EP0638070A1

EP0638070A1 - Fungicidal arylpyrazoles

Info

Publication number: EP0638070A1
Application number: EP93911822A
Authority: EP
Inventors: Richard Cantegril; Denis Croisat; Philippe Desbordes; François Guigues; Jacques Mortier; Raymond Peignier; Jean Pierre Vors
Original assignee: Rhone Poulenc Agrochimie SA
Current assignee: Bayer CropScience SA
Priority date: 1992-04-27
Filing date: 1993-04-26
Publication date: 1995-02-15
Also published as: CN1079735A; BR9306410A; MA22882A1; RO111934B1; CA2134453A1; RU94046018A; HRP930843A2; IL105525A0; BG97668A; ZA932945B; SK130794A3; AU4263993A; BG61711B1; CN1063440C; FI945034A; AP465A; HU9403086D0; HUT69065A; FI945034A0; AP9300522A0

Abstract

The present invention relates to new derivatives of the family of 3-arylpyrazoles, their methods of preparation, the compositions containing them and their utilization for the protection of plants against fungal diseases. The invention relates more particularly to 3-arylpyrazole derivatives having the formula (I) wherein X1 to X5, which may be the same or different, represent a hydrogen atom, or a halogen atom or a nitro or alkyl group; Y represents a halogen atom or a nitro group; and Z represents a hydrogen atom or a group C(Z1)Z2.

Description

FUNGICIDE ARYLPYRAZOLES.

The present invention relates to new derivatives of the 3-arylpyrazole family, their methods of preparation, the compositions containing them and their use for the protection of plants against fungal diseases.

A more specific subject of the invention is 3-arylpyrazole derivatives, characterized in that they are of formula I:

in which:

X ₁ , X ₂ , X ₃ , X ₄ and X ₅ , identical or different, are:

- a hydrogen or halogen atom, a hydroxy, cyano, thiocyanato, nitro, nitroso or amino group optionally substituted by one or two alkyls or phenyls,

- an alkyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl alkylsulfinylalkyl, alkylsulfonylalkyl, benzyl, alkenyl, alkynyl, cyanoalkyl, alkoxy, alkenoxy, alkylthio, formyl, acetyl, alkyl- or alkoxy (thio) -carbonyl, mono or di alkylamino (thio) carbonyl radical , iminocarbonyl, mono- or

diarylamino (thio) carbonyl, carboxyl, carboxylate, carbamoyl or benzoyl, - a phenyl, phenyloxy, phenylthio radical,

an alkyl- or alkoxy- or mono or di alkylamino- or phenyl-sulfenyl or sulfinyl or sulfonyl radical,

a phosphoryl group, substituted by two groups chosen from the group comprising alkyl, alkoxy, alkylthio and dialkylamino, benzyloxy, phenyloxy or phenyl,

- a trialkyl- or alkylphenyl-silyl group,

Two of the adjacent X ₁ , X ₂ , X ₃ X ₄ and X ₅ may also be linked together by a carbon bridge comprising from 2 to 4 links, at least one of which may be replaced by an oxygen or sulfur atom. or nitrogen, the carbons of this bridge may or may not be substituted by at least one halogen atom and / or at least one hydroxy, amino, alkyl, alkoxy .alkylthio, mono or di alkylamino, alkylsulfinyl or -sulfonyl group. alkyl part being as defined above,

provided that X ₁ ά X ₅ and X 3 to X5 cannot each be simultaneously a hydrogen atom; X1 and

Y is a hydrogen or halogen atom, a nitro, nitrile, thiocyanato or alkyl, alkoxy or alkylthio, alkylsulfinyl or -sulfonyl group, the alkyl part of these radicals being optionally mono- or polyhalogenated, an amino optionally substituted by a or two alkyls or phenyls;

Y and X1 or X5 can also be linked together by a carbon bridge comprising from 5 to 7 links, at least one of which can be replaced by an oxygen, sulfur or nitrogen atom, the carbons of this bridge possibly be or not substituted by at least one halogen atom and / or at least one hydroxy, alkoxy, alkylthio, mono or di alkylamino, alkylsulfinyl or - sulfonyl group, the alkyl part being as defined above,

Z is:

- a hydrogen, halogen atom, a cyano, nitro, hydroxy group or - alkyl, haloalkyl, cycloalkyl or cycloalkyl -alkyl the cycloalkyl part which may be substituted by the group GR4, defined below, or

- alkoxy, optionally substituted by hydroxy, alkoxy, alkylthio; or an alkylthio,

-a phenyloxy or phenylthio,

- an amino optionally substituted by one or two alkyls or

- alkenyl or alkynyl, each containing 3 to 7 carbon atoms, possibly substituted

- phenyl or Het, possibly substituted

- a group of formula C (Z ₁ ) Z ₂ in which:

Z ₁ is an oxygen or sulfur atom or an alkylamino or imino or arylamino group and

- Z ₂ is:

- a hydrogen, halogen atom, a hydroxy, sulfhydrile, cyano, amino group,

- alkyl, alkoxy, alkylthio,

- alkenyl or alkynyl, each containing 3 to 7 carbon atoms

- phenyl, phenylalkyl, phenoxy, phenalkyloxy,

-Het or Het- alkyl,

-phenylalkenyl or phenylalkynyl; Het-alkenyl or Het-alkynyl

- mono or di alkylamino, a mono- or diphenyl-amino or -sulfonylamino radical,

a phosphoryl group substituted by two radicals chosen from the group comprising alkyl, alkoxy, alkylthio, dialkylamino, cycloalkyl or cycloalkyl -alkyl, alkenyl or alkynyl, phenyl phenylalkyl, Het or Het-alkyl, phenyl or Het,

possibly stolen;

- or a group S (Z ₁ ) (Z ₃ ) Z ₂ , in which Z ₁ and Z ₂ have the same meanings as above and Z3 has the same meanings without necessarily being equal to Z ₁ , provided that Z n is not a hydrogen atom when X ₃ , X ₄ and X ₅ are each a hydrogen atom;

as well as the tautomeric forms of formula I bis, when Z is a hydrogen atom or a group of formula C (Z ₁ ) Z ₂ , or S (Z ₁ ) (Z ₃ ) Z ₂ ,

their hydracid or perchloric or nitric salts or sulfuric acid or alkyl- or phenyl (optionally substituted) sulfonic acids and their metal or metalloid complexes,

it being understood that in all of the above meanings,

the hydrocarbon part of these groups may comprise from 1 to 7 carbon atoms and may be optionally halogenated (from 1 to 8 halogen atoms), the cycloalkyl part of these groups can comprise from 3 to 7 carbon atoms and be optionally substituted by at least one substituent chosen from the group GR4,

- the phenyl part denotes the phenyl ring optionally substituted with 1 to 5 substituents chosen from the group comprising a halogen atom, an alkyl or alkoxy of 1 to 3 carbon atoms

- Het is a heterocyclic radical, mono or bicyclic, containing from 5 to 10 atoms, of which 4 are heteroatoms (oxygen, sulfur, nitrogen, phosphorus).

Preferably, in the formula, Y is a chlorine or bromine atom. Other preferred derivatives are such that, in formula I, Z is a hydrogen atom or a group C (Z ₁₎ Z ₂ , in which Z ₁ is an oxygen or sulfur atom.

Other preferred derivatives are such that, in formula I, X ₁ , X ₂ and X ₄ are a hydrogen or halogen atom or a nitro or optionally halogenated alkyl group of 1 to 4 carbon atoms.

Other preferred derivatives are such that, in formula I, X ₃ is a hydrogen or fluorine atom.

Other preferred derivatives are such that - in formula I, X ₅ is a hydrogen atom.

Other preferred derivatives are such that, in formula I, two adjacent substituents chosen from X ₁ X ₂ , X ₃ , X ₄ and X ₅ form a bridge comprising 3 or 4 links, in particular a methylenedioxi bridge

optionally halogen and preferably fluorinated.

The compounds of formula I, in which Z is C (Z ₁ ) Z ₂ or

S (Z ₁ ) (Z ₃ ) Z ₂ , in which Z ₁ or Z ₃ is an oxygen or sulfur atom, can be prepared, in a manner known per se, by reaction with a derivative of formula II:

with an acylating agent as described in the compilations

"Comprehensive Heterocyclic Cherràstry", ARKatritzky and CW.Rees 1984, Nol.5, pages 222 to 242, Pergamon Press and in "The chemistry of heterocyclic compounds", LC Behr, R.Fusco and CH.Jardoe, 1967, pages 137 à 140, J. Wiley & sons.1966, Vol. 6, pages 391 to 396, Académie Press and "The chemistry of heterocyclic compounds", L.CBehr, R.Fusco and CH.Jardoe, 1967, pages 84 to 91 and table 41, J. Wiley & sons.

By acylating agent is meant a compound of formula Z ₄ C (Z ₁ ) Z ₂ or Z ₅ S (Z ₁ ) (Z ₃ ) Z ₂ , in which Z ₁ , Z ₂ and Z ₃ are defined as above and Z4 and Z5 are chosen from the group comprising a halogen atom, a hydroxyl, alkoxy, alkylthio, amino, mono- or dialkylamino group, the alkyl part of these groups containing from 1 to 4 carbon atoms.

The derivatives of formula II according to the invention can be prepared using various methods per se known in particular in the compilations "Comprehensive Heterocyclic Chemistry", ARKatritzky and CW.Rees 1984, Nol.5, pages 239 to 241 and 263, Pergamon Press; "Advances in Heterocyclic Chemistry", A.Ν.Kost etI.I.Grandberg, 1966, Vol.6, ρages 391 to 396, Académie Press and "The chemistry of heterocyclic compounds", L.CBehr, R.Fusco and CH.Jardoe, 1967 J.Wiley & sons.

A first process for manufacturing the compounds of formula JJ, in which Z is a hydrogen atom and Y is a halogen atom, consists in reacting a 3-arylpyrazole of formula III:

in which X ₁ , X ₂ , X ₃ , X ₄ and X ₅ and Z have the same meaning as in formula I and Y is a hydrogen atom, with a halogenating agent.

