Fungicides with triazole groups and oligo ethers.

0001The present invention relates to new products, for phytosanitary use, with triazole or imidazole and oligoether groups. The invention also relates to processes for the preparation of said products as well as their application for the protection of plants, especially in the context of the fight against parasitic fungi but also in the regulation of plant growth.

0002Many products with a triazole group, in particular fungicides, are already known. An object of the invention is to provide new products offering new ways of treating plants. Another object of the invention is to provide products having a good activity in particular against rust, powdery mildew, and more especially against powdery mildew of cereals. Another object of the invention is to provide products with polyvalent activity, this activity extending in particular to gray rot (Botrytis) and Sigatoka, to foot rot and to seed diseases. Other objects and advantages of the invention will appear during the description which follows.

0003It has now been found that these objects can be achieved with the products of the invention. These are characterized in that they have the formula:<chemistry id="chem0001" num="0001"><img file="EP0151084A2_D0001.tif" /></chemistry>in which: 1`<ul id="ul0001" list-style="none"><li>X is a halogen atom, preferably fluorine, bromine or chlorine, or a cyano or nitro or alkyl or alkoxy group having from 1 to 12 carbon atoms, preferably from 1 to 4 carbon atoms, and being optionally mono or polyhalogenated (group CF₃ especially),</li><li>n is an integer, positive or zero, less than 6, preferably equal to 2, it being understood that when n is greater than 1, the substituents X can be either identical or different,</li><li>W represents a trivalent group made up either of a group = CH- or of a nitrogen atom = N-</li><li>_R¹ represents the hydrogen atom or an alkyl radical, preferably having from 1 to 4 carbon atoms,</li><li>R² represents a hydrogen atom or an optionally substituted hydrocarbon radical; as more particularly usable radicals, mention may be made of alkyl, cycloalkyl, aryl and aralkyl radicals; as substituents, mention may be made in particular of halogen atoms, preferably chlorine and fluorine, and alkoxy and aryloxy groups. The OR group² is preferably attached to the vicinal carbon atom of the oxygen atom of the heterocycle of formula (I), so that the compound of formula (I) is then provided with an acetal function.</li></ul>

0004Among the compounds corresponding to formula (I), the compounds for which W represents a nitrogen atom are preferred for fungicidal applications

0005A preferred subclass of products according to the invention therefore consists of products of formula in which:<ul id="ul0002" list-style="none"><li>X is a halogen atom,<chemistry id="chem0002" num="0002"><img file="EP0151084A2_D0002.tif" /></chemistry></li><li>n is equal to 1, 2 or 3. With a view to using it against foot-pouring, the compounds in which n = 2 are preferred.</li></ul>

0006The compounds according to the invention can exist in one or more forms of optical isomers depending on the number of asymmetric centers of the molecule. The invention therefore relates both to these optical isomers and to their racemic mixtures and to the corresponding diastereoisomers. The separation of the diastereoisomers and / or of the optical isomers can be carried out according to the methods known per se.

0007The invention also relates to the salified forms of the compounds according to the invention and more especially the hydrochlorides, sulfates, oxalates, nitrates.

0008The present invention also relates to processes for the preparation of the compounds according to the invention.

0009According to a first method, a compound of formula is reacted<chemistry id="chem0003" num="0003"><img file="EP0151084A2_D0003.tif" /></chemistry>in which Z is a chlorine or bromine atom, and X, _not, _R¹ and _R² have the same meaning as in formula (I), with an alkaline derivative (for example a sodium or potassium salt), or a quaternary ammonium or phosphonium derivative) of an imidazole or triazole.

0010The reaction is usually carried out in a polar aprotic solvent medium and can also be catalyzed, for example by adding alkaline iodide; the temperature is generally between 50 and 250 ° C., preferably between 70 and 230 ° C. For economic reasons, the overall reagent concentrations of between 1 and 50% are most often used.

0011Compounds of formula<chemistry id="chem0004" num="0004"><img file="EP0151084A2_D0004.tif" /></chemistry>can be prepared by reaction of an alcohol R²0H with a compound of formula<chemistry id="chem0005" num="0005"><img file="EP0151084A2_D0005.tif" /></chemistry>in the presence of an acid catalyst, R¹, R², X, _Z and n having the same meanings as above and R³ being an organic radical, preferably lower alkyl (C_1-4), two radicals R³can together constitute a divalent organic radical, preferably lower alkylene.

0012The catalyst acid used in this reaction can be a protic or aprotic acid. As protic acids, there may be mentioned hydrochloric, sulfuric, trifluoroacetic, perchloric, benzene-sulfonic, toluene-sulfonic, methane-sulfonic acids. As aprotic acids, mention may be made of Lewis acids such as BF₃, AlCl₃ and SnCl₄. When hydrochloric acid is used as catalyst, the latter can be generated in situ, for example using acyl chloride, and in particular acetyl chloride, which reacts with the alcohol present to give birth at HC1.

0013The reaction is usually carried out by simply heating the reagents indicated. The temperature is generally included in the temperature zone ranging from 50 ° C. to the boiling temperature of the reaction medium. Alcohol R²0H usually plays the role of solvent in the reaction medium. An inert cosolvent can also be added, in particular an aliphatic, alicyclic or aromatic hydrocarbon, halogenated or not, or an ether.

