WO1994029300A1

WO1994029300A1 - Pyrazole fungicides 3-substituted by a heterocyclic ring

Info

Publication number: WO1994029300A1
Application number: PCT/FR1994/000665
Authority: WO
Inventors: Philippe Desbordes; François Guigues; Raymond Peignier
Original assignee: Rhone Poulenc Agrochimie
Priority date: 1993-06-07
Filing date: 1994-06-06
Publication date: 1994-12-22
Also published as: IL109910A0; FR2707295A1; AU6973694A

Abstract

Pyrazoles 3-substituted by a heterocyclic ring. These pyrazoles are of formulae (I) and (Ibis) wherein Het = an optionally substituted heterocyclic ring; Y1, Y2 = hal, nitro, CN, alkyl, alkoxy, acyl; Z = H, nitro, CN, (halo)alkyl, alkylS(O)n, wherein n = 1 or 2, optionally substitued aminoalkyl, acyl, aminocarbonyl, alkoxycarbonyl. Fungicides for agricultural use.

Description

Pyrazole fungicides substituted in position 3 by a heterocycle

The present invention relates to new derivatives of the family of pyrazoles substituted in position 3 by a heterocycle, 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 derivatives of pyrazole of formula I and their tautomeric forms I bis,:

I Ibis

their salts and their metallic or metalloid complexes as well as the corresponding N-oxides, in which:

Yl and Y, which can be different or identical, are:

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

a group, alkoxy or alkylthio, each of these groups being optionally halogen,

an acyl or thio acyl radical which may be: a formyl radical, an alkyl- or alkenyl-carbonyl or -thiocarbonyl group, the alkyl or alkenyl radical possibly being linear or branched,

- an alkoxy- or alkylthio-carbonyl group - an optionally substituted phenoxy,

- an amino substituted or not by one or two alkyls or phenyls,

- an alkylsulfinyl or alkylsulfonyl group, it being understood that the alkyl part of all the above groups comprises from 1 to 4 carbon atoms; Z is:

- a) - a hydrogen atom, a nitro, amino, hydroxy, cyano group,

B) an alkyl- or haloalkyl- or cycloalkyl-thio, -sulfinyl or - sulfonyl, alkoxy- or haloalkoxy-sulfonyl, alkenyl- or alkynyl-sulfonyl, phenyl- or benzyl-sulfenyl or sulfonyl group,

- c) - an aminomethylene group in which the amino radical can be substituted by one or two identical or different groups which are:

an alkyl group optionally substituted with a cyano, nitro, alkoxy, cycloalkyl, alkyl- or alkoxy- or monoalkylamino- or dialkylamino-carbonyl, alkylthio, alkylsulfonyl substituent, an optionally substituted phenyl ring or an optionally substituted heterocyclic radical,

- an alkenyl or alkynyl group, - an optionally substituted phenyl radical

- an optionally substituted heterocyclic radical. When the amino radical is disubstituted, the two substituents can constitute a nitrogenous heterocycle comprising 5 or 6 atoms.

- d) - a linear or branched alkyl radical substituted on the first carbon atom by:

- one or more halogen atoms,

- a cyano, nitro, alkyl- or alkoxy- or monoalkylamino- or dialkylamino-carbonyl, dialkoxy- or dibenzyloxy- or diphenoxy-phosphono, trialkylsilyl group, - one or two alkoxy, alkenoxy, alkynoxy, phenoxy or benzyloxy radicals, which can, when they are two, form a heterocycle with 5 or 6 atoms including 2 of oxygen,

an alkyl- or alkenyl- or alkynyl- or phenyl- or benzylthio group which, when they are two, can form a heterocycle with 5 or 6 atoms, including 2 of sulfur,

an alkyl- or alkenyl- or alkynyl- or phenyl- or benzyl-sulfonyl or -sulfinyl group,

- a hydroxy, acyloxy, alkoxycarbonylo.xy group,

- e) - an acyl or thio acyl radical which may be: - a formyl radical

an alkyl- or alkenyl-carbonyl or -thiocarbonyl group, the alkyl or alkenyl radical possibly being linear or branched, and substituted by one or more halogen atoms, a cyano, nitro, alkoxy, cycloalkyl, alkyl- or alkoxy- or monoalkylamino- or dialkylamino-carbonyl, alkylthio, alkylsulfonyl, dialkyl-, alkylphenyl- or alkylbenzyl-amino, phenyl group optionally substituted or an optionally substituted heterocyclic radical,

- an alkynylcarbonyl group,

- an optionally substituted benzoyl or thio benzoyl radical,

an optionally substituted picolinyl, nicotinyl, isonicotinyl, furoyl and thénoyl radical,

- f) - an aminocarbonyl or aminothiocarbonyl group substituted by two identical or different radicals which may be: a hydrogen atom, an optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl group, an optionally substituted phenyl or benzyl radical,

- g) - an alkoxy- or alkylthio-, cycloalkoxy- or cycloalkylthio-, alkenoxy-, alkynoxy-, phenoxy- or phenylthio-, benzyloxy- or benzylthio-, heterocyclyloxy-carbonyl group, the hydrocarbon radicals being able to be substituted, it being understood that in all of the above:

- an alkyl group contains from 1 to 4 carbon atoms and that, unless otherwise indicated, it may be substituted by one or more halogen atoms, a cyano, nitro, alkoxy, cycloalkyl, alkyl- or alkoxy- or monoalkylamino- group or dialkylamino-carbonyl, benzoyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenylsulfinyl, phenylsulfonyl, trialkylsilyl,

- that the phenyl ring of the aromatic substituents can be substituted by 1 to 5 substituents chosen from the group comprising halogens, nitro groups, cyano, alkyl radicals, alkoxy, alkylthio, haloalkyls, haloalkoxy, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, the part alkyl of these substituents containing from 1 to 4 carbon atoms and that the aromatic heterocyclic rings can contain from 1 to up to 4 substituents, depending on the heterocycles, chosen from the same group. Het is a heterocyclic radical, unsaturated or not, mono- or bi-cyclic comprising 5 to 10 atoms comprising from 1 to 4 heteroatoms which may be an oxygen or sulfur atom and / or one to three nitrogen atoms, such as the furan nucleus. the thiophene nucleus, the pyrrole nucleus, the oxazole, thiazole, isoxazole and isothiazole, imidazole, pyrazole nuclei, 1,2,3-triazole or 1,2,4-triazole, the pyridine ring, the pyridazine, pyrimidine, pyrazine, 1,3,5-triazine and 1,2,4-triazine rings, as well as the condensed heterocyclic rings with a benzene ring such as benzofuran, benzothiophene, indole, quinoline and isoquinoline as well as the N-oxide derivatives of heterocycles comprising at least one nitrogen atom; this heterocycle being linked to the pyrazole ring by any one of its atoms and being able to be substituted by one or more radicals, identical or different, which are:

a halogen atom, a hydroxy, mercapto, cyano, thiocyanato, nitro, nitroso or amino group optionally substituted by one or two alkyls or phenyls or acyls, imines, enamines and amidines derived from this amino group,

- an alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl radical such as benzyl, alkenyl, haloalkenyl, alkynyl, cyanoalkyl, alkoxy, haloalkoxy, alkenoxy, halo, alkenoxy, alkynoxy, formyl, acetyl, alkyl- or alkoxy- or alkylthio-carbonyl, mono or dialkylamino (thio) carbonyl, mono or diarylamino or alkylarylamino (thio) carbonyl, carboxyl, carbamoyl or benzoyl optionally substituted,

- a phenyl, phenoxy or phenylthio, benzyloxy or benzylthio radical which may also be substituted,

an alkyl-, alkoxy-, mono or dialkylamino-, phenyl-sulphenyl or sulfinyl or sulphonyl radical,

- an acyloxy, carbamoyloxy, alkyl- or phenyl-sulfonyloxy or sulfamoyloxy group; it being understood that, in all the radicals mentioned above, the alkyl part can be linear or branched and preferably contains from 1 to 4 carbon atoms, the halogenated alkyl groups can contain one or more identical or different halogen atoms and the phenyl radicals can be substituted by a halogen atom, a methyl, methoxy, methylthio, trifluoromethyl, trifluoromethoxy radical, a nitro, cyano or methylsulfonyl group.

