HUT76819A - Fungicidal compositions containing 3-phenyl-pyrazole derivatives for treating propagative plant stock, novel 3-phenyl-pyrazole derivatives, and fungicidal uses thereof - Google Patents

Description

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

Certain 3-phenylpyrazole derivatives are described in EP 0 538 156 and WO 93/22287, where beneficial properties of the compounds against fungal diseases of plant foliage are found.

The term plant reproductive material includes all plant reproductive organs that can be used for propagation and reproduction of plants. Mention may be made, for example, of crop seeds in the strict sense, that is, not including potatoes, roots, fruits, tubers, onions, rhizomes and parts of plants, or germinated plants and seedlings which are germinated

85061 -3035B-KY / KmO

- to be planted after 2 or after emergence from the soil. These seedlings can be protected by total or partial treatment by immersion before planting. Preferably, the following reproductive organs may be used in the method of the invention:

- dicot seeds: peas, cucumbers, melons, soya, cotton, sunflower, rape, beans, flax, beet,

- monocotyledonous seeds: cereals, maize, rice

- or potato tubers.

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

In the case of tubers, the tubers are preferably coated in an amount corresponding to soaking the product in a formulation containing from 0.1 g / l to 100 g / l of active ingredient.

More particularly, the present invention relates to compositions for treating fungal diseases of the reproductive organs, characterized in that they contain as active ingredient at least one 3-phenylpyrazole derivative of the formula (I), wherein

X ₁ , X ₂ , X ₃ , X ₄ and X ₅ may be the same or different and have the meaning

- hydrogen or halogen, hydroxy, mercapto, cyano, thiocyanato, nitro or nitroso groups or optionally substituted one or two alkyl or phenyl groups,

alkyl, hydroxyalkyl, Ixoxy-alkyl, aminoalkyl, alkylsulfonyl, alkyl-1-thioalkyl, alkylsulfinyl-alkyl, alkylsulfonyl-alkyl -, benzyl, alkenyl, alkynyl, cyanoalkyl, alkoxy, alkenyloxy, alkylthio, alkylsulfonyl, formyl, acetyl, alkyl or alkoxy (thio) carbonyl, mono- or dialkyl- amino (thio) carbonyl, amino (thio) carbonyl, mono- or diarylamino (thio) carbonyl, carboxyl, carboxylate, carbamoyl or benzoyl,

- phenyl, phenoxy or phenylthio,

- alkyl, alkoxy or mono- or di (alkylamino) phenylsulfenyl or sulfinyl or sulfonyl,

- sulfone group, its salts, esters and amides,

- a phosphoryl group substituted by two alkyl, alkoxy, alkylthio and / or dialkylamino, benzyloxy, phenyloxy or phenyl groups,

- a trialkyl or alkylphenylsilyl group, two adjacent groups X _1t X ₂ , X ₃ , X 4 and X ₅ may form a bridge having 2 to 4 chain members, at least one of which is oxygen, sulfur or nitrogen which may be substituted and which may contain one or more of the following atoms or groups: carbon, oxygen, nitrogen, sulfur, C = O, C = S, SO, SO ₂ , CH = CH, and the carbon atoms of this bridge may be unsubstituted or at least one halogen and / or at least one hydroxy, amino, alkyl, alkoxy, alkylthio, mono or dialkylamino, alkylsulfinyl or sulfonyl or alkoxycarbonyl group, the definition of the alkyl moiety follows, with the proviso that X! - X ₅ are not simultaneously hydrogen;

Y is hydrogen or halogen, or nitro, cyano, hydroxy, I-1-carbonoxy, alkoxycarbonyloxy, aminocarbonyloxy, mercapto, carboxyl, carboxylate, formyl, alkyl. (thio) carbonyl, aryl 1-carbonyl, alkoxy (thio) carbonyl, carbamoyl, aminoalkyl, thiocyanato or alkyl, alkenyl, alkynyl, alkoxy or alkylthio , alkylsulfinyl or

