LU85066A1 - NOVEL ETHANOL DERIVATIVES, THEIR PREPARATION AND THEIR USE AS FUNGICIDES - Google Patents

Description

v *

The present invention relates to new ethanol derivatives, their preparation and their use as fungicides to combat phytopathogenic fungi and for the treatment of fungal infections in humans and animals.

The invention relates in particular to the a-aryl-a-Ri-1H-1,2,4-triazole-1-ethanols and the a-aryl-oc-Ri-1H-imidazole-1-ethanols in which Ri represents a halogenated cyclopropyl group linked to the carbon atom a either directly or via an alkyl group, as well as their ethers and esters. These compounds will be designated in the present description, the compounds of the invention.

The expression “carbon atom a” in the present description designates the carbon atom of the ethanol residue to which the R 1, aryl and hydroxy groups are linked.

The α-aryl group of the compounds of the invention is advantageously an aromatic hydrocarbon group, preferably a phenyl group, unsubstituted or substituted, or a ring. heteroaromatic linked by one of its cyclic carbon atoms, for example a 5 or 6-membered ring having 1 or 2 heteroatoms chosen from 0, N and S, preferably a furyl, thienyl or pyridyl group, unsubstituted or substituted.

As an example of a particularly suitable a-aryl group, mention may be made of the phenyl group optionally carrying one or two substituents chosen from halogens, NO2, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C2-alkoxy. Unsubstituted or halogenated C1-C5 and C1-C5 alkylthio, and unsubstituted or substituted phenyl and phenoxy groups. As other examples of suitable a-aryl groups, mention may be made of heteroaromatic groups such as the 3-pyridyl, 2-thienyl and 2-furyl groups which are unsubstituted or monosubstituted by a halogen or by a C1-C5 alkyl group, for example the 5-chloro-2-thienyl and 5-tert.butyl-2-furyl groups.

The a-aryl group is preferably a phenyl group substituted by R2 and R3, where R2 and R3 each signify, independently of one another, hydrogen, halogen, a \ * 2, $ C4 alkyl group -C5, C2-C5 alkenyl, C2-C5 alkynyl, C1-C5 alkoxy or C1-C5 unsubstituted or halogenated alkylthio, an unsubstituted or substituted phenyl or phenoxy group, or NO2.

When R2 and / or R3 signify or contain a halogen, it is for example F, Cl or Br. As examples of suitable substituents of the phenyl group, mention may be made of CH3, Cl, Br, I, CH3O, C6H5, CF3O and C2H5, preferably CH3, C6H5 and especially Cl. In general, the substituents of the phenyl group are preferably located in position 2, 4 (for example 2,4-di-Cl), more preferably in position 4 (monosubstitution).

When the hydroxy group of the compounds of the invention is etherified, these ethers are, for example, C1-C5 alkyl, C3-C5 alkenyls, C3-C5 alkynyls or aralkyl ethers, such as methyl, allyl, propargyl or Benzyl; when this hydroxy group is esterified, these esters are for example derivatives of aliphatic carboxylic acids, such as acetates.

The compounds of the invention contain 1 or more centers of chirality. Such compounds are generally obtained in the form of racemic mixtures or diastereoisomers. These mixtures can, if necessary, be completely or partially separated into individual compounds or desired mixtures of isomers according to known methods.

A class of preferred compounds includes those corresponding to the formula I fi jj OH 'R2

Ri ^ 3 ", 11 in which Ri, R2 and R3 have the meanings given above and Y represents CH or N.

Rl preferably represents a group G

I "“ * 35 - * “(G) r5 * 3 - * in which Χχ represents H, F, Cl or Br, especially Cl or Br, in particular Cl, X2 represents F, Cl or Br, especially Cl or Br, in particular Cl, 5 R4, R5, R6 each represent, independently of each other, H, a C1-C5 alkyl group, for example CH3, or a halogen, A represents a residue CR7R8 or CR7R8-CHRg, the remainder CR7R8 -CHR9 being linked to the halogenated cyclopropyl residue 10 by the carbon atom carrying the substituent Rg, R7, R8> r9 each represent, independently of each other, H or a C1-C5 alkyl group, for example CH3, R7 and Rs can also be linked to form a C3-C6 cycloalkyl group, 15 and n signifies 0 or 1.

