WO1992013451A1

WO1992013451A1 - Imidazole pesticides

Info

Publication number: WO1992013451A1
Application number: PCT/GB1992/000233
Authority: WO
Inventors: Robert John Willis; Mary Josephine O'mahony; Bryan Glyn Roberts; Ian David Marlow; Ian Kenneth Boddy
Original assignee: Schering Agrochemicals Limited
Priority date: 1991-02-11
Filing date: 1992-02-10
Publication date: 1992-08-20
Also published as: AU1191292A

Abstract

Compounds of formula (I) useful in combating pests, especially insects, acarids or animal endoparasites.

Description

Title; Imidazole pesticides

Field of the invention

This invention relates to new imidazoles having pesticidal and especially insecticidal, acaricidal and animal endoparasiticidal activity.

Prior Art

In our EP 412 849, we have disclosed that certain aryl-

1,2,3-triazoles and arylpyrazoles in which an imidazol(in)e group is attached directly or indirectly through its 2-position to the triazole or pyrazole ring, have pesticidal activity. We have now found that other compounds comprising an imidazole, substituted in the 2-position, directly or indirectly by aryl-substituted azolyl groups have good pesticidal activity. The bulk of the compounds have a priority date earlier than the publication date of EP 412 849. The_^prior art disclosed..in that application is incorporated by reference.

Description of the Invention The present invention provides compounds of formula I

R^J where Z is a nitrogen containing heterocycle of formula Z¹, Z², Z³, Z⁴ or Z⁵

(Z¹) (Z²)

(Z³) (Z⁴)

(Z⁵) and salts thereof, in which Ar is aryl; V¹ is N or CR⁹; V² is N or CR¹⁰; w¹ is N or CR⁸;

W² is N or CR¹¹; except W¹ and W² are not both N; W³ is O, S, NR⁴⁰ or -CR⁴¹=CR⁴²-; X is O or S;

Y is O, S or N 12. w⁴ is C or can also be S when Y is 0; A is S(0)_m, 0 or NR¹³;

R¹ and R² are hydrogen, optionally substituted alkyl, cyano, halogen or nitro; R³ is hydrogen, optionally substituted alkyl, acyl, optionally substituted alkoxycarbonyl or sulfamoyl; R⁵ is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, -NR¹⁶R¹⁷, cyano, nitro, S0₂NR¹⁶R¹⁷, CYNR¹⁶R¹⁷, COOR¹⁸ or R¹⁹S(0)_m;

R⁴ and R¹⁰, which may be the same or different, are hydrogen, halogen, hydroxy, mercapto, cyano, nitro, optionally substituted alkyl, optionally substituted alkoxy, -NR¹⁶R¹⁷, -S0₂NR¹⁶R¹⁷, CHO, CH₂OH, COOR¹⁸ or

R¹⁹S(0)_m;

R _6° is substituted alkyl, hydroxy, alkoxy, haloalkoxy, cyano, nitro, R¹⁹S(0)_m or an N-linked 5-membered heteroaryl group containing 1-4 nitrogen atoms; and when R⁵ is cyano, -CYNR¹⁶R¹⁷, -COOR¹⁸, optionally substituted alkoxy, nitro, -NR¹⁶R¹⁷ or _S0₂NR¹⁶R¹⁷, R⁶. can also be hydrogen, halogen, alkyl or -NR¹⁶R¹⁷; R⁷, R⁸ and R¹¹, which may be the same or different, are hydrogen, halogen, optionally substituted alkyl or optionally substituted alkylthio;

R⁹ is hydrogen, halogen, optionally substituted alkyl, for yl, optionally substitutjed_alkoxy_r aryl., cyano, nitro, hydroxy, trialkylsilyloxy, CYNR¹⁶R¹⁷, COOR¹⁸ or R¹⁹S(0)_m;

R¹² is hydrogen, optionally substituted alkyl or acyl;

R¹³ is hydrogen, alkyl or acyl;

R¹⁶ and R¹⁷ are the same or different and are hydrogen, optionally substituted alkyl, acyl or aryl, or together with the nitrogen to which they are attached, form a 5 to 7 membered ring which can contain other hetero atoms;

R¹⁸ is hydrogen or optionally substituted alkyl; R¹⁹ is optionally substituted alkyl;

R⁴⁰ is hydrogen, optionally substituted alkyl or acyl;

R⁴¹ and R⁴², which may be the same or different, are hydrogen or optionally substituted alkyl; and when V¹ is CR⁹ and V² is CR¹⁰, R⁹ and R⁴ together with the carbon atoms to which they are attached can form a six membered ring; and when V¹ and V² are both N, R⁴ can form a sulfur, nitrogen or carbon containing bridge to an ortho carbon atom on Ar; m is 0, 1 or 2; and p is 0 or 1, when Z is Z¹ or Z²and is 0 when Z is Z³, Z⁴ or Z⁵.

Ar is preferably a substituted phenyl or pyridyl group. It is generally preferred that it is a 4-trifluoromethyl- phenyl or 5-trifluoromethyl-2-pyridyl, in which the phenyl or pyridyl is optionally further substituted, generally by halogen, especially chloro, nitro diT cyano. Other substituents include trifluoromethoxy, trifluoromethylthio or trifluoromethylsulfonyl. A particularly preferred group of compounds are those where Ar is 2,6-dichloro- 4-trifluoro ethylphenyl, 2-nitro-4-trifluoromethylphenyl, 2-chloro-6-nitro-4-trifluoromethylphenyl or 2-chloro- 6-cyano-4-trifluoromethylphenyl. -

Alkyl groups are preferably of 1 to 4 carbon atoms and may be substituted by one or more of the same or different groups such as halogen, hydroxy, alkoxy, alkylthio, dihalocyclopropyl, cyano, nitro, optionally substituted amino, optionally substituted imino, acyloxy and aryl. Apart from Ar, aryl groups are usually phenyl, optionally substituted, e.g. by halogen, alkyl, haloalkyl, alkoxy or nitro. The term aryl may include heteroaryl groups such as imidazolyl, thienyl, furyl or pyridyl. The term 'acyl' includes the residue of sulfonic and phosphorus containing acids as well as carboxylic acids. Acyl groups may be for example alkanoyl, e.g. of 1 to 4 carbon atoms, or alkylsulfonyl or haloalkylsulfonyl. Optionally substituted amino groups are generally of formula NR¹⁶R¹⁷. Imino groups may be substituted by groups such as hydroxy or alkoxy. Heterocyclyl groups are generally 4 to 6 membered and can contain various hetero atoms, such as oxygen, nitrogen or sulfur.

When R¹⁶ and R¹⁷ form a ring this is generally a morpholine or piperidine ring. This ring can be fused to another ring and/or can be substituted, e.g. by one or more optionally substituted alkyl groups. Other rings that R¹⁶ and R¹⁷ can form are optionally substituted 5-membered heteroaryl groups containing 1 to 4 nitrogen atoms, preferably pyrrole.

The compounds of the invention have insecticidal and acaricidal activity and are particularly useful in combating a variety of economically important insects, and acarids including animal ectoparasites, e.g. Lepidoptera, including Spodoptera littoralis, Heliothis armiαera, and Pieris brassicae; Diptera, including Musca domestica, Ceratitis*.^capitat , Erioischia bra-gsicae, Lucilia- sericata and Aedes aecrvpti; Homoptera, including aphids such as Meσoura viciae and Nilaparvata luσens; Coleoptera, including Phaedon cochleariae_f Anthonomus grandis and corn rootworms fDiabrotica spp., eg. Diabrotica undecimpunctata. ; Orthoptera, including Blattella σermanica; ticks, e.g. Booohilus microplus and lice, including Damalinia bovis and Linoσnathus vituli.

Some compounds also have activity against plant parasitic nematodes, for example root-knot nematodes, such as Meloidocrvne spp. and cyst forming nematodes, such as Heterodera spp..

The compounds of the invention are also active against animal and human endoparasites and especially helminths, ie nematodes, trematodes and cestodes, especially Trichostronσγloidea, e.g. Haemonchus contortus, Trichostroncrylus spp; Dictvocaulus spp; Ascaridoidea. e.g. Toxocara spp; Stronσylus spp; and Filarioidea. e.g. Dirofilaria immitis. Onchocerca spp: Trematoda. including Fasciola hepatica and Schistosoma spp. ; and Cestoda. including Taenia spp and Moniezia spp., and protozoan parasites, e.g. Plasmodiu spp.; Trvpanosoma spp. and Ei eria spp.

The invention thus provides a method of combating pests, especially insects, acarids or animal endoparasites, at a locus or host for the pest, infested or liable to be infested therewith, which comprises applying to the locus, host and/or the pest, a"compound of formula I, as defined above.

Some novel compounds of formula I have weak pesticidal activity but still have utility as intermediates and such compounds also form one aspect of the invention.

The invention also provides a pesticidal composition which comprises a compound of the invention in admixture with an agriculturally or veterinarily acceptable diluent or carrier.

The invention also provides a pharmaceutical composition which comprises a compound of the invention in admixture with a pharmaceutically acceptable diluent or carrier.

More than one compound of the invention can, of course, be included in the compositions.

In addition the compositions can comprise one or more additional pesticides for example compounds known to possess herbicidal, fungicidal, insecticidal, acaricidal or nematicidal properties. Alternatively the compounds of the invention can be used in sequence with the other pesticides.

The diluent or carrier in the composition of the invention can be a solid or a liquid optionally in association with a surface-active agent, for example a dispersing agent, emulsifying agent or wetting agent. Suitable surface-active agents include anionic compounds such as a carboxylate, for example a metal carboxylate of a long chain fatty acid; an N-acylsarcosinate; mono- or di-esters of phosphoric acid with fatty alcohol ethoxylates or salts of such esters; fatty alcohol sulfates such as sodium dodecyl sulfate, sodium octadecyl sulfate or sodium cetyl sulfate; ethoxylated fatty alcohol sulfates; ethoxylated alkylphenol sulfates; lignin sulfonates; petroleum sulfonates; alkyl-aryl sulfonates such as alkyl-benzene sulfonates or lower alkylnaphthalene sulfonates, e.g. butyl-naphthalene sulfonate; salts of sulfonated naphthalene-formaldehyde condensates; salts of sulfonated phenol-formaldehyde condensates; or more complex sulfonates such as the amide sulfonates, e.g. the sulfonated condensation product of oleic acid and N-methyl taurine or the dialkyl sulfosuccinates, e.g. the sodium sulfonate of dioctyl succinate. Nonionic agents include condensation products of fatty acid esters, fatty alcohols, fatty acid amides or fatty-alkyl- or alkenyl-substituted phenols with ethylene oxide, fatty esters of polyhydric alcohol ethers, e.g. sorbitan fatty acid esters, condensation products of such esters with ethylene oxide, e.g. polyoxyethylene sorbitan fatty acid esters, block copolymers of ethylene oxide and propylene oxide, acetylenic glycols such as 2,4,7,9-tetramethyl- 5-decyne-4,7-diol, or ethoxylated acetylenic glycols. Examples of a cationic surface-active agent include, for instance, an aliphatic mono-, di-, or polyamine as an acetate, naphthenate or oleate; an oxygen-containing amine such a amine oxide or polyoxyethylene alkylamine; an amide-linked amine prepared by the condensation of a carboxylic acid with a di- or polyamine; or a quaternary ammonium salt.

The compositions of the invention can take any form known in the art for the formulation of insecticidal or acaricidal compounds, for example, a solution, a dispersion, an aqueous emulsion, a dusting powder, a seed dressing, a fu igant, a smoke, a dispersible powder, an emulsifiable concentrate, granules or baits; and when being used as an animal or human parasiticide, can be in the form of a preparation, e.g. for oral, parenteral or dermal application, e.g. in the form of powders, solutions, suspensions, tablets, capsules, drenches, boluses, pour-ons-, dips, sprays, injectables or as food additives. Moreover it can be in a suitable form for direct application or as a concentrate or primary composition which requires dilution with a suitable quantity of water or other diluent before application.

As a dispersion, the composition comprises a compound of the invention dispersed in a liquid medium, preferably water. It is often convenient to supply the consumer with a primary composition which can be diluted with water to form a dispersion having the desired concentration. The primary composition can be provided in any one of the following forms. It can be a dispersible solution which comprises a compound of the invention dissolved in a water-miscible solvent with the addition of a dispersing agent. A further alternative comprises a compound of the invention in the form of a finely ground powder in association with a dispersing agent and intimately mixed with water to give a paste or cream which can if desired be added to an emulsion of oil in water to give a dispersion of active ingredient in an aqueous oil emulsion.

An emulsifiable concentrate comprises a compound of the invention dissolved in a water-immiscible solvent together with an emulsifying agent and which is formed into an emulsion on mixing with water.

A dusting powder comprises a compound of the invention intimately mixed with a solid pulverulent diluent, for example, kaolin.

A granular solid comprises a compound of the invention associated with similar diluents to those which may be employed in dusting powders, but the mixture is granulated by known methods. Alternatively it comprises the active ingredient adsorbed or absorbed on a pre-granular diluent, for example. Fuller's earth, attapulgite or limestone grit.

A wettable powder usually comprises the active ingredient in admixture with a suitable surfactant and an inert powder diluent such as china clay.

Another suitable concentrate, particularly when the product is a solid, is a flowable suspension concentrate which is formed by grinding the compound with water, a wetting agent and a suspending agent.

Baits can include an attractant and may comprise a protein hydrolysate e.g. for the control of fruit flies, sugar e.g. for the control of adult Musca spp. or corn cob e.g. for the control of cockroaches. The concentration of the active ingredient in the composition of the present invention is preferably within the range of 1 to 30 per cent by weight, especially 5 to 30 per cent by weight. In a primary composition the amount of active ingredient can vary widely and can be, for example, from 5 to 95 per cent by weight of the composition.

The compounds of the invention may be prepared by a variety of methods known in the art.

For example: compounds where p is 0, can be obtained by a process in which a compound of formula II

Z-CH=N-CR¹=CR²-NH₂ (II) is ring closed to give a compound of formula I, where R³ is hydrogen, and optionally modifying this in known manner to give compounds where R³ is other than hydrogen. Suitable reagents for ring closure include N-chlorosuccinimide and

2,3-dichloro-5,6-dicyano-l,4-benzoquinone.

