SK4697A3 - Fungicidal compositions containing 3-phenyl-pyrazole derivatives, novel 3-phenyl-pyrazole derivatives, and fungicidal uses thereof - Google Patents

Abstract

Fungicidal compositions containing as the active ingredient 3-phenyl-pyrazole derivatives of formula (I), wherein X1 to X5, which are the same or different, are a hydrogen atom, a halogen atom or a nitro or alkyl grouping, etc.; Y is a halogen atom or a nitro group, etc.; and Z is a hydrogen atom or a C(=Z1)Z2 group, phosphoryl, etc. Said compositions are useful in agriculture for protecting propagative plant stock from fungal diseases.

Description

Fungicidal compositions containing 3-phenylpyrazole derivatives, novel 3-phenylpyrazole derivatives and their use as fungicides

Technical field

The invention relates to the use of 3-phenylpyrazole derivatives for the protection of plant propagation material against fungal diseases, compositions containing these derivatives and novel derivatives of the series, to compositions containing these derivatives and to fungicidal compositions containing these derivatives, and to a method of treating plants with these derivatives.

BACKGROUND OF THE INVENTION

Certain 3-phenylpyrazole derivatives have been described, in particular in published applications EP 0 538 156 and WO 93/22287, for their advantageous properties against diseases caused by fungi on plant leaves.

Plant propagation material means all propagating parts of plants that can be used for reproduction and reproduction. This means, for example, seeds (in strict sense of the term) for crops other than potatoes, roots, fruits, bulbs, wildebeest, parts of plants or alternatively germinating plants and young plants which are transplanted after germination or emergence from the soil. These young plants can be protected from transplanting by total or partial immersion. Among the promotional products that are suitable for treatment by the method of the invention, the following preferred products may be mentioned:

dicotyledonous seeds: peas, cucumbers, melon, soy, cotton, sunflower, rape, beans, flax, beets, monocotyledonous seeds: cereals, corn, rice or potatoes.

Preferably, the seeds are coated with 0.1 to 500 g of active ingredient per 100 kg of seed, preferably 1 to 400 g of active ingredient per 100 kg.

In the case of potatoes, it is preferable to cover the amount of active substance corresponding to the infiltration of the potatoes with a composition containing 0.1 g / l to 100 g / l of active substance.

SUMMARY OF THE INVENTION

In particular, the invention relates to compositions for the treatment of plant propagation material against fungal diseases, comprising, as active ingredient, at least one 3-phenylpyrazole derivative of the formula I

From which

X ^1, X ^a, X ^3, X 'and X ^p, which may be the same or different, are a hydrogen or a halogen, hydroxyl, mercapto, cyano, thiocyanato, nitro or nitroso group or an amino group optionally substituted by one or two alkyl alkyl, hydroxy, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, benzyl, alkenyl, alkynyl alkyl, alkynyl, cyanoalkyl, formyl, acetyl, alkyl (thio) carbonyl or alkoxy (thio) carbonyl, monoalkylamino (thio) carbonyl or dialkylamino (thio) carbonyl, amino (thio) carbonyl, monoarylamino (thio) carbonyl or diarylamino (Thio) carbonyl, carboxyl, karboxylatoskupinu, carbamoyl or benzoyl, phenyl, phenoxy or phenylthio, alkylfenylsulfenylovú group or alkylphenylsulfinyl, or alkylphenylsulfonyl, or alkoxyfenylsulfenylovú group or alkoxyfenylsulfinylovú group or alkoxyfenylsulfonylovú group or monoalkylaminofenylsulfenylovú group or monoalkylaminofenylsulfinylovú group or monoalkylaminofenylsulfonylovú group or a di (alkyl) aminophenylsulfenyl group or a di (alkyl) aminophenylsulfinyl group or a di (alkyl) aminophenylsulfonyl group, a sulfo group, its salts, esters and amides,

- a phosphoryl group substituted by two groups selected from the group consisting of alkyl, alkoxy, alkylthio and dialkylamino, benzyloxy, phenyloxy or phenyl, trialkylsilyl or alkylphenylsilyl, two adjacent groups of X ¹ , X ² , X ³ , ^B may form a bridge of from 2 to 4 chain members, of which at least one may be replaced by an oxygen, sulfur or nitrogen atom, and may contain one or more of the following atoms or groups, namely C, O, S, N, C = O , C = S, SO, SO _and CH = CH, wherein the carbon atoms of this bridge may be unsubstituted or substituted by at least one halogen atom and / or by at least one hydroxy, amino, alkyl, alkoxy, alkylthio, monoalkylamino, dialkylamino, alkylsulfinyl or an alkylsulfonyl group, or an alkoxycarbonyl group, wherein alkyl The moiety has the meaning given below, with the proviso that X ¹ to X ® cannot be simultaneously all hydrogen,

Y represents a hydrogen or halogen atom or a nitro group, cyano, hydroxy, alkylcarbonyloxy, alkoxycarbonyloxy, aminocarbonyloxy, mercapto, carboxyl, carboxylate, formyl, alkyl (thio) carbonyl, aminoalkyl, thiocyanato or alkyl, alkenyl, alkynyl, alkoxy or alkylthio, alkylsulfinyl or alkylsulfonyl, the alkyl portion of which may optionally be mono- or polyhalogenated, amino optionally substituted with one or two alkyl or phenyl groups phenyl, phenoxy, phenylthio, arylsulfinyl or arylsulfonyl, wherein Y and X ^x or X ® may form a bridge containing from 1 to 3 members of the chain, which may contain one or more of the following atoms or groups, namely C, O, S, N, C = O, C = S, SO, SO ₂ , CH = CH, wherein the carbon atoms of this bridge may be unsubstituted or substituted by at least one halogen atom and / or at least one hydroxy, alkoxy, alkylthio, monoalkylamino or dialkylamino, alkylsulfinyl or alkylsulfonyl group, wherein the alkyl moiety is as defined below,

Z is hydrogen or halogen or cyano, nitro or hydroxy, or alkyl, haloalkyl, hydroxyalkyl, formyloxyalkyl, alkyl (thio) carbonyloxyalkyl or aryl (thio) carbonyloxyalkyl, alkoxy (thio) carbonyloxyalkyl thio) carbonyloxyalkyl, monoalkylamino (thio) carbonyloxyalkyl or dialkylamino (thio) carbonyloxyalkyl, cycloalkyl or cycloalkylalkyl, wherein the cycloalkyl moiety may be substituted by GR ⁴ as defined below,

an alkoxy group optionally substituted by hydroxy, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl, phenyloxy or phenylthio, phenylsulfinyl or phenylsulfonyl, amino optionally substituted by one or two alkyl groups, each of which contains an alkenyl group or an alkenyl group; 7 carbon atoms and is optionally substituted, phenyl or Het, optionally substituted, a group of formula C (= Z ^x ) Z ^a , wherein

- Z ^x is an oxygen or sulfur atom or an alkylamino or alkylimino or arylamino or arylimino group, and

- Z ^a represents a hydrogen atom or a halogen or hydroxy atom, a mercapto group, a cyano group or an amino group, an alkyl group, an alkoxy group, a haloalkoxy group, an alkylthio group, an alkenyl group or an alkynyl group or alkenyloxy group each containing from 3 to 7 carbon atoms; , phenoxy, phenalkyloxy,

Het or Het-alkyl, phenylalkenyl or phenylalkinyl,

Het-alkenyl or Het-alkynyl, monoalkylamino or dialkylamino, monophenylamino or diphenylamino or alkylsulphonylamino or arylsulphonylamino, phosphoryl substituted with two radicals selected from the group consisting of cycloalkyl, alkyl, dialkylamino, alkoxy, or alkynyl, phenyl, phenylalkyl, Het or Het-alkyl, optionally substituted, or S (= Z ^X ) (= Z ³ ) Z ^a , wherein Z ^x and Z ^a are as defined above and Z ³ has the same meanings, but not the same as Z ^x , and tautomeric forms of formula Ia, wherein Z is hydrogen or isomeric forms, wherein Z is C (= Z ^x ) Z ^a , or S (= Z ^X ) (= Z ³ ) Z ^a ,

salts thereof, for example with hydrochloric acid or perchloric acid or with nitric acid or with sulfuric acid or with alkylsulphonic acid or with phenyl (optionally substituted) sulphonic acid, and their complexes with metals and their N-oxides, in each of the abovementioned alkyl substituents groups, alkoxy, alkenyl and alkynyl groups and moieties contain up to 7 carbon atoms and are optionally halogenated (from 1 to 8 halogen atoms), cycloalkyl groups contain from 3 to 7 carbon atoms and are optionally substituted with at least one substituent selected from the group consisting of GR ⁴ , as defined below, phenyl groups being optionally substituted with 1 to 5 substituents selected from the group consisting of halogen, alkyl or (C 1 -C 3) alkoxy and nitro;

Het represents a monocyclic or bicyclic heterocyclic radical containing from 5 to 10 atoms, of which 1 to 4 are heteroatoms (e.g., oxygen, sulfur, nitrogen, phosphorus), GR ⁴ includes;

a halogen atom or a cyano, nitro, mono or dialkylamino, alkyl, alkoxy, alkylsulfenyl, alkylsulfonyl, alkylcarbonyl, alkylthiocarbonyl, alkoxycarbonyl, alkoxytiokarbonylovú group, a monoalkylaminocarbonyl group or a dialkylaminocarbonyl or monoalkylaminotiokarbonylovú group or dialkylaminotiokarbonylovú group, MO7 noalkylaminosulfonylovú group or a dialkylaminosulfonyl group (wherein the alkyl groups and moieties contain from 1 to 4 carbon atoms and are optionally substituted with 1 to 9 halogen atoms).

In formula I, Y is preferably a chlorine or bromine atom.

Other preferred derivatives are those of formula I wherein Z is H or C (= Z ¹⁾ Z ² wherein Z ¹ is O or S.

Other preferred derivatives are compounds of formula I wherein X ¹ , X ² and X ⁴ are hydrogen or halogen, nitro or amino, or optionally halogenated C 1 -C 4 alkyl.

Other preferred derivatives are those compounds of formula I wherein X ³ is hydrogen or fluoro.

Other preferred derivatives are those of formula I, wherein X ¹ and / or X is ^a hydrogen atom.

Other preferred derivatives are compounds of formula I wherein two adjacent substituents selected from the group consisting of X ¹ , X ² , X ³ , X ⁴ and X ⁵ form a bridge containing 3 or 4 chain members, particularly optionally halogenated and preferably form fluorinated methylenedioxy bridges.

Aryl groups are preferably phenyl groups.

Particularly preferred derivatives are those compounds of formula I wherein

(a) X ¹ , X ³ and X ⁵ are hydrogen and X ² and X ⁴ are each chlorine;

b) X ¹ is nitro, X ² and X ⁴ are each chlorine, X ³ is fluorine and X ® is hydrogen,

c) X ¹ is fluorine, X ² and X ⁴ are each chlorine, X ³ is fluorine and X ³ and X ® are hydrogen.

