight, preferably 0.1 to 10% by weight, of other formulation auxiliaries, such as antioxidants, surfactants, suspension stabilisers and thickening agents, such as, for example, methylcellulose, alginates, polysaccharides, galactomannans and colloidal silicic acid. The addition of colour, flavour and builder substances for animal nutrition is also possible. Acids which form a buffer system together with the base initially introduced or which reduce t here.

The concentra* depends on the 5 the age and ci example, 2 to water, prefera duration of 3 treatment of y V 10 5 to 10 mg/la are used.

Eels are treat about 4 hours.

For a longer t 15 ment, the con lower.

For pond treatr litre of water Formulations f 20 example, the fc a) Active compounc Soya bean protE b) Active compounc Benzyl alcohol 25 HydroxjpropylmE 4 c t a t Le A 29 484 Le A 29 484 48 t I :3 C C C C 0r Le A 29 484 Le A 29 484 35 s~L~1 which reduce here.

the pH of the solution may also be mentioned The concentration of the active compound during use depends on the nature and duration of the treatment and the age and condition of the fish treated. It is, for example, 2 to 50 mg of active compound per litre of water, preferably 5 to 10 mg per litre, over a treatment duration of 3 to 4 hours for short-term treatment. For treatment of young carp a concentration of, for example, 5 to 10 mg/l and a treatment time of about 1 to 4 hours are used.

Eels are treated with concentrations of about 5 mg/l for about 4 hours.

For a longer treatment duration or for long-term treatment, the concentration chosen can be correspondingly lower.

For pond treatments, 0.1 to 5 mg of active compound per litre of water can be used.

Formulations for use as a feed additive have, for example, the following composition: a) Active compound of the formula I 1 10 parts by weight Soya bean protein 49 90 parts by weight b) Active compound of the formula I 0.5 10 parts by weight Benzyl alcohol 0.08 1.4 parts by weight Hydroxrpropylmethylcellulose 0 3.5 parts by weight sa w sl' Water Formulations f treatment have and are preparE 5 c) 2.5 g of acti% 100 ml of trie d) 2.5 g of activi 12.5 g of lacti while heating 10 e) 10.0 g of acti 100 ml of mono( f) Active compouw Propylene glyc Sodium carbonal 15 Water InCtt 0 0* 4 C 4*CC 0 ,20 O CC 00 00 00c 00 0 ~ct g) Active compoun Monoethanolami.

N-Methylpyrrol.

h) Active compoun Sodium carbonal Polyethylene g: The active coi glycol, while 1 therein.

C

C1lC 04 CC O '4 00 0 Le A 29 484 Le A 29 484 49 l r

I

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i Le A 29 484 36 "aamea~rs~laaspa(patr~s~ saarP4lslss~asr n~- 1- -i Water remainder to 100 Formulations for use in "medicinal baths" and for pond treatment have, for example, the following composition and are prepared as follows.

c) 2.5 g of active compound of the formula are dissolved in 100 ml of triethanolamine, while heating.

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

triethanolamine, is dissolved in e) 10.0 g of active compound of the 100 ml of monoethanolamine.

formula (I) tt tri i2 cc

I

I o ir oI S

S

f) Active compound of the formula I Propylene glycol 50.0 Sodium carbonate Water to 100 g) Active compound of the formula I Monoethanolami4ne N-Methylpyrrolidone to 100 h) Active compound of the formula 1 Sodium carbonate Polyethylene glycol 200 to 100 The active compound is dissolved in the polyethylene glycol, while heating, and sodium carbonate is suspended therein.

Le A 29 484 50 lop we 4 -I

I;

i Le A 29 484 37 'w 4 Examle A Cocci Coccidiosis in chickens Chicks 9 to 11 days old were infected with 40,6t) sporulated oocysts of highly virulent strains of Eimeria acervuline, E. maxima and E. tenella, the pathogens of intestinal coccidiosis.

3 days before the infection and 8 days after the infection (end of the experiment), the active compound was administered in the stated concentration as a mixture in the feed of the animals.

The number of oocysts in the faeces was determined with the aid of the McMaster chamber [see Engelbrecht and colleagues "Parasitologische Arbeitsmethoden in Medizin und Veterinarmedizin" (Parasitological working methods in medicine and veterinary medicine), page 172. Akademie- Verlag, Berlin (1965)].

The active compound doses and excretion of oocvsts in are stated for the individual pathogens in the following Table. In this Table, 100% denotes no action and 0% denotes a complete action, that is to say no excretion of oocysts.

Le A 29 484 51

I

4 L A Le A 29 11 p Le A 29 484 -3 38 4, 4 p Table 1 Coccidiosis in chickens Example No.

Dose

PPM

E .acervulina Excretion of oocysts in in comparison with the untreated infected control E. maxima Excretion of oocytes in in comparison with the non- 0 infected untreated control E. tenella Untreated infected control 0 100 100 100 37 250 0.5 0 0 100 28 26 32 250 0.1 0 0 100 11 8 57250 100 0.01 0 0 38 5.3 93 Le A29 484 52carbama reiflux cooled 10 washed trated t c t1 T tt t t phas s: trif luo: c arbamal 14CC

C

#414 I. Ci C C I 4 C C C CC (C Le A 29 ~Db- 1-- 44 Le A 29 484 39 rzs~ Preparation Examples: Example 1: Br

N

F

3 C

N

/l C( JOCH~ A mixture of 9.0 g (0.03 mol) of 4-bromo-2-cyano-6-trifluoromethyl-1I--benzimidazole (compare, for example, EP 239 508), 8.3 g (0.06 mol) of potassium carbonate, 4.2 g (0.03 mol) of methyl N-chloromethyl-.N-methylcarbamate and 105 ml of ethyl acetate is heated at the reflux temperature for 4 hours. For working up, the cooled reaction mixture is filtered and the filtrate is washed with water, dried over sodium sulphate and concentrated in vacua. The residue can be purified by recrystallisation from ether/petroleum ether (1:10) and subsequent column chromatography over silica gel (mobile phase: methylene chloride).

'4 I I

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NO.

2 3 4 10 The f ol.

f ormula accor

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t t~

I

itti I t C St 6.0 g (51% of theory) of methyl N-(4-bromo-2-cyano-6trifluoromethyl-lH-benzimidazol-1-yl-methyl) -N-methylcarbamate of melting point 138-141C are obtained.

so (r{ ''It

I

4' St I

S

I t 'sot

(C

'I,

Le A 29 Le A 29 484 53 polo-

I

1K

I

-t Le A 29 41 Le A 29 484 p The following substituted benzimidazoles of the general formula are obtained in a corresponding manner and in Example No.

9 45 11 4 12 accordance with preparation: the general information regarding '-he 2

N

I ~CN x x4

A

X1 x 2 Vx x Example No.