0014The compounds of formula (III) are usually prepared by reaction of a carbonyl compound of formula<chemistry id="chem0006" num="0006"><img file="EP0151084A2_D0006.tif" /></chemistry>with the organomagnesium derivative prepared from a compound of formula<chemistry id="chem0007" num="0007"><img file="EP0151084A2_D0007.tif" /></chemistry>in which Z 'is a halogen atom, preferably bromine, and X, Z, R¹, R³ and n have the meanings previously indicated. The organomagnesium derivative can be prepared, in a manner known per se, by the action of an α-haloaldehyde ketal on magnesium in a solvent medium. This β-haloaldehyde ketal can itself be prepared according to known methods, for example according to G. Büchi and H. Wüest, J. Org. Chem. 34 1122 (1969) and H. Meerwein, Houben-Weyl, Methoden der Org. Chem. vol VI / 3 p 204, 4th Ed (1965).

0015The reaction of the compound of formula (IIIa) with the organomagnesium derivative of the compound of formula (IIIb) most often takes place at a temperature between -70 ° C and + 100 ° C, preferably between -50 ° C and + 50 ° C. As solvent, mention may be made of ethers, in particular diethyl ether and tetrahydrofuran, or aliphatic, alicyclic or aromatic hydrocarbons, or mixtures thereof.

0016According to another process for the preparation of compounds according to the invention, an alcohol R is reacted²0H with a compound of formula<chemistry id="chem0008" num="0008"><img file="EP0151084A2_D0008.tif" /></chemistry>in the presence of an acid catalyst. The various symbols indicated for the formulas of these two reagents have the meanings given above. As the acid catalyst, it is also possible to use those defined above with regard to the preparation of the compounds of formula (IIa). The other reaction conditions are also similar to those defined for the preparation of these compounds of formula (IIa).

0017The compounds of formula (IV) can be obtained by reaction of imidazole or triazole with a compound of formula<chemistry id="chem0009" num="0009"><img file="EP0151084A2_D0009.tif" /></chemistry>in which the various symbols have the meanings already indicated.

0018The imidazole or triazole is optionally, totally or preferably partially, in the form of an alkaline salt.

0019The reaction is usually carried out at a temperature between room temperature (20 ° C) and the boiling point at reflux, preferably between +50 and + 130 ° C. As solvents, it is possible in particular to use alcohols, ethers, and polar aprotic solvents such as dimethylformamide and dimethylsulfoxide.

0020Under conditions similar to those described by the preparation of compounds of formula (IV) from compounds of formula (V), these compounds of formula (IV) can also be prepared from compounds of formula (III) and at using alkaline derivative of imidazole or triazole.

0021The compounds of formula (V) can be obtained by dehydrohalogenation of compounds of formula (III). This reaction is usually carried out by the action of an organic base or, preferably, inorganic, at a temperature between 0 and 100 ° C. The medium can be aqueous and / or contain a solvent such as a hydrocarbon or an ether, an alcohol, a polar solvent.

0022The following examples, given without implied limitation, illustrate the invention and show how it can be implemented.

0023Examples 1 to 3 and 9 and Table (I) illustrate particular modes of preparation of compounds according to the invention, as well as these compounds themselves. Among the physical properties indicated for these compounds, the displacement (delta) values ​​in NMR of the proton of the group -0-CH-0- (acetal) have been indicated. These displacements are measured in ppm and they are identified with respect to a reference product which is tetramethyl silane. NMR is carried out at 100 MHz in deuterated chloroform.

0024Examples 4 to 7 illustrate the fungicidal properties of the compounds according to the invention as well as their applications.

0025In these examples, the spraying of solutions or suspensions of active materials is carried out under conditions such that the spraying of a solution or suspension of concentration equal to 1 g / 1 corresponds on average to the application of approximately 2 micrograms of material active per cm² of plant leaf.

0026Under the conditions of Examples 4 to 7, the illustrated compounds did not exhibit phytotoxicity.

0027In these examples, it is considered that a product exerts total protection against a fungal disease when the protection is at least 95%; protection is considered good when it is at least 80% (but less than 95%), as fairly good when it is at least 70% (but less than 80%), as average when is at least 50% (but less than 70%).

0028In the present description, the percentages are, unless otherwise indicated and except those relating to yields, percentages by weight. In the case where the percentages are expressed relative to the stoichiometry, these are molar percentages. Regarding the concentrations, some of them are expressed in ppm (parts per million) which corresponds to mg / 1.

Example 1:

0029An organomagnesium derivative is prepared by activating 9.7 g of magnesium (0.4 mole) with 0.5 ml of dibromoethane in 10 ml of anhydrous tetrahydrofuran (THF for short). Maintaining the temperature below 15 ° C., a solution of 47 ml (0.4 mole) of 2-α-bromoethyl-dioxolane-1.3 in 200 ml of THF is added dropwise. A quarter of an hour after the end of the addition, the mixture is cooled to -45 ° C. and a solution of 56.7 g (0.3 mole) of chloromethyl- (parachlorophenyl) ketone in 150 ml of THF is added, the temperature being maintained at -45 ° C. After half an hour, the medium is neutralized using 120 ml of pure acetic acid, then poured into a liter of water. An extraction is carried out using ethyl acetate. The ethyl acetate solution is dried, the solvent evaporated. 100 g of hydrochlorine, melting at 99 ° C. (after recrystallization from cyclohexane) and of formula<chemistry id="chem0010" num="0010"><img file="EP0151084A2_D0010.tif" /></chemistry>

0030A mixture of 0.1 ml of acetyl chloride and a solution of 6 g (0.02 mole) of the product of formula (VI) in 30 ml of methanol is heated to boiling at reflux for 2 hours. The reaction mixture is then poured into an aqueous solution at 5% by weight of sodium carbonate in water. It is extracted with ethyl ether, the ethereal solution is dried and the ether is evaporated. An oil is obtained which is distilled at 140⁰C under an absolute pressure of 0.04 mmHg and 4.7 g of oily product of formula:<chemistry id="chem0011" num="0011"><img file="EP0151084A2_D0011.tif" /></chemistry>

0031A mixture obtained by adding 4.2 g (0.016 mol) of product of formula (VII) to 40 ml of dimethyl sulfoxide containing the sodium salt of triazole prepared from 1 is heated at 170 ° C. for 3 hours at 170 ° C. under an inert atmosphere. 6 g (0.024 mole) of triazole and 0.7 g (0.024 mole) of sodium hydride in an 80% oily suspension.