Some of these derivatives are new and those where in formula I:

¥ is a chlorine atom and Z is a hydrogen atom,

X ¹ is a hydrogen atom or a halogen atom or a nitro, amino or methyl group,

X ² is a halogen atom or a nitro, amino or methyl group,

X ³ is a hydrogen atom or a halogen atom,

X ⁴ is a halogen atom or an amino, nitro or methyl group,

X ® is a hydrogen atom or a halogen atom.

Preferred new derivatives are those wherein in formula I:

¥, Z, X ¹ and X * are as defined above,

X ² is a chlorine atom or a bromine atom,

X ³ and X ⁴ , which may be the same or different, are each a hydrogen atom or a fluorine atom.

The derivatives of the invention can be prepared by known methods as described in published applications EP 0 538 156 and WO 93/22287.

The following examples illustrate the preparation of novel derivatives, their physicochemical characteristics (structures confirmed by NMR analysis), their fungicidal properties in the treatment of leaf diseases, and the fungicidal properties of the typical derivatives of the invention in seed treatment.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

Benzoic acids

(a) 2,3-Dichloro-5-nitrobenzoic acid.

To a solution of 100 g (0.52 mol) of 2,3-dichlorobenzoic acid dissolved in 1000 ml of concentrated sulfuric acid cooled to 5 ° C was added portionwise 58 g (0.57 mol) of potassium nitrate. After 1 hour, the reaction mixture was poured into 8 L of ice and filtered through a frit (63% yield, analysis).

b) 3-Chloro-4-fluoro-5-bromobenzoic acid.

In an argon atmosphere, 10 g (0.0265 mol) of 3,5-dibromo-4-fluorobenzoic acid was dissolved in 200 ml of anhydrous THF. At-70 ^e C was introduced 37 ml of 1.6 M n-BuLi in hexane dissolved. After stirring for one hour, 25.1 g (0.106 mol) of hexachloroethane dissolved in 20 ml of anhydrous THF are added. After 2 hours at -70 ° C, the temperature of the reaction mixture was allowed to rise gradually to room temperature. The reaction mixture is hydrolyzed with 50 ml of water and then extracted with ether. The aqueous phase is acidified by addition of 1N HCl and then extracted with ether. The organic phase is dried over magnesium sulphate and concentrated under reduced pressure. The solid was recrystallized from heptane / ether to give 1.2 g of 3-chloro-4-fluoro-5-bromobenzoic acid (yield: 18%, mp 184 ° C).

c) 3,5-Dibromo-4-fluorobenzoic acid.

Dissolve 60.8 g of sodium hydroxide pellets in 500 ml of water. 26 ml of bromine is added, keeping the temperature below + 10 ° C. While maintaining the temperature of the reaction mixture below + 10 ° C, add 50.0 g (0.169 mol) of 3,5-dibromo-4-fluoroacetophenone dissolved in 50 ml of dioxane. The temperature of the reaction mixture was allowed to rise to room temperature while controlling the exothermic effect so that the temperature did not exceed +35 ° C. Stirring was continued for 1.5 hours at room temperature. The aqueous phase is extracted with ether, acidified to about pH 1 with 1N HCl and extracted again with ether. The organic phase is dried over magnesium sulphate and concentrated under reduced pressure. The solid was triturated in heptane to give 47.5 g of 3,5-dibromo-4-fluorobenzoic acid (yield: 74%, mp 201 ° C).

d) 3,5-Dichloro-2,4,6-trifluorobenzoic acid.

Under argon at-70 ^and C to a solution of

10.4 g (0.090 mol) of TMEDA in 40 ml of anhydrous THF are added dropwise with 57 ml of a 1.6 M solution of n-BuLi in hexane. 15.0 g (0.075 mol) of 3,5-dichloro-2,4,610 are added dropwise at -70 ° C

-trifluorobenzene in 10 mL of anhydrous THF. After stirring at -70 ° C for 1 h, the reaction mixture was poured onto solid carbon dioxide in 100 mL of anhydrous THF. The reaction mixture was stirred while allowing the temperature to gradually rise to room temperature and then hydrolyzed with water and extracted with ether. The aqueous phase is acidified with 1N HCl and extracted with ether. The organic phase is dried over magnesium sulphate and concentrated under reduced pressure. The solid was recrystallized from heptane / ether (yield: 54%, mp 136 ° C).

e) 3,5-Dichloro-2,4-difluorobenzoic acid.

Under argon at -50 ° C, a solution of 14.3 g (0.090 mol) of diisopropylamine in 100 mL of anhydrous THF was added dropwise with 90 mL of a 1.6 M solution of n-BuLi in hexane. After half an hour at-50 ^and C was added dropwise 20.0 g (0.109 mol) of 3,5-dichloro-2,4-difluorobenzene in 70 ml of anhydrous THF. The reaction mixture was stirred for 1 hour at -70 ° C and then poured onto solid carbon dioxide in 100 mL of anhydrous THF. After warming to room temperature, the reaction mixture was hydrolyzed with water and extracted with ether. The aqueous phase is acidified with 1N HCl and extracted with ether. The organic phase is dried over magnesium sulphate and concentrated under reduced pressure. The solid was recrystallized from heptane-ether (yield: 37%, melting point 177 C ^e).

f) 3,5-Dichloro-2,6-difluorobenzoic acid.

9.5 g (0.06 mol) of 2,6-difluorobenzoic acid and 7.8 ml of oxalyl chloride (0.09 mol) were dissolved in 50 ml of 1,2-dichloroethane. 5 drops of DMF are added and the mixture is stirred for 1 hour at room temperature. 24 g (0.18 mol) of aluminum chloride are then added and the mixture is heated to 60-70 ° C. A stream of chlorine is introduced over 5 hours while maintaining the temperature of the reaction mixture between 60 and 70 ° C. The mixture was then poured into 100 mL of 1N HCl. The precipitate was filtered off, washed with water and dried under reduced pressure to give 13 g of a cream solid (yield: ^95.6%; H NMR and ¹³ C).

Using the procedure described above, but with the appropriate reactants, the following acids are prepared:

3-fluoro-5-bromobenzoic acid (yield: 78%, melting point 144 ° C), 2-nitro-3-chloro-5-methylbenzoic acid (yield: 83%, melting point 226 ° C), 3-fluoro acid -5-methoxybenzoic acid (yield: 90%, mp 121 ° C).

Example 2

Acetophenones (see Example 4D of WO 93/22287)

Acetophenones are obtained from the benzoic acids obtained above according to the following procedure:

(a) 2,3-dibromo-5-methylbenzoyl chloride.

2.1 g (0.00714 mol) of 2,3-dibromo-5-methylbenzoic acid dissolved in 20 ml of 1,2-dichloroethane are treated with 0.78 ml (0.107 mol) of thionyl chloride dissolved in 5 ml

1,2-dichloroethane. The resulting mixture was stirred at 60 ° C for about 5 hours and then concentrated under reduced pressure to give an oil: 2,3-dibromo-5-methylbenzoyl chloride.

b) (2,3-dibromo-5-methylphenyl) ethanone.

A mixture of 0.87 g (0.0076 mol) of magnesium ethyl acetate and 1.17 ml (0.0076 mol) of ethyl malonate in 30 ml of ether is refluxed for 3 hours. Then 2 g (0.0064 mol) of the acid chloride obtained above, diluted in 5 ml of ether, are added to this heterogeneous solution. The reaction mixture was then stirred at reflux for 3 hours. After cooling, 10 ml of dilute sulfuric acid solution was added to the reaction mixture, and the mixture was extracted with ether and washed with water. After drying over magnesium sulfate and evaporation of the solvent, an oil is obtained which is directly subjected to the decarboxylation step: dilution in a mixture of 5 ml of acetic acid, 5 ml of water and 1 ml of concentrated sulfuric acid and then heating at 70 ° C for about 2 hours. The reaction mixture was then extracted with ethyl acetate and neutralized with aqueous sodium hydroxide solution. After drying over magnesium sulfate and evaporation of the solvent, an oil is obtained: (2,3-dibromo-5-methylphenyl) ethanone.

From the appropriately substituted benzoic acids obtained above, the following acetophenones are prepared in the same manner (see table below):

X ¹ , x ² , x ³ , x ⁴ , x ^p yield (%) mp (° C) or analysis K, Br, F, Cl, H 50 analysis F, Cl, F, Cl, F 58 analysis F, Cl, F, Cl, H 63 43.5 Me, Cl, F, Cl, H 13 62 Cl, Cl, K, NO 2, H 87 analysis Me, MO :, H, F, H 89 50 F > C, Cl, H, H, H 42 NMR Cl, CCF], H, Br, H 61 NMR Cl, OCF 3, K, NC 2, K 82 NMR Br, OCF 3, H, NO 2, K 89 NMR F, Br, F, Cl, K 50 NMR F, Me, F, Cl, H 10 NMR F, Cl, H, F, H; 46 NMR H, F, H, Br, H 54 73 NO 2, Cl, K, Me, H 70 130 K, F, H, OMe, H 68 66 H, Cl, H, Me, H; 52 NMR

Preparation of (3,5-dichlorophenyl) ethanol from 3,5-dichloroaniline (see Example 4 F of WO 93/22287):

To 48.6 g (0.30 mol) of 3,5-dichloroaniline was added 300 mL of water and 70 mL of concentrated hydrochloric acid. After 30 minutes, 27.5 g (0.40 mol) of sodium nitrite in 32 ml of water are introduced dropwise while maintaining the temperature between 0 and 5 ° C. 16.2 g (0.2 mol) of sodium acetate are added to the filtered reaction mixture. This solution is introduced dropwise into the solution

28.5 g (0.48 mol) of acetaldoxime, 25.0 g (0.10 mol) of copper sulfate pentahydrate, 20.5 g (0.018 mol) of anhydrous sodium sulphite and 121 g (1.50 mol) of sodium acetate in 250 ml of water, maintaining the temperature at 15 ° C. After stirring for 1 hour, the mixture was acidified by the addition of concentrated hydrochloric acid. After steam distillation and chromatography of the crude product on a silica gel column (heptane / ethyl acetate 90:10), 16.6 g (30%) of (3,5-dichlorophenyl) ethanone are obtained as a colorless liquid.

Using the above procedure starting with 3-bromo-5-trifluoromethylaniline, (3-bromo-5-trifluoromethylphenyl) ethanone was obtained (yield: 35%, NMR).

From 4-acetyl-2,6-dichloroaniline:

814 g (4 mol) of 4-acetyl-2,6-dichloroaniline, prepared according to patent DD 273 435 of 15.11.1989, is recrystallized in a mixture of 1200 ml of concentrated hydrochloric acid and 5200 ml of concentrated acetic acid. After cooling to 0 ° C, a solution of 290 g (4.2 mol) of sodium nitrite in 770 ml of water is introduced by gentle flow. After 2 hours and 30 minutes at this temperature the solution was poured into a solution of 2200 ml 50% hypophosphorous acid in water at 5 ^{& C.} The temperature was allowed to rise to room temperature, was added 10 1 of water and the aqueous phase extracted with dichloromethane. After settling and drying the separated organic phase, the crude product is concentrated and distilled off to give 591 g (yield: 78%, bp 91-95 ° C / 133.3 Pa) of (3,5-dichlorophenyl) ethanone as a pale yellow liquid .

