FR2606408A1 - New ethanol derivative, its preparation and its use as a fungicide - Google Patents

Abstract

The subject of the invention is the compound of formula I in which the group R-C IDENTICAL C is situated in the para position, X means hydrogen, R means C6H5, R1 means a cyclopropyl group and Az a 1,2,4-triazol-1-yl group, the said compound being in the free form or in the form of a salt or of a metal complex. This compound can be used as a fungicide.

Description

 The subject of the present invention is new derivatives of ethanol, in particular α-aryl-1H-azole-1-ethanols, their preparation and their use as fungicides for combating phytopathogenic fungi and for the treatment of fungal infections in humans. man and animal.

 The invention relates in particular to a- (ethynylphenyl) -a-hydrocarbyl-1H-azole-1-ethanols in which the azole group is a 1,2,4-triazole-1-yl or imidazole-1-yl group, the ethynyl group is unsubstituted or substituted and the phenyl group may carry an additional substituent, and the ethers of such ethanols. These compounds will be designated in the present description "the compounds of the invention".

 The additional substituent of the phenyl group may for example be one of the substituents indicated for the compounds of formula I below.

 The term "hydrocarbyl" means a saturated or unsaturated, straight or branched chain hydrocarbon residue, this chain being able to be partially or completely cyclic and the ring being able to be aliphatic or aromatic, and the hydrocarbon remaining being able to be unsubstituted or substituted; when the hydrocarbon residue is aliphatic or cycloaliphatic, it advantageously contains up to 8 carbon atoms; when it has an aromatic or cycloaliphatic group, it advantageously contains up to 9 carbon atoms. Halogens may be mentioned as suitable substituents of the aliphatic or cycloaliphatic residues of the hydrocarbyl group, halogens being suitable substituents of the aromatic residues of the hydrocarbyl group, among others, halogens, and C1-C6 alkoxy, alkyl groups. in C1-Cs, CsH5, CF3, OCF3 and N02.

dans laquelle
R représente l'hydrogène, un halogène, un groupe alkyle en C1-Cg,
un groupe alcényle en C2-Cs, un groupe cycloalkyle en C3-C7, ou
un groupe phényle ou (phényl)-alkylène en C1-C3 non substitués ou
substitués sur le noyau benzénique, R1 représente un groupe alkyle en C1-C8 alcényle en C2-Cg
ou alcynyle en C2-Cg non substitués ou substitués par de
l'halogène, un groupe cycloalkyle en C3-C6 ou (cycloalkyl en
C3-C6)-alkylène en C1-C3 non substitués ou substitués par un ou
plusieurs substituants choisis parmi les groupes alkyle en C1-C3
et cycloalkyle en C3-C6, ou un groupe phényle ou (phényl)
alkylène en C1-C3 non substitués ou substitués sur le noyau
benzénique,
Az représente un groupe 1,2,4-triazole-l-yle ou imidazole-1-yle, et
X représente l'hydrogène ou un halogène, un groupe alkyle en C1-C5,
alcoxy en C1-C5, CF3, OCF3, N02 ou phényle, et leurs éthers.An appropriate subgroup of compounds of the invention includes those of formula I

in which
R represents hydrogen, a halogen, a C1-Cg alkyl group,
a C2-C5 alkenyl group, a C3-C7 cycloalkyl group, or
an unsubstituted C1-C3 phenyl or (phenyl) -alkylene group, or
substituted on the benzene ring, R1 represents a C1-C8 alkyl group C2-Cg alkenyl
or C2-C6 alkynyl unsubstituted or substituted by
halogen, a C3-C6 cycloalkyl group or (cycloalkyl
C3-C6)-C1-C3 alkylene unsubstituted or substituted by one or
several substituents chosen from C1-C3 alkyl groups
and C3-C6 cycloalkyl, or a phenyl or (phenyl) group
unsubstituted or substituted C1-C3 alkylene on the nucleus
benzene,
Az represents a 1,2,4-triazole-1-yle or imidazole-1-yle group, and
X represents hydrogen or a halogen, a C1-C5 alkyl group,
C1-C5 alkoxy, CF3, OCF3, NO2 or phenyl, and their ethers.