Physical properties 2 H NO 2 H H CAH

(NO

2 -01Z CO0{,3 3 H NO 2 H H

(NO

2 4 H NO 2 H H Cii,

(NO

2

)I

H NO 2 H H H 2

H

(NO

2 6 H NO 2 H H H- 3

H

(NO

2 ciiic00c 1 11 7 H NO 2 H H H1-CH 'N0 2 8 Br H CF 3 H C2% 1a 2 cfO~ Mv.P. 120- 121 0

C

(69:31) M.P. 99- 102 0

C

(65:35) Mv.P. 92- 96 0

C

(59 :41) Mv.P. 65- 70 0

C

(59 :41) 6.0; 6.05 (72: 28) Mo.P. 78- 82 0

C

M.P. 107- 110 0

C

o 0001 o 4 1 '@44 @044 0004 0* 4 *4 o @1 004 4 @0 00 @0 1 o 0 @0 0 0 4~4400 0 040*0@ o 0 0 0 44404 44* 00 @0 0 0 0 01*1 0040 00 @4 00 4 0 4 Le A 29 Le A 29 484 54 /1 p Le A 29 484 L 94~ 41 Le A 29 484 e

I

I

I)

Li Example No.

Physical Example

NO.

22 properties 9 Br H CF 3

H

H CF_ 3 H Br ;l 11 Br H CF 3 H C2-4

-CH

2 cooqC 12 Br H CF 3 H c 2

H

5 -012 COO4H 13 Br H CF 3 H nCH cnH acXuH 14 H NO 2 H HCI1

(NO

2 -a'2 Coai 5 Br H CF 3 H -CH 2

-COOCH

3 16 Br H CF 3 H -CH 2

-COOC

2

H

5 1H-NMR*): 6.03 H.p. 163- 168 0

C

M.P. 110- 113 0

C

H.p. 84- 87 0

C

lH-NM1R*): 6 .02 H.p. 127- 131 0

C

(65: 31) H.p. 160- 163 0

C

M.p. 113- 117 "C H.p. 105- 108 0

C

17 Br H CF 3

H

00 4 t

-CH

\COOCH

3 00 or 000 18 Br 19 Br

H

H

0004*0 0 0 0000*0 0 0 ,0.0 0 0 0..~oh 0,0 00 0 0 0 0

CF

3 H -CH 2

-NH-COOCH

3 205- 208 0

C

CF

3 H -CH 2 -CN H.p. 157- 160 0

C

g02 H H II3 H.p. 87- H) (O)91 0

C

COCH3 (57: 43) M0O2 H H -CH 2

-COOC

2

H

5 H.p. 96- H) (NO 2 100 0

C

55- 000000 080000 0 0000 0000 0* 00 00 .6 6 0t0 I 1 Le A 29 484 Le A 29 4E L~zr~-~ I Le A 29 484 L 94 Le A 29 4R 42

L

t Example

NO.

X1 x 2 x Physical properties H NO 2

H

(N0 2 H -CHZ-COOCH 3 23 Br H CF 3 N (CFA) (Br) M.p. 141-.

143 0

C

1) M.p. 154- 1570 C (63: 37) 1 4 212- 217 0

C

Example No.

36 24 Br H CF 3

H

0

O~N~Q

Br H CF 3

H

(CF3) (Br) -c

IH-CH=CH

2 N.p. 99 OC (78:22)

-CH

2 -CN 14.p. 170- 172 0

C

H CF, H Br 27 Br H CF 3

H

(CFA) (Br) 'iT2 j-'Q 28 Br H CF 3

H

(CF

3 (Br)

-CH

2

-C

6

H

5 t c1 29 Br H CF3 H -CH 2

-COOH

Br H CF 3 H CH 31 Br H CF 3 H C2CCH as 'rooqc, 33 Br H CF 3

H

(CFA) (B3r) -c -N M.P. 147- 150 0

C

(86:14) Mv.P. 140- 143 0

C

(95:5) Mv.P.

>195 0 C (Li) M.P. 83- 86 0

C

M.P. 90- 93 0

C

M4.P. 97- 101 0

C

Mv.P. 120- 123 0

C

(84: 16) M.P. 101- 105 0

C

6##t o CI 4 'It' 461; 4 4 3Br 44 44 41 4 1

S

#641 *4 C *44811 044111

S

6450 0 1 44 #4 4 1 34 Br H CF 3

H

0*, 04 II #4 1 0464 64 4 444

~II

4 4 441$ 0 4 #444 44 46 44 4

I

i

L

Le A 29 484 56

I

I_ Le A 29 48,

I

I

Le A 29 484 Le A 29 484 43

I

I

p 1 1 L 2 V VA Physical 35 Br H CF H N properties Example No.

(CFA) (Br) -N 36 Br H CF 3 H a~CH 37 Br H CF 3 H uCH 38 Br H CF 3

H

-G C fOH 39 Br H CF 3 H iCH -ax Oi2COH3 Br H CF 3 H CH 3 CHi, CO-H 41 Br H CF 3 H -O-n-C 3

H

7 (CFA) (Br) 14.p. 160- 163 0

C

'-H.NMR*)

6.11 Example K No.

48 I 49 5 51 K 52 1

H-NNIR

4 5.94 1 H-NMiR*): 6.06 Mv.p. 86- 0

C

I4I4. 137- 140 0

C

M.p. 105- 109 0

C

(86:14) 5.98; 6.06 (53: 47) M.p. 73- 76 0

C

(53:47) M.p. 78 0

C

(36: 64) 1

H-NMR*

3 6.49 42 Br H CF 3

H

(CFA) (Br) o 0C4* a 44 4 4 0t~ 0*44 o i 0 4C 04 3 H7

-O--CH

2

-C=CH

4 313r H) H CF 3

H

(CF

3 (.Br) 44 Br H CF 3

H

(CF?