Xl and X2 are preferably identical.

At least one of the substituents R7 and Rs advantageously signifies a C1-C5 alkyl group or else CR7R8 signifies a cycloalkyl group.

When CR7R8 signifies a cycloalkyl group, this group preferably contains from 3 to 5 cyclic carbon atoms.

When one or more substituents R4, R5 and Rβ signify a halogen, it is preferably F, Cl or Br, in particular Cl or Br. When any of the substituents R4, R5 "r6" R7. R8 and Rg signify a C1-C5 alkyl group, it is preferably CH3.

n preferably means 1.

The invention also relates to a process for the preparation of these compounds, a process in which a compound of formula II is reacted

O

Μ (Π) 35

V

4 4

_ ** S

in which M represents H, a metal or a trialkylsilyl group and Y has the meaning given above, with a corresponding 2-aryl-2-Ri-oxirane, in which Ri has the meaning given above, or with a reactive derivative of this compound, and, if necessary, the ethanolic compounds thus obtained are etherified or esterified.

When M represents H in formula II, the reaction is preferably carried out in the presence of a base.

The compounds of the invention may be in the form of the free base, the salt or the metal complex. By salt is meant an addition salt with an acid, for example the hydrochloride, or an alcoholate, for example sodium alcoholate. The metal complex is a complex for example with a metal such as Cu or Zn, and with anions such as chlorides, sulfates and nitrates. The acid addition salts, the alcoholates and the metal complexes can be obtained according to the usual methods from the corresponding free form, and vice versa.

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

CH, j “Ri (ni) ή £ R3 in which Ri, R2 and R3 have the meanings given above, or one of its reactive functional derivatives, hereinafter designated 30 reactive derivatives, with a compound of formula II such as defined above, and, if necessary, by etherifying or then esterifying the ethanolic compounds thus obtained.

The process of the invention can for example be carried out by reaction of a 2-aryl-2-Ri-oxirane as defined above,

V

* 5 's for example a compound of formula III, with an azole of formula II as such (M = H) or in the form of a metal salt (M = metal), preferably in the form of an alkali metal salt, for example of a sodium salt, in a solvent inert under the reaction conditions, for example in dimethylformamide, at a reaction temperature between room temperature and the reflux temperature of the reaction mixture, or with an azole of formula II in which M is a trialkylsilyl group, for example trimethylsilyl, in an inert solvent under the reaction conditions, for example in dimethylformamide, in the presence of catalytic amounts of a base such as NaH, advantageously by heating to a temperature preferably between 70 and 90 ° C.

The term "reactive derivatives" used in connection with the above-defined 2-aryl-2-Ri-oxirans, such as the compounds of formula III, includes any oxirane derivative which, upon reaction with an azole, forms the ethanolic compounds of the invention.

- Various types of these reactive derivatives are known to those skilled in the art; as an appropriate example, mention may be made of the corresponding halohydrins in which the halogen is for example Cl or Br.

The conditions under which the compounds of formula II can react with the reactive derivatives of the 2-aryl-2-Ri-oxiranes defined above, are also known per se. The reaction of the compound of formula II with the halohydrin of the compound of formula III can be carried out under the conditions indicated for the reaction with the oxirane compounds, but preferably in the presence of an additional equivalent of a base.

The esters and ethers of the compounds of the invention can be obtained by known methods of esterification and etherification from the corresponding ethanolic compounds.

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

The 2-aryl-2-Ri-oxirannes defined above are new compounds. The methods suitable for their preparation are, for example, analogous to those indicated below for the preparation of the compounds of formula III.

The compounds of formula III can be obtained according to known methods a) by treatment of the corresponding halohydrins with a base,

5 b) by reaction of the corresponding ketones of formula IV

ÿ> The

10 in which Ri, R2 and R3 have the meanings given above, with a compound of formula V

X © (V) CH, - * SC 3

3 \ D

K13 in which n signifies 0 or 1 X represents a halogen or a methyl sulphate group, and R13 represents an alkyl group, in the presence of a base, such as an alkali metal hydride or hydroxide. When R13 represents a Cß-C18 alkyl group, in particular a Cg-C18 straight chain alkyl group, for example an n-dodecyl group, the compound of formula V can also serve as a phase transfer catalyst.

