GB2142921A

GB2142921A - Triazole derivatives

Info

Publication number: GB2142921A
Application number: GB08417088A
Authority: GB
Inventors: Maximilian Grassberger; Fritz Schaub
Original assignee: Sandoz AG
Current assignee: Sandoz AG
Priority date: 1983-07-08
Filing date: 1984-07-04
Publication date: 1985-01-30
Also published as: GB8417088D0; BR8403366A; BE900063A; DE3423782A1; GR82244B; DK335684A; SE8403590L; PT78859B; IT8448509A0; LU85451A1; NL8402002A; SE8403590D0; IL72323A0; ES534099A0; FR2548665A1; ES8507516A1; PT78859A; ZA845239B; HUT36990A; IT1199152B

Abstract

alpha -Aryl- alpha -R1-1H-1,2,4-triazole-1-ethanols, in which R1 is an olefenic group bearing in the 1-position at the most 1 H-atom and having its double bond in the 2- or 3-position and ethers and esters thereof, are useful as plant fungicides and for treating fungus diseases in man and animals. The compounds may be of the formula:- <IMAGE> wherein R1 is as defined above, and R2 and R3, independently, are H; C1-5alkyl, C2-5alkenyl or C1-5alkoxy, unsubstituted or halogenated; phenyl or phenoxy, unsubstituted or substituted; NO2 or halogen, or are ethers and esters thereof, in free form or in acid addition salt, alcoholate or metal complex form.

Description

SPECIFICATION Novel azole compounds The invention relates to a-a-disubstituted-1 H-azole-1-ethanols.

The invention provides novel a-aryl-a-R1-1 H-1 ,2,4-triazole-i -ethanols, wherein R, is an olefinic group bearing in the 1-position of the a-carbon atom at most 1 H-atom and having its double bond in the 2- or 3-position of the a-carbon atom, and ethers and esters thereof (hereinafter compounds of the inventions).

The invention provides also processes for the preparation of the compounds of the invention, the use of these compounds and compositions comprising such compounds.

The a-aryl group of the compounds of the invention is conveniently an aromatic hydrocarbon (e.g. naphthyl, preferably phenyl) unsubstituted or substituted, or an heteroaromatic ring linked via one of its ring carbon atoms (e.g. a 5- or 6-membered ring with 1 or 2 heteroatoms from the group 0, N and S, preferably furyl, thienyl or pyridyl), unsubstituted or substituted.

Examples of suitable a-aryl groups are phenyl, unsubstituted or mono- or disubstituted by substituents selected from NO2; halogen; C1 5alkyl, C2 5alkenyl, C, 5alkoxy, C1 5haloalkyl, C2 5ha- loalkenyl and C1 5haloalkoxy; phenyl or phenoxy, unsubstituted or substituted. Further examples of suitable a-aryl groups are the heteroatomatic 3-pyridyl group and 2-thienyl and 2-furyl unsubstituted or monosubstituted by halogen or lower alkyl (e.g. 5-CI-thienyl and 5-tert.-butyl-2 furyl).

The a-aryl group is preferably phenyl substituted by R2 and R3 whereby R2 and R3 independently are H; halogen; lower alkyl, lower alkenyl or lower alkoxy, unsubstituted or halogenated; phenyl or phenoxy, unsubstituted or substituted; or NO2.

The term "lower" is used herein in its generally accepted sense indicating that the upper number of carbon atoms is limited, conveniently to 5, preferably to 4 carbon atoms.

Any halogen substituent in the compounds of the invention is conveniently selected from F, Cl and Br.

A preferred subclass of compounds of the invention includes compounds of formula I

wherein R1, R2 and R3 are as defined above, and esters and ethers of such ethanol compounds.

The olefinic group R1 may be straight or branched; it may be aliphatic, bear cycloalkyl- or phenyl-groups resp. can contain additional C-C multiple bonds; any ramifications may be saturated or contain an olefinic and/or an acetylenic (triple) bond.