Using the above procedure starting with 4-acetyl-6-bromo-2-chloroaniline, 89% (3-bromo-5-chlorophenyl) ethanone (NMR) was obtained.

Using the above procedure with the starting 3,4,5-trichloroaniline, (3,4,5-trichlorophenyl) ethanone was obtained (yield: 20%, mp 75 ° C).

Example 3

2-Chloroacetophenones (preparation of chloroacetophenone by chloroacetylation (Friedel-Crafts) of 2-chloro-1- (2-chloro-4-fluoro-5-methylphenyl) ethanone (Example 4 I of WO 93/22287)

14.1 g (0.125 mol) of monochloroacetyl chloride is introduced dropwise into a suspension of 16.66 g (0.125 mol) of anhydrous aluminum chloride in 100 ml of anhydrous 1,2-dichloroethane, maintaining the temperature at -5 ° in an ice-acetone bath. C. 14.46 g (0.1 mol) of 4-chloro-2-fluorotoluene are then added dropwise to the solution obtained at the same temperature. The reaction mixture was stirred at 5 ° C for 1 hour, then allowed to stand overnight and finally heated to 60 ° C until gas evolution ceased. After cooling in an ice bath, a solution of 5 ml of concentrated hydrochloric acid in 100 ml of water is introduced dropwise. After settling, the organic phase is separated and 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. Evaporation of the solvent gave 22.3 g of a pale yellow oil of 2-chloro-1- (2-chloro-4-fluoro-5-methylphenyl) ethanone which crystallized upon cooling (m.p. 32 ° C, yield: 100%).

Similarly, 2-chloro-1- (3-methyl-4-fluoro-5-methylphenyl) ethanone (m.p. 86 ° C, yield: 87%) (FG 993) and 2-chloro-1- (2-fluoro) were obtained. -3,5-dichloro-4-fluorophenyl) ethanone (NMR analysis, yield: 75%).

Example 4

3,5-dibromo-4-fluoroacetophenone

133.5 g (1.00 mol) of aluminum chloride are introduced into 400 ml of 1,2-dichloroethane. The mixture was cooled to + 10 ° C and 13.81 g (0.10 mol) of 4-fluoroacetophenone dissolved in 10 ml was added.

1,2-dichloroethane. The reaction mixture is heated to + 55 ° C and 51 ml of bromine is added dropwise over approximately one hour. Stirring was continued for 5 hours at +55 ° C. The reaction mixture was allowed to cool to room temperature, poured into ice-cooled slightly acidified water and extracted with dichloromethane. The organic phases are dried over magnesium sulphate and then concentrated under reduced pressure. 6.7 g of 3,5-dibromo-4-fluoroacetophenone (yield 23%, mp 59 C ^e).

Example 5

3-methyl-4-fluoro-5-chloroacetophenone

16.7 g (0.123 mol) of aluminum chloride are introduced into 100 ml of 1,2-dichloroethane. The mixture is cooled to + 10 ° C and 8.2 ml of acetyl chloride are added. After half an hour at + 10 ° C, 15.0 g (0.104 mol) of 2-fluoro-3-chlorotoluene dissolved in 10 ml are added.

1,2-dichloroethane. The reaction mixture was allowed to cool to room temperature and then heated to + 50 ^e C for 3 hours. After cooling, the mixture was poured into 1N HCl and extracted with dichloromethane. The organic phases are dried over magnesium sulphate and concentrated under reduced pressure. 11.6 g of 3-methyl-4-fluoro-5-chloroacetophenone are obtained.

Example 6

Enaminones (see Examples 5 and 6 of WO 93/22287)

1- (3,5-dichlorophenyl) -3-dimethylamino-2-propen-l-one.

g (0.053 mol) of 3 ', 5'-dichloroacetophenone is dissolved in 50 ml of Ν, Ν-dimethylformamide dimethyl acetal at room temperature with stirring. Stirring was continued and the reaction mixture was heated at 90 ° C for 2 hours. The reaction mixture was concentrated to dryness under reduced pressure. The residue is taken up in 150 ml of heptane. The orange residue was filtered to give 10.0 g (77% yield, mp 100 ° C) of 1- (3,5-dichlorophenyl) -3-dimethylamino-2-propen-1-one.

Using the same procedure, p-amine derivatives of the following general formula below are prepared from the appropriately substituted acetophenone and the respective second reactant, which are summarized in the following table.

x ⁴

where W = N (CH ₃ ) 2

X ¹ , X =, X ³ , X ¹ , x = yield (%) mp (° C) or analysis H, Br, F, Cl, K 80 analysis H, Br, F, Br, H. 82 143 K, Me, F, Cl, H 28 89 F, Cl, F, Cl, F 81 128 H, Cl, Cl, Cl, H; 85 143 Me, Cl, F, Cl, H 69 127 Cl, Cl, H, NO 2, H 60 analysis H, Cl, H, Me, H; 91 analysis F, Br, F, Cl, H 87 121 F, Me, F, Cl, H 40 NMR H, F, H, OMe, H 76 70

Example 7

Chlórenaminóny

1- (3,5-dimethyl-4-fluorophenyl) 2-chloro-3-dimethylamino-2-propen-1-one

A suspension of 6.0 g (0.03 mol) of 2-chloro-3 ', 5'-dimethyl-4'-fluoroacetophenone in a mixture of 7.15 g (0.06 mol) of dimethylformamide dimethyl acetal and 100 ml of heptane is heated to 50 ° C for 8 hours. After cooling, the reaction mixture was filtered and the obtained crystals were washed with heptane and then dried (3.2 g). Partial evaporation of the filtrate gave a new portion of the same crystals which were treated in the same manner (0.8 g). The two batches were combined and chromatographed on silica gel, eluting with 70% heptane and 30% ethyl acetate followed by 50% heptane and 50% ethyl acetate. From 1.84 g of 2-chloro-3 ', 5'-dimethyl-4'-fluoroacetophenone, 1.55 g of 1- (3,5-dimethyl-4-fluorophenyl) -2-chloro-3-dimethylamino-2 is obtained. -propen-1-one as white crystals which decompose at 177.5 ° C (yield: 20%).

Using a similar procedure, (3,5-dichloro-2,4-difluorophenyl) -2-chloro-3-dimethylamino-2-propen-1-one was prepared from the appropriately substituted acetophenone and the corresponding second reagent (see NMR analysis, yield: 100%).

Example 8

Py-pyrazoles (see Example 7 of WO 93/22287)

3- (3,5-dichlorophenyl) pyrazole--ΙΗ.

To a solution of 9 g (0.0369 mol) of 1- (3,5-dichlorophenyl) -3-dimethylamino-2-propen-1-one in 100 ml of ethanol was slowly added 2.4 g (0.05 mol) at room temperature. ) hydrazine hydrate. The reaction mixture was stirred at room temperature for 2 hours and then concentrated to dryness. The residue was crushed in heptane. 7.1 g (yield: 90%, mp 156 ° C) of 3- (3,5-dichlorophenyl) -1H-pyrazole are obtained.

Using the same procedure, the pyrazole derivatives of the following general formula are prepared from the appropriately substituted enaminone and the respective second reactant, which are summarized in the following table.

X ^1, X ^2, X ', X', x ⁵ yield (%) i. ~. (° C) or analysis 1 E, Br, F, Cl, H 77 261 E, Br, F, Br, H. 86 201 K, Me, F, Cl, H 93 156 F, Cl, F, Cl, F 47 155 E, Cl, Cl, Cl, K 69 208 Me, Cl, F, Cl, H 97 130 Cl, Cl, H, NO 2, H 60 analysis Me, NO 2, H, F, H 81 98 E, Cl, H, Me, H 80 analysis F, Br, F, Cl, H 88 161 F, Cl, H, Cl, F; 70 150 F, CF _3, E, C, H 12 NMR CF 3, Cl, H, H, H 97 NMR Cl, _OCF3, H, Br, H 82 NMR Cl, OCF 3, H, NO 2, H 50 NMR Br, OCF 3, H, NO 2, H 66 NMR F, K, H, Cl, H 75 NMR Cl, H, H, CF ₃ , H 90 NMR K, F, H, Br, H 69 NMR NO 2, Cl, H, Me, H 82 175 E, F, H, OMe, H 38 83 3- (2-naphthyl) 87 162 3- (benzo [b] thiophen-4-yl 60 147

Example 9

4-chloro-pyrazolo.

A) 3- (3,5-dimethyl-4-fluorophenyl) -4-chloropyrazole (compound

Č.L).

To a suspension of 3.10 g (0.0122 mol) of 1- (3,5-dimethyl-4-fluorophenyl) -2-chloro-3-dimethylamino-2-propen-1-one in 20 ml of glacial acetic acid was stirred a cold solution of 1.5 g of hydrazine hydrate in 30 ml of glacial acetic acid is rapidly added at room temperature. After stirring at room temperature for 7 hours, the reaction mixture is poured into 200 ml of water. The solid formed is filtered off, washed with water and dried under reduced pressure in the presence of P ₌ 0 _s , then purified by chromatography on silica gel, eluting with a mixture of 70% heptane and 30% ethyl acetate. 2.09 g of 3- (3,5-dimethyl-4-fluorophenyl) -4-chloropyrazole are obtained in the form of a white solid, m.p. 144 [deg.] C. (yield: 76%).

Using the same procedure, 3- (3,5-difluoro-4-fluorophenyl) -4-chloropyrazole (Compound No. 2) is prepared for the appropriately substituted 1H-pyrazole and the corresponding second reactant.

B) 4-chloro-3- (3,5-dichlorophenyl) -1H-pyrazole (compound no.

3): (Example 9a of WO 93/22287): Halogenation of pyrazoles.

2.3 g (0.0152 mol) of 3- (3,5-dichlorophenyl) -1H-pyrazole are dissolved at room temperature with stirring in 300 ml of dichloromethane. 2.07 g (0.016 mol) of N-chlorosuccinimide are then added and stirring is continued for 4 days at room temperature. The reaction mixture is then concentrated and chromatographed on a silica gel column (eluent: heptane / ethyl acetate 70:30). 1.4 g (yield: 57%, mp 192 ° C) of 4-chloro-3- (3,5-dichlorophenyl) -1H-pyrazole are obtained.