 The compounds of the invention contain one or more centers of chirality. Such compounds are generally obtained in the form of mixtures of racemates or diastereoisomers.

However, these mixtures can, if necessary, be completely or partially separated by known methods into individual isomers or into desired mixtures of isomers.

 When R represents a halogen, it is for example chlorine, bromine or iodine.

 When R and / or R1 represent a phenyl or C1-C3 (phenyl) -alkylene group substituted on the benzene ring, the ring may carry one or more substituents chosen from halogens, for example fluorine, chlorine, bromine or iodine, C1-C6 alkyl groups, for example CH3, C1-Cs alkoxy groups, for example CH30, and groups CF3, OCF3, NO2 and phenyl.

When the groups R and / or R1 contain a C1-C3 alkylene residue, it is, for example, the residue CH2 or CH (CH3)
When R1 represents a C1-C6 alkyl group, it is preferably the isopropyl or tert.-butyl group.

 When R1 represents a C1-C8 alkyl, C2-C8 alkenyl or C2-Cg alkynyl substituted by halogen, the latter may be fluorine, chlorine, bromine or iodine.

 When R1 represents or contains a C3-C6 cycloalkyl group, it is preferably a cyclopropyl group.

 The ethynyl residue is located on the benzene nucleus advantageously in the meta or para position, preferably in the para position.

 When the ethanolic hydroxy group of the compounds of the invention is etherified, these ethers are for example C1-Cs alkyl ethers such as methyl ethers.

 The invention also comprises a process for the preparation of the compounds of the invention, a process in which a 2- (ethynyl-phenyl) -2-hydrocarbyl-oxirane is reacted, in which the ethynyl group can be substituted and the phenyl group can carry an additional substituent, or a reactive functional derivative of such an oxirane, with 1,2,4-triazole or imidazole and, if necessary, the ethynyl group is then substituted, if it is not substituted, with a halogen, and / or the ethanolic compound thus obtained is etherified.

More particularly, to prepare the compounds of formula I a) an oxirane of formula II is reacted

dans laquelle R1, X et Az sont tels que définis plus haut, et Y est un halogène, on substitue l'atome d'hydrogène du reste éthynyle dans un composé de formule Ic

in which R, R1 and X are as defined above,
or a reactive functional derivative of this compound,
with 1,2,4-triazole or imidazole,
and, if necessary, the ethanolic compound is then etherified
thus obtained, or b) to prepare a compound of formula Ib

in which R1, X and Az are as defined above, and Y is a halogen, the hydrogen atom is substituted for the ethynyl residue in a compound of formula Ic

in which R1, X and Az are as defined above,
with a halogen atom Y and, if necessary, etherification
then the ethanolic compound thus obtained.

 Process a) is a reaction known per se for the preparation of azole-1-ethanols, by reaction of an oxirane with an azole, and can be carried out under conditions analogous to the known processes; it is advantageous to use the azole in the form of a salt, for example in the form of an alkali metal salt such as the sodium or potassium salt, or of a trialkylsilyl compound, for example of a trimethylsilyl compound; it is also advantageous to carry out the reaction in the presence of an acid-fixing agent.

 The reaction with oxirane according to method a) is advantageously carried out in an inert solvent under the conditions of the reaction, for example in dimethylformamide. A suitable reaction temperature is between room temperature and the reflux temperature of the reaction mixture. When the azole is in the form of a trialkylsilyl compound, the operation is advantageously carried out at a temperature above ambient temperature, for example between 70 "and 90" C; when a trialkylsilyl-azole is reacted, the reaction is advantageously carried out in the presence of a base such as NaH.

 The expression "reactive functional derivative", used in connection with the 2-aryl-2-R1-oxirans defined above such as the compounds of formula II, includes any derivative of oxirane which, by 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 azoles can react with the reactive functional derivatives of the 2-aryl-2-R1-oxiranes defined above, are also known per se. The reaction of an azole with the halohydrin of the compound of formula II can be carried out under the conditions indicated for the reaction with the oxirannes; however, it is advantageous to operate in the presence of an additional equivalent of a base.