- a 4-sulfonyl group wherein the alkyl moiety in these groups may be optionally mono- or polyhalo, amino optionally substituted by one or two alkyl or phenyl groups;

phenyl, phenoxy, phenylthio, arylsulfinyl or sulfonyl,

X ₃ to X ₅ and Y may also form a bridge having 1 to 3 chain members and which may contain one or more of the following atoms or groups: carbon, oxygen, sulfur, nitrogen, C = O, C = S, SO, SO ₂ , CH = CH, and the carbon atoms of this bridge may be unsubstituted or substituted with at least one halogen atom and / or at least one hydroxy, alkoxy, alkylthio, mono or dialkylamino, alkylsulfinyl or - sulfonyl group and the alkyl moiety is defined as follows:

Z represents

- hydrogen, halogen, cyano, nitro or hydroxy, or

- alkyl, haloalkyl, hydroxyalkyl, formyloxyalkyl, alkyl or aryl (thio) carbonyl-oxyalkyl, alkoxy (thio) -carbonyloxyalkyl, amino (thio) -carbonyloxyalkyl -, mono- or dialkylamino (thio) carboxy-alkoxyalkyl, cycloalkyl or cycloalkylalkyl, and wherein the cycloalkyl moiety may be substituted by a GR4 group as defined below,

- alkoxy optionally substituted by hydroxy, alkoxy, alkylthio, alkylsulfinyl or sulfonyl,

- phenyloxy or phenylthio, phenylsulfinyl or sulfonyl,

- an amino group optionally substituted by one or two alkyl groups, · ·· · · * · *

- alkenyl or alkynyl, each of which contains from 3 to 7 carbon atoms and is optionally substituted,

- phenyl or a group of Seven optionally substituted,

- C (= Z ₁ ) Z ₂ , wherein

Z 1 is oxygen or sulfur or alkylamino, alkylimino or arylamino or arylimino, and

Z ₂ is hydrogen, halogen, hydroxy, mercapto, cyano or amino,

- alkyl, alkoxy, haloalkoxy, alkylthio,

- or alkenyl or alkynyl or alkenyloxy, each having from 3 to 7 carbon atoms,

- phenyl, phenylalkyl, phenoxy, phenylalkoxy,

- Seven or Het-alkyl,

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

- mono or dialkylamino, mono or diphenylamino or alkyl or arylsulfonylamino,

- phosphoryl substituted twice with alkyl, alkoxy, alkylthio, dialkylamino, cycloalkyl or cycloalkylalkyl, alkenyl or alkynyl, phenyl, phenylalkyl, Seven or Hetalkyl, wherein the substituents may also be optionally substituted;

- S (= Zi) (= Z ₃ ) Z ₂ where Z ₁ and Z ₂ are as defined above and Z ₃ is the same without necessarily being identical to Zagy and the tautomeric forms of formula (Ia) wherein Z is hydrogen or isomeric forms when Z is C (= Z ₁ ) Z ₂ or S (= Z ₁ ) (= Z ₃ ) Z ₂ ,

salts, metal complexes and N-oxides of the compounds, such as hydrochloric or perchloric acid, nitric acid, sulfuric acid, alkyl or optionally substituted phenylsulfonic acid, and in the above reports

- alkyl, alkoxy, alkenyl and alkynyl groups, and groups containing these, having up to 7 carbon atoms and optionally halogenated with from 1 to 8 halogens,

- the cycloalkyl groups have from 3 to 7 carbon atoms and are optionally substituted with at least one GR 4 group,

- phenyl groups optionally having from 1 to 5 halogens,

- substituted with C3 alkyl or alkoxy or nitro,

- Sev is a C 5 -C 10 monocyclic or bicyclic heterocyclic group, of which 1 to 4 heteroatoms, for example oxygen, sulfur, nitrogen or phosphorus;

- meaning of group GR4

- halogen, cyano, nitro, mono or dialkylamino,

alkyl, alkoxy, alkylsulfenyl, alkylsulfonyl, alkylcarbonyl, alkylthiocarbonyl, alkoxycarbonyl, alkoxythiocarbonyl, mono- or dialkylaminocarbonyl, or mono- or dialkylaminothiocarbonyl, mono- or dialkylaminosulfonyl (alkyl groups and groups containing 1 to 4 carbon atoms and optionally substituted with 1 to 9 halogens).