Mention may be made, as halogenating agent, as chlorination agent, of chlorine, preferably in an aqueous medium such as in water, or organic such as acetic acid or carbon tetrachloride, or alternatively acid

hypochlorous, hydrochloric acid in the presence of hydrogen peroxide in acetic acid, or sulfuryl chloride or an N-chloroimide such as N-chlorosuccinimide in a chlorinated solvent such as dichloromethane, or phosphorus pentachloride .

The chlorination can be carried out with chlorine in an organic solvent medium, preferably a lower carboxylic acid, at a temperature of

16 to 30 ° C, and preferably at room temperature, the reactants being in a substantially stoichiometric molar ratio. be carried out with N-chlorosuccinimide in an organic solvent medium, preferably a chlorinated solvent such as dichloromethane, 1,2 dichloroethane at a temperature of 0 ° C to 80 ° C, and preferably from 20 ° C to 50 ° C , the reactants being in a substantially stoichiometric molar ratio.

As brominating agent, mention may be made of bromine, preferably in an aqueous solvent such as water, in an acid medium, for example nitric or acetic, in the presence or absence of a base such as sodium acetate, or in an organic solvent such as, for example, chloroform, or alternatively pyridinium perbromide.

The bromination can be carried out, for example, with bromine in an organic solvent medium such as a lower carboxylic acid, at a temperature of 16 ° C. to preferably at room temperature.

As iodination agent, iodine can be used in the presence of hypoiodous acid or in the presence of a base such as an alkali hydroxide or a basic salt such as sodium acetate, or in the presence of a nickel salt ( D); iodine can also be used on the silver salt (J) of the pyrazole of formula III.

The fluorination can be carried out using derivatives of formula II in which Y is an amino group, by preparation of the diazonium tetrafluoroborate derivative derived from an amino group and then irradiation of this compound.

A second method per se known for preparing the derivatives of formula JJ according to the invention, in which Y is a bromine atom, consists in reacting a compound of formula II, in which Y is a formyl group, with bromine in l acetic acid to give 4-bromo-3-phenylpyrazole.

The enaminone compounds of formula lu can be prepared, in a manner known per se, by reaction of a derivative of formula IV:

in which W is a hydroxyl radical or a chlorine atom or a mono or dialkylamino or phenylamino group and X _{1 to} X ₅ have the same meanings as in formula I, with hydrazine hydrate, at a temperature of 10 ° C to 150 ° C, preferably from 20 ° C to 120 ° C, advantageously in an organic solvent medium, preferably a lower carboxylic acid or in an alcohol, in the presence of an organic or inorganic acid catalyst, the molar ratio of 2 reagents being substantially stoichiometric.

The compounds of formula IV, in which W a group

dialkoylamino, X _{1 to} X ₅ being defined as above, can be obtained, in a manner known per se, by reaction of acetophenones of formula V:

in which X ₁ to X ₅ are defined as above, with amide acetals, ester aminals or orthoaminals, preferably in the absence of organic solvent with dialkoyl (preferably dimethyl or diethyl) acetals of the N, N-dimethylformamide, at a temperature of 20 ° C to 130 ° C and preferably from 70 ° C to 130 ° C

The acetophenones of formula V are mostly commercial. Those which are not can be prepared in a manner known per se

- a) either (C. Atkinson etcoll, J.Chem. 1983, vol 26, 1353; W.RBeech in J.Chem.Soc, 1954, 1297) by action of acetaldoxime or one of its derivatives O- substituted, acetaldehyde hydrazone or one of its N-substituted derivatives, in the presence of copper salts and sodium sulfite on an aniline of formula VI:

b) or (GM Rubottom et al. J. Org.Chem. 1983, 48. 1550-15521 by the action of methyllithium, then of trimethylsilyl chloride, on a benzoic acid of formula VII:

It is also possible to prepare, in a manner known per se, certain benzoic acids of formula VII by ortholithiation of the corresponding benzenic derivatives VIII:

and treatment with solid carbon dioxide as described by V.Snieckus in Chem. Rev. 1990, 90, 879.

These acids can also be prepared by treating a benzoic acid of formula IX:

in which one of the Xi, Xj is a group capable of directing in metallo the metallation, by a strong lithiated base (alkyllithiens or dialkylamides of lithium) and reaction with an electrophile, the metallation agent and the electrophile being described in the reference V.Snieckus above.

- c) either by nitrous deamination on an acetophenone of formula V, in which X3 is an amino, with an alkali or alkyl nitrite, preferably at 0 ° C., then reacting the diazonium salt with a reducing agent such as hypophosphorous acid, an alcohol or an ether, preferably at a temperature of 0 ° C at room temperature.

- d) either by action, on a substituted benzene of formula VI, of acetyl chloride, in the presence of anhydrous aluminum chloride;

- E) or by transposition of Fries from an aryl acetate;

- F) or by release of the phenol function (XI is hydroxy) from acetophenones of formula V, in which XI is an alkoxy or an alkylthio;

- g) or by reaction of an acetophenone of formula V, in which at least one of the substituents X is a halogen atom, with a nitrogenous, oxygenated or sulfur-containing nucleophilic agent, preferably a thiolate in a solvent medium, preferably protic apolar.

A second method per se known for the preparation of derivatives of formula II according to the invention, in which Y is a bromine atom, consists in reacting a compound of formula II, in which Y is a formyl group, with bromine in the acetic acid to give 4-bromo-3-phenylpyrazole.

A third process for the preparation of derivatives of formula II according to the invention consists in reacting an enaminone of formula IV, in which W is a hydroxyl, alkoxyl, alkylthio, alkylsulfinyl or -sulfonyl or halogen radical, an amino, mono or dialkylamino group or phenylamino or a halogen and in which X1, X2, X3, X4, X5 have the same meanings as above and Y is halogen or cyano, with hydrazine hydrate at a temperature of 10 ° C to 150 ° C, preferably from 20 ° C to 120 ° C, advantageously in an organic solvent medium, preferably a lower carboxylic acid or in an alcohol in the presence of an organic or inorganic acid catalyst, the molar ratio of the 2 reactants being substantially stoichiometric.

The compounds of formula IV for which Y is a halogen atom or a cyano group, W a dialkoylamino group and X1, X2, X3, X4, X5 being defined as above, can be obtained, by reaction

of acetophenones of formula V, in which X ₁ . at X ₅ are defined as above and Y a halogen atom or a cyano, with amide acetals, ester aminals or orthoaminals, in the absence of organic solvent with dialkyls (preferably dimethyl or diethyl ) acetals of N, N-dimethylformamide, or in an inert organic solvent medium such as toluene cyclohexane, hexane, heptane or tetrahydrofuran, at a temperature of 10 ° C to 50 ° C and preferably from 15 ° C to 40 ° C.

The derivatives of formula V can be prepared, in a manner known per se, by the action of a halogenoacetyl chloride in the presence of anhydrous aluminum chloride on a substituted benzene of formula VI.

The compounds of formula IV for which Y is halogen can also be obtained, in a manner known per se, by reaction of a Ν-halosuccinimide in a chlorinated solvent with the compounds of formula IV for which Y is hydrogen.

A fourth process for the preparation of compounds II consists in reacting a compound of formula II in which at least one of the groups X is halogenated with a nitrogenous or oxygenated or sulfur-containing nucleophile, preferably a thiolate in a solvent medium, preferably apolar protic.

A fifth process for the preparation of compounds II consists in reacting a compound of formula II in which at least one of the groups X is alkylthio with an oxidizing agent, such as hydrogen peroxide, organic or mineral peracids, preferably a persulfate in medium solvent, preferably polar protic.

The following examples are given by way of indication to illustrate the preparation and the fungicidal activity of the derivatives according to the invention. The structure of the latter was confirmed by RMΝ analysis. EXAMPLE 1: 3 ', 5'-dichloroacetophenone.

300 ml of water and 70 ml of concentrated hydrochloric acid are added to 48.6 g (0.30) of 3-5-dichloroaniline. Then, after 30 minutes, 27.5 g (0 , 40 mole) of sodium nitrite in 32 ml of water keeping the temperature between 0 ° C and 5 ° C. To the filtered reaction mixture is added 16.2 g

(0.2 mole) sodium acetate. This solution is poured dropwise onto a solution of 28.5 g (0.48 mole) of acetaldoxime, 25.0 g (0.10 mole) of copper sulphate pentahydrate, of 20.5 g (0.018 mole ) anhydrous sodium sulfite and 121 g (1.50 mole) of sodium acetate in 250 ml of water maintained at 15 ° C. After one hour of stirring, the medium is acidified by addition of concentrated hydrochloric acid. After steam stripping and chromatography of the crude product on a silica column (eluent heptane / ethyl acetate 90/10), 16.6 g (30% yield) of 3 ', 5'-dicholoroacetophenone (compound 1) are recovered. , as a colorless liquid.

EXAMPLE 2 4-acetyl-7-chloro-2,2-difluoro-1,3-benzodioxole (compound 2).

a) 7.5 g (0.038 mole) of 2,2-difluoro-1,3-benzodioxole-4-carboxylic acid, prepared according to the method described in European application 0 333 658, are dissolved, with stirring and under argon atmosphere, in 75 ml of dry tetrahydrofuran (THF). Poured dropwise, at -70 ° C, ml (0.081 mole) of n-butyllithium in solution in hexane. After one hour of stirring, 8.9 g (0.038 mole) of hexachloroethane are poured in solution in 50 ml of dry tetrahydrofuran (THF). After 2 hours at -70 ° C., the temperature is allowed to rise to 10 ° C. The reaction mixture is hydrolyzed with 150 ml of ice water and brought to approximately pH1 by addition of 1N hydrochloric acid. The aqueous phase is extracted with ether, dried over magnesium sulfate and concentrated in vacuo. The solid is washed with heptane to give 3.7 g (0.016 mole) of 7-chloro-2,2-difluoro acid -1,3-benzodioxole-4-carboxylic (yield: 42%; melting point: 185 ° C). b) reacting, at 0 ° C., with stirring and under an argon atmosphere, 3.7 g (0.016 mol) of 7-chloro-2,2-difluoro-1,3-benzodioxole-4- acid carboxylic obtained in a) dissolved in 100 ml of dry THF, with 30 ml (0.047 mol) of methyllithium in solution in ether. The reaction mixture is kept at this temperature for 2 hours and then quickly adds 29 ml (0.235 mol) of chloromethylsilane. The reaction mixture is allowed to return to room temperature and 130 ml of 1N hydrochloric acid are added. Stirring is maintained for 30 min at this temperature then the aqueous phase is extracted with ether, dried over magnesium sulfate and concentrated in vacuo.