The compound of formula II can be prepared by reacting a compound of formula III

Z-CHO (III) with a compound of formula H₂N-CR¹=CR²-NH₂

The compounds of formula III are known or can be prepared by known means. The preparation will depend on the nature of the Z heterocycle. Thus a compound of formula IV

Z-R²³ (IV) where R²³ is cyano or an alkoxycarbonyl group, can be reduced, e.g. using diisobutylaluminiu hydride in an inert solvent at very low temperature. Alternatively a compound of formula IV where R²³ is an alkoxycarbonyl group, may be reduced by methods known in the art, e.g. using lithium aluminium hydride, diisobutylaluminium hydride or zirconium borohydride (prepared in situ from zirconium tetrachloride and sodium borohydride) in an inert solvent, such as tetrahydrofuran, to give a compound of formula IV, where R²³ is hydroxymethyl. This can be oxidised to give the compound of formula III, e.g. using pyridinium dichromate or manganese dioxide.

A compound of formula IV where R²³ is halomethyl, may also be reacted with trimethylamine-N-oxide in dimethyl sulfoxide to give a compound of formula III.

A compound of formula III can also be prepared by cleavage of the compound of formula IV, where R²³ ia an optionally substituted carbon-carbon double bond, e.g. using ozone.

The compound of formula IV where R²³ is hydroxymethyl, can also be prepared by reduction of a carboxylic acid of formula IV where R²³ is carboxyl, by known methods.

The compound of formula III can also be prepared by formylation, e.g. where Z is Z², by reacting a compound of formula V

N

I

Ar with dimethylformamide in the presence of phosphorus oxychloride or phosphorus oxybromide to give respectively the compounds where R⁶ is chlorine or bromine.

A compound of formula V, may be prepared in known manner by reaction of the diazonium salt of an arylamine, ArNH_2^ with a compound of formula VI R⁵CH(COMe)-CH₂COOalkyl (VI)

A compound of formula III where Z is Z² and R⁵ is nitro may be prepared by reaction of an aryl diazonium salt ArN₂+ with diethyl nitrosuccinate in the presence of sodium acetate, followed by cyclisation, for example, with sodium ethoxide. Diethyl nitrosuccinate may be prepared by oxidation of a compound

EtOOC-C(=NOH)-CH₂COOEt with a suitable oxidising agent. This compound may be prepared by reaction of diethyl succinate with hydroxylamine hydrochloride in the presence of acid or base.

A compound of formula IV, where R²³ is alkoxycarbonyl, Z is Z², R⁵ is S0₂C1 and R⁶ is amino, may be obtained from the corresponding compound where R⁵ is optionally substituted benzylthio, by known methods, e.g. by oxidation with chlorine in acetic acid, with optional protection of the amino group. This compound may then be reacted with a compound HNR¹⁶R¹⁷ to give a compound where R⁵ is S0₂NR¹⁶R¹⁷.

The required intermediate of formula VII

(VII)

where R⁵ is optionally substituted benzylthio and R⁶ is amino, may be prepared by reaction of an arylhydrazine

ArNHNH₂ with a compound of formula R⁵ COOR²⁴

/

C=C

N

R^J CN where R⁵ is optionally substituted benzylthio and R²⁴ is optionally substituted alkyl.

An intermediate of formula VIII

Ar where R⁵ is optionally substituted benzylthio and R²³ is cyano, may be similarly prepared by reaction of an arylhydrazine ArNHNH₂ with a compound of formula

R⁵ £N c=c

R⁵ CN where R⁵ is optionally substituted benzylthio.

Other intermediates of formula VIII, in which R²³ is alkoxycarbonyl, may be similarly prepared by reaction of an arylhydrazine

ArNHNH₂ with a compound of formula

R⁵ .COOR²⁴

/ \ alkoxy CN

A compound of formula VII, in which R²³ is alkoxycarbonyl and R⁶ is an N-linked 5-membered heterocycle group containing 1-4 nitrogen atoms may be prepared from a compound of formula VIII by known methods. For example to obtain the compound, where R⁶ is pyrrole, the compound of formula VIII can be reacted with 2,5-dimethoxytetrahydro- furan.

A compound of formula VII, in which R⁶ is halogen, hydrogen, cyano, hydroxy or R¹⁹S, may be prepared from the compound of formula VIII by known methods, e.g. diazotisation.

A compound of formula VII, in which R⁶ is hydroxy may subsequently be modified in known manner, e.g. by alkylation with an alkyl halide or dialkyl sulfate.

A compound of formula VII, in which R⁶ is R¹⁹S(0)_m, where m is 0, may be oxidised in known manner, e.g. using hydrogen peroxide or a per-acid such as m-chloroperbenzoic acid, to give compounds where m is 1 or 2.

A compound of formula VIII, in which R⁵ is optionally substituted alkoxy, may be prepared by reaction of an arylhydrazine, ArNHNH₂ with diethyl cyanomalonate to give a compound of formula VIII, in which R⁵ is hydroxy, followed by treatment with an appropriate alkylating agent in the presence of a base.

A compound of formula VII, in which R⁵ is R¹⁹S(0)_m, where m is 0 and R¹⁹ is optionally substituted alkyl, may be prepared from the corresponding compound where R⁵ is SH, e.g. by alkylation with an alkyl halide,^' in the presence of a, base.

A compound of formula VII, where R⁵ is SH, may be obtained from the corresponding compound where R⁵ is optionally substituted benzyl, in known manner.

A compound of formula VII, where R⁶ is haloalkyl and R²³ is alkoxycarbonyl, may be obtained by reacting a compound of formula IX Ar-NH-N=CH(R⁵)-R²⁵ (IX) where R²⁵ is halogen, e.g. chlorine or bromine, with a compound R⁶COCH₂COOR²⁴, where R²⁴ is optionally substituted alkyl.

A compound of formula IX may be prepared in known manner from the corresponding compound where R²⁵ is hydrogen.

A compound of formula VII, where R⁶ is nitro, may be obtained by nitration of the corresponding compound where R⁶ is hydrogen.

A compound of formula VII, where R⁶ is hydrogen, may be obtained by reaction of a compound of formula IX, where R²⁵ is halogen, with a compound of formula HCsC-COOR²⁴ where R²⁴ is optionally substituted alkyl, in the presence of a base.

A compound of formula VIII, may be modified by reaction with a suitable alkyl or acyl halide in the presence of a base to give compound of formula VII, where R⁶ is NR¹⁶R¹⁷.

Compounds of formula I, where p is 0, Z is Z¹, V¹ is CR⁹ and V² is N, can be obtained by a variety of known methods. For example, a compound of formula X

R³ where R²⁶ is halogen, preferably chlorine, is reacted a) with a compound of formula XI

R⁴-CH=CH-R²⁷ (XI) where R⁴ is hydrogen, nitro or optionally substituted alkyl and R²⁷ is a leaving group, such as alkoxy or substituted amino, e.g. morpholino, to give a compound of formula I, where p is 0, Z is Z¹, V¹ is CR⁹ and V² is N, where R⁹is hydrogen and R⁴ is hydrogen, nitro or optionally substituted alkyl, or b) with a compound of formula XII

R⁹-CH₂-CN (XII) where R⁹ is cyano, nitro, COOR¹⁸, R¹⁹SO or R¹⁹S0₂, to give a compound of formula I, where R⁴ is amino.

When compounds are obtained where R⁴ is amino, the amino group may be modified in known manner to give other desired values for R⁴.

When compounds are obtained where R⁹ is COOR¹⁸ this can also be modified in known manner to give compounds where R^: 9 is another group.

A compound of formula I in which R³ is H may be further modified in known manner, e.g. by alkylation to give other R³ groups.

The compound of formula X is novel and forms one aspect of the invention. It can be obtained by ring closure of a compound of formula XIII Ar-NH-N=CH-CH=N-CR¹=CR²-NH₂ (XIII) in the presence of a halogenating agent. The reagent for ring closure and halogenation is preferably the same compound e.g. an N-halosuccinimide.

The compound of formula XIII can be obtained by reacting a compound of formula XIV

Ar-NH-N=CH-CHO (XIV)

• with a compound of formula H₂N-CR¹=CR²-NH₂

The compound of formula XIV can be obtained by reacting a phenylhydrazine, ArNHNH₂ with glyoxal.

A compound of formula IV, in which R²³ is cyano, Z is Z¹, V¹ is CR⁹ and V² is N, where R⁹ is R¹⁹S(0)m, halogen, nitro, formyl, haloalkyl and R⁴ is NH₂ may be prepared from compound of formula XV

Ar in which R²⁸ is cyano, R⁹ is H and R⁴ is NH₂, in known manner with optional protection of the amino group e.g. by halogenation, nitration etc. Groups such as formyl may be optionally protected or further modified.

A compound of formula XV in which R²⁸ is cyano, R⁹ is H and R⁴ is NH₂, may be prepared in known manner, e.g. as described in EP 295117.

In a compound of formula XV, in which R⁴ is NH₂ the amino group may be optionally protected or modified in known manner to give other values for R⁴.

A compound of formula XV where R²⁸ is alkoxycarbonyl, R⁹ is H and R⁴ is alkoxy or haloalkoxy may be formed from a compound of formula XV, where R²⁸ is alkoxycarbonyl, R⁹ is H and R⁴ is hydroxy, by alkylation in the presence of a base.

A compound of formula XV where R²⁸ is alkoxycarbonyl, R⁹ is formyl and R⁴ is halogen e.g. chloro, may be prepared by reaction of a compound of formula XV where R²⁸ is alkoxycarbonyl, R⁹ is H and R⁴ is hydroxy by reaction with dimethylformamide and phosphorous oxychloride.

The formyl group may be optionally protected or modified in known manner.

A compound of formula XV where R²⁸ is alkoxycarbonyl, R⁹ is hydrogen and R⁴ is hydroxy may be prepared in known manner e.g. as described in EP 385 809.

A compound of formula III, in which Z is Z¹ and V¹ = v² = N, can be prepared for example by reduction of a compound of formula XVI

N π— COOR²⁴

II N (XVI)

R⁴ N

I

Ar where R²⁴ is an ester forming group such as alkyl, e.g. ethyl, using general methods indicated above.

The compound of formula XVI can be obtained by ring closing a compound of formula XVII NH,

Ar-NH-N=C-COOR²⁴ (XVII) using an appropriate carbony1 compound depending on the desired value of R⁴. For example, when R⁴ is hydrogen a suitable reagent is an orthoformate ester, e.g. the triethyl ester; when R⁴ is an optionally substituted alkyl or phenyl, the corresponding alkanoyl or benzoyl chloride can be used. Compounds of formula XVI, where R⁴ is OH can be obtained using phosgene as the ring closing reagent. This group can then be modified in known manner, for example by reaction with phosphorus oxychloride to give a compound where R⁴ is chlorine.

The compound of formula XVII can be obtained by reacting a compound of formula XVIII with ammonia Br

Ar-NH-N=C-COOR²⁴ (XVIII)

The compound of formula XVI, where R⁴ is hydroxy can be obtained by reaction of a compound of formula XVIII with a cyanafe"salt, s c ^' as potassium cyariate.

The compound of formula XVI, where R⁴ is alkylthio can be obtained by reaction of a compound of formula XVI where R⁴ is halogen with a compound of formula, R¹⁹SH in the presence of a base. The alkylthio group can then be oxidised using a suitable oxidising agent, e.g. hydrogen peroxide or m-chloroperbenzoic acid.

The compound of formula XVI, where R⁴ is nitro can be obtained by nitration of a compound of formula XVI where R⁴ is hydrogen.

The compound of formula XVI, where R⁴ is cyano can be obtained by reaction of a compound of formula XVI where R⁴ is trichloromethyl with aqueous ammonia.

Compounds where R⁴ is trichloromethyl can be further modified, e.g. by reaction with sodium hydroxide to give compounds where R⁴ is carboxy. This group can then in turn be modified in known manner as will be apparent to those skilled in the art.

The compound of formula XVIII can be obtained by bro ination of a compound of formula XIX, usually in the presence of an acetate salt

Ac Ar-NH-N=C-C00R²⁴ (XIX) where Ac is an alkanoyl group, usually acetyl.

The compound of formula XIX can be obtained by diazotisation of a compound

ArNH₂ followed by reaction with a compound

AcCH₂C00R²⁴

A compound of formula III, where Z is Z¹ and V¹ = V² = N and R⁴ is a sulfur bridge to an ortho carbon atom of Ar, can be formed by deprotection in known manner of a compound of formula XX

N [j— CH(0Me)₂

|l N (XX) s

N

I

Ar

The compound of formula XX may be prepared by reaction of a compound of formula XXI (XXI)

M where R²⁹ is halogen or methylsulfonyl and M is a metal, with a compound of formula XXII

R³⁰-Ar-R³¹ (XXII) where R³⁰ is a leaving group in the position on the Ar where Ar is attached to the triazole ring in formula XX

*ϊi , _t -yr\ and R^J1 is halogen or nitro and is in position ortho to R , to give a compound of formula XXIII

(XXIII)

where Ar¹ is Ar substituted by R³¹ in the ortho position, and cyclising this compound to the desired compound of formula XX, in the presence of sodium sulfide.

A compound of formula XXIV

Ar¹ (which is equivalent to compound XVI) , where Ar¹ and R²⁹ have the meaning given in formula XXIII can be cyclised in a similar manner and then treated as described for formula XVI.

The compound of formula I, where p is 0, Z is Z¹ and V¹ = V² = N, may also be prepared by ring closure of a compound of formula X, where R²⁶ is amino, using an appropriate carbonyl compound depending on the desired value of R⁴, as described for ring closure of compound XVII .

The compound of formula X, where R²⁶ is amino, is novel and forms one aspect of the invention and may be obtained by reacting a compound of formula X, where R²⁶ is halogen, with ammonia.

A compound of formula IV, where Z is Z¹, V¹ is N and V² is CR¹⁰, and R²³ is for example cyano, alkoxycarbonyl or a group T, where T is

I

may be prepared by reaction of a compound of formula XXV

H with a compound of formula ArR³², where R³² is a leaving group, such as halogen, especially fluorine.