Preferred compounds are those, in formulas I and I bis in which Het is a furan, thiophene, pyridine or pyrimidine ring which may be substituted by one or more radicals, identical or different, which may be: a methyl, allyl, propargyl radical , methoxy, methylthio, trifluoromethyl, trifluoromethoxy, nitro, cyano, amino, mono or dimethylamino, acetoxy, carbomethoxy, methylsulfinyl, methylsulfonyl, mono or dimethylaminosulfonyl, optionally a phenoxy, phenylthio or benzyloxy group substituted on the phenyl ring by a halogen atom, a methyl, methoxy, trifluoromethyl radical or a nitro group.

Particularly preferred are the compounds in formulas I and Ibis of which Het is a thiophene nucleus. Other preferred compounds are those, in formulas I and Ibis of which

Yl and Y2, identical or different, are a hydrogen or halogen atom or a cyano group.

Other preferred compounds are those, in formulas I and Ibis in which Z is a hydrogen atom, a substituted acyl or methyleneamino group or an alkylcarbonyloxyalkylene.

The derivatives of formulas I and I bis, in which Z is different from hydrogen, can be prepared according to obtained according to a process characterized in that it is reacted, on compounds of formulas II and II bis

II Ilbis

in which Het, Yl and Y2 have the same meanings as in formula I, with an acylating agent as described in the compilations "Comprehensive Heterocyclic Chemistry", A.R.Katritzky and CW.Rees 1984, Vol.5, pages 222 to 236,

Pergamon Press and in "The chemistry of heterocyclic compounds", L.C. Behr, R.Fusco and C.H. Gardoe, 1967, pages 137 to 140, J. Wiley & sons.

By acylating agent is meant a compound of formula ZT in which Z is defined as above and T is 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. An anhydride or an acid chloride is preferably used in the presence of an inorganic base such as an alkali carbonate or bicarbonate or an organic base such as triethylamine, pyridine, or 4-dimethylaminopyridine and in a solvent or a mixture of solvents chosen from the group comprising aromatic hydrocarbons such as toluene or xylene and polar aprotic solvents such as diethyl oxide, tetrahydrofuran, acetone or racetonitrile, at temperatures between 0 ° C. and the temperature solvent reflux. According to another first process for the preparation of compounds of formula I, in which Z is Z d) or Z f), an aldehyde or a ketone is made to act, in the presence of a primary or secondary amine, on a pyrazole of formula II and / or Ilbis, at a temperature between ambient and the reflux point, in a solvent medium, optionally in the presence of a catalytic amount of strong acid.

As an example of a solvent medium, it is generally possible to use a solvent, or a mixture of solvents, aromatic chosen from the group comprising toluene and xylene, or a solvent or a mixture of solvents, aprotic chosen from the group comprising diethyl ether , tetrahydrofuran, acetone, acetonitrile or a solvent, or a mixture of solvents, polar protic chosen from the group comprising water, methanol, ethanol, isopropanol and acetic acid.

As an example of a strong acid, acetic acid and para-toluenesulfonic acid can be used.

The compounds of formulas II or II bis in which Yi is a halogen atom can be prepared, in a manner known per se, in the compilations "Comprehensive Heterocyclic Chemistry" AR Katritzky and CWRees 1984, Vol.5, pages 239 to 241 and 263 Pergammon Press; Advancies in Heterocyclic Chemistry., A.N. Kost and I.I. Grandberg, 1966, Vol 6, pages 391 to 396, Aceademic Press and "The chemistry of heterocyclic compounds", LC Behr, R.Fusco and CHJardoe, 1967, pages 84 to 91 and table 41, J. Wiley & sons by halogenation of compounds of formula III in which Het has the same meaning as in formulas I and I bis:

H

The chlorination of these compounds can be carried out using different reagents:

chlorine in an aqueous or preferably organic medium, in a chlorinated solvent such as dichloromethane or preferably in a lower carboxylic acid, such as acetic acid, at a temperature of 10 ° C to 40 ° C and preferably at room temperature, the reagents being in a molar ratio close to the stoichiometry.

an N-chloroimide such as N-chlorosuccinimide in an inert solvent such as dichloromethane, 1,2-dichloroethane or tetrahydrofuran at a temperature ranging from 0 ° C to 80 ° C and preferably between 20 ° C and 50 ° C the reactants being in a molar ratio close to stoichiometry. - sulfuryl chloride in a solvent such as dichloromethane or chloroform at a temperature between 0 ° C and 30 ° C.

Bromination can be carried out by:

- bromine in a solvent which can be water or nitric acid but more advantageously an organic solvent such as chloroform, dichloromethane or a lower carboxylic acid such as acetic acid in the presence or not of a base such as l sodium acetate, at a temperature between 0 ° C and 100 ° C and preferably at room temperature.

When the molar ratio is close to stoichiometry, the bromination takes place mainly in position 4 of the pyrazole nucleus (Yi = Br). When the molar ratio is greater than the stoichiometry and preferably equal to or greater than 2 times the stoichiometry there is also bromination in position 5 of the pyrazole nucleus (Yi = Y2 = Br).

The compounds of formula III can be prepared, in a manner known per se, by reaction of hydrazine, preferably in the form of its hydrate, with a compound of formula IV,

0

in which Het has the same meaning as in formulas I and I bis and W is a halogen atom or a hydroxy, alkoxy, alkylthio or dialkylamino radical, at a temperature ranging from 20 ° C to 110 ° C and preferably included between 50 ° C and 70 ° C, in an organic solvent which is advantageously an alcohol such as ethanol or a water-alcohol mixture or even a lower carboxylic acid such as acetic acid, in the presence or not of an acid catalyst organic or mineral. The molar ratio of hydrazine to the compound of formula IV can be between 1 and 2.5 and preferably of the order of 1.2.

The compounds of formula IV can advantageously be prepared, in a manner known per se, by reaction of heterocyclic methyl ketones of formula V:

Het— C (= O) - CH3

wherein Het has the same meaning as in formulas I and Ia, with an amide acetal, aminal ^ester or formic orthoamide, preferably dialkyl a dialkylformamide such as dimethyl- or diethyl acetal of dimethylformamide, in very clear excess, that is to say 2 to 5 times the stoichiometry, in an inert solvent such as toluene or xylene or without solvent, at a temperature ranging from 20 ° C to 150 ° C and preferably between 70 ° C and 140 ° C, for periods of between 1 hour and 48 hours.

The compounds of formula II or II bis in which Y _\ is a halogen atom or a cyano, acyl, alkoxycarbonyl, alkylsulfonyl group can be prepared, as is known, by reaction of hydrazine, preferably in the form of its hydrate, on a compound of formula IV bis,

in which Het has the same meaning as in formulas I and I bis, W is a halogen atom or a hydroxy, alkoxy, alkylthio or dialkylamino radical and W is a halogen atom or a cyano, acyl, alkoxycarbonyl group, alkylsulfonyl at a temperature ranging from 0 ° C to 110 ° C and preferably between 20 ° C and 80 ° C, in an organic solvent which is advantageously an alcohol such as ethanol or a water-alcohol mixture or also a carboxylic acid lower such as acetic acid, in the presence or absence of an organic or inorganic acid catalyst. The molar ratio of hydrazine to the compound of formula IV can be between 1 and 1.5 and preferably of the order of 1.1.