 The substitution of the hydrogen atom of the ethynyl residue in the compounds of formula Ic by a halogen is also carried out according to methods known per se for this kind of substitution reaction. It can be carried out either directly, by reaction of a compound of formula Ic with a halide cation donor such as an alkali metal hypohalide such as NaClO or KCl0, N-chloro or N-bromo-succinimide or carbon tetrachloride, under strongly alkaline conditions with carbon tetrachloride, or via the dihalogenated adduct with subsequent removal of hydrohalic acid HY from the adduct.

 The ethers of the ethanolic compounds of the invention can be obtained according to known methods of etherification from the corresponding ethanolic compounds. Suitable Oalkylating agents are, for example, the corresponding halides, for example iodides such as methyl iodide.

 The compounds of the invention can be isolated from the reaction mixture and can be purified according to known methods. They are obtained in free form or in the form of a salt or a metal complex. By salt is meant, for example, an acid addition salt with an organic or inorganic acid such as the hydrochloride, or an alcoholate, for example sodium ethanolate. The metal complex is for example a complex with a chloride, sulfate or nitrate of copper or zinc. The metal salts and complexes can be obtained from the corresponding free forms according to known methods and vice versa.

dans laquelle R', X et R1 sont tels que définis plus haut, par réaction avec le diméthyl-sulfonio-méthanure, le diméthyloxosulfonio-méthanure, un (alkyl en Cg-C12)méthyl-sulfoniométhanure ou un polymère lié, par exemple le tolystyryl)-méthyl- sulfonio-méthanure (voir Tetrahedron Letters 3, pp. 203-206 (1979). The oxirannes of formula II are new. They are obtained from the corresponding compounds of formula IV

in which R ', X and R1 are as defined above, by reaction with dimethyl-sulfonio-methanide, dimethyloxosulfonio-methanide, a (C1-C12 alkyl) methyl-sulfoniomethanide or a linked polymer, for example tolystyryl ) -methyl-sulfonio-methanide (see Tetrahedron Letters 3, pp. 203-206 (1979).

 The compounds of formula IV can be obtained according to methods known per se.

dans laquelle R1 et X sont tels que définis plus haut, peuvent par exemple être préparés par réaction d'un composé de formule V

dans laquelle R1 et X sont tels que définis plus haut, avec le triméthylsilylacétylène en présence de quantités catalytiques de dichloro-bis[triphénylphosphine]palladium et d'iodure de cuivre(I) dans des amines telles que la diéthylamine ou la pipéridine, et élimination subséquente du groupe silyle, par exemple par traitement doux avec une solution aqueuse diluée de KOH dans du méthanol (voir Synthesis 1980 (8) p. 627).Le triméthylsilyl-acétylène utilisé dans cette réaction peut être remplacé par le 2-méthyl-3-butyne-2-ol, en utilisant le même catalyseur au palladium et l'iodure de cuivre(I); on obtient ensuite les composés de formule IV par traitement du produit de réaction avec NaOH dans du toluène (voir le brevet américain n" 4 223 172).The compounds of formula IVa

in which R1 and X are as defined above, can for example be prepared by reaction of a compound of formula V

in which R1 and X are as defined above, with trimethylsilylacetylene in the presence of catalytic amounts of dichloro-bis [triphenylphosphine] palladium and copper iodide (I) in amines such as diethylamine or piperidine, and elimination the silyl group, for example by gentle treatment with a dilute aqueous solution of KOH in methanol (see Synthesis 1980 (8) p. 627). The trimethylsilyl-acetylene used in this reaction can be replaced by 2-methyl-3 -butyne-2-ol, using the same palladium catalyst and copper (I) iodide; the compounds of formula IV are then obtained by treatment of the reaction product with NaOH in toluene (see US Patent No. 4,223,172).