Using the same procedure, the 4-chloropyrazole derivatives of the general formula below, which are summarized in the following table, are prepared from the appropriately substituted 1H-pyrazole and the respective second reactant.

bile. no. ^Χ χ, x ^2, X ^{3, Χ} Λ, X ^e Y yield (%) 1.1. (’C) or i analysis i 4! H, Br, 1 ', Cl, K 1 Cl 84 169! 5 i H, Br, F, Br, K Cl 88 169 / * à » K, Me, F, Cl, K Cl 69 174 í 7 F, Cl, F, Cl, F Cl 79 143 with ! K, Cl, Cl, Cl, H Cl 61 208 C F, Cl, F, Cl, H Cl 30 158 10 Me, Cl, F, Cl, H Cl 81 53 11 Cl, Cl, H, NO 2, H Cl 70 172 12 Me, NO :, H, F, H Cl 55 126 13 H, Cl, H, Me, H; Cl 85 175 40 F, Br, F, Cl, H Cl 92 167 41 CF 1, Cl, H, H, H Cl 68 78 42 Cl, F, H, OMe, H Cl 75 156 43 H, F, H, OMe, H Cl 45 127 44 F, Me, F, Cl, H Cl 20 119 45 Cl, OClF, H, Br, H Cl 56 109 46 Cl, OCF ₃ , K, NO :, H Cl 44 132 47 Br, OCF 3, H, NO :, H Cl 86 150 48 H, F, H, Br, H Cl 39 155 49 F, H, H, Cl, H Cl 19 116 50 Cl, H, H, CF 3: H Cl 71 110 51 F, Cl, H, Cl, F; Cl 75 152 52 NO :, Cl, H, Me, H Cl 55 172 53 3- (2-naphthyl) Cl 37 140

C) 4-chloropyrazoles (see Example 12 of WO 93/22287) α-acetylation

To 11.0 g (0.046 mol) of 4-chloro-3- (2,2-difluoro-1,3-benzodioxol-4-yl) -1H-pyrazole (prepared according to French Patent Application No. 91/12647) dissolved in 100 ml THF was added 0.25 g (0.005 mol) of 4-dimethylaminopyridine and 4.25 g (0.042 mol) of triethylamine. To this solution at 0 ^and C is added dropwise a solution of 3.6 g (0.046 mol) of acetyl chloride in 50 ml of THF-mixture is further stirred at room temperature for 3 hours. The reaction mixture was poured into 300 ml of water and extracted with ethyl acetate. After drying the organic phase and concentrating under reduced pressure, the residue is ground in 50 ml of heptane, filtered and dried. 12.8 g of 1-acetyl-4-chloro-3- (2,2-difluoro-1,3-benzodioxol-4-yl) pyrazole (compound 14) are obtained, m.p. 131 ° C.

b- nitration

To 12.8 g of 1-acetyl-4-chloro-3- (2,2-difluoro-1,3-benzodioxol-4-yl) pyrazole dissolved in 21 ml of H _and SO ₄ (96%) and 140 ml of CH ₂ C1 ₂ at 0 ^and C added in small portions 6.3 g (0.063 mole) of KNO _a. The reaction mixture is stirred at 0 ° C for 3 hours and then poured onto 300 cm ^{3 of} ice. The precipitate was collected by filtration, washed with water and then with heptane and dried. There was obtained 8.05 g of 4-chloro-3- (2,2-difluoro-5-nitro-1,3-benzodioxol-4-yl) pyrazole, m.p. 180 ° C (yield: 63%) (compound no. 15).

Using the same procedure, the 4-chloropyrazole derivatives of the general formula above, which are summarized in the following table, are prepared from the appropriately substituted py-pyrazole and the respective second reactant.

bile. no. X ^x, X ^2, X ³ , X, X ^p Y yield (%) mp (° C) or analysis 16 F, Cl, H, NO 2 , H Cl 74 147 17 F, Br, H, NO 2 , H Cl 34 154 18 NO _and Cl, H, Cl, H Cl 55 173 54 F, NO _and , H, Cl, H Cl 46 177 55 Cl, NO _and , H, CF 3 , H Cl 22 128 56 NO _and OMe, H, F, H Cl 50 158

Example 10

3- (2-aminophenyl) -4-chloropyrazoles (see Example 14 of WO 93/22287)

3- (2-Amino-3,5-dichloro) phenyl-4-chloropyrazole (Compound No. 19)

14.6 g (0.05 mol) of 3- (2-nitro-3,5-dichlorophenyl) -4-chloropyrazole obtained according to Example 12b, dissolved in 200 ml of acetic acid, are introduced into a 500 ml three-necked round-bottomed flask. The solution is heated to 50 ° C and 8.4 g (0.15 mol) of iron powder is introduced in portions. The reaction mixture is then kept under stirring at 70 ° C for 5 hours. After cooling, the reaction mixture is poured into 800 ml of water, filtered through a frit, rinsed with water and dried to give a white solid (yield: 90%, mp 300 ° C) 3- (2-amino-3,5) dichlorophenyl) -4-chloropyrazole.

Using the same procedure, 4-chloropyrazole derivatives of the general formula below, which are summarized in the following table, are prepared from the appropriately substituted 4-chloropyrazole.

bile. no. X ¹ , X ² , X ³ , X ', X ⁵ Y yield (%) mp (° C) or analysis 20 NH _and Cl, F, Cl, H Cl 68 160 21 NH ₌ Br, H, Br, H Cl 47 169 22 Cl, Cl, H, NH, _and H Cl 69 150 23 F, Cl, H, NH, _and H Cl 90 145 24 F, Br, H, NH, _and H Cl 75 155 57 NH ₌ Cl, H, Cl, F Cl 85 150 58 NO _a , Cl, H, NH ₂ , H Cl 26 198

Example 11

4-chloropyrazoles (see Example 15 of WO 93/22287) 3- (2-methylthio-3,5-dichlorophenyl) -4-chloropyrazole (Compound No. 25).

This compound was prepared by diazotizing 3- (2-amino-3,5-dichlorophenyl) -4-chloropyrazole and reacting with dimethyl disulfide according to literature procedures, yield: 30%, syrup.

Using the appropriately substituted diazonium salt and reacting with the appropriate reagent, the 3-phenyl-4-chloro- or -bromopyrazoles of the following general formula are prepared, which are summarized in the following table, where the group to be introduced is indicated by an asterisk:

X ⁴

bile. no. X ¹ , X ² , X ³ , X ⁴ , X ^p Y yield (%) mp (° C) or analysis 26 F *, Cl, H, Cl, H Cl 75 180 27 F, Cl, H, Br, H Cl 74 175 28 F, Br, H, Br, H Cl 70 170 29 F @ +, Br, H, Cl, H Cl 63 176 59 F, Br, H, Cl, H Cl 64 176 60 F, Me, H, Cl, H Cl 57 136

Example 12

3- (2-nitrophenyl) -4-chloropyrazoles

3- (2-nitro-3,5-dichloro-4-fluorophenyl) -4-chloropyrazole (Compound No. 30).

To a solution cooled to about +5 ° C (ice water bath), 2.50 g (0.00943 mol) of 3- (3,5-dichloro-4-fluorophenyl) -4-chloropyrazole (prepared according to the patent procedure) WO 93/22287, compound 266) in 25 ml of 100% sulfuric acid is added dropwise 0.43 ml (0.0104 mol) of fuming (100%) nitric acid. The reaction mixture is stirred in the cold state for 20 minutes and then at room temperature for 1 hour and finally poured onto 150 g of ice. The precipitate formed is extracted with 150 ml of ethyl acetate. The solution obtained is washed with 100 ml of water, 100 ml of saturated sodium bicarbonate solution and 100 ml of water, dried over magnesium sulphate and evaporated under reduced pressure.

2.78 g of 3- (2-nitro-3,5-dichloro-4-fluorophenyl) -4-chloropyrazole are obtained in the form of a white solid, m.p. 196.4 ° C (yield: 95%).

Using a similar procedure, 3- (2-nitrophenyl) -4-chloropyrazole derivatives of the above general formula are prepared from the appropriately substituted 4-chloropyrazoles, which are summarized in the following table.

bile. no. X ^1, X ^2, X ^3, X ^4, X ⁵ Y yield (*) mp (° C) or analysis 31 NO _a , Br, H, Br, H Cl 25 196 32 NO _a , Br, F, Br, H Cl 73 221 33 NO _a , Me, F, Cl, H Cl 19 214 34 _And M0, Cl, F, Me, H, Cl 20 205 61 NO _a , Me, H, Br, H Cl 13 184

Example 13

3- (5-fluoro-phenyl) -4-chloro-pyrazolo

3- (2,3-dichloro-5-fluorophenyl) -4-chloropyrazole (Compound No. 35).

3- (5-Amino-2,3-dichlorophenyl) -4-chloropyrazole diazonium tetrafluoroborate is obtained by dropwise adding an aqueous solution of sodium nitrite (0.0021 mol) at 0 ° C to a solution containing 0.002 mol of 3- (5-amino- 2,3-dichlorophenyl) -4-chloropyrazole and 5 ml of tetrafluoroboric acid in 50% aqueous solution. The reaction mixture was stirred at 0 ° C for 1 hour and then poured into 50 ml of water and ice. The precipitate obtained is dried rapidly under reduced pressure and then thermally decomposed to dryness at 145 ° C. After cooling, the reaction mixture was taken up in dichloromethane and purified by chromatography on silica gel using ethyl acetate: heptane (25:75) as an eluent (yield: 19%, mp 122 C ^e).

Using a similar procedure starting from appropriately substitutable Joint 4-chloro-pyrazolo 3- (3-chloro-2,5-difluorophenyl) -4-chloropyrazole (Compound no. 36) (yield: 17%, melting point 150 C ^e).

Example 14

3- (3-chloro-5-hydroxyphenyl) -4-chloropyrazole (comparative derivative A).

To a 1000 mL three-necked flask was added 49.5 g (2 mol) of 4-chloro-3- (3,5-dichlorophenyl) pyrazole (prepared according to Example 9 of WO 93/22287) to 500 mL of NMP (N-methylpyrrolidone). 43.2 g (0.8 mol) of sodium methylate are added and the mixture is heated at 140 ° C for 50 hours. After cooling, the reaction mixture was poured into 500 ml of water, acidified and then extracted with ethyl acetate. After drying the organic phase and concentrating under reduced pressure, the residue is purified by silica gel column chromatography (eluent: heptane / ethyl acetate 60:40). There was obtained 28 g (0.12 mol, yield: 61%, mp 222 ° C) of 4-chloro-3- (3-chloro-5-hydroxyphenyl) pyrazole.

Example 15

3- (3-chloro-5-fluorophenyl) -4-chloropyrazole (Compound No. 37).

To a 500 mL three-necked flask at 0 ^and C of 150 ml (1.20 mol) of fluoroboric acid (50% concentration in water) was added 17.4 g (0.075 mol) of 4-chloro-3- (3-amino-5 (chlorophenyl) pyrazole (prepared according to WO 93/22287, Example 14). While maintaining the temperature between 0 and 5 ° C, 5.7 g (0.826 mol) of sodium nitrite dissolved in 10 ml of water are introduced dropwise. Stirring was continued for 1 hour at room temperature. The solid obtained is filtered on a frit and washed with water and then with pentane. After drying, the solid was quenched at 150 ^and C to give a brown oil which was taken up in isopropanol in a hot state. After chromatography on a silica gel column (eluent: heptane / ethyl acetate 70:30), 7.9 g (0.0342 mol, yield: 45.6%, mp 150 ° C) are obtained. 4-Chloro-3- (3- chloro-5-fluorophenyl) pyrazole.