The compounds of formula IV bis can advantageously be prepared, in a manner known per se, by reaction of heterocyclic ketones of formula V bis:

Het— C (= O) - CH2W

in which Het has the same meaning as in formulas I and I bis, and W the same meaning as in form IV bis with an amide acetal, an ester aminal or an orthoamide for ics, preferably the dialkyl acetal d a dialkylformamide such as dimethyl- or diethyl acetal of dimethylformamide, in molar ratio close to the stoichiometry, in an inert solvent such as toluene, xylene, heptane or cyclohexane or without solvent, at a temperature ranging from 0 ° C to 50 ° C and preferably at. room temperature for periods of between 1 hour and 4 hours. The compounds of formula II or II bis in which Yj is a nitro group can be prepared, in a known manner, by the action of fuming nitric acid, of a mixture of concentrated sulfuric acid and of nitric acid or of '' an alkaline nitrate such as potassium nitrate on a solution in concentrated sulfuric acid of a compound of formula III, at a temperature ranging from 20 ° C to 150 ° C and preferably between 50 ° C and 100 ° vs.

The compounds of formula II or II bis in which Het is a pyridine radical comprising a halogen atom in positions 2, 4, or / and 6 on the pyridine ring can be prepared in a manner known per se in the "Aromatic Amines Oxides" compilations ", E.Ochiai, 1967, Elsevier and" The chemistry of heterocyclic coupounds ", RA..Abramovitch and

EMSmith, 1974, 14, supplement, Part 2, page 1, J. Wiley & sons, by the action of a mineral acid chloride such as sulfuryl chloride or phosphoryl chloride optionally in the presence of phosphorus pentachloride and preferably by the action of phosphoryl chloride on a compound of formula II or II bis in which Het is a pyridine N-oxide group at temperatures between 50 ° C. and the reflux temperature of the mineral acid chloride and preferably at reflux temperature. The derivatives of formula II or II bis in which Het is a pyridine N-oxide group can be prepared in a manner known per se in the compilations cited above by oxidation of compounds of formula II or II bis in which Het is a pyridine radical which at least one of positions 2, 4 and 6 is not substituted.

The oxidizing agents used may be carboxylic peracids such as peracetic acid, perbenzoic acid, monoperphthalic acid, metachloroperbenzoic acid or ^hydrogen peroxide in acetic acid, in a solvent such as chloroform, methylene chloride or acetic acid at temperatures between 0 ° C and 50 ° C and preferably at room temperature.

The compounds of formula II or II bis in which Yi is a halogen atom and Het is a thiophene radical comprising a nitro group on the thiophene nucleus be prepared by nitration of derivatives of formula II or II bis in which Yi is a d atom halogen and Het is a thiophene radical in which at least one of the carbon atoms is not substituted, by the action of fuming nitric acid, of a mixture of concentrated sulfuric acid and nitric acid or a nitrate alkaline such as potassium nitrate in concentrated sulfuric acid at temperatures between -10 ° C and room temperature, and preferably between 0 ° C and 5 ° C.

The compounds of formula III in which Het is a 2-pyrimidinyl radical comprising in position 4 and 6 two identical or different substituents chosen from alkyl radicals, halogenoalkyls, alkoxyalkyls, hydroxy, mercapto, phenyl, aralkyls can be prepared by various methods described in the compilations "The chemistry of heterocyclic coupounds", DJBrown, 16, supplement II, 1985, page 21, J. Wiley &. sons et "Comprehensive heterocyclic chemistry", DJBrown, 1984, vol.3, chap.2.13, page 112, Pergamon press, and in particular by the action of 3-pyrazole-carboxamidine hydrochloride (formula VII) on a compound of formula VI,

vι vπ

in which R and R 'which may be the same or different, are alkyl, halogenoalkyl, alkoxy, alkylthio, phenyl, aralkyl and X and X' radicals, which may be identical or different, are oxygen or sulfur atoms, in acidic or alkaline medium and preferably in an alkaline medium in the presence of a base such as sodium hydroxide using water as solvent, sodium ethylate in ethanol or sodium methylate in methanol at temperatures between the ambient temperature and the reflux temperature of the solvent.

The compounds of formula III in which Het is a 2-pyrimidinyl radical comprising in positions 4 and 6 two identical or different substituents, at least one of which is a chlorine atom and the other of which is a hydrogen or chlorine atom or an alkyl, haloalkyl, phenyl or aralkyl radical can be prepared, as described in "The chemistry of heterocyclic coupounds", DJ Brown, 16, The Pyrimidines, 1962, page 162 and supplement II, 1985, page 157, J. Wiley & sons and in "Comprehensive heterocyclic chemistry", DJBrown ,, 1984, vol.3, chap.2.13, page 89, by the action of an excess mineral acid chloride such as phosphoryl chloride or phosphorus pentachloride in the presence of 'an organic base such as dimethylaniline or diethylaniline and in the presence or absence of a quaternary ammonium salt such as tetramethylammonium chloride, tetraethylammonium, tetrabutylammonium, or benzyl riethylammonium on a derivative of formula III in lesq uels Het is a 2-pyrimidinyl radical comprising in positions 4 and 6 two identical or different substituents, at least one of which is a hydroxy group and the other is a hydrogen atom, a hydroxy group or an alkyl or haloalkyl radical, phenyl or aralkyl at temperatures between ambient and the reflux temperature of the mineral acid chloride.

The compounds of formula II or II bis in which Het is a 2-pyrimidinyl radical comprising in position 4 and 6 two identical or different substituents, at least one of which is an alkoxy or alkylthio radical and the other is a hydrogen atom or chlorine, an alkoxy, alkylthio, alkyl, haloalkyl, phenyl or aralkyl radical, can be prepared, as described in "The chemistry of heterocyclic coupounds", DJBrown, 16, The Pyrimidines, 1962, pages 201 and 205 and supplement 11 , 1985, pages 201 and 207, J. Wiley & sons and "Comprehensive heterocyclic chemistry", DJ Brown, 1984, vol.3, chap. 2.13, pages 100 and 101, Pergamon press, by action of an alcoholate or d '' an alkaline thiolate on a derivative of formula II or II bis in which Het is a 2-pyrimidinyl radical comprising in position 4 and 6 two identical or different substituents, at least one of which is a chlorine atom and the other is a hydrogen or chlorine atom or an alkyl or haloalkyl radical, phenyl or aralkyl, in a solvent which can be an alcohol or a polar aprotic solvent such as dimethylformamide, dimethylsulfoxide or tetrahydrofuran at a temperature between 0 ° C and 100 ° C and preferably between room temperature and 80 ° C .

The 3-pyrazole-carboxamidine hydrochloride (formula VII) can be prepared, in a manner known per se, by the action of anhydrous ammonia on ethyl 3-pyrazole-carboxamidate hydrochloride (formula VIII) in an anhydrous solvent such as an alcohol such as absolute ethanol or methanol, or else chloroform at a temperature between -10 ° C and 50 ° C and preferably at room temperature.