0032The solution is poured into 200 ml of water. It is extracted with ethyl ether, the ethereal solution is dried and evaporated. The residue is purified by chromatography on a silica column. 3.1 g of an oil is thus obtained consisting of a mixture in substantially equal proportions of two diastereoisomers of structural formula:<chemistry id="chem0012" num="0012"><img file="EP0151084A2_D0012.tif" /></chemistry>

Example 2:

0033The product of formula is prepared:<chemistry id="chem0013" num="0013"><img file="EP0151084A2_D0013.tif" /></chemistry>by a process similar to that allowing the preparation of the product of formula (VI) in Example 1, but using as reagent chloromethyl- (orthoparadichlorophenyl) ketone instead of chloromethyl- (parachlorophenyl) ketone.

0034A mixture of 0.3 mole of product of formula (IX) is stirred for 12 h at room temperature with 400 ml of aqueous sodium hydroxide solution with a weight concentration of 15%. The organic phase is diluted with ethyl ether, separated by decantation, washed with water, dried and evaporated.

003564 g of a colorless viscous oil with a boiling point of 147 at 150 ° C. are obtained by distillation under an absolute pressure reduced to 0.02 mmHg and having the formula:<chemistry id="chem0014" num="0014"><img file="EP0151084A2_D0014.tif" /></chemistry>

0036We heat 6 h to 110⁰C a mixture of:<ul id="ul0003" list-style="none"><li>- a solution of 5.8 g (0.02 mole) of product of formula (X) in 20 ml of n-butanol,</li><li>- 1.4 g (0.02 mole) of triazole,</li><li>- 0.9 g (0.01 mole) of triazole sodium salt.</li></ul>

0037Cool to room temperature, dilute with water, extract with ether and then concentrate the ethereal solution. The residue is purified by chromatography on a silica column using a methanol / ethyl acetate / hexane mixture as eluent in respective volume proportions 5 / 47.5 / 47.5.

00385.1 g of product are obtained, melting at 131 ° C. and having the formula:<chemistry id="chem0015" num="0015"><img file="EP0151084A2_D0015.tif" /></chemistry>

0039A mixture of 0.10 ml of acetyl chloride with a solution of 3.1 g of product of formula (XI) in 30 ml of absolute ethanol is heated to boiling at reflux for 4 hours. Let cool. The crystals formed are filtered, washed with cold ethanol. 1.2 g of white crystals are thus obtained, melting at 162 ° C. and corresponding to the most polar diastereoisomer (observed in thin layer chromatography) of the product of structural formula:<chemistry id="chem0016" num="0016"><img file="EP0151084A2_D0016.tif" /></chemistry>

0040The mother liquors from this filtration are concentrated, the residue is diluted with 1 ml of ethanol then 2 ml of isopropyl ether and the crystals formed are separated. Another 0.2 g of the same diastereoisomer, melting at 164 ° C., is obtained.

0041By chromatography on silica of the residual oil of crystallization, a second, less polar diastereoisomer is obtained, which melts at 61 ° C.

Example 3:

0042Using methods similar to that of Example 1 as well as to those of Examples 2 and 9, various other compounds were prepared having the formula:<chemistry id="chem0017" num="0017"><img file="EP0151084A2_D0017.tif" /></chemistry>

0043The nature of the substituents in this formula (XIII) and certain physical characteristics of compounds 1 to 50 are indicated in table (I), which also includes the products prepared (nos. 1, 10, 11 and 29) in examples 1, 2 and 9.

0044However, with regard to compounds n⁰49 and 50, instead of having a parachlorophenyl group substituted ortho by X¹, they comprise a parafluorophenyl group substituted ortho by X. In addition, compound No. 50 has an imidazole group instead of triazole, the preparation process remaining the same, but the reagents being suitably chosen.

0045In the case where R is the hydrogen atom, the compounds have 2 asymmetric carbon atoms and the two diastereoisomers can be distinguished by chromatography on a thin layer of silica using as eluent a methanol / ethyl acetate / hexane mixture. respective volume proportions 5/20/75. The least polar migrates the highest in chromatography and is called A. The most polar migrates the lowest in chromatography and is called B.

0046In the case where R¹ is different from the hydrogen atom, the compounds have 3 asymmetric carbon atoms and there are 4 diastereoisomers. These diastereoisomers are arbitrarily called A, B, C and D. They are sometimes difficult to separate by chromatography but when they can be, A is the least polar, D the most polar, B and C have intermediate polarities.

Example 4:

In vivo test on Erysiphe graminis on barley (barley powdery mildew)

0047An aqueous emulsion of the active ingredient to be tested having the following composition is prepared by fine grinding:<ul id="ul0004" list-style="none"><li>- active ingredient to be tested 40 mg</li><li>- Tween 80 (surfactant consisting of an oleate of polyoxyethylene derivative of sorbitan) diluted to 10% in water 0.4 ml</li><li>- water 40 ml.</li></ul>

0048This aqueous emulsion is then diluted with water to obtain the desired concentration.