Any phenyl group of R, may be substituted, particularly mono- or disubstituted. Examples of suitable substituents of such phenyl groups are halogen, lower alkyl, lower alkoxy, lower haloalkyl (e.g. CH2CI, CF3), lower haloalkoxy (e.g. OCF3, OCHF2). Where the olefinic group (R1) is branched, such ramifications may be linked together to form a cycloaliphatic group (3- to 7-, particularly 3- to 6-membered); The olefinic (double) bond may thereby be incorporated in the cycloaliphatic system (to form a cycloalkyl group which is at least 5 membered).

The carbon atoms of the olefinic (double) bond as well as these of any additional aliphatic C-C-multiple bonds may be substituted by halogen (particularly Cl, preferably Br); in such case preferably only 1 of the carbon atoms of the double bond is monohalogenated; the halogen is then preferably tied to the carbon atom which is most distant from the a-carbon atom.

Where the hydroxy group of the compounds of the invention is etherified, such ethers are particularly C, 5alkyl, C3 5alkenyl, C3 5alkinyl or aralkyl ethers (e.g. benzyl ether), preferably methyl-, allyl- or propargyl ethers (whereby the latter may be halogenated at their double or triple bond); where the hydroxy group is esterified, such esters are particularly of aliphatic carboxylic 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, diastereomeric and/or cis/trans mixtures. However, such mixtures can, if desired, be separated either completely or partly into the individual compounds or desired isomer mixtures by methods known in the art.

R, is particularly a group A CR4R5(CHR6)nCR7 = CR8Rg A wherein n is O or 1, R4, R6 and R8, independently, are H, C1-8alkyl, C3 7cyclo- alkyl, C3-7cycloalkyl-C1-5alkyl; phenyl unsubstituted or substituted, or phenyl-C1-5alkyl unsubstituted or substi tuted in its phenyl moiety, R5 is C1-8alkyl or C3 8alkenyl, R7 is H, halogen (especially chlorine or bromine), C-18- alkyl, C3 7cycloalkyl, C3 7cycloalkyl-C, 5alkyl; phenyl u nsubstituted or substituted or phenyl-C1-5alkyl unsubstituted or substituted in its phenyl moiety, and R9 is H, C1-8alkyl, C3 8alkinyl (especially C#C-tert.C4H9 or halogen (especially chlorine or bromine), whereby R4 and R5 together may be (CH2)2-6, R6 and R8 together may be (CH2)2 4 and R7 and R8 together may be (CH2)2-5.

In the group A preferably not more than 2, more preferably not more than 1 of the symbols R4, R6, R7 and R8 is C3 7cycloalkyl, C3-7cycloalkyl-C1-5alkyl, phenyl (unsubstituted or substituted) or phenyl-C, 5alkyl (unsubstituted or substituted in its phenyl moiety); where 1 or 2 of the symbols R4, R6, R7 and R3 are such a cyclic group, this is preferably R4 and/or R8, more preferably R4.

Where R4 and R5 together are (CH2)2-6, this is preferably (CH2)2-4.

Where R5 is C38alkenyl, the double bond is conveniently not in the 1-position.

Preferred subgroups of A have 1 or more of the following features: R6 is H or C1-8alkyl or, together with R8 is (CH2)2-4; R7 is H or C1-8alkyl or, together with R8 is (CH2)2-5; R8 is H or C1-8alkyl or, together with R6 or R7 is(CH2)2-4 or (CH2)2-5 resp.; R9 is H, Cl, Br, C1-4alkyl or C#C-tert.C4H9; R4 is H, C1 8alkyl or, together with R5 is (CH2)2-6; n is O, R7, R8 and R9 are H or C1-8alkyl; n is O, R4 and R5 are each C1-8alkyl or together are (CH2)2, R7 and R8 are H or C1-8alkyl and R9 is H, C1-8alkyl Cl or Br; n is 0, either R4 is H or C1-8alkyl and R5 is C1-8alkyl or R4 and R5 together are (CH2)2-6, and R7 is H; n is 1, either R4 is H or C1-8alkyl and R5 is C1-8alkyl or R4 and R5 together are (CH2)2 6, and R6, R7, R8 and R9 are H or C1-8alkyl; n is 1, R4 is H or C1-8alkyl and R5 is C1-8alkyl; n is 1, R4 is H or C1-8alkyl, R5 is C1-8alkyl, R8 together with R6 or R7 is(CH2)2-4 or (CH2)2-5 resp., the remaining substituent (R7 or R6 resp.) being H; n is 1, and at least 2 of RB, R7 and R9 are H; R8 and R8 are H or C1-8alkyl, R7 is H and R9 is H, C1-8alkyl, Cl or Br; R6 and R7 as well as one of R8 and R9 are H, either R4 is H or C1-8alkyl or R5 is C1-8alkyl or R4 and R5 together are (CH2)2-6.