dans laquelle R1 et X sont tels que définis plus haut et
R" représente un groupe alkyle en C1-Cg, alcényle en
C2-Cs, un groupe phényle ou (phényl)-alkylène en
C1-C3 non substitués ou substitués sur le noyau
benzénique, sont obtenus par réaction d'un composé de formule V avec un composé de formule VI
HC . C - R" (VI) dans laquelle R" est tel que défini plus haut.The compounds of formula IVb

in which R1 and X are as defined above and
R "represents a C1-Cg alkyl group, a alkenyl group
C2-Cs, a phenyl or (phenyl) -alkylene group in
C1-C3 unsubstituted or substituted on the nucleus
benzene, are obtained by reaction of a compound of formula V with a compound of formula VI
HC. C - R "(VI) in which R" is as defined above.

 The reaction conditions are analogous to those specified for the reaction of the compound of formula V with trimethylsilyl acetylene.

dans laquelle X et R" sont tels que définis plus haut, sous les conditions connues de préparation des cétones selon la méthode de Grignard.Depending on the meaning of R1, it may be advantageous to prepare the compounds of formula IV from compounds of formula VII

in which X and R "are as defined above, under the known conditions for the preparation of ketones according to the Grignard method.

 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, in free form or in the form of salts acceptable from the pharmaceutical or veterinary point of view, possess advantageous biological properties, in particular antifungal properties, and can therefore be used in human or veterinary therapy for the treatment fungal infections in humans or animals. This antifungal activity has been 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 μg / ml, and also by in vivo tests, for example by systemic application by the oral route of doses ranging between approximately 10 and 100 mg / kg to mice in which caused an intravaginal infection with Candida albicans.

 Thanks to these properties, the compounds of the invention can be used in human or veterinary therapy as antifungals. For this use, the compounds of the invention are administered at a daily dose advantageously between 70 and 2000 mg.

 The compounds of the invention can be used in the form of pharmaceutically acceptable acid addition salts, for example in the form of hydrochloride, hydrobromide, sulfate, nitrate, hydrogen fumarate and 1,5-naphthalene -disulfonate.

 The invention therefore relates to the compounds of the invention, in free form or in the form of salts acceptable from the pharmaceutical or veterinary point of view, for use as medicaments, in particular as anti-fungals. The invention also relates to a medicament containing, as active substance, a compound of the invention in free form or in the form of a salt 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 carriers or diluents acceptable from the pharmaceutical or veterinary point of view and, optionally, with other excipients . Such compositions are also part of the present invention. The compounds of the invention may be administered internally in the form of unit doses such as 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 compounds of the invention, in free form or in the form of salts or 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 approximately 0.0008 and 0.05% against Uromyces appendiculatus (bean rust) on row beans, against other rust fungi ( such as Hemileia, Puccinia) on coffee, wheat, geraniums, snapdragons, against Erysiphe cichoracearum on cucumbers and against other oidiums (E. Graminis f.sp. tritici, E. Graminis f. sp. hordei, Podosphaera leucotricha, Uncinula necator) on wheat, barley, apples and vines. Other interesting effects have been observed among others in in vitro tests against Ustilago maydis and in in vivo tests against Rhizoctonia solani. Whereas these tests also indicate excellent plant tolerance and good systemic action, the compounds of the invention are therefore suitable for the treatment of plants, seeds and soil to combat phytopathogenic fungi, for example
Basidiomycetes of the order Uredinales (rust) such as
Puccinia spp, Hemileia spp, Uromyces spp, Ascomycetes of the order of Erysiphales (oidiums) such as Erysiphe spp, Podosphaera spp and
Uncinula 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 used, the type of treatment (plants, soil, seeds), the method of treatment (for example drenching, watering, spraying, dusting, seed treatment ), the objective of the treatment (prophylactic or therapeutic), the type of fungi to be controlled and the period 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 kg / ha, preferably between approximately 0.01 and 1-kg / ha, in the case of treatment of plants or the soil, for example between 0.04 and 0.125 kg of active ingredient (ai) per hectare for cultivated plants such as cereals, or at concentrations of 1 to 5 g of ai per ha for cultivated plants such as fruits, vines and vegetables (at an application volume of 300 to 1000 liters / ha, depending on the size or leaf volume of the cultivated plants, which is equivalent to a dose of about 10-50 g / ha). 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 g / kg of seeds, preferably between approximately 0, 1 and 0.3 g / kg of seeds.

