GB2129000A

GB2129000A - Fungicidal azole compounds

Info

Publication number: GB2129000A
Application number: GB08328492A
Authority: GB
Inventors: Fritz Schaub
Original assignee: Sandoz AG
Current assignee: Sandoz AG
Priority date: 1982-10-28
Filing date: 1983-10-25
Publication date: 1984-05-10
Also published as: ES8504733A1; BR8305935A; PL244326A1; BE898070A; DK493583D0; PT77558A; JPS5998061A; CS786283A2; FI833859A0; GB2129000B; IL70058A0; FR2535321A1; KR840006479A; SE8305878D0; IT1172351B; NL8303651A; DE3337937A1; FR2535321B1; CS243477B2; LU85066A1

Abstract

Novel alpha -aryl- alpha -R1-1H-azole- ethanol compounds in which R1 is an halogenated cyclopropyl linked either directly or via an alkylene group to the alpha -carbon atom, are useful as plant fungicides and for treating fungus diseases in man and animals.

Description

SPECIFICATION Novel azole compounds The invention provides novel a-aryl-a-R1-1 H-i ,2,4-triazol-1 -ethanol and a-aryl-a-R1-1 H-imidazol-1-ethanol compounds in which R1 is an halogenated cyclopropyl linked either directly or via an alkyl to the a-carbon atom, and ethers and esters of such ethanols (hereinafter compounds of the invention), a process for the preparation of the compounds of the invention and their use.

The term a-carbon atom as used herein is intended to indicate the carbon atom of the ethanol moiety to which the R1 group, the aryl group and the hydroxy group are bound.

The a-aryl group of the compounds of the invention is suitably an aromatic hydrocarbon (preferably phenyl), unsubstituted or substituted, or an heteroaromatic ring linked via one of its ring carbon atoms (e.g.

a 5-or fi-membered ring with 1 or 2 heteroatoms selected from 0, N and S; preferably furyl, thienyl or pyridyl), unsubstituted or substituted.

Examples of particularly appropriate a-aryl groups are phenyl, unsubstituted or mono- or disubstituted by substituents selected from NO2; halogen; C1-5alkyl, C2-5alkenyl, C2-5alkinyl, C1-5alkoxy or C1-5alkylthio, unsubstituted or halogenated; phenyl or phenoxy, unsubstituted or substituted. Further examples of particularly appropriate a-aryl groups are heteroaromatic groups such as 3-pyridyl and 2-thienyl and 2-furyl unsubstituted or monosubstituted by halogen or C1-5alkyl (e.g. 5-CI-2-thienyi and 5-tert, butyl-2-furyl).

The a-aryl group is preferably phenyl, substituted by R2 und R3, wherein B2 and B3 are, independently, H; halogen; C1-5alkyl, C2 5-alkenyl, C2 5alkinyl, C1-5alkoxy or C1.5alkylthio unsubstituted or halogenated; phenyl or phenoxy, unsubstituted or substituted; or NO2.

Where B2 and/or R3 are or contain halogen this is e.g. F, Cl or Br. Examples of favourable phenyl substituents are CH3, Cl, Br, I, CH3O, C6H5, CF2O and C2H5, particularly CH3, CeHs and especially CI. In general the phenyl substituents are preferably in 2,4-position (e.g. 2,4-di-CI), more preferably in 4-position (monosubstitution). Where the hydroxy group of the compounds of the invention is etherified, such ethers are e.g. C1-5alkyl, C3-5 alkenyl, C3 5alkinyl or aralkyl ethers, such as methyl, allyl, propargyl or benzyl ethers; where such hydroxy group is esterified, the esters are e.g. esters of aliphatic carbon acids, such as the acetate.

The compounds of the invention contain one or more chiral centers. Such compounds are generally obtained in the form of racemic or diastereomeric mixtures. However, these and other mixtures can, if desired, be separated either completely or partly into the individual compounds or desired isomer mixtures by methods known in the art.