Insofar as otherwise not stated, any Alkyl group has preferably 1 to 4, more preferably 1 or 2 carbon atoms; any cycloalkyl group in the compounds of the invention is preferably 3 to 6membered.

The compounds of the invention are prepared by reaction of a compound of formula II

wherein M is H, a metal or a trialkylsilyl group, with a 2-aryl-2-R1-oxirane compound, wherein R1 is as defined above, or a reactive functional derivative thereof, followed, where desired, by the introduction of a chlorine or bromine substituent at one of the C-atoms of the double bond of R1 in the 2- or 3-position and/or by etherification or esterification of the hydroxy group.

The compounds of formula I are accordingly obtained by the following processes comprising a) reacting a compound of formula Ill

wherein R1, R2 and R3 are as defined above, or a reactive functional derivative thereof, with a compound of formula II, b) obtaining a compound of formula la,

wherein R2, R3 and R4 are as defined above, either R5' is C, 8alkyl or R4 and R5' together are (CH2)2B, R7' is H or phenyl unsubstituted or substituted, and X, is chlorine or bromine, by splitting off HX, from a compound of formula IV

wherein X1, R2, R3, R4, R5' and R7' and n are as defined above.

The process of the invention according to variante a) can be effected under conditions analogous to that known for the preparation of azole-1-ethanols by reaction of an azole with an oxirane.

Where in formula Il M is H, the reaction with the oxirane compound is suitably effected in the presence of a base.

Where in formula II M is a metal, it is preferably an alkalimetal, e.g. Na.

Where in formula II M is trialkylsilyl e.g. trimethylsilyl the reaction is conveniently effected in the presence of a base such as NaH.

The process of the invention is conveniently effected in a solvent which is inert under the reaction conditions, e.g. in dimethylformamide. A suitable reaction temperature is between ambient temperature and reflux temperature of the reaction mixture; where in the formula II M is trialkylsilyl it is conveniently higher than ambient temperature, e.g. between 70 and 90"C.

The term "reactive functional derivative" used in connection with the above 2-aryl-2-R,oxiranes, such as the compounds of formula Ill, is intended to embrace any oxirane derivative that, by reaction with an azole of formula II 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. CI or Br).

The conditions at which the compounds of formula li may be reacted with the reactive derivatives of the above defined 2-aryl-2-R,-oxiranes are also known per se. The reaction of a compound of formula II with the halohydrine derivative of a compound of formula lli, 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.

The splitting off of HX, according to variante b) of the process of the invention may be effected under basic conditions, e.g. using NaH in an organic solvent which is inert under reaction conditions, such as dimethylformamide. The reaction is conveniently carried out with heating, e.g. at 40 to 80"C.

Depending on the significance of the substituents in the dihalogenated side chain of the compounds of formula IV--and insofar as R7' is Ha portion of the compounds of formula IV may also result in compounds of formula I in which the halogen X, is tied to the other olefinic C-atom which is closer to the carbinol group (position isomers of compounds of formula lea).

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

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 can exist in free base form, in salt form, e.g. as acid addition salt with an organic or inorganic acid such as hydrochloride, or as alcoholate e.g. as Na ethanolate, and in metal complex form, e.g. with a metal from the groups lb, lla, llb, VIb, Vllb and VIII of the periodic table, such as copper and zinc, and with anions such as chloride, sulphate and nitrate. The salt forms and metal complex forms may be obtained from the corresponding free forms according to known procedures, and vice versa.

