DESCRIPTION "PESTICIDAL METHOD USING N-PHENYLPYRAZOLES" This invention relates to the use of N-phenylpyrazole derivatives against arthropod, plant 5 nematode and helminth pests, to compositions containing them and to novel N-phenylpyrazole derivatives.

In J. Heter. Chem., 12 (1975), 1199-1205, P.L. Southwick and B. Dhawan have described 10 experiments for the preparation of

4,6-diamino-pyrazolo[3,4-dJpyrimidines in the expectation that such pyrimidine derivatives would have useful pharmacological properties. They employed as starting materials 5-amino-4-cyanopyrazoles L5 carrying on the 1-position a hydrogen atom, a methyl group, a hydroxyethyl group or a phenyl group substituted by one or more chlorine atoms and/or methyl groups, and on the 3-position a hydrogen atom, a methyl group -or a phenyl or benzyl group. This 2.0 publication contains no suggestion that compounds of general formula I possess or would be expected to possess activity against arthropods, helminths or plant ne atodes.

Apparently these pyrazole compounds did not lead 25 (according to the authors of the article) to useful therapeutic (viz. antimalarial) 4,6-diaminopyrazolo[3,4-dJpyrimidines.

US Patent No. 3760084 describes certain

5-amiπo-l-phenyl-pyrazoles as being useful for ameliorating inflammation in warm-blooded animals: the compounds carry on the 3-position hydrogen or a lower alkyl group and on the 4-position a carbamoyl or cyano group.

US Patent No. 3869274 describes certain 4-nitropyrazoles as being useful for the induction of abscission of fruit from fruit-bearing plants. US Patent No. 4066776 describes a very extensive group of l,4-disubstituted-3-nitropyrazoles as having antimicrobial, parasiticidal and herbicidal properties: the great biological activity of the compounds is stated to be limited to the 3-nitropyrazoles disclosed, the characterising feature of the compounds being the 3-nitropyrazole nucleus.

Japanese Patent Publication No. 12644/64 describes a process for the preparation of 4-thiocyanatopyrazole derivatives which are stated to be useful as germicides.

Japanese Patent Publication No. 49-117502 describes certain pyrazole sulphonamides having anti-thrombogenic properties.

None of the foregoing publications describes or suggests that compounds of general formula I possess or would be expected to possess the activity against arthropods, helminths or plant nematodes which has been discovered by the Applicants.

It has now unexpectedly been found after extensive research and experimentation. that the N-phenylpyrazole derivatives of the general formula I depicted hereinafter wherein Y represents a halogen, i.e. fluorine, chlorine, bromine or iodine, atom, the cyano or nitro group or a group RSO2. RSO or RS in which R represents a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms which may be unsubstituted or substituted by one or more halogen atoms, a cycloalkyl group containing from 3 to 5 carbon atoms, a straight- or branched-chain alkenyl group containing from 2 to 6 carbon atoms, the thiocyanato group, the sulphamoyl group which may be unsubstituted or substituted by one or two straight- or branched-chain alkyl groups which may be the same or different and contain from 1 to 6 atoms, the carbamoyl group which may be unsubstituted or substituted by one or two straight- or branched-chain alkyl groups which may be the same or different and contain from 1 to 6 carbon atoms, a straight- or branched-chain alkoxycarbonyl group containing from 2 to 7 carbon atoms, a straight- or branched-chain alkanoyl group containing from 2 to 7 carbon atoms, or a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms which may be unsubstituted or substituted by one or more halogen atoms,

Z represents the hydrogen atom, or the amino group

-NR^-R wherein R ¹ and R ² , which may be the same or different, each represents a hydrogen atom or a straight- or branched-chain alkyl group (containing from 1 to 6 carbon atoms, and which may be unsubstituted or substituted by straight- or branched-chain alkoxycarbonyl of 2 to 5 carbon atoms) , cycloalkyl group containing from 3 to 6 carbon atoms, for yl group, straight- or branched-chain alkanoyl group (which contain from 2 to 7 carbon atoms or together form a 5 or 6 membered cyclic imide with the nitrogen atom to which they are attached and themselves may be unsubstituted or substituted by one or more halogen atoms) or cycloalkylcarbonyl group (which contain from 4 to 7 carbon atoms) or straight- or branched-chain alkoxycarbonyl groups (which contain from 2 to 7 carbon atoms and themselves >are unsubstituted or substituted by one or more halogen a oms), or Z represents a straight- or branched-chain alkylsulphenylamino group containing from 1 to 4 carbon atoms, a straight- or branched-chain alkoxymethyleneamino group containing from 2 to 5 carbon atoms which may be unsubstituted or substituted on methylene by a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms, or represents a halogen, i.e. fluorine, chlorine, bromine or iodine, atom, a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms, the carboxy

group, or a straight- or branched-chain alkylthio, alkylsulphinyl or alkylsulphonyl group containing from 1 to 6 carbon atoms which may be unsubstituted or substituted by one or more halogen atoms, or represents a straight- or branched-chain trialkylsilylmethyl group containing from 1 to 6 carbon atoms in each alkyl group which may be the same or different, a trialkylsilyl group containing from 1 to 6 carbon atoms in each alkyl group which may be the same or different or the cyano or nitro group _;

3 represents a halogen, i.e. fluorine, chlorine, bromine or iodine atom, a straight- or branched-chain alkyl or alkoxy group containing from 1 to 4 carbon atoms which may be unsubstituted or substituted by one or more halogen atoms, (e.g. a trifluoromethyl or trifluoromethoxy group), a straight- or branched-chain alkylthio or alkylsulphinyl group containing from 1 to 4 carbon atoms which is substituted by one or more halogen atoms (e.g. a trifluoromethylthio or trifluoromethylsulphinyl group) , the nitro or cyano group or a straight- or branched-chain alkylsulphonyl group containing from 1 to 4 carbon atoms which may be unsubstituted or substituted by one or more halogen atoms (e.g. the trifluoromethylsulphonyl group) ,. and R represents a halogen, i.e. fluorine, chlorine, bromine or iodine, atom, a cyano or nitro group or a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms which may be unsubstituted or

substituted by one or more halogen atoms, or a cycloalkyl group containing from 3 to 6 carbon atoms, and represents an integer from 1 to 5 inclusive, and, when Z represents a carboxy group, salts thereof with pesticidally-acceptable bases provided that R .

Y and Z do not simultaneously represent three groups of the same genus selected from the genera (i) nitro,

(ii) cyano, (iii) halogen and (iv) unsubstituted alkyl, have valuable activity against arthropod, plant nematode and helminth pests, more particularly by ingestion of the compound(s) of general formula I by the arthropods. When ri represents an integer from 2 to 5 inclusive, atoms and groups represented by R may be the same or different. By the term 'salts with pesticidally acceptable bases' is meant salts the cations of which are known and accepted in the art for the formatidn of salts of pesticidally active acids for agricultural or horticultural use. When intended for application to vertebrates to combat infection or infestation by arthropods or helminths, the salts with bases used will be non-toxic. By the term 'non-toxic' is meant salts with bases the cations of which are innocuous to the vertebrates at the doses administered and which do not vitiate the beneficial effects produced by the anion.

Preferably, the salts are water-soluble. Suitable salts with bases include alkali metal (e.g. sodium and potassium), alkaline earth metal (e.g. calcium and magnesium), ammonium and amine (e-g- diethanolamine, triethanolamine, octylamine, morpholine and dioctylmethylamine) salts. It is to be understood that where reference is made in the present specification to the compounds of general formula I such reference is intended to include also the salts with pesticidally acceptable bases of compounds of general formula I where appropriate.

Preferred compounds of general formula 1 are those with phenyl substitution which is 2,4,6-trichloro, 2,3,5, 6-tetrachloro, 2-chloro-4-trifluoromethyl, 2,3,5,6-tetrafluor0-4-trifluoromethyl, 2,6-dichloro-4-trifluoromethylthio, 2-chloro-3, 5,6-trifluoro-4- rifluoromethyl, 2,6-dichloro-3, 5-difluoro-4-trifluoromethyl, 2,6-dichloro-4-nitro, 2,6-dichloro-4-trifluoromethyl- sulphinyl, 2,6-dichloro-4-methanesulphonyl and

2,6-dichloro-4-trifluorome hanesulphonyl.

3 Compounds of general formula I wherein (R )n represents 2,6-dichloro-4-trifluoromethyl or

2,6-dichloro-4-trifluoromethoxy substitution of the phenyl group are especially preferred.

Preferred compounds are those where

(a) Y and R each represent a cyano group and

Z represents the hydrogen atom, the amino group

-NR 1R'2 or an alkylsulphenylamino group, an alkoxymethyleneamino group which may be unsubstituted or substituted on ethylene by an alkyl group, a halogen atom, an alkyl group, the carboxy group, an alkylthio, alkylsulphinyl or alkylsulphonyl group which is optionally halogen substituted, a trialkylsilylmethyl group, a trialkylsilyl group or the nitro group;

(b) Y represents an alkylsulphonyl group which is optionally halogen substituted, a cycloalkylsulphonyl group or an alkenylsulphonyl group, Z represents the hydrogen atom, the amino

1 o group -NR R or an alkylsulphenylamino group, an alkoxymethyleneamino group which is unsubstituted or substituted on methylene by an . alkyl group, a halogen atom, an alkyl group, the carboxy group, an alkylthio, alkylsulphinyl or alkylsulphonyl group which is optionally halogen substituted, a trialkylsilylmethyl group, a trialkylsilyl group or the cyano or nitro group and R represents a halogen atom or the cyano or nitro group;

(c) R represents the nitro group, Y represents the cyano or nitro group, a carbamoyl group or an alkoxycarbonyl group and

Z represents the hydrogen atom, a halogen atom, an alkyl group, the carboxy group, an alkylthio, alkylsulphinyl or alkylsulphonyl group which is optionally halogen substituted, a trialkylsilylmethyl group, a trialkylsilyl group or the nitro group; (d) R represents a halogen atom, Y represents the cyano or nitro group, a carbamoyl group or an alkoxycarbonyl group and

Z represents the hydrogen atom, the amino group -NR 1R2 or an alkylsulphenylamino group, an alkoxymethyleneamino group which is unsubstituted or substituted on methylene by an alkyl group, a halogen atom, an alkyl group, the carboxy group, an alkylthio, alkylsulphinyl or alkylsulphonyl group which is optionally halogen substituted, a trialkylsilylmethyl group, a trialkylsilyl group or the nitro group; and (e) R represent an alkyl group which is unsubstituted or substituted by one or more halogen atoms or a cycloalkyl group, Y represents a halogen atom, the cyano or nitro group, a group RS0 ₂ , RSO or RS, the thiocyanato group, a sulphamoyl group, a carbamoyl group, an

alkoxycarbonyl group, an alkanoyl group or an alkyl group which is unsubstituted or substituted by one or more halogen atoms,

Z represents the hydrogen atom, the amino group -NR R or an alkylsulphenylamino group, an alkoxymethyleneamino group which is unsubstituted or substituted on methylene by an alkyl group, a halogen atom, an alkyl group, the carboxy group, an alkylthio, alkylsulphinyl or alkylsulphonyl group which is optionally halogen substituted, a trialkylsilylmethyl group, a trialkylsilyl group or the cyano or nitro group.

It will be appreciated that the groups listed above are as hereinbefore defined earlier in the specification.

Compounds of general formula I wherein R represents a trifluoromethyl or methyl group are also preferred.

Compounds of general formula I which are of particular interest against arthropods are: 1 5-Amiπo-3,4-dicyano-l-(2,4,6- trichlorophenyl)pyrazole 2 5-Amino-l-(2,6-dichloro-4-trifluoromethyl- phenyl)-3,4-dicyanopyrazole

3 5-Amino-3,4-dicyano-l-(2, 3,5, 6-tetrachloro- pheny1)pyrazole

4 5-Amino-4-cyano-l-(2,6-dichloro-4-trifluoro- methylpheny1)-3-methylpyrazole

5 5-Amino-4-cyano-l-(2,6-dichloro-4-trifluoro- methylphenyl)-3-trifluoromethylpyrazole

6 _^ 5-Amino-3-chloro-4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)pyrazole 7 5-Amino-3-bromo-4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)pyrazole

8 5-Amino-3-iodo-4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)pyrazole

9 4-Cyano-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-3-me ^' thyl-5-ethanesulphenylamino- pyrazole

10 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-methy1-5-methoxymethyleneamino- pyrazole

11 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-methy1-5-propoxymethyleneamino- pyrazole

12 5-Acetamido-l-(2,6-dichloro-4-trifluoro- methylphenyl)-3,4-dicyanopyrazole

13 5-Dichloroacetamido-l-(2,6-dichloro-4- trifluoromethylphenyl)-3,4-dicyanopyrazole

14 5-Cyclopropylcarbonamido-l-(2,6-dichloro-4- tri luoromethylphenyl)-3,4-dicyanopyrazole 15 5-Pentanamido-l-(2,6-dichloro-4-trifluoro- ethylphenyl)-3,4-dicyanopyrazole

16 5-Propionamido-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3,4-dicyanopyrazole

17 5-Amino-l-(2-chloro-4-trifluoromethylphenyl)- 3,4-dicyanopyrazole

18 .5-Amino-3,4-dicyano-l-(2,3, 5, 6-tetrafluoro- 4- rifluoromethylphenyl)pyrazole

19 5-Amino-4-cyano-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-pentafluoroethylpyrazole 20 5-Amino-3-chlorodifluoromethyl-l-

(2,6-dichloro-4-trifluoromethylphenyl)-4- cyanopyrazole 21 5-Amino-l-(2,6-dichloro-4-tri luoromethyl¬ phenyl)-4-cyano-3-difluoromethylpyrazole 22 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-methanesulphonyl-3-trifluoro- methylpyrazole

23 5-Amino-4-carbamoyl-l-(2,6-dichloro-4- trifluoromethylphenyl)-3-trifluorome hy1- pyrazole

24 5-Amino-l-(2, 6-dichloro-4-trifluoromethyl- phenyl)-4-methoxycarbony -3-trifluoromethy1- pyrazole

25 5-Acetamido-4-cyano-l-(2,6-dichloro-4- trifluorome hylphenyl)-3-trifluorome hy1- pyrazole 26 l-(2,6-Dichloro-4-trifluoromethylphenyl)-

3,4-dicyano-5-(2,2-dimethylpropionamido)- pyrazole

27 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-ethoxymethyleneamino- 3-trifluoromethylpyrazole

28 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-dimethylamino-3-trifluoromethyl¬ pyrazole

29 4-Cyano-l-(2,6-dichloro-.4-trifluoromethyl- pheny1)-5-ethoxycarbonylmethylamino-

3-trifluoromethylpyrazole

30 4-Cyano-5-methylamino-l-(2, 6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethyl¬ pyrazole 31 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-(2,2-dimethylpropionamido)- 3-trifluoromethylpyrazole

32 5-Amino-4-bromo-l- (2 , 6-dichloro-4- trifluoromethylphenyl)-3- rifluoromethyl¬ pyrazole

33 5-Bromo-4-cyano-l-(2,6-dichloro-4- trifluoromethylpheny1)-3-trifluoromethyl¬ pyrazole

34 5-Amino-4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)-3-fluoromethyl¬ pyrazole 35 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ pheny1)-4-nitro-3-trifluoromethylpyrazole 36 5-Amino-4-cyano-l-(2,6-dichloro-4- trifluoromethoxyphenyl)-3-trifluoromethyl¬ pyrazole 37 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-bis(ethoxycarbony1)amino- 3- rifluoromethylpyrazole

I

38 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-bis(cyclopropanecarbonyl)amino- 3-trifluoromethylpyrazole

39 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-cyclopropanecarbonamido-

3-trifluorome hylpyrazole

40 5-Amino-4-chloro-l-(2,6-dichloro-4- trifluoromethylpheny1)-3-trifluoromethyl¬ pyrazole

41 4-Cyano-l-(2,6-dichloro-4- rifluoromethyl¬ phenyl)-5-ethoxycarbonylamino-

3- rifluoromethylpyrazole

42 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl- phenyl)-3-t ifluoromethylpyrazole

43 4-Cyano-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-5-iodo-3-trifluoromethylpyrazole

44 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5- ethy1-3-trifluoromethylpyrazole 45 5-Amino-l-(2,6-dichloro-4-trifluoromethyl- phenyl)-4-(N,N-dimethylsulphamoyl)- 3- rifluoromethylpyrazole

46 5-Amino-4-cyano-3-cyclopropyl- l-(2,6-dichloro-4-trifluoromethy1- phenyl)pyrazole

47 5-Amino-4-cyano-l-(2,6-dichloro-

4-trifluoromethylphenyl)-3-heptafluoropropy1- pyrazole

48 5-Amino-3,4-dicyano-l-(2,6-dichloro- 4-trifluoromethylthiophenyl)pyrazole

49 5-Amino-l-(2-chloro-3, 5, 6-tri luoro-

4- ifluorome hylphenyl)-3,4-dicyanopyrazole,

50 5-Amino-l-(2,6-dichloro-3, 5-difluoro- 4-trifluoromethylphenyl)-3,4-dicyanopyrazole, 51 5-Amino-l-(2,6-dichloro-4-trifluoromethoxy- phenyl)-3, -dicyanopyrazole, 52 5-Amino-4-cyano-3-ethyl-l-(2,6-dichloro- 4- rifluorome hylphenyl)pyrazole

53 5-Amino-l-(2,6-dichloro-4- rifluoromethy1- phenyl)-4-methanesulphonyl-3-methylpyrazole

54 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-methy1-4-ethoxycarbonylpyrazole 55 5-Amino-l-(2,6-dichloro-4-trifluoromethoxy- phenyl)-4-methanesulphonyl-3-methylpyrazole 56 5-Amino-l-(2-chloro-3, 5,6-trifluoro-

4-trifluoromethylphenyl)-4-cyano-3-trifluoro¬ methylpyrazole 57 5-Amino-4-cyano-l-(2,6-dichloro-4-trifluoro¬ methy1thiophenyl)-3-trifluoromethylpyrazole

58 5-Amino-3-chlorofluoromethy1-4-cyano-1-

(2,6-dichlor0-4-trifluoromethylphenyl)pyrazole

59 5-Amino-4-cyano-l-(2,6-dichloro-3, 5-difluoro- 4-trifluoromethylphenyl) _, -3-trifluoromethyl¬ pyrazole

60 4-Cyano-l-(2, 6-dichloro-4-trifluoromethyl- phenyl)-5-(l-ethoxyethylideneamino)-

3-methylpyrazole 61 -4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-methy1-5-succinimidopyrazole 62 5-Acetamido-l-(2, 6-dichloro-4-trifluoro¬ methylphenyl)-4-methanesulphony1- 3- rifluoromethylpyrazole 63 5-Acetamido-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-methyl-4-methanesul^)honyl- pyrazole

64 5-Amino-1-(2,6-dichloro-4-nitrophenyl)- 3,4-dicyanopyrazole

65 l-(2,6-Dichloro-4-trifluoromethylphenyl)- 3,4-dicyano-5-methylaminopyrazole 66 l-(2,6-Dichloro-4-trifluoro ethylphenyl)-

3,4-dicyano-5-ethylaminopyrazole 67 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-(N-methyl-N-ethoxycarbonylamino)- 3-trifluoromethylpyrazole 68 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ pheny1)-5-(N-acetyl-N-trimethylacetylamino)- 3-trifluoromethylpyrazole

69 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-(N-propionyl-N-trimethylacetylamino)- 3-trif.luoromethylpyrazole

70 l-(2,6-Dichloro-4-trifluoromethylphenyl)- 4-nitr0-3-trifluoromethy1-5- r^methy1- acetylaminopyrazole

71 l-(2,6-Dichloro-4-trifluoromethylphenyl)- . 5-ethoxycarbonylamino-4-nitro-3-trifluoromethyl¬ pyrazole

72 3-Chloro-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-cyano-5-trimethylacetyl- aminopyrazole 73 3-Chloro-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-cyano-5-bis(ethoxy- carbonyl)aminopyrazole

74 3-Chloro-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-cyano-5-ethoxycarbonyl- aminopyrazole

75 4-Cyano-5-diacetylamino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoro¬ methylpyrazole

76 5-(N-Acetyl-N-ethoxycarbonylamino)-

4-cyano-1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3- rifluoromethylpyrazole 77 l-(2,6-Dichloro-4-trifluoromethylphenyl)-

5-bis(ethoxycarbonyl)amino-3,4-dicyano¬ pyrazole

78 l-(2,6-Dichloro-4-trifluoromethylphenyl)- 5-bis(ethoxycarbonyl)amino-4-methane- sulphony1-3-trifluoromethylpyrazole

79 l-(2,6-Dichloro-4-trifluoromethylpheny1)- 5-ethoxycarbonylamino-4-methane _l sulphonyl- 3- rifluoromethylpyrazole

80 l-(2,6-Dichloro-4-trifluoromethylpheny1)- 3,4-dicyano-5-ethoxycarbonylaminopyrazole

81 5-Amino-l-(2,6-dichloro-4-trifluo ^" romethyl- phenyl)-4-iodo-3- rifluoromethylpyrazole

82 5-Amino-l-(2,6-dichloro-4-trifluo-romethy1- pheny1)-4-iodo-3-methylpyrazole 83 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-methy1-4-nitropyrazole

84 5-Acetamido-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-nitro-3-trifluoromethyl¬ pyrazole

85 l-(2,6-Dichloro-4-trifluoromethylphenyl) - 4-nitr0-3-trifluoromethylpyrazole

86 l-(2, 6-Dichloro-4-trifluoromethylphenyl)- 3-methy1-4-me hanesulphonylpyrazole

87 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ pheny1)-3-fluoropyrazole 88 l-(2,6-Dichloro-4-trifluoromethylphenyl)-

4-methanesulphony1-3-trifluoromethylpyrazole 89 5-Chloro- ^' l-(2,6-dichloro-4-trifluoro- methylphenyl)-4-cyano-3-trifluoromethyl¬ pyrazole 90 5-Amino-l-(2,6-dichloro-4- rifluoromethyl¬ phenyl)-4-(N-ethylsulphamoy1)- 3-trifluoromethylpyrazole

91 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-(N-methylsulphamoyl)- 3-trifluoromethylpyrazole

92 l-(2,6-Dichloro-4-trifluoromethylphenyl)- 4-cyano-3-nitropyrazole

- 93 l-(2,6-Dichloro-4-trifluoromethylphenyl)- 3,4-dicyano-5-nitropyrazole 94 5-Amino-l-(2, 6-dichloro-4-trifluoromethyl¬ phenyl)-4-cyano-3-fluoropyrazole

95 5-Amino-3-chloro-l-(2, _. 6-dichloro- 4-trifluoromethoxyphenyl)-4-cyanopyrazole

96 5-Amino-3-chloro-4-cyano-l-(2,6-dichloro-

3, 5-difluoro-4- rifluoromethylphenyl)pyrazole 97 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl- phenyl)-3-trifluoromethyl-5-trimethyl- silylpyrazole

98 5-tert-Butyldimethylsilyl-4-cyano-

1-(2,6-dichlor0-4-trifluoromethylphenyl)- 3-trifluoroύiethylpyrazole

99 4-Cyano-l-(2, 6-dichloro-4-trifluoromethyl¬ phenyl)-5-methylthio-3-trifluorome hyl¬ pyrazole

100 4-Cyano-l-(2,6-dichlor0-4-trifluoromethy1- phenyl)-3-trifluoromethyl-5-trifluoro¬ methylthiopyrazole

101 5-Carboxy-4-cyano-l-(2, 6-dichlσro- 4-trifluoromethylphenyl)-3- rifluoro¬ methylpyrazole 102 l-(2,6-Dichloro-4-trifluoromethylpheny1)-

4-ni ro-3-trifluorome hy1-5-trimethy1- silylpyrazole 103 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3- rifluoromethy1-5- rime hy1- silylmethylpyrazole

104 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-methoxycarbonylamino-

3-trifluoromethylpyrazole

105 l-(2,6-Dichloro-4-trifluoromethylphenyl)- 4,5-dicyano-3-trifluoromethylpyrazole

106 5-Amino-3-cyano-l-(2,6-dichloro-

4-trifluoromethylphenyl)-4-methane- sulphonylpyrazole 107 4-Acetyl-l-(2,6-dichloro-4-trifluoro- methylphenyl)-3-trifluoromethylpyrazole

108 5-Amino-l-(2, 6-dichloro-4-trifluoromethyl¬ phenyl)-4-methylsulphiny1-3-trifluoro¬ methylpyrazole

109 5-Amino-l-(2,6-dichloro-4-trifluoromethy1- pheny1)-4-ethylsulphiny1-3-trifluoro- methylpyrazole

110 5-Amino-l-(2,6-dichloro-4-trifLuoromethyl¬ phenyl)-4-ethylsulphiny1-3-methylpyrazole

111 5-Amino-4-cyano-l-(2,6-dichloro- 4-trifluoromethylsulphinylphenyl)-

3-trifluoromethylpyrazole

112 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl- phenyl)-5-methylsulphiny1-3-trifluoro¬ methylpyrazole 113 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-ethylsulphony1-3-trifluoro¬ methylpyrazole

114 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-ethyIsulphony1-3-methylpyrazole

115 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-methy1-4-propanesulphony1- pyrazole

116 5-Amino-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-4-trichloromethanesulphonyl-

3-methylpyrazole

117 5-Amino-1-(2,6-dichlor0-4-trifluoromethy1- pheny1)-4-ethylthio-3-methylpyrazole

118 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-methy1-4-methylthiopyrazole

119 5-Amino-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-4-n-propylthio-3-methylpyrazole 120 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ pheny1)-4-ethylthio-3-trifluoromethyl¬ pyrazole I

121 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-methylthio-3-trifluoromethy1- pyrazole

122 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-thiocyana o-3- rifluoromethyl¬ pyrazole

123 5-Amino-l-(2,6-dichloro-4-trifluoromethyl- phenyl)-3-methy1-4- hiocyanatopyrazole

124 5-Amino-4-cyano-l-(2,6-dichloro-4-methane- sulphonylphenyl)-3-trifluoromethyl¬ pyrazole

125 5-Amino-l-(2, 6-dichloro-4-trifluoromethyl- phenyl)-3-meth 1-4-trichloromethylthio- pyrazole

126 4-Cyano-l-(2,6-dichloro-4-trifluoro- ethanesulphonylphenyl)-5-nitro-

3- rifluoromethylpyrazole 127 l-(2,6-Dichloro-4-trifluoromethylphenyl)-

4-difluoromethy1-3-trifluorometh l¬ pyrazole 128 5-Amino-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-4-methy1-3- rifluoromethy1- pyrazole

The numbers 1 to 128 are assigned to the above compounds for identification and reference hereinafter. Especially preferred compounds of general formula I are numbered:- 2; 22; 37; 53; 71; 106 and 118.