The residue is chromatographed on a silica column (eluent

heptane / ethyl acetate 90/10) to give 1.35 g (0.006 mole) of 4-acetyl-7-chloro-2,2-difluoro-1,3-benzodioxole (yield: 37%; melting point: 40 ° VS).

EXAMPLE 3.

a) 29.0 g (0.200 mol) of 6-chloro-2-fluorotoluene are dissolved, with stirring, in 200 ml of dry THF. After cooling to -70 ° C, 151.0 ml (0.24 mole) of n-butyl lithium in solution in hexane are added dropwise. After two hours. The reaction mixture maintained at -70 ° C. is poured onto solid carbon dioxide. After returning to room temperature, an aqueous solution of ammonium chloride is added. The aqueous phase is extracted with ether, acidified with 6N hydrochloric acid, extracted with ether. The organic phases are dried over magnesium sulfate and concentrated to dryness. The residue is washed with heptane to give 9.0 g (0.048 mole) of 4-chloro-2-fluoro-3-methyl benzoic acid, in the form of a white powder (yield: 24%; melting point : 198 ° C).

b) by operating as in Example 2b, 1-acetyl-4-chloro-2-fluoro-3-methylbenzene is obtained (yield: 67%; melting point: 57 ° C) (compound 3). EXAMPLE 4.

By operating as in Example 2, starting from the appropriately substituted acid, the derivatives of formula V and VII were obtained, collected in Table A below:

Example 4A (passage from VIII to VI) 2,4-difluoro-3-chloro benzoic acid (compound 47)

294 ml (0.471 mole) of a 1.6 N solution of n-butyl lithium in hexane are added dropwise at -70 ° C. to a solution of 71 ml (0.471 mole) of tetramethyl ethylene diamine (TMEDA) in 300 ml of dry tetrahydrofuran (THF). With stirring, under argon and at -70 ° C, 33.8 g (0.214 mole) of 2,4-difluoro benzoic acid in 100 ml of tetrahydrofuran

(THF) dry are added dropwise to the previous solution. After one hour of stirring, 111.5 g (0.471 mole) of hexachloroethane are poured in solution in 150 ml of dry THF. After 2 hours at -70 ° C., the temperature is allowed to rise to 10 ° C. The reaction medium is hydrolyzed with 150 ml of ice water and brought to pH1 approximately by addition of 3N hydrochloric acid. The aqueous phase is extracted with ether, dried over magnesium sulfate and concentrated. The residue is recrystallized from heptane / ether. 16.5 g are obtained (40% yield) of 2,4-difluoro-3-chloro benzoic acid. The following acids were obtained by lithiation of the corresponding acids and then reaction with the appropriate reagent.

Example 4B: (passage from VII to VI) (compound 54)

29.0 g (0.2 mole) of 6-chloro-2-fluorotoluene are dissolved, with stirring, in 200 ml of dry THF. After cooling to -70 ° C., it is added dropwise

151 ml (0.24 mole) of n-butyllithium in solution in Fhexane. After two hours, the reaction mixture maintained at -70 ° C is poured onto solid carbon dioxide. After returning to room temperature, an aqueous solution of ammonium chloride is added. The aqueous phase is extracted with ether, acidified with 6N hydrochloric acid, extracted with ether. the organic phases are dried over magnesium sulfate and concentrated to dryness. The residue is washed with heptane to give 9.0 g (0.048 mole) of 4-chloro-2-fluoro-3-methylbenzoic acid, in the form of a white powder (yield: 24%; ponitde fusion: 198 °)

Example 4 C (synthesis of VI from another VI by diazonium) 3-bromo-2-chloro-5-methyl benzoic acid (compound 55)

Diazonium chloride of 2-amino-3-bromo-5-methyl benzoic acid is obtained by pouring dropwise at -5 ° C an aqueous solution of sodium nitrite (0.013 mole) onto a solution containing 0.0109 mole of 2-amino-3-bromo-5-methyl benzoic acid, 10 ml of hydrochloric acid, 10 ml of water and 30 ml of acetic acid. The reaction medium is thus stirred at 0 ° C for 30 minutes then poured into a large volume flask containing 0.013 mole of copper chloride in 10 ml of acetic acid. The mixture obtained is brought to 60 ° C, stirred for 2 hours, then hydrolyzed after cooling by adding ice. The precipitate obtained is filtered and washed with water. 3-bromo-2-chloro-5-methyl benzoic acid is obtained: (Yield 58%, mp 160 ° C)

In the same way as above, the following compounds are obtained:

EXAMPLE 4 D: (synthesis of acetophenones V from benzoic acids VI.

T = Cl)

The acetophenones are obtained from the benzoic acids previously obtained according to the following procedure:

a) 2,3-Dibromo-5-methyl benzoic acid chloride (compound 63). 2.1 g (0.00714 mole) of 2,3-dibromo-5-methyl benzoic acid in solution in 20 ml of 1,2-dichloroethane are treated by the addition of 0.78 ml (0.107 mole) of thionyl chloride in solution in 5 ml of 1,2-dichloroethane. The mixture thus obtained is stirred at 60 ° C for about 5 hours then concentrated in vacuo to yield an oil: 2,3-dibromo-5-methyl benzoic acid chloride.

b) (2,3-dibromo-5-methylphenyl) ethanone (compound 64)

A mixture of 0.87 g is refluxed with 30 ml of ether for 3 hours

(0.0076 mole) magnesium ethylate and 1.17 ml (0.0076 mole) ethyl malonate. Then added to this heterogeneous solution 2g (0.0064 mole) of acid chloride obtained previously diluted in 5 ml of ether. The reaction medium is then stirred at reflux for 3 hours. After cooling, 10 ml of a dilute sulfuric acid solution are added to the reaction medium which is then extracted with ether and washed with water. After drying over MgSO4 and evaporation of the solvent, an oil is obtained which is directly engaged in the decarboxylation step: dilution in a mixture of 5 ml of acetic acid, 5 ml of water and 1 ml of concentrated sulfuric acid then heating to 70 ° C for about 2 hours. The reaction medium is then extracted with ethyl acetate and neutralized with an aqueous sodium hydroxide solution. After drying over MgSO4 and evaporation of the solvent, an oil (2,3-dibromo-5-methylphenyl) ethanone is obtained.

In the same way as above, the following acetophenones are obtained from suitably substituted benzoic acids:

* decarboxylation is carried out by heating in a DMSO-water mixture.

EXAMPLE 4 E: (synthesis of acetophenones V from benzoic acids VI.

T = OH)

4-acetyl-7-chloro-2,2-difluoro-1,3-benzodioxole (compound 87).

3.7 g (0.016 mole) of 7-chloro-2,2-difluoro-1,3-benzodioxole carboxylic acid dissolved in 100 ml of reaction medium are reacted at 0 ° C. with stirring and under an argon atmosphere. Dry THF, with 30 ml (0.047 mole) of methyllithium in solution in ether. the reaction mixture is maintained for two hours at this temperature and then 29 ml (0.0235 mole) of chlorotrimethylsilane are rapidly added. The reaction mixture is allowed to return to ambient temperature and 130 ml of 1N hydrochloric acid are added. stirring is maintained for 30 min at this temperature then the aqueous phase is extracted with ether, dried over magnesium sulfate and concentrated in vacuo. The residue is chromatographed on a silica column (eluent heptane / ethyl acetate 90/10) to give 1.35 g (0.006 mole) of 4-acetyl-7-chloro-2,2-difluoro-1,3-benzodioxole ( yield: 37%; melting point: 40 ° C).

By operating as above, the following benzoic acids are obtained:

EXAMPLE 4 F: Preparation of G.5-dichlorophenyl) ethanone (compound 90) a) from 3.5-dichloroaniine (passage from IV to V):

300 ml of water and 70 ml of concentrated hydrochloric acid are added to 48.6 g (0.30 mole) of 3,5-dichloroanline. 30 minutes later, 27.5 g (0.40 mole) of sodium nitrite in 32 ml of water are poured in dropwise while maintaining the temperature between 0 ° and 5 ° C. To the filtered reaction mixture is added 16.2 g (0.2 mole) of sodium acetate. This solution is poured dropwise onto a solution of 28.5 g (0.48 mole) of acetaldoxime, 25.0 g (0.10 mole) of copper sulphate pentahydrate, of 20.5 g (0.018 mole) of anhydrous sodium sulfite and 121 g (1.50 mole) of sodium acetate in 250 ml of water maintained at 15 ° C. After 1 h of stirring, the medium is acidified by addition of concentrated hydrochloric acid . After steam entrainment and chromatography of the crude product on a silica column (heptane 90, ethyl acetate 10), 16.6 g (30%) of (3,5-dichlorophenyl) ethanone are recovered, in the form of a colorless liquid.