The starting materials may be obtained according to known procedures. Examples of some of such procedures are given below. Depending on the meaning of the substituents, other procedures may be more appropriate.

The compounds of formula Ill may be obtained a) from the corresponding halohydrines by treatment with a base b) from the corresponding ketones of the formula V

wherein R1, R2 and R3 are as defined above by treatment with a compound of formula VI

wherein m is O or 1 X is halogen or CH3SO4 R3 is alkyl, in the presence of a base (alkalimetal-hydroxide or -hydride), under conditions or analogous to conditions known from the literature. Where R,3 is C8 ,8alkyl, particularly straight C8 ,8alkyl, e.g.

n-dodecyl, the compound of formula VI may also serve as phase transfer catalyst.

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 in free form or in-the form of pharmaceutically (resp.

veterinary) acceptable salt or metal complex form 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. applications of dosages of ca. 3 to 100 mg/kg body weight to rats which have been intra-vaginally infected with Candida albicans.

For the above mentioned use, the dose administered will, of course, vary depending on the relative activity of the compound employed, the mode of administration and the treatment desired. Test results with e.g. 1 -bromine-4-(4-chlorophenyl)-3, 3-dimethyl-5-( 1,2, 4-triazol- 1 -yl) pent-1-en-4-ol at the model of the vaginal candidasis of the rat indicate that the dosages to be applied will be analogous to that generally recommended for ketoconazole. In general, satisfactory results will be obtained when internally administered at a daily dosage of from 3 to 100 mg/kg of animal body weight, conveniently given in divided doses two to four times daily, or in sustained release form. For larger mammals having an approximate body weight of 70 kg the corresponding daily dosage are for example in the range of from 200 to 2000 mg; dosage forms suitable for e.g. oral administration comprise then from 50 to 1000 mg of active ingredient.

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) or metal complexes. 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 used in a manner analogous to that known for the use of standard compounds, such as ketoconazol. 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. With topical application forms satisfactory results are in general obtained at concentrations of from 0.05 to 5, in particular 0.1 to 1 wt.%.

The compounds of the invention in free form or in agriculturally acceptable salt (acid addition salt or alcoholate) or metal complex 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 0.00005 to 0.05% against Uromyces appendiculatus (bean rust) on pole beans, against other rusts fungi (such as Hemileia, Puccinia) on coffee, 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 10 to 1 60 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, and of the order Pleosporales such as Venturia spp; as well as Phoma, Rhizoctonia, Helminthosporium, Pyricularia, Pellicularia (= Corticium), Thielaviopsis and Stereum spp.

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; e.g. 0.04 to 0.125keg of active ingredient (a.i.) per ha in crops such as cereals, or concentrations of 1 to 5 g of a.i. per hl in crops such as fruits, vineyards and vegetables (at an application volume of from 300 to 1000 I/ha---depending on the size or leaf volume of the crop--which is equivalent to an application rate of approximately 10-50 g/ha).

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. apple, pears, prunes) and are particularly appropriate for use in cereals (e.g. wheat, oats, barley, rice) and in apples.

Particularly the compounds of formula I having one or more of the following features possess valuable biological properties: R2 is 4-CI R3 is H or 2-CI R4 is H or CH3, particularly CH2 RB is CH3 RB, R7 and RB are H R9 is H, Cl or Br n is 0.

So show the compounds no. 1, 35, 34 and 33 hereinafter, and particularly the latter, valuable biological activity.

The invention also provides fungicidal compositions, comprising as a fungicide a compound of the invention in free form, or in agriculturally acceptable salt or metal complex form in association with an agriculturally acceptable diluent (hereinafter 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 usable 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% by weight fungicidally acceptable surfactant and from 10 to 99.99% by weight diluent(s).