The compounds of formula IV can also be obtained by known methods.

The compounds of formula IVa X’i h r2 _ ° 2 - (A) n-Ç — CR5R6 (IVa) 30 R3 * S- / R4

in which R2, R3, R4, R5 "R6, A, X2 and n have the meanings given above and X'i represents F, Cl or Br, can be obtained by addition of the group: CX'1X2 (in which X ' i and X2 have the meanings given above) has a compound of formula VI

* 7 ^ 10 “C- <A) n-CVCR5R6 R3 (VI) 5 in which R2, R3, R4, R5, Rß, A and n have the meanings given above,

or starting from compounds of formula VII

R2 <0HH '(A) "' CVCR5R6 10RI0 (VII) in which R2, R3, R4, R5, Rß, A and n have the meanings given above and Rio represents H or a protective group of the OH group, for example a tetrahydropyrannyl group, by addition of the group: CX "1X2 on the double bond and subsequent oxidation of the alcohol function to carbonyl group optionally after removal of the protective group. The addition of the group: CX ^ 1X2 and the oxidation can be carried out according to known methods.

The carbenes of formula: CX'1X2 can, for example, be obtained a) by elimination of hydrohalic acid from a trihalomethane using an alkali hydroxide, for example under the conditions of a reaction of phase transfer, b) by thermal decomposition (decarboxylation) of a trihaloacetate, for example a sodium or lithium trihaloacetate, at a temperature between 80 ° C and 120 ° C, for example in mixtures of solvents containing glyme or diglyme (dimethyl ethers of ethylene glycol and diethylene glycol), c) by thermal decomposition of CßHßHgCXs, where X is halogen, for example in benzene, at reflux.

The starting materials of formula VI, in which n signifies 1 and A represents the group CR7R8-CHR9, are obtained for example by alkylation of an acetophenone with a halide

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* 8 of allyl, and those of formula VII, in which (A) n represents a covalent bond or CR7R8 and Rio represents hydrogen, are obtained for example by reaction of a vinyl or al 1ylic Grignard compound with a benzaldehyde possibly substituted.

When the preparation of the starting materials is not described, these are known or can be obtained by methods analogous to the known methods or to those described in the present application.

The compounds of the invention have valuable biological properties, in particular antifungal properties and can therefore be used therapeutically for the treatment of fungal infections in humans and animals. This antifungal activity can be demonstrated by in vitro tests, for example by serial dilution tests on various families and species of fungi, such as yeasts, molds and dermatophytes, at concentrations of between approximately 0.05 and approximately 50 pg / ml, and also by in vivo, for example systemic, tests by oral administration of doses of between approximately 10 and 100 mg / kg to mice to which an intravaginal infection has been transmitted. with Candida albicans.

Thanks to these properties, the compounds of the invention can be used as antifungals. For their use, the dose administered will naturally depend on the compound used, the mode of administration and the treatment desired. However, satisfactory results are generally obtained when the compounds of the invention are administered at a daily dose of between approximately 1 and 100 mg / kg, advantageously in divided doses 2 to 4 times per day, or in a release form. delayed. In human therapy the corresponding daily dose will be between 70 and 2000 mg of active substance; the appropriate unit doses for oral administration include, for example, between 17.5 and 1000 mg of active substance.

The compounds of the invention can be prepared and used in the form of a free base or in the form of salts (salts \ 9.

/ addition of acids or aloolates) or metal complexes, acceptable from the pharmaceutical or veterinary point of view. In general, the salts have the same order of activity as the free bases. Examples of acids which can be used for the preparation of acid addition salts include hydrochloric, hydrobromic, sulfuric, nitric, fumaric and naphthalene-1,5-disulfonic acid.