By operating as above, starting from 3-bromo-5-trifluoromethylaniline, the (3-bromo-5-trifluoromethylphenyl) ethanone is obtained (yield: 35%; melting point: RMΝ).

b) from 4-acetyl-2,6-dichloroaniline (passage from V, X3 = ΝH2 to V X3 =

H):

814 g (4 moles) of 4-acetyl-2,6-dichloroaniline, prepared according to patent DD 273,435 of 15/11/1989, are reoristallized in a mixture of 1,200 ml of concentrated hydrochloric acid and 5,200 ml of acid concentrated acetic. After cooling to 0 ° C., a solution of 290 g (4.2 moles) of sodium nitrite in 770 ml of water is run in stream. After 2:30 at this temperature, the solution is poured into a solution at 5 ° C of 2200 ml of 50% hypophosphorous acid in water. At the end of the pouring, the mixture is allowed to return to ambient temperature then 10 l of water are added and the aqueous phase is extracted with dichloromethane. After the decanted organic phase has dried, concentration and distillation of the crude, 591 g is obtained (78% yield, boiling point: 91-95 ° C under 1mm Hg) of (3,5-dichloro) phenyl ethanone in the form of a light yellow liquid.

By operating as above from 4-acetyl-6-bromo-2-chloroaniline, 89% of (3-bromo-5-chloro) phenyl ethanone (compound 91) is obtained

EXAMPLE 4 G: (2-methoxy-3,5-diιnethyl) phenyl ethanone :( passage from X to

V)

a) (2,4-dimethyl) phenyl acetate (compound 92)

To a solution of 120 ml (1 mole) of 2,4-dimethyl phenol in 400 ml of dichloromethane cooled to 5 ° C., 83 ml (1.02 mole) of pyridine are added. After stirring for 15 minutes and cooling the reaction mixture to -10 ° C, 73 ml (1.02 mol) of acetyl chloride dissolved in 100 ml of dichloromethane are added dropwise. The reaction medium is then brought to reflux for 2 hours then cooled and treated by the addition of 200 ml of water, then acidified to pH 1. The organic phase is extracted, dried over MgSO4, and filtered through a bed of silica, to lead to the production of a yellow oil: (2,4-dimethyl) phenyl acetate: Yield 98%

b) 2-acetyl-4,6-dimethyl phenol (compound 93)

307 g (2.3 mole) of aluminum chloride are gradually added in portions to 160 g (0.97 mole) of (2,4-dimethyl) phenyl acetate previously obtained and placed in a 1 liter three-necked flask. The reaction medium is brought gradually to 130 ° C for 2 hours then poured while still warm carefully into a solution containing 2 liters of water and ice.

The hydrolysis is completed by the acidification of the solution to pH 2. The precipitate obtained is filtered through sintered glass and then recrystallized from heptane to lead to the production of an orange powder: 2,4-dimethyl- 6-acetyl phenol:

Yield 55%

c) (2-methoxy-3,5-dimethylphenyl) ethanone (passage from V X1 = OH to V Xl = OMe) (compound 94)

16.4 g (0.1 mole) of the 2,4-dimethyl-6-acetyl phenol previously obtained are dissolved in 100 ml of acetone and treated by the addition of 13.8 g (0.1 mole) of K2CO3 and 10.4 ml (0.11 mole) of dimethyl sulfate. The reaction medium is brought to reflux for 14 hours then, after cooling, 300 ml of water are added and then extracted with dichloromethane. After drying the organic phase over MgSO4 and evaporation, the residue obtained is purified by passage over a column of silica (Heptane / Ethyl acetate 1/1) to lead to the production of an oil: (2-methoxy -3,5-dimethylphenyl) ethanone used crude. In the same way is obtained (2-methoxy-3,5-dichlorophenyl) ethanone (78% yield, NMR), as well as (4-ethoxy-3-chlorophenyl) ethanone (compound 95).

Example 4H: (2-difIuoromethoxy-3,5-dimethvIphenyl) ethanonefcomposed 96) (passage from V X1 = OH to V X1 = OCHF2)

To a solution of 8.2 g (0.05 mole) of 2-acetyl-4,6-dimethyl phenol previously obtained in Example XXX in dichloromethane are added 10 ml of an aqueous sodium hydroxide solution 30% and 8 , 5 g (0.025 mole) of tetrabutylammonium hydrogen sulfate. A stream of chlorodifluoromethane is then passed through the reaction medium for 30 minutes and the latter is then stirred at room temperature for 4 hours.

The reaction medium is then extracted with dichloromethane and washed with water. After drying the organic phase over MgSO4 and evaporation, the residue obtained is purified by passage over a column of silica (dichloromethane) to lead to the production of a liquid:

(2-difluoromethoxy-3,5-dimethylphenyl) ethanone: Yield 21% Example 41: (preparation of chloracetophenone V by chloracetylation

(Friedel-Crafts) deVII)

2-chloro-1- (2-chloro-4-fluoro-5-methylphenyl) ethanone (compound 97)

14.1 g (0.125 mole) of monochloroacetyl chloride are poured in dropwise into a suspension of 16.66 g (0.125 mole) of anhydrous aluminum chloride in 100 ml of dry 1,2-dichlorethane maintained at the temperature of -5 ° C by an ice-acetone bath. 14.46 g (0.1 mol) of 4-chloro-2-fluorotoluene are then poured in dropwise at the same temperature in the solution obtained. The reaction mixture is stirred for 1 hour at -5 ° C and then left to stand overnight, finally brought to 60 ° C until the end of gas evolution. After cooling in an ice bath, a solution of 5 ml of concentrated hydrochloric acid in 100 ml of water is poured dropwise. After decantation, the organic phase is washed successively with 50 ml of water, 50 ml of saturated NaHCO ₃ solution and 50 ml of water and then dried over anhydrous magnesium sulfate. After evaporation of the solvent, 22.3 g of pale yellow oil of 2-chloro-1- (2-chloro-4-fluoro-5-methylphenyl) ethanone which crystallizes on cooling (melting point: 32 ° C .; : 100%)

Using the same conditions and replacing chloracetyl chloride with acetyl chloride, the following acetophenones are obtained:

EXAMPLE 5: 1- (3,5-dichlorophenyl) -3-dimethylaminopropen-2-one-1 (derivative 6).

10 g (0.053 mole) of 3 ', 5'-dicholoroacetophenone are dissolved at room temperature and with stirring in 50 ml of N, N-dimethylformamide dimethylacetal. Stirring is continued and the reaction mixture is heated for 2 hours at 90 ° C. The medium is concentrated to dryness, under reduced pressure. The residue is taken up with 150 ml of heptane. The orange residue is filtered to give 10.0 g (77% yield, melting point: 100 ° C) of 1- (3,5-dichlorophenyl) -3-dimethylaminopropen-2-one-1.

EXAMPLE 6.

The procedure is as in Example 5, starting with the suitably substituted acetophenone and the second suitable reagent.

We obtained the enaminone derivatives of formula IV, in which W is the dimethylamino group, gathered in table B.

EXAMPLE 7: 3- (3,5-dichIorophenyl) 1H-pyrazole (derivative 18).

2.4 g (0.05 mole) of hydrazine hydrate are slowly added at room temperature to a solution of 9 g (0.0369 mole) of 1- (3,5-dichlorophenyl) -3-dimethylaminopropen -2-one-1 in 100 ml of ethanol. The reaction mixture is stirred for 2 hours at room temperature and then concentrated to dryness. The residue is triturated in heptane. 7.1 g (90% yield, melting point 156 ° C.) of 3- (3,5-dichlorophenyl) 1H-pyrazole are obtained.

EXAMPLE 8.

By operating as in Example 7, except for the compound 24 obtained in acetic acid at reflux, starting from the appropriately substituted enaminone, the unsubstituted pyrazole derivatives in 4 of formula III obtained in Table C below were obtained :

EXAMPLE 9 Halogenation of pyrazoles. a) 4- chloro-3- (3,5-dichorophenyl) 1H-pyrazole (compound 31): 2.3 g (0.0152 mole) of 3- (3.5-) are dissolved at room temperature and with stirring dichlorophenyl) 1H-pyrazole in 300 ml of dichloromethane. 2.07 g (0.016 mole) of N-chlorosuccinimide is then added, followed by stirring for 4 days at room temperature. The reaction mixture is then concentrated then chromatography on a silica column (eluent heptane / ethyl acetate 70/30). 1.4 g (yield: 57%, melting point: 192 ° C.) of 4-chloro-3- are obtained. (3,5-dichlorophenyl) 1H-pyrazole. b) 4-chloro-3- (4-chlorophenyl) 1H-pyrazole (compound 32):

1.0 g (0.006 mole) of 3- (4-chorophenyl) 1H-pyrazole is dissolved at room temperature and with stirring in 20 ml of acetic acid. 0.5 g (0.007 mole) of chlorine is then introduced into the reaction mixture. The white precipitate formed is filtered, washed with water and heptane then chromatography on a silica column (eluent heptane / ethyl acetate 70/30). 0.7 g (0.002 mole) is obtained (yield: 58%, Point mp: 158 ° C) of 4-chloro-3- (4-chlorophenyl) 1H-pyrazole. c) 4-bromo-3- (4-chlorophenyl) 1H-pyrazole (compound 33):

1.5 g (0.0084 mol) of 3- (4-chlorophenyl) 1 H-pyrazole, prepared in the previous example (19), are dissolved at ambient temperature and with stirring, in 25 ml of acetic acid. 1.6 g (0.01 mol) of bromine are then poured in drop by drop while maintaining the temperature below 30 ° C. The stirring is continued for 3 hours 30 minutes then the reaction mixture is poured into water. The precipitate is filtered, washed with water and heptane. 2.1 g (0.0084 mole) are obtained

(yield: 100%; Melting point: 143 ° C) of 4-bromo-3- (4-chlorophenyl) 1H-pyrazole.

d) 4-chloro-3- (3,5-dibromophenyl) pyrazole (compound 199)

4 g (0.0132 mole) of 3- (3,5-dibromophenyl) pyrazole and 1 g of pyridine (0.0132 mole) are dissolved at room temperature and with stirring in 50 ml of 1,2-dichloro ethane. 2 g (0.0145) are then added dropwise at 50 ° C. mole) of sulfuryl chloride in 10 ml of dichloro-1,2-ethane, then stirring is continued for 30 minutes at this temperature. After cooling, the precipitate is filtered and recrystallized from 200 ml of dich! Oro-1,2-ethane. 2.9 g are obtained (yield: 66%; melting point: 188 ° C.) of 4-chloro-3- (3,5-dibromophenyl) pyrazole

e) 4-iodo-3- (3,5-dichlorophenyl) pyrazole (compound 200)

2.13 g (0.01 mole) of 3- (3,5-dichlorophenyl) pyrazole are dissolved at room temperature and with stirring in 50 ml of dichloromethane. 2.5 g (0.011 mole) of n-iodosuccinimide are then added, followed by stirring for 4 days. The reaction mixture is then concentrated, the solid obtained washed with heptane and put to boil in 100 ml of 1N sodium hydroxide. After cooling, the solid is filtered, washed with water, dried to give 2g (yield 59%, melting point: 170 ° C) of 4-iodo-3- (3,5-dichlorophenyl) pyrazole. EXAMPLE 10.