Where R²³ = T, R³ may be for example a protecting group, e.g. one of those described in "Protective Groups in Organic Synthesis" by T W Greene, published by John Wiley & Sons.

A compound of formula XXV may be prepared by a variety of methods known in the art for synthesis of imidazole rings such as those described in Comprehensive Heterocyclic Chemistry, Volume 5, ed. Katritzky and Rees, Chapter 4.08, pp 457, Pergamon 1984. When compounds are obtained where R⁴ or R¹⁰ is NH₂, the amino group may be modified in known manner, for example by diazotisation, to give other desired values for R⁴ or R¹⁰, such as halogen, cyano or alkylthio or by reaction with e.g. 2 ,5-dimethoxytetrahydrofuran to give compounds where R⁴ or R¹⁰ is pyrrole.

A compound of formula III, where Z is Z¹, V¹ is N and V² is CR¹⁰, in which R¹⁰ is amino, may also be prepared by formylation of a compound of formula XXVI

I Ar in which R⁴ is hydrogen, optionally substituted alkyl or halogen, e.g. with dimethylformamide and phosphorous oxychloride.

A compound_of formula XXVI in which R⁴ -is-hydrogen, may be obtained by cyclising a compound of formula XXVII

Ar-N=C-NHCH₂-R³⁴ (XXVII)

R³³ in which R³³ is hydrogen and R³⁴ is cyano, in the presence of a base.

The compound of formula XXVII may be prepared by reacting a compound of formula XXVIII

Ar-N=CH-OR³⁵ (XXVIII) in which R³⁵ is alkyl, with a compound of formula NH₂CH₂CN.

A compound of formula XXVIII may be prepared by reaction of ArNH₂ With HC(OR³⁵)₃. A compound of formula XXVI in which R⁴ is optionally substituted alkyl or halogen may be prepared from a compound of formula XXVII in which R³⁴ is cyano and R³³ is optionally substituted alkyl or halogen.

A compound of formula XXVII, in which R³⁴ is cyano and R³³ is optionally substituted alkyl or halogen may be prepared by reacting a compound of formula XXIX

Ar-N=C-R³⁶ (XXIX)

R³³ in which R³³ is optionally substituted alkyl or halogen and R³⁶ is halogen, with a compound of formula NH₂CH₂CN.

A compound of formula XXIX may be- repared-in known manner. Other useful intermediates are compounds of formula XXX

I Ar in which R³³ is as defined above. These may be prepared from a compound of formula XXVII in which R³⁴is alkoxycarbonyl. This latter compound may be prepared by reaction of a compound of formula XXIX with NH₂CH₂R³⁴.

Compounds of formula XXX may be further transformed, e.g. by a reaction with dimethylformamide and phosphorous oxychloride to give compounds of formula III where Z is Z¹, V¹ is N and V² is CR¹⁰, in which R¹⁰ = chlorine and R⁴ is R³³.

A compound of formula III where Z is Z¹, V¹ is CR⁹ and V² is CR¹⁰, may also be prepared by formylation of a compound of formula XXXI

Ar in which R³⁷ is hydrogen, e.g. with dimethylformamide and phosphorous oxychloride.

A compound of formula XXXI, in which R³⁷ is hydrogen, cyano, alkoxycarbonyl or an optionally protected formyl group, may be prepared by reaction of a compound of formula XXXII

(XXXII)

I

H in which R³⁷ is hydrogen, cyano, alkoxycarbonyl or a protected formyl group, with a compound of formula Ar-R³², where R³² is a leaving group, such as halogen, especially chlorine or fluorine.

A compound of formula XXXII may be prepared by a variety of methods known in the art for synthesis of pyrrole rings such as those described in Comprehensive Heterocyclic Chemistry Volume 4, ed. Katritzky and Rees, Chapter 3.06, pp 313, Pergamon 1984.

A compound of formula XXXI in which R⁴ and R¹⁰ are optionally substituted alkyl can also be prepared by reaction of a compound of formula XXXIII

R⁴-CO-CH(R⁹)-CH₂-CO-R¹⁰ (XXXIII) with a compound Ar-NH₂, in the presence of an acid catalyst.

A compound of formula III in which Z is Z¹, V¹ is CR⁹ and V² is CR¹⁰, where R⁹ is cyano, R⁴ is hydrogen and R¹⁰ is amino may be prepared by hydrolysing a compound of formula XXXIV NC_ R³⁸ ^Sj (XXXIV) \

N NH*,

I

Ar in which R³⁸ is a bis(alkylthio)methyl or bis(arylthio)- methyl group.

A compound of formula XXXIV may be prepared from a compound of formula XXXIV in which R³⁸ is hydrogen, by reaction with a tris(alkylthio)methane or tris(arylthio)- methane in the presence of a Lewis acid, e.g. dimethyl( ethylthio) sulfonium tetrafluoroborate.

A σompound-of formula XXXIV'in which R³⁸ is hydrogen, may be prepared by reaction of formylsuccinonitrile or its alkali metal salt with Ar-NH₂.

A compound of formula XXXI in which R⁹ is a formyl group, R⁴ is an amino group, R¹⁰ is hydrogen and R³⁷ is a cyano group (prepared as above) may be transformed using methods for conversion of formyl groups known to those skilled in the art. For example, the formyl group may be converted to a difluoromethyl group using diethylaminosulfur trifluoride.

A compound of formula XXXI in which R⁹ is R¹⁹S, R⁴ is amino, R¹⁰ is hydrogen and R³⁷ is cyano may be prepared by reacting the corresponding compound in which R⁹ is hydrogen with a sulfenyl halide of formula R¹⁹S-Hal (where Hal represents halogen) in the presence of an acid acceptor, e.g. a tertiary amine.

A compound of formula XXXI in which R⁴ is amino, R¹⁰ is hydrogen and R³⁷ is cyano may be halogenated to the corresponding compound in which R¹⁰ is halogen or sulfenylated using a sulfenyl halide of formula R¹⁹S-Hal to the corresponding compound in which R¹⁰ is R¹⁹S.

A compound in which R⁹, R⁴ or R¹⁰ represents a group of formula R¹⁹S0 or R¹⁹S0₂ may be prepared by oxidising the corresponding compound in which R⁹, R⁴ or R¹⁰ represents R¹⁹S, using, for example a per-acid.

The compound of formula III in which Z is Z³ or Z⁴ are known or can be prepared by known means, as described for example in EP 259 048 and 396 250.

Compounds of formula I may also be prepared by reacting a compound of formula XXXV

where Z' is the heterocyclic radical Z, in which the Ar is replaced by H, with a compound Ar-R³², where R³² is a leaving group, such as halogen, e.g. fluorine or chlorine, in the presence of a base. R³ may be a protecting group such as those described in "Protective Groups in Organic Chemistry" by T W Greene, published by John Wiley and Sons.

The compound of formula XXXV, may be prepared in a similar manner to that previously described for the preparation of compound I, e.g. starting from a compound Z'CHO, reacting this with H₂N-CR¹=CR²-NH₂ and ring closing the resulting compound. Other methods for preparing the compound of formula XXXV will be readily apparent those skilled in the art.

A compound of formula I where p is 0, Z is Z⁵, Y is NR¹² and R¹² is hydrogen, may be prepared from a compound of formula X, where R²⁶ is halogen, preferably chlorine, by reaction with a metal thiocyanate, preferably sodium, thiocyanate, in the presence of a base, e.g. triethylamine. This compound may be further derivatised, e.g. by alkylation or acylation, to give other values of R¹².

A compound of formula I where p is 0, Z is Z⁵ and Y is 0, W³ is S and W⁴ is C, may be prepared by heating a compound of formula XXXVI

(XXXVI)

Ar where Y' is NNO, in a solvent.

The compound of formula XXXVI may be prepared by diazotising a compound of formula I where p is 0, Z is Z , Y is NH, W³ is S and W⁴ is C, e.g. by reaction with a nitrite, e.g. sodium nitrite, in acetic acid.

A compound of formula III, where Z is Z⁵ and ϊ is O, W⁴ is C and W³ is NR⁴⁰, can be prepared for example by reduction of a compound of formula XXXVII (XXXVII )

where R²⁴ is an ester forming group such as alkyl, e.g. ethyl, using general methods indicated above.

The compound of formula XXXVII can be obtained by reaction of the compound of XVIII with potassium cyanate, followed by alkylation or by reaction with a substituted isocyanate of formula R^NCO.

A compound of formula III, in which Z is Z⁵ and Y is 0, W⁴ is C and W³ is -CR⁴¹=CR⁴²-, can be prepared for example by reduction of a compound of formula XXXIX

(XXXIX)

Ar where R²⁴ is an ester forming group such as alkyl, e.g. ethyl, R⁴¹ is methyl and R⁴² is hydrogen, using general methods indicated above.

The compound of formula XXXIX can be obtained by reaction of the compound of formula XIX with triethyl phosphonoacetate and sodium hydride in tetrahydrofuran.

A compound of formula III, in which p is 0, Z is Z⁵ and Y is 0, W⁴ is S and W³ is NH, can be prepared for example by reduction of a compound of formula XXXX (XXXX)

N i

The compound of formula XXXX can be obtained by reaction of the compound of XVII with thionyl chloride.

Compounds of formula I where R¹, R² and R³ are hydrogen may be obtained by reaction of a compound of formula XXXXI

Z-C .HC1 (XXXXI)

OEt with a compound of formula XXXXII H₂N-CH₂-CH(OMe)₂ (XXXXII)

The compound of^"formula XXXXI may be prepared from a compound of formula IV, where R²³ is cyano by reaction with e.g. gaseous hydrogen chloride in ethanol.

The compound of formula IV is known or may be prepared in known manner.

A compound of formula I, where R² and R³ are hydrogen, may be obtained by reaction of a compound of formula III, with a compound of formula _R ^l__C0-.cHBr₂ and ammonia.

Compounds where R¹ and/or R² are hydrogen may be modified by known methods such as e.g. electrophilic substitution reactions to give compounds of formula I where R¹ and/or R² are e.g. halogen, nitro etc. These groups may be modified by methods known to those skilled in the art to give other R¹ and R² groups. In some cases it may be necessary to have a suitable protecting group at R³, which can subsequently be removed, in known manner.

Thus, where R¹ is e.g. trifluoromethyl, this may be further reacted with ammonia to give a compound of formula I, where R¹ is cyano.

Where R¹ is e.g. cyano or trifluoromethyl and R² is hydrogen, the compound may be reacted with a brominating agent, e.g. N-bromosuccinimide, to give a compound of formula I, where R² is bromo.

A compound of formula I in which p is 1 may be obtained by reaction of a compound of formula XXXXIII

Z-AH (XXXXIII) with a compound of formula XXXXIV

R³⁹— (XXXXIV)

in which R³⁹ is a leaving group, such as a halogen, under basic conditions.

A compound of formula XXXXIV may be formed from a compound of formula XXXXV

₅39 (XXXXV)

R^

H by a variety of known methods, e.g. as described in "Protective Groups in Organic Synthesis" by T W Greene, published by John Wiley and Sons.

Where, in a compound of formula XXXXIV, the group R³ is a protecting group, e.g. containing silicon, the resulting compound of formula I may be optionally further modified in known manner, e.g. by hydrolysis or reaction with a source of fluoride ion to give compounds of formula I in which R³ is H.

Where A is S, this group can be oxidised using a suitable oxidising agent, e.g. m-chloroperbenzoic acid.

It will be evident to those skilled in the art that in compounds of formula I where R¹ and R² are different and R³ is H, tautomeric forms exist. These tautomers and any mixture thereof form part of the invention. Similarly in compounds of formula I where R¹ and R² are different and R³ is not hydrogen, then isomers are possible. These isomers and any mixture thereof comprise part of the invention.

The compounds of formula I in which R³ is hydrogen may form pesticidally and pharmaceutically acceptable salts with organic or inorganic bases, especially where R¹ and/or R² are electron withdrawing groups. These salts also form part of the invention.

Pesticidally acceptable salts means salts, the cations of which are known and accepted in the art as being suitable for the formation of salts of pesticidally active acids for use in agriculture or horticulture.

Similarly, pharmaceutically acceptable salts means salts, the cations of which are known and accepted in the art as being suitable for the formation of salts of biologically active acids for use in veterinary or human medicine.

Generally the salt is an alkali metal, alkaline earth metal, quaternary ammonium or an amine salt. Amine salts include salts derived from primary, secondary and tertiary amines, including amino sugars, such as N-methylglucamine. Salts may be prepared by reacting the compound of the invention, in known manner, with a suitable base.

It will be apparent that substituents on the various Z groups in a compound of formula I or its precursors may be modified in known manner to give other desired substituents. Thus for example compounds containing an alkoxycarbonyl group may be reduced, e.g. with diisobutylaluminium hydride at low temperature to give to give the corresponding carboxaldehyde. Alternatively they may be reduced by methods known in the art, e.g. using lithium aluminium hydride, diisobutylaluminium hydride or zirconium borohydride (prepared in situ from zirconium tetrachloride and sodium borohydride) in an inert solvent, such as tetrahydrofuran, to give a compound containing a hydroxymethyl group. This compound can then be oxidised to the carboxaldehyde, e.g. using pyridinium dichromate or manganese dioxide. Carboxaldehydes can be converted to oximes which in turn can be dehydrated to the corresponding nitrile. Compounds containing methyl groups may be halogenated to convert the methyl to halomethyl, in known manner and the halomethyl group can then be oxidised to give the corresponding carboxaldehyde.

Compounds and intermediates where Z is Z⁵ and Y is S may be obtained from the corresponding compound where Y is O, by reaction with a sulfurising agent such as Lawesson's reagent. The invention is illustrated in the following examples. Structures of isolated novel compounds were confirmed by elemental and/or other appropriate analyses.