3 (Br) Br H CF 3 H -CH 2 -O-CO-t- (CFA) (Br) C 4 H9 44 ft 04 C 4 0404 44 04 4 46 Br H CF 3

H

(CF

3 (Br)

C

5 H5 (66: 34)

H-NMR*):

5.96; 6.05 M.p. 175- 180 0

C

c L c 59 004401 15 47 Br H CF 3 H 0 0 11 HI .1 4414 4 4 ~4 4* 44 S O 4

CC

4 C 4CCC tC CC

IC

I

C

Le A 29 484 57

I

Le A 29 484 Le A 29 484 44

I

CA,

Example X1' 2 x3 x A Physical No. properties 48 Br H CF 3 H Ii 4 lH-NMR*):

(CF

3 (Br) 6.03 ~~(76:24) 49 Br H CF 3 H C46H M.P. 930 Example Br H CF 3

H

51 Br H CF 3

H

(CF

3 (Br) 52 Br H CF 3

H

(CFA) (Br) 53 Br H CF 3

H

54 Br H CF 3

H

(CFA) (Br) -ai, COa{R

QI

n-C 3

H,

-Qilz coocAS M.p. 105- 108 0

C

M.p. 86- 90 0 c (81:19) lH-1NMR*): 5.95; 6.35 (80:20) lH-NM1R*): 6.05 lH-NI4R*) 5.95 (76:24) 5.95; 6.35 (72:28) Mv.p. 115- 120 0

C

Mv.p. 112- 116 0

C

14.p. 135- 140 0

C

1.p. 173- 176 0

C

M.p. 40 0

C

Br H CF 3 H n-CqH7

(CF

3 (Br) -c z ooq4Hf 56 Br H CF 3 H 14PH 57 Br H CF 3 H CIC 58 Br H CF 3

H

59 14 H CF 3 H -O-C 2 Hs 69 HI 70 H 71 H 72 H 73 H 74 H

CC

CL

C

C C (C 4

(C

C C CC (C

C

15 60 H H CH-CF 2 0-

-O-C

2

H

5

CC

C C Le A 29 484 Le A 29 484 58

A

I.

I

I

I

1~ Le A 29 484 Le A 29 484 45 Example XI X A Physical No. properties 5.91 Example X1 No.

75 H 76 H 5 77 H 78 H The deutero suiphox 10 as the

N-CH

2

-N-

62 H CH 5

H

(CAH)

63 H (CH 2 2 -0- 64 H (CH2) 2 -0- H -O-CF 2 -CFC1- 0- (-0-CFC1.-

CF

2 66 H -0-CF 2 -CFC1- 0- (-O-CFC1-

CF

2

O-)

67 H -0-CF 2 -CFC1- 0- (-0-CFC1-

CF

2 68 H -O-CF 2 -CFC1- 0- (-0-CFC1-

CF

2 69 H -O-CF 2 -CFC1- 0- (-0-CFCl-

CF

2 H -O-CF 2

-CF

2 -0- 71 H -0--CF 2 -CF2-0- 72 H -O-CF 2

-CF

2 -0- 73 H -O-CF 2

-CF

2 -0- 74 H -0-CF 2

CF

2

-O-

H -0-C 2 H5 'H-NMR*): 5.87; 5.92 H -0-C 2 HS H.p. 150- 151 0

C

H H~ 162- N 164 0

C

H

4 =coo, H.p. 127- 13O0 H -0-C 2

H

5 H.p. 96- 10C 1) -CHl 0cA~cH 1C', a-C L Ocr-,

,NCH

1

H-NMR*):

5.91 M.p. 130- 133 0

C

H.p. 62- 66 0

C

-0-C 2

H

5 M.P. 90- 93C 44 0445 4 4* 4 4 4,44 44*1 4 4 4444 4 4 t~ 4 44 444 44 44 44 C 4 .44.

H -CH 2

(C"

2 2

OCH

3

H,

-a{H2 COOCA~ H.p. 140- 144 0 M p. 60- 64 0

C

H.p. 53- 57 O H.p. 123- 125 0

C

4444 *4 4 4 4 4441*4 44., 4 4 444.

44 44 44 4 4 Le A 29 484 Le A 29 484 59 K -~p Le A 29 484 Le A 29 484 46 r7 2

I

Example No.

X1 x Physical properties H -O-CF 2

-CF

2 76 H -O-CF 2

-CHF-O.-

77 H -O-CF 2

-O-

78 H -O-CF 2 H CH -c~coocili H -O-C 2

H

5 H -O-C 2 Hr, M.P. 73 0

C

M.P. 0

C

M.P. 110- 113 0

C

M.P. 147- 150 0

C

Preparation c Example 11-1: -c2 coc The 1 H-NMR spectra deuterochioro form (CDCl 3 were recorded in or hexadeutero -dimethyl sulphoxide (DMSO-d 6 using tetramethylsilane (TMS) as the internal standard. The chemical shift of the

N-CH

2 grou7- is stated as the value in ppm.

A solution o methyl-6-trif 5 example, EP dropwise to 9 at 15C to ended, the mi: hour. For wor pH 1 with acid and extz chloride each with sodiumg oil which re 15 silica gel

(M

and crystallil o 55 e a I 5,4' at,, o 4 aat4

S

as

C

a. .a a a 4 a a a a. a a S a 4 sass a S

S

a. as S S 4 a S 4 4 t 9 t I 49.1 g methyl- lH-ben obtained.

Le A 29 484 60

I

L

Le A 29 484

II

LeA2 8 ~~Le A 29 484 The f olli Preparation of the startingr compounds: generlf Example II-i: Br

N

K

-CN

-~N

H

Example

NO.

A solution of 120 g (0.3 mol) of 4-bromo-2-trichloro- 11-2 methyl-6-trifluoromethyl-1H-benzimidazole (compare, for 1example, EP 239 508) in 300 ml of ethanol is added 1dropwise to 900 ml of saturated aqueous ammonia solution at 15C to 25C, while stirring, and, when the addition has 11-4 ended, the mixture is stirred at room temperature for one 1hour. For working up, the reaction mixture is brought to pH 1 with 4000 ml of 20 per cent strength hydrochloric acid and extracted three times with 300 ml of methylene chloride each time. The combined organic phases are dried 1with sodium sulphate and concentrated in vacuo and the oil which remains is purified by chromatography over 11-8 silica gel (mobile phase: cyclohexane/ethyl acetate 2:1) 1and crystallisation from petroleum ether.

I 11-10 494 J.1 g (55 of theory) of 4-bromo-2-cyano-6-trifluoro- 15 11-15 methyl-1H-benzimidazole of melting point 130-134C are obtained. Y711-12 a 2 Le 2948 Le-4 29 4816 £0 (0 9 0 0 Le A 29 484 Le A29 484 48

I

r- The following substituted 1H-benzimidazoles of the general formula (II) are obtained in a corresponding manner: x x 2

(II)

V Physical properties Example

NO.

00 o oio~ 9 9 10 00 Ott 10'.

9 00 9 Os 909 11-2 11-3 11-4 11-5 11-6 11-7 11-8 11-9 11-10 11-11 11-12 H -O-CF 2 -CFCl-O- (-O-CFC1-CF 2 -0-CF 2

-CF

2

-O-

H

(CF

3

H

(C

2

H

5

-O-

(F

2

CH-CF

2

-O-

CF

3

(H)

C

2

H

5

-O-

(H)

F

2

CH-CF

2

-O-

(H)

N0 2 H M. P.

>240 0

C

H M. P.

>230 0

C

H M. P.