 The expression soil, as used in the present description, designates any usual growth 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), beets , sugar cane, cotton, flax, malus, vines, pome and stone fruits (such as apples, pears and plums), and cereals (such as wheat, oats, barley, rice).

 Due to the good tolerance of cultivated plants, many compounds of the invention are particularly indicated for fungicidal treatments where good tolerance of cultivated plants is desirable or essential, for example in fruits such as apples. Various compounds of the invention, for example the compound of Example 2.33 below, also exert a favorable curative activity.

Particularly favorable results are obtained inter alia with the compounds of formula I having one or more of the following characteristics:
X represents hydrogen, the C-CR group is located in the para position,
R represents hydrogen, Cl, Br, CH3, C4H8 (for example n-C4Hg or
tert.-C4Hg) or an unsubstituted or substituted phenyl group, in
in particular a phenyl group substituted by Br or a group
unsubstituted phenyl, preferably of the latter, R1 represents iso-C3H7, tert.-C4Hg, a C3-C6 cycloalkyl group
(in particular cyclopropyl) or a group (cycloalkyl in
C3-C6)-C1-C3 alkylene, in particular (cyclopropyl) -alkylene
in C1-C3, preferably cyclopropyl-CH (CH3) -,
Az represents a 1,2,4-triazole-1-yl group.

 The present invention also relates to 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 association 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 herein, denotes a liquid or solid material acceptable in agriculture which can be added to the active material to transform it into a simpler or more easily applicable form, or to dilute it in order to obtain a desirable or usable power. Examples of such diluents include talc, kaolin, diatomaceous earth, xylene or 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, a 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 material, from 0 to 20% of surfactant acceptable in agriculture 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. The usual spray suspensions may contain, for example, 0.0005 to 0.05%, preferably 0.001 to 0.02%, for example 0.001, 0.002 or 0.005% by weight of active material.

 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 to improve adhesion to plants, corrosion inhibitors, anti-foaming agents and dyes. In addition, other fungicides having similar or complementary fungicidal activity, for example sulfur, chlorothalonile, dithiocarbamates such as mancozeb, maneb, zineb, propinbe, trichloromethane-sulfenylphthalimides and the like such as captan, captafol and folpel, benzimidazoles such as benomyl, or other materials with beneficial action, such as insecticides, may be present in the formulations.

The following examples illustrate the preparation of fungicidal formulations for the treatment of plants (parts are by weight): a) Wettable powder
10 parts of a compound of the invention are mixed with 4 parts of synthetic fine silica, 3 parts of sodium lauryl sulphate, 7 parts of sodium ligninesulfonate, 66 parts of finely divided kaolin and 10 parts of diatomaceous earth and are ground up to an average particle size of around 5 microns. A wettable powder is obtained which can be diluted in water before use in the form of a slurry which can be applied by foliar spraying as well as by watering the roots.

b) Granules
In a drum mixer, 0.5 part of a binder (non-ionic surfactant) is sprayed on 94.5 parts of quartz sand and the whole is mixed thoroughly. 5 parts 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 of a compound of the invention are mixed with 10 parts of an emulsifying agent and 65 parts 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 B dye. 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 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. The Rf values are on silica gel.