Example 16

N-substituted pyrazoles (Example 19D of WO 93/22287) 1-acetoxymethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole (Compound No. 38)

To a solution of 2.55 g (0.01 mol) of 4-chloro-3- (3,5-dichlorophenyl) pyrazole and 0.90 g (0.030 mol) of paraformaldehyde in 70 ml of THF is added at room temperature 0.15 ml of 1.8 The reaction mixture is stirred at room temperature for 4 hours, then a solution of 1.20 g (0.015 mol) of acetyl chloride in 10 ml of THF is added dropwise at 0 ° C. The reaction mixture was concentrated to dryness and the residue was taken up in 15 ml of heptane and then dried to give 3.05 g of 1-acetoxymethyl-4-chloro-3- (3, 5-methylphenol). 5-dichlorophenyl) pyrazole, m.p. 95 ° C.

Using a similar procedure, the starting substituted ΙΗ-4-pyrazole coder derivatives of formula I are prepared below.

bile. no. X ¹ , X ^a , X ³ , X ⁴ , X ^p Y FROM yield (%) tt ( ^e C) or analysis 39 _And NO, Cl, F, Cl, H Cl CH OAc 2 97 100 40 F, Cl, H, Cl, H Cl CH OAc 2 95 90

Example 17

4-Chloro-3- (5-chloro-3-cyano-2-fluorophenyl) pyrazole (Compound No. 62).

3- (3-Bromo-5-chloro-2-fluorophenyl) -4-chloropyrazole (0.45 g, 0.0014 mol) and copper cyanide (0.14 g, 0.0015 mol) were dissolved in dimethylformamide (DMF) (10 ml) and the mixture was heated at 180 ° C for 8 hours. After cooling to room temperature, the mixture was poured into a 14% NH 4 OH solution (50 mL), then extracted with ethyl acetate (2x50 mL), dried over magnesium sulfate and evaporated under reduced pressure. Purification of the oily residue on a dry silica column (eluting with 30% ethyl acetate in heptane) gave 0.1 g of a yellow solid (yield: 28%, mp 128 ° C).

Example 18

4-chloro-1- (4-methylphenylsulfonyl) pyrazole (Compound No. 63).

The pyrazole (34 g, 0.5 mol) was dissolved in CH ₂ Cl ₂ (350 mL) at 10 ° C and then a solution of sulfuryl chloride (77.6 g, 0.575 mol) in CH ₂ Cl ₂ (150 mL) was added dropwise. ml). After the addition was complete, the mixture was heated at reflux for 18 hours. The dichloromethane was then removed under reduced pressure, the residue was suspended in pyridine (200 mL), and p-toluenesulfonyl chloride (95.33 g, 0.5 mol) was added portionwise. The mixture was then heated to reflux and allowed to cool to room temperature. The mixture was cooled in an ice bath and water (800 mL) was added with vigorous stirring. After 1 hour a solid formed. This was filtered, washed with water and recrystallized from ethanol to give 102 g of 4-chloro-1- (4-methylphenylsulfonyl) pyrazole as a white powder (yield: 80%, mp 96-97 ° C).

Example 19

4-Chloro-5- (3-fluorophenyl) -1- (4-methylphenylsulfonyl) pyrazole (Compound No. 64).

2.4 g (0.0093 mol) of 4-chloro-1- (methylphenylsulfonyl) pyrazole was dissolved in tetrahydrofuran (THF) (20 ml) and cooled to -78 ° C under an argon atmosphere. Over 10 minutes was added dropwise 2.5 M n-butyl lithium (3.92 ml, 0.0098 mol) and the mixture was kept stirring at-78 ^and C for 1.25 h. A solution of zinc chloride in THF (10 mL, 0.01 mol) was then added dropwise over 10 minutes. The reaction mixture is kept under stirring at -78 ° C for 0.5 hours and then at room temperature for 2 hours. Tetrakis (triphenylphosphine) palladium (Pd (PPh ₃ ) 4) (0.35 g, 0.0003 mol) was then added followed by a solution of 3-fluoroiodobenzene (1.4 g, 0.0062 mol) in 15 ml THF. The mixture was then heated at reflux for 18 hours, allowed to cool to room temperature, diluted with EDTA solution (50 mL) and then extracted (3 x 50 mL) with ether. The organic extract was washed with water, dried (MgSO4), filtered and evaporated. A yellow oil (4.1 g) was obtained. Purification on a dry silica column (elution with 10% ethyl acetate in heptane) afforded 1.05 g of 4-chloro-5- (3-fluorophenyl) -1- (4-methylphenylsulfonyl) pyrazole (yield: 48%, mp 110-120). 111 ° C).

Using the method described above, starting from 4-chloro-1- (methylphenylsulfonyl) pyrazole and a suitable further reactant, the compounds of the formula below are summarized and are summarized in the following table:

bile. no. R yield (%) mp (° C) 65 benzo [b] thiophen-4-yl 56 133 66 2-carbomethoxybenzo [b] thien-4-yl 69 170 67 [b] furan-4-yl 67 102

The appropriate intermediates are obtained as follows:

(a) 2-carbomethoxy-4-iodobenzo [b] thiophene:

30.0 g (0.012 mol) of 2-fluoro-6-iodobenzaldehyde was dissolved in anhydrous dimethylsulfoxide (150 ml) at room temperature under argon. Methylthioglycolate (14.05 g, 0.0119 mol) was added dropwise over one minute followed by triethylamine (25.85 g, 0.255 mol). The mixture was heated to 60 ^e C for 2 hours, cooled to room temperature and poured with stirring into ice-water (1000 ml). The yellow precipitate is filtered off, air-dried, suspended in 300 ml of methanol and heated to reflux for 10 minutes. The solution is cooled to 0 ° C, the precipitate is filtered off and dried under reduced pressure to give 30.2 g of 2-carbomethoxy-4-iodobenzo [b] thiophene as a cream-colored solid (yield: 79%, mp 123) to 124 ° C).

(b) 2-carbomethoxy-4-iodobenzo [b] furan:

4.36 g (0.0109 mol) of sodium hydride (60%, dispersed in oil) were suspended in 100 ml of tetrahydrofuran under argon. The reaction mixture was cooled to between + 5 ° C and + 10 ^e C in an ice / cold water bath. A solution of 10.3 g (0.115 mol) of methylthioglycolate in 50 ml of THF was added dropwise over 30 minutes. The mixture was stirred at this temperature for 5 minutes. A solution of 21 g (0.084 mol) was then added dropwise over 30 minutes.

Of 2-fluoro-6-iodobenzaldehyde in 50 mL of THF. The temperature of the reaction mixture rose spontaneously to +40 ° C. Stirring was continued for 1 hour at room temperature. The reaction mixture was treated with 2 mL of methanol and 50 mL of water and then concentrated under reduced pressure. The solid residue is washed with water, crushed with methanol in the cold state and dried under reduced pressure. 11.3 g of a white solid are obtained (yield: 45%, mp 141-143 ° C).

(c) 2-carboxy-4-iodobenzo [b] thiophene:

To a mixture of 17.0 g (0.053 mol) of 2-carbomethoxy-4-iodobenzo [b] thiophene in 150 ml of ethanol was added 10 M aqueous sodium hydroxide solution (5.8 ml). The mixture was heated to reflux for 1 hour and then concentrated to dryness under reduced pressure. The residue was dissolved in water (300 mL) and washed with ethyl acetate (100 mL). The aqueous phase is acidified to pH 1 with 36% HCl. The precipitate was filtered off, washed with water and diisopropyl ether and dried under reduced pressure at 70 ° C. 15.0 g of a white solid are obtained (yield: 93%, mp 260 ° C).

(d) 4-iodobenzo [b] thiophene:

4.3 g of barium-additive chromite are suspended in 70 ml of quinoline and the mixture is heated to 200 ° C. 13.0 g (0.043 mol) of 2-carboxy-4-iodobenzo [b] thiophene are then added portionwise. After gas evolution ceased (approximately 15 minutes), the mixture was cooled to room temperature, poured into a mixture of 36% HCl (100 mL) and ice and filtered through Celite. The celite was rinsed with water (200 mL) and ethyl acetate (100 mL). The filtrate was re-extracted with ethyl acetate (2 x 150 mL), washed with water (400 mL), dried (MgSO ₄ ) and concentrated under reduced pressure. 11.65 g of a brown oil is obtained. Purification on a silica column (elution with pure heptane) gave 9.6 g of a yellow solid (yield: 86%, mp 37-39 ° C).

Example 20

4-Chloro-3- (benzo [b] thien-4-yl) pyrazole (Compound No. 68).

5- (Benzo [b] thien-4-yl) -4-chloro-1- (4-methylphenylsulfonyl) -pyrazole (3.3 g, 0.00844 mol) was dissolved in DMF (25 mL) and the mixture was then ^e at 110 C for 18 hours. After cooling to room temperature, the mixture was poured on ice to stirring to form an oily product. This was extracted with ethyl acetate (2 x 50 mL), washed with water (3 x 100 mL) and dried. Elution on a dry silica column (20% ethyl acetate in heptane) gave, after crushing, 1.4 g of a yellow solid (70% yield, mp 123 ° C).

Using the above procedure, 4-chloro-3- (benzo [b] furan-4-yl) pyrazole was obtained from the appropriate starting material (yield: 64%, mp 122 ° C) (compound No. 69).

Example 21 (Methylation):

4-Chloro-3- (5-chloro-2-fluoro-3-phenylthiophenyl) pyrazole (Compound No. 70).

3- (3-Bromo-5-chloro-2-fluorophenyl) pyrazole (1.10 g, 0.0035 mol) was dissolved in tetrahydrofuran (THF) (20 mL) and cooled to -78 ° C under an argon atmosphere. 1.6 M n-butyllithium (5.5 mL, 0.0088 mol) was added dropwise over 10 minutes and the mixture was maintained at -78 ° C for half an hour. Then diphenyl disulfide (1.53 g, 0.007 mol) dissolved in THF (10 mL) was added dropwise and the mixture was stirred at -78 ° C for 1 hour and then at room temperature until the next day. Water (100 ml) was added and the mixture was extracted with ethyl acetate (2 x 50 ml), dried (MgSO 4) and evaporated under reduced pressure. An oily residue is obtained. This was purified on a dry silica column (eluting with 30% ethyl acetate in heptane) to give 0.45 g.

4-chloro-3- (5-chloro-2-fluoro-3-phenylthiophenyl) pyrazole (38%, ¹³ C NMR).