The ethyl 3-pyrazole-carboximidate hydrochloride (formula VIII) can be prepared, in a manner known per se, by the action of anhydrous ethanol in the presence of anhydrous hydrochloric acid on the 3-cyanopyrazole (formula IX) without solvent or with a solvent which may be chloroform, diethyl oxide or anhydrous tetrahydrofuran at a temperature between -10 ° C and room temperature, and preferably between 0 ° C and 10 ° C.

wine ιx

3-cyanopyrazole (formula IX) can be obtained by dehydration of 3-pyrazolecarboxaldoxime by various agents such as acetic anhydride, formic acid or thionyl chloride and preferably by the action of thionyl chloride in a solvent such than tetrahydrofuran or choroform at a temperature between ambient and 110 ° C. The 3-pyrazole-carboxaldoxime itself can be prepared by the successive action of hydrazine hydrate at room temperature and hydroxylamine chlorhyrate in water at a temperature between 50 ° C and 100 ° C, on a 4 - dialkylamino-1,1-dialkoxybut-3-ene-2-one such as 4-dimethylamino-1,1-dimethoxybut-3-ene-2-one (formula X) (J. Chem. Soc. Perkin Trans. I 1987, 653).

The following examples are given to illustrate the preparation and the fungicidal properties of the compounds according to the invention.

Example 1: Preparation of 3-f2.5-dichloro-3-thienyl) -4-chloropyrazole (compound No. 1

(formula II)

3.20 g (0.024 mole) of N-chlorosuccinimide is added at room temperature and with vigorous stirring to a suspension of 5.00 g (0.0228 mole) of 3- (2,5-dichloro-3-thienyl ) pyrazole in 110 ml of dry dichloromethane. After 4 hours of stirring, there is complete dissolution, giving a clear yellow liquid. After 2 hours of additional stirring, the reaction medium is washed with 50 ml of water, decanted, dried over anhydrous magnesium sulfate and the solvent is evaporated. Obtained: 6.63 g of beige crystalline solid which is recrystallized from 150 ml of cyclohexane giving 4.62 g of white crystals melting at 121 ° C (yield = 80%). In the same way, starting from the correctly substituted pyrazoles, with N-chloro- or N-bromo-succinimide, the compounds of formula II are obtained gathered in the following table

Compound Het Yl Y2 PC yield n ° (%)

2 2-thienyl Cl H 34 128

3 5-chloro-2-thienyl Cl H 61 114

4 3-thienyl Cl H 52 123

5 5-methyl-2-thienyl Cl H 55 85

6 5-chloro-2-thienyl Cl H 63 145

7 2-pyridyl Cl H 75 163

8 3-pyridyl Cl H 72 142

9 4-pyridyl Cl H 11 135

10 5-methyl-3-pyridyl Cl H 50 119

11 3,4,5-trichloro-2- Cl H 55 175 thienyl

12 5-methyl-3-pyridyl Br H 76 116

13 3,5-dimethyl-3- Br H 84 131 pyridyl

20 4-methyl-2-pyridyl Br H 57 147

21 4-methyl-2-pyridyl Cl H 56 156

22 2-methyl-3-pyridyl Br H 63 116

23 2-methyl-3-pyridyl Cl H 58 116

24 2-pyridyl-l -oxide Cl H 60 172

25 4,6-dimethyl-2- Cl H 29 112 pyridyl

26 2-Thiazolyl Cl H 57 187

27 2-Thiazolyl Br H 58 182

28 3,4-dichloro-2- Cl H 64 132 thienyl

125 3,4-dibromo-2- Cl H 40 135 thienyl

126 2,5-dibromo-2- Cl H 43 178 thienyl

127 5-bromo-2-thienyl Cl H 56 158

128 3-bromo-2-thienyl Cl H 48 121 129 3-chloro-4-methyl-2- Cl H 15 105 thienyl

130 3,5-dichloro-4- Cl H 24 112 methyl-2-thienyl

131 3-chloro-4-nitro-2- Cl H 27 154 thienyl

132 2-chloro-3-pyridyl Cl H 71 159

133 5-bromo-3-pyridyl Cl H 75 197

134 4,6-dimethyl-2- Br H 84 131 pyridyl

135 4,5-dichloro-l- Br H 91 224 methvl-2-imidazole

Example 2 Bromination of 3- (3-pyridyl) pyrazole

4.38 g (0.0246 mole) of N-bromosuccinimide is added at room temperature with stirring to a suspension of 3.0 g (0.0205 mole) of 3- (3-pyridyl) pyrazole. There is immediate dissolution. After stirring overnight at room temperature, the reaction medium is washed three times with 100 ml of water each time, dried over anhydrous magnesium sulfate and evaporated. 3.85 g of a brown solid are obtained. A thin layer chromatochraphy reveals that this solid is a mixture of 2 constituents which are then separated by chromatography on silica gel with elution using a mixture of ethyl acetate and dichloromethane at 65% of the second. : 2.85 g of 3- (3- pyridyl) -4-bromopyrazole (compound 14) (formula II), cream powder melting at 145 ° C (yield = 56%) and 0.79 g of 3- (3- pyridyl) -4,5-dibromopyrazole (compound 15) (formula II), beige powder melting at 145 ° C (yield = 13%).

Similarly, with N-bromo-succinimide or excess chlorine gas, the compounds of formula II are obtained

Compound Het Yl Y2 PC yield n ° (%)

16 2-pyridyl Br Br 3 215

17 2-pyridyl Br H 55 205

18 4-pyridyl Br Br 11 223

19 4-pyridyl Br H 50 147 29 6-Methyl-2- Br H 58 116 pyridyl

30 6-Methyl-2- Br Br 54 160 pyridyl

31 6-Methyl-2- Cl Cl 34 148 pyridyl

32 6-Methyl-2- Cl H 28 111 pvridvl

Example 3 ^* Preparation of 3-f3-Chloro-2-thienyl) pyrazole (formula III) (compound 100): A solution of 7 is stirred for 3 hours at a temperature between 55 ° C. and 60 ° C. 55 g (0.035 mole) of 1- (3-chloro-2-thienyl) -3-dimethylamino-2-propen-1-one and 2.00 g (0.040 mole) of hydrazine hydrate in 75 ml d 95% ethanol. The reaction medium is then evaporated to dryness giving a whitish solid which is recrystallized from 100 ml of cyclohexane. 6.03 g of beige crystals are obtained, melting at 110 ° C. (yield = 93%).

Similarly, from the corresponding dimethylaminopropenones, the compounds of formula III are obtained

Compound n ° Het PC yield (%)

101 2-thiénvl 94 98

102 3-thiénvl 83 112

103 3-Methyl-2-thienyl 87 80

104 5-méthvl-2-thiénvl 96 126

105 5-chloro-2-thienyl 86 167

106 2,5-dichloro-3-thienvl 71 147

107 2-pvridyl 90 119

108 3-pyridyl 93 NMR

109 4-pvridyl 88 152

110 5-méthvl-3-pvridvl 69 123

111 4,6- dimethvl-2-pvridyl 82 80

123 2-methvl-3-pyridvl 88 86

124 3- pvrazolvl 65 252

136 3,4-dibromo-2-thienyl 85 135

137 2,5-dibromo-3-thienvl 79 134

138 5-bromo-2-thienyl 84 165

139 3-bromo-2-thienyl 84 131

140 3-chloro-4-methyl-2- 91 153 thienyl

141 3-chloro-4-nitro-2-thienyl 97 201

142 2-chloro-3-pvridvl 90 133

143 5-bromo-3-pvridvl 90 206

144 2-thiazolvl 66 149

145 4,5-dichloro-l-methyl-2- 62 102 pvrrolvl

146 4,5-dichloro-l-methyl-2- 70 220 imidazolvl Example 4: Preparation of l -C4.6-dimétl, yl-2-pyridyl) -3-diméthylnmino-2-propèn-l - one (compound 1 12) (formula IV)