A preferred class of compounds of the inventions are therefore compounds of formula I

in which | R1, R2 and B3 are as defined above and Y is CH or N.

R1 is particularly a group G

in which X1 is H, F, Cl or Br (especially Cl or Br, particularly Cl) X2 is F, Cl or Br (especially Cl or Br, particularly Cl) R4, R5, R6, independently, are H, C1 5alkyl (e.g. Ch3) or halogen, A is CR7R8 or CR7R8-CHRg (whereby the CHRs group is tied to the halogenated cyclopropyl moiety) R7, R8, R9, independently, are H or C1 5alkyl (e.g. CH3), whereby R7 and R8 may also be linked to form a C3 6cycloalkyl and n is O or 1. X1 and X2 are preferably identical.

Suitably at least one of R7 and B8 is C1-5alkyl or CR7R8 is cycloalkyl. Where CR7R8 is cycloalkyl, this group contains preferably 3 to 5 ring carbon atoms. Where one or more of R4, B5 and B6 are halogen, this is preferably F, Cl or Br, particularly Cl or Br. Where any of R4, R5, R6, R7, B8 and Rg is C1-5alkyl, this is preferably CH3.

n is preferably 1.

The compounds of the invention are obtained by reaction of a compound of formula ll

in which M is H, a metal or a trialkylsilyl group and Y is as defined above, with the corresponding 2-aryl-2-B1-oxirane, in which R1 is as defined above, or a reactive derivative thereof, followed, if desired, by a etherification or esterification of the so-obtained ethanol compounds.

This process also forms part of the invention.

Where M is H in the formula 11, the reaction is preferably effected in the presence of a base.

The compounds of the invention may be obtained in free base form in salt form (in acid addition salt form, e.g. in hydrochloride form, or in alcoholate form, e.g. as Na-ethanolate), and in metal complex form, e.g. with a metal such as Cu or Zn, and with anions such as chloride, sulphate and nitrate.

The acid addition salts, alcoholates and the metal complexes may be obtained from the corresponding free form in conventional manner and vice versa.

The compounds of formula I are obtained by reacting a compound of formula Ill

wherein B1, R2 und R3 are as defined above, or reactive functional derivatives (hereinafter designated reactive derivatives) of such compounds, with a compound of formula II (as defined above), and where desired, subsequent etherification or esterification of the so obtained ethanol compounds.

The process of the invention may for example be effected, by reacting a 2-aryl-2-B1-oxirane (as defined above), e.g. a compound of formula Ill, with an azole of formula 11 as such (M=H) or in the form of its metal salt (M = metal), preferably as alkalimetal salt, e.g. as Na-salt, in a solvent which is inert under the reaction conditions, e.g. in dimethyl formamide, at a reaction temperature between ambient temperature and reflux temperature of the reaction mixture, or with an azole of formula II in which M is trialkylsilyl, e.g.

trimethylsilyl, in a solvent which is inert under the reaction conditions, e.g. in dimethylformamid, in the presence of catalytic amounts of a base such as NaH, conveniently with heating, preferably at 70-90"C.

The term "reactive derivatives" used in connection with the above defined 2-aryl-2-R1-oxiranes, such as the compounds of formula II, is intended to embrace any oxirane derivative that, by reaction with an azole, results in ethanol compounds of the invention. Various examples of such reactive derivatives are known to a person skilled in the art; a suitable example thereof are the corresponding halohydrines (wherein the halogen is e.g. Cl or Br).

The conditions at which the compounds of formula II may be reacted with reactive derivatives of the above defined 2-aryi-2-R1 oxiranes are also known per se. The reaction of a compound of formula II with the halohydrine derivative of a compound of formula Ill, can be effected under the conditions disclosed for the reaction with the oxirane compounds, conveniently, however, in the presence of an additional equivalent of a base.

Ester and ether derivatives of the ethanol compounds of the invention may be obtained according to known esterification or etherification procedures starting from the corresponding ethanols.

The compounds of the invention may be isolated from the reaction mixture and purified according to methods known per se.