Example 1 A solution of 3-[(2-amino-l,2-dicyanoethenylimino)methyl]- 1-(2 ,6-dichloro-4-trifluoromethylphenyl)-2 ,5-dimethyl- pyrrole, (0.53 g) and 2,3-dichloro-5,6-dicyano- 1,4-benzoquinone (0.28 g) in dioxane was heated under reflux for 6 hours. The mixture was poured into water and extracted with ethyl acetate. The extract was washed with dilute hydrochloric acid, dried and evaporated to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-(4,5-dicyano- lH-imidazol-2-yl)-2,5-dimethylpyrrole, as a gum. (Compound la) .

In a similar manner there was obtained:

(i) 2,5-dichloro-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-(4,5-dicyano-lH-imidazol-2-yl)-4-methylpyrrole, m.p. 115-120°. (Compound lb).

(ii) 2,5-dichloro-l-(2,6-dichloro-4-trifluoromethyl- phenyl)-4-(4,5-dicyano-lH-imidazol-2-yl)imidazole, m.p. 203-5°. (Compound lc)

(iii) 1-(2,6-dichloro-4-trifluoromethylphenyl)-

3-(4 ,5-dicyano-lH-imidazol-2-yl)-1H-1 , 2 ,4-triazole, m.p. 172-174°. (Compound Id)

(iv) 1-(2,6-dichloro-4-trifluoromethylphenyl)- 4-(4 ,5-dicyano-lH-imidazol-2-yl)-5-pyrrol-l-yl- lH-pyrazole, m.p. 216-219° (Compound le) . (v) 1-(2,6-dichloro-4-trifluoromethylphenyl)- 4-(4,5-dicyano-lH-imidazol-2-yl)-5-methylthio-lH-pyrazole, m.p. 192-196° (Compound If) .

(vi) 5-chloro-l-(2,6-dichloro-4-trifluoromethylphenyl)- 4-(4,5-dicyano-lH-imidazol-2-yl)-3-ethoxycarbonyl- lH-pyrazole, m.p. 131-3°. (Compound lg) .

(vii) 5-bromo-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-(4,5-dicyano-lH-imidazol-2-yl) imidazole, m.p. 236-241°. (Compound lh)

(viii) 5-chloro-l-(2,6-dichloro-4-trifluoromethylphenyl)- 4-(4,5-dicyano-lH-imidazol-2-yl)-3-methoxycarbonyl- lH-pyrazole, m.p. 288-90°. (Compound li) . (cyclisation by method described in Example 6) .

(ix) 1-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4,5-dicyano-lH-imidazol-2-yl)-4-methylpyrrole, m.p. 135-138°. (Compound lj).

(x) 1-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4,5-dicyano-lH-imidazol-2-yl)-5-trichloromethyl- lH-l,2,4-triazole, m.p. 281-3° (dec.) (Compound Ik)

(xi) l-(2,6-dichloro-4-trifluoromethylphenyl)-

3-(4,5-dicyano-lH-imidazol-2-yl)-5-dichloromethyl- lH-l,2,4-triazole, m.p. 292-3° (dec.) (Compound 11). (xii) 1-(2,6-dichloro-4-trifluoromethylphenyl)- 4-(4,5-dicyano-lH-imidazol-2-yl)-3,5-bis(trifluoromethyl)- lH-pyrazole, m.p. 186-7°. (Compound lm) .

(xiii) 5-bromo-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4,5-dicyano-lH-imidazol-2-yl)-4-methoxy-lH-pyrazole, m.p. 213-6° (Compound In) . (xiv) 5-bromo-l-(2 ,6-dichloro-4-trifluoromethylphenyl)- 3-( ,5-dicyano-lH-imidazol-2-yl)-4-difluoromethoxy- lH-pyrazole, m.p. 265-8° (dec.) (Compound Ip) .

(xv) 1-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4 ,5-dicyano-lH-imidazol-2-yl)-5-methoxy-lH-pyrazole , m.p. 129-30° (Compound lq) .

(xvi) 5-chloro-l-(2 ,6-dichloro-4-trifluoromethylphenyl)- 3-(4 ,5-dicyano-lH-imidazol-2-yl)-4-difluoromethy1- lH-pyrazole, m.p. 193-7° (Compound lr) .

(xvii) 5-chloro-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4 ,5-dicyano-lH-imidazol-2-yl)-1H-1 , 2 ,4-triazole, m.p. 258-9°. (Compound is)

(xviii) 1-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4,5-dicyano-lH-imidazol-2-yl)-4-methoxy-lH-pyrazole, m.p. 220-3° (Compound It).

(xix) 1-(2,6-dichloro-4-trifluoromethylphenyl)-

3-(4,5-dicyano-lH-imidazol-2-yl)-4-difluoromethoxy-

IH-pyrazole, m.p. 272-5° (Compound lu) .

(xx) 1-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4,5-dicyano-lH-imidazol-2-yl)pyrrole, m.p. 212-4° (Compound lv) .

(xxi) 1-(2,6-dichloro-4-trifluoromethylphenyl)-

3-(4,5-dicyano-lH-imidazol-2-yl)-4,5-dihydro-4-methyl-

5-oxo-lH-l,2,4-triazole, m.p. 338-9°. (Compound lw) .

(xxii) l-(2,6-dichloro-4-trifluoromethylphenyl)-

4-(4,5-dicyano-lH-imidazol-2-yl)-3-methoxy-lH-pyrazole, m.p. 225-6°. (Compound lx) . (xxiii) 5-chloro-l-(2,6-dichloro-4-trifluoromethylphenyl) 3-(4,5-dicyano-lH-imidazol-2-yl)-lH-pyrazole, m.p. 201-2° (Compound ly) .

(xxiv) 1-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4,5-dicyano-lH-imidazol-2-yl)-4-[ (dimethyl) (tert.- butyl)silyloxyJ-lH-pyrazole, m.p. 95-7°. (Compound lz) .

(xxv) 1-(2 ,6-dichloro-4-trifluoromethylphenyl)-

3-(4 ,5-dicyano-lH-imidazol-2-yl)-4,5-dihydro-4-ethyl-

5-oxo-lH-l,2,4-triazole, m.p. 230° (dec.) (Compound laa).

(xxvi) 3-(2,6-dichloro-4-trifluoromethylphenyl)-

5-(4,5-dicyano-lH-imidazol-2-yl)-2,3-dihydro-2-oxo- 1,3,4-oxadiazole, m.p. 242-244.5°. (Compound lbb) .

(xxvii) 5-(4,5-dicyano-lH-imidazol-2-yl)-2,3-dihydro- 3-(2-nitro-4-trifluoromethylphenyl)-2-oxo- 1,3,4-thiadiazole, m.p. 94.4° (dec). (Compound lcc).

Preparation of starting materials

a) Compound la - starting material

2,5-Dimethylpyrrole (2.29 ml) was stirred with sodium hydride (0.54 g of 60% dispersion in oil) for half an hour. l,3-Dichloro-2-fluoro-5-trifluoromethylbenzene (5 g) was added and the mixture heated under reflux for 2 hours. The mixture was poured into water and extracted with ethyl acetate. The extract was washed with water, dried and evaporated and the oil purified by silica gel chromatography to give 1-(2,6-dichloro-4-trifluoro¬ methylphenyl)-2 ,5-dimethylpyrrole, as an oil. This product (0.87 g) in dimethylformamide (10 ml) was added to mixture of phosphorus oxychloride (0.29 ml) and dimethylformamide (0.24 ml) and the mixture stirred for 15 minutes at 0°. The mixture was poured into aqueous potassium carbonate, extracted with ether and the extract worked up to give 1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-2,5-dimethylpyrrole-3-carboxaldehyde, m.p. 93-95°. A mixture of this product (0.74 g) and diaminomaleonitrile (0.24 g) and a trace of p-toluenesulfonic acid in methanol was stirred at room temperature for 18 hours. The solvent was removed and the residue purified by silica gel chromatography to give 3-[(2-amino-l,2-dicyanoethenyl- imino)methyl]-1-(2 ,6-dichloro-4-trifluoromethylphenyl)- 2,5-dimethylpyrrole, m.p. 130-131°.

b) Compound lb - starting material 3-Methoxycarbonyl-4-methylpyrrole was reacted with l,3-dichloro-2-fluoro-5-trifluoromethylbenzene, in the presence of sodium hydride to give l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-methoxycarbony1-4-methyl- pyrrole, m.p. 123-5°. A solution of this product (7.02 g) in ether (150 ml), was treated with sulfuryl chloride (2.9 ml) at 0°. The mixture was stirred for % hour at this temperature and then evaporated. The residue was worked up to give 2,5-dichloro-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-methoxycarbony1-4-methylpyrrole, m.p. 119-120°. This product (3.8 g) in dry tetrahydrofuran (30 ml) at -78°, was treated with diisobutylaluminium hydride in hexane (27 ml of one molar solution) . The mixture was stirred for 3 hours at this temperature, warmed to room temperature, cooled to -10° and water (10 ml) added, followed by silica (25 g) . The mixture was allowed to warm to room temperature, filtered and the filtrate evaporated to give 2,5-dichloro-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-hydroxymethyl-4-methylpyrrole, m.p. 93-5°. A solution of this (2.7 g) in chloroform (50 ml) was stirred for 24 hours with manganese dioxide. The mixture was filtered and the filtrate evaporated. The residue was worked up to give 1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-2,5-dichloro-4-methylpyrrole-3-carboxaldehyde, m.p. 107-8°, which itself was converted to 3-[(2-amino- 1,2-dicyanoethenylimino)methyl]-2,5-dichloro- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methylpyrrole, m.p. 188-190°.

c. Compound lc - starting material

Sodium hydride (0.41 g of a 90% dispersion in oil) was added portionwise to a solution of 5-amino-4-ethoxy- carbonylimidazole (2.4 g) in dimethylformamide (30 ml), cooled in an ice-bath. A solution of 1,3-dichloro- 2-fluoro-5-trifluoromethylbenzene (4.0 g) in dimethylformamide (10 ml) was added dropwise and the mixture stirred overnight at room temperature. The solvent was removed under reduced pressure and the residue triturated with hexane. The mixture was then extracted with ethyl acetate and the extract worked up^' to give 5-amino-l-(2 ,6-dichloro-4-trifluoromethylphenyl)- 4-ethoxycarbonylimidazole, m.p. 208-210°. This was treated with sulfuryl chloride in a similar manner to that described above to give 5-amino-2-chloro- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethoxycarbonyl- imidazole, m.p. 145-150°.

A solution of this product (3.7 g) in hydrochloric acid (60 ml) was treated with cuprous chloride (4.6 g) . The mixture was cooled on an ice/water bath and nitrosyl- sulfuric acid (11.8 g) , in sulfuric acid (20 ml), added. The mixture was stirred for 48 hours at room temperature, poured into ice and extracted with ethyl acetate. The extract was dried and evaporated and the residue worked up to give 2,5-dichloro-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-ethoxycarbonylimidazole, as an oil. This was reduced in a similar manner to that described above to give 2 ,5-dichloro-l-( 2 ,6-dichloro-4-trifluoro¬ methylphenyl)-4-hydroxymethylimidazole, m.p. 133-7° , which in turn was oxidised in a similar manner to that described above to give 2,5-dichloro-l-(2,6-dichloro- 4-trifluoromethylphenyl)imidazole-4-carboxaldehyde, m.p. 81-85°, which itself was converted to 4-[(2-amino- 1,2-dicyanoethenylimino)methyl]-2,5-dichloro- l-(2,6-dichloro-4-trifluoromethylphenyl)imidazole, m.p. 213-5°.

d) Compound Id - starting material Sodium nitrite (45 g) in concentrated sulfuric acid (340 ml) was added to a solution of 2,6-dichloro- 4-trifluoromethylaniline (140 g) in acetic acid (550 ml) , whilst maintaining the temperature below 25°. The mixture was stirred at room temperature for 1 hour and added to a solution of ethyl acetoacetate (80 g) , sodium acetate

(180 g) , ethanol (300 ml) and ice water (3 litres) , and the mixture stirred for 1 hour. The precipitate was collected and combined with further precipitate (resulting from allowing the filtrate to stand) , to give ethyl 2-(2,6-dichloro-4-trifluoromethylphenylhydrazono)- 3-oxobutanoate.

This product was added to a mixture of glacial acetic acid (30 ml) and acetic anhydride (180 ml) containing sodium acetate (81 g) . The mixture was cooled on an ice bath and bromine (40 g) in acetic acid (60 ml) was added dropwise. The mixture was stirred for 30 minutes at this temperature and then for 2 hours at room temperature. It was poured into ice water and allowed to stand over the weekend. The precipitate was filtered off to give ethyl 2-bromo- 2-(2,6-dichloro-4-trifluoromethylphenylhydrazono)acetate, m.p. 116-117°.

A suspension of this product (30g) in ethanol (150 ml) , was added to aqueous ammonia (500 ml) and water (500 ml) . The mixture was stirred for 10 minutes, the solid filtered off, triturated with hexane, filtered, dried and purified by silica gel column chromatography to give ethyl 2-amino- 2-(2,6-dichloro-4-trifluoromethylphenylhydrazono)acetate, m.p. 133-134°.

A mixture of this product (19 g) and triethyl orthoformate (28 g) was heated under reflux for 4 hours. After cooling, the mixture was added to hexane and the mixture cooled in a dry ice/acetone, the solid was filtered off to give 1-(2,6-dichloro-4-trifluoro ethyphenyl)-3-ethoxycarbonyl- lH-l,2,4-triazole, m.p. 128-129°.

This product (11.5 g) in dry tetrahydrofuran (65 ml) at -78°, was treated with diisobutylaluminium hydride in hexane (30 ml of one molar solution) whilst maintaining the temperature at below -65°. The mixture was allowed to warm to -10° over 1 hour and water (10 ml) added, followed by silica (10 g) . The mixture was allowed to warm to room temperature, filtered and the filtrate evaporated. The residue was triturated with hexane and the solid collected to give 1-(2,6-dichloro-4-trifluoromethylphenyl)- 1H-1,2,4-triazole-3-carboxaldehyde, m.p. 126-127°.