Heated in an oil bath at 120 ° C, for 9 hours, a mixture of 5.10 g (0.035 mole) of 2-acetyl-4,6-dimethylpyridine and 8.31 g (0.070 mole) of dimethylacetal from dimethylformamide. Then 4.16 g (0.035 mole) of the last reagent is added and the mixture is again heated for 5 hours. The reaction medium is then evaporated to dryness, giving 7.19 g of an orange honey which crystallizes on cooling. It is recrystallized from 15 ml of isopropyl ether and we obtain: 5.90 g of bright yellow crystals melting at 84 ° C. (yield = 83%) In the same way, from the suitable acetylated heterocycles, the compounds are prepared. of formula IV with W = N (CHβ) 2

In an analogous manner, starting from the appropriate cyanoacetylated heterocycles, the compounds of formula IV bis are prepared with W = N (CH. ^* 2 and W '= CN Compound Het PC Yield (%)

155 2-methyl-3-pyridyl 65 163 156 5-bromo-3-pyridyl 58 127

And similarly, from the appropriate chloroacetylated heterocycles, the compounds of formula IV bis are prepared with W = N (CH.- ^* ,) 2 and W '= Cl

Compound Het Yield F ° C n ° (%)

157 3,4,5-trichlorothienyl 13 NMR 158 3,4-dichlorothienyl 15 NMR

Exen riple 5 - Preparation of 3- (3.4.5-dichloro-2 -thiénvπ-4-chloroD ^' vrazole (compound n ° 1 1)

(forπ iule ïï

A solution of 0.50 g (0.01 mol) of hydrazine hydrate in 10 ml of glacial acetic acid is added dropwise at room temperature with stirring to the suspension of 0.98 g (0.003 mole) of 1- (3,4,5-trichlorodιienyl) -2-chloro-3-dimethylamino-2-propen-1-one in 15 ml of glacial acetic acid. ^' After 4 hours of stirring and one night's rest, the reaction medium is poured, with stirring, into 100 ml of water. The precipitate formed is filtered, washed with water and dried under reduced pressure in the presence of P2O5. After purification by chromatography on a silica column, eluting with a mixture of 80% heptane and 20% ethyl acetate, 0.49 g of yellow powder is isolated, which decomposes at 175 ° C (yield = 56 %).

In the same way, from the appropriate pyrazole, 3- (4,5-dichloro-2-thienyl) - 4-chloropyrazole (compound n ° 28) (formula II) is prepared: yellow powder melting at 132 ° C ( yield = 64%).

Example 6 Preparation of 3-f3-chloro-5-nitro-2-thienyl) -4-chloropyrazole (compound No. 159) (formula II)

Were added ^'dropwise 0.79 g (0.01254 mole) of fuming nitric acid 100% to a solution of 2.50 g (0.0114 mole) of 3- (3-chloro-2-thienyl) - 4-chloropyrazole in 25 ml of 98-100% sulfuric acid cooled to about 5 ° C by an ice water bath. After returning to ambient temperature, 5 hours of stirring and one night of rest, the reaction medium is poured into 150 ml of ice water and the mixture is extracted with 150 ml of ethyl acetate. The organic phase is washed with 100 ml of water and then with 50 ml of saturated sodium bicarbonate solution, finally with 50 ml of water and dried over anhydrous magnesium sulfate. After evaporation, a yellow solid is obtained which is purified on a silica column, eluting with a mixture of 75% heptane and 25% ethyl acetate. 1.31 g of yellow powder, melting at 181 ° C. (yield = 447c), are isolated. In the same way, from the suitable pyrazole, 3- (3,4-dibromo-5-nitro-2-thienyl) -4-chloropyrazole (compound No. 160) (formula II) is prepared: yellow powder melting at 197 ° C (yield = 60%).

Example 7 - Preparation of 3- ⁽ 6-cl ^* ιloro-2-pyridyl) -4-chloropyrazole ( ^" compound n ° 161) (formula II)

A suspension of 1.00 g (0.0051 mol) of 3- (6-chloro-1-oxide-2-pyridyl) -4- chloropyrazole in 5 ml of phosphoryl chloride is heated to reflux with stirring for 3 hours. After cooling, the reaction medium is concentrated to dryness, taken up in ice water, neutralized to pH 7 with solid potassium carbonate and extracted with 2 times 50 ml of ethyl acetate. The combined organic extracts are dried over anhydrous magnesium sulfate and evaporated, giving a creamy solid which is purified by chromatography on a silica cake, eluting with a mixture of 80% heptane and 207c of ethyl acetate. 0.52 g of white powder is obtained, the ¹ H NMR spectrum of which corresponds to the expected structure (yield = 47%).

In the same way, from the correctly substituted 1-oxydepyridylpyrazoles, the compounds of formula II are obtained, gathered in the following table

Compound Het Yl Y2 Yield F ° C n ° (%)

162 2-chloro-4-pyridyl Cl H 53 178

163 6-chloro-4-methyl-2- Cl H 48 158 pyridyl

164 2,6-dichloro-4-pvridyl Cl H 53 254

Example 8 Preparation of 3-π-oxide-2-pyridyl) -4-chloiOpyrazole (compound No. 165) (formula ID)

15.77 g (0.064 mole) of metachloroperbenzoic acid is added in portions at room temperature to a solution of 10.47 g (0.0583 mole) of 3- (2-pyridyl) -4- chloropyrazole in 500 ml dichloromethane. The mixture is then stirred at room temperature for 2 days and then washed with a solution of 8.9 g (0.064 mole) of potassium carbonate in 100 ml of water finally in pure water until pH 7. After drying on anhydrous magnesium sulfate and concentration, a beige solid is obtained which is purified first by chromatography on silica cake with elution with a mixture of 98% dichloromethane and 2% methanol then by trituration in isopropyl ether to hot. In this way, 8.02 g of cream powder, melting at 172 ° C. (yield = 70%), are isolated.

Similarly, from the pyridylpyrazoles coirectement substituted, we obtain the compounds of formula II gathered in the following table Compound Het Yl Y2 PC yield n ° (%)

166 l-oxide-4-pyridyl Cl H 83 251

167 1-oxide-4-methyl-2- Cl H 68 172 pyridyl

168 1 -oxvde-2-chloro-4-pvridvl Cl H 75 NMR

Example 9 - Preparation of 3- (5-bromo-3-pyridyl) -4-nitropyrazole (compound No. 169 ^{^} ) (formula II))

0.43 g (0.00693 mole) of 100% fuming nitric acid is added dropwise at approximately 30 ° C to a solution of 1.41 g (0.0063 mole) of 3- (5-bromo-3 -pyridyl) pyrazole in 10 ml of 98-100% sulfuric acid. The mixture is then heated at 75 ° C for 10 hours then poured into 250 ml of water and neutralized to pH 7 by the addition of 28% ammonia. After cooling, the solid formed is filtered, washed with water and dried at 70 ° C under reduced pressure in the presence of P2O5 - 1.59 g of cream powder melting at 280 ° C is obtained (yield = 94%).

In the same way, starting from the appropriate pyrazole, 3- (3-pyridyl) -4- nitropyrazole (compound No. 170) (formula II) is prepared: cream powder melting at 230 ° C. (yield = 90%).