The above defined 2-aryl-2-B1-oxirane compounds are novel. Suitable processes for their preparation are for example those analogous to the reactions indicated hereinafter for the preparation of compounds of formula III. Compounds of formula Ill may be obtained a) by treating the corresponding halohydrines with a base b) by reacting the corresponding ketones of formula IV

wherein R1, R2 and B3 are as defined above, with a compound of formula V

wherein n is O or 1 X is halogen or methylsulfate R13 is alkyl in the presence of a base (alkali metal hydride or hydroxide), with the aid of resp. analogous to known methods.Where B13 is C8 18alkyl, particularly straight C8 18alkyl, e.g. n-dodecyl, the compound of formula V may also serve as a phase transfer catalyst.

Compounds of formula IV may also be obtained according to known methods.

Compounds of formula IVa

wherein R2, R3, R4, R5, R6, A, X2 and n are as defined above and Xis F, Cl or Br, may be obtained by addition of the group; CX'1X2 (wherein X'1 and X2 are as defined above) to a compound of formula VI

wherein R2, R3, R4, R5, R6, A and n are as defined above, or starting from compounds of formula VII

wherein R2, R3, R4, R5, R6, A and n are as defined above and R1O is H or a protecting group of the OH group (e.g. a tetrahydropyranyl group) by addition of the CX'1X2 group (wherein X'1 and X2 are as defined above) to the double bound and subsequent oxydation of the alcohol function (optionally after splitting off the protecting group) to the keto group.The addition of the : CX'1X2 group and the oxydation may be effected analogous to known methods.

The carbenes of formula :CX'1X2 may for example be obtained by a) splitting off hydrohalogenide from trihalomethane with the aid of an alkalihydroxide (e.g. under the conditions of a phase transfer reaction) b) thermic desintegration (decarboxylation) of a trihaloacetate, e.g. a trihalosodium- oder triahalolithium acetate, at 800-120"C (e.g. in glyme- or diglyme-containing solvent mixtures).

c) thermic desintegration of C6H5HgCX3 (X is halogen), e.g. in benzene, under reflux.

The starting compounds of formula VI, wherein n is 1 and A is CR7R8-CHRg are for example obtained by alkylation of an acetophenone with an allylhalogenide, those of formula VII wherein (A)n is a covalent bound or CR7R8 and R1O is hydrogen are for example obtained by reaction of a vinyl- or allyl-Grignard-compound with an optionally substituted benzaldehyde.

Insofar as the preparation of the starting materials is not described, those are known or may be obtained according to resp. analogous to procedures described herein or to known procedures.

The compounds of the invention possess interesting biological, particularly antimycotic properties and are therefore indicated to be suitable for use as drug in the treatment of fungus diseases of humans and other animals. The antimycotic activity can be established by in vitro tests, e.g. the in vitro series dilution test on various families and species of mycetes, such as yeasts, mold fungi and dermatophytes at concentrations of about 0.05 to about 50,ug/ml and also by in vivo tests, e.g. by systemic, p.o. application of dosages of ca. 10 to 100 mg/kg body wight to mice which have been intra-vaginally infected with Candida albicans.

For the above mentioned use, the dose administered will, of course, vary depending on the compound employed, mode of administration and treatment desired. However, in general, satisfactory results are obtained when administered at a daily dosage of from 1 to 100 mg/kg of animal body weight, conveniently given in divided doses two to four times daily, or in sustained release form. For the larger mammals the corresponding daily dosage are in the range of from 70 to 2000 mg; dosage forms suitable for e.g. oral administration comprise from 17.5 to 1000 mg.

The compounds of the invention may be prepared and used in the free base form or in the form of pharmaceutically (resp. veterinary) acceptable salts (acid addition salts or alcoholates), metal complexes, ethers or esters. In general the salt forms exhibit the same order of activity as the free base forms. Acids that may be used in preparing acid addition salt forms include by way of illustration hydrochloric, hydrobromic, sulphuric, nitric, fumaric and naphthaline-1 ,5-disulphonic acids.