This was then reacted with diaminomaleonitrile, as described above, to give 3-[(2-amino-l,2-dicyanoethenyl- imino)methyl]-1-(2,6-dichloro-4-trifluoromethylphenyl)- lH-l,2,4-triazole, m.p. 259-261°.

e. Compound le - starting material

A solution of 2,6-dichloro-4-trifluoromethylphenyl- hydrazine (10 g) and ethyl 2-cyano-3-ethoxyacrylate (7.0 g) in absolute ethanol (200 ml) was heated under reflux with stirring for 24 hours. Evaporation of solvent and recrystallisation from diisopropyl ether gave ethyl 5-amino-l-(2,6-dichloro-4-trifluoromethylphenyl)- lH-pyrazole-4-carboxylate, m.p. 131-134°.

A mixture of this compound (7.1 g) , 2,5-dimethoxy- tetrahydrofuran (7.8.ml) and acetic acid (1.6 ml) was heated under reflux, under nitrogen overnight. The mixture was added to water and extracted with ether. The extract was worked up to give ethyl 1-(2,6-dichloro-4-trifluoro¬ methylphenyl)-5-pyrrol-l-yl-lH-pyrazole-4-carboxylate, m.p. 131-134°. A solution of this product (6.4 g) in tetrahydrofuran (25 ml) was added dropwise to mixture of zirconium chloride (4.3 g) in tetrahydrofuran (65 ml) to which had been added sodium borohydride (2.9 g) under nitrogen. The mixture was stirred at room temperature overnight added to ice water and worked up to give l-(2,6-dichloro-

4-trifluoromethylphenyl)-4-hydroxymethyl-5-pyrrol-l-yl- lH-pyrazole. A mixture of this compound (2.2 g) and manganese dioxide (7.9 g) in chloroform (40 ml) was stirred at room temperature for two days. It was then filtered, evaporated and a solution of the residue in dichloromethane purified by silica gel column chromatography to give

1-(2,6-dichloro-4-trifluoromethylphenyl)-5-pyrrol-l-yl- lH-pyrazole-4-carboxaldehyde, m.p. 159-163°.

This was treated with diaminomaleonitrile in a similar manner to that previously described to give 4-[(2-amino- 1,2-dicyano-ethenylimino)methyl]-1-(2,6-dichloro- 4-trifluoromethylphenyl)-5-pyrrol-l-yl-lH-pyrazole, m.p. 212-214°.

f. Compound If - starting material t-Butyl nitrite (3.3 ml) was added with stirring to a solution of ethyl 5-amino-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-lH-pyrazole-4-carboxylate, prepared as described above, and dimethyl disulfide (3.45 ml) in chloroform (100 ml) . The mixture was stirred for one hour, washed with brine, the organic layer evaporated and the residue purified by silica gel column chromatography to give ethyl 1-(2 ,6-dichloro-4-trifluoromethylphenyl)- 5-methylthio-lH-pyrazole-4-carboxylate, as an oil. This was reduced as described above to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-hydroxymethyl- 5-methylthio-lH-pyrazole, as an oil.

This product (1.1 g) in dichloromethane (50 ml) was stirred with pyridinium dichromate (1.75 g) for 18 hours at room temperature. Ether (150 ml) and silica (5 g) were added and the mixture stirred for 45 minutes, filtered, evaporated and the oil which solidified was triturated with hexane to give 1-(2,6-dichloro-4-trifluoro¬ methylphenyl)-5-methylthio-lH-pyrazole-4-carboxaldehyde, m.p. 88-89°. This was treated with diaminomaleonitrile in a similar manner to that previously described to give 4-[(2-amino- 1,2-dicyanoethenylimino)methyl]-1-(2,6-dichloro- 4-trifluoromethylphenyl)-5-methylthio-lH-pyrazole, m.p. 225-228°.

g. Compound lg - starting material Sodium nitrite (13.8 g) was added to a solution of 2,6-dichloro-4-trifluoromethylaniline (46 g) in concentrated hydrochloric acid (150 ml) at 0°. The mixture was stirred for 15 minutes, filtered into a flask maintained at 0° and then added slowly to a mixture of diethyl acetylsuccinate (43.2 g) in water (500 ml) and sodium acetate (270 g) in water (1 L) . The mixture was allowed to heat up to room temperature over an hour and aqueous ammonia (25%; 150 ml) was added and the mixture heated at 60° for 1 hour. It was extracted with diethyl ether and the extract worked up to give an oil which was passed though a silica gel column to remove the dark baseline. The purified material was heated under reflux for 48 hours with p-toluenesulfonic acid (5 g) in ethanol. The solvent was evaporated and the residue recrystallised from ethyl acetate to give 1-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-ethoxycarbonyl-lH-pyrazolin-5(4H)-one, m.p. 265-6°. This compound (5.72 g) was added to a preformed mixture of phosphorus oxychloride (71.6 ml) and dimethylformamide (1.35 ml) . The resulting mixture was then heated under reflux overnight and excess phosphorus oxychloride removed under reduced pressure. Ice was added to the residue and the mixture extracted with dichloro- methane. The extract was worked up to give an oil which was passed through a silica gel column using ether as eluent and the fraction having an R_f value of 0.83 was collected, which was shown by nmr to be 5-chloro- 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxy- carbonyl-4-formyl-lH-pyrazole.

This product was treated, without further purification, with diaminomaleonitrile in a similar manner to that previously described to give 5-chloro-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-ethoxycarbonyl-4-[ (2-amino- 1,2-dicyanoethenylimino)methyl]-lH-pyrazole, m.p. 201-3°.

h) Compound in - starting material t-Butyl nitrite (1.2 ml) was added portionwise to a solution of 5-amino-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-ethoxycarbonylimidazole, prepared as described above, (1.22 g) in bromoform (6 ml), maintained under nitrogen. The mixture was stirred at room temperature overnight, the solvent evaporated under reduced pressure and the residue extracted with dichloromethane. The extracts were worked up to give 5-bromo-l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-ethoxycarbonylimidazole, m.p. 99-101°.

This product was then reduced with diisobutylaluminium hydride in a similar manner to that previously described to give 5-bromo-l-(2,6-dichloro-4-trifluoromethylphenyl)- 4-formylimidazole, m.p. 129-131°.

This product was treated with diaminomaleonitrile in a similar manner to that previously described to give 4-[ (2-amino-l,2-dicyanoethenylimino)methyl]-5-bromo- 1-(2,6-dichloro-4-trifluoromethylphenyl)imidazole, m.p. 195-200°. i. Compound li - starting material

Dimethylformamide dimethyl acetal (16 ml) was added dropwise to a solution of l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-methoxycarbonyl-lH-pyrazol-5-one. The mixture was stirred overnight at room temperature, evaporated and the residue worked up to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(dimethyl- aminomethylene)-3-methoxycarbonyl-lH-pyrazol-5-one , m.p 223-224°.

A mixture of this product (31.89 g) and phosphorus oxychloride (375 ml) was heated under reflux for 16 hours and excess phosphorus oxychloride removed under reduced pressure. Ice was added to the residue and the mixture extracted with ethyl acetate. The extract was worked up to give 5-chloro-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3-methoxycarbonyl-4-formyl-lH-pyrazole, m.p. 138.5-139°.

This product was treated with diaminomaleonitrile in a similar manner to that previously described to give 4-[(2-amino-l,2-dicyanoethenylimino)methyl]-5-chloro- 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methoxy- carbonyl-lH-pyrazole, m.p. 209.4-210.5°.

i. Compound li - starting material

1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-methoxy- carbonyl-4-methylpyrrole was reduced as described above to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-hydroxy- methy1-4-methylpyrrole, m.p. 87-9°. This in turn was oxidised to 1-(2,6-dichloro-4-trifluoromethylphenyl)- 4-methylpyrrole-3-carboxaldehyde, m.p. 90-94°, which itself was converted to 3-[(2-amino-l,2-dicyanoethenyl- imino)methyl]-1-(2,6-dichloro-4-trifluoromethylphenyl)- 4-methylpyrrole, m.p. 174-7°. k and 1. Compounds lk and 11 - starting materials A mixture of ethyl 2-amino-2-(2,6-dichloro-4-trifluoro¬ methylphenylhydrazono)acetate (10 g) and trichloroacetic anhydride (30 ml) was heated at 200° for 1% hours. It was added to ice-water stirred for 1% hours and the solid collected and treated with diisopropyl ether on a steam bath and cooled in ice and filtered to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-ethoxycarbonyl- 5-trichloromethyl-lH-l,2,4-triazole, m.p. 143-4°.

This was then reduced with lithium borohydride, in a manner similar to that described in the preparation of the starting material for compound Is. NMR indicated that there was obtained a crude mixture, of..l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-hydroxymethyl-5-trichloro- methyl-lH-l,2,4-triazole and 1-(2,6-dichloro-4-trifluoro¬ methylphenyl)-5-dichloromethyl-3-hydroxymethyl- 1H-1,2,4-triazole.

This mixture was treated with pyridinium dichromate to give a crude mixture of l-(2,6-dichloro-4-trifluoromethyl- phenyl)-5-trichloromethyl-lH-l,2,4-triazole-

3-carboxaldehyde and 1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-dichloromethyl-lH-l,2,4-triazole- 3-carboxaldehyde.

This mixture was then reacted with diaminomaleonitrile, as described above, followed by purification by silica gel column chromatography to give 3-[ (2-amino-l,2-dicyano- ethenylimino)methyl]-1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-trichloromethyl-lH-l,2,4-triazole and 3-[(2-amino-l,2-dicyanoethenylimino)methyl]- 1-(2,6-dichloro-4-trifluoromethylphenyl)-5-dichloromethyl- 1H-1,2 ,4-triazole. m. Compound 1m - starting material Ethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)- 3,5-bis(trifluoromethyl)-lH-pyrazole-4-carboxylate was reduced with diisobutylaluminium hydride in a similar manner to that previously described, to give l-(2,6-dichloro-4-trifluoromethylphenyl)-4-hydroxymethyl- 3,5-bis(trifluoromethyl)-lH-pyrazole, m.p. 97-8°. This in turn was oxidised, using pyridinium dichromate, to l-(2,6-dichloro-4-trifluoromethylphenyl)- 3,5-bis(trifluoromethyl)-lH-pyrazole-4-carboxaldehyde, m.p. 60-61°, which itself was converted to 4-[ (2-amino-l,2-dicyanoethenylimino)methyl]- 1-(2,6-dichloro-4-trifluoromethylphenyl)- 3,5-bis(trifluoromethyl)-lg-pyrazole, m.p..176-7°.

n) Compound In - starting material

Ethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-hydroxy- lH-pyrazole-3-carboxylate was brominated with N-bromosuccinimide in chloroform to give ethyl 5-bromo- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-hydroxy- lH-pyrazole-3-carboxylate, m.p. 139-140°. This was then methylated using methyl iodide/sodium hydride in tetrahydrofuran to give ethyl 5-bromo-l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-methoxy-lH-pyrazole- 3-carboxylate, m.p. 91-5°. This was reduced with zirconium tetrachloride/sodium borohydride to give 5-bromo-

1-(2,6-dichloro-4-trifluoromethylphenyl)-3-hydroxymethyl- 4-methoxy-lH-pyrazole, m.p. 99-100°. This in turn was oxidised, using pyridinium dichromate, to 5-bromo- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methoxy- lg-pyrazole-3-carboxaldehyde, m.p. 62-3°, which itself was converted to 3-[(2-amino-l,2-dicyanoethenylimino)methyl]- 5-bromo-l-(2,6-dichloro-4-trifluoromethylphenyl)- 4-methoxy-lH-pyrazole, m.p. 148-150°. p. Compound lp - starting material

Ethyl 5-bromo-l-(2,6-dichloro-4-trifluoromethylphenyl)-4- hydroxy-lH-pyrazole-3-carboxylate, prepared as above was treated with chlorodifluoromethane in the presence of sodium hydroxide to give 5-bromo-l-(2,6-dichloro-

4-trifluoromethylphenyl)-4-difluoromethoxy-lH-pyrazole- 3-carboxylic acid, m.p. 131-4°. This was reduced with zirconium tetrachloride/sodium borohydride to give to give 5-bromo-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3-hydroxymethyl-4-difluoromethoxy-lH-pyrazole, m.p. 86-8°. This in turn was oxidised, using pyridinium dichromate, to 5-bromo-l-(2,6-dichloro-4-trifluoromethylphenyl)- 4-difluoromethoxy-lH-pyrazole-3-carboxaldehyde, m.p. 55-7°, which itself was converted to 3-[(2-amino- 1,2-dicyanoethenylimino) ethyl]-5-bromo-l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-difluoromethoxy-lH-pyrazole, m.p. 115-8°.

q. Compound lq - starting material Ethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)- 4,5-dihydro-5-oxo-lH-pyrazole-3-carboxylate, was treated with dimethyl sulfate/sodiu hydride to give ethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methoxy- lH-pyrazole-3-carboxylate, m.p. 127-8°.

This was reduced with diisobutylaluminium hydride to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methoxy- lH-pyrazole-3-carboxaldehyde, m.p. 96-8°, which itself was converted to 3-[ (2-amino-l,2-dicyanoethenylimino)methyl]- 1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methoxy- lH-pyrazole, m.p. 235-8°. r. Compound lr - starting material Diethylaminosulfur trifluoride (17.4. l) was added dropwise to a solution of 5-chloro-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-methoxycarbonyl-4-formyl- lH-pyrazole (18.05 g) in dichloromethane (150 ml).

The mixture was stirred for room temperature, overnight, water added and extracted with ethyl acetate. The extract was dried and evaporated and the residue worked up to give 5-chloro-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3-methoxycarbonyl-4-difluoromethyl-lH-pyrazole, m.p. 119-120°. This was reduced with diisobutylaluminium hydride to give 5-chloro-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-hydroxymethyl-4-difluoromethyl- lH-pyrazole, m.p.. 76--8°.