Example 10 Preparation of 3- (5-bromo-3-pyridyl) -4-cvanopyrazole (compound No. 171) (formula II)

A solution of 3.70 g (0.01321) of 1- (5-bromo-3-pyridyl) -2-cyano-3-dimethylamino-2-propen-1-one (formula IV bis) and 0.73 g (0.01453 mole) of hydrazine hydrate in 100 ml of acetic acid is heated at 70 ° C for 8 hours. The reaction medium is concentrated to dryness then taken up in 200 ml of water and neutralized to pH 7-8 by addition of solid potassium carbonate. Extraction is carried out with 3 times 250 ml of ethyl acetate. The combined organic extracts are dried over anhydrous magnesium sulfate and evaporated. The light brown solid obtained is purified by chromatography on a silica cake, eluting with a mixture of 507o of heptane and 50% ethyl acetate. 1.70 g of yellow powder are obtained, melting at 235 ° C. (yield = 527c). Likewise, from the appropriate pyrazole, 3- (2-methyl-3-pyridyl) -4- cyanopyrazole (compound No. 172) (formula II) is prepared: white powder melting at 216 ° C. (yield = 67%).

Example 11 - Preparation of l-acety1-3- (5-bromo-3-pyridvP-4-cyanopyrazoIe (compound no.

173) (formula I with Z = CH ^ α≈O)

A solution of 0.28 g (0.00352 mole) of acetyl chloride in 5 ml of anhydrous tetrahydrofuran is added dropwise at room temperature with stirring to a solution of 0.80 g (0.0032 mole ) of 3- (5-bromo-3-pyridyl) -4-cyanopyrazole and 0.43 g (0.00352 mole) of 4-dimethylaminopyridine in 100 ml of anhydrous tetrahydrofuran. After 1.5 hours of additional stirring at room temperature, the reaction medium is concentrated to dryness and the residue obtained is chromatographed on silica, eluting with pure dichloromethane. 0.61 g of white powder is obtained, melting at 165 ° C. (yield = 65%).

In the same way, from the appropriate pyrazole, l-acetyl-3- (2-methyl-3-pyridyl) -4-cyanopyrazole (compound No. 174) is prepared (formula I with Z = CH C (= O )): white powder melting at 160 ° C (yield = 777c).

Example 12 Preparation of 3- ⁽ 4-chloro-6-methyl-2-pyrimidinyl) pyrazole (compound no.

1751 (formula III)

A suspension of 6.40 g (0.0363 mole) of 3- (4-hydroxy-6-methyl-2-pyrimidinyl) pyrazole, 6.02 g (0.0363 mole) of hydrated tetraethylammonium hydrochloride and 4 drops of N, N-diethylaniline in 150 ml of phosphoryl chloride is brought to 80 ° until complete dissolution. The reaction medium is then maintained at this temperature for 1 hour.

After cooling, it is evaporated to dryness under reduced pressure. The residue is taken up in 100 ml of ice water and neutralized by adding potassium carbonate to pH 7. It is extracted 3 times with 100 ml of ethyl acetate. The combined organic phases are dried over anhydrous magnesium sulfate. and evaporated. The white product obtained is purified by filtration on silica gel with elution with a mixture of 50% heptane and 50% ethyl acetate.

5.26 g of white powder are obtained, melting at 185 ° C. (yield = 74%). In the same way, from the correctly substituted pyrazoles, the compounds of formula III obtained in the following table are obtained:

Compound Het Yield PC n ° (%)

176 3- (4,6-dichloro-2- 83 204 pyrimidinyl

177 3- (4-chloro-4-94 NMR trifluoromethyl-2-pyrimidinyl

Example 13 Preparation of 3- ⁽ 4-chloro-6-methyl-2-pyrimidinvD-4-chloropyrazole (compound No. 178 (formula ID

4.58 g (0.0339 mole) of sulfuryl chloride is added dropwise to a solution of 6.00 g (0.0308 mole) of 3- (4-chloro-6-methyl-2-pyrimidinyl) pyrazole and 3 drops of dimethylformamide in 250 ml of 1,2-dichloroethane brought to the boil. The reaction medium is then maintained at reflux for 1 hour. 1.25 g (0.0093 mol) of sulfuryl chloride are then added and the mixture is again refluxed for 1 hour and a half. After cooling, the reaction medium is washed with 100 ml of 10% sodium carbonate solution, then with 100 ml of water, dried over anhydrous magnesium sulfate and evaporated. 7.35 g of white solid are obtained which is purified by chromatography on a silica cake with elution with a mixture of 70% heptane and 30% ethyl acetate. 5.12 g of white powder are finally obtained, melting at 144 ° C. (yield = 77%).

In the same way, from the correctly substituted pyrazoles, the compounds of formula II are obtained, gathered in the following table

Compound Het Yl Y2 Yield F ° C n ° (%)

179 3- (4,6-dichloro-2- Cl H 95 179 pyrimidinyl)

180 3- (4,6-dimethyl-2- Cl H 42 149 pyrimidinyl)

181 3- (4-chloro-4- Cl H 56 164 trifluoromethyl-2-pyrimidinyl)

* 182 3- (4,6-dimethyl-2- Br H 93 153 pvrimidinvl)

* this compound was prepared in an analogous manner by replacing sulfuryl chloride with bromine.

Example 14 - Preparation of 3- (4.6-dimethoxy-2-pyrimidinyl) -4-chloropyrazole (compound no. 183) (formula in

0.680 g (0.0126 mole) (3.15 equivalents) of sodium methanolate is added, with stirring and at room temperature, to a solution of 1.00 g (0.004 mole) of 3- (4,6-dichloro-2 -pyrimidinyl) -4-chloropyrazole in 80 ml of methanol. After 6 hours of stirring the reaction medium is concentrated to dryness, taken up in 100 ml of water, neutralized to pH: 7 by addition of a normal solution of hydrochloric acid finally extracted with 250 ml of dichloromethane. The chloromethylenic solution is washed with 50 ml of water, dried over anhydrous magnesium sulfate and evaporated. 0.89 g of a whitish solid is obtained which is purified by chromatography on silica cake with elution with a mixture of 75% heptane and 257c of ethyl acetate. Finally obtained 0J8 g of white powder melting at 180 ° C (yield = 817c). Similarly, 3- (4-chloro-6-methoxy-2-pyrimidinyl) -4-chloropyτazole (compound no. 184) ^" (foπ ^* nule II) is prepared by the action of 0.150 g (0.00277 mole) (1.05 equivalent) of sodium methanolate on 0.66 g (0.00264 mole) of 3- (4,6-dichloro-2-pyrimidinyl) -4- chloropyrazole. 0.61 g of white powder is obtained. melting at 185 ° C. (yield = 94%) In the same way, from the correctly substituted pyrazoles, the compounds of formula II are obtained, gathered in the following table Compound Het Yl Y2 Yield F ° C n ° (%)

185 3- (4-chloro-6-methoxy-2- H H 100 190 pyrimidinyl)

186 3- (4-methyl-6-methoxy-2- Cl H 77 131 pyrimidinyl)

187 3- (4-methoxy-6- Cl H 100 207 trifluoromethyl-2-pyrimidinyl)

* 188 3- (4-methyl-6-methylthio- Cl H 55 152 2-pvrimidinvl)

* this compound was prepared in an analogous manner by replacing sodium methanolate with sodium methanethiolate.

Example 15 Preparation of 3- ⁽ 4-hvdroxy-6-methyl-2-pyrimidinyl) pyrazole

(compound n ° 189) (formula III)

8.87 g (0.0682 mole) of ethyl acetylacetate are added dropwise at room temperature with stirring to a solution of 10.00 g (0.0682 mole) of 3-pyrazolecarboxamidine hydrochloride in 136 ml. normal soda solution. The reaction medium is then stirred for 2 hours and left to stand overnight. Neutralized to pH 7 by adding 68 ml of normal hydrochloric acid solution. The white precipitate formed is filtered, washed with water and dried under reduced pressure at 75 ° C in the presence of P2O5. 7.23 g of white powder are obtained, melting at 282 ° C (yield = 60%).