By operating as in Example 9, starting from a suitably substituted 3-phenyl-1H-pyrazole, the 3-phenyl-4-chloro or bromo) pyrazoles derivatives of formula II were obtained, collected in Table D below. :

Example 1:

The compounds 3- (phenyl-4-chloro or bromo) pyrazoles of formula II collected in the following table E are obtained by oxidation of methylthio corresponding to the oxone in methanol.

EXAMPLE 12 Obtaining a compound of formula II from another compound of formula II by nitration: (compound 291)

a - Acetylation:

A 11.0 g (0.046 mol) of 4-chloro, 3- (2,2-difluorobenzo-1,3-dioxol-4-yl) pyrazole 1H (prepared as described in patent PH 91-033) dissolved in 100 0.25 g of THF are added 0.25 g (0.005 mole) of 4-dimethylaminopyridine and 4.25 g (0 „042 mole) of triethylamine. A solution of 3.6 g (0.046 mole) of acetyl chloride in 50 ml of THF is poured onto this solution dropwise at 0 ° C. Stirring is continued for 3 h at room temperature. The reaction mixture is poured into 300 ml of water and extracted with ethyl acetate.

After drying the organic phase and concentrating under vacuum, the residue is triturated with 50 ml of heptane, filtered and dried. We obtain 12.8 g of 1-acetyl-4-chloro-3- (2,2-difluorobenzo-1,3-dioxol-4-yl) pyrazole melting at 131 ° C b- Nitration:

A 12.8 g of 1- (acetyl), 4-chloro, 3- (2,2-difluorobenzo-1,3-dioxol-4-yl) pyrazole dissolved in 21 ml H2SO4 (96%) and 140 ml CH ₂ CI ₂ are added, in small portions and at 0 ° C, 6.3 g (0.063 mole) of KNO ₃ . The reaction medium is stirred for 3 h at 0 ° C. then poured poured onto 300 cm ³ of ice. The precipitate is recovered by filtration, washed with water and then with heptane and dried. We obtain 8.05 g of 4-chloro-3- (2,2-difluoro-5-nitrobenzo-1,3-dioxol-4-yl) pyrazole melting at 180 ° C

(yield 63%).

In the same way, the 3- (3,5-dichloro) phenyl-4-chloro pyrazole is nitrated to obtain the 3- (3,5-dichloro-2-nitrophenyl) -4-chloro pyrazole (compound 292) (Yield 55%, mp 173 ° C) and 3- (3,5-dichloro-4-nitrophenyl) -4-chloro pyrazole (yield 8%, mp 177 ° C) (compound 293)

EXAMPLE 13 Obtaining a compound of formula II from another compound of formula II by reduction (compound 294)

6.0 g (0.02 mole) of 4-chloro-3- (2,2-difluoro-5-nitrobenzo-1,3-dioxol-4-yl) pyrazole, dissolved in 60 ml of ethanol, are poured, at room temperature, onto a mixture of 30 ml 36% HCl and 20.2 g (0.09 mole) of SnCl ₂ , 2H ₂ O in 60 ml of ethanol. The reaction medium is stirred for 2 h at room temperature, neutralized with 10% NaOH, then filtered. The insoluble material is washed with ethanol. The alcoholic phase is concentrated under reduced pressure and the residue taken up in ethyl acetate. After drying the organic phase and concentrating under vacuum, the residue is triturated with 50 ml of heptane, filtered and dried. We obtain 4.6 g of 4-chloro, 3- (5-amino, 2,2-difluorobenzo-1,3-dioxol-4-yI) pyrazole melting at 195 ° C (yield 84%).

The pyrazole 4-chloro-3- (3-amino-2,5-dimethylphenyl) pyrazole (compound 295) is obtained in an identical manner (melting point 70 ° C; yield 85%).

EXAMPLE 14 3- (2-amino-3.5-dichloro) phenyl-4-chloro pyrazolef compound

296)

14.6 g (0.05 mole) of 3- (2-nitro-3,5-dichlorophenyl) 4-chloro pyrazole, dissolved in 200 ml of acetic acid, are introduced into a 500 ml three-necked flask. The solution is brought to 50 ° C. and 8.4 g (0.15 mol) of powdered iron are introduced in portions. The reaction medium is then kept under stirring at 70 ° C for 5 hours. After cooling, the reaction medium is poured into 800 ml of water, filtered through sintered glass, rinsed with water and dried to give a white solid (yield: 90%, mp: decomposition at 300 ° C) 3- (2-amino-3,5-dichlorophenyl) 4-chloro pyrazole.

The pyrazole 4-chloro-3- (3-amino-5-chlorophenyl) pyrazole is obtained identically with a melting point of 150 ° C. (yield 41%) (compound 297).

The pyrazole 4-chloro-3- (4-amino-3,5-dichlorophenyl) pyrazole (compound 298) is obtained in an identical manner melting point 217 ° C (yield 82%).

EXAMPLE 15 3- (2-methyl-3,5-dichloro) phenyl-4-chloro pyrazole (compound 299)

This compound is obtained by diazotization of 3- (2-amino-3,5-dichlorophenyl) -4- chloro pyrazole, according to the methods described in the literature: Yield 30%, honey.

By a similar process with the appropriate reagent, the following 3-phenyl-4-chloro or bromo) pyrazoles compounds of formula II are obtained:

EXAMPLE 16 Obtaining a compound of formula II from another compound of formula II by aromatic nucleophilic substitution.

3- (5-chloro-2-nitro-3-methylthio) phenyl-4-chloro pyrazole (compound 305) 5.85 g (0.02 mole) of 3- (3, 5-dichloro-2-nitrophenyl) 4-chloro pyrazole) obtained in Example No. XXX, and 1.5 g (0.021 mole) of sodium methanethiolate in 50 ml of DMF. The reaction medium is heated at 50 ° C for 1 hour then hydrolyzed with 200 ml of water and extracted with ethyl acetate. After drying over MgSO4 and evaporation of the solvent, a yellow oil is obtained: Yield 89%.

By a similar process starting from 3- (3,5-dichlorophenyl) -4-chloro pyrazole and 3 equivalents of sodium methanolate in the NMP, the 3- (3-chloro-5) is obtained with a yield of 50% -mercaptophenyl) -4-chloro pyrazole, melting point 175 ° C (compound 306)

EXAMPLE 17 Obtaining of 4-halo-3-phenyl-pyrazole salts:

4-chloro-3- (3,5-dichlorophenyl) pyrazole hydrochloride (compound 307): 2 g (0.008 mol) of 4-chloro-3- (3,5-dichlorophenyl) are dissolved at room temperature and with stirring pyrazole in 200ml of diethyl ether. Hydrochloric acid is then bubbled until the precipitation stops, the white solid is filtered, rinsed with ether to give 1.1 g (52% yield, melting point: 175 ° C) of hemichlorohydrate. 4-chloro-3- (3,5-dichlorophenyl) pyyazole. By operating as in the example above, the following salts were obtained:

EXAMPLES 18 Pyrazoles substituted in 4 by a substituent Y different from a halogen atom

18 A) 3- (4-bromophenyl) -4-methylsulfonyl pyrazoIe (compound 310) 47.7 g (0.15 mol) of 4-bromoacetophenone dissolved in

500 ml of acetonitrile to 15.3 g (0.15 mol) of sodium methylsulfinate and brought to reflux for 48 hours. After cooling and evaporation of the acetonitrile, the reaction medium is washed with water and extracted with CH ₂ Cl _2. The crude residue obtained is purified by trituration in diisopropyl ether and leads to the production of a beige powder : Yield 72% PF 165 ° C

8.3 g (0.03 mole) of (4-bromophenyl) methylsulfonylacetophenone are dissolved in 30 ml of N, N dimethylformamide dimethylacetal and the mixture is heated to 70 ° C. according to the procedure described in Example No. 5 and then added after isolation of the intermediate enaminone of 2.85 ml (0.06 mol) of hydrazine hydrate according to the procedure described in Example No. 7. After purification by trituration in diisopropyl ether, a beige powder is obtained : Yield: 88% PF 70 ° C

18 B) 3- (3,5-dichlorophenyl) -4-methylthio pyrazole (compound 311): i) 2-bromo-1- (3,5-dichlorophenyl) ethan-1-one

3.77 g (0.019 mole) of (3,5-dichlorophenyl) ethanone, dissolved in 50 ml of acetic acid are added 1.03 ml (0.02 mole) of bromine at room temperature. After 12 hours of stirring, the evaporation of the acetic acid leads to the production of a yellow precipitate: 2-bromo-1- (3,5-dichlorophenyl) ethan-1-one (yield 81%).

ii) 1- (3,5-dichlorophenyl) -2-methylthio ethan-1-one:

3.7 g (0.015 mole) of 1- (3,5-dichlorophenyl) -2-methylthio ethan-1-one are prepared by adding 1.23 g (0.017 mole) of sodium methanethiolate in solution at 0 ° C. in 10 ml of methanol on 4.28 g (0.016 mole) of 2-bromo-1- (3,5-dichlorophenyl) ethan-1-one obtained previously. iii) 3- (3,5-dichlorophenyl) -4-methylthio pyrazole:

2.3 g (0.0098 mole) of 1- (3,5-dichlorophenyl) -2-methylthio ethan-1-one are dissolved in 4ml (0.029 mole) of N, N dimethylformamide dimethylacetal and heated to 70 ° C. the procedure described in example 5 then added after isolation of the intermediate enaminone of 0.9 ml (0.019 mole) of hydrazine hydrate according to the procedure described in example 7. After purification by trituration in heptane, 1.12 g of the desired compound are obtained: Yield 44%, mp 148 ° C.