>230 0

C

H 173- 176 0

C

H M4.P. 86- 90C H M.P. 130- 132 0

C

H Mv.P. 194- 198 0

C

H M. P.

>2 30 0

C

H M. P.

>230 0

C

H Mv.P. 60 0

C

H M. P.

>220 0

C

H

H

-4

I

~0Q 9900 0000 9 4 0*00 90 0 O 0* 9 00 0 0 0 09 #0 0 90 0 09* 0 4 0 *0 09 9 4 00 0 090 0 0.0400 00 9*90 which comprisE thereof, an el benzimidazole The claims 1 A H CF 3

CF

3 09 91 H C 6 H.9

(C

6

H

5 j) (H)

(CH

2 3 -0- -0-CF 2

-CHF-O-

(-O-CHF-CF

2

-O-CF

2 i tt t c 0991 9 9 0919 99 (0 0 A 0 0 Le A 29 484 62

I

Ii

P

Claims (5)

1. A method of combating parasitic protozoa which comprises applying thereto,-or to a habitat thereof, an effective amount of a CN-substituted benzimidazole of the formula (I) IT 00 Il :00 0*0* 0000 .1 0000 <0 0 0 1100 0 <00 0 ~~OOi 0 f~O 00 4 0 0 000 0 0000 01 100001 C I En which X1, X 2 X' and each case rE nitro, orj substituted al1kyl su lphin representI dioxyalkylen alkylcarbony. oxycarbonyl, substituted in each cE aryloxy, ary] arylsulphonyj azylazo or ai but wherein C- X 2 X 3 and X 4 i., and wherein R1 represents hy( optionally sub., R 2 represents hyd: each case optic alkinyl, alk alkylthio, antin alkylcarbonylo~x aryl, (hetero carbonyl, I (he tero) arylami 00 0 00 0 0000 3 N x 2' R R t i V 63 I 4 S. o 0 1 I Le A 29 484 50 En which X1, X 2 X3 and V 4 independently of one another in each case represent hydrogen, halogen, cyano or nitro, or represent in each case optiontilly substituted alkyl, alkoxy, alkylilio, alk-ylsuiphinyl, alkylsuiphonyl or cycloalkyl. or represent optionally substituted, fused-on dioxyalkylene, or represent hydroxycarboiiyl, alkylcarbonyl, alkoxycarbonyl or cycloalkyl- oxycarbonyl, or represent in each case optiontally substituted amino or aminocarbonyl, or represent in each case optionally substituted ar~yl, aryloxy, arylthio, arylsuiphinyl, arylsulphoriyl, aryl sulphonyloxcy, arylcarbonyl, aryloxyc arbo nyl, azylazo or arylthiomethylsulphonyl, but wherein at least one of the substituents x', X 2 X-3 and X 4 is other than hydrogen and halogen, and wherein feet: 0 0 0 R~represents hydrogen or alkyl, optionally substituted aryl and or represents rersnshdoy or cyano, or represents in each case optionally substituted alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, amino, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, dialkoxyphosphoryl, (hetero) aryl, (hetero) arylcarbonyl., (he tero) aryloxy- carbonyl, (hetero).arylcarbonyloxy or (he tero) arylatinocarboniylamLnocarbonylox 64 I I 'U' 0s (C 8 C Le A 29 484 51 p c UI-PPIUh-~U-~~ i "-g k I,

2. The method according to claim 1, in which -:i i i ii ii:: ii i I r! (D -C or a ra o a I I r o D I e a or r X 1 X 2 X 3 and 3 4 independently of one another in each case represent hydrogen, fluorine, chlorine, bromine, iodine, cyano or nitro, or represent in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsuiphinyl or alkylsuiphonyl having in each case 1 to 8 carbon atoms, or repr2sent cycloalkyl having 3 to 8 carbon atoms, or represent in each case straight-chain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoal.kylsulphinyl or halogenoalkylsuiphonyl having in each case 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms, or represent divalent dioxyalkylene having 1 to 5 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen and straight- chain or branched a1 7 yl having 1 to 4 carbon atoms and straight-chain oc branched halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms, or furthermore represent hydroxycarbonyl, or represent in each case straight-chain or branched alkylcarbonyl or alkoxycarbonyl having in each case 1 to 6 carbon atQms in the alkyl moity, or represent cycloalkyloxycarbonyl hanving 3 to 8 carbon atoms in the cycloalkyl moiety, or represent amino or aminocarbonyl, in each case optionally mono- or Ii I; C ;I t i 04 00 8 I 800 8 Cr I, polysubstil selected f3 in each ca: carbon ator to 13 halo each case moieties, o arylmethylE in the ar) polysubstil substituer being thosE or furth( arylsuiphir aryloxycarl each case E case option identical c the aryl hereinbelo but whereir is other t- ocs o a I r II o a a C. 0, i .44* 4* *1 4£ 4 4 f 4t;4t Le A 29 Le A 29 484 52 L. CI C i: jd E;1 Y xi. iii a 1 *44*" '4 a 4£ 4 44 polysubstituted by identical or different substituents selected from the group consisting of in each case straight-chain or branched alkyl having 1 to 6 carbon atoms, halogenoalkyl having 1 to 6 carbon atoms and 1 to 13 halogen atoms, alkoxyalkyl or alkylcarhonyl having in each case 1 to 6 carbon atoms in the individual alkyl moieties, or arylcarbonyl, arylsulphonyl, arylaminocarbonyl or arylmethylsuiphonyl having in each case 6 to 10 carbon atoms in the aryl moiety and in each case optionally mono- or polysubstituted in the aryl moiety by identical or different substituents, optional substituents on the aryl in each case being those mentioned for RI hereinbelow, or furthermore represent aryl, aryloxy, arylthio, arylsuiphinyl, arylsulphonyl, arylsuiphonyloxy, arylcarbonyl, aryloxycarbonyl, arylthiomethylsulphonyl or arylazo having in each case 6 to 10 carbon atoms in the aryl moiety and in each case optionally mono- or polysubstituted in the aryl moiety by identical or different substituents, optional substituents on the aryl in each case being those mentioned for R 1 hereinbelow, but wherein at least one of the substituents X, X 3 and X 4 is other than hydrogen and halogen, and wherein RI represents] alkyl havin is optiona" different s halogen, cyi alkyl, alkc having in straight-ch halogenoa halogenoalk and 1 to 13 straight-ch too. alkanoyl, a case 1 to divalent di optionally substituent straight-ch and straigI carbon atom or phenyl identical c consisting having 1 t halogenoal] j 7 66 i: j r kb~~" (C C C .44 44 44 4 Le A 29 4 Le A 29 484 53 -I 21 I-- R 1 represents hydrogen, or represen' 3 straight-chain or branched alkyl having 1 to 8 carbon atoms, or represents phenyl which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of or differen C. 4, 4 44 .O 4 halogen, cyano, nitro, in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsuiphinyl or alkylsulphonyl having in each case 1 to 6 carbon atoms, in each case straight-chain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsulphinyl or halogenoalkylsulphonyl having in each case 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms, in each case straight-chain or branched alkoxyalkyl, alkoxyalkoxy, alkanoyl, alkoxycarbonyl or alkoximinoalkyl having in each case 1 to 6 carbon atoms in the individual alkyl moieties, divalent dioxyalkylene having 1 to 5 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen and straight-chain or branched alkyl having 1 to 6 carbon atoms and straight-chain or branched halogenoalkyl having 1 to 6 carbon atoms and 1 to 13 identical or different halogen atoms, or phenyl which is optionally mono- or polysubstituted by identica.l or different substituents selected from the group consisting of halogen and straight-chain or branched alkyl having 1 to 6 carbon atoms and straight-chain or branched halogenoalkyl having 1 to 6 carbon atoms and 1 to 13 identical H. ,,l *I C *4