In an analogous manner, starting from acetylacetone, ethyl malonate and ethyl trifluoroacetylacetate respectively, the compounds of formula III prepared in the following table are prepared

Compound Het Yield F ° C n ° (%)

190 3- (4,6-dimethyl-2- 24 168 pyrimidinyl)

191 3- (4,6-dihydroxy-4- 49> 340 trifluoromethyl-2-pyrimidinyl

192 3- (4-hydroxy-4- 47 325 trifluoromethyl-2- pvrimidinvl

Example 16 Preparation of 3-pyrazolecarboxamidine hydrochloride (formula VII) Anhydrous ammonia gas is saturated, at room temperature and with stirring, a solution of 20.00 g (0.11139 mole) of ethyl 3-ρyrazolecarboximidate in 200 ml of absolute ethanol. After 2 hours of stirring and one night's rest, the reaction medium is concentrated to 1/4 of its volume and taken up in 300 ml of diethyl ether. After standing overnight in the freezer, the precipitate formed is filtered, washed with diethyl ether and dried at 50 ° C under reduced pressure. 13.08 g of white powder are obtained, the IR and NMR * H spectra are in accordance with the expected structure, (yield = 78%).

Example 17 Preparation of ethyl 3-pyrazolecarboximidaτe hydrochloride (formula VIII)

Anhydrous hydrochloric acid is saturated, with stirring, a solution of 50.00 g (0.537 mole) of 3-cyanopyrazole in 125 ml of absolute ethanol and 500 ml of chloroform, cooled to approximately 5 ° C. by an ice-cold mixture. acetone. After returning to room temperature, 2 hours of stirring and overnight resting the solid formed is filtered, washed twice with 400 ml of chloroform and dried at 75 ° C under reduced pressure. 89.72 g of white powder are obtained, the IR and NMR H and ¹³ C spectra are in accordance with the expected structure (yield = 95%).

Example 1 - Preparation of 3-cvanopyrazole (formula IX) 40.76 g (0.814 mole) of hydrazine hydrate is added dropwise at room temperature with stirring to a solution of 141.06 g (0.814 mole) of 4 -dimethylamino-1,1-dimethoxybut-3-ene-2-one. After stirring overnight at room temperature, a solution of 62.24 g (0.814 mol) of ^{hydroxylamine} hydrochloride in 100 ml of water was added dropwise with stirring into the reaction mixture, and the mixture is heated to 85 ° C for 3.5 hours. After cooling, it is neutralized to pH 7 by addition of potassium carbonate and the aqueous solution is extracted continuously with ethyl acetate for 14 hours. The organic phase is dried over anhydrous magnesium sulfate and evaporated. 82.77 g of 3-pyrazolecarboxaldoxime (brown honey) are obtained (gross yield = 917c) which are dissolved in 500 ml of anhydrous teσahydrofuran. Then added with stirring 177 g (1.488 mole) of thionyl chloride. The temperature rises to 50 ° C. After back to ambient the mixture is stirred for 1 hour and a half then concentrated to 1/4 of its volume and poured into 500 ml of water. The aqueous solution is neutralized to pH 7 by addition of solid sodium carbonate and exu ^* aite with 4 times 200 ml of ethyl acetate. The combined organic phases are washed with 200 ml of saturated brine, dried over anhydrous magnesium sulfate and evaporated, yielding 75.47 g of a brown oil which crystallizes on standing. After purification by filtration on silica, eluting with dichloromethane, 52.51 g of beige crystals are obtained, melting at 82.5 ° C. (yield = 767c)

EXAMPLE 19: German hrassicae in vivo test on radish

An aqueous suspension, with a concentration of 1 g / l, of the active ingredient tested is obtained by grinding 60 mg of it in the following mixture:

- acetone: 5 ml

- surfactant (TWEEN 80, oleate of polyoxyethylene derivative of sorbitan) diluted to 10%: 0.3 ml then the volume is adjusted to 60 ml with water.

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

Radish plants (Pernot variety), sown on a 50/50 peat soil-pozzolan substrate and grown in a greenhouse, are treated at the cotyledon stage by spraying the suspension of active ingredient described above.

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

24 hours after treatment, the plants are contaminated by spraying with an aqueous solution of spores (40,000 sp / ml) harvested from a culture aged 13 days.

After contamination, the plants are placed at 18-20 ° C, in an atmosphere saturated with humidity.

The grading, in comparison with the control plants, is carried out 6 days after contamination.

Under these conditions, at the dose of 1 g / 1, good (at least ...) or total protection is observed with the compounds 3, 5, 6, 10, 11, 17, 18, 125, 126, 127, 129, 130, 133, 134, 164,

165, 169, 184.

EXAMPLE 20 In vivo test on Pyricularia on ' ^→ zae responsible for rice piriculariosis: An aqueous suspension of the active ingredient 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.

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 Pyήcularia oryzae spores, obtained from a 15-day culture, is applied to the leaves, then suspended in a proportion of 100,000 units per cir. 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 / 1, good (at least 75%) or total protection is observed with the following compounds: 1, 3, 6, 8, 11, 13, 20, 21, 25, 31 , 125, 126, 127, 129, 130, 133, 134, 161, 165, 169, 177, 179, 183.

EXAMPLE 21: 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

- Tween 80 surfactant, oleate of polyoxyethylene derivative of sorbitan) diluted to 107c 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.

Vine cuttings (Vins 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 in a proportion of 100,000 units by CIΠ The contaminated plants are then incubated for two days at approximately 18 ° C, in an atmosphere saturated with humidity, 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 / 1, good (at least 75%) or total protection is observed with the following compounds: 3 to 6, 10 to 13, 18, 20, 25, 27, 30, 31, 125, 126, 127, 129, 130, 133, 140, 159, 161, 164, 165, 169, 172, 176, 177, 179, 180 ..

These results clearly show the good fungicidal properties of the derivatives according to the invention against fungal plant diseases caused by fungi belonging to the most diverse families such as Phycomycetes, Basidiomycetes, Ascomycetes, Adelomycetes or fungi imperfecti, in particular Alternaria 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 at least one compound according to the invention as described above in admixture with solid or liquid carriers, acceptable in agriculture and the surfactants also acceptable in agriculture. usable inert and usual supports and usual surfactants. 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 foπnulation.

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 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, 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 or naphthalene sulfonic acids, polycondensates of oxide ethylene 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, esters of fatty acids and polyols, the sulfate, sulfonate and phosphate derivatives of the above 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 content of surfactant is advantageously between 5% and 40% by weight.

These compositions according to the invention are themselves in fairly diverse form, solid or liquid. As forms of solid compositions, mention may be made of powders for dusting

(with a compound content of up to 100%) and the granules, in particular those obtained by extrusion, by compaction, by impregnation of a granulated support, by granulation from a powder (the content of compound in these granules being between 0.5 and 80% for the latter cases), 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), pastes, gels. Emulsifiable or soluble concentrates most often include 10 to 80

% of active ingredient, the emulsions or solutions ready for application containing, for their part, 0.001 to 20% of active ingredient.