The compounds of the invention may be admixed with conventional pharmaceutically (resp. veterinary) acceptable inert carriers, and, optionally, other excipients. They may be administered in such internally administrable unit dosage forms as tablets or capsules, or alternatively be administered topically in such conventional forms as ointments or creams or parenterally. The concentrations of the active substance will, of course, vary depending on the compound employed, the treatment desired and the nature of the form etc.

In general, however, satisfactory results are obtained e.g. in topical application forms at concentrations of from 0.05 to 5, in particular 0.1 to 1 wt %.

The compounds of the invention may be used in a manner analogous to that known for the use of standard compounds, such as ketoconazol. Particularly the compounds of formula I wherein A is CR7R8-CHRg show useful pharmacological activity.

An appropriate daily dosage for a given compound of the invention will depend on various factors, e.g. its relative activity. This has for example been established for 2-(4-Chlorophenyl)-4-(2,2-dichlorocyclopropyl) 3,3-dimethyl-1 -(1 H-1 ,2,4-triazol-1 -yl)butan-2-ol at the model of the vaginal candidasis of the mouse and resulted in a recovery after oral application of 4 x 12.5 mg/kg body weight. The compounds of the invention may therefore be used in dosages analogous to that generally used for ketoconazol.

The compounds of the invention in free form or in agriculturally acceptable salt (acid addition salt or alcoholate) metal complex, ether or ester ester form are also useful as fungicides in the combatting of phytopathogenic fungi. Their advantageous fungicidal activity is established by in vivo tests with test concentrations of from about 0.0008 to 0.5% against Uromyces appendiculatus (bean rust) on pole beans, against other rusts fungi (such as Hemileia, Puccinia) on coffe, wheat, pelargonium, snapdragon, against Erysiphe cichoracearum on cucumber and against other powdery mildew fungi (E. graminis f.sp. tritici, E.

Graminis f.sp. hordei, Podosphaera leucotricha, Uncinula necator) on wheat, barley, apple, grapevine.

Further interesting activities are i.a. observed in vitro against Ustilago maydis with test concentrations of from about 0.8 to 200 ppm, in vivo against Rhizoctonia solani with test concentrations of from about 10 to 160 ppm (calculated per volume substrate). Since these tests indicate also a good plant tolerance and a good systemic action, the compounds of the invention are indicated for treatment of plant, seeds and soil to combat phytopathogenic fungi e.g. Basidiomycetes, Ascomycetes and Deuteromycetes, particularly, Basidiomycetes of the order Uredinales (rusts) such as Puccinia spp, Hemileia spp, Uromyces spp, Ascomycetes of the order Erysiphales (powdery mildew) such as Erysiphe spp, Podosphaera, spp, and Uncinula spp, as well as Phoma, Rhizoctonia, Helminthosporium.

The amount of compound of the invention to be applied, will depend on various factors such as the compound employed, the subject of the treatment (plant, soil, seed), the type of treatment (e.g. drenching, sprinkling, spraying, dusting, dressing), the purpose of the treatment (prophylactic or therapeutic), the type of fungi to be treated and the application time.

In general, satisfactory results are obtained, if the compounds of the invention are applied in an amount of from about 0.005 to 2.0, preferably about 0.01 to 1 kg/ha, in the case of a plant or soil treatment. The treatment can, if desired, be repeated, e.g. at intervals of 8 to 30 days. Where the compounds of the invention are used for seed treatment, satisfactory results are in general obtained, if the compounds are used in an amount of from about 0.05 to 0.5, preferably about 0.1 to 0.3 g/kg seeds.

The term soil as used herein is intended to embrace any conventional growing medium, whether natural or artificial.

The compounds of the invention may be used in a great number of crops, such as soybean, coffee, ornamentals (i.a. pelargonium, roses), vegetables (e.g. peas, cucumber, celery, tomato and bean plants), sugarbeet, sugarcane, cotton, flax, maize (corn), vineyards, pomes and stone fruits (e.g. apply, pears, prunes) and are particularly appropriate for use in cereals (e.g. wheat, oats, barley) especially in wheat.