This in turn was oxidised, using pyridinium dichromate, to 5-chloro-l-(2,6-dichloro-4-trifluoromethylphenyl)- 4-difluoromethyl-lH-pyrazole-3-carboxaldehyde, m.p. 77-9°, which itself was converted to 3-[ (2-amino-1,2-dicyano¬ ethenylimino)methyl]-5-chloro-l-(2,6-dichloro-4-trifluoro- methylphenyl)-4-difluoromethyl-lH-pyrazole, m.p. 210-212°.

s) Compound Is - starting material

A mixture of ethyl 2-bromo-2-(2,6-dichloro-4-trifluoro¬ methylphenylhydrazono)acetate (80 g) and potassium cyanate (34.4 g) in methanol (2 1) was heated under reflux for 6 hours and allowed to stand at room temperature overnight. Hydrochloric acid (40 ml) was added and the mixture heated under reflux for 2 hours. The solvent was evaporated, water added and the solid collected, washed with hexane and dried to give l-(2,6-dichloro-4-trifluoromethyl- phenyl)-3-methoxycarbonyl-4 ,5-dihydro-5-oxo- lH-l,2,4-triazole, m.p. 230-1°.

Lithium borohydride (4.3 g) was added to a solution of this product (35 g) in dry tetrahydrofuran (700 ml) . The mixture was stirred for % hour at room temperature, and then heated under reflux for 2 hours. It was poured into ice/hydrochloric acid and extracted with ethyl acetate. The extract was dried and evaporated and the residue worked up to give 1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4,5-dihydro-3-hydroxymethyl-5-oxo- lH-l,2,4-triazole, m.p. 231-2°.

A mixture of this product (21 g) and phenylphosphonic dichloride (75 ml) was heated at 180-185° overnight. It was poured into water and extracted with ethyl acetate. The extract was dried and evaporated and the residue worked up to give 5-chloro-3-chloromethyl-l-(2,6-dichloro- 4-trifluoromethylphenyl)-1H-1,2,4-triazole, m.p. 1-18-9°. A mixture of this product (7.5 g) , anhydrous trimethylamine N-oxide (6.2 g) and dimethyl sulfoxide (40 ml) was stirred for 1.25 hours at room temperature, poured into brine and extracted with ethyl acetate. The extract was dried and evaporated to give 5-chloro- 1-(2,6-dichloro-4-trifluoromethylphenyl)- lH-l,2,4-triazole-3-carboxaldehyde, m.p. 85-6°.

This was then reacted with diaminomaleonitrile, as described above, to give 3-[ (2-amino-l,2-dicyanoethenyl- imino)methyl]-5-chloro-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-1H-1,2,4-triazole, m.p. 240-2° (dec).

t) Compound It - starting material

Ethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-hydroxy- lH-pyrazole-3-carboxylate was methylated using methyl iodide/sodium hydride in tetrahydrofuran to give ethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methoxy- lH-pyrazole-3-carboxylate, m.p. 148-151°. This was reduced with zirconium tetrachloride/sodium borohydride to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-hydroxymethyl- 4-methoxy-lH-pyrazole, m.p. 91-3°. This in turn was oxidised, using pyridinium dichromate, to l-(2,6-dichloro- 4-trifluoromethylphenyl)-4-methoxy-lH-pyrazole- 3-carboxaldehyde, m.p. 122-3°, which itself was converted to 3-[(2-amino-l,2-dicyanoethenylimino)methyl]-

1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methoxy- lH-pyrazole, m.p. 178-9°.

u) Compound lu - starting material

Chlorodifluoromethane was bubbled through a mixture of ethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-hydroxy- lH-pyrazole-3-carboxylate (10 g) and aqueous sodium hydroxide (100 ml of 2M) and dioxane (100 ml) . Solvent was evaporated, the residue acidified and the solid collected and dried to give l-(2,6-dichloro-4-trifluoromethyl- phenyl)-4-difluoromethoxy-lH-pyrazole-3-carboxylic acid, m.p. 177-8°.

This was reduced with zirconium tetrachloride/sodium borohydride to give 1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-hydroxymethyl-4-difluoromethoxy-lH-pyrazole, m.p. 77-8°. This in turn was oxidised, using pyridinium dichromate, to 1-(2,6-dichloro-4-trifluoromethylphenyl)- 4-difluoromethoxy-lH-pyrazole-3-carboxaldehyde, as an oil, which itself was converted to 3-[(2-amino-l,2-dicyano- ethenyli ino)methyl]-1-(2,6-dichloro-4-trifluoromethyl- phenyl)-4-difluoromethoxy-lH-pyrazole, m.p. 160-4°.

v. Compound lv - starting material A mixture of 2,6-dichloro-4-trifluoromethylaniline (11.5 g) , 2,5-dimethoxytetrahydrofuran-3-carboxaldehyde (8 g) and a trace of β-toluenesulfonic acid was heated at 90-110° under nitrogen for 1 hour. The mixture was purified by silica gel column chromatography to give 1-(2,6-dichloro-4-trifluoromethylphenyl)pyrrole- 3-carboxaldehyde, which itself was converted to 3-[ (2-amino-1,2-dicyanoethenylimino)methyl]- 1-(2,6-dichloro-4-trifluoromethylphenyl)pyrrole, m.p. 175-7°.

w. Compound lw - starting material 1-(2,6-Dichloro-4-trifluoromethylphenyl)-3-methoxy- carbonyl-4,5-dihydro-5-oxo-lH-l,2,4-triazole, (prepared under the compound Is starting material) was methylated using methyl iodide/sodium hydride in dimethylformamide to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methoxy- carbonyl-4,5-dihydro-4-methy1-5-oxo-lH-l,2,4-triazole, m.p. 188-9°.

This was reduced with lithium borohydride as previously described, to give l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)- ,5-dihydro-3-hydroxymethyl-4-methyl-5-oxo- lH-l,2,4-triazole, m.p. 150-1°.

This in turn was oxidised, using pyridinium dichromate, to 1-(2,6-dichloro-4-trifluoromethylphenyl)-4,5-dihydro- 4-methyl-5-oxo-lH-l,2,4-triazole-3-carboxaldehyde, which itself was converted to 3-[ (2-amino-l,2-dicyanoethenyl- imino)methyl]-l-(2,6-dichloro-4-trifluoromethylphenyl)- 4,5-dihydro-4-methyl-5-oxo-lH-l,2,4-triazole, m.p. 245-6°.

x. Compound lx - starting material A solution of 2,6-dichloro-4-trifluoromethylphenyl- hydrazine (2.6 g) and diethyl 2-cyanomalonate (2.4 g) in absolute ethanol (30 ml) was heated under reflux with stirring for 4 hours. Evaporation of solvent and work-up of the residue gave ethyl 5-amino-l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-hydroxy-lH-pyrazole- 4-carboxylate, m.p. 198.5-202.5°. This was deaminated using t-butyl nitrite in tetrahydrofuran to give ethyl l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-hydroxy-lH-pyrazo1e- 4-carboxylate, m.p. 153-6°, which in turn was methylated with methyl iodide/potassium carbonate in acetone to give ethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methoxy- lH-pyrazole-4-carboxylate, m.p. 97-9°.

This was reduced with zirconium tetrachloride/sodium borohydride to give l-(2,6-dichloro-4-trifluoromethyl- phenyl)-4-hydroxymethyl-3-methoxy-lH-pyrazole, m.p.

131.5-3°. This in turn was oxidised, using pyridinium dichromate, to 1-(2,6-dichloro-4-trifluoromethylphenyl)- 3-methoxy-lH-pyrazole-4-carboxaldehyde, m.p 89-90°, which itself was converted to 4-[(2-amino-l,2-dicyano- ethenylimino)methyl]-1-(2,6-dichloro-4-trifluoromethy1- phenyl)-3-methoxy-lH-pyrazole, m.p. 210-2°.

y. Compound ly - starting material

A solution of 5-amino-3-cyano-l-(2^6-dichloro-4-trifluoro¬ methylphenyl)-lH-pyrazole (7 g) in ether (150 ml) at 0° was treated with copper (I) chloride (4.2 g) and nitrosylsulphuric acid (14 g) in concentrated sulphuric acid (35 ml). After 2 hours at 5-15°, the mixture was poured onto ice and the pH adjusted to 8 with aqueous ammonia. It was extracted with ethyl acetate and the extract worked up to give 5-chloro-3-cyano-

1-(2,6-dichloro-4-tri luoromethylphenyl)-lH-pyrazole, m.p. 91-3°.

This was reduced with diisobutylaluminium hydride to give 5-chloro-l-(2,6-dichloro-4-trifluoromethylphenyl)- lH-pyrazole-3-carboxaldehyde, m.p. 81-3° which in turn was converted to 3-[(2-amino-l,2-dicyanoethenylimino)methyl]- 5-chloro-l-(2,6-dichloro-4-trifluoromethylphenyl)- lH-pyrazole, m.p. 220-1°. z. Compound lz - starting material

Ethyl 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-hydroxy- lH-pyrazole-3-carboxylate and imidazole in dimethylformamide was reacted with (dimethyl) (tert.- butyl)silyl chloride to give, after work up, ethyl

1-(2,6-dichloro-4-trifluoromethylphenyl)-4-[ (dimethyl)- (tert.-butyl)-silyloxy]-lH-pyrazole, m.p. 73-76°.

This was reduced with lithium borohydride as previously described, to give l-(2,6-dichloro-4-trifluoromethyl- phenyl)-4-[ (dimethyl) (tert.-butyl)silyloxy]-

3-hydroxymethyl-lH-pyrazole-3-carboxylate, m.p. 39-41°.

This in turn was oxidised, using pyridinium dichromate, to l-(2,6-dichloro-4-trifluoromethylphenyl)-4-[ (dimethyl)- (tert.-butyl)silyloxy]-lH-pyrazole-3-carboxaldehyde, m.p. 111-112°, which itself was converted to 3-[(2-amino- 1,2-dicyanoethenylimino)methyl]-1-(2,6-dichloro- 4-trifluoromethylphenyl)-4-[ (dimethyl) (tert.-butyl)- silyloxy]-lH-pyrazole, m.p. 82-4°.

aa. Compound laa - starting material l-(2,6-Dichloro-4-trifluoromethylphenyl)-3-methoxy- carbony1-4,5-dihydro-5-oxo-lH-l,2,4-triazole, (prepared as for the compound Is starting material) was ethylated using ethyl iodide/sodium hydride in dimethylformamide to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-methoxy- carbonyl-4,5-dihydro-4-ethyl-5-oxo-lH-l,2,4-triazole.

This was reduced with lithium borohydride as previously described, to give 1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4,5-dihydro-3-hydroxymethyl-4-ethyl-5-oxo- lH-l,2,4-triazole, m.p. 129-130°.

This in turn was oxidised, using pyridinium dichromate, to 1-(2,6-dichloro-4-trifluoromethylphenyl)-4,5-dihydro- 4-ethyl-5-oxo-lH-l,2,4-triazole-3-carboxaldehyde, which itself was converted to 3-[(2-amino-1,2-dicyanoethenyl¬ imino)methyl]-1-(2,6-dichloro-4-tri luoromethylphenyl)- 4,5-dihydro-4-ethyl-5-oxo-lH-l,2,4-triazole, m.p. 165-7°.

bb. Compound lbb - starting material

A solution of cinnamoyl chloride (32 g) in tetrahydrofuran (100 ml) was added dropwise to a solution of 2,6-dichloro- 4-trifluoromethylphenylhydrazine (46.8 g) and triethylamine (20 g) in tetrahydrofuran (200 ml) , cooled on an ice-water bath. The product was worked up to give N¹-cinnamoyl-N²-(2,6-dichloro-4-trifluoromethylphenyl)- hydrazine_r m.p. 150° (dec). This was then ring closed using trichloromethyl chloroformate, in the presence of triethylamine, to give 3-(2,6-dichloro-4-trifluoro¬ methylphenyl)-5-styryl-2,3-dihydro-2-oxo-l,3,4-oxadiazole, m.p. 164-166°.

Ozone was bubbled through a solution of this product (8.5 g) in methanol (220 ml) maintained at -60°, over 2 hours. Dichloromethane (30 ml) was added, followed by dimethyl sulphide (2 ml) and the mixture allowed to warm to room temperature. The mixture was worked up to give 3-(2,6-dichloro-4-trifluoromethylphenyl)-2,3-dihydro- 2-oxo-l,3,4-oxadiazole-5-carboxaldehyde, which itself was converted to 3-[(2-amino-l,2-dicyanoethenylimino)methyl]- 1-(2,6-dichloro-4-trifluoromethylphenyl)-2,3-dihydro- 2-oxo-l,3 ,4-oxadiazole. cc) Compound lcc - starting material

In a similar manner to that described in the preparation of the starting material for Compound Id 2-nitro- 4-trifluoromethylaniline was converted to ethyl 2-(2-nitro-4-trifluoromethylphenylhydrazono)-

3-oxobutanoate, which in turn was converted to ethyl 2-bromo-2-(2-nitro-4-trifluoromethylphenylhydrazono)- acetate, m.p. 68.5-69.5°. This was ring closed with potassium thiocyanate to give 5-ethoxycarbonyl-3-(2-nitro- 4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-imine, m.p. 135.6-136.5°. This was treated in a manner similar to Example 13 to give 5-ethoxycarbonyl-3-(2-nitro- 4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-one, m.p. 81.6-81.8°.

This was reduced with lithium borohydride as previously described, to give 5-hydroxymethyl-3-(2-nitro- 4-trifluoromethylphenyl)-l,3,4-thiadiazol-2-one, which in turn was oxidised, using pyridinium dichromate, to 4,5-dihydro-3-(2-nitro-4-trifluoromethylphenyl)-2-oxo- lH-l,3,4-thiadiazole-5-carboxaldehyde, which itself was converted to 3-[ (2-amino-l,2-dicyanoethenylimino)methyl]- 3-(2-nitro- -trifluoromethylphenyl)-4,5-dihydro-5-oxo- 1H-1 ,3,4-thiadiazole.

Example 2 l,l-Dibromo-3,3,3-trifluoroacetone (7 g) was added to a solution of sodium acetate trihydrate (7 g) in water (25 ml) and the resulting solution heated on a steam bath for 30 mins. The mixture was cooled to room temperature and added slowly to a solution of l-(2,6-dichloro- 4-trifluoromethylphenyl)-1H-1,2,4-triazole- 3-carboxaldehyde (6.8 g) and aqueous ammonia (30 ml) in methanol (60 ml) . The suspension was stirred for 3 hours, reduced in volume and water added. The solid was collected by filtration, purified by silica gel chromatography and recrystallised from ethyl acetate/hexane to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-(4-trifluoro- methyl-lH-imidazol-2-yl)-lH-l,2,4-triazole, m.p. 270-271°. (Compound 2a) .