0049Barley, in pots, sown in loam, is treated at the 10 cm high stage by spraying with an aqueous emulsion (called slurry) at the concentration indicated below. The test is repeated twice. After 48 hours, the barley plants are dusted with Erysiphe graminis spores, the dusting being carried out using diseased plants.

0050Reading is done 8 to 12 days after contamination.

0051Under these conditions, the following results are observed:<ul id="ul0005" list-style="none"><li>At a dose of 1 g / 1, good or total protection with the compounds 1, 2, 4, 5, 6, 7, 8, 17, 18, 19, 20.</li><li>At the dose of 0.33 g / 1, total protection with the compounds 8, 14, 16, 27.</li><li>At the dose of 0.11 g / 1, total protection with the compounds 11, 12, 13, 15, 28.</li><li>At the dose of 0.033 g / 1, total protection with compounds 9 and 10.</li></ul>

Example 5:

In vivo test on "Puccinia recondita" responsible for wheat rust

0052Wheat, in pots, sown in loam, is treated at the 10 cm height stage by spraying with aqueous emulsions (called boiled) of the same composition as that described in Example 4 and at various concentrations of the test compound . The test is repeated twice with each concentration.

0053After 48 hours, an aqueous suspension of spores (50,000 sp / cm³) is sprayed on wheat; this suspension was obtained from contaminated plants. The wheat is then placed for 48 hours in an incubation cell at approximately 18 ° C. and at 100% relative humidity.

0054After these 2 days, the relative humidity is reduced to 60%. The condition of the plants is checked between the 11th and 15th day after contamination by comparison with the untreated control.

0055Under these conditions, the following results are observed:<ul id="ul0006" list-style="none"><li>At a dose of 1 g / 1, good protection with compounds 4, 5, 6, 7, 9, 13, 14, 15, 16, 17, 18, and 21.</li><li>At the dose of 0.33 g / 1, total protection with compounds 10 and 11.</li></ul>

Example 6:

Test on Botrytis cinerea on tomato:

0056Tomatoes grown in a greenhouse (Marmande variety) aged 30 to 40 days are treated by spraying with aqueous emulsions (called boiled) of the same composition as that described in Example 4 and at various concentrations of the test compound. The test is repeated twice with each concentration.

0057After 24 or 48 hours, the leaves are cut and placed in 2 Petri dishes (diameter llcm), the bottom of which has been previously filled with a disc of wet filter paper (5 leaflets per box).

0058The inoculum is then brought using a syringe by depositing drops (3 drops per leaflet) of a suspension of spores. This suspension of Botrytis cinerea spores was obtained from a 15-day culture, then suspended in a nutritive solution (80,000 units / cm³).

0059The control is done 3 days after contamination by comparison with an untreated control.

0060Under these conditions, at the dose of 1 g / 1, good or total protection is observed with compounds no. 8, 10 and 16.

Example 7:

In vitro tests on seed fungi and soil fungi

0061The action of the compounds according to the invention on the following fungi responsible for secondary cereal diseases is studied:<tables id="tabl0001" num="0001"><img file="EP0151084A2_D0018.tif" /></tables><tables id="tabl0002" num="0002"><img file="EP0151084A2_D0019.tif" /></tables>

0062The indications appearing in brackets will be used to represent these fungi in the taoleau (II).

0063For each test, the procedure is as follows: a nutritive medium consisting of potato, glucose and agar (PDA medium) is introduced by supercooling into a series of Petri dishes (20 ml per dish) after sterilization with autoclave at 120 ° C.

0064During the filling of the boxes, an acetone solution of the active material is injected into the supercooling medium to obtain the desired final concentration.

0065We take as a petri dish analogous to the previous ones, into which are poured similar amounts of a nutrient medium containing no active material.

0066After 24 or 48 h each dish is seeded by depositing a fragment of mycelium from a previous culture of the same fungus.

0067The boxes are kept for 2 to 10 days (depending on the fungus tested) at 22 ° C and the growth of the fungus in the boxes containing the active ingredient to be tested is then compared to that of the same fungus in the box used as a control.

0068The lowest dose is thus determined for each compound tested, making it possible to inhibit the development of the fungus under consideration at 80-100%. This dose is called "Minimum inhibitory dose".

0069These minimum inhibitory doses, expressed in ppm, are reported in Table (II), in which the abbreviations have the meaning indicated above.

0070The compounds according to the invention can therefore be used for the preventive as well as curative fight against fungi, in particular of the basidiomycetes, ascomycetes, adelomycetes or fungi-imperfecti type, in particular rusts, powdery mildew, foot-rot, fusarium worms, helminthosporioses, septorioses , rhizoctones of plants and plants in general and in particular of cereals such as wheat, barley, rye, oats and their hybrids and also rice and corn.

0071The products of the invention are particularly advantageous by their broad spectrum in terms of cereal diseases (powdery mildew, rust, black mold, helminthosporiosis, septoria and in particular fusarium wilt difficult to combat). They are also of great interest due to their activity on gray mold (Botrytis) and Sigatoka, and, therefore, they can be applied to crops as varied as vines, market gardening and arboriculture

0072Finally, they exhibit excellent selectivity with regard to crops.

0073They advantageously apply at doses of 0.02 to 5 kg / ha, preferably 0.05, more specifically from 0.1 to 2 kg / ha.