According to a feature of the present invention, there is provided a method for the control of arthropod, plant nematode or helminth pests at a locus which comprises the treatment of the locus (e.g. by application or administration) with an effective amount of a compound of general formula I, or a pesticidally acceptable salt thereof, wherein the various symbols are as hereinbefore defined. The compounds of general formula I may, in particular, be used in the fields of veterinary medicine and livestock husbandry and in the maintenance of public health against arthropods or helminths which are parasitic internally or externally upon vertebrates, particularly warm-blooded vertebrates, for example man and domestic animals, e.g. cattle, sheep, goats, equines, swine, poultry, dogs, cats and fishes, for example Acarina, including ticks (e.g. Ixodes spp., Boophilus spp. e.g. Boophilus microplus, Amblyomma spp., Hyalomma spp., Rhipicephalus spp. e.g. Rhipicephalus appendiculatus, Haemaphysalis spp.,

Dermacentoτ spp., Ornithodorus spp. (e.g. Ornithodorus moubata) and mites (e.g.- Damalinia spp., Dermahyssus gallinae, Sarcoptes spp. e.g. Sarcoptes scabiei, Psoroptes spp., Chorioptes spp., Pernodex spp., Eutrombicula spp.,); Diptera (e.g. Aedes spp., Anopheles spp., Musca spp., Hypoderma spp., Gasterophilus spp., Simuliu spp.);

Hemiptera (e.g. Triatoma spp.); Phthiraptera (e.g. Damalinia spp., Linognathus spp.); Siphonaptera (e.g. Ctenocephalides spp.); Dictyoptera (e.g. Periplaneta spp., Blatella spp.); Hymenoptera (e.g. Monomorium pharaonis) ; for example against infections of the gastro-intestinal tract caused by parasitic nematode worms, for example members of the family Trichostrongylidae, Nippostrongylus brasiliensis, Trichinella spiralis, Haemonchus contortus, Trichostrcngylus colubriformis, Nematodirus battus, Ostertagia circumcincta, Trichostrongylus axei, Cooperia spp. and Hymenolepis nana; in the protection of stored products, for example cereals, including grain and flour, groundnuts, animal feedstuffs, timber and household goods, e.g. carpets and textiles,- against attack by arthropods, more especially beetles, including weevils, ^' moths and mites, for iβxample Ephestia spp. (flour moths), Anthrenus spp. (carpet beetles), Tribolium spp. (flour beetles), Sitophilus spp. (grain weevils) and Acarus spp. (mites), in the control of cockroaches, ants and similar arthropod pests in infested domestic and industrial premises and in the control of mosquito larvae in waterways, wells, reservoirs or other running or standing water; in agriculture, against adults, larvae and eggs of

Lepidoptera (butterflies and moths) , e.g. Heliothis spp. such as Heliothis virescens (tobacco budworm) ,

Heliothis armigera and Heliothis zea, Spodoptera spp. such as S.exempta, S.littoralis (Egyptian cotton worm), S.eridania (southern army worm), Mamestra configurata (bertha army worm); Earias spp. e.g. E.insulana (Egyptian bollworm) , Pectinophora spp. e.g. Pectinophoτa gossypiella (pink bollworm), Ostrinia spp. such as O.nubilalis (European cornborer) , Trichoplusia ni (cabbage looper) , Pieris spp. (cabbage worms), Laphygma spp. (army worms), Agrotis and Amathes spp. (cutworms) , Wiseana spp. (porina moth) , Chilo spp. (rice stem borer) , Tryporyza spp. and Diatraea spp. (sugar cane borers and rice borers), Sparganothis pilleriana (grape berry moth) , Cydia pomonella (codling moth) , Archips spp. (fruit tree tortrix moths), Plutella xylostella (diamond back moth); against adults and larvae of Coleoptera (beetles) e.g. Hypothenemus hampei (coffee berry borer), Hylesinus spp. (bark beetles), Anthonomus grandis (cotton boll weevil), Acalymma spp. (cucumber beetles), Lema spp., Psylliodes spp., Leptinotarsa decemlineata (Colorado potato beetle), Diabrotica spp. (corn rootworms) , Gonocephalum spp. (false wire worms), Agriotes spp. (wireworms) , Dermolepida and Heteronychus spp. (white grubs), Phaedon cochleariae (mustard beetle), Lissorhoptrus oryzophilus (rice water weevil), Meligethes spp. (pollen beetles),

Ceutorhynchus spp., Rhynchophorus and Cosmopolites spp. (root weevils); against Hemiptera e.g. Psylla spp., Bemisia spp., Aphis spp., Myzus spp., Megoura viciae, Phylloxera spp., Adelges spp., Phorodon humuli (hop damson aphid), Aeneolamia spp., Nephotettix spp. (rice leaf hoppers), Empoasca spp., Nilaparvata spp., Perkinsiella spp., Pyrilla spp., Aonidiella spp. (red scales), Coccus spp., Psuedococcus spp., Helopeltis spp. (mosquito bugs), Lygus spp., Dysdercus spp., Oxycareπus spp., Nezara spp.; Hymenoptera e.g.

Athalia spp. and Cephus spp. (saw flies), Atta spp. (leaf cutting ants); Diptera e.g. Hylemyia spp. (root flies), Atherigona spp. and Chlorops spp. (shoot flies), Phytomyza spp. (leaf miners), Ceratitis spp. (fruit flies); Thysanoptera such as Thrips tabaci; Orthoptera such as Locusta and Schistocerca spp. (locusts) and crickets e.g. Gryllus spp., and Acheta spp.; Collembola e.g. Sminthurus spp. and Onychiurus spp. (springtails) , Isoptera e.g. Odontotermes spp. (termites), Der aptera e.g. Forficula spp. (earwigs) and also other arthropods of agricultural significance such as Acari (mites) e.g. Tetranychus spp., Panonychus spp. and Bryobia spp. (spider mites), Eriophyes spp. (gall mites), Polyphago arsonemus spp.; Blaniulus spp. (millipedes), Scutigeτella spp. (symphilids) , Oniscus spp. (woodlice) and Triops spp. (crustacea); nematodes which attack plants and trees of importance to

agriculture, forestry, horticulture either directly or by spreading bacterial, viral, mycoplasma or , fungal diseases of the plants, root-knot nematodes such as Meloidogyne spp. (e.g. M. incognita) ; cyst nematodes such as Globodera spp. (e.g. G_. rostochiensis);

Heterodera spp. (e.g. _H. avenae) ; Radopholus spp. (e.g. R. similis); lesion nematodes such as Pratylenchus spp. (e.g. P_. pratensis); Belonolaimus spp. (e.g. B_. gracilis); Tylenchulus spp. (e.g. T. semipenetrans); Rotylenchulus spp. (e.g. R. reniformis); Rotylenchus spp. (e.g. R. robustus); Helicot lenchus spp. (e.g. . multicinctus) ; Hemicycliophora spp. (e.g. . gracilis) ; Criconemoides spp. (e.g. £. similis); Trichodorus spp. (e.g. T. primitivus) ; dagger nematodes such as Xiphinema spp. (e.g. 5C. diversicaudatum) , Longidorus spp. (e.g. L. elongatus); Hoplolaimus spp. (e.g. H. coτonatus); Aphelenchoides spp. (e.g. A. ₍ ritzema-bosi , A. besseyi); stem and bulb eelworms such as Ditylenchus spp. (e.g. D. dipsaci) . The invention also provides a method for the control of arthropod or nematode pests of plants which comprises the application to the plants or to the medium in which they grow of an effective amount of a compound of general formula I or a pesticidally acceptable salt thereof.

Thβ compounds of general formula I may be applied in solid or liquid compositions to the soil principally to control those nematodes dwelling therein but also to the foliage principally to control those nematodes attacking the aerial parts of the plants (e.g.

Aphelenchoides spp. and Ditylenchus spp. listed above). The compounds of general formula I are of value in controlling pests which feed on parts of the plant remote from the point of application, e.g. leaf feeding insects are killed by the subject compounds applied to roots.

In addition the compounds may reduce attacks on the plant by means of antifeeding or repellant effects. The compounds of general formula I are of particular value in the protection of field, forage, plantation, glasshouse, orchard and vineyard crops, of ornamentals and of plantation and forest trees, for example, cereals (such as maize, wheat, rice, sorghum), cotton, tobacco, vegetables and salads (such as beans, cole crops, curcurbits, lettuce, onions, tomatoes and peppers), field crops (such as potato, sugar beet, ground nuts, soyabean, oil seed rape), sugar cane, grassland and forage (such as maize, sorghum, lucerne), plantations (such as of tea, coffee, cocoa, banana, oil palm, coconut, rubber,

spices), orchards and groves (such as of stone and pip fruit, citrus, kiwifruit, avocado, mango, olives and walnuts), vineyards, ornamental plants, flowers and shrubs under glass and in gardens and parks, forest trees (both deciduous and evergreen) in forests, plantations and nurseries.

They are also valuable in the protection of timber (standing, felled, converted, stored or structural) from attack by sawflies (e.g. Urocerus) or beetles (e.g. scolytids, platypodids, lyctids, bostrychids, cerambycids, anobiids).

They have applications in the protection of stored products such as grains, fruits, nuts, spices and tobacco, whether whole, milled or compounded into products, from moth, beetle and mite attack. Also protected are stored animal products such as skins, hair, wool and feathers in natural or converted form (e.g. as carpets or textiles) from moth and beetle attack; also stored meat and fish from beetle, mite and fly attack.

The compounds of general formula I are of particular value in the control of arthropods or helminths which are injurious to, or spread or act as vectors of diseases in man and domestic animals, for example those hereinbefore mentioned, and more especially in the control of ticks, mites, lice, fleas, midges and biting, nuisance and myiasis

flies. The compounds of general formula I are particularly useful in controlling arthropods or helminths which are present inside domestic host animals or which feed in or on the skin or suck the blood of the animal, for which purpose they may be administered orally, parenterally, percutaneously or topically.

The compositions hereinafter described for topical application to man and animals and in the protection of stored products, household goods, property and areas of the general environment may, in general, alternatively be employed for application to growing crops and crop growing loci and as a seed dressing. Suitable means of applying the compounds of general formula I include:- to persons or animals infested by or exposed to infestation by arthropods or helminths, by parenteral, oral or topical application of compositions in which the active ingredient exhibits an immediate and/or prolonged action over a period of time against the arthropods or helminths, for example by incorporation in feed or suitable orally-ingestible pharmaceutical formulations, edible baits, salt licks, dietary supplements, pour-on formulations, sprays, baths, dips, showers, jets, dusts, greases, shampoos, creams, wax-smears and livestock self-treatment systems;

to the environment in general or to specific locations where pests may lurk, including stored products, timber, household goods, and domestic and industrial premises, as sprays, fogs, dusts, smokes, wax-smears, lacquers, granules and baits, and in tricklefeeds to waterways, wells, reservoirs and other running or standing water; to domestic animals in feed to control fly larvae feeding in their faeces. The compounds of general formula I may be applied to control arthropods or helminths in compositions of any type known to the art suitable for internal or external administration to vertebrates or application for the control of arthropods in any premises or indoor or outdoor area, containing as active ingredient at least one compound of general formula I in association with one or more compatible diluents or adjuvants appropriate for the intended use. All such compositions may be prepared in any manner known to the art.

Compositions suitable for administration to vertebrates or man include preparations suitable for oral, parenteral, percutaneous, e.g. pour-on, or topical administration.

Compositions for oral administration comprise one or more of the compounds of general formula I in association with pharmaceutically acceptable carriers or coatings and include, for example, tablets, pills, capsules, pastes, gels, drenches, medicated feeds, medicated drinking water, medicated dietary supplements, slow-release boluses or other slow-release devices intended to be retained within the gastro-intestinal tract. Any of these may incorporate active ingredient contained within microcapsules or coated with acid-labile or alkali-labile or other pharmaceutically acceptable enteric coatings. Feed premixes and concentrates- containing compounds of the present invention for use in preparation of medicated diets, drinking water or other materials for consumption by animals may also be used.

Compositions for parenteral administration include solutions, emulsions or suspensions in any suitable pharmaceutically acceptable vehicle and solid or semisolid subcutaneous implants or pellets designed to release active ingredient over a protracted period and may be prepared and made sterile in any appropriate manner known to the art.

Compositions for percutaneous and topical administration include sprays, dusts, baths, dips, showers, jets, greases, shampoos, creams, wax-smears, or pour-on preparations and devices (e.g. ear tags) attached externally to animals in such a way as to provide local or systemic arthropod control.

Solid or liquid baits suitable for controlling arthropods comprise one ^' or more compounds of general formula I and a carrier or diluent which may .include a food substance or some other substance to induce consumption by the arthropod.

Liquid compositions include water miscible concentrates, emulsifiable concentrates, flowable suspensions, wettable or soluble powders containing one or more compounds of general formula I which may be used to treat substrates or sites infested or liable to infestation by arthropods including premises, outdoor or indoor storage or processing areas, containers or equipment and standing or running water.

Solid homogenous or heterogenous compositions containing one or more compounds of general formula I, for example granules, pellets, briquettes or capsules, may be used to treat standing or running water over a period of time. A similar effect may be achieved using trickle or intermittent feeds of water dispersible concentrates as described herein.

Compositions in the form of aerosols and aqueous or non-aqueous solutions or dispersions suitable for spraying, fogging and low- or ultra-low volume spraying may also be used. Suitable solid diluents which may be used in the preparation of compositions suitable for applying the compounds of general formula I include aluminium silicate, kieselguhr, corn husks, tricalcium phosphate, powdered cork, adsorbent carbon black, magnesium silicate, a clay such as kaolin, bentonite or attapulgite, and water soluble polymers and such solid compositions may, if desired, contain one or more compatible wetting, dispersing, emulsifying or colouring agents which, when solid, may also serve as diluent.

Such solid compositions, which may take the form of dusts, granules or wettable powders, are generally prepared by impregnating the solid diluents with solutions of the compound of general formula I in volatile solvents, evaporating the solvents and, if necessary, grinding the products so as to obtain powders and, if desired, granulating or compacting the products so as to obtain granules, pellets or briquettes or by encapsulating finely divided active ingredient in natural or synthetic polymers, e.g. gelatin, synthetic resins and polyamides.

The wetting, dispersing and emulsifying agents which may be present, particularly in wettable powders, may be of the ionic or non-ionic types, for example sulphoricinoleates, quaternary ammonium derivatives or products based upon condensates of ethylene oxide with nonyl- and octyl-phenol, or carboxylic acid esters of anhydrosorbitols which have been rendered soluble by etherification of the free hydroxy groups by condensation with ethylene oxide, or mixtures of these types of agents. Wettable powders may be treated with water immediately before use to give suspensions ready for application.

Liquid compositions for the application of the compounds of general formula I may take the form of - solutions, suspensions and emulsions of the compounds of general formula I optionally encapsulated in natural or synthetic polymers, and may, (if desired, incorporate wetting, dispersing or emulsifying agents. These emulsions, suspensions and solutions may be prepared using aqueous, organic or aqueous-organic diluents, for example acetophenone, isophorone, toluene, xylene, mineral, animal or vegetable oils, and water soluble polymers (and mixtures of these diluents) , which may contain wetting, dispersing or emulsifying agents of the ionic or non-ionic types or mixtures thereof, for example

those of the types described above. When desired, the emulsions containing the compounds of general formula I may be used in the form of self-emulsifying concentrates containing the active substance dissolved in the emulsifying agents or in solvents containing emulsifying agents compatible with the active substance, the simple addition of water to such concentrates producing compositions ready for use. Compositions containing compounds of general formula I which may be applied to control arthropod, plant nematode or helminth pests, may also contain synergists (e.g. piperonyl butoxide or sesamex) , stabilizing substances, other insecticides, acaricides, plant nematocides or anthelmintics, fungicides (agricultural or veterinary as appropriate e.g. benomyl, iprodione) , bactericides, arthropod or vertebrate attractants or repellants orι pheromones, reodorants, flavouring agents, dyes and auxiliary therapeutic agents, e.g. trace elements. These may be designed to improve potency, persistence, safety, uptake where desired, spectrum of pests controlled or to enable the composition to perform other useful functions in the same animal or area treated.

Examples of other pesticidally-active compounds which may be included in, or used in conjuntion with, the compositions of the present invention are:- acephate, chlorpyrifos, demeton-S-methyl, disulfoton, ethoprofos, fenitrothion, malathion, monocrotophos, parathion, phosalone, pirimiphos-methyl, triazophos, cyfluthrin, cypermethrin, deltamethrin, fenpropathrin, fenvalerate, permethrin, aldicarb, carbosulfan, methomyl, oxamyl, pirimicarb, bendiocarb, teflubenzuron, dicofol, endosulfan, lindane, benzoximate, cartap, cyhexatin, tetradifon, avermectins, ivermectin, milbemycins, thiophanate, trichlorfon and dichlorvos.

The compositions for application to control arthropods usually contain from 0.00001% to 95%, more particularly from 0.0005% to 50%, by weight of one or more compounds of general formula I or of total active ingredients (that is to say the compound(s) of general formula I together with other substances toxic to arthropods and plarrt nematodes, anthelmintics, . synergists, trace elements or stabilisers). The actual compositions employed and their rate of application will be selected to achieve the desired effects(s) by the farmer, livestock producer, medical or veterinary practitioner, pest control operator or

other person skilled in the art. Solid and liquid compositions for application topically to animals, timber, stored products or household goods usually contain from 0.00005% to 90%, more particularly from 0.001% to 10%, by weight of one or more compounds of general formula I. For administration to animals orally or parenterally, including percutaneously^ solid and liquid compositions normally contain from 0.1% to 90% by weight of one or more compoundsof general formula I. Medicated feedstuffs normally contain from 0.001% to 3% by weight of one or more compounds of general formula I. Concentrates and supplements for mixing with feedstuffs normally contain from 5% to 90%, and preferably from 5% to 507o, by .weight of one or more compounds of general formula I. Mineral salt licks normally contain from 0.1% to 10% by weight of one or more compounds of general formulai I.

Dusts and liquid compositions for application to livestock, persons, goods, premises or outdoor areas may contain 0.0001% to 15%, and more especially 0.005% to 2.0%, by weight of one or'more compounds of general formula I. Suitable concentrations in treated waters are between 0.0001 ppm and 20 ppm, and more especially 0.001 ppm to 5.0 ppm, of one or more compounds of general formula I and may also be used therapeutically in fish farming with appropriate exposure times.

Edible baits may contain from 0.017- to 5% and preferably 0.01% to 1.0%, by weight of one or more compounds of general formula I.

When administered to vertebrates parenterally, orally or by percutaneous or other means, the dosage of compounds of general formula I will depend upon the species, age and health of the vertebrate and upon the nature and degree of its actual or potential infestation by arthropods. A single dose of 0.1 to 100 mg, preferably 2.0 to 20.0 mg, per kg body weight of the animal or doses of 0.01 to 20.0 mg, preferably 0.1 to 5.0 mg, per kg body weight of the animal per day for sustained medication are generally suitable by oral or parenteral administration. By use of sustained release formulations or devices, the daily doses required over a period of months may be combined and administered to animals on a single Occasion.

The present invention accordingly provides an archropodical, plane nemaCocidal or anthelmintic composition which comprises at least one compound of general formula I , or a salt thereof, in association with one or more compatible diluents or carriers with Che provisos that (1) when the composition comprises a single compound of general formula I wherein R and Z both represent methyl, Y represents thiocyanato and (R ) _n represents 2-, 3- or 4-nitro, 4-methyl, 4-ehloro or 2,4-dinitro substitution; or R represents methyl, Y represents cyano, Z represents

3 unsubstituted amino and (R ) represents 4-chloro,

2,4-dichloro, 3,4-dichloro, 3-chloro-4-methyl or

2-methyl-4-chloro substitution, the composition is not an association of a single compound of general formula

I alone with water or a common organic solvent; (2) when the composition comprises a single _f compound of general formula I wherein R represents methyl, Y represents cyano or CONH^ _* Z represents unsubstiCuCed- amino and (R represents 3- or

4-fluoro substitution; or R represents ethyl, Y represents cyano or C0NH2t Z represents unsubstituted amino and (R ) represents 3- or

4-chloro, 2-, 3- or 4-fluoro or methyl, 3-bromo or 3-nitro substitution; or represents propyl, Y represents cyano or CONHo, Z represents

3 unsubstituted amino and (R ) represents 3-fluoro

substitution; or R represents methyl, Y represents

3 sulphamoyl, Z represents chloro and (R ) represents 4-chloro substitucion; the composition comprises an agriculturally acceptable surface active agent or a feedstuff; (3) when R represents methyl, Y represents nitro, and Z represents chloro or

4 R represents chloro, Y represents nitro, and Z

3 represents methyl and (R ) represents 4-nitro, the composition comprises a pharmaceutically acceptable adjuvant or a feedstuff or is substantially sterile and pyrogen-free or is in unit dosage form; and (4) excluding compositions comprising l-(4-nitrophenyl)-3-nitro-4-pyrazole-carbonitrile or carboxamide. ^■

Medicated feeds which comprise known compounds of general formula I and arthropόdicidally- or anthelmintically-acceptable salts thereof and an edible carrier or diluent form a feature of the present invention.

In experiments on activity against arthropods carried out on representative compounds, the following results (wherein 'Dose mg/kg' indicates the dose of test compound administered in mg per kg animal body weight and ppm indicates the concentration of the compound in parts per million of the test solution applied) have been obtained:-

Test 1

One or more dilutions of the compounds to be tested were made in 50% aqueous acetone, a)Test species: Plutella xylostella (Diamond-back Moth) and Phaedon cochleariae (Mustard Beetle) .

Turnip leaf discs were set in agar in petri-dishes and infected with 10 larvae (2nd instar Plutella or 3rd instar Phaedon) . Four replicate dishes were assigned to each treatment and were sprayed under a Potter Tower with the appropriate test dilution. Four or five days after treatment the dishes were removed from the constant temperature (25°C) room in which they had been held and the mean percentage mortalities of larvae were determined. These data were corrected against the mortalities in dishes treated with 50% aqueous acetone alone which served as controls .

I b)Megoura viciae (Vetch Aphid)

Potted tic bean plants previously infected with mixed stages of Megoura were sprayed to run-off using a laboratory turntable sprayer. Treated plants were held in a greenhouse for 2 days and were assessed for aphid mortality using a scoring system, judging the response in comparison with plants treated with 50% aqueous acetone alone, as controls .

Score

3 all aphids dead

2 few aphids alive

1 most aphids alive 0 no significant mortality

According to the above method (a) an application of 500 ppm of the following compounds was totally effective against the larvae of Plutella xylostella, producing 100% mortality. Compound No.

5, 6, 7, 8, 20, 21, 22, 28, 30, 31, 32, 35, 36, 37, 38, 39, 41, 42, 43, 44, 68, 69, 70, 71, 72, 73, 76, 79, 80, 81, 85, 87, 94, 99, 102, 103, 104, 105, 106, 108, 111, 120, 121 According to the above method (a) an application of 5 ppm of the following compounds was totally effective against the larvae of Phaedon cochleariae,

I producing 100% mortality. Compound No. 36, 53, 57, 58, 70, 71, 74, 79, 80, 85, 90, 91, 97, 98, 99, 102, 104, 106, 108, 109, 111, 112, 113, 116, 118, 120, 121

According to the above method (b) an application of 50 ppm of the following compounds was totally effective against Megoura viciae producing 100% mortality, that is giving a score of 12 from 4 replicates. Compound No

4, 5, 20, 21, 36, 48, 53, 57, 58, 82, 83, 92, 93, 98, 102, 106, 109, 111, 116, 117, 118, 120

The data quoted in Tables 1-3 summarise the results from a number of different experiments carried out to the protocols a) and b) above.

Table 1

Plutella Phaedon Megoura

No. %m 500 ppm %m 10 ppm score/12 50 ppm

5 100

6 100 9

7 100 10

19 100* 100 10

20 100

21 100

42 100 10

10 73 45 10

43 100 11

Table 2

Plutella Phaedon

No. %m 500 ppm %m 10 ppm

8 93

2 89 100

47 96 100

35 100

22 100

23 58 100

24 10 100

10

30 100

28 56

29 48 100

25 21* 100

31 16

15

38 85

41 100

37 100

33 44 100

44 100

20

32 84

40 98 21

39 100

25

Table 3

Phaedon Megoura

No. %m 10 ppm score/12 50 ppm 4 98

45 100 11

9 68 10+

* % mortality at 100 ppm + score at 10 ppm

Test 2

Some 20 larvae of Rhipicephalus appendiculatus were placed in plastic capsules attached to the shaved flank of guinea-pigs. After 3 hours and then at 23 hourly intervals, the guinea-pigs were given a total of 4 subcutaneous injections of the test compound. . Approximately 100 hours after infestation, the guinea- pigs were killed and the engorged tick larvae recovered, counted and kept at 23°C in a humidity cabinet for 14 to 21 days. After this period, the percentage survival through moulting was assessed. Results obtained are given below in Table 4.