FINAL PRODUCTS
Example 1: 2- (4-ethynylphenyl) -3,3-dimethyl-1- (1H-1,2,4-triazole-1-yi) -butane-2-ol
At room temperature, 17.2 g of docecyl-dimethylsulfonium methyl sulfate are added to a solution of 6.5 g of 1- (4-ethynylphenyl) -2,2-dimethyl-propane-1-one in 80 ml of anhydrous toluene . The mixture is stirred for -15 minutes and 3.8 g of sprayed KOH are added. This mixture is further stirred for 22 hours at 35 ". The reaction mixture is poured onto ice, the pH is adjusted to 7 with 6N H 2 SO 4 and it is extracted with diethyl ether. The organic phase is washed with water, we dry it on
Na2SO4 and evaporated under vacuum. The residue, containing 2- (4 ethynylphenyl) -2- (1,1-dimethylethyl) -oxirane, is reacted directly without prior purification.

 The residue is added dropwise over 10 minutes and at 90 "to a suspension of 4 g of 1,2,4-triazole and 14.5 g of K2CO3 in 80 ml of anhydrous dimethylformamide and the mixture is stirred for 4 hours at 900. The reaction mixture is then cooled, poured onto ice and extracted with diethyl ether, the ethereal solution is washed with water, dried and concentrated in vacuo. residue with hexane, the insoluble solid product is filtered off and the residue is recrystallized from a hexane / toluene mixture. The title compound is obtained in the form of colorless crystals. F = 101 "(Rf = 0.35 in a mixture of ethyl acetate / hexane 6: 4).

Example 2
By proceeding analogously to that described in Example 1, the following compounds of formula I are obtained in which X = H and or the group RC ~ C is located in the para position, unless otherwise indicated, from the corresponding ketones of formula IV, via the corresponding oxirannes of formula II.

Table 1
Example R R1 Az Rf. F
2.1 H i-C3H7 Tr (1) 1210
2.2 CH3 i-C3H, Tr 98-99
2.3 CH3 1-C3H7 Im (2) 1800
2.4 C6H5 i-C3H? Tr 71
2.5 C6H5 i-C3H7 Im 1880
2.6 C6H5 t-C4H9 Tr Rf = 0.35 (3)
2.7 C6H5 t-C4Hj Im Rf = 0.35 (4)
2.8 CH3 t-C4Hg Tr 99
2.9 CH3 t-C4Hg Im 2.10 n-C4H9 t-C4Hg Tr 77-78 2.11 n-C4H9 t-C4Hg 2.12 n-C4H9 i-C3H7 Tr 650 2. 3 n-C4H9 i-C3H7 tm 2.14 4-Cl-C6H4 t -C4Hg Tr 125-127 2.15 4-C1-C6H4 t-C4Hg Im 158 2.16 4-F-C6H4 i-C3H7 Tr 1500 2.17 4-F-C6H4 i-C3H7 Im 2.18 4-CH30-C6H4 i-C3H7 Tr 132- 133 2.19 4.CH30-C6H4 i-C3H7 Im 175-176 2.20 4-CH30-C6H4 t-C4H9 Tr 1400 2.21 4-CH3O-C6H4 t C4Hg Im 142-143 2.22 4-Cl-C6H4 i-C3H7 Tr 1290 2.23 C6H5 CH2-CH (CH3) 2 Tr 1190 2.24 C6H5 CH (CH3) -CH (CH3) 2 Tr 970 2.25 C6H5 C (CH3) 2-CH (CH3) 2 Tr 2.26 CH3 CH2-CH (CH3) 2 Tr 2.27 CH3 CH (CH3) -CH (CH3) 2 Tr 117 2.28 CH3 C (CH3) 2-CH (CH3) 2 Tr 2.29 t-C4H9 i-C3H7 Tr 1980 2.30 t-C4Hg t-C4H9 Tr 268-2690 2.31 n-C4H9 CH2 -CH (CH3) 2 Tr 660 2.32 4-NO2-C6H4 t-C4H9 Tr 2270 2.33 C6H5 CH (CH3) -C3H5 (5) Tr (6) 2.34 C6H5 1-C3H7 Tr 83-840 IR-C # Cen
meta position
Example R R1 Az Rf, F 2.35 C6H5 CH (CH3) -C3H5 Im 1390 (diastatic mixture) 2.36 4-F-C6H4 t-C4Hg Tr 1220 2.37 C6H5 cyclopropyl Tr 1260 2.38 H cyclopropyl Tr 880 2.39 nC4Hg cyclopropyle Tr Rf = O.35 (ethyl acetate / hexane 6: 4) 2.40 C6H5 C (CH3) 2-CH2-CH = CH2 Tr Rf = 0.45 (toluene / (1) = 1,2,4-triazole-1- yl ethyl acetate 6: 4)
F = 58-60 (2) = imidazole-l-yle
(3) = ethyl acetate / hexane 6: 4
(4) 1 ethyl acetate / ethanol 40: 1
(5) s C3H5 = cyclopropyl
(6) = mixture of diastereoisomers, separated by TLC
Diastereomer A: Rf = 0.3 (ethyl acetate / hexane 6: 4)
Diastereomer B: Rf = 0.4 (ethyl acetate / hexane 6: 4)
the latter (form B) can be crystallized; F = 91-92
Example 3: 2- (4-bromoethynylphenyl) -3,3-dimethyl-1- (1H-1,2,4-
triazole-1-yl) butane-2-ol
2 g of bromine are added to 10 ml of an aqueous solution of
2.5N NaOH and added dropwise over 15 minutes and under
stirring, 2.7 g solution of 2- (4-ethynyl-phenyl) -3.3
dimethyl-1- (1H-1,2,4-triazole-1-yl) -butane-2-ol in 20 ml of
dioxane.