The invention therefore relates to the compounds of the invention, in the form of a free base or of pharmaceutically or veterinary acceptable salts or metal complexes, for use as medicaments, in particular as antifungals. The invention also relates to a medicament containing, as active substance, a compound of the invention in the form of a free base or of a salt or of a metal complex acceptable from the pharmaceutical or veterinary point of view.

As medicaments, the compounds of the invention can be used in the form of pharmaceutical or veterinary compositions containing the active substance in combination with inert pharmaceutical or veterinary acceptable carriers or diluents and, optionally, with other excipients. Such compositions also form part of the present invention. The compounds of the invention may be administered internally in the form of tablets or capsules, or be applied locally in the form of ointments or creams, or alternatively be administered in a form suitable for the parenteral route. The concentrations of active substance will naturally vary depending on the compound used, the treatment desired and the mode of administration chosen. In general, however, satisfactory results are obtained for example by topical application at concentrations of between 0.05 and 5, in particular between 0.1 and 1% by weight.

The compounds of the invention can be used in a manner analogous to that known for the use of known compounds such as ketoconazole. The compounds of formula I in which A represents a group CR7R8-CHR9 have a particularly advantageous pharmacological action.

The appropriate daily dose for a given compound of the invention will depend on various factors, i.e., its relative activity. This has for example been established for 2- (4-chlorophenyl) -4- (2,2-dichlorocyclopropyl) -3,3-dimethyl-l- (1H-1,2,4-triazole-1-yl) butane -2-ol in the vaginal candidiasis model in mice, healing appeared after oral administration of 4 x 12.5 mg / kg. The compounds of the invention can therefore be used in doses analogous to those generally used for ketoconazole.

The compounds of the invention, in free form or in the form of salts (addition salts of acids or alcoholates) or of metal complexes acceptable in agriculture, are also useful as fungicides for combating phytopathogenic fungi. Their advantageous fungicidal effect has been demonstrated in in vivo tests at concentrations between about 0.0008 and 0.05¾ against Uromyces appendiculatus (bean rust) on row beans, against other rust fungi ( such as Hemileia, Puccinia) on coffee, wheat, geranium, snapdragons, against Erysiphe cichoracearum on cucumber and against other powdery mildew (E.

graminis f.sp. tritici, E. Graminis f.sp.hordei, Podosphaera leucotricha, Uncinula necator) on wheat, barley, apples, vines. Other interesting effects have been observed among others in in vitro tests against Ustilago b \ il 'ί 11 maydis at concentrations between approximately 0.8 and 200 ppm, and in vivo against Rhizoctonia solani at concentrations between approximately 10 and 160 ppm (calculated by volume of substrate). Since these tests also indicate good plant tolerance and good systemic action, the compounds of the invention are suitable for the treatment of plants, seeds and soil for combating phytopathogenic fungi such as Basidiomycetes, Ascomycetes and Deuteromycetes , in particular Basidiomycetes of the order Uredinales (rust) 10 such as Puccinia spp, Hemileia spp, üromyces spp, Ascomycetes of the order of Erysiphales (powdery mildew) such as Erysiphe spp, Podosphaera spp, and üncinula spp, as well as Phoma, Rhizoctonia, and Helminthosporium.

The amount of compound of the invention to be applied will depend on various factors such as the compound used, the type of treatment (plants, soil, seeds), the method of treatment (for example watering of the soil or the plant, spraying, dusting, seed treatment), the objective of the treatment (prophylactic or therapeutic), the type of fungi to be combated and the time of application.

In general, satisfactory results are obtained by applying the compounds of the invention at doses of between approximately 0.005 and 2.0, preferably between approximately 0.01 and 1 kg / ha, in the case of a treatment for plants. or ground. The treatment can, if necessary, be repeated, for example at intervals of 8 to 30 days. When the compounds of the invention are used to treat seeds, satisfactory results are generally obtained by using the compounds at doses of between approximately 0.05 and 0.5, preferably between approximately 0.1 and 0.3 g per 30 kg of seeds.

\ 12 The expression soil, as used below, designates any usual culture medium, natural or artificial.