Table 4

Compound ^Dos

N ^e o. aa ^e tt ee< ^m aaSccjhh{ ^k S

Result repetition)

5 No ticks recovered

4 No ticks recovered

12 3 Less than five engorged ticks recovered

2.5 Ticks engorged normally but only 62.5 per cent survived

5 No ticks recovered

4 No ticks recovered

3 Number of engorged ticks reduced, only 8.3 per cent survived

2.5 Ticks engorged normally but only 30.0 per cent survived

1.0 Ticks engorged normally but only 47.9 per cent survived 10 No ticks recovered

26

5 Less than five engorged ticks recovered

15 No ticks recovered i

25 5 No ticks recovered

2.5 No ticks recovered

Tes ^

The high activity of the compounds of general formula against the cockroach species Periplaneta americana is demonstrated by results from the following experiment.

0.2 microlitres of an acetone solution of the compound was injected through the soft cuticle between the leg and thorax of ten insects, to give a dose rate of 5 micrograms per g of insect body weight. Ten cockroaches were similarily injected with 0.2 microlitres of acetone alone to serve as controls. After treatment the insects were held in plastic boxes with appropriate food. Five days after treatment the numbers of dead and alive insects were counted and percentage mortalities calculated.

According to the above method a dose of 5 micrograms/g insect body weight of the following compounds was totally effective against the cockroach species Periplaneta americana producing 100% mortality. Compound No.

2, 5, 14, 17, 22, 53

The following Examples illustrate compositions for use against arthropod, plant nematode or helminth pests which comprise, as active ingredient, compounds of general formula I.

Example A A dusting powder may be prepared by intimately mixing:- 5-amino-4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)- 1 to 10% w/w

3-trifluoromethylpyrazole (weight/weight)

Talc superfine to 100% by weight

This powder may be applied to a locus of arthropod infestation, for example refuse tips or dumps, stored products or household goods or animals infested by, or at risk of infestation by, arthropods to control the arthropods by oral ingestion. Suitable means for distributing the dusting powder to the locus of arthropod infestation include mechanical blowers, handshakers and livestock self treatment devices.

The 5-amino-4-cyano-l-(2, 6-dichloro-4-trifluoro¬ methylphenyl)-3-trifluoromethylpyrazole may, if

I desired, be replaced in the above dusting powder by any other compound of general formula I. Example B

An edible bait may be prepared by intimately mixing:- 5-amino-4-cyano-l-(2,6-dichloro-4- trifluoro eChylphenyl)- 0.1 Co 1.0% w/w 3-CrifluoromeChylpyrazole

Wheat flour ,. 80% w/w

Molasses to 100% w/w

This edible bait may be distributed at a locus, for example domestic and industrial premises, e.g. kitchens, hospitals or stores, or outdoor areas, infested by arthropods, for example ants, locusts, cockroaches and flies, to control the arthropods by oral ingestion.

The 5-amino-4-cyano-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-trifluoromethylpyrazole may, if desired, be replaced in the above edible bait by any other compound of general formula I.

Example C A solution may be prepared containing:- 5-amino-4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)- 15% w/v 3-trifluoromethylpyrazole (weight/volume)

DimeChylsulphoxide to 100% by volume by dissolving the pyrazole derivative in a portion of the dimethylsulphoxide and then adding more dimethyl- sulphoxide to the desired volume. This solution may be applied to domestic animals infested by arthropods, percutaneously as a pour-on application or, after sterilisation by filtration through a polytetrafluoro- ethylene membrane (0.22 um pore size), by parenteral injection, at a rate of application of from 1.2 to 12 ml of solution per 100 kg of animal body weight.

The 5-amino-4-cyano-l-(2,6-dichloro-4-trifluoro- methylphenyl)-3-trifluoromethylpyrazole may, if desired, be replaced in the above solution by similar amounCs of any oCher compound of general formula I. Example D

A weCCable powder may be formed from:-

5-amino-4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)- 50% w/w

3-trifluoromethylpyrazole Ethylan BCP (a nonylphenol/ethylene oxide condensate containing 9 moles of ethylene oxide per mol of phenol) 5% w/w

Aerosil (silicon dioxide of microfine- particle size) 5% w/w Celite.PF (synthetic magnesium silicate carrier) 40% w/w by adsorbing the Ethylan BCP onto the Aerosil, mixing with the other ingredients and grinding the mixture in a hamme -mill to give a wettable powder, which may be diluted with water to a concentration of from .0.001% to 2% w/v of Che pyrazole compound and applied Co a locus of infesCaCion by arChropods, for example dipCerous larvae, or plane nemaCodes by spraying, or to domestic animals infested hy, or at risk of infestation by, arthropods, by spraying or dipping, or by oral administration as drinking water, to control the arthropods or helminths.

The 5-amino-4-cyano-l-(2,6-dichloro-4-trifluoro- methylphenyl)-3-trifluoromethylpyrazole may, if desired, be replaced in the above wettable powder by any other compound of general formula I. Example E

A slow release bolus may be formed from granules containing a density agent, binder, slow-release agent and 5-amino-4-cyano-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-trifluoromethylpyrazole compound at varying percentage compositions. By compressing the mixture a bolus with a specific gravity of 2 or more can be formed and may be administered orally to ruminant domestic animals for retention within the reticulo-rumen to give a continual slow release of pyrazole compound over an extended period of time to control infestation of the ruminant domestic animals by arthropods or helminths. ,

The 5-amino-4-cyano-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-trifluoromethylpyrazole may, ^" if desired, be replaced in the above bolus by any other compound of general formula I.

Example F A slow release composition may be prepared from:- 5-amino-4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)- 0.5 to 25% w/w 3-trifluoromethylpyrazole polyvinylchloride base to 100% w/w by blending the polyvinylchloride base with the pyrazole compound and a ^' suitable plasticiser, e.g. dioctyl phthalate, and melt-extruding or hot-moulding the homogenous composition into suitable shapes, e.g. granules, pellets, brickettes or strips, suitable, for example, for addition to standing water or, in the case of strips, fabrication into collars or ear-tags for attachment to domestic animals, to control insect pests by slow release of the pyrazole compound.

Thβ compounds of general formula I can be prepared by the application or adaptation of known methods (i.e. methods heretofore used or described in the chemical literature), generally heterocycle formation followed where necessary by changing substituents with protection/deprotection of other substituents if necessary, for example as hereinafter described.

In the following description when symbols appearing in formulae are not specifically defined it is to be understood that they are "as hereinbefore defined" in accordance with the first definition of each symbol in this specification.

Compounds of general formula I conforming to general formula IA wherein Y' represents the cyano or nitro group or a group RSO , RSO or RS, a straight- or branched-chain alkoxycarbonyl group containing from 2 to 7 carbon atoms, or a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms which may be unsubstituted or substituted by one or more halogen atoms, Z' represents the unsubstituted amino group or a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms, and R represents a fluorine, chlorine or bromine atom, the cyano group or a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms which may be unsubstituted or substituted by one or more halogen

atoms, or a cycloalkyl group containing from 3 to 6 carbon atoms, may be prepared by the process which comprises

(i) the reaction of a compound of the general formula II, or an acid addition salt thereof, e.g. the hydrochloride, with (1), when R in the compound of general formula IA represents a fluorine, chlorine or bromine atom, an optionally halogenated straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms or a cycloalkyl group containing from 3 to 6 carbon atoms, a compound of the general formula III, wherein R represents the cyano group or a straight- or branched-chain alkanoyl group containing o from 2 to 5 carbon atoms and R represents a straight- or branched-chain alkoxy group containing from 1 to 4 carbon atoms, preferably ethoxy, the hydroxy group or a fluorine, chlorine or ¹ bromine atom, or (2), when in the compound of general formula IA represents the cyano group (and Y' represents the cyano group and Z' represents the unsubstiCuCed amino group), Cetracyanoethylene.

The reaccion of a compound of general formula II wich a compound of general formula III (opcionally prepared _in siCu) or CeCracyanoeChylene may be effecced in Che presence of an inerC organic solvenC, for example an alkanol conCaining from 1 to 4 carbon atoms, e.g. ethanol, acetic acid, ethoxyethanol or an ether, and at a CemperaCure from ambienC Cemperature to Che reflux CemperaCure of Che reaccion mixCure and opcionally in Che presence of an alkali eCal, e.g. sodium or potassium, acetate, carbonate or bicarbonate or organic base e.g. triethylamine. When an acid addition salt of the compound of general formula II is used, the reaction with Che compound of general formula III is effec ed in Che presence of an alkali meCal, e.g. sodium or potassium, acetate, carbonate or bicarbonate.

(ii) Compounds of general formula IA wherein Z' represents the unsubstituted amino group may alternatively be prepared directly by reacting a compound of general formula 'CH2CN with a compound of general formula II in the presence of a compound of general formula R C(R°) _β wherein R represents a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms which may be unsubstiCuCed or subsCiCuCed by one or more halogen aComs or a cycloalkyl group conCaining from 3 Co 6 carbon aComs and R° represencs an alkoxy group which may be

sCraighC- or branched-chain and preferably conCains from 1 o 4 carbon aComs, in an inerC organic solvenC, preferably eChanol, aC a CemperaCure from a bienC Co reflux. (iϋ) Compounds of general formula IA wherein Z' represenCs the unsubstituted amino group and R represents the cyano group may be obtained by the reaction of a compound of. the general formula IV with a molar equivalent of compound of general formula 'CH2CN, i.e. malononitrile when Y' represents the cyano group, generally in the presence of an anhydrous inert organic solvent, e.g. ethanol, and a molar equivalent of a base, e.g. sodium hydride, and at a temperature from 0 to 50°C. The compounds of general formula IA may be prepared by reaction of a compound of general formula II with a compound of general formula III or tetracyanoethylene with isolation of an intermediate compound of general formula V from the reaction mixture. When the reaccion of a compound of general formula II wich a compound of general formula III is effecced in aceCic acid, in Che absence or presence of an alkali meCal, e.g. sodium or poCassium, acetate, the intermediate compound of general formula V may • separate from Che reaccion mixCure, depending upon iCs solubiliCy in Che reaccion medium, and may, if desired, be isolaCed before being cyclised as

hereinbefore described Co a compound of general formula IA. The cyclisaCion of a compound of general formula V, which consCiCuCes a feaCure of Che invenCion may be effecced in Che presence of an inerC organic solvenC, for example an alkanol conCaining from 1 Co 4 carbon atoms, e.g. ethanol, acetic acid or ethoxyethanol, at a temperature of from ambient temperature up to the reflux temperature of the reaction mixCure, and opcionally in Che presence of sodium eChoxide when Che solvenC is eChanol.

Ic will be appreciaCed chaC in Che preparacion of compounds of general formula I Che following subsidiary processes or adapCaCions chereof may be performed in an appropriaCe combinaCion Co achieve Che compound soughC.

Compounds of general formula I which conform to general formula IB wherein R represents an group, wherein R9 represents a straight- or branched-chain alkyl or alkoxy group conCaining from 1 Co 6 carbon acorns, or a cycloalkyl group

2 conCaining from 3 Co 6 carbon acorns and R represenCs a hydrogen aCo or an R C(=*0)- group

Q which is idencical Co Che group R C( ^β 0)- represenCed by 1 ^x or -NR1R represenCs a cyclic imide as hereinbefore defined, may be prepared by Che reaccion

of a compound of general formula I wherein Z represents Che unsubsCiCuCed amino group, or an alkali meCal sale Chereof, wich a compound of Che general formula:- R ⁹ C0X VI wherein X represenCs a chlorine or bromine atom, or with a compound of the general formula: -

(R ⁹ C0) ₂ 0 VII or with a dicarboxylic acid derivative. The reaction may be conducted in the absence or presence of an inert organic solvent, for example acetonitrile, tetrahydrofuran, a ketone, e.g. acetone, an aromatic hydrocarbon, e.g. benzene or toluene, chloroform, dichloromethane or dimethylformamide, and optionally in the presence of an acid-binding agent, for example pyridine, trieChylamine or an alkali meCal, e.g. sodium or poCassium, carbonaCe or bicarbonaCe, aC a CemperaCure from 0°C Co Che reflux CemperaCure of Che reaccion medium, Co give a compound of general formula IB wherein R 1 represenCs an group wherein

R 9 is as hereinbefore defined and R2 represenCs a

9 hydrogen aCo or an R C^O)- group, depending upon ehe reaccion condicions chosen and/or Che use of an excess of Che compound of general formula VI or VII.

-62-

Compounds of general formula IB wherein R

2 represenCs a formyl group and R represenCs a hydrogen acorn may be prepared by reaccion of a compound of general formula I, wherein Z represenCs che unsubsCiCuCed amino group wich formic acid. The reaccion may be conducted in an inert organic solvent, for example a ketone e.g. methylisobutyl ketone, or an aromatic hydrocarbon, e.g. benzene or toluene, at the reflux CemperaCure of Che reaccion mixCure. Compounds of general formula IB wherein R

2 represents a formyl group and R represents a hydrogen atom or a formyl group, may be prepared by the reaction of a compound of general formula I, wherein Z represents the unsubstiCuCed amino group wich formylaceCic anhydride. FormylaceCic anhydride may be prepared from formic acid and aceCic anhydride and Che reaccion wich Che compound of geheral formula I may be conducted in Che absence or presence of an inerC organic solvenC, for example a keCone, e.g. aceCone, or an aromaCic hydrocarbon, e.g. benzene or Coluene, and opcionally in Che presence of an acid-binding agenC, for example pyridine, CrieChylamine or an alkali meCal, e.g. sodium or potassium, carbonate or bicarbonate, at a temperature from 0°C to the reflux temperature of Che reaccion mixCure, Co give a compound of general formula IB

wherein R1 represenCs a formyl group and R2

represenCs a hydrogen aCom or a formyl group, depending upon the reaction conditions chosen and/or the use of an excess of formylacetic anhydride. Compounds of general formula IB wherein R represents a formyl group or a group R C(-0)- and

2 R represents a hydrogen atom may be prepared by the a selective removal by hydrolysis of an R C(=0)- group or a formyl group from a compound of general formula IB wherein R ¹ and R ² both represent a R ⁹ C(=0) group or a formyl group. Hydrolysis is effected under mild conditions, for example by treatment with an aqueous-ethanolic solution or suspension of an alkali metal, e.g. sodium or potassium, bicarbonate, or with aqueous ammonia.

Compounds of general formula IB wherein R represents a straight- or branched-chaiη alkoxycarbonyl group containing from 2 to 7 carbon atoms which is unsubstiCuCed or substituted by one or more halogen atoms, and R represents a hydrogen atom may be prepared by the reaction of a compound of Che general formula VIII, wherein R represenCs an alkoxycarbonyl group R ¹¹ C(=»0), wherein R ¹ represenCs a sCraighC- or branched-chain alkoxy group conCaining from 1 Co 6 carbon aComs (which is unsubsCiCuCed or subsCiCuCed by one or more halogen aComs) or a phenoxy group, wich a compound of Che

general formula:-

R ^U H I

Co replace a firsC group represenCed by Che symbol R by a hydrogen aCom, and Co replace the second group represented by the symbol R by an alkoxycarbonyl group when R represents a phenoxycarbonyl group, or, if desired, to replace the second group represented by Che symbol R by anoCher alkoxycarbonyl group when R in formula VIII represenCs an alkoxycarbonyl group. As will be apparenC Co Chose skilled in Che arc, Che desired compound of general formula IB is obCained by seleceion of Che appropriaCe compounds of general formulae VIII and IX. The reaccion may be effecced in waCer or an inerC aqueous-organic or organic solvenC, for example an alkanol conCaining 1 Co 4 carbon aComs, e.g. echanol, or an aromatic hydrocarbon, e.g. benzene or toluene, or which is preferably an excess of the compound of general formula IX, at a CemperaCure from ambienC CemperaCure Co Che reflux CemperaCure of Che reaccion mixCure and, if necessary, aC elevaCed pressure, and opcionally in Che presence of a base, for example an alkali metal alkoxide, e.g. of the compound of general formula IX.

Compounds of general formula IB wherein R and

2

R , which may be Che same or differenC, each represenCs a formyl group or a R C(=0)- group, may be prepared by the reaction of an alkali metal, e.g. sodium or potassium, derivative of a compound of general formula IB wherein R represents a group

R C(=0)- as hereir.ϊefors defined, or a forsyl group, and

2 R represents a hydrogen atom with formic acid, formylacetic anhydride or a compound of general formula VI. Reaction may be effected in an inert aprotic solvent, e.g. dimethylformamide, at a temperature from laboratory temperature to Che reflux CemperaCure of the reaction mixture.

Alkali metal derivatives of compounds of general formula _I (wherein Z represents the unsubstituted amino group) or IB wherein R represents a group and R2 represents a hydrogen atom may be prepared iτx situ by reaction with an alkali metal, e.g. sodium or potassium, hydride, in an inert aprotic solvent, e.g. dimethylformamide, at a temperature from laboraCory CemperaCure Co Che reflux CemperaCure of

Che reaccion mixCure.

Compounds of general formula VIII wherein R represenCs a group R C(=0)-, may be prepared as hereinbefore described. Compounds of general formula

VIII wherein R represenCs a phenoxycarbonyl group may be prepared by Che reaccion of a compound of

general formula I (wherein Z represenCs Che unsubsCiCuCed amino group), wich a compound of Che general formula:-

R ¹² C0X VIA

17 , wherein R represenCs a phenoxy group, or wich a compound of Che general formula:-

(R ¹² CO) ₂ 0 VIIA using Che reaccion condicions hereinbefore described for Che reaccion of a compound of general formula I wich a compound of formula VI or VII.

Compounds of general formula IB wherein R represenCs a group R 13 which represenCs a sCraighC- or branched-chain alkyl group conCaining from 1 Co 6 carbon aComs (which may be unsubsCiCuCed or subsCiCuCed by alkoxycarbonyl groups conCaining from 2

Co 5 carbon aComs) or a cycloalkyl group conCaining

2 from 3 Co 6 carbon aComs, and R represenCs a hydrogen aCom may be prepared by Che removal of Che group R C(=0)- of a compound of Che general formula IB, wherein R represenCs a group R ^J and R represenCs a group R C(=0)- . Removal of Che group R C(=0)- may be effecced by seleccive hydrolysis under mild condicions, for example by CreaCmenC wich an alkali meCal, e.g. sodium or potassium, hydroxide in water or an inert organic or aqueous-organic solvent, for example a lower alkanol, e.g. methanol, or a mixture of water and lower alkanol, at a

temperaCure from laboraCory CemperaCure up Co Che reflux CemperaCure of Che reaccion mixCure.

Compounds of general formula IB, wherein R represenCs a group R 13 and R2 represenCs a group

_ g

-> R C("0)-, may be prepared by reaccion of a compound of general formula IB wherein R represents a hydrogen atom , or an alkali metal, e.g., sodium or potassium, derivative thereof, with a compound of the general formula:- 0 _R 13 _χ l _χ

, wherein X represents a chlorine, bromine or iodine atom. Reaction may be effected in an inert organic solvent, e.g. dichloromethane, tetrahydrofuran, or dimechylformamide, aC a 5 CemperaCure from laboraCory CemperaCure up Co Che reflux CemperaCure of Che reaccion mixCure and, when a compound of general formula IB is used, in Che presence of a base, e.g. Tricon B; or by reaccion of a compound of general formula IB wherein R represenCs 13 0 Che hydrogen aCom and R represenCs a group R. wich a compound of general formula VI or VII.

Compounds of general formula I wherein Z represenCs an N-(alkyl or cycloalkyl)-N-formylamino group as hereinbefore described may be prepared in a 5 similar manner to Che process above using, where appropriate, formylacetic anhydride instead of a compound of general formula VI or VII.

Compounds of general formula IB wherein one of R and R ² or both of R and R ² represent straight- or branched- chain alkyl group conCaining from 1 Co 6 carbon aComs or cycloalkyl group conCaining from 3 Co 6 carbon aComs, groups represenCed by Rl and R2 being idenCical, may be prepared by reaccion of a compound of general formula I, wherein Z represenCs Che unsubsCiCuCed amino group, or an alkali meCal, e.g. sodium or poCassium, derivaCive Chereof, wich a compound of general formula X, in Che absence or presence of an inerC organic solvenC, for example an aromaCic hydrocarbon, e.g. benzene or Coluene, chloroform, dichloromeChane, CeCrahydrofuran or dimeChylformamide, and opcionally in Che presence of an acid-binding agenC, for example pyridine, CrieChylamine or an alkali meCal, e.g. sodium or poCassium, bicarbonate, at a temperature from 0°C up to the reflux temperature of the reaction mixture. Alkali metal derivaCives of compounds of formulae IB (wherein represenCs a hydrogen aCom) and I (wherein Z represenCs Che unsubsCiCuCed amino group) may be prepared in sicu by Che reaccion of Che compounds, wich an alkali meCal, e.g. sodium or poCassium, hydride, aC a CemperaCure from laboraCory CemperaCure Co Che reflux CemperaCure of the- reaction mixture.

Compounds of general formula I wherein Z represenCs a sCraighC- or branched-chain alkoxymeChyleneamino group conCaining from 2 Co 5 carbon atoms which may be unsubstituted or substituted on methylene by a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms may be prepared by the reaction of a compound of general formula I (wherein Z represents the unsubstituted amino group) with a trisalkoxyalkane in the presence of an acidic catalyst, e.g. p-toluenesulphonic acid, at a temperature from ambient temperature to the reflux temperature of the reaction mixture.

Compounds of general formula I, wherein Z represents a straight- or branched-chain alkylsulphenylamino group containing from 1 to 4 carbon atoms, may be prepared by the reaction of compounds of general formula I (wherein Z represenCs Che unsubsCiCuCed amino group) wich an alkanesulphenyl chloride in Che presence of a base, e.g. sodium hydride, and opcionally in Che presence of a crown echer caCalyst, e.g. 15-crown-5.

The reaccion may be performed in a solvenC, e.g. CeCrahydrofuran, aC a CemperaCure from 0°C Co Che reflux CemperaCure of Che reaccion mixCure.

Compoun s o general formula I w ere n Z represenCs -NHC^R wherein R represenCs Che hydrogen aCom or a sCraighC- or branched-chain alkyl group conCaining from 1 Co 4 carbon aComs may be prepared by reaccion of a compound of general formula I wherein Z represenCs -N=C(0R )R wherein R represenCs a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms with a reducing agent, preferably sodium borohydride. The reaction may be effected in an inert organic solvent, ethanol or methanol being preferred, at a CemperaCure from 0°C Co Che reflux CemperaCure of Che reaccion mixCure.

Compounds of general formula I wherein Y represenCs may be prepared by parCial hydrolysis of a compound of general formula I wherein Y represenCs -CN preferably wich sulphuric acid aC a CemperaCure from ambienC CemperaCure Co ₍ 100°C. Compounds of general formula I wherein Y represenCs Che chlorine, bromine or iodine aCom may be prepared by reaccion of a compound of general formula XI wich a halogenaCing agenC, preferably N-halosuccinimide in an inerc solvenC, preferably carbon CeCrachloride, aC a CemperaCure from ambienC CemperaCure Co Che reflux CemperaCure of Che reaccion mixCure.

Compounds of general formula I wherein Z represenCs Che chlorine, bromine or iodine atom may be prepared by diazotisation of a compound of general formula I wherein Z represents -NH2 with an alkyl nitrite, preferably tert-butyl nitrite, in the presence of a halogenating agent preferably bromoform, iodine or anhydrous copper chloride at a temperature from 0°C to 100°C.

Compounds of general formula I wherein Y represents the nitro group may be prepared by reacting a compound of general formula XI with a nitrating agent, preferably nitric acid optionally in the presence of sulphuric acid or nitric acid in a solvent such as acetic acid or acetic anhydride at a temperature from 0°C to 100°C.

Compounds of general formula I wherein Y represents -S0 ₂ NR ¹⁶ R ¹⁷ wherein R ¹⁶ and R ¹⁷ , which may be the same or different, each represent the hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms" may be prepared by reacting a compound of general formula XIV with an amine of the general formula R NH in a solvent such as toluene or water at a temperature from 0°C to the reflux temperature of the reaction mixture.

Compounds of general formula I wherein Y represents -CONR R may be prepared by reacting

2 a compound of general formula XV wherein X represents a chlorine or bromine atom or activated ester moiety e.g. 4-nitrophenoxy group, especially the chlorine atom, with an amine of the general formula

R R NH, in a solvent such as toluene or water, at a temperature from 0°C to the reflux temperature of the reaction mixture. Intermediates of general formula XI may be prepared by decarboxylation of a compound of general formula XVI, performed by heating at a temperature from 100°C to 250°C optionally in the presence of an inert organic solvent, particularly

Φ N,N-dimethylaniline.

Intermediates of general formula XI wherein Z is the unsubstituted amino group and R represents a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms which may be unsubstituted or substituted by one or more halogen atoms may also be prepared by reaction of an appropriate β-ketonitrile or derivative thereof e.g. the imine with an arylhydrazine in an inert organic solvent such as ethanol optionally in che presence of an acidic or, basic caCalysC aC a CemperaCure from ambienC Co 100°C.