Where desired, such formulations may be further diluted prior to the application. Concentrated forms of composition, e.g. emulsifiable concentrates, contain in general from about 2 to 90%, preferably from between 5 and 70% by weight of active agent. Application forms of formulation contain in general from 0.00005 to 10% by weight of a compound of the invention as active agent. Atypical spray-suspensions may, for example, contain 0.0005 to 0.05, preferably 0.001 to 0.02% e.g. 0.001, 0.002 or 0.005% 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. stabilizers, desactivators (for solid formulations, on carriers with an active surface), agents for improving the adhesion to plants, corrosion inhibitors, anti-foaming agents and colorants. Moreover, further fungicides with similar or complementary fungicidal activity, e.g. sulfur, chlorothalonil, dithiocarbamates such as mancozeb, maneb, zineb, propineb, trichloromethane-sulphenylphthalimides and analoges such as captan, captafol and folpet, benzimidazoles such as benomyl. or other beneficially-acting materials, such as insecticides may be present in the formulations.

Examples of plant fungicide formulations are as follows (parts are by weight): a) Wettable Powder Formulation 10 Parts of a compound of the invention are mixed and milled with 4 parts of synthetic fine silica, 3 parts of sodium lauryl sulphate, 7 parts of sodium lignin sulphonate, 66 parts of finely divided kaolin and 10 parts of a diatomaceous earth 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 to the plants to be treated.

c. Emulsion Concentrate 10 Parts by weight of a compound of the invention are mixed with 10 parts by weight of an emulsifier and 80 parts by weight of isopropanol. 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.

The following examples further illustrate the present invention. All temperatures are in centigrade. Rf values are on silica-gel.

FINAL COMPOUNDS Example 1: 2-(4-Chlorophenyl)-3, 3-dimethyl- '-(1,2, 44riazol- 1-yl)-hex-5-en-2-ol Step 1 5.6 9 1-(4-Chlornphenyl)-2,2-dimethyl-pent-4-en-1one are added to 68 ml toluene. Thereto are added 12.9 g dodecyldimethylsulfonium-methylsulfate and the mixture is stirred during 10-15 minutes. To the so obtained suspension are added 2.8 g finely pulverized KOH. This mixture is stirred for 22 hours at 35 , poured onto ice and extracted with ether. The organic extract is washed 3 times with water and then with saturated aqueous NaCI soludion (brine), dried over MgSO4 and concentrated by roto-evaporation.The thus obtained residue is a colourless oil, containing 50.5% of 2(4-chlorophenyl)-2-(1,1-dimethyl-3-butenyl)-oxirane (according to gaschromatographic determination), beside dodecyjmethylsulfide.

Step 2 To 1.6 g 1,2,4-Triazole in 31 ml dimethylformamide (DMF) are added 5.8 g K2CO3 and the mixture heated at 90" inside temperature. Thereto are added, within 10 minutes, 9.6 g of the impute (50.5%) oxirane reaction product of step 1, and this mixture is stirred for 18 hours at 90". The reaction mixture is then cooled to room temperature, taken up in CH2CI2 and washed 3 times with water. The organic phase is dried over MgSO4, evaporated (by roto-evaporation) and stripped of the remaining DMF under high vacuum. The residue is recrystallized from CH2CI2/Hexane to give the pure title compound in the form of white crystals, m.p. 87-89".

Following the procedure of Example 1, employing the appropriate starting material of formula Ill, the following compounds of formula I are obtained.