The reaction mixture is kept at the temperature
ambient for 3 hours, then diluted with 100 ml of water and
it is extracted with diethyl ether. Wash the solution
ethereal with water, dried and the solvent removed by
evaporation. The residue is recrystallized from a hexane /
toluene, which gives colorless crystals. F 138 (Rf = 0.4 in
a mixture of ethyl acetate / hexane 6: 4).

Example 4
By following a procedure analogous to that described in Example 2 and using the corresponding starting materials of formula Ic, the following compounds of formula I are obtained in which X = H and the group RCC- is located in the para position.

Example R R1 Az Rf, F Cl Cl t-C4Hg Tr 45-460
4.2 Cl i-C3H7 Tr
4.3 I i-C3H7 Tr 1220
4.4 Br i-C3H, Tr 1970
Tr = 1,2,4-triazole-l-yl
30 contaminated with perchloro compound
Example 5 2- (4-chloroethynylphenyl) -3-methyl-1- (1H-1,2,4-triazole-1-yl) butane-2-ol
To a stirred mixture of 12 g of 2- (4-ethynyl phenyl) -3-methyl-1- (1H-1,2,4-triazole-1-yl) -butane-2-ol in 50 ml of hexamethylphosphotriamide 24.8 g of N- Chloro-succinimide are added in portions over a period of 15 minutes. The reaction is slightly exothermic (the reaction temperature rises from 20 to 30). The reaction mixture is slightly cooled while maintaining the reaction temperature at 25-30, with stirring for 1 hour.

 The light yellow reaction solution is poured into 1000 ml of water and extracted with diethyl ether. The ethereal phase is washed 1 time with water, dried and the solvent is removed by evaporation. The oily residue is chromatographed on silica gel in a toluene / ethyl acetate mixture 3: 7, which gives the impure title compound (Rf = 0.35).

Example 6 2- (4-iodoethynylphenyl) -3-methyl-1- (1H-1,2,4-triazole-1-yl) -butane-2-ol
To a solution of 5.1 g of 2- (4-ethynylphenyl) -3-methyl1- (1H-1,2,4-triazole-1-yl) butane-2-ol in 100 ml of anhydrous CH3OH is added simultaneously , with stirring at a temperature of 20-25 ", 2.6 g of iodine and 10 ml of a 30% NaOH solution. The reaction mixture is stirred for 24 hours at room temperature, it is poured then in 500 ml of water and extracted with CH2Cl2, the organic phase is washed, dried and evaporated, the residue is stirred in a fraction of hexane and kept at rest for 16 hours . The precipitate is drained and dried, which gives the title compound in the form of colorless crystals. F = 122 ".