4.4 R 2 represents alkinyl, alkylcarbon dialkoxyphoE the individi each case op different sL halogen, st carbon atomE optionally m substituents mentioned fo R 2 furthermore optionally m substituents straight-cha straight-cha cycloalkyl I alkylthio-cai thiocarbonyl individual I L

67- L" r ,z.z a~srr~lrse~8~u~o~kRP~~ Ir~i .1 1 4 4 *r C I Le A 29 484 54 II I i X or different halogen atoms, and 4,o I f 1 .0,4' 4 K 4 Ii R 2 represents hydroxyl or cyano, or represents alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkoxyphosphoryl having in each case up to 8 carbon atoms in the individual alkyl or alkenyl or alkinyl moieties and in each case optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, straight-chain or branched alkoxy having 1 to 8 carbon atoms or aryl having 6 to 10 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents, optional substituents on the aryl being those mentioned for R 1 or R 2 furthermore represents amino or aminocarbonyl, in each case optionally mono- or disubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkyl having 1 to 8 carbon atoms, straight-chain or branched alkenyl having 2 to 8 carbon atoms, cycloalkyl having 3 to 8 carbon atoms, alkoxycarbonyl, alkylthio-carbonyl, alkoxythiocarbonyl or alkylthio- thiocarbonyl having in each case 1 to 8 carbon atoms in the individual straight-chain or branche alkyl moieties, Le A 29' divalent, cyc atoms in the each case 6 t appropriate, branched alk' polysubstitut optional sub: mentioned foz R 2 furthermore i arylcarbonylc each case 6 t toot .iC case optiona different sul each case be: R 2 furthermore heteroarylox, arylaifiinocarl carbon atoms the heteroar polysubstitu- optional sub substituents I I1 3. Th 68 r P d~ ~li- i~8 POW ~a 1- -1 i i 0 0 i i Le A 29 484 55 I 0rc0 Le? A 29 4E -;l-i-i II: i i-I Ii. liii; divalent, cyclic alkanediyloxycarbonyl having 2 to 6 carbon atoms in the alkanedlyl moiety, or arylalkyl or aryl having in each case 6 to 10 carbon atoms in the aryl moiety and, where appropriate, 1 to 6 carbon atoms in the straight-chain or branched alkyl moiety and in each case optionally mono- or polysubstituted by identical or different substituents, optional substituents on the aryl 4.n each case being those mentioned for R 1 or R2 furthermore represents aryl, arylcarbonyl, aryloxy-carbonyl, arylcarbonyloxy or aryl minocarbonylaminocarbonyloxy having in each case 6 to 10 carbon atoms in the aryl moiety and in each case optionally mono- or polysubstituted by identical or different substituents, optional substituents on the arylin each case being those mentioned for R 1 or rt east *44554 0 Ce beot S Se -1 x 2 X 3 and X 4 ir hydrogen, f1 represent ix alkoxy, alky' each case 1It 3 to 7 carbor or branched h: halogenoalky. each case 1 different ha: having 1 to hexasubstitu selected fro chain or br straight-cha: atoms and 1 further reprE straight-cha: havinq in eac or represent in the cycloa in each case different sut furthermore represents heteroaryl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylcarbonyloxy or hetero- arylaiiinocarbonylaminocarbonyloxy having in each case 2 to 9 carbon atoms and 1 to 5 identical or different hetero atoms in the heteroaryl moiety and in each case optionally mono- or polysubstituted by identical or different substituents, optional substituents on the heteroaryl in each case being the substituents on the aryl mentioned for R 1 in each case carbon atoms, 3. The method accord:..g to claim 1, in which 69 Ba~BP~si~L~-gapaP~lpas~l~a~ -~,oil I~ 1~3 IIP~q~C)~--dl I L--~lu*~rwr~ *o 900* 0 *404 I- Ir Le A 29 484 56 I, Le A 29 48. XA, X 2 X 3 and X 4 independently of one another in each case represent hydrogen, fluorine, chlorine, bromine, cyano or nitro,, or represent in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsuiphinyl or alkylsuiphonyl having in each case 1 to 6 carbon atoms, or represent cycloalkyl having 3 to 7 carbon atoms, or represent in each case straight-chain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsulphinyl or halogenoalkylsulphonyl having in each case 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms, or represent divalent dioxyalkylene having 1 to 4 carbon atoms which is optionally mono- to :hexasubstituted by identical or different substituents 0000 selected from the group consisting of halogen and straight chain or branched alkyl having 1 to 4 carbon atoms and 444 straight-chain or branched halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms, or further represent hydroxycarbonyl, or represent in each case 00 uI straight-chain or branched alkylcarbonyl or alkoxycarbonyl havinq in each case 1 to 4 carbon atoms in the alkyl nfoiety, or represent cycloalkyloxycarbonyl having 3 to 7 carbon atoms in the cycloalkyl moiety, or represent amino or aminocarbonyl, in each case optionally mono- or disubstituted by identical or different substituents selected from the group consisting of in each case straight-chain or branched alkyl having 1 to 4 carbon atoms, halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 halogen each case 1 moieties, or a arylmethylsul aryl moiety pentasubstitu substituents, being those m or furthern arylsulphinyl aryloxycarbon each case 6 t case optional by identical on the aryl i but wherein a is other than 00 0 0 Rl represents hy alkyl having is optionall different su: 70 Luusli~asi~si~ Yri--P~i 44.4 4 #44 (4 44 4' 1 o 44 44 4L I Le A 29 484 57 Le A 29 484 iII- -e itcoa~ to 9 halogen atoms, alkoxyalkyl or alkylcarbonyl having in each case 1 to 4 carbon atoms in the individual alkyl moieties, or arylcarbonyl, arylsulphonyl, arylaminocarbonyl or ar~ylmethylsulphonyl having in each 6 to 10 carbon atoms in the aryl moiety and in each case optionally mono- to pentasubstituted in the aryl moiety by identical or different substituents, optional substituents on the aryl in each case being those mentioned for R 1 hereinbelow, or furthermore represent aryl, aryloxy, arylthio, arylsulphinyl, arylsulphonyl, arylsuiphonyloxy, arylcarbonyl, aryloxycarbonyl, aryithiomethylsuiphonyl or arylazo having in each case 6 to 10 carbon atoms in the aryl moiety and in each case optionally mono- to pentasubstituted in the aryl moiety by identical or different substituents, possible substituents on the aryl in each case being those mentioned for R 1 but wherein at least one of the substituents X 1 X 2 X 3 and X 4 is other than hydrogen and halogen, and wherein .4 1 4 44i 4. 