Alternatively intermediates of general formula XI may be prepared directly from esters of compounds of general formula XVI by heating in an inert organic solvent preferably acetic acid at a temperature from 50°C to reflux, in the presence of a strong acid preferably hydrobromic acid.

Intermediates of general formula XVI may be prepared by hydrolysis of esters of general formula I

18 1ft wherein Y represents -C00R wherein R ⁱ⁰ represents a straight- or branched- chain alkyl group containing from 1 to 6 carbon atoms, preferably with an alkali metal hydroxide in a solvent such as an aqueous alcohol at a temperature from 0°C to the reflux temperature of the reaction mixture. Intermediates of general formula XIV may be prepared by reacting a compound of general formula XI with chlorosulphonic acid at a temperature from 0°C to 150°C.

Intermediates of general formula XV are prepared by reacting a compound of general formula XVI wich a chlorinaCing or brominaCing agenC or e.g. 4-niCrophenol (preferably Chionyl chloride) aC a temperature from ambient temperature to the reflux temperature of the reaction mixture.

Compounds of general formula I wherein Y represenCs wherein R18 represenCs a sCraighC- or branched-chain alkyl group containing from 1 to 6 carbon atoms may be prepared by the reaction of a compound of general formula XI with an acylating agent such as R 18C0C1 in the presence of a catalyst such as aluminium chloride and in an inert organic solvent such as 1,1,2,2-tetrachloroethane and at a temperature from 0°C to the reflux temperature of Che reaccion mixCure.

When Z is an amino group iC may also be acylated " and subsequent hydrolysis using an acid such as hydrochloric or hydrobromic acid in a solvent such as dioxan or acetic acid may be necessary. . Compounds of general formula I wherein Y represents -C(=0)R 18 may also be prepared by the reaction of nitriles of the general formula I wherein

Y represents -CN with an organometallic reagent such as a compound of general formula R tgX in an inert organic solvent such as diethyl ether or tetrahydrofuran, at a CemperaCure from 0°C Co reflux.

Compounds of general formula IC may be prepared by Che reaccion of a compound of general formula I wherein Y represenCs Che ChiocyanaCo group wich an organomeCallic reagenC such as a compound of general formula R gX^ in an inerC organic solvenC such as

dieChyl eCher or CeCrahydrofuran, and aC a temperature from ambienC CemperaCure Co Che reflux temperature of the reaction mixture.

Compounds of general formula IC wherein RS is other than a 1-alkenylthio group may also be prepared by reacting a compound of general formula I wherein Y represents the thiocyanato group with a base, preferably sodium hydroxide, or a reducing agent, preferably sodium borohydride, in the presence of a reagent of general formula R'X wherein R' is as hereinbefore defined for R with the exclusion of 1-alkenyl groups, for example methyl iodide in an inert organic or aqueous-organic solvent such as an alcohol e.g. ethanol or a mixture of an alcohol and water, the reaction being performed at a temperature from ambient to reflux.

Alternatively compounds of general formula IC wherein RS is other than a 1-alkenylthio group may be prepared by reductive alkylation of disulphides of general formula XVII employing a reducing agent preferably sodium dichionice or sodium borohydride, in Che presence of a base, preferably sodium hydroxide or sodium carbonaCe, and of a reagenC of general formula R'X such as meChyl iodide in an inerC organic or aqueous-organic solvenC such as an alcohol e.g. eChanol or a mixCure of an alcohol and waCer, aC a CemperaCure from ambienC Co reflux.

AlCernaCively compounds of general formula IC may. be prepared from a halide of general formula I wherein Y represenCs a bromine or iodine aCom by metal exchange using a strong base, preferably butyl lithium, and subsequent addition of the appropriate disulphide of general formula R-S-S-R in an inert organic solvent such as tetrahydrofuran, and the reaction is performed at a temperature from -78°C to ambienC. AlCernaCively, compounds of general formula IC wherein RS represenCs a straight- or branched-chain alkylthio group containing from 1 to 6 carbon atoms which may be unsubstituted or substituted by one or more halogen atoms may be prepared by reacting a compound of general formula XI with an alkanesulphenyl halide (which may be optionally substituted by one or more halogen atoms) in an inert organic 'solvent, preferably chloroform, in the presence of a base such as pyridine, and ^' at CemperaCures from 0° Co reflux.

Compounds of general formula IC wherein RS represents a methylthio group which is substituted by three halogen atoms which may be the same or different may also be prepared by the reaction of a compound of general formula I wherein Y represents the thiocyanato group with a source of halogenocarbene, such as chloroform and sodium hydroxide, preferably with phase transfer catalysis using for example benzyl- • triethy1ammonium chloride or tetrabutylammonium chloride.

Compounds of general formula IC wherein RS represents a straight- or branched-chain alkylthio group containing from 1 to 6 carbon atoms which is substituted by one or more fluorine atoms may also be prepared by a halogen exchange reaction of a compound of general formula IC wherein RS represents a straight- or branched-chain alkylthio grOup containing from 1 to 6 carbon atoms which is substituted by one or more chlorine atoms wich a fluorinaCing agenC such

as a mixCure of anCimony Crifluoride and anCimony penCachloride, KF or CsF in an aproCic solvenC such as sulfolane aC a CemperaCure from 50°C Co reflux. Compounds of general formula I wherein Y represenCs Che ChiocyanaCo group may be prepared by

Che reaccion of a compound of general formula XI wich a Chiocyanacing agenC such as alkali meCal or ammonium sales of Chiocyanic acid (e.g. NaSCN) and bromine in an inerc organic solvenC such as mechanol, and aC a CemperaCure from 0°C Co 100°C.

InCermediaCes of general formula XVII may be prepared by hydrolysis of chiocyanaCes of general formula I wherein Y represenCs Che ChiocyanaCo group, preferably using hydrochloric acid in Che presence of eChanol aC a CemperaCure from ambienC Co reflux

CemperaCure; Chey may also be prepared by reduccion of Che ChiocyanaCes by sodium borohydride in an alcohol preferably eChanol aC a CemperaCure from ambienC Co reflux. Compounds of general formula I wherein Y represenCs a group RSO may be prepared by Che oxidaCion of compounds of general formula IC by an oxidising reagenC preferably 3-chloroperbenzoic acid in an inerC organic solvenC such as dichloromeChane or by hydrogen peroxide in aceCic acid aC a

CemperaCure from 0°C Co Che reflux CemperaCure of Che reaccion medium.

Compounds of general formula I wherein Y represents a group RS0 ₂ may also be prepared by the above process, by employing an excess of Che oxidising agent. Compounds of general formula I wherein Y represents a group RSO2 wherein R represents a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms which is substituted by one or more fluorine atoms may also be prepared by a halogen exchange reaction of a compound of general formula I wherein Y represents a group RS0 ₂ wherein R represents a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms which is substituted by one or more chlorine atoms with a fluorinating agent such as a mixture of antimony trifluoride and antimony pentachloride, KF or CsF at a temperature from 50°C to 200°C. •

Compounds of general formula I wherein Y represenCs a group RS0 may also be prepared by reaccion of a compound of general formula XI wich Che appropriaCe sulphonic anhydride of general formula (RS0 ₂ O for example CrifluoromeChanesulphonic or meChanesulphonic anhydride and in Che presence of aluminium chloride as caCalysC, and employing an inerC organic solvenC such as 1,1,2,2-CeCrachloroethane at a temperature from ambient to 150°C.

Compounds of general formula I wherein Z represents a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms, the carboxy group, a group R 19S wherein R19 represents a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms which may be unsubstituted or substituted by one or more halogen atoms or Z represents a trialkylsilyl group containing from 1 to

6 carbon atoms in each alkyl group which may be the same or different may be prepared by the reaction of a compound of general formula I wherein Z represents a hydrogen, bromine or iodine atom with a lithiating agent preferably lithium diisopropylamide or n-butyl lithium, and reaction with the appropriate substrate from alkyl halide, carbon dioxide, dialkylsulphides or trialkylsilyl halides respectively at a temperature from -78°C to ambient temperature, and in an inert solvent, preferably tetrahydrofuran.

Compounds of general formula I wherein Z represents a hydrogen aCom may be prepared by diazoCisaCion of an amine of general formula I wherein Z represenCs Che unsubsCiCuCed amino group using an alkyl niCriCe, preferably CerC-buCyl niCriCe, in an inerc solvenC preferably CeCrahydrofuran, aC a CemperaCure from ambienC CemperaCure Co Che reflux CemperaCure of Che reaccion mixCure.

Compounds of general formula I wherein Z represenCs a group R 19SO may be prepared by Che reaccion of a compound of general formula I wherein Z represenCs a group R 19S wich an oxidising agenC, preferably 3-chloroperbenzoic acid in a solvenC such as dichloromechane, or by hydrogen peroxide in acetic acid at a CemperaCure from 0°C Co Che reflux

CemperaCure of Che reaccion mixCure.

Compounds of general formula I wherein Z represenCs a group R 19S0 ₂ may also be prepared by the above process, by employing an excess of the oxidising agent.

Compounds of general formula I wherein Z represenCs Che fluorine a om or Che cyano group may be prepared by Che reaccion of a halide of general formula I wherein Z represenCs Che chlorine or bromine aCom wich an alkali meCal fluoride, preferably caesium fluoride, or wich an alkali meCal cyanide preferably KCN, under anhydrous condicions in an inerC solvenC, preferably sulfolane, and at a temperature from ambient temperature to 150°C.

Compounds of general formula I wherein Z represents Che niCro group may be prepared by oxidacion of amines of general formula I wherein Z represenCs Che unsubsCiCuCed amino group wich an oxidanC, preferably CrifluoroperaceCic acid or m-chloroperbenzoic acid and in an inerC organic solvenC preferably dichloromeChane aC a CemperaCure from 0°C Co reflux.

Compounds of general formula I wherein Z represents Che cyano group may be prepared by dehydraCion of the corresponding amide preferably by heating with phosphorous pentoxide at a temperature from 50°C to 250°C.

The amides may be prepared (i) by reacting a carboxylic acid of general formula I wherein Z represents a carboxy group with a chlorinating agent preferably thionyl chloride, and (ii) reacting the resultant acid chloride of general formula XVIII with ammonia:- (i) the reaction with a chlorinating agent preferably thionyl chloride is generally conducted at a temperature from ambient temperature to the reflux temperature of the reaction mixCure; (ii) Che reaccion wich ammonia is generally conducCed in a solvenC which may be inerC, preferably coluene, or in Che presence of waCer, and aC a CemperaCure from 0°C o 100°C.

Compounds of general formula I wherein Y represenCs a group RS0 ₂ is oCher than a 1-alkenylsulphonyl group may be prepared alternatively by reaction of sulphinate metal (e.g. sodium) salts with a reagent of general formula R'X or preferably a sulphate of general formula (R') ₂ S0/, in a solvent such as water and in the presence of sodium bicarbonate at a temperature from 0°C to 100°C.

The intermediate sulphinate sodium salts may be prepared by reaction of sulphonyl chlorides of general formula XIV with sodium sulphite in the presence of sodium bicarbonate and water as solvent, at a temperature from 50°C Co reflux.

Intermediates of general formula XIV may also be

Φ prepared from the thiocyanates of general formula I wherein Y represents a thiocyanato group by chlorination using chlorine in a solvent!, preferably water, at a temperature from ambient to reflux.

3

Compounds of general formula I wherein represents a haloalkylsulphinyl group may be prepared by oxidation of a haloalkylthio derivative of general formula I, preferably with m-chloroperbenzoic and in an inert organic solvent preferably dichloromechane, aC a CemperaCure from 0°C Co reflux. Compounds of general formula I wherein R represenCs a haloalkylsulphonyl group may be prepared in a similar manner, by employing Cwo molar equivalenCs of oxidanC.

Compounds of general formula I wherein Y represents the fluorine atom may be prepared by diazotisation of corresponding amines using sodium nitrite in CeCrafluoroboric acid and sulphuric acid aC a CemperaCure from -10°C Co +10°C, followed by phoColysis in Che presence of excess sodium CeCrafluoroboric acid aC a temperature from -30°C to ambient.

Intermediate amines above may be prepared by reduction of nitro compounds of general formula I wherein Y represents a nitro group, preferably with zinc in ethanol at a temperature from ambient to reflux.

Compounds of general formula I wherein Y represents the methyl group may be prepared by ' reduction of an acid of general formula XVI using a reducing agenC, preferably borane-CeCrahydrofuran complex in a solvenC preferably CeCrahydrofuran aC a CemperaCure from .-30°C Co re lux. Compounds of general formula I wherein Z represenCs a CrialkylsilylmeChyl group as hereinbefore defined may be prepared by Che reaccion of a compound of general formula I wherein Z represenCs Che meChyl group wich a lichiacing agenC preferably lichium diisopropylamide or n-buCyl lichium, and reaccion wich a Crialkylsilyl halide aC a CemperaCure from -78°C Co ambienC, and in an inerC organic solvenC preferably CeCrahydrofuran, opcionally in an inerC aCmosphere.

The following processes opcionally followed by Che subsidiary processes hereinbefore described permic Che preparacion of Che remaining compounds of general formula I noC described above, as well as some whose preparacion is described above.

Compounds of general formula I wherein R represents a chlorine, bromine or iodine atom and Z represents Che unsubsCiCuCed amino group, may be prepared by Che diazoCisaCion of Che (diamino) compounds of general formula I in which Z represents and R is replaced by amino, using a molar equivalent of sodium nitrite in a mineral acid, for example a mixture of concentrated sulphuric acid and acetic acid, at a temperature from 0 to 60°C, and by subsequent reaction with the appropriate copper salt and appropriate mineral acid or with an aqueous solution of potassium iodide (when R represents an iodine atom) at a temperature from 0 to 100°C.

The diamino compounds above wherein Y represenCs che cyano group may be prepared by Che reaccion of poCassium cyanoform KC(CN) ₃ wich a phenylhydrazine of general formula II in Che presence of hydrochloric acid, aC a CemperaCure from 50°C Co Che reflux CemperaCure of Che reaccion mixCure.

Compounds of general formula I wherein R represenCs Che fluoro eChyl group may be prepared by reacCing a compound of general formula XII wich a fluorinaCing agenC, preferably dieChylaminosulphur trifluoride, in an inert organic solvent, preferably dichloromethane, at a temperature from -78°C to the reflux temperature of the reaction mixture.

Intermediates of general formula XII may be prepared by reduction of compounds of general formula XIX preferably with lithium borohydride in an inert organic solvent e.g. tetrahydrofuran at a temperature from 0°C Co Che reflux CemperaCure of Che reaccion mixCure.

InCermediaCes of general formulae XIX (wherein represenCs an _τ alkyl group) and XX wherein Z represenCs Che unsubsCiCuCed amino group may be obcained by Che reaccion of a compound d£ Che general formula XIII (wherein R° represenCs an alkoxy group) wich a molar equivalent of compound of general formula Y'CH CN, i.e. alononitrile when Y represents Che cyano group., in Che presence of an anhydrous solvenC, e.g. eChanol, and a molar equivalenC of a base, e.g. sodium hydride, and aC a CemperaCure from 0 Co 50°C followed, if desired, by hydrolysis of Che escers of general formula XIX wich an aqueous base, e.g. sodium hydroxide, wich a co-solvenC, e.g. eChanol, aC a CemperaCure from 0°C Co Che reflux CemperaCure of Che reaccion mixCure.

•Intermediates of general formulae IV and XIII may be prepared by chlorination of the appropriate unsubstituted compound using chlorine or other chlorinating agent. Intermediates of general formulae IV and XIII may be prepared by diazotisation of the appropriate aniline with a solution of a molar equivalent of sodium nitrite in a mineral acid, e.g. a mixture of concentrated sulphuric acid and acetic acid at a temperature from 0 to 60°C, and then reacting with the compound of formula CH COCH(Cl)CN or a compound of general formula CH ₃ C0CH(C1)C0R° wherein R° represents an alkoxy group in the presence of an inert solvent, e.g. a mixture of water and ethanol, _^ buffered, e.g. with excess sodium acetate, and at a temperature from 0 to 50°C. Compounds of general formula I wherein R represents the nitro group may be prepared by oxidation of Che corresponding amine wich an oxidanC, preferably CrifluoroperaceCic acid or m-chloro- perbenzoic acid in an inerC organic solvenC preferably dichloromeChane aC a CemperaCure from 0°C Co reflux. By employing known proCecCing agenCs in Chis process compounds of general formula I wherein Z represenCs Che amino group may be prepared.

Compounds of general formula I wherein R represenCs Che fluorine aCom may be prepared by the diazotisation of the corresponding amine of general formula I in which R is replaced by -NH-. using for example a solution of sodium nitriCe in a mineral acid, for example sulphuric acid and in the presence of fluoroboric acid or its sodium salt and subsequent thermolysis or phoColysis of Che diazonium fluoroboraCe derivaCive by meChods known per se. Amine inCermediaCes above wherein Z represenCs Che hydrogen aCom may be prepared by performing a CurCius rearrangemenC of Che corresponding acid azide by heaCing in an inerC organic solvenC such as Coluene aC a CemperaCure from 50° Co 150°C Co give an isocyanaCe which is Chen reacCed wich for example CerC-buCanol Co give a carbamaCe, which in Curn is hydrolysed using diluCe acid preferably hydrochloric acid in eChanol aC a CemperaCure from ambienC Co reflux. InCermediaCe acid azides may be prepared by reaccion of a carboxylic acid of general formula XX wherein Z represenCs Che hydrogen aCom wich a chlorinaCing agenC, preferably Chionyl chloride aC CemperaCures from ambienC Co reflux, followed by reaccion of Che inCermediaCe acid chloride wich sodium azide in a polar solvenC, preferably aceCone and waCer aC a CemperaCure from 0°C Co ambienC.

Compounds of general formula I wherein represents the cyano group may also be prepared by reacting a carboxylic acid of general formula XX wich a chlorinaCing agenC, preferably thionyl chloride at ambient to reflux temperature, followed by reaction of the intermediate acid chloride with ammonia to give an intermediate amide which is then dehydrated by heating with a dehydrating reagent, preferably phosphorus pencoxide aC a CemperaCure from 50-250°C. InCermediaCes of general formula XX may be prepared by hydrolysis of Che corresponding esCers of general formula XIX preferably using a base such as sodium hydroxide and a solvenC such as aqueous alcohol, and aC a CemperaCure from 0°C Co Che reflux CemperaCure of Che reaccion mixCure.

Compounds of general formula I wherein Y represenCs a 1,1-diflu ^' oroalkyl group which may be subsCiCuCed by one or more addicional halogen atoms may be prepared by the reaccion of a compound of general formula I wherein Y represenCs a sCraighC- or branched-chain alkanoyl group conCaining from 2 Co 6 carbon aComs or Che corresponding compound in which Y is replaced by Che formyl group or a sCraighC- or branched-chain alkanoyl group conCaining from 2 Co 6 carbon aComs which is subsCiCuCed by one or more halogen aComs wich a fluorinaCing agent, preferably

dieChylaminosulphur Crifluoride or sulphur CeCrafluoride in an inerC organic solvenC, preferably dichloromeChane, aC a CemperaCure from -78°C to ambient. Compounds of general formula I wherein Y represents the trifluoromeChyl group or a trifluoromeChylalkyl group conCaining from 2 Co 6 carbon aComs which may be subsCiCuCed by one or more addicional halogen aComs may be prepared by Che reaccion of a fluorinaCing agenC, e.g.sulphur

CeCrafluoride, with an acid of general formula XVI or the corresponding carboxyalkyl compound (it being understood that the carboxy group may be attached to any position of the alkyl moiety) at a temperature from ambient to 150°C.

Salts with pesticidally-acceptable bases of compounds of general formula I wherein Z represents the carboxy group may be prepared from the corresponding compounds of general formula I by methods known per se, for example by reacting stoichiomeCric quanCiCies of Che compound of general formula I and Che appropriaCe base, for example an alkali meCal hydroxide, carbonaCe or bicarbonaCe, an alkaline earCh meCal hydroxide or carbonaCe, ammonia or an amine (e.g. dieChanolamine, CrieChanolamine, ocCylamine, morpholine or diocCylamine), in a suiCable solvenC. The sales may, if necessary, be purified by recrysCallisaCion from one, Cwo or more suiCable solvenCs.

Compounds of general formula I noC hicherCo disclosed or described in Che chemical liCeraCure, CogeCher wich Cheir processes of preparacion form furCher feaCures of Che presene invencion. The presenC invenCion accordingly provides Che compounds of general formula I, wherein Che various symbols are as hereinbefore defined, and sales Chereof, wich Che exclusion of Che compounds wherein:

R and Z boCh represenC meChyl, Y represenCs ChiocyanaCo and (R ) represenCs 2-, 3- or

4-niCro, 4-meChyl, 4-chloro or 2,4-diniCro subsCiCuCion; R represenCs meChyl, Y represenCs cyano, Z represenCs unsubsCiCuCed amino and (R ) represenCs 4-chloro, 2,4-dichloro, 3,4-dichloro, 3-chloro-4-meChyl or 2-methyl-4-chloro substiCuCion;

4 R represenCs meChyl, Y represenCs cyano or C0NH ₂ ,

3 Z represenCs unsubsCiCuCed amino and (Rι) _n represenCs 3- or 4-fluoro subsCiCuCion; R represenCs eChyl, Y represenCs cyano or C0NH ₂ , Z represenCs unsubsCiCuCed amino and (R ) represenCs 3- or 4-chloro, 2-, 3- or 4-fluoro or

4 mechyl, 3-bromo or 3-niCro subsCiCuCion; R

« represenCs propyl, Y represenCs cyano or C0NH , Z

3 represenCs unsubsCiCuCed amino and (R ) represenCs 3-fluoro subsCiCuCion; R represenCs meChyl, Y represenCs sulphamoyl, Z represenCs chloro and (R ) represenCs 4-chloro subsCiCuCion; R

-92- represenCs meChyl, Y represenCs nicro, and Z represenCs chloro or R represenCs chloro, Y represenCs nicro, and Z represenCs meChyl and (R ) represenCs 4-niCro; and R represenCs niCro, Y represenCs cyano or C0NH ₂ , Z represenCs

3 hydrogen and (R ) represents 4-nitro substitution.

According to a further feature of the present invention there are provided intermediates for the preparation of certain compounds of general formula I i.e. compounds for which in Cheir alCernaCive meanings Y represenCs Che hydrogen aCom, Che formyl or carboxy group, a sCraighC- or branched-chain alkanoyl group conCaining from 2 Co 6 carbon aComs which is substituted by one or more halogen atoms, -the dithio group (which joins two pyrazole rings), Che amino group, Che -SO^Cl group, a sCraighC- or branched-chain carboxyalkyl group conCaining from 2 Co 6 carbon aComs, Z represenCs Che carbamoyl group or a straight- or branched-chain alkoxycarbonyl group containing from 2 to 7 carbon atoms or the diphenoxycarbonylamino group, ( substitution is a preferred combination given earlier in the specification or R represents the amino, hydroxymethyl, carboxy or carbamoyl group or a straight- or branched-chain alkoxycarbonyl or alkoxycarbonylamino group containing from 2 to 7 carbon atoms.

The following Examples and Reference Examples illustrate Che preparacion of compounds of general formula I according Co Che presenC invenCion:-

EXAMPLE 1 Compound No.l

A mixCure of 2,4, 6-CrichlorophenyIhydrazine (21.1 g) and CeCracyanoeChylene (13.3 g) in eChanol (100 ml) was heaCed aC reflux for 15 inuCes. The reaccion mixCure was cooled and Che solid precipiCaCe was filCered off and washed wich dietbyl eCher Co give 5-amino-3,4-dicyano-l-(2,4,6-Crichlorophenyl)pyrazole (13 g), as a buff coloured solid, .p. 267-27l°C.

EXAMPLE 2 Compounds Nos.2 and 3 TeCracyanoethylene (1.9 g) and 2,6-dichIoro-

4-trifluoromethylphenyIhydrazine (3.7 g) was added to a magnetically-stirred solution of sodium ,acetate (0.6 g) in glacial acetic acid (15 ml) at laboratory temperature. After sCirring for 15 minuCes, a colourless solid precipiCaCed from Che soluCion and stirring was continued overnight. The mixCure was Chen filCered. The solid obCained was washed successively wich aceCic acid, waCer, aqueous sodium bicarbonaCe soluCion and waCer, Co give 5-amino-l-(2,6-dichloro-4-CrifluoromeChylphenyl)- 3,4-dicyanopyrazole (2.5 g) , as beige crysCals, m.p. 221-222°C.

By proceeding in a similar manner, buC replacing Che 2,6-dichloro-4-CrifluoromeChylphenyIhydrazine by 2,3, 5,6-CeCrachlorophenyIhydrazine, here was obCained:- 5-Amino-3,4-dicyano-l-(2,3, 5, 6-CeCrachlorophenyl)- pyrazole, m.p. greaCer Chan 330°C, in Che form of a buff-coloured powder.

REFERENCE EXAMPLE 1 Phenylhydrazines used as sCarCing maCerials in Examples 1, 2 and 11. noc hiCherCo described in Che chemical liCeraCure were prepared as follows:-

2,6-Dichloro-4-CrifluoromeChylphenylaniline (4.3 g) was dissolved wich sCirring, in glacial aceCic acid (23 ml). A soluCion of sodium niCriCe (1.5 g) in concenCraCed sulphuric acid (11 ml) was Chen added aC 55-60°C. The soluCion Chus obCained was cooled Co 0-5°C and a soluCion of sCannous chloride (16.4 g) in concenCraCed hydrochloric acid (14 ml) was added wich vigorous sCirring. A cream-coloured solid precipitated. The mixture was filtered and the solid obtained was added to a mixture of aqueous ammonia solution and ice. The mixture thus obtained was extracted with diethyl ether (6 x 500 ml) and the combined ethereal exCracCs were dried over sodium sulphaCe, filCered and evaporaCed Co dryness Co give 2,6-dichloro-4-CrifluoromeChylphenyIhydrazine (3.7 g) m.p. 54-56°C, in Che form of a colourless crysCalline solid.