18 C) 3- (3,5-dichloro) phenyl-4-methoxy pyrazole (compound 312):

i) 1- (3,5-dichlorophenyl) -2-methoxy ethan-1-one:

1- (3,5-dichlorophenyl) -2-methoxy ethan-1-one is obtained by adding 5.74 g (0.023 mole) of 3,5-dichlorophenyl magnesium bromide to a solution in 10 at 5 ° C. ml of THF 1.77 ml (0.0213 mole) of methoxyacetonitrile. The medium is stirred at room temperature for 2 hours then hydrolyzed by pouring it into an ice-cold solution of water and IN hydrochloric acid. The aqueous phase is extracted with ethyl acetate and the organic phase is brought to a basic pH by washing with a saturated solution of sodium bicarbonate. After drying over MgSO4 and evaporation of the solvents, the oily residue obtained is purified by chromatography on silica gel (Ethyl acetate / Heptane 10/90).

ii) 3- (3,5-dichlorophenyl) -4-methoxy pyrazole:

0.47 g (0.0021 mole) of 1- (3,5-dichlorophenyl) -2-methoxy ethan-1-one thus obtained are dissolved in 1 ml (0.0074 mole) of N, N dimethylformamide dimethylacetal and heated to 70 ° C according to the procedure described in Example 5 then added after isolation of the intermediate enaminone of 0.12 ml (0.0024 mole) of hydrazine hydrate according to the procedure described in Example n ° 7. After purification by trituration in heptane, 0.27 g of the desired compound are obtained:

Yield 52% mp 173 ° C. 18 D) 3- (3,5-dichloro) phenyl-4-dimethylamino pyrazole (compound 313): This compound is prepared by analogy with the procedure described in "II Farmaco Ed. Sc. 39, 618,1983 by P. GIORI et al with 3,5-dichlorophenylacetonitrile as raw material Yield 33% Honey.

18 E) Obtaining compounds of formula II by cyclization between Y and

X5:

8-bromo-4,5-dihydro-2H-benz {g} indazole (compound 314)

This compound is prepared from 1.66 g (0.0059 mole) 6-bromo-2-dimethylaminomethylene tetralone and 0.58 g (0.008 mole) of hydrazine hydrate in ethanol as described in Example 7 : yield: 31%, melting point: 155 ° C

EXAMPLES 19: Pyrazoles substituted at 1 by a substituent Z other than a hydrogen atom:

19A) 1-isopropylaminocarbonyl-4-chIoro-3- (3,5-dichlorophenyl) pyrazole (compound 315):: 0.95 g (0.011 mol) of isopropyl isocyanate are added, dropwise and at 0 ° C, to a solution of 2.55 g (0.01 mole) of 4-chloro-3- (3,5-dichlorophenyl) pyrazole 1H and 1.55 ml (0.011 mole) of triethylamine in 20 ml of anhydrous DMF . Stirring is continued for 2 h at room temperature. The reaction mixture is poured into 100 ml of water and extracted with ethyl acetate. After drying the organic phase and concentrating under vacuum, the residue is triturated with 50 ml of heptane, filtered and dried. We obtain 2.10 g of 1-isopropylaminocarbonyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole melting at 127 ° C

19 B) 1-acetyl-4-chIoro-3- (3,5-dichlorophenyl) pyrazole (compound

316):

To 2.55 g (0.01 mole) of 4-chloro-3- (3,5-dichlorophenyl) pyrazole dissolved in 30 ml of THF are added 0.35 g (0.003 mole) of 4-dimethylaminopyridine and 1.55 ml (0.011 mole) of triethylamine. On this solution is poured, dropwise and at 0 ° C, a solution of 0.85 g (0.011 mole) of acetyl chloride in

10 ml of THF. Stirring is continued for 2 h at room temperature. The reaction mixture is poured into 100 ml of water and extracted with ethyl acetate. After drying the organic phase and concentrating under vacuum, the residue is triturated with 50 ml of heptane, filtered and dried. We obtain 2.80 g of 1-acetyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole melting at 125 ° C

19 C) 1-methoxycarbonyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole (compound 317):

To 2.55 g (0.12 mole) of 4-chloro-3- (3,5-dichlorophenyl) pyrazole dissolved in 300 ml of THF are added 2.52 g (0.0204 mole) of 4-dimethylaminopyridine and 18 , 3 ml (0.132 mole) of triethylamine. A solution of 12.5 g (0.132 mole) of methyl chloroformate in 100 ml of THF is poured onto this solution dropwise at 0 ° C. Stirring is continued for 20 h at room temperature. The reaction mixture is poured into 500 ml of water and extracted with ethyl acetate. After drying the organic phase and concentrating under vacuum, the residue is triturated with 150 ml of heptane, filtered and dried. We obtain 33.5 g of 1-methoxycarbonyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole melting at 144 ° C

The following 1-substituted-4-chloro-3-phenyl) pyrazoles compounds are prepared as in Example 19 C:

19 D) l-acetoxymethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazόle (compound 323): 0.15 ml of 1,8-diazabicydo (5.4.0) undecen-7-ene is added, at room temperature, to a solution of 2.55 g (0.01 mole) of 4-chloro-3- (3 , 5-dichlorophenyl) pyrazole and 0.90 g (0.030 mole) of paraformaldehyde in 70 ml of THF. The reaction mixture is stirred for 4 h at room temperature. A solution of 1.20 g (0.015 mole) of acetyl chloride in 10 ml of THF is poured dropwise at 0 ° C and stirring is continued for 6 h at room temperature. The reaction medium is concentrated to dryness. The residue is taken up in 15 ml of heptane and then dried. We obtain 3.05 g of 1-acetoxymethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole melting at 95 ° C

19 E) 1-chloromethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazoIe

(compound 324):

0.15 ml of 1,8-diazabicyclo (5.4.0) undecen-7-ene is added, at room temperature, to a solution of 2.55 g (0.01 mole) of 4-chloro-3- (3 , 5-dichlorophenyl) pyrazole and 0.90 g (0.030 mole) of paraformaldehyde in 70 ml of THF. The reaction mixture is stirred for 4 h at room temperature. A solution of 4.75 g (0.015 mol) of thionyl chloride in 20 ml of THF is added dropwise at 0 ° C. The stirring is continued for 4 h at room temperature. The reaction medium is concentrated to dryness. The residue is taken up in 15 ml of heptane and then dried. We obtain 2.15 g of 1-chloromethyl-4-chloro-3- (3,5-dichlorophényI) pyrazole melting at 88 ° C

19 F) 1-azidomethyl-4-chIoro-3- (3,5-dichlorophenyl) pyrazole (compound 325):

0.70 g (0.010 mole) of sodium azide is added, at room temperature, to a solution of 1.85 g (0.005 mole) of 1-chloromethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole in 25 ml of DMF. The reaction medium is stirred for 12 h, diluted with 100 ml of H 2 O and extracted with ether. After drying the organic phase and concentrating under vacuum, the residue is triturated with 20 ml of heptane, filtered and dried. We obtain 1.30 g of 1-azidomethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazoIe melting at 74 ° C 19 G) 1-triphenylphosphonomethyl-4-chloro-3- (3,5-dichlorophenyl) -pyrazole chloride (compound 326):

1.85 g (0.005 mole) of 1-chloromethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole and 1.65 g (0.00625 mole) of triphenylphosphine in 30 ml of THF are brought to reflux for 8 a.m. (inert atmosphere). After returning to ambient temperature, the insoluble material is recovered by filtration, triturated with 15 ml of heptane, filtered and dried. We obtain 0.50 g of 1-triphenylphosphonomethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole chloride which decomposes at 260 ° C.

19 H) 1-t-butoxycarbonylmethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole (compound 327):

A solution of 5.00 g (0.033 mole) of t-butyl chloroacetate in 30 ml of DMF is poured, dropwise and at room temperature, into a mixture of 7.62 g (0.030 mole) of 4-chloro -3- (3,5-dichlorophenyl) pyrazole and 5.60 g (0.040 mole) of K ₂ CO ₃ . The reaction medium is stirred for 12 h at room temperature, diluted with 200 ml of H ₂ O and extracted with ether. After drying the organic phase and concentrating under vacuum, the residue is triturated with 20 ml of heptane, filtered and dried. We obtain 10.20 g of 1-t-butoxycarbonylmethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole melting at 86 ° C

19 1) 1-carboxymethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole

(compound 328):

A solution of 6.85 g (0.0185 mol) of 1-t-butoxycarbonylmethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole in 100 ml of trifluoroacetic acid is stirred for 16 h at room temperature. The reaction medium is poured onto 300 cirβ of an ice-water mixture. The insoluble material is recovered by filtration, washed with heptane and dried. We obtain 5.65 g of 1-carboxymethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole melting at 182 ° C 19 J) 1-carboxymethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole

(compound 329):

A solution of 3.25 g (0.010 mole) of 1-carboxymethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole and 0.80 g of sodium hydroxide pellets in 50 ml of ethanol is brought to reflux for 1 hour. After returning to ambient temperature, the insoluble material is recovered by filtration, triturated with 30 ml of heptane, filtered and dried. We obtain 2.65 g of the sodium salt of 1-carboxymethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole melting at 246 ° C

EXAMPLE 20 In Vivo Test on Botrytis ceunerea on excised tomato leaf:

(sensitive strains and strains resistant to benzimidazoles):

An aqueous suspension of the active material to be tested having the following composition is prepared by fine grinding:

- active ingredient: 60 mg

- Tween 80 surfactant, oleate of polyoxyethylene derivative of sorbitan) diluted to 10% in water: 0.3 ml

- make up to 60 ml of water.