Using the method described above, starting from 4-chloro-3- (3-bromo-5-chloro-2-fluorophenyl) pyrazole and a suitable additional reagent, the compounds of the following general formula are summarized in the following table, where substituents are introduced. starred.

bile. no. X ^1, X ^2, X ^3, x *, X ^B Y yield (%) t .t. (° C) 71 F, CO, _and H *, H, Cl, H Cl 37 184 72 F, CHO +, H, Cl, H Cl 26 NMR 73 F, CO, _and Et, H, Cl, H Cl 51 100

Example 22

Metal complex of 4-chloro-3- (3,5-dichlorophenyl) pyrazole and copper chloride (Compound No. 74).

Copper chloride dihydrate (1.70 g, 0.01 mol) was dissolved in absolute ethanol (10 mL) and triethyl orthoformate (1 mL) was added. The mixture is kept under stirring at room temperature for 0.5 hours and then 4-chloro-3- (3,5-dichlorophenyl) pyrazole (4.95 g, 0.02 mol) dissolved in absolute ethanol (10 mL) is added. . The mixture is kept under stirring at room temperature until the next day. The precipitate was filtered off, washed with ethyl ether and dried under reduced pressure. 11.8 g of a pale green solid are obtained (yield: quantitative, m.p. 288 DEG C. (decomposition)).

Using the procedure described above, the corresponding starting pyrazole and metal salt are prepared in quantitative yield of the compound of formula I-L M * -I, which are shown in the following table:

bile. no. X ^1, X ^a, X ^3, X ^4, X = M * L " color mp (° C) 75 H, Cl, H, Cl, H; CU br greenish 264 (dec) 76 H, Cl, H, Cl, H; CU NO 3 blue 190 (dec) 77 H, Cl, H, Cl, H; Zn Cl White 195 (dec) 78 H, Cl, H, Cl, H; Zn And what White > 300 79 H, Cl, H, Cl, H; Ni Cl cream > 300 80 _And NO, Cl, F, Cl, H Cu Cl blue 255 (dec) 81 F, Cl, H, Cl, H CU Cl green 287 (dec)

Other compounds of formula I and known from European application 0 538 156 are also tested:

compound 82: 4-chloro-3- (2 ', 2'-difluoro-1', 3'-benzodioxolyl) pyrazole (compound 25 of European application 0 538 156) compound 83: 4-chloro-3- (2,3 -dichlorophenyl) pyrazole (compound No. 12 of European application 0 538 156) compound 84: 4-chloro-3- (2-nitro-3-chlorophenyl) pyrazole (compound No. 120 of European application 0 538 156).

The present invention also relates to a method of treating crops suffering from or susceptible to fungal diseases, comprising administering to the propagation material of these plants an effective dose of a compound of formula I or a salt thereof, a metal complex thereof or an N-oxide thereof. An effective dose is an amount sufficient to control or control the fungi present on these crops. These dosages to be used may vary widely depending upon the type of fungi being suppressed, the type of crop and the climatic conditions and the compound used.

In practice, the compounds are preferably administered in doses of 0.1 to 500 g of active ingredient per 100 kg of seed, and preferably 1 to 400 g per 100 kg.

Fungal diseases are diseases caused by phytopathogenic fungi, in particular Oomycetes, Ascomyce35 tes and Basidiomycetes.

Crops which may be subjected to fungicidal treatment with the compounds according to the invention include rice, cereals, in particular wheat and barley, and legumes. Rice is the preferred crop for fungicidal treatment with the compounds of the invention.

Example 23

In vivo seed disinfection test

Two protocols were used, depending on whether natural infected seeds (Drechslera graminea / Drechslera teres on barley) or artificially infected seeds (Cochliobolus sativus / Fusarium culmorum / Fusarium nivale / Septoria nodorum) were used:

g of seeds are treated in the HEGE bowl with the active compound according to the invention in the form of an aqueous suspension concentrate at a concentration of 1.5 liters per 100 kg. 30 seeds are sown on peat and pozzolan substrate in pots (7x7x8 cm) and 3 pots are prepared for treatment. Under the same conditions, contaminated untreated control and uncontaminated control (in the case of artificial contamination) shall be sown.

In the case of artificial contamination, healthy seeds are sown and a spore suspension based on a 10 ml aqueous suspension is applied to the pot.

The concentration of the suspension varies according to the pathogen examined:

pathogen crop number of spores Cochliobolus sativus barley 200 000 Furarium culmorum / Fusarium nivale wheat, barley 400 000 Septoria nodorum wheat 250 000

The pots are placed in a controlled greenhouse at 5 ° C and saturated relative humidity for a time that depends on the test being performed, in particular for three weeks for Drechslera graminea / Drechslera teres and Cochliobolus sativus and for two weeks for Fusarium culmorum / Fusarium nivale / Septoria nodorum.

The pots are then transferred to an environmentally controlled greenhouse at 10 ° C (photoperiod: 8 hours daily 16 hours night), 80% relative humidity until symptoms appear.

Evaluation is done visually compared to a contaminated untreated control.

Under these conditions, good protection (at least 75% or total protection) was achieved at a dose of 100 g / 100 kg:

on Drechsler graminea: with the following derivatives: 3, 4, 5, 7, 10, 18, 26, 30, 68, 69, on Drechsler teres: with the following derivatives: 3, 26, 30, 82, 83, 84, on Cochliobolus sativus: with the following derivatives: 3,

26, 30, for Fusarium culmorum: with the following derivatives: 3, 26, 30, 82, 83, 84, for Fusarium nivale: with the following derivatives: 1, 3, 4, 7, 8, 9, 12, 20, 26, 27, 30, 37, 82, 83, 84

- for Septoria nodorum: with the following derivatives: 3, 26,

30, 82, 83, 84.

The present invention also relates to a method of treating crops suffering or susceptible to fungal diseases, comprising administering to the above-ground portions of these plants an effective dose of a novel compound of formula I as defined above. An effective dose is an amount sufficient to control or control the fungi present on these crops. These dosages to be used may vary widely depending upon the type of fungi being suppressed, the type of crop and the climatic conditions and the compound used.

In practice, the compounds are preferably applied at doses of 0.002 to 5 kg / ha and preferably 0.005 to kg / ha.

Fungal diseases are diseases caused by phytopathogenic fungi, in particular Oomycetes, Ascomycetes and Basidiomycetes.

Crops which may be subjected to fungicidal treatment with the compounds according to the invention include rice, cereals, in particular wheat and barley, as well as legumes. Rice is the preferred crop for fungicidal treatment with the compounds of the invention.

Example 24

In vivo test for Botrytis cinerea on cut off leaves of tomatoes: (susceptible strains and strains resistant to benzimidazoles):

A fine suspension of the test drug is prepared by finely grinding with the following composition:

- active substance: 60 mg

- Tween 80 surfactant (polyoxyethylene sorbitan oleate) diluted with water to a concentration of 10%: 0.3 ml

- make up to 60 ml with water.

The aqueous suspension is then diluted with water to the desired concentration of active ingredient.

day tomatoes grown in a greenhouse (variety Marmande) are treated by spraying with the aqueous suspensions defined above and with different concentrations of the test compound. At the end of the 24 hour period, the leaves were cut and placed on a Petri dish (14 cm diameter), the bottom of which was pre-coated with a damp filter paper disc (10 leaflets per dish).

The inoculum was then applied via a syringe as drops (3 per leaf) of a benzimidazole-sensitive or benzimide-resistant zinc-resistant suspension of Botrytis cinerea spores obtained by cultivation for 15 days and then suspended at 150,000 units per cm ³ .

Monitoring is performed 6 days after contamination compared to the untreated control.

Under such conditions, good (at least 75%) or complete protection is observed for the following compounds at a dose of 1 g / l: 1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 19, 20 21, 26, 27, 28, 30, 31, 32, 33, 34, 35, 36, 37, 39, 40, 62, 68, 70, 74, 75, 76, 77, 78, 79, 80, 81 on Botrytis sensitive to benzimidazoiy.

Example 25

In vivo test for Pyricularia oryzae causing rice piricullariosis:

A fine suspension of the test drug is prepared by finely grinding with the following composition:

- active substance: 60 mg

- Tween 80 surfactant (polyoxyethylene sorbitan oleate) diluted with water to a concentration of 10%: 0.3 ml

- make up to 60 ml with water.

The aqueous suspension is then diluted with water to the desired concentration of active ingredient.

Rice plants planted in pots containing a 50:50 mixture of enriched peat and pozzolan are sprayed at the 10 cm height with the above suspension.

After 24 hours, an aqueous spore suspension of Pyricularia oryzae, obtained by culturing for 15 days and suspending the spores at 100,000 units per cm ^3, is applied to the leaves of the plants.

The rice plants are then placed in an incubator (25 ° C, 100% relative humidity) for 24 hours and placed in an observation cell under the same conditions for 5 days.

Evaluation is performed 6 days after contamination.

Under such conditions, a good (at least 75%) or complete protection is observed for the following compounds at a dose of 1 g / l: 1, 5, 6, 8, 9, 10, 12, 13, 17, 19, 20, 21, 23 24, 26, 27, 28, 30, 31, 32, 33, 34, 35, 36, 37, 39, 40, 68, 70, 80, 81.

Example 26

In vivo test for Plasmopara viticola:

A fine suspension of the test drug is prepared by finely grinding with the following composition:

- active substance: 60 mg

- Tween 80 surfactant (polyoxyethylene sorbitan oleate) diluted with water to a concentration of 10%: 0.3 ml

- make up to 60 ml with water.

The aqueous suspension is then diluted with water to the desired concentration of active ingredient.

Vine cuttings (Vitis vinifera), variety Chardonnay are cultivated in pots. After 2 months (stage 8 to 10 leaves, height from 10 to 15 cm), the plants are sprayed with the above aqueous suspension.

Plants used as controls are treated with an aqueous solution containing no active ingredient.

After drying for 24 hours, each plant is contaminated by spraying with an aqueous spore suspension of Plasmopara viticola, obtained by cultivating for 7 days and suspending at 100,000 units per cm ³ .

The contaminated plants are then incubated for 2 days at about 18 ° C in an atmosphere of saturated humidity, and then for 5 days at about 20-22 ° C at 90-100% relative humidity.

Evaluation is carried out 7 days after contamination compared to control plants.

Under these conditions, good (at least 75%) or complete protection at 1 g / l can be observed for the following compounds: 1, 2, 3, 4, 5, 6, 8, 9, 11, 13, 16, 20, 21 23, 24, 26, 27, 30, 31, 33, 35, 36, 37, 39, 40, 62, 68, 70, 72, 73, 74, 77, 78, 79, 80, 81.

Example 27

Test in vi vo for Puccinia recondita:

A fine suspension of the test drug is prepared by finely grinding with the following composition:

- active substance: 60 mg

- Tween 80 surfactant (polyoxyethylene sorbitan oleate) diluted with water to a concentration of 10%: 0.3 ml

- make up to 60 ml with water.

The aqueous suspension is then optionally diluted with water to the desired concentration of active ingredient.