In a similar manner there was obtained:

(i) 1-(2,6-dichloro-4-trifluoromethylphenyl)-

5-(4-trifluoromethyl-lH-imidazol-2-yl)-4-trifluoromethyl-

2(lH)-pyridone, m.p. 204-20 ^ "(Compound 2b).

(ii) 1-(2 ,6-dichloro-4-trifluoromethylphenyl)-5-methyl- thio-4-(4-trifluoromethyl-lH-imidazol-2-yl)-lH-pyrazole, m.p. 196-7°. (Compound 2c).

Example 3

Compound 2a (2 g) was heated at 70° in 5% aqueous ammonia (300 ml) and ethanol (40 ml) for 6 hours. The mixture was cooled and filtered. The filtrate was acidified with glacial acetic acid and the resulting white precipitate was filtered and dried. The product was recrystallised from acetonitrile to give l-(2,6-dichloro-4-trifluoro- methylphenyl)-3~(4-cyano-lH-imidazol-2-yl)- lH-l,2,4-triazole, m.p. 295-296°. (Compound 3a) In a similar manner,

(i) compound 9a, gave 4-(5-bromo-4-cyano-lH-imidazol- 2-yl)-1-(2,6-dichloro-4-trifluoromethylphenyl)-5-methyl- sulfonyl-lH-pyrazole, m.p. 193-4°. (Compound 3b). (ii) compound 2c gave 1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-(4-cyano-lH-imidazol-2-yl)-5-methylthio- lH-pyrazole, m.p. 171-4°. (Compound 3c).

Example 4

A mixture of compound 2a (2 g) , N-bromosuccinimide (0.86 g) and dimethylformamide was stirred at room temperature overnight. This mixture was then poured into water, extracted with ether and the extract worked up to give 3-(5-bromo-4-trifluoromethyl-lH-imidazol-2-yl)- 1-(2,6-dichloro-4-trifluoromethylphenyl)- lH-l,2,4-triazole, m.p. 154-156°. (Compound 4a).

In a similar manner,

(i) compound 3a gave 3-(5-bromo-4-cyano-lH-imidazol-2-yl)- 1-(2,6-dichloro-4-trifluoromethylphenyl)- lH-l,2,4-triazole, m.p. 85-87°. (Compound 4b).

(ii) compound 2b gave 5-(5-bromo-4-trifluoromethyl-

1-(2 ,6-dichloro-4-trifluoromethy1-phenyl)-lH-imidazol- 2-yl)-4-trifluoromethy1-2-pyridone, m.p. 251-253°. (Compound 4c) .

(iii) compound 2c gave 4-(5-bromo-4-trifluoromethyl- lH-imidazol-2-yl)-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-5-methylthio-lH-pyrazole, m.p. 175-177°. (Compound 4d) .

(iv) compound 3c gave 4-(5-bromo-4-cyano-lH-imidazol- 2-yl)-1-(2,6-dichloro-4-trifluoromethylphenyl)- 5-methylthio-lH-pyrazole, m.p. 227-9°. (Compound 4e) . Example 5

A mixture of 2-[(amino) (2,6-dichloro-4-trifluoromethyl- phenylhydrazono)methyl]-4 ,5-dicyano-lH-imidazole (0.7 g) , acetic anhydride (20 ml) and acetic acid (15 ml) was heated under reflux for 6 hours, poured into water, extracted with ether and the extract worked up to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-(4,5-dicyano- lH-imidazol-2-yl)-5-methyl-lH-l,2, -triazole. (Compound 5a) .

Preparation of starting material for compound 5a

A suspension of 2,6-dichloro-4-trifluoromethylphenyl- hydrazine (28 g) in acetic acid (150 ml) was added with stirring ^"to a mixture of aqueous glyoxal^~(40%; 225 g in water (750 ml) . The mixture was stirred for two hours and filtered to give crude (2,6-dichloro-4-trifluoromethyl- phenylhydrazono)acetaldehyde.

This product (10 g) was suspended in methanol (120 ml) and diaminomaleonitrile (3.8 g) added. The mixture was stirred at room temperature for 3% days and filtered. The solid was recrystallised from acetonitrile to give 2-amino- 3-[(2,6-dichloro-4-trifluoromethylphenylhydrazono)- ethylidenamino]maleonitrile, m.p. >150°.

This product (10.5 g) , nicotinamide (13.8 g) and N-chlorosuccinimide (7.5 g) in dimethylformamide (90 ml) was stirred at 55° for 10 minutes. The mixture was poured into water and the resulting solid was purified by column chromatography to give 2-[(chloro) (2,6-dichloro- 4-trifluoromethylphenylhydrazono)methyl]-4,5-dicyano- lH-imidazole, m.p. 207-8°.

This product (3 g) was treated with aqueous ammonia

(40 ml) and water (100 ml) , the mixture stirred for 5 minutes at room temperature, extracted with ethyl acetate and the extract dried and evaporated to give 2-[ (amino)- (2,6-dichloro-4-trifluoromethylphenylhydrazono)methyl]- 4,5-dicyano-lH-imidazole, m.p. 282-284°.

Example 6

A mixture of 5-[ (2-amino-l,2-dicyanoethenylimino)methyl]- 1-(2 ,6-dichloro-4-trifluoromethylphenyl)-4-trifluoro- methyl-2(lH)-pyridone, (0.5 g) , N-chlorosuccinimide (0.27 g) and nicotinamide (0.15 g) in dimethylformamide (15 ml) was stirred at 60° for 3 hours. The mixture was added to water, extracted with ethyl acetate and the extract worked up to give, after recrystallisation from ethyl acetate/ hexane to give 1-(2,6-dichloro-4-trifluoro¬ methylphenyl)-5-(4,5-dicyano-lH-imidazol-2-yl)- 4-trifluoromethy1-2-pyridone, m.p. 279-282°. (Compound 6a)

In a similar manner

(i) 4-[ (2-amino-l,2-dicyanoethenylimino)methyl]- 1-(2,6-dichloro-4-tri luoromethylphenyl)-3-methoxy- lH-pyrazole (starting material for compound lx) gave 5-chloro-l-(2,6-dichloro-4-trifluoromethylphenyl)-

4-(4,5-dicyano-lH-imidazol-2-yl)-3-methoxy-lH-pyrazole, m.p. 215°. (Compound 6b).

(ii) 4-[ (2-amino-l,2-dicyanoethenylimino)methyl]-

1-(2,6-dichloro-4-trifluoromethylphenyl)-3-difluoro- methoxy-lH-pyrazole gave 1-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-(4,5-dicyano-lH-imidazol-2-yl)- 3-difluoromethoxy-lH-pyrazole, m.p. 213-215°. (Compound 6c) .

Preparation of starting material for compound 6a A mixture of 1-(2,6-dichloro-4-trifluoromethylphenyl)- 5-formyl-4-trifluoromethyl-2-pyridone (1 g) and diaminomaleonitrile (0.27 g) and a trace of p-toluenesulfonic acid in methanol was stirred at room temperature for 4 hours. The mixture was evaporated and the residue recrystallised from ethyl acetate/hexane to give 5-[ (2-amino-l,2-dicyanoethenylimino)methyl]- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoro- methyl-2-pyridone, m.p. 246-248°.

Preparation of starting material for compound 6c In a similar manner to that used for the starting material to Compound lu, ethyl l-(2,6-dichloro-4-trifluoromethyl- phenyl)-3-hydroxy-lH-pyrazole-4-carboxylate was treated with chlorodifluoromethane to give l-(2,6-dichloro- 4-trifluoromethylphenyl)-3-difluoromethoxy-lH-pyrazole- 4-carboxylic acid, m.p. 106-108.5°.

This was reduced with zirconium tetrachloride/sodium borohydride to give 1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-difluoromethoxy-4-hydroxymethyl-lH-pyrazole, which was oxidised, using pyridinium dichromate, to l-(2j6-dichloro-4-trifluoromethylphenyl)-3-difluoro- methoxy-lH-pyrazole-4-carboxaldehyde, which itself was converted to 4-[(2-amino-l,2-dicyanoethenylimino)methyl]- 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-difluoro- methoxy-lH-pyrazole.

Example 7

Sodium (0.17 g) was dissolved in ethanol (15 ml) and ethyl cyanoacetate (0.84 g) was added with stirring. The mixture was stirred for 10 minutes at room temperature and then 2-[(chloro) (2,6-dichloro-4-trifluoromethylphenyl¬ hydrazono)methyl]-4,5-dicyano-lH-imidazole (1 g; prepared as described above - see preparation of starting material for compound 5a) was added. The mixture was stirred at room temperature for 40 minutes and poured into dilute hydrochloric acid. The solid was filtered off, dried and recrystallised from acetonitrile to give 5-amino- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-ethoxy- carbonyl-3-(4,5-dicyano-lH-imidazol-2-yl)-lH-pyrazole, m.p. 290-1°. (Compound 7a).

In a similar manner: a) using methylsulfonylacetonitrile, there was obtained 5- amino-1-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4 ,5-dicyano-lH-imidazol-2-yl)-4-methyl- sulfonyl-lH-pyrazole, m.p. >350°. (Compound 7b).

b) using malononitrile, there was obtained

5-amino-4-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4,5-dicyano-lJ-imidazol-2-yl)-lH-pyrazole, m.p. >350°. (Compound 7c) .

Example 8 A mixture of vinyl butyl ether (1.13 ml) and triethylamine (1.21 ml) in toluene (2 ml) was added dropwise to a stirred suspension of 2-[ (chloro) (2,6-dichl ro- ... , 4-trifluoromethylphenylhydrazono)methyl]-4 ,5-dicyano- 1H-imidazole (1.75 g) in toluene (3 ml) at 90°. The mixture was heated at this temperature for 3 hours, cooled and filtered. 2N Hydrochloric acid was added and the mixture extracted with ethyl acetate. The extract was worked up to give 1-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-3-(4,5-dicyano-lH-imidazol-2-yl)-lH-pyrazole, m.p. 175-8°. (Compound 8a).

In a similar manner, using propen-2-yl methyl ether, there was obtained 1-(2,6-dichloro-4-trifluoromethylphenyl)- 3-(4,5-dicyano-12-imidazol-2-yl)-5-methyl-lH-pyrazole, m.p. 198-9° (Compound 8b). Example 9

A solution of oxone (i.io g) in water (35 ml) was added to a solution of compound 4d (0.65 g) in methanol (35 ml) kept on an ice bath. The mixture was stirred at room temperature for 18 hours, poured into water and extracted with dichloromethane. The extract was worked up to give 4-(5-bromo-4-trifluoromethyl-lH-imidazol-2-yl)- l-(2,6-dichloro-4-trifluoromethylphenyl)-5-methyl- sulfonyl-lH-pyrazole, m.p. 174-176°. (Compound 9a).

Example 10

A mixture of compound lg (2.9 g) and lithium hydroxide hydrate (0.5 g) in water (60 ml) and tetrahydrofuran (6 ml) was stirred for 5 hours at room temperature. It was then acidified with 2M hydrochloric acid (10 ml) , extracted with ether and the extract worked up to give 3-carboxy-5-chloro-l-(2,6-dichloro-4-trifluoromethyl¬ phenyl)-4-(4,5-dicyano-lH-imidazol-2-yl)-lH-pyrazole, m.p. 225-7°. (Compound 10a).

Example 11 A mixture of compound 10a (2.01 g) and thionyl chloride (40 ml) was heated under reflux for 2 hours. Excess thionyl chloride was evaporated and the residue dissolved in tetrahydrofuran (20 ml) and added to aqueous ammonia (40 ml) . The mixture was stirred at room temperature for 15 minutes and water (200 ml) was added. The mixture was extracted with ethyl acetate and the extract worked up to give 3-carbamoyl-5-chloro-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-(4,5-dicyano-lH-imidazol-2-yl)- lH-pyrazole, m.p. 262-4°. (Compound lla). Example 12

A mixture of 2-[ (chloro) (2,6-dichloro-4-trifluoromethy1- phenylhydrazono)methyl]-4,5-dicyano-lH-imidazole (l g; prepared as described above - see preparation of starting material for compound 5a), potassium thiocyanate (2.87 g) and methanol (30 ml) was heated under reflux for 15 hours. It was the poured into water containing dilute hydrochloric acid and filtered. The solid was dried and recrystallised from acetonitrile and dried in vacuo to give 3-(2,6-dichloro-4-trifluoromethylphenyl)-

5-(4,5-dicyano-lH-imidazol-2-yl)-1,3,4-thiadiazol-2-imine, m.p. >300°. (Compound 12a).

Example 13

Compound 12a (0.6 g) was dissolved in acetic acid (15 ml) and saturated aqueous sodium nitrite (4 ml) was added dropwise. The mixture was stirred for 1 hour at room temperature and then poured into water, neutralised with 10% aqueous sodium hydroxide and filtered to give 3-(2,6-dichloro-4-trifluoromethylphenyl)-5-(4 ,5-dicyano- lH-imidazol-2-yl)-N-nitroso-l,3,4-thiadiazol-2-imine. This was suspended in xylene (50 ml) and the mixture heated under reflux for 2 hours, cooled and filtered. The solid was purified by silica gel column chromatography to give 3-(2,6-dichloro-4-trifluoromethylphenyl)-5-(4,5-dicyano- lH-imidazol-2-yl)-l,3,4-thiadiazol-2-one, m.p. 263-4°. (Compound 13a) .

Example 14

A mixture of compound 12a (0.6 g) and acetic anhydride (30 ml) was stirred for 5 hours at 80° and the overnight at room temperature. It was poured into water, the mixture stirred at room temperature for 30 minutes, filtered, the solid dried, heated with boiling acetonitrile, filtered and dried to give N-acetyl-3-(2,6-dichloro-4-trifluoro¬ methylphenyl)-5-(4,5-dicyano-lH-imidazol-2-yl)- l,3,4-thiadiazol-2-imine, m.p. 300°. (Compound 14a).