Compound No. R1 R2 R3 Rf/m.p. 1 C(CH3)2-CH2-cH-CH2 4-C1 H 87-89 2 C(CH3)2-CH2-C(CH3)CH2 4-C1 H 83-84o(1) 3 ,C(CH3)2-CH2-CH.CH-CH3 4-C1 H 6l-63(2) 4 CH(CH3)-CH=CH2 2-C1 4-C1 l02-l04cA)/ 135-137((B)(3) 5 C(CH3)2-CH2-CH=CH-CoC-t.C4H9 4-C1 H HCl::1150 (decamp.) 6 G CH2-CH' CH2 4-C1 H 7 C(CH3)2-CH2-C(CH3).CH2 4-F H 8 C(CH3)2-CH2-CH.C(CH3)2 4-C1 H 9 C(CH3)2-a 4-C1 H 10 C(CH3)2-CH2-a 4-C1 H 11 C(CH3)2-CH2-CH=CHeFC1 4-C1 H 12 C(CH3)2-CH2-CC1sCH2 4-C1 H 13 C(CH3)2-CH2-CBr=CH2 4-C1 H 14 C-CH2-CH.CH2 4-Cl H 15 CH(CH3)-CH2-CH.CH2 4-C1 H 250 16 CH(CH2-CH'CH2)2 4-C1 H oCH -CHsCH 17 CH 2 2 4-C1 H CH -"',C6H5 18 -CHECH2-C(CH3)CH232 4-C1 H 74-760 19 CH(4F-C6H5)CH2-CH-CH2 4-Cl H CH3 20 C(C6H5)-CH2-CH"CH2 4-C1 H 22.4.-dicl-C6H3) 21 CH 4-C1 H oCH2-C(CH3)sCH2 22 oCH2-(4-cH3o-c6H4) 4-C1 H CH sCH2-C(CH3)sCH2 23 C(CH3)2-CHsCH2 4-C1 2-C1 24 C(CH3)2-C(CH3).CH2 4-C1 H 25 C(CH3)2-CH.CH-CH3 4-C1 H 26 C(CH3)2-CH.C(CH3)2 4-Cl H 27 CH(CH3)-CHCH2 4-C1 H 28 CH(C2N5)-CH.CH2 4-C1 H 29 ,,'C(CH3).CH2 4-Cl H CK sCH2-C(CH3)aCH2 30 CH(C6H5)-CH-CH2 4-C1 H 31 CH(CH2C6Hs)-C(CH3)=CH2 4-C1 H 32 C(CH3)2-CH.CH2 H 4-C1 92-95 33 C(CH3)2-CH.CHBr 4-C1 H 104-1060 34 C(CH3)2-CH=CHC1 4-C1 H 114-1160 35 CH(CH3)-CHsCHBr 4-C1 2-C1 155-1610

(1) Purification by chromatography on silicagel with hexane/ethyl acetate (9:1), and pure ethyl acetate.

Crystallisation from CH2CI2/Hexane (colourless crystals).

(2) As under (1); crystallisation however from hexane.

(3) Diastereomeric forms A and B from the corresponding diastereomeric starting material.

Example 2: 1 -Bromo-4-(2, 4-dichlorophenyl)-3-methyl-5-( 1,2, 4-triazol- 1 -yl)pent- 1 -en-4-ol To 1 g 4-(2,4-dichlorophenyl)-3-methyl-5-(1,2,4-triazol-1-yl)pent-1-en-4-ol in 20 ml of CHCI3 is added with cooling (using ice water) and stirring a solution of 0.5 g Br2 in 3 ml CHCl3. The mixture is allowed to warm-up to room temperature, evaporated under vacuum and the residue taken up in 10 ml dry DMF. After the addition of 77 mg NaH, the mixture is stirred for 20 hours at 60" and poured into water.This mixture is extracted with ethyl acetate, the organic phase is evaporated to dryness, the resulting residue purified by chromatography on silicagel with ethyl acetate and recrystallized from CHCl3/diisopropyl ether (m.p. 155-161").

Following the procedure of Example 2, employing the appropriate starting material, compound No. 33 (m.p. 104-106") may be obtained. Compound No. 33 is however preferably prepared according to the process of Example 1.

INTERMEDIATES A. 5-Chloro-4-(2, 4.dichlorophenyl)-3-methyl-pent- 1 -en-4-ol: a,2,4-Trichlornacetophenone is reacted with crotylbromide to give a diastereomeric mixture that is separated by chromatography on silica-gel with toluene/hexane (1:1).