By proceeding in a similar manner, buC replacing

Che 2,6-dichloro-4-CrifluoromeChylaniline by Che hereinafCer indicaCed aniline Chere were prepared:-

2-Chlor0-4-CrifluoromeChylphenyIhydrazine, m.p. 38-39°C, in Che form of a colourless solid, from

2-chloro-4-Crif1uoromeChyIaniline.

EXAMPLE 3

Compound No.4

EChoxyeChylenemalononiCrile (44.5g) and 2,6-dichloro-4-CrifluoromeChylphenylhydrazine (80.Og) were added Co a sCirred soluCion of sodium aceCaCe (13.4g) in glacial aceCic acid (110 ml) aC laboraCory CemperaCure. A Chick suspension was obCained and was sCirred overnight, after which a dark solution had formed. The solvent was evaporated iτ vacuo, and the residue was diluted with aqueous sodium bicarbonate solution (100ml) and extracted with dichloromethane (3 x 100ml), and the combined extracts were washed with sodium bicarbonate solution (50ml) , then with water (100ml), dried over anhydrous magnesium sulphate and evaporated ^ιι vacuo to give a dark syrup. This was heated at reflux with 2-eChoxyeChanol (200ml) for 1 hour, and then evaporaCed in vacuo to give a dark oil. The oil was dissolved in dichloromeChane, washed wich sodium bicarbonaCe soluCion (50ml) , Chen wich waCer (100ml), dried over anhydrous magnesium sulphaCe, CreaCed wich charcoal, and evaporaCed iτi vacuo Co give

a black solid. The solid was recrysCallised Cwice from a mixCure of coluene and peCroleum eCher (b.p. 60-80°C)

Co give 5-amino-4-cyano-l-(2,6-dichloro-

4-crifluoromeChylphenyl)-3-meChylpyrazole (49.3g) , m.p. 194-196°C, in Che form of pale brown cryscals.

EXAMPLE 4

Compounds Nos.5, 22, 24 and 36

To a mechanically sCirred soluCion of

2,6-dichloro-4-CrifluoromeChylphenyIhydrazine (180.3 g) in dry dieChyl eCher (700 ml) was added anhydrous poCassium carbonaCe (112 g) , and Che ^• mixCure was cooled Co 0°C. To this mixCure was added dropwise during half-an-hour a soluCion of 2-chloro-l,l-dicyano-2-CrifluoromeChyleChylene (132.1 g) in dry dieChyl eCher (350 ml). The ice-bach was removed aC Che end of Che reaccion, and Che mixCure was lefC overnighc and Chen poured onto water (2000 ml) . The ethereal layer was separated and the aqueous solution extracted with diethyl ether (2 x 300 ml) . The combined extracts were dried over anhydrous magnesium sulphate, filtered, and evaporated in vacuo to give a buff solid (350 g) . Recrystallisation from toluene/hexane gave white crystals (169.5 g) m.p. 202-204°C of 5-amino-4-cyano-l-(2,6-dichloro-

4-trifluoromethylphenyl)-3-trifluoromethylpyrazole.

By proceeding in a similar manner, buC replacing Che 2-chloro-l,l-dicyano-2-CrifluoromeChyl- eChylene by 2-chloro-l-cyano-l-meChanesulphonyl- 2-Crifluoro eChyleChylene Chere was prepared:- 5-Amino-1-(2,6-dichlor0-4-CrifluoromeChyl¬ phenyl)-4-meChanesulphony1-3-Crifluoro eChylpyrazole in Che form of buff crysCals m.p. 215-218 ^β C, from Coluene-hexane.

By proceeding in a similar manner, but replacing the 2-chloro-l,l-dicyano-2-CrifluoromeChyl¬ eChylene by 2-chloro-l-cyano.-l-methoxycarbonyl- 2-trifluoromethylethylene there was prepared:-

5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-meChoxycarbonyl-3-CrifluoromeChylpyrazole in Che form of fawn crysCals, m.p. 114-115°C, from hexane.

By proceeding in a similar manner, buC replacing Che 2,6-dichloro-4-CrifluoromeChylphenyl- hydrazine by 2,6-dichloro-4-CrifluoromeChoxyphenyl- hydrazine there was prepared:- 5-Amino-4-cyano-l-(2,6-dichloro-4-Crifluoro- meChoxyphenyl)-3-CrifluoromeChylpyrazole in Che form of whiCe crysCals, m.p. 160-160.5°C from Coluene- hexane.

EXAMPLE 5 Compounds Nos.19, 20, 21 and 47

Anhydrous sodium acetate (0.246 g) was added to a stirred solution of 2-chloro-l,l-dicyano- 2-pentafluoroethylethylene (1.38 g) in acetic acid (5 ml). To this mixture was added

2,6-dichloro-4-trifluoromethylphenyIhydrazine (1.47 g) during 5 minutes. After stirring overnight the mixture was neutralised with sodium bicarbonate solution, and extracted with dichloromethane (2 x 50 ml). The combined extracts were washed with water, dried over anhydrous magnesium sulphate, filtered, and evaporated in vacuo to give a buff solid (2.1 g) . This solid was heated under reflux with 2-ethoxyethanol (10 ml) for 1 hour, and evaporated in vacuo to give a brown oil (2.2 g) . This oil was chromatographed on silica (Merck, 230-400 mesh, 0.7 kg

__2 cm ) using a mixture of dichloromethane and ethyl aceCaCe (98:2) to give a yellow solid. Recrystallisation from a mixture of dichloromethane and petroleum ether gave 5-amino-4-cyano- l-(2,6-dichloro-4-trifluoromethylphenyl)-3-pentafluoro- ethylpyrazole as white crysCals, m.p. 160-162 ^β C. By proceeding in a similar manner, but replacing Che 2-chloro-l,l-dicyano-2-pentafluoro- ethy1-ethylene.by 2-chloro-l,l-dicyano-2-chloro- difluoro eChyleChylene Chere was prepared:-

5-Amino-3-chlorodifluoromethyl-l-(2,6- dichloro-4-trifluoromethylphenyl)-4-cyanopyrazole in the form of white prisms, m.p. 192°C, from toluene- hexane. By proceeding in a similar manner, but replacing the 2-chloro-l,l-dicyano-2-penCafluoroethyl- eChylene by 2-chloro-l,l-dicyano-2-difluoromeChyl- eChylene Chere was prepared:-

5-Amino-l-(2,δ-dichloro-'.-trifluoromethyl- phenyl)-4-cyano-3-difluoromeChylpyrazole in Che form of a colourless solid, m.p. 184.5°C (from Coluene- peCroleum eCher) .

By proceeding in a similar manner, buC replacing Che 2-chloro-l,l-dicyano-2-penCafluoroeChyl- eChylene by 2-chloro-l, l-dicyano-2-hepCafluoropropyl- eChylene Chere was prepared:-

5-Amino-l-(2,6-dichloro-4-CrifluoromeChyl- phenyl)-4-cyano-3-hepCafluoropropylpyrazole in Che form of colourless prisms, m.p. 139-140°C (from Coluene-peCroleum eCher) .

REFERENCE EXAMPLE 2 Chloro-dicyanoeChylenes used as scarcing materials in Che above Examples, noC hiCherCo described in Che chemical literature were prepared as follows:-

A suspension of 2-cyano-3-hydroxy-4-chloro- 4,4-difluorobuC-2-eneniCrile sodium sale (18.56 g) in dichloromeChane (60 ml) was sCirred aC room temperature and treated with phosphorus pentachloride (19.27 g). The suspension was heated under reflux for 6 hours, cooled and filtered, and the filtraCe was disCilled. A Widmer fracCionaCing column was used Co give 2-chloro-l,l-dicyano-2-chlorodifluoromeChyl- eChylene as a liquid, b.p. 88 ^β C (44 mmHg) (71 g) . By proceeding in a similar manner, buC replacing 2-cyano-3-hydroxy-4-chloro-4,4-difluorobuC- 2-eneniCrile sodium sale by 2-cyano-3-hydroxy-4,4- difluorobuC-2-eneniCrile sodium sale there was prepared 2-chloro-l,l-dicyano-2-difluoromeChyl-eChylene as a liquid, b.p. 94°C (46 mmHg).

By replacing 2-cyano-3-hydroxy-4-chloro-4,4- difluorobuC-2-eneniCrile sodium sale by 3-hydroxy-2- meChanesulphonyl-4,4,4-CrifluorobuC-2-eneniCrile sodium salt and proceeding in a similar manner Chere was prepared 2-chloro-l-cyano-l-meChanesulphonyl-2- trifluoromeChyleChylene as a pale brown liquid.

By replacing 2-cyano-3-hydroxy-4-chloro-4,4- difluorobuC-2-eneniCrile sodium sale by 3-hydroxy-2- meChoxycarbonyl-4„4,4-CrifluorobuC-2-eneniCrile sodium salt and proceeding in a similar manner Chere was prepared 2-chloro-l-cyano-l-meChoxycarbonyl-2- CrifluoromeChyleChylene as a colourless oil, b.p. 86-92 ^β C at 23-25 mm Hg.

By replacing 2-cyano-3-hydroxy-4-chloro-4,4- difluorobuC-2-eneniCrile sodium sale by 2-cyano- 3-hydroxy-4,4,5, 5,6,6,6-hepCa luorohex-2-eneniCrile sodium sale and proceeding in a similar manner Chere was prepared 2-chloro-l,l-dicyano-2-hepCafluoropropyl- echylene as a pale yellow liquid, b.p. 110°C at 60 mmHg.

REFERENCE EXAMPLE 3 The sodium salts used in the above Reference Examples as starting materials, not hitherto described in the chemical literature were prepared as follows:-

To a solution of sodium methoxide (5.61 g) in anhydrous methanol (70 ml) was added malononitrile (6.85 g) and the yellow solution treated with methyl chlorodifluoroacetate (15 g) . The mixture was heated under reflux for 4 hours, the solvent was evaporated in vacuo and re-evaporaCed afCer addieiqn of Coluene Co give 2-cyano-3-hydroxy-4-chloro-4,4-difluoro- buC-2-eneniCrile sodium sale as a brown solid (18.9g). This was dried in a vacuum desiccator.

By proceeding in a similar manner, but replacing methyl chlorodifluoroacetate by ethyl difluoroacetate there was obtained 2-cyano-3-hydroxy- 4,4-difluorobut-2-enenitrile sodium salt as a light brown solid.

By proceeding in a similar manner, buC replacing meChyl chlorodifluoroaceCaCe by meChyl

r , n - sulphonylacetonitrile there was obtained 3-hydroxy- 2-methanesulphonyl-4,4,4-trifluorobut-2-enenitrile sodium salt as a brown solid. By proceeding in a similar manner, but replacing methyl chlorodifluoroacetate by methyl- trifluoroacetate, and the malononitrile by methyl- cyanoacetate there was obtained 3-hydroxy-2-methoxy- carbonyl-4, , -trifluorobut-2-enenitrile sodium salt as a buff solid.

By proceeding in a similar manner, but replacing methyl chlorodifluoroacetate by methyl- heptafluorobutyrate there was obtained 2-cyano- 3-hydroxy-4,4,5,5,6, 6,6-heptafluorohex-2-enenitrile sodium salt as a light brown hygroscopic solid.

EXAMPLE 6 Compound No.23

I

To stirred 80% sulphuric acid (22 ml) was added 5-amino-4-cyano-l-(2,6-dichloro-4-trifluoro- methylphenyl)-3-trifluoromethylpyrazole (3.98 g) at 80°C. After 1 hour the cooled solution was poured onto ice and extracted with dichloromethane (3x) . The combined exCracCs were washed wich waCer, dried over anhydrous magnesium sulphaCe, filCered, and evaporaCed In vacuo Co give a whiCe solid. This solid was recrysCallised from eChyl acetate-petroleum ether to give 5-amino-4-carbamoyl-l-(2,6-dichloro-

4-CrifluoromeChylphenyl)-3-CrifluoromeChylpyrazole

(3.5 g) , m.p. 169-171°C in Che form of whiCe crysCals.

EXAMPLE 7

Compounds Nos.6, 7 and 8

5 3,5-Diamino-4-cyano-l-(2,6-dichloro-4-Cri- fluoromeChylphenyl)pyrazole (3.9g; prepared as described below) was dissolved wich sCirring in glacial aceCic acid (60ml) aC 15°C. A soluCion of sodium niCriCe (0.88g) in concenCraCed sulphuric acid 0 (5.85ml) was Chen added over 5 minuCes, mainCaining aC 15°C. AfCer 15 minuCes longer aC Chis CemperaCure, Che dark red oil soluCion was poured during 1 minute onto a sCirred soluCion of cuprous chloride (2.32g) in concenCraCed hydrochloric acid (36ml). AfCer 15 5 minuCes aC laboraCory CemperaCure, by which Cime Che evoluCion of niCrogen had compleCely subsided, Che reaccion mixCure was poured onCo excess ice and waCer, and exCracCed wich dichloromeChane (3 x 50ml). The combined exCracCs were washed* wich waCer (2 x 50ml), Q Chen wich sodium bicarbonaCe soluCion (50ml), dried over anhydrous magnesium sulphaCe, and evaporaCed in vacuo Co give a brown semi-solid (4.1g).

ChromaCography on silica (Merck, 230-400 mesh,

_2 0.7 kg cm ) using a mixCure of dichloromeChane and 5 eChyl aceCaCe (98:2) as eluenC gave afCer evaporaCion of Che eluate and recrysCallisaCion of Che residue from a mixCure of dichloromeChane and peCroleum eCher

(b.p. 60-80°C) 5-amino-3-chloro-4-cyano-l- (2, 6- dichloro-4-CrifluoromeChylphenyl)pyrazole (0.95g) , m.p. 189-191°C, in Che form of whiCe crysCals. By proceeding in a similar manner buC replacing Che cuprous chloride and concenCraCed hydrochloric acid by cuprous bromide and 48% w/v hydrobromic acid respecCively Chere was prepared:-

5-Amino-3-bromo-4-cyano-l-(2,6-dichloro-4- CrifluoromeChylphen 1)pyrazole, m.p„ 182-183°C, in Che form of whiCe crysCals.

By replacing Che cuprous chloride and concenCraCed hydrochloric acid by a soluCion of poCassium iodide in waCer Chere was prepared:-

5-Amino-3-iodo-4-cyano-l-(2,6-dichloro-4- CrifluoromeChylphenyl)pyrazole, m.p. 208-210°C, in Che form of whiCe crysCals.

REFERENCE EXAMPLE 4

I

A suspension of 2,6-dichloro-4-erifluoro¬ meChylphenyIhydrazine (14.7g) in waCer (40ml) was sCirred wich concenCraCed hydrochloric acid (5.2ml), and potassium cyanoform (8.52g) added. The suspension was sCirred and heaCed under reflux for 16 hours, and left Co cool overnight. The mixCure was washed inCo a separaCing funnel wich the aid of eChyl aceCaCe and waCer, and Che organic phase collecCed. The aqueous phase was re-exCracCed wich eChyl aceCaCe (2 x 80ml) , and ehe combined organic solutions washed with water

(2 x 50ml), dried over anhydrous magnesium sulphate, and evaporated it vacuo to give an orange solid (20.9g). Two recrystallisations from a mixture of ethyl acetate and petroleum ether (b.p. 60-80°C) gave 3,5-diamino-4-cyano-l-(2,6-dichloro-4-CrifluoromeChyl¬ pheny1)pyrazole (7.75g), m.p. 208-210°C in Che form of whiCe crysCals.

EXAMPLE 8 Compound No.9 A soluCion of eehaneChiol (2.1g) in Coluene

(10ml) was added dropwise aC 5-10°C Co a sCirred suspension of N-chlorosuccinimide (4.7g) in Coluene (40ml). The reaccion mixCure was filCered afCer 20 minuCes Co give a soluCion of eChanesulphenyl φ chloride. This filCraCe was added dropwise wich sCirring Co a soluCion of 5-amino-4-cyano-l-(2,6- dichloro-4-CrifluoromeChylphenyl)-3-meChylpyrazole sodium sale [prepared ^_n siCu by reaccion of 5-amino- 4-cyano-l-(2,6-dichloro-4-trifluoromethylpheny1)-3- methylpyrazole (5g) with sodium hydride (0.4g)] in tetrahydrofuran (50ml) containing 15-crown-5 (3 drops) at a CemperaCure of 5-10°C. AfCer 2 hours, aqueous sodium bicarbonate solution (50ml) was added, and Che organic phase was separaCed and washed wich waCer (2 x 50ml), and dried over anhydrous magnesium sulphaCe.

Evaporation of Che solvent jji vacuo gave a dark brown gum, which was chromaCographed on silica (Merck

230-400 mesh, 0.7 kg cm ) using dichloromeChane as eluenC. EvaporaCion of Che eluaCes gave an orange gum, which Chen recrysCallised from a mixCure of eChyl aceCaCe and hexane Co give 4-cyano-l-(2,6-dichloro-4- CrifluoromeChylphenyl)-3-meChyl-5-eChanesulphenylamino- pyrazole (2.3g), m.p. 160-161°C, in Che form of a pale yellow solid.

EXAMPLE 9 Compounds Nos.10, 11 and 27 A mixCure of 5-amino-4-cyano-l-(2,6-dichloro-

4-CrifluoromeChylphenyl)-3-meChylpyrazole (5g) and p-Coluenesulphonic acid hydraCe (O.lg) in CrimeChylorChoformaCe (20ml) was heaCed aC reflux for 4.5 hours. AfCer cooling, Che reaccion mixCure was evaporaCed Co dryness in vacuo. The residue was dissolved in dieChyl eCher and lefC Co crysCallise aC 0°C. The dark coloured solid was recrysCallised from a mixCure of eChanol and waCer Co give 4-cyano-l- (2,6-dichloro-4-trifluoromeChylphenyl)-3-meChyl-5- meChoxymeCHyleneaminopy azole (4.67g), m.p. 75-78°C, in Che form of buff crysCals.

By proceeding in a similar manner buC replacing Che CrimeChylorChoformaCe by Cripropyl- orChofor aCe Chere was prepared:- 4-Cyano-l-(2,δ-dichloro-4-CrifluoromeChyl¬ pheny1)-3-meChyl-5-propoxymeChyleneaminopyrazole, m.p. 77-79°C, in Che form of buff crysCals.

By proceeding in a similar manner but replacing the 5-amino-4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)-3-methylpyrazole by 5-amino- 4-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)-3- trifluoromethylpyrazole, and the trimethylortho- formate by triethyl orthoformate, there was prepared:-

4-Cyano-l-(2,6-dichlor0-4-trifluoromethy1- phenyl)-5-ethoxymethyleneamino-3-trifluoromethyl¬ pyrazole, m.p. 160-162°C, from hexane, in the form of white crystals.

EXAMPLE 10 Compounds Nos.12, 13, 14, 15, 16, 26 and 25

A suspension of-5-amino-l-(2,6-dichloro-4- trifluoromethylphenyl)-3,4-dicyanopyrazole (15.Og) in chloroform (250ml) was treated wich aceCyl chloride (42.8ml) wich mechanical sCirring aC 0°C. A soluCion of dry pyridine (7.0ml) in chloroform (3,0ml) was added dropwise during 30 minuCes, keeping aC 0°C. The mixCure was sCirred overnighC aC laboraCory CemperaCure, and Chen heaCed under reflux condicions in order Co compleCe Che reaccion. AfCer cooling, Che soluCion was poured onCo a mixCure of ice and diluCe hydrochloric acid, and Che chloroform layer separaCed. The aqueous soluCion was re-exCracCed with chloroform (2 x 100ml) , and the combined organic extracts were washed with water (100ml), dried over anhydrous magnesium sulphate, and evaporaCed rn vacuo Co give a

buff-coloured solid (23.Og). RecrysCallisaCion from a mixCure of eChyl aceCaCe and peCroleum eCher (b.p. 60-80°C) gave 5-acetamido-l-(2,6-dichloro-4- trifluoromethylphenyl)-3,4-dicyanopyrazole, m.p. 208-209°C, in the form of white crystals.

By proceeding in a similar manner, the following phenylpyrazoles were obtained by acylatioπ of 5-amino-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3,4-dicyanopyrazole with the appropriate acid chloride:-

5-Dichloroacetamido-l-(2,6-dichloro-4- trifluoromethylphenyl)-3,4-dicyanopyrazole, m.p. 186-187 ^β C after purification by trituration with carbon tetrachloride and subsequent recrystallisation from a mixture of ethanol and water, in the form of an off-white solid. The reaction was performed at laboratory temperature. ₍

5-Cyclopropylcarbonamido-l-(2,6-dichloro-4- trifluoromethylphenyl)-3, ,dicyanopyrazole, m.p. 217-218°C after recrystallisation from a mixture of ethanol and water, in Che form of an off-whiCe solid. The reaction was performed at laboratory temperature.

5-Pentanamido-l-(2,6-dichlor0-4-trifluoro¬ methylphen l)-3,4-dicyanopyrazole in the form of a pale yellow glass. Infra-Red Absorption bands:

3260, 3100, 2960, 2940, 2880, 2240, 1730, 1700 ^* , 1315, 880, 820 cm ^"1 (liquid film) . The reaction was

performed at 0°C during the addition, and at laboratory temperature ChereafCer.

5-Propionamido-l-(2,6-dichloro-4-Crifluoro- meChylphenyl)-3,4-dicyanopyrazole, m.p. 188-189°C afCer purificaCion by chromaCography on silica (Merck,

__2 230-400 mesh, 0.7 kg cm ) using a mixCure of aceCone and hexane (2:3) as eluenC, and subsequenC

CriCuraCion wich Coluene, in Che form of a whiCe powder. The reaccion was performed at laboratory temperature.

By proceeding in a similar manner, but replacing the solvent by acetonitrile, the following phenylpyrazole was obtained by acylation of 5-amino- 1-(2,6-dichloro-4-trifluoromethylphenyl)-3,4-dicyano- pyrazole with trimethylacetyl chloride:-

1-(2,6-Dichlor0-4-trifluoromethylphenyl)-3,4- dicyano-5-(2,2-dimethylpropionamido)pyrazole as white crystals, m.p. 202-203°C from toluene-hexane, and after purification by chromatography on silica (Merck,

_2 230-400 mesh, 0.7 kg cm ) using a mixture of dichloromethane and eChyl aceCaCe (9:1) as eluent.

By proceeding in a similar manner but replacing 5-amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3,4-dicyanopyrazole by 5-amino-4-cyano-l-(2,6- dichloro-4-CrifluoromeChylphenyl)-3-CrifluoromeChyl¬ pyrazole and by heaCing under reflux for 18 hours Chere was obCained:-

5-AceCamido-4-cyano-l-(2,6-dichloro-4- CrifluoromeChylphenyl)-3-CrifluoromeChylpyrazole, m.p. 225-227°C, from eChyl aceCaCe-hexane, in Che form of whiCe crysCals. EXAMPLE 11

Compounds Nos.17 and 18

Anhydrous sodium aceCaCe (l.Og) was dissolved in sCirred aceCic acid (40ml), and CeCracyanoeChylene (3.5g) was added aC laboraCory CemperaCure. 2-Chloro- 4-CrifluoromeChylphenylhydrazinε (5.25g) was added in one porCion, and Che mixCure was sCirred overnighc. AfCer diluCion wich waCer, Che precipiCaCed solid was filCered off Co give, afCer drying,

5-amino-l-(2-chloro-4-Crifluoromethylphenyl)-3,4-dicyano pyrazole, m.p. 209-210°C in the form of a white powder.

By proceeding in a similar manner but replacing the 2-chloro-4-trifluoromethylphenylhydrazine by 2,3,5,6-tetrafluoro-4-trifluoromethylphenyIhydrazine and with cooling during addition of the phenylhydrazine to the tetracyanoethylene solution, there was prepared:-

5-amino-3,4-dicyano-l-(2,3, 5, 6-tetrafluoro-4- trifluoromethylphenyl)pyrazole, m.p. 262-263°C in the form of a buff powder.

EXAMPLE 12 Compounds Nos.28 and 29

Sodium hydride (80%, 0.25 g) was added to a stirred solution of 5-amino-4-cyano-l-(2,6-dichloro-4- trifluoromeChylphenyl)-3-CrifluoromeChylpyrazole (2.9 g) in dry CeCrahydrofuran (50 ml). AfCer 3 hours aC room CemperaCure, 15-crown-5 (1 drop) and meChyl iodide (2 g) was added aC 0°C, and Che mixCure left overnight at room temperature. The solution was evaporated ^n vacuo, and the residue was dissolved in dichloromeChane (50 ml), washed wich waCer, diluCe hydrochloric acid and waCer. AfCer drying over anhydrous magnesium sulphate, filtration, and evaporation j i vacuo a yellow oil was obtained. Purification by chromatography using Merck silica (230-400 mesh, 0.7 kg cm -2) with dichloromethane as eluent gave 4-cyano-l-(2,6-dichloro-4-tr.ifluoromethyl¬ phenyl)-5-dimethylamino-3-trifluoromethylpyrazole as a white solid, m.p. 105-107°C. By proceeding in a similar manner but replacing the methyl iodide by ethyl bromoacetate, and employing dioxan as solvent in place of tetrahydrofuran there was obtained 4-cyano-l-(2,6- dichloro-4-trifluoromethylphenyl)-5-ethoxycarbonyl- methylamino-3-trifluoromethylpyrazole as white crystals, m.p. 104-106°C from ethyl acetate-petroleum ether.