0074For their practical use, the compounds according to the invention are rarely used alone. Most often they are part of compositions. These compositions, which can be used for protecting plants against fungal diseases, or in compositions which regulate plant growth, contain as active material a compound according to the invention as described above in combination with solid or liquid carriers, acceptable in agriculture and surfactants also acceptable in agriculture. In particular, the usual inert supports and the usual surfactants can be used.

0075These compositions can also contain all kinds of other ingredients such as, for example, protective colloids, adhesives, thickeners, thixotropic agents, penetrating agents, stabilizers, sequestering agents, etc. other known active ingredients with pesticidal properties (in particular insecticides or fungicides) or with properties which promote plant growth (in particular fertilizers) or with properties which regulate plant growth. More generally, the compounds according to the invention can be combined with all the solid or liquid additives corresponding to the usual techniques of formulation.

0076These doses of use in the case of use as fungicides of the compounds according to the invention can vary within wide limits, in particular according to the virulence of the fungi and the climatic conditions.

0077In general, compositions containing 0.5 to 5000 ppm of active substance are very suitable; these values ​​are indicated for the compositions ready for application. Ppm means "part per million". The 0.5 to 5000 ppm zone corresponds to a 5x10 zone^-5 at 0.5 _% (weight percentages).

0078As regards the compositions suitable for storage and transport, they more advantageously contain from 0.5 to 95% (by weight) of active substance.

0079Thus, the compositions for agricultural use according to the invention can contain the active materials according to the invention within very wide limits, ranging from ₅.₁₀-⁵_% to 95 _% (in weight).

0080According to what has already been said, the compounds according to the invention are generally associated with supports and optionally surfactants.

0081By the term "support", in the present description, is meant an organic or mineral, natural or synthetic material, with which the active material is associated to facilitate its application on the plant, on seeds or on the soil. This support is therefore generally inert and it must be acceptable in agriculture, in particular on the treated plant. The support can be solid (clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers, etc.) or liquid (water, alcohols, ketones, petroleum fractions, aromatic or paraffinic hydrocarbons, chlorinated hydrocarbons, liquefied gases , etc ...).

0082The surfactant can be an emulsifying, dispersing or wetting agent of ionic or nonionic type. Mention may be made, for example, of salts of polyacrylic acids, salts of lignosulfonic acids, salts of phenolsulfonic or naphthalene sulfonic acids, polycondensates of ethylene oxide on fatty alcohols or on fatty acids or on fatty amines , substituted phenols (in particular alkylphenols or arylphenols), ester salts of sulfosuccinic acids, taurine derivatives (in particular alkyltaurates), phosphoric esters of polyoxyethylated alcohols or phenols. The presence of at least one surfactant is generally essential when the active material and / or the inert support are not soluble in water and the vector agent for the application is water.

0083For their application, the compounds of formula (I) are therefore generally in the form of compositions; these compositions according to the invention are themselves in fairly diverse forms, solid or liquid.

0084As forms of solid compositions, mention may be made of powders for dusting or dispersion (with a content of compound of formula (1) which can range up to 100%) and granules, in particular those obtained by extrusion, by compacting, by impregnation of a granulated support, by granulation from a powder (the content of compound of formula (I) in these granules being between 1 and 80% for the latter cases).

0085As forms of liquid compositions or intended to constitute liquid compositions during application, mention may be made of solutions, in particular water-soluble concentrates, emulsifiable concentrates, emulsions, concentrated suspensions, aerosols, powders wettable (or powder spray), pasta.

0086The emulsifiable or soluble concentrates most often comprise 10 to 80% of active material, the emulsions or solutions ready for application containing, for their part, 0.01 to 20% of active material. In addition to the solvent, emulsifiable concentrates can contain, when necessary, 2 to 20% of suitable additives, such as stabilizers, surfactants, penetrating agents, corrosion inhibitors, dyes, adhesives. As an example, here is the composition of some concentrates:<ul id="ul0007" list-style="none"><li>Example F (formulation) 1<img file="EP0151084A2_D0020.tif" /></li></ul>

0087According to another formula of emulsifiable concentrate, the following are used:<ul id="ul0008" list-style="none"><li>Example F 2:<img file="EP0151084A2_D0021.tif" /></li></ul>

0088From these concentrates, emulsions with any desired concentration can be obtained by dilution with water, which are particularly suitable for application to the leaves.

0089The concentrated suspensions, also applicable in spraying, are prepared so as to obtain a stable fluid product which does not deposit and they usually contain from 10 to 75% of active material, from 0.5 to 15% of surfactants, from 0 , 1 to 10% of thixotropic agents, from 0 to 10% of suitable additives, such as defoamers, corrosion inhibitors, stabilizers, penetrating agents and adhesives and, as a support, water or an organic liquid in which the active ingredient is little or not soluble: certain organic solids or mineral salts can be dissolved in the support to help prevent sedimentation or as antifreezes for water.

0090Wettable powders (or spray powder) are usually prepared in such a way that they contain 20 to 95% of active ingredient, and they usually contain, in addition to the solid support, 0 to 5% of a wetting agent, 3 10% of a dispersing agent, and, when necessary, 0 to 10% of one or more stabilizers and / or other additives, such as penetrating agents, adhesives, or anti-caking agents, coloring agents, etc ...