The compounds of the invention can be used on a large number of cultivated plants, such as soybeans, coffee, ornamental plants (such as geraniums, roses), vegetables (for example peas, cucumbers, celery, tomatoes and beans), sugar beet, sugarcane, cotton, flax, corn, grapevine, pome and stone fruits (such as pears and plums), and are particularly suitable for cereals (such as wheat, oats, barley), especially wheat .

The compounds of the invention particularly suitable for use in agriculture are the compounds of formula I in which (A) n is a covalent bond or the group CR7R8. The other subgroups of compounds of formula I having a particularly advantageous fungicidal effect are, inter alia, those in which Χχ and X2 represent bromine and those in which (A) n represents CH (C1-C6 alkyl -CHRg and / or those in which R4 represents a C1-C4 alkyl group, for example CH3.

A subject of the present invention is also fungicidal compositions comprising, as active material, a compound of the invention in free form or in the form of a salt or metal complex acceptable in agriculture, in combination with a diluent acceptable in agriculture. These compositions can be obtained according to the usual methods, for example by mixing a compound of the invention with a diluent and optionally with other ingredients such as surfactants.

The term diluent as used below denotes a liquid or solid material acceptable in agriculture which can be added to the active material respectively to transform it

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13 in a simpler or more easily applicable form, or to dilute it in order to obtain a desirable or usable activity. Examples of such diluents include talc, kaolin, diatomaceous earth, xylene and water.

The formulations used in the form of a spray, such as concentrates dispersible in water or wettable powders, may contain surfactants such as wetting or dispersing agents, for example the condensation product of formaldehyde with a naphthalenesulfonate, an alkylarylsulfonate, a ligninesulfonate, a fatty alcohol sulfate, an ethoxylated alkylphenol and an ethoxylated fatty alcohol.

In general, these formulations contain from 0.01 to 90% by weight of active ingredient, from 0 to 20% of surfactant acceptable for a fungicide and from 10 to 99.99% of one or more diluents. Concentrated forms, for example emulsifiable concentrates, generally contain from about 2 to 90%, preferably between 5 and 70% by weight of active material. The application forms generally contain from 0.0005 to 10% by weight of a compound of the invention as active material. Typical spray suspensions may contain, for example, 0.0005 to 0.05, preferably 0.001 to 0.02% by weight of active ingredient.

In addition to the usual diluents and surfactants, the compositions of the invention may contain other additives having specific effects, for example stabilizers, deactivators (for solid formulations on active surface supports), agents for improving adhesion to plants, corrosion inhibitors, anti-foaming agents and dyes. In addition, other fungicides with similar or complementary fungicidal activity, or other beneficial materials, such as insecticides, may be present in

V

14 ^ * • * the formulations.

The following examples illustrate the preparation of fungicidal formulations for the treatment of plants.

A. Wetted powder 5 25 parts of a compound of the invention are mixed with 25 parts of synthetic fine silica, 2 parts of sodium lauryl sulphate, 3 parts of sodium ligninesulfonate and 45 parts of finely divided kaolin and are ground to at an average particle size of about 5 microns. A wettable powder is obtained which is diluted in water before use in the form of a spray liquor, and which can be applied by foliar spray as well as by watering the roots.

B. Granules

0.5 part by weight of a binder (non-ionic surfactant) is sprayed onto 94.5 parts by weight of quartz sand in a drum mixer and the whole is mixed thoroughly. 5 parts by weight of a compound of the invention are then added and mixing is continued thoroughly to obtain a granule whose particle size is between 0.3 and 0.7 mm. The granules can be applied by incorporation into the soil adjacent to the plants to be treated.

C. Emulsifiable concentrate

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

D. Seed treatment

45 parts of a compound of the invention are mixed with 1.5 parts of diamylphenol decaglycolic ether, 2 parts of pin oil, 51 parts of fine talc and 0.5 part of the rhodamine dye B. mixing in a contraplex mill operating at 10,000 revolutions per minute until the average particle size is less than 20 microns. The resulting dry powder has good adhesion and can be applied to seeds, for example by mixing it for 2 to 5 minutes in a slowly rotating container.

The following examples describe the preparation of the compounds of the invention; temperatures are given in degrees Celsius.