This aqueous suspension is then diluted with water to obtain the desired concentration of active material.

- Tomatoes grown in a greenhouse (Marmande variety) 30 days old are treated by spraying with aqueous suspensions as defined above and at various concentrations of the test compound.

After 24 hours the leaves are cut and put in a Petri dish (diameter 14 cm), the bottom of which has been previously lined with a disc of wet filter paper (10 leaflets per box).

The inoculum is then supplied using a syringe by depositing drops (3 per leaflet) of a suspension of Botrvtis cinerea spores. sensitive to benzimidazoles or resistant to benzimidazoles, obtained from 15 day cultures, then suspended at a rate of 150,000 units per cm ³ .

The control is made 6 days after the contamination in comparison with an untreated control.

Under these conditions, at the dose of 1 g / l, good (at least 75%) or total protection is observed with the following compounds: 20, 31, 45, 46, 199, 202, 204 to 207, 212, 213, 218, 219, 221, 222, 225, 234, 238, 239, 241 to 247, 250, 253 to 255, 296, 307, 316, 319, 321 and 322 on Botrytis sensitive to benzimidazoles.

EXAMPLE 21 In vivo test on Pyricularia oryzae responsible for rice piriculariosis:

- active ingredient: 60 mg

- make up to 60 ml of water.

Rice, sown in pots in a 50/50 mixture of enriched peat and pozzolan, is treated at the 10 cm height stage by spraying the above aqueous suspension.

After 24 hours, an aqueous suspension of Pyricularia oryzae spores, obtained from a 15-day culture, is applied to the leaves, then suspended at the rate of 100,000 units per cm ³

The rice plants are placed for 24 hours in incubation (25 ° C, 100% relative humidity), then placed in an observation cell, under the same conditions, for 5 days. Reading is done 6 days after contamination.

Under these conditions, at the dose of 1 g / l, good (at least 75%) or total protection is observed with the following compounds: 7, 20, 22, 31, 36, 37, 38, 42, 45, 46, 202 to 207, 209, 211 to 213, 218 to 226, 231, 238, 239, 241 to 246, 249, 250, 253 to 256, 293, 294, 301, 305, 316 to 318, 321.

EXAMPLE 22 In vivo test on Plasmopara viticola:

An aqueous suspension of the active ingredient to be tested having the following composition is prepared by fine grinding:

- active ingredient: 60 mg

- make up to 60 ml of water.

Vine cuttings (Vitis vinifera). Chardonnay variety, are grown in pots. When these plants are 2 months old (8 to 10 leaf stage, 10 to 15 cm high), they are treated by spraying with the above aqueous suspension.

Plants, used as controls are treated with an aqueous solution not containing the active ingredient.

. After drying for 24 hours, each plant is contaminated by spraying with an aqueous suspension of Plasmopara viticola spores obtained from a 7-day culture, then suspended at the rate of 100,000 units per cm ³ .

The contaminated plants are then incubated for two days at approximately 18 ° C, in an atmosphere saturated with humidity and then for 5 days at approximately 20-22 ° C under 90-100% relative humidity.

The reading is done 7 days after contamination, in comparison with the control plants. Under these conditions, at the dose of 1 g / l, good (at least 75%) or total protection is observed with the following compounds: 20, 21, 25, 31, 33, 34, 36, 37, 41, 43, 200 to 204, 206, 207, 212, 213, 219 to 221, 223 to 228, 230, 231, 234, 236 to 239, 243 to 245, 248, 254 to 256, 291, 294, 305, 307 and 313.

EXAMPLE 23 In vivo test on Puccinia recondita (wheat rust):

- active ingredient: 60 mg

- Tween 80 surfactant (oleate of polyoxyethylene derivative of sorbitan) diluted to 10% in water: 0.3 ml

- Make up to 60 ml of water to obtain a suspension / solution at 1 g / l. This aqueous suspension is then optionally diluted with water to obtain the desired concentration of active material.

Wheat, in pots, sown on a 50/50 peat soil peat soil substrate, is treated at the 10 cm height stage by spraying the above aqueous suspension.

After 24 hours, an aqueous suspension of spores (100,000 sp / cm ³ ) is sprayed onto the wheat; this suspension was obtained from contaminated plants. The wheat is then placed for 24 hours in an incubation cell at approximately 20 ° C. and at 100% relative humidity, then for 7 to 14 days at 60% relative humidity.

The condition of the plants is checked between the 8th and 15th day after contamination, by comparison with an untreated control.

Under these conditions, at the dose of 1 g / l, good (at least 75%) or total protection is observed with the following compounds: 22, 35, 37, 31 and 32, 204, 206, 207, 213, 218, 221, 223, 225, 238, 239, 246, 248, 251, 253, 294, 307, 316, 322.

These results clearly show the good fungicidal properties of the derivatives according to the invention against fungal diseases of plants due to fungi belonging to the most diverse families such as

Phycomycetes, Basidiomycetes, Ascomycetes, Adelomycetes or fungi imperfecti, in particular Botrytis sp., Pyricularia oryzae, downy mildew.

For their practical use, the compounds according to the invention are rarely used alone. Most often these compounds are part of compositions. These compositions, which can be used as fungicidal agents, contain as active material a compound according to the invention as described above in admixture 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. These compositions also form part of the invention.

These compositions can also contain all kinds of other ingredients such as, for example, protective colloids, adhesives, thickeners, thixotropic agents, penetration agents, stabilizers, sequestrants, etc. More generally the compounds used in the invention can be combined with all the solid or liquid additives corresponding to the usual techniques of formulation.

In general, the compositions according to the invention usually contain from 0.05 to 95% approximately (by weight) of a compound according to the invention (hereinafter called active material), one or more solid or liquid carriers and, optionally, one or more surfactants.

By the term "support", in the present description, is meant an organic or mineral, natural or synthetic material, with which the compound is combined to facilitate its application on the plant, on seeds or on the ground. 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, in particular butanol, etc.).

The surfactant can be an emulsifying, dispersing or wetting agent of ionic or nonionic type or a mixture of such surfactants. Mention may be made, for example, of salts of polyacrylic acids, salts of lignosulfonic acids, salts of phenolsulfonic acids or

naphthalenesulfonic, polycondensates of ethylene oxide on fatty alcohols or on fatty acids or on fatty amines, substituted phenols (in particular alkylphenols or arylphenols), salts of esters of sulfosuccinic acids, derivatives of taurine (in particular alkyltaurates), phosphoric esters of polyoxyethyl alcohols or phenols, esters of fatty acids and of polyols, the derivatives containing sulfates, sulfonates and phosphates of the preceding compounds. The presence of at least one surfactant is generally essential when the compound and / or the inert support are not soluble in water and the vector agent for the application is water.

Thus, the compositions for agricultural use according to the invention can contain the active materials according to the invention within very wide limits, ranging from 0.05% to 95% (by weight). Their surfactant content is

advantageously between 5% and 40% by weight.

These compositions according to the invention are themselves in fairly diverse forms, solid or liquid.

As solid composition forms, there may be mentioned powders for dusting (with a compound content of up to 100%) and granules, in particular those obtained by extrusion, by compacting, by impregnation of a granulated support, by granulation with from a powder (the compound content in these granules being between 0.5 and 80% for the latter cases), the effervescent tablets or tablets. The 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.

As 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 spray powder), pasta, gels.

The emulsifiable or soluble concentrates most often comprise 10 to 80% of active material, the emulsions or solutions ready for application containing, for their part, 0.001 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, penetration agents, corrosion inhibitors, dyes or adhesives previously mentioned- From these concentrates, emulsions of any desired concentration can be obtained by dilution with water, which are particularly suitable for application to crops.

As an example, here is the composition of some emulsifiable concentrates:

Example CE 1:

- active ingredient 400 g / l

- alkaline dodecylbenzene sulfonate 24 g / l

- oxyethylated nonylphenol with 10 molecules

ethylene oxide 16 g / l

- cyclohexanone 200 g / l - aromatic solvent qsp1 liter

According to another formula of emulsifiable concentrate,

Example CE 2

- active ingredient 250 g

- epoxidized vegetable oil 25 g

- mixture of alkylaryl sulfonate and

polyglycol ether and fatty alcohols 100 g

- dimethylformamide 50 g

- xylene 575 g

The 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, 0 to 10% of suitable additives, such as defoamers, corrosion inhibitors, stabilizers, penetrating agents and adhesives and, as support, water or an organic liquid in which the active ingredient is sparingly or not very soluble: certain organic solids or mineral salts can be dissolved in the support to help prevent sedimentation or as antifreeze for water.

As an example, here is a concentrated suspension composition

Example SC 1:

- active ingredient 500 g

- polyethoxylated tristyrylphenol phosphate 50 g

- polyethoxylated alkylphenol 50 g

- sodium polycarboxylate 20 g

- ethylene glycol 50 g

- organopolysiloxane oil (antifoam) 1 g

- polysaccharide 1.5 g

- water 316.5 g Wettable powders (or spray powder) are usually prepared so that they contain 20 to 95% of active ingredient, and they usually contain, in addition to the solid support, 0 to 30% of a wetting agent, 3 to 20% of a dispersing agent, and, when necessary, from 0.1 to

10% of one or more stabilizers and / or other additives, such as penetration agents, adhesives, or anti-caking agents, colorants, etc.

To obtain the sprayable powders or wettable powders, the active ingredients are intimately mixed in the appropriate mixers with the additional substances and ground with mills or other suitable grinders. This gives sprayable 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.

Instead 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.