Diastereomer A: Rf = 0.34 B: Rf = 0.45 B. 1 -(4-Chlorophenyl)-2, 2-dimethyl-pent-4-en- 1-one To a reaction mixture of 28 g pulverized KOH in 500 ml toluene are added, at room temperature, with stirring, within 30 minutes 45.6 g of 4-chlorophenyl-isopropyl ketone and then 8.1 9 tetrabutylammoniumbromide, whereby the inside temperature rises to 30". After 2 hours of stirring 28.7 g of allylchloride in 100 ml toluene are added. The mixture is then stirred overnight at room temperature, poured into ice water, extracted with ether, the organic phase washed with water and brine, dried over MgSO4 and evaporated. Fractional distillation of the crude residue gives the title compound as a colourless oil, b.p. 95'/0.4 mmHg.

C. 1 -(4-Chlorophenyl)-2, 2, 4-trimethyl-pent-4-en- 1-one A solution of 36 g 4-chlorophenyl-isopropyl ketone in 40 ml DMF is added dropwise, under a blanket of N2, to a suspension of 129 80% NaH in 30 ml DMF and the mixture is stirred further for 2 hours at 40". Thereto is added dropwise, innert 1 5 minutes and at room temperature, a solution of 36.2 g of 3-chloro-2-methyl-1-propene in 40 ml of DMF and the mixture stirred a further hour. After the addition of water, the reaction mixture is taken up in ether, washed with water and brine, dried over MgSO4 and evaporated. Fractional distillation of the crude residue gives the title compound as a colourless oil, b.p. 104-1 1O"/0.4 mmHg.

D. 1 -(4-Chlorophenyl)-2, 2,8,8, -tetramethylnon-4-en-6-yn- 1-on is obtained analogous to B. using 4-chlorophenyl-isopropyl-ketone and 1-bromo-6,6-dimethylhept-2-en-4-yne as starting materials.

E. (E)- 1 -(4.Chlorophenyl)-2, 2-dimethyl-hex-4-en- 1-one is obtained analogous to C. using (E)-1-bromo-2-butene instead of 3-chloro-2-methyl-1propene.

F. 1 -(4-Chlorophenyl)-2, 2-dimethylbut-3-en- 1-one is obtained by alkylation of 1-(4-chlorophenyl)-2-methylbut-3-en-1-one with iodomethane according to the procedure of C.

G. 4-Bromo- 1 -(4-chlorophenyl)-2, 2-dimethylbut-3-en- 1-one is obtained by Br2 addition to 1-(4-chlorophenyl)-2,2-dimethylbut-3-en-1-one followed by splitting off HBr from the Br-addition product.

USE-FUNGICIDAL ACTIVITY 1. Laboratory test The interesting fungicidal activity of the compounds of the invention is illustrated by the following test results with Compound No. 1.

Fungus Plant EC 90" Mildew Erysiphe cucumber 7 Erysiphe wheat 6 Podosphaera apple 15 Uncinula grape 8 Rust Uromyces bean 2 Puccinia triti wheat 25 * concentration of the spray liquor in ppm allowing 90% control of fungal disease (after spray application until the run-off).

Particularly favourable activity is observed in these tests after treatment with Compound No.

33.

2. Field Experiments 2.1 Mildew control in wheat Wheat infested with Erysiphe graminis is treated with a spray liquor comprising Compound No. 1 as active ingredient (a.i.) at a concentration of 300 mg a.i./l spray liquor. A spray volume of 500 I/ha is applied. The treatment allows a significant control of the mildew infestation.

2.2 Rust control in wheat When infested with Puccinia striiformis (yellow rust) is treated with a spray liquor comprising Compound No. 1 at a concentration of 100 mg a.i./l spray liquor. A spray volume 1000 I/ha is applied. The treatment allows a significant control of the rust infestation.

Claims

1. Novel a-aryl-a-R1-1 H-1 ,2,4-triazole-1 -ethanols, wherein R is an olefinic group bearing in the 1-position of the a-carbon atom at most 1 H-atom and having its double bond in the 2- or 3position of the a-carbon atom, and ethers and esters thereof, in free form or in acid addition salt, alcoholate or metal complex form.

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

wherein R1 is as defined in Claim 1, and R2 and R3, independently, are H; C1 5alkyl, C2 salkenyl or C1 5alkoxy, unsubstituted or halogenated; phenyl or phenoxy, unsubstituted or substituted; NO2 or halogen, and ethers and esters thereof, in free form or in acid addition salt, alcoholate or metal complex form.