EXAMPLE 13 Compound No.30

To a suspension of 4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)-5-ethoxymethyleneamino-3- trifluoromethylpyrazole (1.0 g) in methanol (10 ml) stirred at room temperature was added sodium borohydride (0.17 g) . After 2 hours an additional 0.17 g of sodium borohydride was added, and another 0.34 g added after 1 hour. One hour later the mixture was poured onto water (80 ml) and extracted with dichloromethane (3 x 25 ml). The combined extracts were dried over anhydrous magnesium sulphate, filtered, and evaporated in vacuo. The white solid thus obtained was purified by chromatography on silica (Merck, 230-400 mesh, 0.7 kg cm ^"2 ) with dichloro¬ methane as eluent, to furnish 4-cyano-5-methylamino-l- (2,6-dichloro-4-trifluoromethylphenyl)-3<-trifluoro¬ methylpyrazole as a white solid (0.6 g) , m.p. 200-202°C. EXAMPLE 14

Compounds Nos.31, 37 and 38

Sodium hydride (80%, 0.3 g) was added to a stirred solution of 5-amino-4-cyano-l-(2,6-dichloro- 4-trifluoromeChylphenyl)-3-trifluoromeChylpyrazole (2.9 g) in dry CeCrahydrofuran (50 ml). AfCer 3 hours, 15-crown-5 (1 drop) and trimethylacetyl chloride (1.8 g) was added, and the mixCure sCirred

overnight. Evaporation ^n vacuo gave a buff semisolid, which was dissolved in dichloromeChane. This soluCion was washed wich waCer, diluCe hydrochloric acid and wich waCer again and finally dried over anhydrous magnesium sulphaCe. Filtration followed by evaporation i _j n vacuo gave a yellow oil, which was purified by chromatography on silica (Merck, 40-230 mesh, 0.7 kg cm ^"2 ). Elution with dichloromethane gave after evaporation 4-cyano- 1-(2,6-dichloro-4-trifluoromethylphenyl)-5-(2,2- dimethylpropionamido)-3-trifluoromethylpyrazole as a white solid, m.p. 198-200°C.

By proceeding in a similar manner but replacing the trimethylacetyl chloride by ethyl chloroformate there was obtained, after recrystallisation from toluene,

4-cyano-l-(2,6-dichloro-4-trifluoromethylpheny1)- 5-bis(ethoxycarbonyl)amino-3- rifluoromethylpyrazole as white crystals, m.p. 62°C. By proceeding in a similar manner but. replacing the trimethylacetyl chloride by cyclopropanecarboxylic acid chloride there was obtained 4-cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-bis-(cyclopropanecarbonyl)amino-3- trifluoromethylpyrazole as a pale yellow solid, m.p. 126-127°C.

EXAMPLE 15

Compound No.39

A solution of 4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)-5-bis(cyclopropanecarbonyl)- amino-3-trifluoromeChylpyrazole (1.0 g) in eChanol

(50 ml) was heaCed under reflux wich saCuraCed sodium bicarbonaCe soluCion (25 ml) for 45 minuCes. AfCer cooling, and evaporaCion of Che solvenC ^ri vacuo, Che residue was diluCed wich water and extracted with dichloromethane. The extract was dried over anhydrous magnesium sulphate, filtered, and evaporated in vacuo to give 4-cyano-l-(2,6-dichloro-4-trifluoro- methylphenyl)-5-cyclopropanecarbonamido-3-trifluoro¬ methylpyrazole as a white solid m.p. 210-212°C. EXAMPLE 16

Compound No.33

A stirred mixture of 5-amino-4-cyano-i- (2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoro- ^" methylpyrazole (3.89 g) and bro oform (13 ml) was treated with tert-butyl nitrite (2.26 ml) at room temperature. After 15 minutes the mixture was heated to 50°C for 1 hour, and evaporated in vacuo to yield a red oil. This was purified by chromatography on silica (Merck, 40-230 mesh, 0.7 kg cm ^"2 ) eluting with a mixture of dichloromethane and petroleum ether (1:2) to furnish 5-bromo-4-cyano-l-(2,6-dichloro-4- trifluoromethylphenyl)-3-trifluoromethylpyrazole as a fawn solid m.p. 85-87°C (3.7 g) .

EXAMPLE 17 Compound No.34

A solution of 5-amino-4-cyano-l-(2,6-dichloro- 4-CrifluoromeChylphenyl)-3-hydroxymeChylpyrazole (1.25 g) in dichloromeChane (10 ml) was added slowly Co a sCirred soluCion of dieChylaminosulphur Crifluoride (0.66 g) in dichloromeChane (6 ml) cooled Co -78°C. AfCer 30 minuCes aC Chis CemperaCure Che soluCion was warmed Co room CemperaCure and sCirred for 2 hours. The mixCure was Chen poured onCo waCer (20 ml) and Che dichloromeChane layer was separaCed, dried over anhydrous magnesium sulphate, filtered and evaporated iτ vacuo. The product was purified by chromatography on silica (Merck, 40-230 mesh,

„2 0.7 kg cm ) eluting with a mixture of dichloro¬ methane and ethyl acetate (98:2), and subsequent recrystallisation from dichloromethane-petroleum ether to give 5-amino-4-cyano-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-fluoromethylpyrazole as a white solid m.p. 139-141°C.

REFERENCE EXAMPLE 5 5-Amino-4-cyano-l-(2,6-dichlor0-4-trifluoro¬ methylphenyl)-3-hydroxymethylpyrazole was prepared as follows:- A solution of 5-amino-4-cyano-l-(2,6- dichloro-4-trifluoromethylphenyl)-3-ethoxycarbony1- pyrazole (1.0 g) in dry tetrahydrofuran (15 ml) was

a e un

(0.06 g) with sCirring aC room CemperaCure for 18 hours. EChyl aceCaCe (5 ml) followed by saCuraCed sodium chloride soluCion (5 ml) was added, and Che mixCure was acidified wich diluCe hydrochloric aciά and exCracCed wich dichloromeChane. The exCracC was dried over anhydrous magnesium sulphaCe, filCered, and evaporaCed in vacuo. The.residual oil was purified by chromaCography on silica (Merck, 40-230 mesh,

_2 0.7 kg cm ) elucing wich a mixCure of dichloromeChane and eChyl aceCaCe (1:1), and Che pure fracCions were evaporaCed ^n vacuo and recrysCallised from eChyl aceCaCe-peCroleum eCher Co give Che cicle compound as a whiCe solid m.p. 159-161°C

5-Amino-4-cyano-l-(2,6-dichloro-4-Crifluoro¬ meChylphenyl)-3-eChoxycarbonylpyrazole was prepared as follows:-

To sodium hydride (80%, 0.9 g) in dry eChanol (30 ml) was added, with stirring, malononiCrile

(1.98 g). Ethyl chloro-(2,6-dichloro-4-trifluoro¬ methylphenyDhydrazono-acetate (11.0 g) was then added with stirring and cooling. The internal temperature quickly rose to 20°C and was kept at that for 1 hour, before filtration of the pale yellow solid. The filtrate was evaporated ^n vacuo to give an orange solid. The combined solids were dissolved in ethyl

aceCaCe, washed Cwice wich waCer, dried over anhydrous magnesium sulphaCe, filCered and evaporaCed ^n vacuo

Co give an orange solid (11.0 g) . Recrystallisation from ethyl acetate-petroleum ether gave Che CiCle compound as fawn crysCals (8.3 g) m.p. 208-209°C.

EChyl chloro-(2,6-dichloro-4-CrifluoromeChyl- phenyDhydrazonoaceCaCe was prepared as follows:-

Sodium niCrite (3.04 g) was added during 15 minutes to stirred concentrated sulphuric acid (24 ml) at 30-50°C. The solution was cooled Co 20°C, and added dropwise during 15 minuCes Co a soluCion of 2,6-dichloro-4-CrifluoromeChylaniline (9.2 g) in aceCic acid (90 ml), mainCaining aC 35-40°C This soluCion was Chen cooled Co +10°, and added dropwise Co a sCirred soluCion of anhydrous sodium aceCaCe (54 g) and eChyl chloroacetoacetate (7.0. g) in a mixCure of waCer (72 ml) and eChanol (48 ml) during 45 minuCes wich cooling such that the temperature was kept at 10°C. After 1 hour at room temperature the mixture was diluted with water, filtered, and the solid dissolved in dichloromethane. This solution was dried over anhydrous magnesium sulphate, filtered, and evaporaCed tn vacuo to give the title compound as a white solid (11.9 g) m.p. 96-98°C.

EXAMPLE 18 Compounds Nos.32 and 40

A mixture of 5-amino-l-(2,6-dichloro-4- trifluoromethylphenyl)-3-trifluoromethylpyrazole (3.64 g) and N-bromosuccinimide (1.78 g) in carbon tetrachloride (30 ml) was stirred and heated under reflux for 1 hour. Further N-bromosuccinimide (0.89 g) was added, and reflux was continued for a further 1 hour. The mixture was cooled, filtered, and the filtraCe was evaporaCed ^n vacuo Co give an orange solid. RecrysCallisaCion from peCroleum eCher gave

5-amino-4-bromo-l-(2,6-dichloro-4-CrifluoromeChyl¬ phenyl)-3-CrifluoromeChylpyrazole in Che form of whiCe crysCals (2.6 g) m.p. 119-120°C.

By proceeding in a similar manner but replacing N-bromosuccinimide by N-chlorosuccinimide there was obtained 5-amino-4-chloro-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole as ^' white crystals m.p. 99-100°C. No excess of chlorinating agent was required in this case.

REFERENCE EXAMPLE 6 5-Amino-l-(2,6-dichloro-4-Crifluoromethyl¬ phenyl)-3-trifluoromethylpyrazole was prepared as follows:-

A solution of 5-amino-4-carboxy-l- (2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoro-

meChylpyrazole (10.5 g) in N,N-dimeChylaniline (13 ml) was heaCed under reflux for 3 hours. The cooled mixCure was poured onCo concenCraCed hydrochloric acid (15 ml) and exCracCed wich eCher (4 x 30 ml). The combined exCracC was washed wich 6N hydrochloric acid (3 x 30 ml), wich waCer (2 x 30 ml), dried over anhydrous magnesium sulphaCe, filCered, and evaporaCed in vacuo. The produce was recrysCallised from cyclohexane Co give Che Cicle compound (5.7 g) as whiCe needles m.p. 126-128°C.

5-Amino-4-carboxy-l-(2,6-dichloro-4-crifluoro¬ meChylphenyl)-3-CrifluoromeChylpyrazole was prepared as follows:-

A mixCure of 5-amino-l-(2,6-dichloro-4- CrifluoromeChylphenyl)-4-meChoxycarbony1-3-Crifluoro¬ meChylpyrazole (101.2 g; hereinbefore described in Example 4) and sodium hydroxide (48 g) in waCer (170 ml) and meChanol (550 ml) was sCirred aC room temperature for 2 days, evaporated ^n vacuo, and the residue triturated with dilute hydrochloric acid.

The solid was filtered, dissolved in ethyl acetate, and the resulting solution was washed with sodium chloride solution. After drying over anhydrous magnesium sulphate, filtration, and evaporation _rn vacuo a semisolid residue was obtained. This residue was triturated with hexane and the solid was recrystallised from toluene-hexane to give the title compound as a cream solid, m.p. 212-215°C.

EXAMPLE 19 Compound No.41

Ethyl chloroformate (1.6 g) was added to a stirred solution of 5-amino-4-cyano-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole (3.9 g) in pyridine (15 ml). After stirring overnight another addition of ethyl chloroformate (1.0 ml) was made, and Che mixture was left for a further 12 hours. The solvent was evaporated iji vacuo and the residue was acidified with dilute hydrochloric acid, and extracted with dichloromethane. This extract was washed with water (3x) , dried over anhydrous magnesium sulphate, filtered, and evaporaCed jL_n vacuo. Purification by chromaCography on silica (Merck, 40-230 mesh, 0.7 kg

^■ _2 cm ) elucing wich eChyl aceCaCe - peCroleum eCher

(1:1) gave a whiCe solid, which was recrysCallised from a mixCure of dichloromeChane and hexane Co furnish white crystals of 4-cyano-l-(2,6-dichloro- 4-trifluoromethylphenyl)-5-ethoxycarbonylamino- 3-trifluoromethylpyrazole, m.p. 177-179°C.

EXAMPLE 20 Compound No.35

A solution of 5-amino-l-(2,6-dichloro-4- trifluorome hylphenyl)-3-trifluoromethylpyrazole

(3.0 g) in concentrated sulphuric acid (10 ml) ^' at 0°C was treated with fuming nitric acid (9 ml) during 15

minutes, keeping the temperature at 5-15°C. After 30 minutes the mixture was poured onto excess ice, and the precipitated solid was filtered off and dissolved in ethyl acetate. After drying over anhydrous magnesium sulphate, filCraCion, and evaporaCion in vacuo a brown oil was obCained. This oil was dissolved in Che minimum of eChyl aceCaCe and diluced wich hexane. A pale yellow solid crysCallised and Chis was discarded. The filCraCe was evaporaCed i_n vacuo Co give a solid which was recrysCallised from

Coluene-hexane Co furnish a yellow solid. One furcher recrysCallisaCion from Che same solvenC pair gave 5-amino-l-(2,6-dichloro-4-CrifluoromeChylpheny1)- 4-niCro-3-CrifluoromeChylpyrazole as whiCe crysCals, m.p. 214-215°C. ^'

EXAMPLE 21 Compound No.42 '

To a soluCion of 5-amino-4-cyano-l- (2,6-dichloro-4-CrifluoromeChylphenyl)-3- . trifluoromethylpyrazole (2.33 g) in dry tetrahydro¬ furan (30 ml) was added with stirring at room temperature, a solution of tert-butyl nitriCe (1.36 ml) in dry CeCrahydrofuran (5 ml) during 2 minutes. The solution was then heated under reflux for 1 hour and cooled, and additional tert-butyl nitrite (2.72 ml) was added. The solution was heated under reflux for 30 minutes, and left to cool

overnight. Evaporation ii vacuo gave an orange oil, which was purified by chromatography on silica (Merck,

_2

40-230 mesh, 0.7 kg cm ) eluting with dichloromethane- hexane (1:1). The product was finally recrystallised from hexane to give

4-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3-trifluoromethylpyrazole, m.p. 121-123°C, as whiCe crysCals.

EXAMPLE 22 Compound No.43

To a soluCion of 5-amino-4-cyano-l-(2,6- dichlor0-4-trifluoromethylphenyl)-3-trifluoromethyl¬ pyrazole (2.33 g) in chloroform (30 ml) stirred at room temperature, was added iodine (3.0 g) followed by

Φ tert-butyl nitrite (1.1 g) . After 2 hours the mixture was heated under reflux for 1.5 hours, cooled and filtered, and the filtrate was washed with sodium thiosulphate solution to remove excess iodine. After washing with water, drying over anhydrous magnesium sulphate and evaporation In vacuo, a yellow solid was obtained. This was chromatographed on silica (Merck, 40-230 mesh, 0.7 kg cm ^"2 ) eluting with dichloro- methane-hexane (1:2) to give a yellow oil. Dissolution in hot hexane gave, on cooling, 4-cyano- 1-(2,6-dichloro-4-trifluoromethylpheny1)-5-iodo-3- trifluoromethylpyrazole as white crystals, m.p. 86-87°C.

EXAMPLE 23 Compound No.44

To dry diisopropylamine (0.135 g) in dry tetrahydrofuran (4 ml) stirred at -78°C under nitrogen, was added via a syringe, a solution of n-buCyl lichium (0.52 ml of a 2.6 M soluCion in hexane). AfCer warming Co room CemperaCure during 1 minuCe, Che soluCion was re-cooled Co -78°C, and added via a syringe Co a sCirred soluCion of 4-cyano-l-(2,6- dichloro-4-CrifluoromeChylphenyl)-3-CrifluoromeChyl¬ pyrazole (0.5 g) in dry CeCrahydrofuran (4 ml) under nicrogen aC -78°C. ^' The addicion, during 2 minuCes, was exoChermic and Che inCernal CemperaCure was mainCained aC -60°C for a furCher 15 minuCes. MeChyl iodide (0.1 ml) was added. AfCer 1.5 hours aC Chis CemperaCure Che soluCion was poured onCo excess waCer and excracced wich dichloromeChane (3x)_ The combined organic phase was washed wich waCer, dried over anhydrous magnesium sulphaCe, and evaporaCed jir vacuo Co give a solid. ChromaCography on silica (Merck, 40-230 mesh, 0.7 kg cm ^"2 ) eluCing wich dichloromeChane-hexane (1:3) gave a whiCe solid (0.2 g) . RecrysCallisaCion from hexane furnished 4-cyano-l-(2,6-dichloro-4-tr fluoromethylphenyl)- 5-methyl-3-trifluoromethylpyrazole as white crystals, m.p. 90-92°C.

EXAMPLE 24

Compound No.45

A mixture of 5-amino-4-chlorosulphonyl-l- (2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoro- methylpyrazole (1.2 g) and dimethylamine (17.6 ml of a 40% aqueous solution) was heated on a steambath for 1 hour, cooled, and poured onto crushed ice (50 g) to give a brown solid. This solid was filtered, dried, and recrystallised from toluene to give 5-amino-l-(2,6-dichloro-4-trifluoromethylphenyl)- 4-(N,N-dimethylsulphamoyl)-3-trifluoromethyl¬ pyrazole (0.8 g) as light brown crystals, m.p. 177.6-178.6°C.

REFERENCE EXAMPLE 7 5-Amino-4-chlorosulphonyl-l-(2,6-dichloro-

4-trifluoromethylphenyl)-3- rifluoromethylpyrazole used in the above example was prepared as follows:- 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-trifluoromethylpyrazole (9.1 g) was added portionwise to stirred cooled chlorosulphonic acid (16.2 ml), keeping the internal temperature below 10°C. The orange solution was stirred at room temperature for 30 minutes, then at 120°C for 5 hours, and poured onto iced water (300 ml) to give a pale brown solid. This solid was filtered, dried, and recrystallised from cyclohexane to give the title compound as yellow crystals.

EXAMPLE 25 Compound No.46

A solution of 2,6-dichloro-4-trifluoromethyl- phenylhydrazine (3.8 g) and 1,l-dicyano-2-cyclopropyl- 2-methoxyethylene (2.23 g) in methanol (30 ml) was stirred and treated wich sodium hydride (80%, 30 mg) . AfCer 4 hours Che soluCion was evaporaCed iri vacuo and Che residue was dissolved in eChyl aceCaCe (40 ml), treated with charcoal and washed with water. The organic phase was evaporated _in vacuo, the residual oil was dissolved in petroleum ether and crystals of 5-amino-4-cyano- 3-cyclopropyl ^' -l-(2,6-dichloro- 4-trifluoromethylphenyl)pyrazole, m.p. 197-199°C, were obtained.

EXAMPLE 26

Compounds Nos. 48, 49 and 50

By proceeding in a similar manner to that hereinbefore described in Example 1, but replacing 2,4,6-trichlorophenylhydrazine by 2,6-dichloro-

4-trifluoromethylthiophenylhydrazine, there was obtained:-

5-Amino-3,4-dicyano-l-(2,6-dichloro-

4-trifluoromethylthiophenyl)pyrazole, m.p. 226-227°C, in the form of an off-white solid, after recrystallisation from toluene.

By employing 2-chloro-3, 5,6-trifluoro-

4-trifluoromethylphenyIhydrazine there was prepared: -

5-Amino-l-(2-chloro-3, 5, 6-trifluoro- 4-trifluoromethylpheny1)-3,4-dicyanopyrazole, m.p. 242-243°C, in the form of an orange solid, after recrystallisation from a mixture of ethanol and water.

By employing 2,6-dichloro-3,5-difluoro-

4-trifluoromethylphenyIhydrazine there was prepared:- 5-Amino-l-(2,6-dichloro-3,5-difluoro-

4-trifluoromethylphenyl)-3,4-dicyanopyrazole, m.p. 245-247 ^β C, in the form of an off-white solid.

REFERENCE EXAMPLE 8

2,6-Dichloro-4-trifluoromethylthiophenyIhydrazine was prepared by following the procedure of Reference

Example 1, by proceeding in a similar manner, but replacing the 2,6-dichloro-4-trifluoromethylaniline by

2,6-dichlorό-4-trifluoromethyIthioaniline.

REFERENCE EXAMPLE 9 2-Chloro-3, 5,6-Crifluoro-4-CrifluoromeChyl¬ phenyIhydrazine was prepared as follows:-

3-Chloro-2,4,5,6-CeCrafluorobenzoCrifluoride (12.1 g) and hydrazine hydraCe (3.4 g) were heaCed under reflux wich eChanol (50 ml) for 3.5 hours. The mixture was poured onto ice/water mixture (500 ml), stirred, and the product was filtered. After washing with water and drying in a desiccator the title compound was obtained in the form of white crystals, m.p. 91-92°C.

By proceeding in a similar manner but replacing 3-chloro-2,4,5,6-tetrafluorobenzotrifluoride by 3,5-dichloro-2,4,6-CrifluorobenzoCrifluoride Chere was prepared 2,6-dichloro-3,5-difluoro-4-Crifluoro¬ meChylphenyIhydrazine in Che form of pale yellow crysCals, m.p. 78-80°C.

EXAMPLE 27 Compound No. 51 By proceeding in a similar manner Co chaC hereinbefore described in Example 2, buC employing 2,6-dichloro-4-CrifluoromeChoxyphenylhydrazine Chere was obtained:-

5-Amino-l-(2,6-dichloro-4-trifluoromethoxy- phenyl)-3, -dicyanoρyrazole, m.p. 231-232°C in Che form of a brown solid, afCer recrystallisation from toluene.

REFERENCE EXAMPLE 10

2,6-Dichloro-4-trifluoromethoxyphenylhydrazine used in the above Example 27 was prepared by following the procedure of Reference Example 1, by proceeding in a similar manner, but replacing the 2,6-dichloro-

4-trifluoromethylaniline by 2,6-dichloro-4-trifluoro- meChoxyaniline. The CiCle compound was obCained as fawn crysCals, m.p. 64-65°C.

EXAMPLE 28 Compounds Nos. 52. 53. 54 and 55

By proceeding in a similar manner Co ChaC hereinbefore described in Example 3, but replacing the ethoxyethylenemalononitrile by ethoxypropylene- malononitrile there was prepared:- 5-Amino-4-cyano-3-ethyl-l-(2,6-dichloro-

4-trifluoromethylphenyl)pyrazole in the form of white crystals, m.p. 158-160 ^β C, after recrystallisation from a mixture of ethyl acetate and hexane.

By proceeding in a similar manner but replacing the ethoxyethylenemalononitrile by ethoxy- eChylenemeChanesulphonylaceConiCrile, and by replacing Che sodium aceCate and glacial acetic acid by ethanol containing 10 mol % of triethylamine at reflux, there was prepared:- 5-Amino-l-(2,6-dichloτo-4-trifluoromethyl¬ phenyl)-4-methanesulphonyl-3-methylpyrazole in the form of a white solid, m.p. 195°C, after recrystallisation from a mixture of ethyl aceCaCe and hexane.

By proceeding in a similar manner but replacing the ethoxyethylenemalononitrile by ethoxy- ethylenecyanoacetic acid ethyl ester there was prepared:- 5-Amino-l-(2,δ-dichloro-4-CrifluoromeChyl¬ phenyl)-3-meChyl-4-eChoxycarbonylpyrazole in Che form of whiCe crysCals, m.p. 115-118°C afCer recrysCallisaCion from a mixCure of Coluene and peCroleum ether. By proceeding in a similar manner but replacing the ethoxyethylenemalononitrile by ethoxy- ethylenemethanesulphonylacetonitrile, and by replacing the 2,δ-dichloro-4-trifluoromethylphenyIhydrazine by 2,6-dichloro-4-trifluoromethoxyphenyIhydrazine and by performing the reaction in a 1:1 v/v mixture of ethanol and triethylamine at ambient temperature, there was obtained:- '

5-Amino-l-(2,6-dichloro-4-trifluoromethoxy¬ phenyl)-4-methanesulphonyl-3-methylpyrazole, in the form of a fawn solid, m.p. 180-181°C.

REFERENCE EXAMPLE 11 3-Ethoxy-2-methanesulphonylbut-2-ene-nitrile, used in the above Example 28 was prepared as follows:-

A mixture of methanesulphonylacetonitrile (200 g) , triethylorthoacetate (348 g) and zinc chloride (21 g) was stirred in hexane (1200 ml) with heating under reflux. The distillate was collected via a Mclntyre head, with additional hexane added Co the reaction mixture as necessary. Hexane (2800 ml) was collected

during 8 hours. After cooling, the mixture was evaporated in vacuo, and re-evaporated after addition of toluene (100 ml). The residue was dissolved in ethyl acetate and recrystallised from a mixture of ethyl acetate with hexane, twice, to give white crystals, m.p. 99°C, of the title compound.

EXAMPLE 29 Compounds Nos. 56, 57, 58 and 59

By proceeding in a similar manner to that hereinbefore described in Example 4, but replacing the 2,6-dichloro-4-trifluoromethylphenylhydrazine by 2-chloro-3, 5,6-trifluoro-4-trifluoromethylphenyl- hydrazine there was obtained:-

5-Amino-l-(2-chloro-3,5,6-trifluoro- 4-trifluoromethylphenyl)-4-cyano-3-trifluoromethyl¬ pyrazole, in the form of white crystals, m.p. 187-189°C, after recrystallisation (from toluene.