As an example, here are various compositions of wettable powders (or spraying powders):

Example PM 1

- active ingredient 50%

. - ethoxylated fatty alcohol (wetting agent) 2.5%

- ethoxylated phenylethylphenol (dispersing agent) 5%

- chalk (inert support) 42.5%

Example PM 2:

- active ingredient 10%

- branched type oxo synthetic alcohol,

C13 ethoxylated with 8 to 10 ethylene oxide

(wetting agent) 0.75%

- neutral calcium lignosulfonate (agent dispersant) 12%

- calcium carbonate (inert filler) q.s.p. 100%

Example PM 3:

This wettable powder contains the same ingredients as in the previous example, in the proportions below:

- active ingredient 75%

- wetting agent 1.50%

- dispersing agent 8%

- calcium carbonate (inert filler) q.s.p. 100%

Example PM 4:

- active ingredient 90%

- ethoxylated fatty alcohol (wetting agent) 4%

- ethoxylated phenylethylphenol (dispersing agent) 6%

Example PM 5:

- active ingredient 50%

- mixture of anionic surfactants and

non-ionic (wetting agent) 2.5%

- sodium lignosulfonate (dispersing agent) 5%

. - kaolin clay (inert support) 42.5%

The 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". The compounds according to the invention can be formulated in the form of water-dispersible granules also included within the scope of the invention.

These dispersible granules, of apparent density generally comprised between approximately 0.3 and 0.6 have a particle size generally comprised between approximately 150 and 2000 and preferably between 300 and 1500 microns.

The active material content of these granules is generally between approximately 1% and 90%, and preferably between 25% and 90%.

The rest of the granule is essentially composed of a solid filler and optionally surfactant additives giving the granule properties of dispersibility in water. These granules can be essentially of two distinct types depending on whether the selected filler is soluble or not in water. When the filler is water-soluble, it can be mineral or, preferably, organic. Excellent results have been obtained with urea. In the case of an insoluble filler, it is preferably mineral, such as for example kaolin or bentonite. It is then advantageously accompanied by surfactants

(at a rate of 2 to 20% by weight of the granule) of which more than half is, for example, constituted by at least one dispersing agent, essentially anionic, such as an alkaline or alkaline earth polynaphthalene sulfonate or an alkaline or alkaline lignosulfonate -teιτeux, the rest being constituted by nonionic or anionic wetting agents such as an alkali or alkaline-earth alkyl naphthalene sulfonate.

Furthermore, although this is not essential, other adjuvants can be added such as anti-foaming agents.

The granule according to the invention can be prepared by mixing the necessary ingredients and then granulation according to several techniques known per se (bezel, fluid bed, atomizer, extrusion, etc.). It generally ends with a crushing followed by sieving to the particle size chosen within the limits mentioned above.

Preferably, it is obtained by extrusion, operating as indicated in the examples below. Example GD1: Dispersible granules

In a mixer, 90% by weight of active material and 10% urea pearls are mixed. The mixture is then ground in a pin mill. A powder is obtained which is moistened with approximately 8% by weight of water. The wet powder is extruded in a perforated roller extruder. A granule is obtained which is dried, then crushed and sieved, so as to keep respectively only the granules of a size between 150 and 2000 microns. Example GD2: Dispersible granules

In a mixer, the following constituents are mixed:

- active ingredient 75%

- wetting agent (sodium alkylnaphthalene sulfonate) 2%

- dispersing agent (sodium polynaphthalene sulfonate) 8%

- inert filler insoluble in water (kaolin) 15%

This mixture is granulated in a fluid bed, in the presence of water, then dried, crushed and sieved so as to obtain granules of size between 0.15 and 0.80 mm.

These granules can be used alone, in solution or dispersion in water so as to obtain the desired dose. They can also be used to prepare combinations with other active materials, in particular fungicides, the latter being in the form of wettable powders, or aqueous granules or suspensions.

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

A subject of the invention is also the use of the compounds according to the invention for combating fungal diseases of plants by treatment preventive or curative, on the foliage or the propagation material, of the latter or their place of growth.

Claims

1) 3-Arylpyrazole derivatives characterized in that they are of formula (I)

in which: X ₁ , X ₂ , X ₃ , X ₄ and X ₅ , identical or different, are:

- an alkyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl benzyl, alkenyl, alkynyl, alkoxy, alkylthio, formyl, acetyl, alkyl- or alkoxy (thio) -carbonyl, mono or di alkylamino (thio) carbonyl, carboxyl, carboxylate, carbamoyl or benzoyl radical ,

- a phenyl, phenyloxy, phenylthio radical,

a phosphoryl group, substituted by two groups chosen from the group comprising alkyl, alkoxy, alkylthio and dialkylamino, - a trialkyl- or alkylphenyl-silyl group,

Two of the adjacent X ₁ , X ₂ , X ₃ X ₄ and X ₅ may also be linked together by a carbon bridge comprising from 2 to 4 links, at least one of which may be replaced by an oxygen or sulfur atom. or nitrogen, the carbons of this bridge may or may not be substituted by at least one halogen atom and / or at least one hydroxy, amino, alkyl, alkoxy, alkylthio, mono or di alkylamino, alkylsulfinyl or -sulfonyl group. alkyl part being as defined above,

with the proviso that X \ to X5 cannot each be simultaneously a hydrogen atom;

Y is a hydrogen or halogen atom, a nitro, nitrile, thiocyanato or alkyl, alkoxy or alkylthio group, optionally mono or

polyhalogenated, an amino optionally substituted by one or two alkyls or phenyls;

Z is:

- a hydrogen, halogen atom, a cyano, nitro, hydroxy group or

- alkyl, haloalkyl, cycloalkyl or cycloalkyl -alkyl the cycloalkyl part which may be substituted by the group GR4, defined below, or

- a phenyloxy or phenylthio,

- an amino optionally substituted by one or two alkyls or

- alkenyl or alkynyl, each containing 3 to 7 carbon atoms, possibly substituted

- phenyl or Het, possibly substituted

- a group of formula C (Z ₁ ) Z ₂ in which:

Z ₁ is an oxygen or sulfur atom or an alkylamino or imino or arylamino group and - Z ₂ is:

- a hydrogen, halogen atom, a hydroxy, sulfhydrile, cyano, amino group,

- alkyl, alkoxy, alkylthio,

- alkenyl or alkynyl, each containing 3 to 7 carbon atoms

- phenyl, phenylalkyl, phenoxy, phenalkyloxy, - Het or Het-alkyl,

-phenylalkenyl or phenylalkynyl; Het-alkenyl or Het-alkynyl

- mono or di alkylamino, a mono- or diphenyl-amino or -sulfonylamino radical,

possibly stolen;

;

- or a group S (Z ₁ ) (Z ₃ ) Z ₂ , in which Z ₁ and Z ₂ have the same meanings as above and Z3 has the same meanings without necessarily being equal to Z ₁ , provided that Z n is not a hydrogen atom when X3, X4 and X5 are each a hydrogen atom;

it being understood that in all of the above meanings,

the hydrocarbon part of these groups may comprise from 1 to 7 carbon atoms and may be optionally halogenated (from 1 to 8 halogen atoms),

the cycloalkyl part of these groups can comprise from 3 to 7 carbon atoms and be optionally substituted with at least one substituent chosen from the group GR4,

- the phenyl part denotes the phenyl nucleus optionally substituted with 1 to 5 substituents chosen from the group comprising a halogen atom, an alkyl or alkoxy of 1 to 3 carbon atoms.

- Het is a heterocyclic radical, mono or bicyclic, containing 5 to 10 atoms, of which 4 are heteroatoms (oxygen, sulfur, nitrogen, phosphorus). 2) Derivatives according to claim 1, characterized in that, in the formula, Y is a chlorine or bromine atom.

3) Derivatives according to claim 1, characterized in that, in the formula, Z is a hydrogen atom or a group C (Z ₁ ) Z ₂ in which Z ₁ is an oxygen or sulfur atom.

4) Derivatives according to one of claims 1 to 3, characterized in that, in formula I, X ₁ , X ₂ and X ₄ are a hydrogen or halogen atom or an optionally halogenated nitro or alkyl group, from 1 to 4 carbon atoms.

5) Derivatives according to one of claims 1 to 4, characterized in that X ₃ is a hydrogen or fluorine atom. 6) Derivatives according to one of claims 1 to 5, characterized in that

X ₅ is a hydrogen atom.

7) Process for the preparation of derivatives according to one of claims 1 to 6, characterized in that a phenylpyrazole of formula III is reacted, in which X ₁ to X ₅ have the same meanings and Y and Z are each an atom hydrogen, with a halogenating agent.

8) Method according to claim 7, characterized in that acts, in aqueous or organic solution, a chlorinating agent such as chlorine, hypochlorous acid, hydrochloric acid in the presence of hydrogen peroxide, chloride sulfuryl, an N chloroimide such as for example N chloro succinimide or phosphorus pentachloride.

9) Method according to claim 7, characterized in that reacts a brominating agent such as bromine in aqueous or organic solution, pyridinium perbromide. 10) Process according to claim 7, characterized in that an iodination agent such as iodine is acted alone or in acid or basic solution. 11) Method according to claim 7, characterized in that one carries out the preparation of the tetrafluoroborate of the diazonium derivative of the amino in 4 of the derivative of formula II.

12) Process for the preparation of derivatives of formula I, in which Z is a group C (Z ₁ ) Z ₂ , characterized in that a derivative of formula II is acted on, in which Z is a hydrogen atom, with an acylating agent of formula Z ₄ C (Z ₁ ) Z ₂ , in which Z4 is a halogen atom or a group

hydroxyl, amino, alkoxy, mono or di alkylamino alkylthio. 13) Process for the preparation of derivatives of formula V, in which

X \, X ₂ and X4 are defined as in claim 1, characterized in that a derivative of formula VI is acted on, in which X ₁ , X ₂ and X ₄ are defined as above, with acetaldoxime or a of its O-substituted derivatives, or the hydrazone of acetaldehyde or one of its N-substituted derivatives or the semicarbazone or semithiocarbazone of acetaldehyde or one of their derivatives

N ₂ or N ₃ -substituted, in the presence of copper salts and sodium sulfite.

14) Fungicidal composition for the protection of plants against fungal diseases, characterized in that it contains, as active material, a derivative according to one of claims 1 to 6.

15) Use of a derivative according to one of claims I to 6 for the protection of plants against fungal diseases.