FINAL PRODUCTS Example 1: 2- (4-Chlorophenyl) -4- (2,2-dichlorocyclopropyl) “3,3-dimethyl-l- (1H-1, 10 2,4-triazole-1-yl) butane-2 -ol a) 5.1 g of dodecyl dimethylsulfonium methyl sulfate are added to a solution of 3.0 g of 1- (4-chlorophenyl) -3- (2,2-dichloro-cyclopropyl) -2,2-dimethyl -propane-l-one in 30 ml of dry toluene at room temperature, and the mixture is stirred for 15

, 15 minutes. 1.1 g of KOH are added to the resulting suspension

sprayed and the mixture is stirred for 2 hours at 35 °. The reaction mixture is cooled, poured onto ice and extracted with diethyl ether. The organic extracts are washed 3 times with water, then with a saturated aqueous NaCl solution, the extracts are dried over MgSO4 and evaporated in vacuo. A residue is obtained in the form of a colorless oil containing 50% of 2- (4-chlorophenyl) -2- [2- (2,2-dichlorocyclopropyl) -1, 1-dimethyl-ethyljoxirane and 50% of dodecyl sulfide and methyl.

B) In the course of 10 minutes, the crude oxirane thus obtained is added dropwise to a mixture of 1.0 g of 1,2,4-triazole which is heated to 90 °, and the mixture is stirred for 18 hours while maintaining the reaction temperature at 90 °.

The reaction mixture is cooled, poured onto

V

16 ice and extracted with CH2Cl2. The organic extracts are washed successively with water and with a saturated aqueous NaCl solution, they are dried over MgSO 4 and the solvent is eliminated by evaporation under vacuum. The title compound 5 is obtained in the form of colorless crystals after chromatography on silica gel with a belt first eluting a fraction of hexane / ethyl acetate (9: 1 originally, then 1: 1) and then with ethyl acetate, and subsequent crystallization from a mixture of diethyl ether / hexane fraction; M = 117-123 °. 10 (mixture of diastereoisomers).

Example 2 * By proceeding in a manner analogous to that described in Example 1, the following compounds of formula la are obtained

15 N = V? H

"A> 1 * 2 20 by reaction of an azole with the corresponding oxirane:

Ex. R R (A) n yx2 * 5 "6 YCharacter-

No._L_j_ ristiQues

25 2.1 4-C1 H - Cl / Cl CH3 H H N

2 »» _ u "" "" CH

3. Br / Br "" "N

4 »» _ "" "" "CH

5. F / F ...... N

30

0 ... "" "" "CH

7. F / Cl "" "N

g. "" "" "CH

9 - Cl / Cl H "" N

V

I * 17%.

Ex. K R3 (A) X / X R R r y Cararte-

Nq. L_ ^ b b J: '5tiques

10 "2-C1 - ...... CH3 CH3 N

11 h h _ "» "» "çn 5 12" H C (CH3) 2 ...... H H N Rf = 0.24 / '1 3 il II II II II II H II AcE *

14 "" CH2 "" "" "" N

J ς II H U II II II II II £ | _ |

16 "" CH (CH3) »" "" "N

ÏO i7 "" "" ·· "" "CH

18 4-C1 H · C (CH3) 2-CH2 Cl / Cl HH H CH F = 140-55ü 19 "" "Br / Br" ”” ”N Rf = 0.30 / 20" "" "" "" "" CH AcE *

21 "" "F / F" "" N

15 22 "" "" "...... CH

23 "" CH2-CH2 C1 / C1 N

24 "" »" "" "" CH

25 "" CH (CH3) -CH2 .......... N Rf = 0.28ytE

n ^ ° = l, 5598

2Q 2ß H 11 II II "Il * 1 II QJ_J

27 "" "" "ci" »^ 28" "" 11 "" »It ςμ

29 "“ C (CH3) 2-CH2 H / C1 ...... N

30 11 "" "" "" "25 31" 11 "Cl / Cl CH3" - N F = 100 - S. ° - ^ * mixture of diastereoisomers - AcE = Ethyl acetate ** mixture of isomers