Compounds of the invention particularly appropriate for agricultural use are compounds of formula I wherein (A)n is a covalent bond orthe group CR7R8. Other sub-groups of compounds of formula I having particularly useful fungicidal activity are i.a. such wherein X1 and X2 are bromine and such wherein (A)n is CH(C1.4alkyl)-CHB9 and/or such wherein R4 is C1.4-alkyl (e.g. OH3).

The invention also provides fungicidal compositions, comprising as a fungicide a compound of the invetion in free form, or in agriculturally acceptable salt, metal complex, ether or ester form in association with a agriculturally acceptable diluent. They are obtained in conventional manner, e.g. by mixing a compound of the invention with a diluent and optionally additional ingredients, such as surfactants.

The term diluents as used herein means liquid or solid, agriculturally acceptable material, which may be added to the active agent to bring it in an easier or better applicable form, resp. to dilute the active agent to a usuable or desirable strength of activity. Examples of such diluents are talc, kaolin, diatomaceous earth, xylene or water.

Especially formulations used in spray form, such as water dispersible concentrates or wettable powders, may contain surfactants such as wetting and dispersing agents, e.g. the condensation product of formaldehyde with naphthalene sulphonate, an alkylarylsulphonate, a lignin sulphonate, a fatty alkyl sulphate, an ethoxylated alkylphenol and an ethoxylated fatty alcohol.

In general, the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% fungicidally acceptable surfactant and from 10 to 99.99% diluent(s). Concentrated forms of composition, e.g. emulsion concentrates, contain in general from about 2 to 90%, preferable from between 5 and 70% by weight of active agent. Application forms of formulation contain in general from 0.0005 to 10% by weight of a compound of the invention as active agent. Typical spray-suspensions may, for example, contain 0.0005 to 0.05, preferably 0,001 to 0.02% by weight of active agent.

In addition to the usual diluents and surfactants, the compositions of the invention may comprise further additives with special purposes, e.g. stabilisers, desactivators (for solid formulations on carriers with an active surfact), agents for improving the adhesion to plants, corrosion inhibitors, anti-foaming agents and colorants. Moreover, further fungicides with similar or complementary fungicidal activity, or other beneficially-acting materials, such as insecticides may be present in the formulations.

Examples of the production of plant fungicide formulations are as follows: a. Wettable powder formulation 25 Parts of a compound of the invention are mixed and milled with 25 parts of synthetic fine silica, 2 parts of sodium lauryl sulphate, 3 parts of sodium lignin sulphonate and 45 parts of finely divided kaolin until the mean particle size is about 5 micron. The resulting wettable powder is diluted with water before use to a spray liquor, which may be applied by foliar spray as well as by root drench application.

b. Granules Onto 94.5 parts by weight of quartz sand in a tumbler mixer are sprayed 0.5 parts by weight of a binder (non-ionic tenside) and the whole thoroughly mixed. 5 Parts by weight of a compound of the invention are then added and thorough mixing continued to obtain a granulate formulation with a particle size in the range of from 0.3 to 0.7 mm. The granules may be applied by incorporation into the soil adjacent the plants to be treated.

c. Emulsion concentrate 25 Parts by weight of a compound of the invention are mixed with 10 parts by weight of an emulsifier and 65 parts by weight of xylene. The concentrate is diluted with water to the desired concentration.

d. Seed dressing 45 Parts of a compound of the invention are mixed with 1.5 parts of diamyl phenoldecaglycolether ethylene oxide adduct, 2 parts of spindle oil, 51 parts of fine talcum and 0.5 parts of colorant rhodamin B. The mixture is ground in a contraplex mill at 10,000 rpm until an average particle size of less than 20 microns is obtained. The resulting dry powder has good adherance and may be applied to seeds, e.g. by mixing for 2 to 5 minutes in a slowly turning vessel.