By employing 2,6-dichloro-4-trifluoromethyl- thiophenyIhydrazine there was obtained:- 5-Amino-4-cyano-l-(2,6-dichloro-4-Cri luoro¬ meChylChiophenyl)-3-CrifluoromeChylpyrazole, in Che form of pale yellow crysCals, m.p. 133.5-134.5°C, afCer recrysCallisaCion from hexane.

By replacing the 2-chloro-l,1-dicyano- 2-CrifluoromeChyleChylene by 2,3-dichloro-l,1-dicyano- 3-fluoromethylethylene there was obtained:-

5-Amino-3-chlorofluoromethy1-4-cyano-l-

(2,6-dichloro-4-trifluoromethylphenyl)pyrazole in the form of a cream solid, m.p. 186-188°C, after recrystallisation from a mixture of toluene and hexane. By employing 2,6-dichloro-3,5-difluoro-

4-trifluoromethylphenylhydrazine there was obtained:-

5-Amino-4-cyano-l-(2,6-dichloro-3,5-difluoro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole in the form of a light brown solid, m.p. 176-177°C. REFERENCE EXAMPLE 12

Chloro-dicyanoethylene used as starting material in the above Example 29, not hitherto described in the chemical literature was prepared as follows:- By proceeding in a similar manner to that hereinbefore described in Reference Example 2, but replacing 2-cyano-3-hydroxy-4-chloro-4,4-difluorobut- 2-enenitrile sodium salt by 2-cyano-3-hydroxy- 4-chloro-4-fluorobut-2-enenitrile sodium salt there Was prepared 2-chloro-2-chlorofluoromethyl-l,l-dicyano- ethylene as a liquid, b.p. 90°C (46 mmHg).

By proceeding in a similar manner to that hereinbefore described in Reference Example 3, but replacing methyl chlorodifluoroacetate by ethyl chloro- fluoroacetate, there was obtained 2-cyano-3-hydroxy- 4-chloro-4-fluorobut-2-enenitrile sodium salt as an orange-red solid.

EXAMPLE 30 Compound No. 60

By proceeding in a similar manner to that hereinbefore described in Example 9, but replacing the trimethylorthoformate by triethylorthoacetate there was prepared:-

4-Cyano-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-5-(1-ethoxyethylideneamino)-3-methylpyrazole as a white solid, m.p. 50-53°C, after purification by chromatography on silica (Merck 230-400 mesh, 0.7 kg

_2 cm ) using dichloromethane as eluent.

EXAMPLE 31 Compounds Nos. 61, 62 and 63

By proceeding in a similar manner to that hereinbefore described in Example 10, but replacing the 5-amino-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3,4-dicyanopyrazole by 5-amino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-cyano-3-methylpyrazole and acylating with succinyl dichloride there was obtained:- 4-Cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3-methyl-5-succinimidopyrazole in the form of a white solid, m.p. 202-204°C, after purification by chromatography on silica (Merck 230-400 mesh, 0.7 kg

_,2 cm ) using dichloromethane/ethyl acetate (98:2) as eluent.

By proceeding in a similar manner but replacing the 5-amino-1-(2,6-dichloro-4-trifluoro¬ methylphenyl)^,4-dicyanopyrazole by 5-amino- l-(2,6-dichloro-4-trifluoromethylphenyl)-4-methane- sulphonyl-3-trifluoromethylpyrazole, and employing acetonitrile as solvent for the acylation, there was prepared:-

5-Acetamido-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-methanesulphonyl-3-trifluoromethylpyrazole in the form of a white solid, m.p. 194-195°C, after recrystallisation from toluene.

By proceeding in a similar manner (to Example 10) but replacing the 5-amino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3,4-dicyanopyrazole by 5-amino-l-(2,6-dichlor0-4-trifluoromethylpheny1)-

3-methyl-4-methanesulphonylpyrazole Chere was prepared 5-acetamido-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3-methyl-4-methanesulphonylpyrazole in the form of yellow crystals, m.p. 202-203°C. EXAMPLE 32

Compound No. 64

By proceeding in a similar manner to that hereinbefore described in Example 11, but replacing the 2-chloro-4-trifluoromethylphenyIhydrazine by 2,δ-dichloro-4-nitrophenyIhydrazine there was prepared:- 5-Amino-l-(2,6-dichloro-4-nitrophenyl)- 3,4-dicyanopyrazole, in the form of a pale brown solid, m.p. 289-290°C.

EXAMPLE 33 Compounds Nos. 65 and 66

By proceeding in a similar manner to ChaC hereinbefore described in Example 12, buC replacing che 5-amino-4-cyano-l-(2,6-dichloro-4-CrifluoromeChyl¬ phenyl)-3-CrifluoromeChylpyrazole by 5-amino- 1-(2,δ-dichloro-4-CrifluoromeChylphenyl)-3,4-dicyano¬ pyrazole and using an appropriate quantity of methyl iodide there was prepared:- 1-(2,6-Dichloro-4-trifluoromethylphenyl)-

3,4-dicyano-5-methylaminopyrazole in the form of a pale yellow solid, m.p. 165-166°C, after recrystallisation from toluene.

By proceeding as above, but employing ethyl iodide, there was prepared:- l-(2,6-Dichloro-4-trifluoromethylphenyl)- 3,4-dicyano-5-ethylaminopyrazole in the. form of an off-white solid, m.p. 245-246°C, after purification by chromatography on silica (Merck 230-400 mesh, 0.7 kg

_2 cm ) using a mixture of ethyl acetate and petroleum ether (15:85).

EXAMPLE 34 Compounds Nos. 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78 and 79

By proceeding in a similar manner Co ChaC hereinbefore described in Example 14, buC replacing Che 5-amino-4-cyano-l-(2,6-dichloro-4-CrifluoromeChyl¬ phenyl)-3-CrifluoromeChylpyrazole and the trimethyl¬ acetyl chloride by the following phenylpyrazoles and acylating agents, there were prepared:- 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ pheny1)-5-(N-meChyl-N-eChoxycarbonylamino)- 3-CrifluoromeChylpyrazole in Che form of a whiCe solid, m.p. 88-90 ^β C, afCer recrysCallisaCion from hexane, using 4-cyano-l-(2,6-dichloro-4-Crifluoro- meChylphenyl)-5-meChylamino-3-CrifluoromeChylpyrazole and eChyl chloroformaCe;

4-Cyano-l-(2,6-dichloro-4- rifluoromethy1- phenyl)-5-(N-acetyl-N-trimethylacetylamino)-3-trifluoro¬ methylpyrazole in the form of an off-white solid, m.p. 83.5-84°C, after recrystallisation from hexane, using 4-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)- 5- rimethylacetylamino-3-trifluoromethylpyrazole and acetyl chloride;

4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ pheny1)-5-(N-propionyl-N-trimethylacetylamino)- 3-trifluoromethylpyrazole in the form of a white solid, m.p. 56-56.5°C, after recrystallisation from hexane, using 4-cyano-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-5-trimethylacetylamino-3-trifluoromethyl¬ pyrazole and propionyl chloride; l-(2,δ-Dichloro-4-trifluoromethylphenyl)- 4-nitr0-3- rifluoromethy1-5-trimethylacetylamino- pyrazole in the form of a white solid, m.p. 219°C, using 5-amino-l-(2,6-dichlor0-4-trifluoromethylphenyl)- 4-nitro-3-trifluoromethylpyrazole and trimethylacetyl chloride; l-(2,δ-Dichloro-4-trifluoromethylphenyl)- 5-ethoxycarbonylamino-4-nitr0-3-trifluoromethylpyrazole in the form of pale yellow crystals, m.p. 124°C, using 5-amino-l-(2,6-dichloro-4-trifluorpmethylphenyl)- 4-nitro-3-trifluoromethylpyrazole and ethyl chloroformate; and 3-Chloro-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-cyano-5-trimethylacetylaminopyrazole, in the form of a white solid, m.p. 203-204°C;

3-Chloro-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-cyano-5-bis(ethoxycarbonyl)amJnopyrazole, in the form of an orange crystalline solid, m.p. 67-69°C;

and 3-Chloro-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-cyano-5-ethoxycarbonylaminopyrazole, in the form of a yellow solid, m.p. 175-179°C;

[The latter three compounds were obtained by reaction of 5-amino-3-chloro-l-(2,6-dichloro-

4-trifluoromethylphenyl)-4-cyanopyrazole with the appropriate acyl chlorides]

4-Cyano-5-diacetylamino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole in the form of white crystals, m.p. 138-139°C; and 5-(N-Acety1-N-ethoxycarbonylamino)-4-cyano- 1-(2,6-dichloro-4-trifluoromethylphenyl)-3- rifluoro¬ methylpyrazole in the form of a white solid, m.p. 101-102°C; [The above two compounds were obtained by reaction of 5-acetylamino-l-(2,6-dichloro-4-trifluoro¬ methyl)-4-cyano-3-trifluoromethylpyrazole and the appropriate acyl chlorides] and l-(2,6-Dichloro-4-t.rifluoromethylpheny1)- 5-bis(ethoxycarbonyl)amino-3,4-dicyanopyrazole and l-(2,6-dichloro-4-trifluoromethylphenyl)-5-bis(ethoxy- carbonyl)amino-4-methanesulphony1-3-trifluoromethyl¬ pyrazole were prepared in a similar manner to the procedure described in Example 14, but replacing the

-am no- -cyano- - , - c oro- - r uorome ¬ phenyl)-3-trifluoromethylpyrazole by 5-amino- 1-(2,6-dichlor0-4-trifluoromethylphenyl)-3,4-dicyano¬ pyrazole and by 5-amino-l-(2,6-dichloro-4-trifluoro- methylphenyl)-4-methanesulphonyl-3-trifluoromethyl¬ pyrazole respectively. The trimethylacetyl chloride was replaced by the appropriate quantity of ethyl chloroformate (two equivalents) and 2 equivalents of sodium hydride were also used. The products were white crystals with m.p. 74-76°C, and 148-151°C, respectively.

EXAMPLE 35 Compounds Nos. 79 and 80

By proceeding in a similar manner to that hereinbefore described in Example 15, but replacing the 4-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)-

5-bis(cyclopropanecarbonyl)amino-3-trifluoromethyl¬ pyrazole by l-(2,6-dichloro-4-trifluoromethylphenyl)-

I

5-bis(ethoxycarbonyl)amino-4-methanesulphonyl- 3-trifluoromethylpyrazole there was obtained:- l-(2,6-Dichloro-4-trifluoromethyIpheny1)-

5-ethoxycarbonylamino-4-methanesulphony1-3-trifluoro¬ methylpyrazole in the form of a white solid, m.p. 138-141°C.

By proceeding in a similar manner but replacing the 4-cyano-l-(2,6-dichloro-4-trifluoro¬ methylpheny1)-5-bis(cyclopropanecarbonyl)amino- 3-trifluoromethylpyrazole by l-(2,6-dichloro- 4-trifluoromethylphenyl)-5-bis(ethoxycarbony1)amino- 3,4-dicyanopyrazole there was obtained:- l-(2,6-Dichloro-4-trifluoromethylphenyl)- 3,4-dicyano-5-ethoxycarbonylaminopyrazole in the form of a white solid, m.p. 161-163°C. EXAMPLE 36

Compounds Nos. 81 and 82

By proceeding in a similar manner to that hereinbefore described in Example 18, but replacing N-bromosuccinimide by N-iodosuccinimide there was obtained:-

5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-iodo-3-trifluoromethylpyrazole^ in the form of a white solid, m.p. 129°C.

By replacing N-bromosuccinimide by N-iodosuccinimide, and replacing 5-amino-

1-(2,6-dichlor0-4-trifluoromethylphenyl)-3-trifluoro¬ methylpyrazole by 5-amino-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-methylpyrazole (hereinafter described in Reference Example 13), there was obtained:- 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-iodo-3-methylpyrazole in the form o a buff solid, m.p. 108-109°C, after recrystallisation from hexane.

5-Amiπo-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-methylpyrazole was prepared as follows:- 5-Amino-4-carboxy-l-(2,δ-dichloro-4-trifluoro- methylphenyl)-3-methylpyrazole (28 g) was heated to 190°C under nitrogen, and maintained at this temperature until gas evolution ceased. After cooling, the title compound was obtained (22 g) as a yellow gum. 5-Amino-4-carboxy-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-methylpyrazole used above was prepared by proceeding in a similar manner to Reference Example 6 but replacing 5-amino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-methoxycarbony1-3-trifluoro- methylpyrazole by 5-amino-l-(2,6-dichloro-4-trifluoro- methylphenyl)-4-ethoxycarbony1-3-methylpyrazole (hereinbefore described in Example 28) , and by

I performing the base hydrolysis at the reflux temperature in ethanol for 13 hours. The title compound was obtained as a white solid, m.p. 183-184°C.

EXAMPLE 37 Compounds Nos. 83, 84 and 85

By proceeding in a similar manner to that hereinbefore described in Example 20, but replacing 5-amino-l-(2,6-dichloro-4-trifluoromethylphenyl)-

3-CrifluoromeChylpyrazole by 5-amino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-methylpyrazole, and

replacing the mixture of concentrated sulphuric and fuming nitric acids by concentrated niCric acid alone, chere was obtained:-

5-Amino-l-(2,6-dichloro-4-CrifluoromeChy1- phenyl)-3-meChyl-4-niCropyrazole in Che form of orange . crysCals, m.p. 229-231*C, afCer recrysCallisaCion from a mixCure of oluene and peCroleum eCher.

By proceeding in a similar manner buC replacing 5-amino-l-(2,6-dichloro-4-CrifluoromeChy1- phenyl)-3-CrifluoromeChylpyrazole by 5-aceCamido- l-(2,6-dichloro-4-CrifluoromeChylphenyl)-3-Crifluoro¬ meChylpyrazole, and replacing Che mixCure of concenCraCed sulphuric and fuming niCric acids by a mixCure of aceCic acid and aceCic anhydride Co which was added fuming niCric acid, Chere was obtained:- 5-Acetamido-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-nitro-3-trifluoromethylpyrazole in the form of a cream solid, m.p. 194-195°C.

By proceeding in a similar manner but replacing 5-amino-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-3-trifluoromethylpyrazole by l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole, and replacing the mixture of concentrated sulphuric and fuming nitric acids by acetic anhydride to which was added fuming nitric acid, there was obtained:- l-(2,6-Dichloro-4-trifluoromethylphenyl) ^* - 4-nitro-3-trifluoromethylpyrazole in the form of an orange solid, m.p. 110-112 ^β C, after recrystallisation from a mixture of toluene and hexane.

REFERENCE EXAMPLE 14 l-(2,6-Dichlor0-4-trifluoromeChylphenyl)- 3-trifluoromeChylpyrazole used in Che above Example 37 was prepared by Che procedure described in Example 21 by replacing 5-amino-4-cyano-l-(2,6-dichloro-

4-CrifluoromeChylphenyl)-3-CrifluoromeChylpyrazole by 5-amino-1-(2,6-dichlo o-4-CrifluoromeChylphenyl)- 3-CrifluoromeChylpyrazole. The CiCle compound was obCained as a pale yellow oil. 5-AceCamido-l-(2,6-dichloro-4-CrifluoromeChyl¬ phenyl)-3-CrifluoromeChylpyrazole used in Che above Example 37 was prepared by Che procedure described in Example 15, buC replacing Che 4-cyano-l-(2,6-dichloro- 4-CrifluoromeChylphenyl)-5-bis(cyclopropanecarbonyl)- amino-3-CrifluoromeChylpyrazole by 5-bis(aceCyl)amino- l-(2,6-dichloro-4-CrifluoromeChylphenyl)-3-Crifluoro¬ meChylpyrazole. The CiCle compound was obCained as i whiCe crysCals, m.p. 142-144°C, afCer recrysCallisaCion from eChyl aceCaCe and hexane. 5-Bis(acetyl)amino-l-(2,6-dichloro-

4-trifluorome hylphenyl)-3-trifluoromethylpyrazole, used above, was prepared by the procedure of Example 19 but replacing 5-amino-4-cyano-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole by 5-amino-l-(2,6-dichloro-4-trifluoromethyIphenyl)-

3-trifluoromethylpyrazole, and the ethyl chloroformate by acetyl chloride. The title compound was obtained as a white solid, m.p. 130-131*C.

EXAMPLE 38

Compound Nos. 86, 87 and 88

By proceeding in a similar manner to that hereinbefore described in Example 21, but replacing the 5-amino-4-cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-trifluoromethylpyrazole by 5-amino- l-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl- 4-methanesulphonylpyrazole, there was obtained l-(2,6-dichloro-4-trifluoromethylphenyl)-3-methyl- 4-methanesulphonylpyrazole in the form of yellow crystals, m.p. 168-169*C.

By proceeding in a similar manner but replacing the 5-amino-4-cyano-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole by 5-amino-4-cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-fluoropyrazole, there was obtained 4-cyano- 1-(2,6-dichlor0-4-trifluoromethylphenyl)-3-fluoro- pyrazole in the form of white crystals, m.p. 120-121°C. 1-(2,6-Dichloro-4-trifluoromethylpheny1)- 4-methanesulphonyl-3-trifluoromethylpyrazole was prepared in a similar manner by replacing 5-amino- 4-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3-trifluoromethylpyrazole by 5-amino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-methanesulphony1-3-trifluoro- methylpyrazole. The title compound was obtained in the form of white needles, m.p. 154-155°C.

Compound No. 89

By proceeding in a similar manner to that hereinbefore described in Example 22, but replacing the iodine by anhydrous cupric chloride, and by replacing the chloroform by anhydrous acetonitrile, there was obtained:-

5-Chloro-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-cyano-3-trifluoromethylpyrazole in the form of a yellow oil, after purification by chromatography

_2 on silica (Merck, 40-230 mesh, 0.7 kg cm ) eluting with a mixture of dichloromethane and hexane (1:2).

Infra-Red Absorption bands: 2260, 1495, 1405, 1325,

1160 cm ^"1 (liquid film) EXAMPLE 40

Compound Nos. 90 and 91

By proceeding in a similar manner to that hereinbefore described in Example 24, but replacing the dimethylamine by the appropriate amines there was prepared the following phenylpyrazoles:-

5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-(N-ethylsulphamoyl)-3-trifluoromethyl¬ pyrazole in the form of a cream solid, m.p. 200 ^β C, after recrystallisation from a mixture of toluene and petroleum ether.

5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-(N-methylsulphamoyl)-3-trifluoromethyl¬ pyrazole in the form of a light brown solid, m.p. 199-200°C, after recrystallisation from toluene.

Compounds Nos. 92 and 93

Trifluoroacetic anhydride (3.5 ml) was added dropwise to a stirred mixture of 85% w/v hydrogen peroxide solution (0.56 ml) in dichloromethane (15 ml) maintaining at 0-10°C. After warming to 20*C during 5 minutes, a solution of 3-amino-l-(2,6-dichloro- 4-trifluoromeChyl-phenyl)-4-cyanopyrazole (1.0 g; hereinafter described in Reference Example 15) in dichloromethane (10 ml) was added dropwise over 5 minutes. A temperature rise of 10*C was observed during the addition, and the mixture heated under reflux for 1.5 hours. After cooling, the solution was poured onto excess water, and the organic solution washed in turn with solutions of sodium bicarbonate and sodium bisulphite. Drying over anhydrous magnesium sulphate, followed by evaporation in vacuo gave a buff solid, which was purified by chromatography on silica (Merck, 40-230 mesh, 0.7 kg cm ^"2 ) eluting with dichloromethane. The resultant white solid was recrystallised from a mixture of dichloromethane apd hexane to give

1-(2,δ-dichloro-4-trifluoromethylphenyl)-4-cyano- 3-nitropyrazole as white crystals (0.7 g) , m.p. 163-165*C.

. - H ^β - By proceeding in a similar manner buC replacing 3-amino-l-(2,6-dichloro-4-CrifluoromeChyl¬ phenyl)-4-cyanopyrazole by 5-amino-l-(2,6-dichloro- 4-CrifluoromeChylphenyl)-3, -dicyanopyrazole (hereinbefore described in Example 2) , Chere was obCained:- l-(2,6-Dichloro-4-trifluoromethylphenyl)- 3,4-dicyano-5-niCropyrazole as orange crysCals, m.p. 138-140*C, afCer recrysCallisaCion from cyclohexane.

REFERENCE EXAMPLE 15 3-Amino-l-(2,6-dichloro-4-CrifluoromeChyl¬ phenyl)-4-cyanopyrazole was prepared as follows:- A soluCion of 3-CerC-buCoxycarbonylamino- l-(2,6-dichloro-4-CrifluoromeChylphenyl)-4-cyanoρyrazole (2.8 g) in eChanol (100 ml) was CreaCed wich 50% v/v hydrochloric acid (10 ml), and Che mixCure heaCed under reflux for 1 hour. AfCer sCanding overnighc aC room CemperaCure, sodium carbonate was added to pH 8, and the mixture extracted three times with dichloromethane. The extract was washed.with water, dried over anhydrous magnesium sulphate, and evaporated in vacuo to give a buff solid. RecrysCallisaCion from a mixture of ethyl acetate and petroleum ether gave Che title compound (1.4 g) in the form of white crystals, m.p. 159-160°C.

3-tert-Butoxycarbonylamino-l-(2,6-dichloτo- 4-trifluoromethylphenyl)-4-cyanopyrazole was prepared as follows:-

A mixCure of 3-carboxy-4-cyano- l-(2,6-dichloro-4-CrifluoromeChylphenyl)pyrazole (11 g) and Chionyl chloride (35 ml) and N,N-dimeChylformamide (3 drops) was heaCed under reflux for 2 hours. The solvenC was evaporaCed in vacuo, and re-evaporated in vacuo after addition of dry toluene (20 ml). The resultant gum was dissolved in dry acetone (50 ml) and stirred, whilst a solution of sodium azide (2.9 g) in water. (15 ml) was added during 5 minutes keeping at 10-15*C. After 30 minutes the mixture was poured onto water (250 ml) and extracted wich dichloromeChane (3 x 80 ml). The combined exCract was washed with water, dried over anhydrous magnesium sulphate, and evaporaCed in vacuo aC equal Co or below 40*C Co give a buff solid (13 g).

The resulcing azide was dissolved in dry Coluene (200 ml) and heaCed under reflux for half-an-hour, wich smooch evoluCion of niCrogen. AfCer cooling, Chis was CreaCed wich Cert-buCanol (40 g) , and Che mixCure heaCed under reflux overnight. After evaporation in vacuo, the resulting brown oil (\5 g) was purified by chromatography on silica (Merck, 230-400 mesh, 0.7 kg

2 cm ) eluting with dichloromethane and ethyl aceCaCe

(98:2) Co give Che title compound (8.0 g) as a white solid, m.p. 154-155*C.

3-Carboxy-4-cyano-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)pyrazole was prepared as follows:-

A suspension of 4-cyano-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-ethoxycarbonylpyrazole (5.0 g) in ethanol (100 ml) was treated with a solution of sodium hydroxide (0.63 g) in water (15 ml) and stirred at room CemperaCure for 1.5 hours. AfCer evaporaCion in vacuo aC equal to or below 40*C, the residue was dissolved in water (150 ml) and extracted with dichloromethane (1 x 100 ml). This extract- as back-washed with water (2 x 50 ml), and the combined aqueous solutions brought to pH 1 with dilute hydrochloric acid, and then extracted with eChyl aceCaCe (3 x 50 ml) . This exCracC was dried over anhydrous magnesium sulphaCe, and evaporaCed in vacuo to give a buff solid (4.6 g) . Recrystallisation from a mixCure of toluene and hexane gave the ⁽ title compound in the form of buff crystals (4.4 g) , m.p. 203-205°C. 4-Cyano-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-3-ethoxycarbonylpyrazole was prepared by following the method described in Example 21, and replacing 5-amino-4-cyano-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-trifluoromethylpyrazole by 5-amino- 4-cyano-l-(2,6-dichloro-4-trifluoromethylpheny1)- 3-ethoxycarbonylpyrazole. The title compound was obtained in the form of buff crystals, m.p. 198-199*C.

EXAMPLE 42 Compounds Nos. 94, 95 and 96

Silver(I) fluoride (5 g) was added in portions during 40 minutes to a vigorously stirred solution of 1, l-dichloro-2,2-dicyanoethylene in acetonitrile (15 ml), maintained at 0-10*C by external cooling. The stirring was continued at room temperature for 1 hour, and Che solid filtered off. The filtrate containing 1,1-difluoro-2,2-dicyanoethylene was stirred and cooled whilst a solution of 2,6-dichloro-4-trifluoromethyl¬ phenyIhydrazine (4.9 g) in acetoniCrile (15 ml) was added dropwise at 5*C. After stirring overnight the solid was filtered off and the filtrate evaporated in vacuo to give a dark orange oil (6 g) . This was purified by chromatography or silica (Merck, 230-400

_2 mesh, 10 lb in ) eluting with dichloromethane to give a white solid. Recrystallisation from a mixture of cyclohexane and ethyl acetate gave 5-amino-

1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano- 3-fluoropyrazole (0.9 g) as a white solid, m.p. 193-194*C..