Example 15 Compound lg was reduced with lithium borohydride in a manner similar to that described in the preparation of the starting material for compound is, to give 5-chloro- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,5-dicyano- lH-imidazol-2-yl)-3-hydroxymethyl-lH-pyrazole, m.p. 186-8°. (Compound 15a) .

Example 16

Compound 15a was oxidised with pyridinium dichromate in a manner similar to that previously described to give 5-chloro-l-(2 ,6-dichloro-4-trifluoromethylphenyl)- 4-(4,5-dicyano-lH-imidazol-2-yl)-3-formyl-lH-pyrazole, m.p. 260-2°. (Compound 16a).

Example 17 —

Hydroxylamine hydrochloride (0.12 g) and sodium acetate (0.24 g) in water (5 ml) was added to a solution of compound 16a (0.8 g) in ethanol (20 ml) . The mixture was stirred for 4 hours at room temperature, solvent evaporated, and the residue extracted with ethyl acetate. The extract was dried and evaporated and the residue worked up to give 5-chloro-l-(2,6-dichloro-4-trifluoro- methylphenyl)-4-(4,5-dicyano-lH-imidazol-2-yl)-

3-hydroximinomethyl-lH-pyrazole, m.p. 216°. (dec). (Compound 17a) .

Example 18

Trifluoroacetic anhydride (0.08 g) was added to a solution of Compound 17a (0.16 g) and pyridine (0.11 g) in dioxane (5 ml) . with ice-cooling. The mixture was stirred at room temperature overnight, and then heated under reflux for 4 hours. It was diluted with 2M hydrochloric acid, extracted with ether and the extract worked up to give 5-chloro- 3-cyano-l-(2,6-dichloro-4-trifluoromethylphenyl)- 4-(4,5-dicyano-lH-imidazol-2-yl)-lH-pyrazole, m.p. 119-123°. (Compound 18a).

Example 19

In a manner similar to that described in Example 6,

3-[ (2-amino-l,2-dicyanoethenylimino)methyl]- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-methoxy- lH-pyrazole, (see preparation of starting material for compound It was reacted with N-chlorosuccinimide/ nicotinamide to give 5-chloro-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-(4 ,5-dicyano-lH-imidazol-2-yl)-4-methoxy- lH-pyrazole, m.p. 247-52° (Compound 19a) .

Example 20

In a manner similar to that described in the preparation of—the-star-ting -material for compound Hi, -reaction of tert-butyl nitrite/bromoform with

(i) Compound 7a gave 5-bromo-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-3-(4,5-dicyano-lH-imidazol-2-yl)-4-ethoxy- carbonyl-lH-pyrazole, m.p. 230-1° (Compound 20a) . and (ii) Compound 7c gave 5-bromo-l-(2,6-dichloro-4-trifluoro¬ methylphenyl)-4-cyano-3-(4,5-dicyano-lH-imidazol-2-yl)- lH-pyrazole, m.p. 330-1° (Compound 20b) .

Example 21

Triethylamine (1.4 g) was added dropwise to a stirred mixture of 2-[ (chloro) (2,6-dichloro-4-trifluoromethyl- phenylhydrazono)methyl]-4,5-dicyano-lH-imidazole (5.5 g) , fumaronitrile (2.1 g) , chloroform (100 ml) and silver acetate (2.5 g) . The mixture was heated under reflux 5 hours and then subjected to flash column chromatography to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano- 3-(4,5-dicyano-lH-imidazol-2-yl)-lH-pyrazole, m.p. 308-9° (Compound 21a) .

Example 22 tert-Butyl nitrite (3 ml) was added dropwise to a mixture of compound 7c (3 g) and copper (II) chloride (2 g) in acetonitrile (100 ml) . The mixture was stirred overnight at room temperature, poured into dilute hydrochloric acid and extracted with ethyl acetate. The extract was dried and evaporated and the residue worked up to give 5-chloro- 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-cyano- 3-(4,5-dicyano-lH^"-imidazol-2-yl)-lH-pyrazole, m.p. >300° (dec) (Compound 22a).

Example 23

An ethereal solution of compound ly was washed with saturated aqueous sodium hydrogen carbonate and the mixture worked-up to~giw-the sodium-sa±t^~σf-δ-^chloro- 1-(2 ,6-dichloro-4-trifluoromethylphenyl)-3-(4 ,5-dicyano- lH-i idazol^-ylJ-lH-pyrazole, m.p. 320°. (Compound 23a).

Example 24

A mixture of compound lz (2.15 g) and tetrabutylammonium fluoride (2.6 g) in tetrahydrofuran (50 ml) was stirred a room temperature for 20 minutes. It was poured into 2M hydrochloric acid and extracted with ether. The extract was dried and evaporated and the residue worked up to give 1-(2,6-dichloro-4-trifluoromethylphenyl)-3-(4,5-dicyano- lH-imidazol-2-yl)-4-hydroxy-lH-pyrazole, m.p. 136-140°. (Compound 24a) . Example 25

Compound 24 was brominated using N-bromosuccinimide in a similar manner to that described for the preparation of the starting material of Example In to give 5-bromo-

1-(2,6-dichloro-4-trifluoromethylphenyl)-3-(4,5-dicyano- lH-imidazol-2-yl)-4-hydroxy-lH-pyrazole, m.p. 136-9°.

(Compound 25a) .

Test Examples

Compounds are assessed for activity against one or more of the following:

Lucilia sericata (sheep blow fly) a) contact test (LS) b) systemic test (LSS) Boophilus icroplus (blue tick) a) injection test (BMI) Musca domestica (house fly) a) contact test (MD)

Blattella germanica (cockroach) a) contact test (BG) b) bait test (BGB) Helminths a) Trichostrongylus colubriformis (TC) b) Heligmosomoides polygyrus (HP)

The tests are carried out as follows:

(Lucilia sericata. - contact test

1 ml aliquots of acetone solutions or suspensions, containing test compound at various concentrations, are applied to cotton wool dental rolls (1 cm x 2 cm) , contained in glass vials 2 cm diameter x 5 cm long. After drying, the treated materials are then impregnated with 1 ml of nutrient solution, infested with approximately 30 first instar larvae of sheep blow fly (Lucilia sericata) , closed by a cotton wool plug and held at 25°C for 24 hours. The activity is then assessed in comparison to controls. Compounds are considered active if the LC₅₀ is less than 300 ppm.

(Lucilia sericata) - systemic test

100 mg of test compound are dissolved in 0.2 ml dimethyl sulfoxide and diluted with corn oil to the desired concentration. Approx 0.25 ml doses are fed to male mice, using 5 mice for each dose. 4 hours after treatment the mice are killed with carbon dioxide and the upper parts of hind legs removed and skinned. These are placed individually into sample tubes which are infested with first instar larvae of sheep blow fly (Lucilia sericata) , closed by a cotton wool plug and held at 25° for 24 hours. The activity is then assessed in comparison to controls. Compounds are considered active if the LC₅₀ is less than 100 mg/kg of mouse.

.Boophilus microplus)

Test compounds are dissolved in a suitable solvent to a desired concentration. Using a microapplicator, 2 microlitres of the solution are injected into the blood filled stomach of a tick (Boophilus microplus.. 5 replicate ticks are treated at each concentration and subsequently each tick is retained separately in partitioned petri dish held at 25°C and >80% R.H. , until mortality of ticks or fecundity and viability of eggs produced by survivors can be assessed. The percentage reduction in total reproductive capacity (i.e. the combined effects of adult mortality, reduced fecundity and mortality of eggs) is then recorded and compared with controls. Compounds are considered active if they result in at least 50% reduction of reproductive capacity at a concentration of 20 microgram/tick or less.

Musca domestica

Aliquots (0.7 ml) of acetone solutions or suspensions of test compounds at various concentrations are applied to filter papers (9 cm diameter) placed in the bottom of petri dishes (9 cm diameter) closed by glass lids. After evaporation of solvent, the treated surfaces, together with controls treated with acetone alone, are then infested with adult houseflies, (Musca domestica) and held at 22°C for 24 hours. The percentage mortality of the insects is then recorded. Compounds are considered active if the LC₅₀ is less than 1000 mg/m².

Blattella germanica - contact test

Aliquots (1 ml) of solutions or suspensions of test compounds in a suitable solvent at various concentrations are applied to glass plates (10cm x 10cm) . After evaporation of solvent, the treated surfaces, together with controls treated with solvent alone, are infested with approximately 10 first instar nymphs of the German cockroach, (Blattella germanica) , retained on the treated surface within PTFE-coated glass rings 6 cm in diameter and held for 24 hours at 25°C. The percentage mortality of the insects is then recorded. Compounds are considered active if the LC₅₀ is less than 100 mg/m².

Blattella germanica - bait test

First/second instar nymphs of the German cockroach,

(Blattella germanica) are placed on glass plates and retained within glass rings. The nymphs are fed a diet of the test peanut butter/flour bait containing the test compound at various concentrations. The percentage mortality of the insects after 6 days is then recorded. Compounds are considered active if the LC₅₀ is less than 1000 ppm.

Anthelmintic test a) Trichostrongylus colubriformis

Adult worms of the parasitic nematode Trichostrongylus colubriformis are cultured in multi-well plates containing sterile culture medium and test compound at a concentration of 100 ppm. The cultures are maintained in a sterile carbon dioxide incubator at 37°, at a constant air/carbon dioxide ratio of 95:5 (v/v). After 5 days the mortality is assessed in comparison with controls. Compounds are considered active if the LC₅₀ is less than 100 ppm.

b) Heligmosomoides polygyrus

Groups of five mice are infected orally with 100 infective stage larvae (L3) of the murine gastrointestinal nematode Heligmosomoides polygyrus. After six days the mice are orally dosed with 50 μl of the test compound at the desired concentration in a carrier solution containing 1% wetter and 0.05% ethyl cellulose. A control group receives carrier only. After 7 days the mice are killed and the small intestine examined for worm count. Compounds are considered active if they give >50% worm reduction compared with the controls at a rate of 100 mg/kg mouse body weight.

Activities were demonstrated as follows (+ = active) ,

Compound LS LSS BMI MD BG BGB TC HP

No

+ +

+ + + +

+ + + + + +

+ + +

+

+ + +

+

Compound LS LSS BMI MD BG BGB TC HP No

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Claims

1. A compound of formula I

where Z is a nitrogen containing heterocycle of formula

Z¹, z². z³, Z⁴ or Z⁵

(Z¹) (Z²)

Ar Ar

(Z³) (Z⁴)

Ar (Z⁵) and salts thereof, in which Ar is aryl; V¹ is N or CR⁹; V² is N or CR¹⁰;

W¹ is N or CR⁸;

W² is N or CR¹¹ ; except W¹ and W² are not both N; W³ is 0, S, NR⁴⁰ or -CR¹=CR⁴²-; X is 0 or S; Y is 0, S or NR¹²;

W⁴ is C or can also be S when Y is 0; A is S(0)_m, 0 or NR¹³;

R¹ and R² are hydrogen, optionally substituted alkyl, cyano, halogen or nitro; and R³ is hydrogen, optionally substituted alkyl, acyl, optionally substituted alkoxycarbonyl or sulfamoyl, R⁵ is hydrogen, halogen, optionally substituted alkyl, optionally substituted alkoxy, -NR¹⁶R¹⁷, cyano, nitro, S0₂NR¹⁶R¹⁷, CYNR¹⁶R¹⁷, COOR¹⁸ or R¹⁹S(0)_m; R⁴ and R¹⁰, which may be the same or different, are hydrogen, halogen, hydroxy, mercapto, cyano, nitro, optionally substituted alkyl, optionally substituted alkoxy, -NR¹⁶R¹⁷, -S0₂NR¹⁶R¹⁷, CHO, CH₂0H, COOR¹⁸ or R¹⁹S(0)_m; R⁶ is substituted alkyl, hydroxy, alkoxy, haloalkoxy, cyano, nitro, R¹⁹S(0)_m or an N-linked 5-membered heteroaryl group containing 1-4 nitrogen atoms; and when R⁵ is cyano, -CYNR¹⁶R¹⁷, -COOR¹⁸, optionally substituted alkoxy, nitro, -NR¹⁶R¹⁷ or S0₂NR¹⁶R¹⁷, R⁶ can also be hydrogen, halogen, alkyl or -NR¹⁶R¹⁷; R⁷, R⁸ and R¹¹, which may be the same or different, are hydrogen, halogen, optionally substituted alkyl or optionally substituted alkylthio; R⁹ is hydrogen, halogen, optionally substituted alkyl, formyl, optionally substituted alkoxy, aryl, cyano, nitro, hydroxy, trialkylsilyloxy, CYNR¹⁶R¹⁷, COOR¹⁸ or R¹⁹S(0)_m;

R¹² is hydrogen, optionally substituted alkyl or acyl; R¹³ is hydrogen, alkyl or acyl;

R¹⁶ and R¹⁷ are the same or different and are hydrogen, optionally substituted alkyl, acyl or aryl, or together with the nitrogen to which they are attached, form a 5 to 7 membered ring which can contain other hetero atoms; R¹⁸ is hydrogen or optionally substituted alkyl; R¹⁹ is optionally substituted alkyl;

R⁴⁰ is hydrogen, optionally substituted alkyl or acyl; R⁴¹ and R⁴², which may be the same or different, are hydrogen or optionally substituted alkyl; and when V¹ is CR⁹ and V² is CR¹⁰, R⁹ and R⁴ together with the carbon atoms to which they are attached can form a six membered ring; and when V¹ and V² are both N, R⁴ can form a sulfur, nitrogen or carbon containing bridge to an ortho carbon atom on Ar; m is 0, 1 or 2; and p is 0 or 1, when Z is Z¹ or Z²and is 0 when Z is Z³, Z⁴ or Z⁵.

2. A method of combating pests, especially insects, acarids or animal endoparasites, at a locus or host for the pest, infested or liable to be infested therewith, which comprises applying to the locus, host and/or the pest, a compound of formula I, as claimed in claim 1.

3. A pesticidal composition which comprises a compound a compound of formula I, as claimed in claim 1 in admixture with an agriculturally or veterinarily acceptable diluent or carrier.

4. A pharmaceutical composition which comprises a compound of formula I, as claimed in claim l in admixture with a pharmaceutically acceptable diluent or carrier.