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* 18 "k * * INTERMEDIATE PRODUCTS Example 3: l- (4-chlorophenyl) -3- (2,2-dichlorocyclopropyl) -2,2-dimethylpropane-l one 5 a) To a solution of 28 g of KOH sprayed in 500 ml of toluene is added with stirring, over 30 minutes and at room temperature, 45.6 g of 4-chlorophenyl-isopropylketone and then, 8.1 g of tetrabutylammonium bromide, the internal temperature rising to 30 °. After stirring for 2 hours, 28.7 g of allyl chloride in 100 ml of toluene are added dropwise at room temperature and the mixture is stirred overnight at room temperature. The mixture is poured into ice water, extracted with ether, the combined organic extracts are washed successively with water and a saturated aqueous NaCl solution, dried over MgSO4 and dried. evaporates. The fractional distillation of the residue in the remaining raw state gives 1- (4-chlorophenyl) -2,2-dimethyl-pent-4-ene-1-one as a colorless oil (E = 95 ° / 0.4 mmHg).

b) At a temperature of 0, 500 g of a 50¾ aqueous NaOH solution are slowly added to a solution of 64 g of 1- (4-chorophenyl) -2,2-dimethyl-pent-4-ene-1. -one in 500 ml of CHCl 3 and, over the course of 15 minutes, 5 g of triethylbenzylammonium chloride (TEBA) are added in portions. When the addition is complete, the mixture is stirred for 8 hours at a temperature between 0 and 5 ° and, after dilution with 500 ml of CHCl 3, it is further stirred for 18 hours at room temperature. The reaction mixture is then poured onto ice, extracted with CH2Cl2, the organic extracts are combined, the overall organic phase is washed with water, dried over MgSO4 and evaporated in vacuo . The title compound is obtained in the pure state by chromatography on gel. silica with, as eluent, a mixture of hexane / diethyl ether (1-3%). Rf = 0.23 by thin layer chromatography on silica gel with ---------------------------------- -

V

19 t * * * eluting a mixture of hexane / diethyl ether 96: 4.

Example 4

By following a procedure analogous to that described in Example 3b), the following compounds of formula IVa 5 are obtained by reaction of the dihalocarbene with the corresponding unsaturated compounds of formula VI:

Comp. R2 R3 (A) n X1 / X2 R4 R5 R6 Rf Eluent 10 4.1 4-C1 HC (CH3) 2CH2 Br / Br HHH 0.34 HX / AcE (1) 95: 5 4.2 4-C1 H CH (CH3) CH2 Cl / Cl HHH 0.31 (2) HX / AcE 9: 1 4.3 4-C1 HC (CH3) 2 Cl / Cl HHH 0.29 HX / AcE 9: 1 (1) HX / AcE = fraction of hexane / ethyl acetate 15 (2) mixture of diastereoisomers

Example 5: 4-chlorophenyl- (2,2-di chloro-1-methylcyclopropyl) ketone To a solution of 7.0 g of 1- (4-chlorophenyl) -2-methyl-prop-2-ene-1-one in 70 ml of chloroform is added slowly at 0 ° 20 and with vigorous stirring, 16 g of an aqueous solution of NaOH at 50%, then 4.3 g of triethylbenzylammonium chloride. When the addition is complete, the ice bath is removed until a strong exothermic reaction begins. The reaction mixture is then cooled again so that the reaction temperature is originally maintained for 1 hour at 34-40 °, then slowly lowered to room temperature. After 5 hours of reaction, the mixture is poured onto ice and extracted with diethyl ether. The organic extracts are combined, washed with water, dried over MgSO4 and evaporated in vacuo. The residue is chromatographed on silica gel using a 9: 1 hexane / diethyl ether mixture as eluent, which gives the title compound: nD = 1.5689, Rf = 0.24 ("thin layer chromatography with as eluent a fraction mixture of hexane / diethyl ether 9: 1).