FINAL COMPOUNDS Example 1: 2-64-ChlorophenylJ-4-(2,2-dichlorocyclopropyl)-3,3-dimethyl- 1-(1H- 1,2,4-triazol- l-yl)butan-2-ol a) 5.1 g Dodecyl-dimethylsulfoniummethylsulfat are added to a solution of 3.0 g 1 -(4-chlorophenyl)-3-(2,2- dichlorocyclopropyl)-2,2-dimethylpropan-1 -one in 30 ml dry toluene at ambient temperature, and the mixture stirred for 15 minutes. To the resulting suspension are added 1.1 g pulverised KOH and the mixture stirred for 2 hours at 35 . After cooling the reaction mixture is poured onto ice and extracted with diethylether. The organic extracts are successively washed 3 times with water, then with saturated aqueous NaCI-solution; then the extracts are dried over MgSO4 and evaporated in vacuum.The residue is a colourless oil consisting of 50% of 2-(4-chlorophenyl)-2-[2-(2,2-dichlorocyclopropyl)-1,1-dimethyl- ethyl]oxirane and 50% dodecylmethyl-sulfide b) The crude oxirane reation product is added dropwise, within 10 minutes, to a mixture of 1.0 g 1,2,4-triazole that had been heated to 90 , and the mixture stirred for 18 hours while maintaining the reaction temperature at 90".

After cooling, the reaction mixture is poured onto ice and extracted with CH2C12. The organic extracts are successively washed with water and with saturated aqueous NaCI-solution, dried over MgSO4, and freed of the solvent by evaporation in vacuum. The title compound is obtained after chromatography on silica gel using first hexane fraction/ethylacetate (initially 9:1, then 1:1) and then ethylacetate as eluant and subsequent crystallisation from diethylether/hexane fraction in the form of colourless crystals of the m.p.

1 17-1230(diastereomeric mixture).

Example 2 Analogous to the procedure of Example 1, the following compounds of formula la

are obtained by reaction of an azole with the corresponding oxirane: Ex. Character No. R2 B3 (A)n X1/X2 R4 R5 R6 Y isation 2.1 4-Cl H - Cl/CI CH3 H H N 2 4-Cl H - Cl/CI CH3 H H CH 3 4-Cl H - Br/Br CH3 H H N 4 4-Cl H - Br/Br CH3 H H CH 5 4-Cl H - F/F CH3 H H N 6 4-Cl H - F/F CH3 H H CH 7 4-Cl H - F/Cl CH3 H H N 8 4-Cl H - F/CI CH3 H H CH 9 4-Cl H - Cl/Cl H H H N 10 4-Cl 2-Cl - Cl/CI H CH3 CH3 N 11 4-Cl 2-Cl Cl/Cl H CH3 CH3 CH 12 4-Cl H C(CH3)2 Cl/Cl H H H N Rf=0.24/EAc* 13 4-Cl H C(CH3)2 Cl/CI H H H CH 14 4-Cl H CH2 Cl/CI H H H N 15 4-Cl H CH2 Cl/CI H H H CH 16 4-Cl H CH(CH3) Cl/CI H H H N 17 4-Cl H CH(CH3) Cl/CI H H H CH 18 4-Cl H C(CH3)2-CH2 Cl/Cl H H H CH m.p. 140-55 19 4-Cl H C(CH3)2-CH2 Br/Br H H H N Rf=0.30/EAc* 20 4-Cl H C(CH3)2-CH2 Br/Br H H H CH 21 4-Cl H C(CH3)2-CH2 F/F H H H N 22 4-Cl H C(CH3)2-CH2 F/F H H H CH 23 4-Cl H CH2-CH2 Cl/CI H H H N 24 4-Cl H CH2-CH2 Cl/CI H H H CH Ex. Character No.R2 R3 (A)n X1/X2 R4 R5 R6 Y isation 25 4-Cl H C(CH3)2-CH2 Cl/Cl H H H N Rf=0.28/EAc** nD20=1.5598 26 4-Cl H C(CH3)2-CH2 Cl/Cl H H H CH 27 4-CI H CH(CH3)-CH2 Cl/CI Cl H H N 28 4-CI H CH(CH3)-CH2 Cl/CI Cl H H CH 29 4-CI H C(CH3)2-CH2 H/CI Cl H H N 30 4-CI H C(CH3)2-CH2 H/CI Cl H H CH 31 4-CI H C(CH3)2-CH2 Cl/CI CH3 H H N m.p. 100-8 )* * diastereomeric mixture - EAc = Ethylacetate ** mixture of isomers INTERMEDIATES Example 3 1-(4-(Chlorophenyl)-3-92,2-dichlorocyclopropyl)-2,2-dimethylpropan-1-one a) To a solution of 28 g pulverized KOH in 500 ml toluene are added within 30 minutes, at ambient temperature and with stirring, 45.6 g of 4-chlorophenyl-isopropylketone and thereafter 8.1 g tetrabutylammoniumbromide, whereby the inside temperature rises to 30 . After stirring for 2 hours 28.7 g allylchioride in 100 ml toluene are added dropwise at ambient temperature, and the mixture then stirred over night at room temperature. The mixture is poured onto ice water, extracted with ether, the combined organic extracts washed successively with water and saturated aqueous NaCI solution, dried over MgS04 and evaporated.