In addition to the solvent, the emulsifiable concentrates can contain, when necessary, 2 to 20% of suitable additives such as stabilizers, surfactants, penetration agents, corrosion inhibitors, dyes or adhesives previously cited. From these concentrates, emulsions with 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 / 1

- alkaline dodecylbenzene sulfonate 24 g / 1

- oxyethylated nonylphenol containing 10 molecules of ethylene oxide 16 g / 1

- cyclohexanone 200 g / 1

- aromatic solvent q.s.p. l liter According to another formula of emulsifiable concentrate, the following is used: 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 matters or mineral salts can be dissolved in the support to help prevent sedimentation or as antifreezes 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 (defoamer) i 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 20% of a dispersing agent, and, when necessary, 0.1 to 10% of one or more stabilizers and / or other additives, such as penetrating agents, adhesives, or anti-caking agents, dyes, etc.

To obtain powders to be sprayed or wettable powders, are intimately mixed active ingredients in appropriate mixers with the additional substances and are ground using mills or auu ^* are suitable grinders. This gives sprayable powders whose wettability and suspension are advantageous; can be suspended with water at any desired concenu ^* ation and these suspensions can be used very advantageously in particular for application to plant leaves.

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 material 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 (dispersing agent) 12%

- calcium carbonate (inert filler) qs 100% Example PM 3:

This wettable powder contains the same ingredients as in the previous example, in the following proportions: - active material 757c

- 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 and nonionic surfactants (wetting agent) 2.57c

- 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 17% 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 charge selected 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 a polynaphthalene alkaline or alkaline earth sulfonate or an alkaline or alkaline earth lignosulfonate, the remainder being 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 granulate 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 is generally done by 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 GDI: 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 material 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 ingredients, 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 preventive or curative treatment, on the foliage or the propagation material, of the latter or of its place of growth.

Claims

1. Pyrazole derivatives, foππule I and their Ibis tautomeric foπnes:

I Ibis

the sponding coπ ^* N-oxides, as well as the metal or metalloid salts and complexes of these derivatives, in which

Yl and Y2, which can be different or identical, are:

an alkoxy or alkylthio group, each of these groups being optionally halogen,

- an alkoxy- or alkylthio-carbonyl group

- an optionally substituted phenoxy,

- an amino substituted or not by one or two alkyls or phenyls,

- a) - a hydrogen atom, a nitro, amino, hydroxy, cyano group,

an alkyl group optionally substituted with a cyano, niα ^* o, alkoxy, cycloalkyl, alkyl- or alkoxy- or monoalkylamino- or dialkylamino-carbonyl, alkylthio, alkylsulfonyl substituent, an optionally substituted phenyl ring or an optionally substituted heterocyclic radical,

- an alkenyl or alkynyl group, - an optionally substituted phenyl radical

- an optionally substituted heterocyclic radical. When the amino radical is disubstituted, the two substituents can constitute a nitrogenous heterocycle comprising 5 or 6 atoms;

- one or more halogen atoms,

- a cyano, nitro, alkyl- or alkoxy- or monoalkylamino- or dialkylamino-carbonyl, dialkoxy- or dibenzyloxy- or diphenoxy-phosphono, trialkylsilyl group, - one or two alkoxy, alkenoxy, alkynoxy, phenoxy or benzyloxy radicals, which can, when they are two, form a heterocycle with 5 or 6 atoms including 2 of oxygen.

an alkyl- or alkenyl- or alkynyl- or phenyl- or benzylthio group which, when they are two, can form a heterocycle with 5 or 6 atoms, 2 of which are sulfur,

- a hydroxy, acyloxy, alkoxycarbonyloxy group,

- e) - an acyl or thio acyl radical which may be: - a foπnyl radical

- an alkynylcarbonyl group,

- an optionally substituted benzoyl or thio benzoyl radical,

an optionally substituted picolinyl, nicotinyl, isonicotinyl, furoyl.thenoyl radical,

- that the phenyl ring of the aromatic substituents can be substituted by 1 to 5 substituents chosen from the group comprising halogens, nitro groups, cyano, alkyl radicals, alkoxy, alkylthio, haloalkyls, haloalkoxy, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, the part alkyl of these substituents containing from 1 to 4 carbon atoms and that the aromatic heterocyclic rings can contain from 1 to up to 4 substituents, depending on the heterocycles, chosen from the same group. Het is a heterocyclic radical, unsaturated or not, mono- or bi-cyclic comprising 5 to 10 atoms comprising from 1 to 4 heteroatoms which may be an oxygen or sulfur atom and / or one to three nitrogen atoms, such as the furan nucleus, the thiophene nucleus, the pyrrole nucleus, the oxazole, thiazole, isoxazole and isothiazole, imidazole, pyrazole nuclei, 1,2,3-triazole or 1,2,4-triazole, the pyridine ring, the pyridazine, pyrimidine, pyrazine, 1,3,5-triazine and 1,2,4-triazine rings, as well as the condensed heterocyclic rings with a benzene ring such as benzofuran, benzothiophene, indole, quinoline and isoquinoline as well as the N-oxide derivatives of heterocycles comprising at least one nitrogen atom; this heterocycle being linked to the pyrazole ring by any one of its atoms and being able to be substituted by one or more radicals, identical or different, which are:

2. Derivatives according to claim, characterized in that in the formulas I and Ibis, Het is a furan nucleus. thiophene, pyridine or pyrimidine which may be substituted by one or more radicals, identical or different, which may be: a methyl, allyl, propargyl, methoxy, methylthio, u ^* ifluoromethyl, trifluoromethoxy, nitro, cyano, amino, mono or dimethylamino radical , acetoxy, carbomethoxy, methylsulfinyl, methylsulfonyl, mono or dimethylaminosulfonyl, a phenoxy group, phenylthio or benzyloxy optionally substituted on the phenyl ring by a halogen atom, a methyl, methoxy, trifluoromethyl radical or a nitro group.

3. Derivatives according to claim 2, characterized in that in formulas I and I bis, Het is a thiophene radical.

4. Derivatives according to claim 1, characterized in that in formulas I and I bis, Yi and Y2, identical or different, are a hydrogen or halogen atom or a cyano group.

5. Derivatives according to claim 1, characterized in that in formulas I and Ibis, Z is a hydrogen atom, an acyl, substituted methyleneamino or carbonyloxyalkylene group,

6- Process for the preparation of the derivatives of formula I and Ibis, in which Z is different from hydrogen and, characterized in that it is reacted, on compounds of formulas II and II bis

II Ilbis

in which Het, Yl and Y2 have the same meanings as in formula I, an acylating agent-

7. Process for the preparation of the derivatives of formula I and Ibis, in which Z is Z d) or Z f), characterized in that it is reacted, on compounds of formulas II and II bis →

II Ilbis

in which Het, Yl and Y2 have the same meanings as in formula I, an aldédyhe or a ketone, in the presence of a primary or secondary, on a pyrazole of formula II, at a temperature between ambient and point reflux, in a solvent medium, optionally in the presence of a catalytic amount of strong acid.

8. Process for the preparation of derivatives of formulas II and II bis, in which Yl is a halogen atom and Y2 is a hydrogen atom, characterized in that a halogenation of compounds of formula III is carried out:

H

9. Process for the preparation of derivatives of formula III, by reaction of hydrazine on an enone compound of formula:

Het. W

^

IV

O

in which Het has the same meaning as in formulas I and I bis and W is a halogen atom or a hydroxy, alkoxy, alkylthio or dialkylamino radical, at a temperature ranging from 20 ° C to 110 ° C.

10. Compounds of formulas III and IV,

H O

usable as intermediates.

11. Compositions for the protection of plants against fungal diseases characterized in that they contain, as active material at least one compound of formula I according to claim 1.

12. Method for treating cultures against fungal diseases, characterized in that at least one compound of formula I is applied according to one of claims 1 to 5.