Example 7 Methyl ether of 2-E4- (phenylethynyl) phenyl] -3-methyl- 1- (1H-1,2,4-triazole-1-yl) -butane-2-ol
NaH (1.6 g, 80%) is stirred in 60 ml of anhydrous dimethylformamide, then added dropwise over 60 minutes and at room temperature to a solution of 16.6 g of the compound of Example 2.4 in 60 ml of dimethylformamide and the mixture is stirred for 30 minutes. Then 7.4 g of methyl iodide are added, the mixture is stirred for 15 hours at room temperature and diluted with water. The solid precipitate is drained, washed with water and dried, giving the title compound as colorless crystals.

F = 181 (in petroleum ether); Rf = 0.6 (CHCl3 / CH30H 95: 5).

Example 8 Fungicidal activity 8.1 Control of powdery mildew in wheat
Wheat infested with Erysiphe graminis was treated with a spray mixture comprising the compound of Example 2.4 as active ingredient (ai) at a concentration of 300 mg ai / liter. A spray volume of 500 L / hu was applied.

The treatment provided effective protection against powdery mildew.

8.2 Control of wheat rust
Wheat infested with Puccinia striiformis (yellow rust) was treated with a spray mixture comprising the compound of Example 2.4 at a concentration of 100 mg ai / liter. A spray volume of 1000 L / hu was applied. The treatment provided effective protection against rust.

INTERMEDIATE PRODUCTS
Example 9 1- (4-ethynylphenyl) -2,2-dimethylpropane-1-one
At room temperature, 1.4 g of dichlorobis- (triphenylphosphine) palladium and 0.19 g of copper iodide are added to a solution of 10.5 g of trimethylsilylacetylene and 23.6 g of 1- (4-bromophenyl ) -2,2-dimethylpropane-1-one in 350 ml of anhydrous diethylamine. The reaction mixture is stirred for 20 hours at room temperature, evaporated to dryness in a rotary evaporator and the residue is extracted several times with toluene. The toluene is removed by evaporation and the viscous oil is chromatographed on silica gel with a 2: 1 hexane / toluene mixture as mobile phase, giving 1- (4-trimethylsilyl ethynyl-phenyl) -2,2-dimethylpropane -1-one.

 21.6 g of this residue are stirred for 4 hours in a mixture of 100 ml of CH30H and 80 ml of 1N aqueous KOH. The CH3OH is removed by evaporation in a rotary evaporator. The remaining oil is dissolved in diethyl ether and the concentration of said reaction mixture gives the title compound as a viscous oil (Rf = 0.35 in toluene).

Example 10 1-E4- (1-propynyl) -phenyl) -2-methylpropane-1-one
11.2 g of Mg and an iodine crystal are introduced into 100 ml of anhydrous tetrahydrofuran in a three-necked flask purged with nitrogen and equipped with a stirrer. A mixture of 20 g of 1- (4-bromophenyl) -1-propyne and 5 g of ethyl bromide is added dropwise with stirring, at a rate allowing the temperature to rise to 65 " Immediately afterwards, an additional 70 g of 1- (4-bromophenyl) -1-propyne are added in 100 ml of anhydrous tetrahydrofuran, so as to maintain a reflux limited to 65 ".

Claims (4)

1.- The compound of formula I

 in which the R-CC- group is located in the para position, X signifies hydrogen, R signifies C6H5, R1 signifies a cyclopropyl group and Az signifies a 1,2,4triazole-1-yl group, said compound being in free form or in the form of a salt or a metal complex.  2. The compound according to claim 1, in free form or in the form of a salt or a metal complex acceptable in agriculture, for use as a fungicide to combat phytopatogenic fungi.  3. A fungicidal composition, characterized in that it contains, as active material, the compound according to claim 1, in free form or in the form of a salt or a metal complex acceptable in agriculture, in combination with a thinner acceptable in agriculture.  4. A process for combating phytopathogenic fungi, characterized in that an effective amount of the compound according to claim 1 is applied to the place of culture, in free form or in the form of an acceptable salt or metal complex in agriculture.