Fractional distillation of the remaining crude residue gives 1 -(chlorophenyl)-2,2-dimethyl-pent-4-en-1 -one as a colourless oil, bp. 95'/0.4 mmHg.

b) 500 g of a 50% aqueous NaOH solution are slowly added to a solution of 64 g 1-(4-chlorophenyl)-2,2dimethyl-pent-4-en-1-one in 500 ml CHCl3 at 0 and to that mixture are added portionwise, in 15 minutes, 5 g of triethylbenzylammoniumchloride (TEBA). When the addition is complete, the mixture is stirred for 8 hours at 0-5 and then, after dilution with 500 ml CHCl3, a further 18 hours at ambient temperature. The reaction mixture is poured onto ice, extracted with CH2CI2, the combined organic extracts then washed with water, dried over MgSO4 and evaporated in vacuum. The pure title compound is obtained by chromatography on silicagel with hexane fraction/diethylether (1-3%). Rf = 0.23 on silicagel thin layer plates, using hexane fraction/diethylether 96:4 as eluant.

Example 4 Analogous to the procedure of Example 3b), the following compounds of formula IVa are obtained by reaction of dihalocarbenes with the corresponding unsaturated compounds of formula VI: Cpd. B2 R3 (A)n X1/X2 R4 R5 R6 Rf Eluant 4.1 4-CI H C(CH3)2CH2 Br/Br H H H 0.34 HX/EAc(1) 95:5 4.2 4-Cl H CH(CH3)CH2 Cl/CI H H H 0.31(2) HX/EAc 9:1 4.3 4-Cl H C(CH3)2 Cl/CI H H H 0.29 HX/EAc 9::1 (1) HX/EAc = hexane fraction/ethyl acetate (2) diastereomeric mixture Example 5 4-Chlorophenyl-12,2-dichloro- 1-meth ylcycloprop yl)-ketone To a solution of 7.0 g 1-(4-chlorophenyl)-2-methyl-prop-2-en-1-one in 70 ml chloroform are slowly added, at 0 , with vigorous stirring, 16 g 50% aqueous NaOH solution, followed by 4.3 g triethylbenzylammonium chloride. When the addition is complete, the cooling bath is taken away until a strong exothermic reaction is starting. The reaction is then cooled again, such that the reaction temperature is kept initially for one hour at 34-40 and then decreases slowly to ambient temperature. After a reaction time of 5 hours, the mixture is poured onto ice and then extracted with diethylether. The organic extracts are unified, washed with water, dried over MgSO4 and evaporated in vacuum. The residue is chromatographed on silica gel with hexane fraction/diethyiether 9:1 to give the title compound having a nD20=1.5689 and an Rf value of 0.24 (thin layer chromatography) when using hexane fraction/diethylether 9:1 as eluant.