04 4 halogen, cyan alkyl, alkox3 having in ez straight-chai halogenoal: halogenoalkyl and 1 to 9 id( straight-chai alkanoyl, alk case 1 to 4 divalent diox optionally mor substituents s straight-chair and straight-( carbon atoms a or phenyl whi identical or c consisting of having 1 to 4 halogenoalkyl or different h represents hyd alkinyl, alk alkylcarbonyl, R 1 represents hydrogen, or represents straight-chain or branched alkyl having 1 to 6 carbon atoms, or represents phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of 71 a"Mur 1 1, 1 l4 i~ i a ii, S1' 4 9(C 4 491 Le A 29 484 58 K-. Le A 29 484 I SI, 9* 99S 90r 9 9* 9 halogen, cyano, nitro, in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsuiphinyl or alkylsuiphonyl having in each case 1 to 4 carbon atoms, in each case straight-chain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsuiphinyl or halogenoalkylsulphonyl having in each case 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms, in each case straight-chain or branched alkoxyalkyl, alkoxyalkoxy, alkanoyl, alkoxycarbonyl or alkoximinoalkyl having in each case 1 to 4 carbon atoms in the individual alkyl moieties, divalent dioxyalkylene having 1 to 4 carbon atoms which is optionally mono- to hexasubstituted by identical or different substituents selected from the group consisting of halogen and straight-chain or branched alkyl having 1 to 4 carbon atoms and straight-chain or branched halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms, or phenyl which is optionally mono- to pentasubstituted by identical or different substituents selected from the group consisting of halogen and straight-chain or branched' alkyl having 1 to 4 carbon atoms and straight-chain or branched halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 identical or different halogen atoms, and represents hydroxyl or cyano, or reprsents alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkoxyphospho the individual each case optior different halo alkinyl, alkc alkylcarbonyl, dialkoxyphosphc the individual each case optic different subsi straight-chain or aryl having 0 to trisubstitt i optional subst, R ,or i:R2 furthermore re I j 9.99.9 optionally monc substituents s( straight-chain straight-chain cycloalkyl haN alkylthio-carb thiocarbonyl h; 72 C CC C *o C Le A 29 484 59 Le A 29 484 i I i- r- -iii-- i :B i. i !I ii i: j '4 'd jl r rt As A dialkoxyphosphoryl having in each case up to 6 carbon atoms in the individual alkyl or alkenyl or alkinyl moieties and in each case optionally mono- to pentasubstituted by identical or different halogen atoms, or represents alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkoxyphosphoryl having in each case up to 6 carbon atoms in the individual alkyl or alkenyl or alkinyl moieties and in each case optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkoxy having 1 to 6 carbon atoms, or aryl having 6 or 10 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents, optional substituents on the aryl being those mentioned for R 1 or furthermore represents amino or aminocarbonyl, in each case optionally mono- or disubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkyl having 1 to 6 carbon atoms, straight-chain or branched alkenyl having 2 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, alkoxycarbonyl, alkylthio-carbonyl, alkoxythiocarbonyl or alkylthio- thiocarbonyl having in each case 1 to 6 carbon atoms in the A, A2 *s C A. *s A *s A C4) A A *CCCr A A A A. AZ individual sti divalent, cycli atoms in the all each case 6 to appropriate, 1 branched alkyl trisubstituted optional substi mentioned for R furthermore rep arylcarbonyloxy each case 6 or I case optionally different subst: eaci case being furthermore r( heteroaryloxy( heteroarylaminoc 2 to 9 carbon at atoms in the he mono- to pent substituents, or case being the s *AAAAA 73 1 4* f 4 4444l 44 4* 4 4 4IS 44( .4 E .4 4 Le A 29 484 60 Le A 29 484 I I 'C i i .4, *4 4 44 S 4 4. 4 4 *r 44 *44C individual straight-chain or branched alkyl moieties, divalent, cyclic alkanediyloxycarbonyl havinq 2 to 5 carbon atoms in the alkanediyl moiety, or arylalkyl or aryl having in each case 6 to 10 carbon atoms in the aryl moiety and, where appropriate, 1 to 6 carbon atoms in the straight-chain or branched alkyl moiety and in each case optionally mono- to trisubstituted by identical or different substituents, optional substituents on the aryl in each case being those mentioned for R 1 or furthermore represents aryl, arylcarbonyl, aryloxycarbonyl, arylcarbonyloxy or arylamiiocarbonylaminocarbonyloxy having in each case 6 or 10 carbon atoms in the aryl moiety and in each case optionally mono- to pentasubstituted by identical or different substituents, optional substituents on the aryl in eaci case being those mentioned for R 1 or furthermore represents heteroaryl, heteroarylcarbonyl, hetefoaryloxycarbonyl, heteroarylcarbonyloxY- or heteroarylaminocarbonylaminocarbonyloxy having in each case 2 to 9 carbon atoms and 1 to 4 identical or different hetero atoms in the heteroaryl moiety and in each case optionally mono- to pentasubstituted by identical or different substituents, optional substituents on the heteroaryl in each case being the substituents on the aryl mentioned for R 1 i 'I- 4- 4 H 44 4 r (44( XI, X 2 X 3 and X 4 indepe hydrogen, chiori each case straigI alkylsulphinyl o carbon atoms, or atoms, or repres halogenoalkyl, halogenoalkylsul each case 1 to different haloge having 1 to 3 tetrasubstituted selected from tl chain or brancl straight-chain o atoms and 1 to furthermore repi case straight alkoxycarbonyl b alkyl moiety, or 6 carbon atoms i aminocarbonyl, i by identical or( consisting of 4. The me I Iy. 74 rI *i i Iltr Ii I i Le A 29 484 61 I_ I I__ r, I~ ~II-~ 4. The method according to claim 1, in which it IC I I C CI C, I C XI, X 2 x 3 and X 4 independently of one another in each case represent hydrogen, chlorine, bromine, cyano or nitro, or represent in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsuiphinyl or alkylsuiphonyl having in each case 1 to 4 carbon atoms, or represent cycloalkyl having 3, 5 or 6 carbon atoms, or represent in each case straight-chain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsulphinyl or halogenoalkylsulphonyl having in each case 1 to 3 carbon atoms and 1 to 7 identical or different halogen atoms, or represent divalent dioxyalkylene having 1 to 3 carbon atoms which is optionally mono- to tetrasubstituted by identical or different substituents selected from the group consisting of halogen and straight- chain or branched alkyl having 1 to 3 carbon atoms and straight-chain or branched halogenoalkyl having 1 to 3 carbon atoms and 1 to 7 identical or different halogen atoms, or furthermore represent hydroxycarbonyl, or represent iri each case straight-chain or branched alkylcarbonyl or alkoxycarbonyl having in each case 1 to 3 carbon atoms in the alkyl moiety, or represent cycloalkoxycarbonyl having 3, 5 or 6 carbon atoms in the cycloalkyl moiety, or represent amino or aminocarbonyl, in each case optionally mono- or disubstituted by identical or different substituents selected from the group consisting of C CC I* o I *r I *r I 0414 9 CC CC CC C DIC *414* 1 1 in each case stx carbon atoms, ha to 7 halogen at( each case 1 to moieties, 01 phenylaminocarbo optionally mono- identical or dif: the phenyl in hereinbelow, or furthermore phenylsulphinyl, phenylcarbonyl, or phenylazo, in in the phenyl ma optional substit mentioned for R 1 but wherein at I is other than hy R' represents hydro alkyl having 1 t is optionally mo. substituents se. 75 t4t4 a I f Ip I I; Le A 29 484 62 I i -4u- CI -c in each case straight-chain or branched alkyl having 1 to 3 carbon atoms, halogenoalkyl having 1 to 3 carbon atoms and 1 to 7 halogen atoms, alkoxyalkyl or alkylcarbonyl having in each case 1 to 3 carbon atoms in the individual alkyl moieties, or phenylcarbonyl, phenylsuiphonyl, phenylaminocarbonyl or phenylmethylsuiphonyl, in each case optionally mono- to trisubstituted in the phenyl moiety by identical or different substituents, optional substituents on the phenyl in each case being those mentioned for R 1 