Wheat sown in pots containing a 50:50 peat and pozzolanic substrate is sprayed at the 10 cm height with the above aqueous suspension.

Plants used as controls are treated with an aqueous solution containing no active ingredient.

After 24 hours, an aqueous spore suspension (100,000 spores / cm ³ ) is sprayed onto the wheat to recover from the contaminated plants. The wheat is then placed in an incubator at about 20 ° C and 100% RH for 24 hours and then at 60% RH for 7-14 days.

Monitoring of plant condition will be performed between 8 and 15 days after contamination compared to the untreated control.

Under such conditions, good (at least 75%) or complete protection is observed for the following compounds at a dose of 1 g / l: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 20 21, 26, 27, 28, 30, 31, 32, 33, 35, 37, 40.

The present invention also provides compositions useful as fungicidal agents, comprising as active ingredient (s) one (or more) of the compounds of formula (I) above, together with solid or liquid agriculturally acceptable carriers with surfactants which are also agriculturally acceptable. In particular, standard inert carriers and standard surfactants can be used.

These compositions may also contain any other additives such as protective colloids, adhesives, thickeners, thixotropic agents, penetration agents, stabilizers, masking agents and the like. Even more generally, the compositions of the invention may be combined with all solid or liquid additives corresponding to conventional formulation techniques.

In general, the compositions of the invention typically comprise from about 0.05 to 95% by weight of a compound of the invention (hereinafter referred to as the active ingredient), one or more solid or liquid carriers, and optionally one or more surfactants.

As used herein, the term "carrier" means a natural or synthetic, organic or inorganic material with which the compound is combined to facilitate its application to plants, seeds or soil. This carrier is therefore generally inert and must be agriculturally acceptable, especially for the treated plants. The carrier may be solid (clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers, etc.) or liquid (water, alcohols, especially butanol, and the like).

The surfactant may be an emulsifying agent, a dispersing agent or a wetting agent of the ionic or non-ionic type, or a mixture of such surfactants. Examples include polyacrylic acid salts, lignosulphonic acid salts, phenolsulfonic or naphthalenesulfonic acid salts, polycondensates of ethylene oxide with fatty alcohols or fatty acids or fatty amines, substituted phenols (especially alkylphenols or arylphenols), salts of sulfosuccinic acid derivatives (sulfosuccinic acid derivatives) especially alkyltaurates), polyoxyethylenated esters of phosphoric acid with alcohols or phenols, esters of fatty acids and polyols, derivatives containing sulfate, sulfonate and phosphate functions of the above compounds. The presence of at least one surfactant is generally necessary when the compound and / or the inert carrier are insoluble in water and the carrier medium for application is water.

The compositions for agricultural use according to the invention may contain the active compounds according to the invention within very wide limits, from 0.05% to 95% by weight. These compositions preferably contain between 5% and 40% by weight of a surfactant.

The compositions according to the invention themselves have various solid or liquid forms.

Solid forms of these compositions may include powders for dusting (up to 100% active ingredient) and granules, in particular granules obtained by extrusion, compression, impregnation of a granular carrier or powder granulation (up to 0.5% to 80% active ingredient). in the latter form) as well as tablets, including effervescent tablets.

The compounds of the formula I can also be used in the form of powders for dusting. A composition comprising 50 g of active ingredient and 950 g of talc, a composition comprising 20 g of active ingredient, 10 g of finely divided silica and 970 g of talc may also be used. The ingredients are mixed and ground and the resulting mixture is applied by powdering.

Liquid form preparations or forms intended to form liquid formulations immediately prior to application include solutions, in particular water-soluble concentrates, emulsifiable concentrates, emulsions, suspension concentrates, aerosols, wettable powders (or spray powders), pastes and gels.

Emulsifiable or soluble concentrates usually contain 10 to 80% active ingredient and emulsions or solutions ready for application contain 0.001 to 20% active ingredient.

The emulsifiable concentrates may, if necessary, contain, in addition to the solvent, 2 to 20% of suitable additives such as stabilizers, surfactants, penetrating agents, corrosion inhibitors, dyes or adhesives as mentioned above.

Emulsions of any desired concentration, which are particularly suitable for application to crop plants, can be obtained from these concentrates by dilution with water.

The following are some examples of emulsifiable concentrate compositions:

Example EC 1

- active substance 400 g / l

- alkali metal dodecylbenzenesulfonate 24 g / l

- an oxyethylenated nonylphenol containing an ethylene oxide molecule of 16 g / l

- cyclohexanone 200 g / l

- make up the aromatic solvent to 1 liter

In another emulsifiable concentrate formulation:

Example EC 2

- active substance 250 g

- epoxidized vegetable oil 25 g

- mixture of alkylarylsulphonate and polyglycol ether and fatty alcohols 100 g

- dimethylformamide 50 g

- xylene 575 g

Suspension concentrates, which are also sprayable, are prepared so as to obtain a stable, non-settling liquid, and these concentrates usually contain from 10 to 75% active ingredient, from 0.5 to 15% surfactant, from 0.1 up to 10% of thixotropic agents, from 0 to 10% of suitable additives, such as antifoams, corrosion inhibitors, stabilizers, penetrating agents and adhesives, and as a carrier they contain water or an organic liquid in which the active ingredient is sparingly soluble or insoluble. Certain solid organic substances or inorganic salts may be dissolved in such a carrier to prevent sedimentation or act as antifreeze agents.

The following is an example of the suspension concentrate composition:

Example SC 1

- active substance 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 powders for spraying) are usually prepared containing 20 to 95% active ingredient, containing in addition to a solid carrier from 0 to 30% wetting agent, 3 to 20% dispersing agent and, if necessary, 0.1 up to 10% of one or more stabilizers and / or other additives such as penetrating agents, adhesives or anti-caking agents, colorants and the like.

For the preparation of sprayable powders or wettable powders, the active substances are intimately mixed in a suitable mixer with other substances and the mixture is ground in a mill or other suitable disintegrator. In this way, sprayable powders are obtained which have advantageous wettability and suspensibility. These powders can be suspended in water to any desired concentration and these suspensions are very advantageously useful for application to the foliage of plants.

Pastes may be prepared instead of wettable powders. The conditions of preparation and applicability of these pastes are analogous to those used for wettable or sprayable powders.

The following are some examples of wettable (or sprayable) powder formulations:

Example WP 1

- active substance 50%

- ethoxylated fatty alcohol (wetting agent) 2,5%

- ethoxylated phenylethylphenol (dispersing agent) 5%

- chalk (inert carrier) 42,5%

Example WP 2

- active substance 10%

- synthetic C _{x and} branched oxo-alcohol ethoxylated with 8 to 10 ethylene oxide units (soaking agent) 0,75%

- neutral calcium lignosulfonate (dispersing agent)

- calcium carbonate (inert filler)% to 100%

Example WP 3

This wettable powder contains the same ingredients as in the previous example, in the following ratios:

- active substance 75%

- soaking agent 1,5%

- dispersing agent 8%

- calcium carbonate (inert filler) up to 100%

Example WP 4

- active substance 90%

- ethoxylated fatty alcohol (soaking agent) 4%

- ethoxylated phenylethylphenol (dispersing agent) 6%

Example WP 5 active substance mixture of anionic and non-ionic surfactants (wetting agent) sodium lignosulfonate (dispersing agent) kaolin clay (inert carrier)%

2.5% 5%

42.5%

Also included within the general scope of the invention are aqueous dispersions and emulsions, for example formulations obtained by diluting a wettable powder or emulsifiable concentrate of the invention with water. The emulsions may be of the water-in-oil type or of the oil-in-water type and may have a thick consistency like mayonnaise ”.

The compounds of the invention may be formulated as water-dispersible granules, which are also within the scope of the invention.

These dispersible granules having a bulk density generally between about 0.3 and 0.6 have a particle size generally between about 150 and 2000 gm, and preferably between 300 and 1500 gm.

The active ingredient content of these granules is generally between about 1% and 90% and preferably between 25% and 90%.

The remainder of the granules essentially consist of a solid filler and optionally surfactants which impart dispersibility in water to the granules. These granules may be essentially of two different types, depending on whether the filler is water-soluble or water-insoluble. If the filler is water soluble, it may be inorganic or preferably organic in nature. Excellent results were obtained with urea. In the case of an insoluble filler, it may preferably be an inorganic filler, such as kaolin or bentonite. In this case, it is preferably accompanied by surfactants (in an amount of 2 to 20% by weight of the granules) of which more than half are, for example, at least one substantially anionic dispersant such as an alkali metal or alkaline earth metal polynaphthalenesulfonate or alkali metal or metal lignosulfonate alkaline earth metal, the remainder being nonionic or anionic wetting agents such as an alkali metal or alkaline earth metal alkyl naphthalenesulfonate.

Other additives, such as antifoams, may be added, although not necessary.

The granules according to the invention can be prepared by mixing the necessary ingredients and then granulating by various known techniques (in a granulator, fluid bed, spraying, extrusion, etc.). The preparation of the granules is usually completed by grinding and then sieving to obtain particles with the desired size range. The granules obtained according to the above-described process may also be used and then impregnated with the active ingredient-containing composition.

The granules are preferably obtained by extrusion using the procedure described in the Examples below.

Example DG 1

Dispersible granules

90% and 10% bead urea are mixed in the blender. Roller crusher mixture. A powder is obtained by weight of water. The wet powder is crushed. The granules obtained are sieved and sieved to obtain between 150 and 2000 μιη.

by weight of the active ingredient is then comminuted in a toothed gear which is soaked with about 8% extruded in a perforated valvary, then the granules with particle size are comminuted

Example DG 2

Dispersible granules

The following components are mixed in the mixer:

- active substance 75%

- soaking agent (sodium alkylnaphthalenesulfonate) 2%

- dispersing agent (sodium polynaphthalenesulfonate) 8%

- inert filler insoluble in water (kaolin) 15%

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

The granules may be used as such or in solution or dispersion in water to obtain the desired dosage. These granules can also be used for the preparation of mixtures with other, in particular fungicidal, active substances, the latter being in the form of wettable powders or granules or aqueous suspensions.

More preferably, from about 0.5% to about 95% by weight of the active ingredient, the compositions are intended for storage and transport.