Claims

1. Novel α-aryl-α-R1-H-1,2,4-triazol-1-ethanol and α-aryl-α-R1-1H-imadazol-1-ethanol compounds in which R1 is an halogenated cyclopropyl linked either directly or via an alkyl to the carbon atom in free form and in acid addition salt, alcoholate, metal complex, ether and ester form thereof.

2. A compound according to Claim 1, which is of formula I

in which R1 is as defined in Claim 1 R2 and R3, independently, are H; halogen, Ca.5 alkyl, C25-alkenyl, C2.5alkinyl, C1 5alkoxy or C15alkylthio unsubstituted or halogenated; phenyl or phenoxy unsubstituted or substituted; or NO2 and Y is CH or N, in free form or in acid addition salt, alcoholate, metal complex, ether or ester form.

3. A compound according to Claim 2, wherein R1 is a Group G

in which X1 is H, F, Cl or Br (especially Cl or Br, particularly Cl) X2 is F, Cl or Br (especially Cl or Br, particularly Cl) R4, R5, R6, independently, are H, C1-5alkyl (e.g. CH3 or halogen, A is CR7R8 or CR7R8-CHRg (whereby the CHRs group is tied to the halogenated cyclopropyl moiety) R7, R8, P9, independently, are H or C1.salkyl (e.g. CH3), whereby R7 and R8 may also be linked to form a C36cycloalkyl and n is 0 or 1.

4. The compound of Claim 3 which is 2-(4-chlorophenyl)-4-(2,2-dichlorocyclopropyl)-3,3-dimethyl-1-(1H- 1,2,4-triazol-1-yl)butan-2-ol.

5. The compound of Claim 3, wherein R2, R3, (A)n, R4 R5, R6, X1, X2 and Y are: a) 4-CI, H, C(CH3)2-CH2, H, H, H, Br, Br and N resp.

b) 4-CI, H, CH(CH3)-CH2, H, H, H, Cl, Cl and N resp.

c) 4-CI, H, covalent bound, CH3, H, H, Cl, Cl and N resp.

d) 4-CI, H, C(CH3)2, H, H, H, Cl, Cl and N resp.

6. A process for preparing a compound as defined in any one of Claims 1 to 5, which comprises reacting a compound of formula II

in which M is H, a metal or a trialkylsilyl group and Y is as defined in Claim 2, with the corresponding 2-aryl-2-P1-oxirane, in which R1 is as defined in Claim 1, or with a reactive functional derivative of such oxirane, followed if desired by an etherification esterification of the thus obtained ethanol compounds, and recovering the thus obtained compounds in free form or in the form of an acid addition salt, an alcoholate or a metal complex.

7. A compound as stated in Claim 1, whenever obtained by a process claimed in Claim 6.

8. A plant fungicidal composition comprising a compound according to any one of Claims 1 to 5 and 7 in free form or in agriculturally acceptable salt, metal complex, ether or ester form and an agriculturally acceptable diluent.

9. A method of combatting phytopathogenic fungi which comprises applying to the locus thereof a fungicidally effective amount of a compound claimed in any one of Claims 1 to 5 and 7 in free form or in agriculturally acceptable salt, metal complex, ether or ester form.

10. A pharmaceutical or veterinary composition which comprises a compound according to any one of Claims 1 to 5 and 7 in free form or in a pharmaceutically or veterinary acceptable salt, metal complex, ether or ester form thereof and a pharmaceutically or veterinary acceptable diluent or carrier.

11. A compound according to any one of Claims 1 to 5 and 7 in free form or in a pharmaceutically or veterinary acceptable salt, metal complex, ether or ester form for use as a pharmaceutical.

12. A method of treatment of mycosis in man or animal which comprises administering to the man or animal an effective amount of a compound as claimed in any one of Claims 1 to 5 or 7 in free form or in pharmaceutically or veterinary acceptable salt, metal complex, ether or ester form.