hereinbelow, or furthermore represent phenyl, phenyloxy, phenylthio, phenylsulphinyl, phenylsuiphonyl, phenylsulphonyloxy, I phenylcarbonyl, phenyloxycarbonyl, phenyithiomethylsuiphonyl or phenylazo, in each case optionally mono- to trisubstituted in the phenyl moiety by identical or different substituents, optional substituents on the phenyl in each case being those o mentioned for R 1 hereinbelow, but wherein at least one of the substituents X 1 X 2 X3 or X4 is other than hydrogen and halogen, and wherein R 1 represents hydrogen, or represents straight-chain or branched alkyl having 1 to 4 carbon atoms, or represents phenyl which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of 3 ?il ij" i E6 i: i:% I ia 14 g rI r r a i t I I halogen, cyano, ni alkyl, alkoxy, a] having in each straight-chain oi halogenoalkylt halogenoalkylsulp] and 1 to 7 identic straight-chain alkanoyl, alkoxyc case 1 to 3 carb divalent dioxyall< optionally mono-t a substituents sele a.1 straight-chain or 4 and straight-chaj a carbon atoms and a. a or phenyl which 'a 0 a identical or dif: consisting of ha having 1 to 3 c halogenoalkyl ha, or different halc RZ represents hydro: alkinyl, alkox alkylcarbonyl, 76 (hetero) arylami I bL. IH ST1q Ii 63 -C-UU~L L~I s~ 3 ig ,:a i1 EH p; en S S St So enS o S rtt t0*t S S) halogen, cyano, nitro, in each case straight-chain or branched alkyl, alkoxy, alkylthio, alkylsuiphinyl or alkylsulphonyl having in each case 1 to 3 carbon atoms, in each case straight-chain or branched halogenoalkyl, halogenoalkoxy, halogenoalkylthio, halogenoalkylsulphinyl or halogenoalkylsulphonyl having in each case 1 to 3 carbon atoms and 1 to 7 identical or different halogen atoms, in each case straight-chain or branched alkoxyalkyl, alkoxyalkoxy, alkanoyl, alkoxycarbonyl or alkoximinoalkyl having in each case 1 to 3 carbon atoms in the individual alkyl moieties, divalent dioxyalkylene having 1 to 3 carbon atoms which is optionally mono- to tetrasubstituted by identical or different substituents selected from the group consisting of ha]ogen and straight-chain or branched alkyl having 1 to 3 carbon atoms and straight-chain or branched halogenoalkyl having 1 to 3 carbon atoms and 1 to 7 identical or different halogen atoms, or phenyl which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of halogen and straight-chain or branched" alkyl having 1 to 3 carbon atoms and straight-chain or branched halogenoalkyl having 1 to 3 carbon atoms and 1 to 7 identical or different halogen atoms, 4 .5 C S S 55 4 551 4 "5 5 I, 561 St 5 5 R Ser *51 t 4~ dialkoxyphosphory the individual a] each case optiona different haloge: alkinyl, alkoxy alkylcarbonyl, dialkoxyphosphory: the individual al each case optiona different substit. straight-chain or or phenyl which identical or diffe the phenyl being t furthermore repreE optionally mono- c substituents selec straight-chain or straight-chain or I cycloalkyl having alkylthio-carbonyl thiocarbonyl havin, individual straig R 2 represents hydroxyl or cyano, or represents alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or 77 Sa°, in Lerojary ar onyloxy or (hetero) arylaminocarbonylamLnocarbonylox' 64 I 7- ©1 dialkoxyphosphoryl having in each case up to 4 carbon atoms in the individual alkyl or alkenyl or alkinyl moieties and in each case optionally mono- to trisubstituted by identical or different halogen atoms, or represents alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkylthio, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or dialkoxyphosphoryl having in each case up to 4 carbon atoms in the individual alkyl or alkenyl or alkinyl moieties and in each case optionally mono- or disubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkoxy having 1 to 3 carbon atoms I r or phenyl which is optionally mono- or disubstituted by identical or different substituents, optional substituents on the phenyl being those mentioned for R' or straight-chain or branched alkyl having 1 to 4 carbon atoms straight-chain or branched alkenyl having 2 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, alkoxycarbonyl, alkylthio-carbonyl, alkoxythio-carbonyl or alkylthio- thiocarbonyl having in each case 1 to 4 carbon atoms in the individual straight-chain or branched alkyl moieties, I 78 aiiy± motley, or represelL- u 8 carbon atoms in the cycloalkyl moiety, or represent amino or aminocarbonyl, in each case optionally mono- or is other th 65 ~n 4l-i benzimidazol-l'y i II divalent, cy A.ic alkanediyloxycarbonyl having 2 to 4 carbon atoms in the alkanediyl moiety, or phenylalkyl or phenyl having, where appropriate, 1 to 3 carbon atoms in the straight-chain or branched alkyl moiety and in each case optionally mono- or disubstituted by identical or different substituents, optional substituents on the ph'-nyl in each case being those mentioned for R 1 or R 2 furthermore represents phenyl, phenylcarbonyl, phenyloxycarbonyl, phenylcarbonyloxy or phenylaminocarbonylaminocarbonyloxy, in each case optionally mono- to trisubstituted by identical or different substituents, optional substituents on the phenyl in each case being those mentioned for R1, or R2 furthermore represents heteroaryl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroarylcarbonyloxy or heteroarylaminocarbonylaminocarbonyloxy having in each case 2 to 9 carbon atoms and 1 to 3 identical -Nr different hetero atoms in the heteroaryl moiety and in each case optionally mono- to trisubstituted by identical or different substituents, optional substituents on the heteroaryl in each case being the substituents on the phenyl mentioned for R 1 6. compound is ",benzimidazoll-y 01vt *0* 4& 00 4 *O 0 004 4 0*04 04 44 0 7. T compound is mixt compounds are benzimidazol-l-y is The method according to claim 1, wherein such methyl N-(4-bromo-2-cyano-6-trifluoromethyl-lH- compound 79 J.1 UL- W L Lt-L L X Lt:- CXU L. UJI IJ .L L [L :)LJ L U t, LL A ?I L, 4\ is other than hydrogen and halogen, and wherein Cons i L119 having 1 t halogenoalk 66 1~ benzimidazol-1-y1-methyl) -N-methyl carbamate of the formula B~r N F 3 C NcHl 3 coocii 6. The method according to claim 1, wherein .'uch is ethyl N-(4-bromo-2-cyano-6-trifluoromethyl-lH- ,benzimidazol1-yl-methy1)-N-benzyl carbamate of the formula S t4 W Br I 'I I a SI. a. a, t a t a t a. S a a, Ia 8 4 a 55 a, a a a a a o a a a a a. a a a a a I S a F 3 C a CH 2- IS a8. T compound is is, benzimidazol-1-y COOC 2H5 7. The method according to claim 1 wherein such compound is mixture of compounds according to claim 6, wherein such compounds are t-butyl N- (bromo-trifluoromethyl-2-cyano-ll- benzimidazol-l--yl-methyl) carbamates of the formula 80 COfilIS~uiI9 Ut IIIdiOyt_-L I aIU t cczLtl4--n having 1 to 6 carbon atoms and straight-chain or branched halogenoalkyl having 1 to 6 carbon atoms and 1 to 13 identical I thiocarbonyl individual 67 Iwo I Iw o p (4 i A Fl H *4a8 a. a 49 49 eta a a~ C ,a Caa a; Br -s N H F3C xat-N COO-C 4H9- t 9. parenterally, and Hi .1 At a Ia tac 1 t~ C I eta. A tttt C a a a It tt I: t a Spat e claims 1 examples. DATED this H COD-C 'H H9 BAYE R A By their Pa DAVIES C C a te a tttt If at a C CS a8. The method according to claim 1, wherein such compound is isopropyl N-(4-bromo-2.-cyano-6-trifluorometh~yl-lH- a abimidlllmthyl)Nb l carbamate of the formula Br 0N Coo-C 3 l 1