Claims (14)

Composition for the treatment of plant propagation material against diseases caused by fungi, characterized in that it contains at least one 3-phenylpyrazole derivative of the general formula I as active substance. From which X ^1, X ^a, X ^3, X 'and X ^5, which may be the same or different, are a hydrogen or a halogen, hydroxyl, mercapto, cyano, thiocyanato, nitro or nitroso group or an amino group optionally substituted by one or two alkyl alkyl, hydroxy, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, benzyl, alkenyl, alkynyl alkyl, alkynyl, cyanoalkyl, a formyl group, acetyl group, alkyl (thio) carbonyl group or alkoxy (thio) carbonyl group, monoalkylamino (thio) carbonyl group or dialkylamino (thio) carbonyl group, amino (thio) carbonyl group, monoarylamino50 (thio) carbonyl group or diarylamyl group amino (thio) carbonyl, carboxyl, karboxylatoskupinu, carbamoyl or benzoyl, phenyl, phenoxy or phenylthio, alkylfenylsulfenylovú group or alkylphenylsulfinyl, or alkylphenylsulfonyl, or alkoxyfenylsulfenylovú group or alkoxyfenylsulfinylovú group or alkoxyfenylsulfonylovú group or monoalkylaminofenylsulfenylovú group or monoalkylaminofenylsulfinylovú group or monoalkylaminofenylsulfonylovú or a di (alkyl) aminophenylsulfenyl group or a di (alkyl) aminophenylsulfinyl group or a di (alkyl) aminophenylsulfonyl group, a sulfo group, its salts, esters and amides, a phosphoryl group substituted by two groups selected from alkyl, alkoxy, alkylthio and dialkylamino, benzyloxy, phenyloxy or phenyl, trialkylsilyl or alkylphenylsilyl; however, two adjacent groups of X ¹ , X ^a , X ³ , X ⁴ and X ⁼ may form a bridge of from 2 to 4 chain members of which at least one may be replaced by an oxygen, sulfur or nitrogen atom, and may contain one or more from the following atoms or groups, namely C, O, S, N, C = O, C = S, SO, SO _and CH = CH, wherein the carbon atoms of this bridge may be unsubstituted or substituted by at least one halogen atom and / or at least one hydroxy, amino, alkyl, alkoxy, alkylthio, monoalkylamino, dialkylamino, alkylsulfinyl or alkylsulfonyl, or alkoxycarbonyl group, wherein the alkyl moiety is as defined below, with the proviso that X ¹ to X ⁵ cannot be simultaneously all hydrogen . Y is hydrogen or halogen or nitro, cyano, hydroxy, alkylcarbonyloxy, alkoxycarbonyloxy, aminocarbonyloxy, mercapto, carboxyl, carboxylate, formyl, alkyl (thio) carbonyl, thiocarbonyl, thiocarbonyl, thiocarbonyl, thiocarbonyl, thiocarbonyl, aminoalkyl, thiocyanato or alkyl, alkenyl, alkynyl, alkoxy or alkylthio, alkylsulfinyl or alkylsulfonyl, the alkyl portion of which may optionally be mono- or polyhalogenated, amino optionally substituted with one or two alkyl or phenyl groups groups, phenyl, phenoxy, phenylthio, arylsulfinyl or arylsulfonyl, wherein Y and X ¹ or X ® may form a bridge containing from 1 to 3 members of the chain that may contain one or more of the following atoms or groups, namely C, O, S, N, C = O, C = S, SO, SO _and CH = CH, wherein the carbon atoms of this bridge may be unsubstituted or substituted by at least one halogen atom and / or at least one hydroxy, alkoxy, alkylthio, monoalkylamino or dialkylamino, alkylsulfinyl or alkylsulfonyl group, wherein the alkyl moiety is as defined below, Z is hydrogen or halogen or cyano, nitro or hydroxy, or alkyl, haloalkyl, hydroxyalkyl, formyloxyalkyl, alkyl (thio) carbonyloxyalkyl or aryl (thio) carbonyloxyalkyl, alkoxy (thio) carbonyloxyalkyl thio) carbonyloxyalkyl, monoalkylamino (thio) carbonyloxyalkyl or dialkylamino (thio) carbonyloxyalkyl, cycloalkyl or cycloalkylalkyl, wherein the cycloalkyl moiety may be substituted by GR ⁴ as defined below, alkoxy, alkyl, optionally substituted with hydroxy, alkyl, hydroxy, alkyl, hydroxy, or an alkylsulfonyl group, - phenyloxy or phenylthio, phenylsulfinyl or phenylsulfonyl, amino optionally substituted by one or two alkyl groups, alkenyl or alkynyl groups each containing from 3 to 7 carbon atoms and is optionally substituted, phenyl or Het, optionally substituted, a group of formula C (= 2 ^{1) 2} Z, wherein Z ¹ represents an oxygen or sulfur atom or an alkylamino or alkylimino or arylamino or arylimino group, and Z ² represents a hydrogen or halogen atom or a hydroxy, mercapto, cyano or amino, alkyl, alkoxy, haloalkoxy, alkylthio, alkenyl or alkynyl or alkenyloxy, each of which contains 3-7 carbon atoms, phenyl, phenylalkyl, phenoxy, phenalkyloxy, Het or Het-alkyl, phenylalkenyl or phenylalkinyl, Het-alkenyl or Het-alkynyl, monoalkylamino or dialkylamino, monophenylamino or diphenylamino or alkylsulfonylamino or arylsulfonylamino, phosphoryl substituted with two radicals selected from alkyl, cycloalkyl, alkyl, alkoxy, alkyl, alkoxy a group, phenyl, phenylalkyl, Het or Het-alkyl, optionally substituted, or S (= Z ^X ) (= Z ³ ) Z ² , wherein Z ¹ and Z ² are as defined above and Z ³ has the same meanings , but not the same meaning as Z ¹ , as well as tautomeric forms of formula Ia, wherein Z is hydrogen or isomeric forms, wherein Z is C (= Z ¹ ) Z ^a , or S (= Z ^X ) (= Z ³⁾ Z ² , their salts, their metal complexes or their N-oxides, all of which are substituted above those alkyl, alkoxy, alkenyl and alkynyl groups and moieties contain up to 7 carbon atoms and are optionally halogenated (from 1 to 8 halogen atoms), cycloalkyl groups contain from 3 to 7 carbon atoms and are optionally substituted with at least one substituent selected with the GR * group as defined below, the phenyl groups being optionally substituted with 1 to 5 substituents selected from the group consisting of halogen, alkyl or (C 1 -C 3) alkoxy and nitro, Het represents a monocyclic or bicyclic heterocyclic radical containing from 5 to 10 atoms, of which 1 to 4 are heteroatoms (oxygen, sulfur, nitrogen, phosphorus), GR ⁴ includes: a halogen atom or a cyano, nitro, mono or dialkylamino, alkyl, alkoxy, alkylsulfenyl, alkylsulfonyl, alkylcarbonyl, alkylthiocarbonyl, alkoxycarbonyl, alkoxytiokarbonylovú group, a monoalkylaminocarbonyl group or a dialkylaminocarbonyl or monoalkylaminotiokarbonylovú group or dialkylaminotiokarbonylovú group, monoalkylaminosulfonylovú group or dialkylaminosulfonyl a group (wherein the alkyl groups and moieties contain from 1 to 4 carbon atoms and are optionally substituted with 1 to 9 halogen atoms). Composition according to claim 1, characterized in that it contains, as active ingredient, a compound of the formula (I) in which Y represents a chlorine atom or a bromine atom. Composition according to claim 1 or 2, characterized in that it contains, as active ingredient, a compound of the formula I in which Z represents a hydrogen atom or a C (= Z ¹ ) Z ^{2 group} , wherein Z ¹ is an oxygen atom or a sulfur atom. Composition according to claims 1 to 3, characterized in that it contains, as active ingredient, a compound of the formula I, wherein X ¹ , X ² and X ⁴ are hydrogen or halogen, nitro or amino, or optionally a halogenated alkyl group C 1-4 alkyl. 5. Device by claims 1 to 3, marked u- by that like active substance contains a compound of formula I, where X ³ is a hydrogen atom or a fluorine atom. 6. Device by claims 1 to 3, marked u- by that like active substance contains a compound of formula I wherein X ¹ and / or X ® are hydrogen. Composition according to claims 1 to 3, characterized in that it contains a compound of the formula I as active ingredient, wherein the two adjacent substituents selected from the group consisting of X ¹ , X ² , X ³ , X * and X ® form a bridge containing 3 or 4 chain members, in particular optionally halogenated and preferably form a fluorinated methylenedioxy bridge. Composition according to claims 1 to 3, characterized in that it contains, as active ingredient, a compound of the formula I, wherein X ¹ , X ³ and X ® are hydrogen and X ² and X * are each chlorine. Composition according to claims 1 to 3, characterized in that it contains a compound of the formula I as active substance, wherein X ¹ is nitro, X ² and X ⁴ are each chlorine, X ³ is fluorine and X ® is hydrogen . 10. The composition of claim 7, wherein characterized in that as an active ingredient a compound of formula I, wherein X ¹ is F, X ² and X * are each chloro, X ³ is F, and X ³ and X ^s are hydrogen. 11. A method of treating a plant propagation material against fungal diseases, the method comprising treating the material with a 3-phenylpyrazole derivative of the formula I as defined in claim 1, or a salt thereof, a metal complex or an N-oxide thereof. . 12. New 3-phenylpyrazole derivatives of the general formula I From which Y is chlorine and Z is hydrogen, X ¹ is a hydrogen atom or a halogen atom or a nitro, amino or methyl group, X ² is a halogen atom or a nitro, amino or methyl group, X ³ is a hydrogen atom or a halogen atom, X ⁴ is a halogen atom or an amino, nitro or methyl group, X ⁵ is a hydrogen atom or a halogen atom, or salts, metal complexes or N-oxides thereof. Compounds according to claim 12, wherein in formula I X ² is a chlorine atom or a bromine atom, X ³ and X ⁴ , which may be the same or different, are each a hydrogen atom or a fluorine atom. X ¹ = H, X ¹ = NO X ¹ X ¹ X ¹ X ¹ X ¹ X ¹ = NH = F, = H, = F, = F, = CH X ¹ = F, X ¹ = F, X ¹ = H, Derivatives according to claim 12 selected from the group consisting of X ² X ² X ² X ² X ² X ² X ² X ² X ² X ² = Cl, X ³ = H, X ¹ = F, X ² = Cl, X ³ = HX ² s všeol Beci Lél as well as formula I, in which = CH ₃ , X ³ = F, X ⁴ = CH ₃ and X ⁵ = H = Cl, X ³ - F, X ⁴ = Cl and X ^B = H = Cl, x ³ = F, X ⁴ = Cl and X ⁵ = H = Cl, x ³ = F, X ⁴ = Cl and X = F = Cl, x ³ = H, X ⁴ = F and X = H = Cl, x ³ = H, X ⁴ = Cl and X ⁵ = H = br. x ³ H, X ⁴ = Br and X ^B = H = N0 _a , x ³ H, X ⁴ = F and X ^B = H = Cl, x ³ = F, X ⁴ = Cl and X ^B = H = Cl, x ³ = H, X ¹ = F, X ² = Cl, Cl, x ³ = F, X ⁴ = Cl and X ^B = H Composition for the treatment of foliage of plants against diseases caused by fungi, characterized in that it contains at least one 3-phenylpyrazole derivative according to any one of claims 11 to 13 or a salt thereof, a metal complex or an N-oxide thereof as active ingredient. A method of treating a leaf of a plant against a disease caused by a fungus, characterized in that the plant is treated with at least one 3-phenylpyrazole derivative according to one of claims 11 to 13 or a salt thereof, a metal complex or an N-oxide thereof.