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Claims (12)

1. The <x-aryl-o-Ri-Hl, 2,4-triazole-1-ethanols and Â-aryl-aR ^ -lH-imidazole-1-ethanols in which Ri represents a halogenated cyclopropyl group bonded to the carbon atom has either directly or via an alkyl group, and their ethers and esters, in free form or in the form of addition salts of acids, alcoholates or metal complexes. 2. A compound according to claim 1, characterized in that it corresponds to the formula I V ^ N ^ OH yR2 15. J in which Ri has the meaning given to claim 1, R2 and R3 each represent, independently of one another, H, a halogen, a C1-C5 alkyl group, C2-C5 alkenyl, alkynyl C2-C5, C1-C5 alkoxy or C1-C5 alkylthio unsubstituted or halogenated, an unsubstituted or substituted phenyl or phenoxy group, or NO2, and Y represents CH or N, and its ethers and esters, 25 free form or in the form of an acid addition salt, an alcoholate, or a metal complex. 3. A compound according to claim 2, characterized in that Ri represents a group G n * 1 30 h 1 -'ΐι R5 (G) \ * * 21 in which Χχ represents H, F, Cl or Br, X2 represents F , Cl or Br, R4, R5, Rß each represent, independently of one another, H, a C1-C5 alkyl group or a halogen, A represents a residue CR7R8 or CR7R8-CHR9, the remainder CR7R8-CHR9 being linked to the halogenated cyclopropyl group by the carbon atom carrying the substituent Rg, 1 10 R7, R8> r9 each represent, independently of one another, H or a C1-C5 alkyl group, R7 and R8 which can also be linked to form a C3-C6 cycloalkyl group, and n signifies 0 or 1. „15 4. A compound according to claim 3, characterized in that R2, R3, (A) n, R4> R5, R6" Xl, X2 and Y represent respectively: a) 4-C1, H, C (CH3) 2-CH2, H, H, H, Br, Br and N, b) 4-C1, H, CH (CH3) -CH2, H, H, H, Cl, Cl and N, 20 c) 4-C1, H, a covalent bond, CH3, H, H, Cl, Cl and N, d) 4-C1, H, C (C3) 2, H, H , H, Cl, Cl and N. 5. A compound according to claim 3, characterized in that it is 2- (4-chlorophenyl) -4- (2,2-dichlorocyclopropyl) - 3,3-dimethyl-l- (1H-1, 2,4-triazole-1-yl) butane-2-ol. 6. A process for the preparation of a compound according to any one of claims 1 to 5, characterized in that a compound of formula II U (II) 30 “M 4 V 22 4“ • * is reacted M represents H, a metal or a trialkylsilyl group and Y has the meaning given in claim 2, with a corresponding 2-aryl-2-Ri ~ oxirane, in which Ri has the meaning given in claim 1, or with a derivative reactive functional group 5 of such an oxirane, and, if necessary, etherification or esterification of the ethanolic compounds thus obtained, and the compounds thus obtained are recovered in free form or in the form of an acid addition salt, d 'an alcoholate or a metal complex. 7. A compound according to any one of claims 1 to 5, in free form or in the form of a salt or a metal complex acceptable in agriculture, for use as a fungicide to combat phytopathogenic fungi. 8. A fungicidal composition for the treatment of plants, characterized in that it contains, as active material, a compound according to any one of claims 1 to 5, in free form or in the form of a salt or a metal complex acceptable in agriculture, in combination with a diluent acceptable in agriculture. 9. A method for combating phytopathogenic fungi, characterized in that an effective amount of a fungicidal compound according to any one of claims 1 to 5 is applied to a place of culture, in free form or in the form of a salt or a metal complex acceptable in agriculture. 10. A compound according to any one of claims 1 to 5, in free form or in the form of a salt or a metal complex acceptable from the pharmaceutical or veterinary point of view, for use as a medicament. 11. A medicament, characterized in that it contains, as active principle, a compound according to any one of claims 1 to 5, in free form or in the form of a salt or an acceptable metal complex of the point of view, pharmaceutical. V * - * _ ♦, '23 12. A pharmaceutical or veterinary composition, characterized in that it contains a compound according to any one of claims 1 to 5, in free form or in the form of a salt or a metal complex acceptable from the point of view. pharmaceutical or veterinary, in combination with a diluent or vehicle acceptable from the pharmaceutical or veterinary point of view. * »Ô \