81. alkylthio-carbonyl, alkoxythiocarboflYl or alkyith '0- thiocarbonyl having in each case 1 to 8 carbon atoms in the individual straight-chain or branched alkyl moieties, 3. Th( 68 0, F fri V '4 II *644 ((It IC I 9 I 4 I~tt C 4 Ci i 4 4 '4 9. A method of combating parasitic protozoa which comprises enterally, parenterally, dermally or nasally administering to an animal an effective amount of a CN-substituted benzimidazole as claimed in any one of claims 1 to 8. 10. A method of combating parasitic protozoa according to anyone of claims 1 through 9 substantially as hereinbefore described with reference to the examples. DATED this 30th day of May 1995. BAYER AKITIENGESELLSCHAFT By their Patent Attorneys DAVIES COLLISON CAVE Use of CN The invei benzimida 5 X1, X 2 X case repr alko. 10 cycl( fUSE hyd~ A cyci optil repr 15 aryll aryo. aryl, but i wher Le A 29 4 -82 -'\WIIDOCS\Nf I 489060.OUj I I substituents on the aryl mentioned for R. 3. The method accordig to claim 1, in which 69 i i. I r Use of CN-substituted benzimidazoles in each case carbon atoms, S- R' repr4 Opti( I R 2 repr case alko: V alky:' dial] carb( aryl( 10 carbc as agentE particula3 3;.t Abstract j i. i; 1 i i- a :,i :1' 1 1 i 1~1 ~I i.s 1 i-i The invention relates to the use of CN-substituted benzimidazoles of the general formula (I) x X2 X N x R 5 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, alkythio, alkysuiphinyl, alkysulphonyl or cycloalkyl, or represent optionally substituted, .0 fused-on dioxyalkylene, or represent hydroxycarbonyl, alkyoxycarbonyl, alkoxycarbonyl or cycloalkyloxycarbonyl, or represent in each case optionally substituted amino or aminocarbonyl, or represent in each case optionally substituted aryl, .5 aryloxy, arylthio, aerylsulphinyl, arylsuphonyl, aryosulphonyloxy, arylcarbonyl, aryloxycarbonyl, arylazo or arylthiomethylsulphonyl, but wherein at least one of the substituents XI, X 2 X 3 and X 4 is other than hydrogen and halogen, and wherein Le A 2 9 ,48 Le A 29 484 different sub in each case straight-chain or branched alkyl having 1 to 4 carbon atoms, halogenoalkyl having 1 to 4 carbon atoms and 1 70 B R1 represents hydrogen or alkyl, or represents optionally substituted aryl and R 2 represents hydroxyl or cyano, or represents in each case optionally substituted alkyl, alkenyl, alkinyl, alkoxy, alkenyloxy, alkinyloxy, alkyithic, amino, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy, dialkoxyphosphoryl, (hetero)aryl, (hetero)aryl- carbonyl, (hetero)aryloxycarbonyl, (hetero)- arylcarbonyloxy or (hetero)arylaminocarbonylamino- carbonyloxy, as agents for combating parasitic protozoa, and in particular coccidia. 9 4 S~ tC tt ILe A 29 484