3. A compound according to Claim 2, in which R1 is a group A CR4RB(CHRB)nCR7 = CR8Rg A wherein n is O or 1, R4, R6 and Re, independently, are H, C1-8alkyl, C3 7cyclo- alkyl, C3-7cycloalkyl-C1-5alkyl; phenyl unsubstituted or substituted, or phenyl-C1-5alkyl unsubstituted or substit tuted in its phenyl moiety, R5 is C1-8alkyl or C3-8alkenyl, R7 is H, halogen, C1.8- alkyl, C3 7cycloalkyl, C3-7cycloalkyl-C1-5alkyl; phenyl unsubstituted or substituted or phenyl-C1-5alkyl unsubstituted or substituted in its phenyl moiety, and R9 is H, C1-8alkyl, C3-8alkinyl or halogen, whereby R4 and R5 together may be (CH2)2.6, Re and Re together may be (CH2)2 and R7 and R8 together may be (CH2)2-5.

4. A 1 H-i ,2,4-triazole-1 -ethanol according to Claim 3 wherein n isO, R2 is 4-CI, R3 is H or 2-CI, R4 is H or CH3, R5 is CH, R7 and R8 are H and R9 is H, CI or Br.

5. A compound according to Claim 4, which is a) 1 -bromo-4-(4-chlorophenyl)-3,3-dimethyl-5-(1,2,4-triazol-1-yl)pent-1-en-4-ol or b) 1-chloro-4-(4-chlorophenyl-3,3-dimethyl-5-(1,2,4-triazol-1-yl)pent-1-en-4-ol, c) 1-bromo-4-(2,4-dichlorophenyl)-3-methyl-5,2,4-triazol-1-yl)pent-1-en-4-ol.

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

wherein M is H, a metal or a trialkylsilyl group, with a 2.aryl.2.R1-oxirane compound, wherein R1 is as defined in Claim 1, or a reactive functional derivative thereof, followed, where desired, by the introduction of a chlorine or bromine substituent at one of the C-atoms of the double bond of R1 in the 2- or 3-position and/or by etherification or esterification of the hydroxy group, and recovering the thus obtained compound in free form or in the form of an acid addition salt, an alcoholate or a metal complex.

7. A process according to Claim b tor preparing a compound ot tormula I as detained In Claim 2, comprising a) reacting a compound of formula Ill

wherein RX, R2 and R3 are as defined in Claim 2, or a reactive functional derivative thereof, with a compound of formula II, b) obtaining a compound of formula la,

wherein R2, R3 and R4 are as defined in Claims 2 and 3, either R5' is C1alkyl or R4 and R5' together are (CH2)2 6, R7' is H or phenyl unsubstituted or substituted, and X1 is chlorine or bromine, by splitting off HX1 from a compound of formula IV

wherein X1, R2, R3, R4, R5' and R7' are as defined in this claim and Claims 2 and 3.

8. A process according to Claims 6 and 7 substantially as described herein by way of Example.

9. A product by a process according to Claim 6, 7 or 8.

10. A plant fungicidal composition comprising a compound according to Claims 1 to 5 and 9 in free form or in agriculturally acceptable acid addition salt, alcoholate or metal complex form and an agriculturally acceptable diluent.

11. 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 9 in free form or in agriculturally acceptable acid addition salt, alcoholate or metal complex form.

12. A pharmaceutical or veterinary composition which comprises a compound according to any one of Claims 1 to 5 and 9 in free form or in a pharmaceutically or veterinary acceptable acid addition salt, alcoholate or metal complex form thereof and a pharmaceutically or veterinary acceptable diluent or carrier.

1 3. A compound according to any one of Claims 1 to 5 and 9 in free form or in a pharmaceutically or veterinary acceptable acid addition salt, alcoholate or metal complex form for use as a pharmaceutical.

14, 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 9 in free form or in pharmaceutically or veterinary acceptable acid addition salt, alcoholate or metal complex form.