0091As an example, here are various compositions of wettable powders:

Example F 3

0092<tables id="tabl0003" num="0003"><img file="EP0151084A2_D0022.tif" /></tables>

0093Another 70% spray powder composition uses the following constituents:

Example F 4:

0094<tables id="tabl0004" num="0004"><img file="EP0151084A2_D0023.tif" /></tables>

0095Another 40% spray powder composition uses the following constituents:

Example F 5:

0096<tables id="tabl0005" num="0005"><img file="EP0151084A2_D0024.tif" /></tables>

0097Another 25% spray powder composition uses the following constituents:

Example F 6:

0098<tables id="tabl0006" num="0006"><img file="EP0151084A2_D0025.tif" /></tables>

0099Another 25% spray powder composition uses the following constituents:

Example F 7:

0100<tables id="tabl0007" num="0007"><img file="EP0151084A2_D0026.tif" /></tables><tables id="tabl0008" num="0008"><img file="EP0151084A2_D0027.tif" /></tables>

0101Another 10% spray powder composition uses the following constituents:

Example F 8:

0102<tables id="tabl0009" num="0009"><img file="EP0151084A2_D0028.tif" /></tables>

0103To obtain these sprayable powders or wettable powders, the active materials are intimately mixed in appropriate mixers with the additional substances and ground with mills or other suitable grinders. This gives spraying powders whose wettability and suspension are advantageous; they can be suspended with water at any desired concentration and these suspensions can be used very advantageously in particular for application to the leaves of plants.

0104Instead of wettable powders, pasta can be made. The conditions and methods of making and using these pastes are similar to those of wettable powders or spraying powders.

0105As has already been said, aqueous dispersions and emulsions, for example the compositions obtained by diluting with water a wettable powder or an emulsifiable concentrate according to the invention, are included in the general scope of the present invention. The emulsions can be of the water-in-oil or oil-in-water type and they can have a thick consistency like that of a "mayonnaise".

0106The granules intended to be placed on the ground are usually prepared so that they have dimensions of between 0.1 and 2 mm and they can be manufactured by agglomeration or impregnation. In general, the granules contain 0.5 to 25% of active material and 0 to 10% of additives such as stabilizers, slow release modifiers, binders and solvents.

0107According to an example of a granule composition, the following constituents are used:

Example F 9:

0108<tables id="tabl0010" num="0010"><img file="EP0151084A2_D0029.tif" /></tables>

0109In this particular case, the active ingredient is mixed with epichlorohydrin and dissolved with 60 g of acetone; the polyethylene glycol and the cetyl ether of polyglycol are then added. The kaolin is sprayed with the solution obtained and the acetone is then evaporated under vacuum. Advantageously, such a microgranulate is used to combat soil fungi.

0110The compounds of formula (I) can also be used in the form of powders for dusting; one can also use a composition comprising 50 g of active material and 950 g of talc; one can also use a composition comprising 20 g of active material, 10 g of finely divided silica and 970 g of talc; these constituents are mixed and ground and the mixture is applied by dusting.

0111Other examples have also been made. In these examples the following abbreviations have been used:<tables id="tabl0011" num="0011"><img file="EP0151084A2_D0030.tif" /></tables><tables id="tabl0012" num="0012"><img file="EP0151084A2_D0031.tif" /></tables><tables id="tabl0013" num="0013"><img file="EP0151084A2_D0032.tif" /></tables><ul id="ul0009" list-style="none"><li>Signing it means "greater than"</li><li>The sign ≤ means "less than or equal to"</li></ul>

0112The pied-verse is designated above by Cercosporella herpotrichoides, but it is normally called Pseudocercosporella herpotrichoides.

0113Tables (III), (IV) and (VI) present the minimum in vitro inhibitory dose of various compounds with respect to various fungi according to the application method used in Example 7.

0114Table (V) presents the minimum greenhouse inhibitory dose (in vivo) of various compounds with respect to various fungi according to the application methods used in Examples 4 to 6.

0115Table (VII) shows the efficacy of products in the open field with regard to various compounds.

0116The nature of the test used in the greenhouse (in vivo) against Cercospora beticola (Example 8) and the conditions of the field tests (Example 8a) are given below.

Example 8:

0117Seedlings of sugar beets 7 to 10 cm high are treated preventively with the slurry to be tested, this slurry being similar to that described in Example 4. The test is repeated 2 times at each concentration.

011824 hours after treatment, the beet seedlings are contaminated by spraying with an aqueous suspension of 0.2 g / ml of mycelium from Cercospora Beticola.

0119It is left to incubate for 72 h at 25 ° C and 100% relative humidity and then after 3 days the seedlings are placed under light (10,000 lux; 14 hours per day). The condition of the plants is checked 14 days after contamination and is expressed as a percentage compared to an untreated control. An effect identical to the control is noted 0%.

0120Complete protection of the plant is noted 100%.

Example 8a:

0121The specific conditions of the various tests are indicated in table (VII). The general conditions are as follows: The tests were repeated 4 times each, on plots of 3 to 5 m². The contaminations are natural for powdery mildew (ERYG), artificial for foot rot (CERC) and yellow rust (PUCR). The plants were treated with a widespread spray mixture at a rate of 500 to 1000 l / ha under a pressure of 3 kg /_cm2_.

0122The treatment was preventive for powdery mildew and yellow rust, (treatment repeated every 15 days), curative for the footwell. The results were observed on a sample of 25 leaves for powdery mildew and yellow rust (determination of the percentage of leaf area affected by the disease), or on a sample of 25 stems for the footwell (determination of the percentage of stems reached).