By proceeding in a similar manner but replacing the 2,6-dichloro-4-trifluoromethylphenyl- hydrazine by 2,6-dichloro-4-trifluoromethoxyphenyl- hydrazine and by employing 1,1-dichloro- 2,2-dicyanoeChylene insCead of 1,1-difluoro- 2,2-dicyanoeChylene, and by using dieChyl eCher as solvent, there was prepared

5-amino-3-chloro-l-(2,6-dichloro-4-trifluoromethoxy- phenyl)-4-cyanopyrazole in the form of a yellow solid, m.p. 175-177*C.

By proceeding as immediately above but replacing the 2,6-dichloro-4-trifluoromethoxyphenyIhydrazine by

2,6-dichloro-3, 5-difluoro-4-trifluoromeehylphenyl- hydraziπe, Chere was prepared 5-amino-

3-chloro-4-cyano-l-(2,6-dichloro-3, 5-difluoro-

4-trifluoromethylphenyl)pyrazole, in the form of yellow crystals, m.p. 206-208*C.

EXAMPLE 43 Compounds Nos. 97, 98,- 99, 100, 101, 102 and 103

A stirred solution of 4-cyano-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole (1.5 g) in dry tetrahydrofuran cooled to -78°C was treated with a solution of n-butyl lithium (2.6 M in hexane, 1.71 ml) dropwise under nitrogen. The temperature was kept below -65*C during the addition, and the resultant solution kept at -78*C for 1 hour. A solution of trimethylsilyl chloride (0.56 ml) in dry

CeCrahydrofuran (2 ml) was then added, dropwise, during 2 minutes. The mixture was allowed to reach room temperature over 2 hours, left overnight and evaporated in vacuo to give a pale yellow solid. This was dissolved in dichloromethane, washed with water, dried over anhydrous magnesium sulphate, and evaporaCed in vacuo. The product was recrystallised from hexane to

give 4-cyano-l-(2,δ-dichloro-4-CrifluoromeChylpheny1)- 3-CrifluoromeChyl-5-CrimeChylsilylpyrazole as whiCe crysCals, m.p. 108-110*C.

By proceeding in a similar manner buC replacing Che CrimeChylsilyl chloride by Che reagenCs lisCed below, Che following phenylpyrazoles were obtained:-

5-CerC-BuCyldimeCh lsilyl-4-cyano- l-(2,6-dichloro-4-CrifluoromeChylphenyl)-3-Crifluoro¬ meChylpyrazole in Che form of whiCe crysCals, m.p. 113-115*C; from CerC-buCyldimeChylsilyl chloride. 4-Cyano-l-(2,6-dichloro-4-CrifluoromeChyl- phenyl)-5-meChylchio-3-CrifluoromeChylpyrazole, in Che form of a whiCe powder, m.p. 73-74*C; from meChylthiocyanate. 4-Cyano-1-(2,6-dichlor0-4- rifluoromethyl¬ phenyl)-3-trifluoromethyl-5-CrifluoromeChylchiopyrazole, in the form of white crystals, m.p. 120-122°C; from bis[trifluoromethyl]disulphide.

5-Carboxy-4-cyano-l-(2,6-dichloro-4-Crifluoro- meChylphenyl)-3-CrifluoromeChylpyrazole, in Che form of a whiCe solid, m.p. 177-179*C, by pouring Che liChiaCed pyrazole soluCion onCo a large excess of powdered solid carbon dioxide.

By proceeding in a similar manner buC replacing Che 4-cyano-l-(2,6-dichloro-4-Crifluoro¬ meChylphenyl)-3-CrifluoromeChylpyrazole by 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-nitro- 3-trifluoromethylpyrazole, there was prepared:-

1-(2,6-Dichloro-4-trifluoromethylphenyl)- 4-nitro-3-trifluoromethy1-5-trimethylsilylpyrazole, in the form of a pale green solid, m.p. 101-103°C.

By proceeding in a similar manner but replacing the 4-cyano-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-trifluoromethylpyrazole by 4-cyano-l-(2,6-dichlor0-4-trifluoromethylphenyl)- 5-methy1-3-trifluoromethylpyrazole (hereinbefore described in Example 23), there was prepared:- 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-trifluoromethy1-5-trimethylsilylmethyl- pyrazole, in the form of a colourless oil. Infra-Red Absorption bands: 2250, 1400, 1325, 1260, 1180, 1150, 860cm ^"1 (liquid film) Nuclear Magnetic Resonance: chemical shift (delta) for -Si-CH ₂ - 2.8ppm in dimethylsulphoxide-Dg

EXAMPLE 44 Compound No. 104

Sodium methoxide (0.3 g) was added to an ice cold stirred mixture of 4-cyano-l-(2,6-dichloro- 4-trifluoromethylpheny1)-5-bis(phenoxycarbonyl)amino- 3-trifluoromethylpyrazole (3.1 g) in methanol (30 ml), and heated under reflux for 2 hours. This was poured onto water (200 ml) and extracted with dichloromethane. The organic solution was washed with sodium carbonate solution, then with water, dried over anhydrous magnesium sulphate, and evaporated it

vacuo. The resulCanC whiCe solid was 4-cyano- l-(2,6-dichloro-4-CrifluoromeChylphenyl)-5-methoxy- carbonylamino-3-trifluoromethylpyrazole, m.p. 182-183*C.

REFERENCE EXAMPLE 16 4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-bis-(phenoxycarbonyl)amino-3-CrifluoromeChyl¬ pyrazole used in Che above Example 44 was prepared by following Che procedure of Example 14, buC replacing trimethylacetyl chloride by phenyl chloroformate. The title compound was obtained as a white solid, m.p. 168-169*C.

EXAMPLE 45 Compounds Nos. 105 and 106

5-Carbamoyl-4-cyano-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole

(3.57 g) was heated to 200*C wich phosphorus penCoxide (2.82 g) wich sCirring. AfCer 3 hours, ¹ Che cooled produce was CreaCed wich ice, and exCracCed wich dichloromeChane (3 x 50 ml). The organic soluCion was washed wich waCer, dried over anhydrous magnesium sulphate, and evaporated in vacuo to give a solid. Recrystallisation from hexane gave l-(2,6-dichloro- 4-trifluoromethylphenyl)-4,5-dicyano-3-trifluoromethyl¬ pyrazole in the form of white crystals (1.8 g) , m.p. 80*C.

By proceeding in a similar manner but replacing the 5-carbamoyl-4-cyano-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole by 5-amino-3-carbamoyl-l-(2,6-dichloro-4-trifluoromethyl- phenyl)-4-methanesulphonylpyrazole there was prepared: -

5-Amino-3-cyano-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-methanesulphonylpyrazole in the form of a white solid, m.p. 214*C.

REFERENCE EXAMPLE 17 5-Carbamoyl-4-cyano-l-(2,6-dichloro-

4-trifluoromethylphenyl)-3-trifluoromethylpyrazole used in the above Example 45, was prepared as follows:- 5-Carboxy-4-cyano-l-(2,6-dichloro-4-trifluoro- ethylphenyl)-3-trifluoromethylpyrazole (6.0 g; hereinbefore described in Example 43) was added to thionyl chloride (30 ml) and the stirred solution heated to reflux for 4 hours. The solvent was evaporated in vacuo, and re-evaporated after addition of dry toluene (30 ml). The resultant orange oil was dissolved in dry ether (10 ml) and added dropwise to a stirred solution of ammonia (0.88, 20 ml) cooled by an ice bath. After stirring overnight, water (150 ml) was added, and the mixture extracted with dichloromethane (3 x 50 ml) . The combined extract was washed with water, dried over anhydrous magnesium sulphate, and evaporated in vacuo to give a white solid (7.0 g) . Recrystallisation from a mixture of ethyl acetate and petroleum ether gave the title

compound (4.3 g) , in the form of white crystals, m.p. 180-181*C.

5-Amino-3-carbamoyl-l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-methanesulphonylpyrazole used in the above Example 45 was prepared by the same procedure, but by replacing Che 5-carboxy-4-cyano- l-(2,6-dichloro-4-CrifluoromeChylphenyl)-3-Crifluoro¬ meChylpyrazole by 5-amino-3-carboxy-l-(2,6-dichloro- 4-CrifluoromeChylphenyl)-4-meChanesulphonylpyrazole. The CiCle compound was obCained in Che form of an off-whice solid, m.p. 223-224*C.

5-Amino-3-carboxy-l-(2,6-dichloro-4-Crifluoro¬ meChylphenyl)-4-meChanesulphonylpyrazole used above was prepared as follows:- 5-Amino-1-(2,6-dichloro-4-CrifluoromeChy1- phenyl)-3-eChoxycarbony1-4-meChanesulphonylpyrazole (8.15 g) was added Co sCirred 80% sulphuric acid (80 ml), and heaCed aC 100*C for 5 hours. AfCer cooling, the solution was poured onto ice, the solid filtered off and dried over phosphorus pentoxide in a vacuum desiccator. Recrystallisation from a mixture of methanol and petroleum ether gave the title compound as a white solid, m.p. 203-205*C.

5-Amino-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-3-ethoxycarbonyl-4-methanesulphonylpyrazole, used above, was prepared by the procedure of Reference Example 5, by replacing malononiCrile by

methanesulphonylacetonitrile. The title compound was obtained in the form of a white solid, m.p. 255°C, after recrystallisation from ethanol.

EXAMPLE 46 Compound No. 107

A solution of meChylmagnesium iodide [prepared from magnesium (0.26 g) and meChyl iodide (1.5 g) in dieChyl eCher (25 ml)], was CreaCed wich a soluCion of l-(2,6-dichloro-4-trifluoromethyl- phenyl)-4-cyano-3-CrifluoromeChylpyrazole (2 g) in dieChyl eCher (20 ml), dropwise. The resulcing pale yellow soluCion was refluxed for 24 hours, cooled, and CreaCed wich hydrochloric acid (2N, 10 ml). AfCer sCirring for 0.5 hour aC room CemperaCure, Che reaccion mixCure was diluCed wich eCher (50 ml). The eChereal extract was washed with water (50 ml), dried over anhydrous magnesium sulphate, and evaporated in vacuo to give a yellow gum. This was purified by chromatography on silica (Merck, 230-400 mesh, 0.7 kg

__2 cm ) eluting with a mixture of dichloromethane and petroleum ether (4:1) to give

4-acetyl-l-(2,δ-dϊchloro-4-trifluoromethylphenyl)- 3-trifluoromethylpyrazole as a white solid, m.p. 134*C.

EXAMPLE 47 Compounds Nos. 108 - 116

A stirred solution of 5-amino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-methylthio-3-trifluoromethyl¬ pyrazole (1.0 g) in chloroform (40 ml) was treated

with m-chloroperbenzoic acid (0.42 g) , portionwise at room temperature. After stirring for 6 hours, the solution was diluted wich dichloromeChane and washed in Curn wich sodium sulphiCe soluCion, sodium hydroxide soluCion, and waCer. The soluCion was dried over anhydrous magnesium sulphaCe, and evaporaCed in vacuo Co give a yellow oil. PurificaCion by _. chromatography on silica (Merck, 230-400 mesh, 0.7 kg cm ^"2 ) eluCing wich dichloromeChane-eChylaceCaCe (4:1) gave 5-amino- l-(2,6-dichloro-4-trifluoromethylphenyl)-4-methyl- sulphinyl-3-CrifluoromeChylpyrazole in Che form of a whiCe solid, m.p. 142-145*C wich decomposicion. By proceeding in a similar manner buC replacing 5-amino-l-(2,6-dichloro-4-CrifluoromeChyl¬ phenyl)-4-meChylChio-3-CrifluoromeChylpyrazole by Che appropriaCe alkylchio phenylpyrazoles Chere were prepared:-

5-Amino-l-(2,δ-dichloro-4-Crifluoromethyl- phenyl)-4-eChylsulphinyl-3-CrifluoromeChylpyrazole in Che form of a whiCe solid, m.p. 170*C from 5-amino- 1-(2,6-dichloro-4-CrifluoromeChylphenyl)-4-eChylChio- 3-CrifluoromeChylpyrazole.

5-Amino-l-(2,6-dichloro-4-trifluoromethyl- phenyl)-4-ethylsulphinyl-3-methylpyrazole in the form of a buff solid, m.p. 157-158°C from 5-amino- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthio- 3-methylpyrazole.

5-Amino-4-cyano-l-(2,6-dichloro-4-trifluoro- methylsulphinylphenyl)-3-trifluoromethylpyrazole, in the form of an orange solid, m.p. 76*C, from 5-amino- 4-cyano-l-(2,6-dichloro-4-trifluoromethylthiophenyl)- 3-trifluoromethylpyrazole.

4-Cyano-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-methylsulphiny1-3-trifluoromethylpyrazole, in the form of white crystals, m.p. 97-98*C, from 4-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)- 5-methylthio-3-trifluoromethylpyrazole.

By proceeding in a similar manner but replacing 5-amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-methylthio-3-trifluoromethylpyrazole by the appropriate alkylthiophenylpyrazoles, and employing 2 molar equivalents of m-chloroperbenzoic acid there was prepared:-

5-Amino-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-4-ethylsulphonyl-3-trifluoromethylpyrazole, in the form of white crystals, m.p. 206-207*C, from 5-amino-l-(2,6-dichlor0-4-trifluoromethylphenyl)- 4-ethylthio-3- rifluoromethylpyrazole.

5-Amino-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-4-ethylsulphonyl-3-methylpyrazole, in the form of a white solid, m.p. 193°C, from 5-amino- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethylthio- 3-methylpyrazole.

By proceeding in a similar manner but replacing the 5-amino-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-methylChio-3-CrifluoromeChylpyrazole by 5-amino-l-(2,6-dichloro-4-CrifluoromeChylpheny1)- 4-n-propylChio-3-meChylpyrazole, Chere was obCained 5-amino-l-(2,6-dichloro-4-CrifluoromeChylphenyl)- 3-meChyl-4-propanesulphonylpyrazole in Che form of a whiCe solid, m.p. 145.5-147*C.

By proceeding in a similar manner Chere was prepared:-

5-Amino-1-(2,6-dichlor0-4-CrifluoromeChy1- phenyl)-4-CrichloromeChanesulphony1-3-meChylpyrazole in Che form of a pale pink solid, m.p. 183-184*C, from 5-amino-l-(2,6-d.ichloro-4-CrifluoromeChylphenyl)- 4-CrichloromeChylchio-3-meChylpyrazole.

EXAMPLE 48 Compounds Nos. 117, 118 and 119 <

A mixCure of bis[5-amino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-methylpyrazole-4-yl]- disulphide (4.0 g) , sodium dichionice (2.02 g) and sodium hydroxide (0.46 g) was sCirred and heaCed under reflux in a mixCure of ethanol and water (60 ml, 1:1) for 4 hours. The cooled yellow solution was treated with ethyl iodide (2.17 g) and the mixture stirred and heated under reflux for 2 hours. After evaporation in vacuo, the yellow gum was dissolved in ether (100 ml), washed with water, dried over anhydrous magnesium sulphate, and re-evaporated in vacuo. The

resultant gum was purified by chromatography on silica (Merck, 230-400 mesh, 0.7 kg cm ^"2 ) eluting with dichloromethane, to furnish 5-amino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-ethylthio-3-methylpyrazole in the form of a white solid, m.p. 117°C, after recrystallisation from hexane.

By proceeding in a similar manner, but replacing the ethyl iodide by methyl iodide there was prepared:- 5-Amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-methyl-4-methylthiopyrazole, in the form of a white solid, m.p. 112*C, after recrystallisation from hexane.

By proceeding in a similar manner but replacing the sodium hydroxide by sodium carbonate, and the methyl iodide by n-propyl iodide, there was obtained 5-amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-n-propylthio-3-methylpyrazole in the form of a white solid, m.p. 100-102*C. REFERENCE EXAMPLE 18

Bis[5-Amino-l-(2,6-dichlor0-4-trifluoromethy1- phenyl)-3-methylpyrazole-4-yl]disulphide was prepared as follows:-

A solution of 5-amino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-methy1-4-thiocyanatopyrazole (3.0 g; hereinafter described in Example 50) in a mixture of ethanol and water (1:1, 100 ml) was acidified by the addition of hydrochloric acid (10 N,

20 ml). The mixture was heated under reflux for 8 hours, concentrated to half volume ij vacuo, cooled in an ice bath, and sodium hydroxide solution added until the pH reached 9-10. The precipitated product was filCered, washed wich waCer, and dried in vacuo Co furnish Che CiCle compound (2.68 g) as an amorphous yellow powder, m.p. 211-213*C.

EXAMPLE 49 Compounds Nos. 120 and 121 A soluCion of eChyl magnesium bromide, prepared from magnesium (0.57 g) and eChyl bromide (2.6 g) in dry dieChyl eCher (25 ml), was added dropwise Co a sCirred soluCion of 5-amino- l-(2,6-dichloro-4-trifluoromethylphenyl)-4-thiocyanato- 3-CrifluoromeChylpyrazole (5.0 g) in dry eCher (50 ml) aC -20*C. AfCer sCirring for a furCher 2 hours aC room CemperaCure, waCer (130 ml) was carefully added, and sCirring mainCained for 0.25 hour. The eCher layer was separaCed, dried over anhydrous magnesium sulphate, and evaporated in vacuo to give a yellow gum. Purification by chromatography on silica (Merck, 230-400 mesh, 0.7 kg cm ^"2 ) eluting with dichloromethane-petroleum ether (1:1) gave a product, which recrystallised from hexane to furnish 5-amino- 1-(2,δ-dichloro-4-trifluoromethylphenyl)-4-ethylthio- 3-trifluoromethylpyrazole, in the form of white needles, m.p. 116-116.5*C.

By proceeding in a similar manner, but replacing the ethyl magnesium iodide by methyl magnesium iodide there was obtained:-

5-Amino-l-(2,6-dichloro-4-trifluoromethyl- phenyl)-4-methylthio-3-trifluoromethylpyrazole, in the form of a white solid, m.p. 108*0, after recrystallisation from hexane.

EXAMPLE 50 Compounds Nos. 122 and 123 A stirred mixture of 5-amino-l-(2,6-dichloro-

4-trifluoromethylphenyl)-3-trifluoromethylpyrazole (0.7 g) and potassium thiocyanate (0.55 g) in methanol (15 ml) was treated with a solution of bromine (0.3 g) in methanol (2 ml) at 0-5*C. Stirring was maintained at this temperature for 1.5 hours, and the mixture was poured onto ice water, and brought to pH 9 by the addition of sodium carbonate. The product was filtered, washed with water and dried. Purification by chromatography on silica (Merck, 230-400 mesh, 0.7

2 kg cm ) eluting with dichloromethane gave

5-amino-l-(2,6-dichloro-4-trifluoromethylpheny1)-

4-thiocyanato-3-trifluoromethylpyrazole, in the form of a white solid, m.p. 49-50°C.

- By proceeding in a similar manner but replacing 5-amino-l-(2,6-dichloro-4-trifluoromethy1- phenyl)-3-trifluoromethylpyrazole by 5-amino- l-(2,6-dichloro-4-trifluoromethylphenyl)-3-methy1- pyrazole there was obtained 5-amino-l-(2,6-dichloro-

4-CrifluoromeChylphenyl)-3-meChy1-4-ChiocyanaCopyrazole in Che form of a whiCe solid, m.p. 133.5*C, afCer recrysCallisaCion from a mixCure of hexane and eChyl aceCaCe. EXAMPLE 51

Compound No. 124

By proceeding in a similar manner Co ChaC hereinbefore described in Example 4, buC replacing Che 2,6-dichloro-4-CrifluoromeChylphenyIhydrazine by 2,6-dichloro-4-meChanesulphonylphenylhydrazine Chere was obtained:-

5-Amino-4-cyano-l-(2,6-dichlord-4-methane- sulphonylphenyl)-3-trifluoromethylpyrazole in Che form of whiCe crysCals, m.p. 270-272*C. REFERENCE EXAMPLE 19

By proceeding in a similar manner Co ChaC hereinbefore described in Reference Example 1, buC replacing Che 2,6-dichloro-4-CrifluoromeChylaniline by 2,6-dichloro-4-meChanesulphonylaniline, Chere was prepared:-

2jδ-Dichloro-4-meChanesulphonylphenyIhydrazine in the form of white crystals, m.p. 163-166*C.

EXAMPLE 52 Compound No. 125

To a stirred ice cold solution of 5-amino- 1-(2,6-dichlor0-4-trifluoromethylphenyl)-3-methyl- pyrazole (2.0 g) in chloroform (40 ml) and pyridine (0.51 g) was added dropwise a solution of trichloro- methanesulphenyl chloride (1.2 g) in chloroform (10 ml). The resulting brown solution was stirred at 0*C for 2 hours, then at room temperature for 2 hours. A further addition of trichloromethane- sulphenyl chloride (0.5 g) was made and the mixture stirred for 2 hours at room temperature. Water (100 ml) and dichloromethane (100 ml) was then added and the organic layer washed with water (1 x 100 ml) , dried over anhydrous magnesium sulphate and evaporated in vacuo to give a yellow gum (2.9 g) . This was purified by chromatography on silica (Merck, 100-230

_2 mesh, 0.7 kg cm ) eluting with dichloromethane- petroleum ether (3:2) to give a white solid (0.98 g) . Recrystallisation from hexane gave

5-amino-l-(2,6-dichlor0-4-trifluoromethylphenyl)- 3-methyl-4-trichloromethylthiopyrazole in the form of white crystals, m.p. 156*C.

EXAMPLE 53 Compound No. 126 m-Chloroperbenzoic acid (2.1 g) was added Co a soluCion of 5-amino-4-cyano-l-(2,6-dichloro- 4-Crifluoromechylchiophenyl)-3-CrifluoromeChylpyrazole (2.3 g) in dichloromeChane (20 ml) cooled Co 10*C. AfCer sCirring overnighc at room temperature, the solution was heated under reflux for 4 hours, cooled, and a further addition of m-chloroperbenzoic acid (2.1 g) made. The mixture was stirred at room temperature for 4 hours and heated under reflux for 4 hours. The cooled solution was washed with sodium bicarbonate solution (20 x 20 ml), then wich waCer (2 x 20 ml), dried over anhydrous magnesium sulphaCe, filCered, and evaporaCed in vacuo Co give an orange solid. PurificaCion by chromaCography on silica (Merck, 100-230 mesh, (3.7 kg cm ^"2 ) eluting with ethyl acetate-petroleum ether (1:9) gave 4-cyano- l-(2,6-dichloro-4-trifluoromethanesulphonylphenyl)- 5-nitro-3-trifluoromethylpyrazole (0.5 g) in the form of an orange solid, m.p. 168-169°C.

EXAMPLE 54 Compound No. 127

To a sCirred solution of diethylaminosulphur trifluoride (1.5 g) in dichloromethane (13 ml) cooled to -70*C, was added dropwise under niCrogen a soluCion of l-(2,6-dichloro-4-trifluoromethylphenyl)-4-formyl- 3-crifluoromeChylpyrazole (3.1 g) in dichloromeChane (17 ml). AfCer 1 hour at -70*C, the mixture was allowed to stand at room temperature overnight, then poured onto excess iced water. Extraction with dichloromethane gave a solution which was washed with water (2 x) , dried over anhydrous magnesium sulphate and evaporated in vacuo to give a brown oil (3.26 g) . Purification by chromatography on silica (Merck, 40-230 mesh, 0.7 kg cm ^"2 ) eluting with hexane-ethyl acetate (5:1) gave l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-difluoromethy1-3-trifluoro¬ methylpyrazole (1.15 g) [from ethyl acetate-hexane] in the form of a pale yellow solid, m.p. 88-90*C; REFERENCE EXAMPLE 20

A mixture of 4-cyano-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-trifluoromethylpyrazole (5.0 g; hereinbefore described in Example 21) and formic acid (120 ml) was treated with Raney nickel (5.1 g) and the mixture heated under reflux overnight. After cooling, the mixture was filtered, and the filtrate diluted with water (900 ml) and extracted with dichloromethane (4 x 100 ml). The

combined extract was washed with sodium bicarbonate solution (2 x) , then wich waCer (1 x) , dried over anhydrous magnesium sulphaCe, and evaporaCed in vacuo to give a brown solid (3.7 g) , m.p. 80-82*C. This was l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-formy1-3-trifluoromethylpyrazole.

EXAMPLE 55 Compound No. 128

To a stirred solution of 5-amino-4-carboxy- 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-trifluoro¬ methylpyrazole (15.0 g; hereinbefore described in Reference Example 6) in dry tetrahydrofuran (50 ml) was added, under nitrogen, a solution of borane- tetrahydrofuran complex (1 Molar, 27.5 g) during 10 minutes keeping at -20*C. The solution was allowed to reach room temperature and stirred overnight. A further addition of the borane was made (10 ml), and the solution heated under reflux overnight. After cooling, a further addition of the borane (20 ml) was made, and the solution again heated under reflux for 4 hours. After cooling, sodium hydroxide (6 N) solution was added to pH 11, and the solution extracted with dichloromethane. The organic phase was washed with water, dried over anhydrous magnesium sulphate, and evaporated in vacuo to give a brown oil. Purification by chromatography on silica (Merck, 40-230 mesh, 0.7 kg cm ^"2 ) eluting with

hexane-ethyl acetate (2:1) gave 5-amino- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methy1- 3-trifluoromethylpyrazole (2.0 g) , from toluene-hexane, m.p. 97-100*C, in the form of white crystals.

following formulae it is to be understood that*

A represents ^{r B}

A represents

A , represents

,8

C-=.C /

III

\ R 5^

N— A ^a

I 3

R ¹

10.

R N-A ^β YIII

10

R

H- XI

-T CH ₂ 0H

XII

cio ₂ s A ⁶ XIY

HOOC- -A ^v J ES- I c

Cl-C — A ^β XYIII II 0

20

^■ COOS' •COCE xx