Example 9:

0123A solution of 296 g (4.23 moles) of methacrolein in 1 l of dichloromethane is cooled to 0 ° C. 343 g of gaseous HBr are bubbled while maintaining the temperature. After 1/4 hour, 0.9 l of methanol is added at 0 ° C., the temperature at which the mixture is kept for 3 h. 2 l of water containing 100 ml of concentrated (aqueous) ammonia are added. The mixture is decanted, the organic phase is separated and the aqueous phase extracted with 200 ml of dichloromethane. The organic phases are combined, washed with an aqueous solution of sodium bisufite; it is concentrated and then distilled in the presence of diethylaniline. 452 g of bromoacetal of formula Br-CH2-CH (CH3) -CH (OCH3) 2 are obtained. Yield: 54%; boiling point 44 at 50 ° C under pressure reduced to 4 mmHg.

0124A magnesium derivative is then prepared by adding a solution of 19.7 g of bromoacetal in 40 ml of tetrahydrofuran, dropwise on magnesium, between 15 and 22 ° C and in the presence of a few drops of 1,2-dibromo ethane.

012540 ml of tetrahydrofuran are then added, cooled to -20⁰C then add dropwise a solution of 20.1 g of trichloroacetophenone in 50 ml of THF. The temperature is kept still at -20 ° C. 6 ml of acetic acid are added and the mixture is poured into 500 ml of water at room temperature. Extracted with ether; the organic solution is dried and concentrated so as to obtain 30 g of yellow oil essentially consisting of chlorohydrin of formula

0126<chemistry id="chem0018" num="0018"><img file="EP0151084A2_D0033.tif" /></chemistry>

0127(This procedure for preparing non-cyclic acetal is that which allows access to the compounds of Example 3 in which R¹ is other than the hydrogen atom).

0128A solution of 1 mol of KOH in 200 ml of methanol is poured into a solution of 442 g of hydrochloride in 1.51 of ethanol, until the medium becomes basic. It is concentrated under vacuum, diluted with ether, washed with water, dried over sodium sulfate, evaporated, distilled under reduced pressure (121 to 140 ° C under 0.01 mm of mercury). 138 g of a mixture of two diastereoisomers of general formula are obtained<chemistry id="chem0019" num="0019"><img file="EP0151084A2_D0034.tif" /></chemistry>

0129To a solution of 126.5 g of this epoxide in 500 ml of dimethylformamide is added 57.2 g of triazole then 172 g of K₂C0₃. The mixture is heated at 120 ° C. for 4 h, filtered, washed with dimethylformamide and evaporated. The residue is poured into 2 l of water, extracted with CHCl₃, washed with water, dried over Na₂s0₄, evaporated under vacuum. 148.2 g of light brown oil are obtained which is triturated in 100 ml of heptane. One filters and obtains 117.5 g of beige powder melting at 117 ° C. (yield: 78%) and consisting of the mixture of the two diastereoisomers of formula<chemistry id="chem0020" num="0020"><img file="EP0151084A2_D0035.tif" /></chemistry>

0130The displacements (delta) in NMR at 100 megahertz in deuterated chloroform are identified for the protons of the methoxy group. Displacements are observed at 3.23 and 3.19 ppm for one diastereoisomer and at 3.38 and 3.20 ppm for the other diastereoisomer.

0131To a solution of 75 g of this hydroxytriazole in 700 ml of ethanol is added 7.3 g of HCl gas and then heated for 15 hours at boiling point at reflux. The ethanol is evaporated in vacuo; the residue is taken up in ethyl acetate, washed with an aqueous bicarbonate solution, washed with water, dried over Na₂SO₄. The solvent is evaporated. 68.6 g of light brown oil are obtained. Yield 96% of formula oroduct<chemistry id="chem0021" num="0021"><img file="EP0151084A2_D0036.tif" /></chemistry>

0132Among the products of formulas (I) and (Ia) according to the invention, the compounds in which R are preferred¹ is R¹⁰, the radical R¹⁰ being an alkyl radical. These compounds constitute a class having particularly advantageous properties and are a particular object of the present invention. Correspondingly to these compounds, the intermediate products of formula (II), (IIa), (III), (IIIb), (IIIc), (IV) and (V) in which R¹ is R¹⁰, also constitute a class of compounds which are the subject of the present invention. Similarly, the processes making it possible to prepare these various compounds, according to the routes previously described but by choosing R¹⁰ in place of R¹ are also a particular object of the invention.

0133Even more preferably, in these various compounds and processes, R¹⁰ represents a lower alkyl radical (C₁ at C₄), and more specifically a methyl radical.

0134The various methods described above apply to the various compounds of formula (I) to (V) as well when R¹ is the hydrogen atom only when R¹ is R¹⁰. However, the preparation of the compound of formula (III) from reagents of formula (IIIa) and (IIIb) differs depending on whether R¹ is H or that R¹ is R¹⁰ : when _R¹ is the hydrogen atom, the reagent of formula (IIIb) is a reagent of formula<chemistry id="chem0022" num="0022"><img file="EP0151084A2_D0037.tif" /></chemistry>in which Z 'has the meaning already indicated and the two radicals R³ can either be distinct (identical or different), or else (and this is preferred) constitute a single divalent radical; when R¹ is R¹⁰, the reagent of formula (IIIb) has the formula<chemistry id="chem0023" num="0023"><img file="EP0151084A2_D0038.tif" /></chemistry>in which Z 'and R¹⁰ have the meanings already indicated and the two radicals R³⁰ have the same meanings as those given for R³ except that the two radicals R must be distinct (and not constitute a single divalent radical). The reference H. Wüest, J. Org. Chem. 34 1122 (1969) relates to products of formula (IIIb) in which the two radicals R³ constitute a unique divalent radical. The reference Houben-Weyl vol. VI / 3 P. 204, 4th Ed, 1965 corresponds to products of formula (IIIb2) in which the two radicals_R³⁰ are distinct.

0135The products of formulas (I) and (Ia) in which R² is a halogenated, especially chlorinated or fluorinated alkyl radical also constitute an object of the invention.

0136The application of the various compounds of formulas (I), (Ia), in which R¹ and R² and the other substituents have the various meanings indicated above, in the fight against fungal damage to cereals, constitutes yet another object of the invention.

0137In addition to the applications already described above, the products according to the invention also exhibit excellent biocidal activity with regard to many other varieties of microorganisms among which mention may be made, without limitation, of fungi such as those of the genera:<ul id="ul0010" list-style="none"><li>- Pullularia like the species P. Pullulans,</li><li>- Chaetomium like the species C. Globosum,</li><li>- Aspergillus like the Aspergillus niger species,</li><li>- Coniophora like the species C. Puteana,</li></ul>

0138Because of their biocidal activity, the products of the invention make it possible to effectively combat microorganisms whose proliferation creates many problems in the agricultural and industrial fields. For this purpose, they are very particularly suitable for the protection of plants or industrial products such as wood, leather, paints, paper, ropes, plastics, industrial water circuits;

0139They are particularly well suited for the protection of lignocellulosic products and in particular wood, whether it is furniture wood, framework or wood exposed to the weather such as fence wood, vine stakes, railway sleepers.

0140In the compositions of the invention, the products according to the invention used in wood treatments can be optionally combined with one or more known biocidal products such as pentachlorophenol, metal salts, in particular copper, manganese, cobalt, chromium, zinc derived from mineral or carboxylic acids (heptanoic, octanoic, naphthenic acids); organic tin complexes, mercaptobenzothiazole.

0141Example 10 below illustrates the biocidal activity of compounds according to the invention.

Example 10:

0142A microsuspension of the product is prepared to determine its fungistatic threshold. This microsuspension is prepared as follows:<ul id="ul0011" list-style="none"><li>In a ball milling machine, the following are charged per tube:</li></ul><ul id="ul0012" list-style="none"><li>- 6 ml of an aqueous solution containing 2 wetting agents (4% of polyglycol 400 and 0.4% of Tween 80)</li><li>- 5 g of glass beads with a diameter of 3 mm</li><li>- 3 g of glass beads with a diameter of 5 mm.</li></ul>

0143This load is subjected to stirring until a homogeneous microsuspension is obtained.

0144Determined amounts of microsuspension thus obtained are introduced into an agar culture medium contained in hemolysis tubes. Each medium is then seeded with a determined strain of a fungus. For each culture, the quantity of biocidal product is varied. The fungistatic threshold is expressed by the quantity of biocidal product per 100 ml of culture medium from which an influence of the product on the development of the strain is noted.

0145The mixtures have been classified into five categories of increasing fungistatic efficacy:

Class

0146<ul id="ul0013" list-style="none"><li>0 totally ineffective at 1.10^-2</li><li>0⁺ efficiency close to 1.10^-2</li><li>1 efficiency between 1.10^-2 and ₁.₁₀-³</li><li>1⁺ efficiency close to 1.10^-3</li><li>2 efficiency between 1.10^-3 and ₁.₁₀-⁴</li><li>2⁺ efficiency between 1.10^-4</li><li>3 efficiency between 1.10^-4 and 1.10^-5</li><li>3⁺ efficiency close to 1.10-⁵</li><li>4 efficiency between 1.10^-5 and ₁.1₀-⁶</li><li>4⁺ efficiency close to 1.10^-6</li><li>5 efficiency between 1.10^-6 and 1.10^-7</li></ul>

0147The fungistatic thresholds of the mixtures are determined for the following strains:<ul id="ul0014" list-style="none"><li>- Coriolus versicolor,</li><li>- Coniophora Puteana,</li><li>- Pullularia Pullulans,</li><li>- Chaetomium globosum,</li><li>- Sterrigmatocystis nigra (Aspergillus niger)</li></ul>

0148The results obtained are recorded in the following table and given by comparison with those obtained under the same experimental conditions with pentachlorophenol.<tables id="tabl0014" num="0014"><img file="EP0151084A2_D0039.tif" /></tables><tables id="tabl0015" num="0015"><img file="EP0151084A2_D0040.tif" /></tables><tables id="tabl0016" num="0016"><img file="EP0151084A2_D0041.tif" /></tables><tables id="tabl0017" num="0017"><img file="EP0151084A2_D0042.tif" /></tables><tables id="tabl0018" num="0018"><img file="EP0151084A2_D0043.tif" /></tables><tables id="tabl0019" num="0019"><img file="EP0151084A2_D0044.tif" /></tables><tables id="tabl0020" num="0020"><img file="EP0151084A2_D0045.tif" /></tables><tables id="tabl0021" num="0021"><img file="EP0151084A2_D0046.tif" /></tables><tables id="tabl0022" num="0022"><img file="EP0151084A2_D0047.tif" /></tables><tables id="tabl0023" num="0023"><img file="EP0151084A2_D0048.tif" /></tables><tables id="tabl0024" num="0024"><img file="EP0151084A2_D0049.tif" /></tables><tables id="tabl0025" num="0025"><img file="EP0151084A2_D0050.tif" /></tables><tables id="tabl0026" num="0026"><img file="EP0151084A2_D0051.tif" /></tables><tables id="tabl0027" num="0027"><img file="EP0151084A2_D0052.tif" /></tables>