In formula I, Y is preferably chlorine or bromine.

• · ·········. · * • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ··· ··· ·· ·

- 7 - '

Other preferred derivatives are those wherein, in formula (I), Z is hydrogen or C (= Z ₁ ) Z _2> wherein Z _{1 is} oxygen or sulfur.

Other preferred derivatives are those wherein, in formula (I), X ₁ , X ₂ and X _{4 are} hydrogen or halogen, nitro or amino, or optionally C 1-4 halogenated alkyl.

Other preferred compounds of formula (I) in which X ₃ is hydrogen or fluorine.

Also preferred are those wherein Xt and / or X ₅ is hydrogen, and the preferred compounds are those compounds of formula (I), wherein two adjacent X _1t X _2, X _3, X ₄ or X ₅ 3 - form a chain 4-membered bridge, particularly optionally halogenated and preferably fluorinated methylene dioxide.

Of the aryl groups, phenyl is preferred.

Particularly preferred derivatives are those of formula (I)

a) X ₁ , X ₃ and X ₅ hydrogen atoms, X ₂ and X ₄ chlorine atoms,

(b) X _{4 is} nitro, X ₂ and X _{4 are} chlorine, X _{3 is} fluorine and X _{5 is} hydrogen;

c) Xi is fluoro, X ₂ and X ₄ Cl, X ₃ is fluoro, X ₃ and X ₅ are hydrogen.

Some of the derivatives are new, such as those represented by formula (I)

Y is chlorine and Z is hydrogen,

Xi is hydrogen or halogen or nitro, amino or methyl,

X _{2 is} halogen, nitro, amino or methyl,

X _{3 is} hydrogen or halogen,

X _{4 is} halogen or amino, nitro or methyl; ···· · · · · · · · · · · · · · · · · · · · · · · · · · ·

- 8 X ₅ hydrogen or halogen.

Preferred novel derivatives are those of formula (I)

Y, Z, X, and X ₄ are as defined above,

X _{2 is} chlorine or bromine,

X ₃ and X ₅ may be the same or different and are hydrogen or fluorine.

The derivatives of the present invention can be prepared in a known manner and are described in EP 0 538 156 and WO 93/22287.

The following examples illustrate the preparation of the novel derivatives, their physicochemical properties (structure confirmed by NMR analysis), their fungicidal properties in the treatment of tuberculosis, and their fungicidal properties in all derivatives and seed treatments of the present invention.

Example 1

benzoic acid

a) To a solution of 2,3-dichloro-5-nitrobenzoic acid, g, 0.57 mol of potassium nitrate in 100 g, 0.52 mol of 2,3-dichlorobenzoic acid, cooled to 0 ° C in 1000 ml of concentrated sulfuric acid . After 1 hour, the reaction mixture was poured onto ice (8 L), filtered through sintered glass and dried.

Yield: 63% Analysis.

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

Under argon, 10 g, 0.0265 moles of 3,5-dibromo-4-fluorobenzoic acid are dissolved in 200 ml of anhydrous tetrahydrofuran. 37 ml of 1.6M n-butyl lithium dissolved in hexane was added dropwise to -70 C C · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · -you. After stirring for 1 hour, 25.1 g (0.106 mol) of hexachloroethane dissolved in 20 ml of anhydrous tetrahydrofuran are added. After 2 hours at -70 ° C, the mixture was gradually raised to room temperature. The reaction mixture was hydrolyzed with water (50 mL) and extracted with ether. The aqueous phase was acidified by the addition of 1 N hydrochloric acid and extracted with ether. The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. The solid was recrystallized from a mixture of heptane and 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

60.8 g of sodium hydroxide pellet are dissolved in 500 ml of water, 26 ml of bromine are added while maintaining the reaction temperature below 10 ° C. 50 g of 0.169 mol of 3,5-dibromo-4-fluoroacetophenone dissolved in 50 ml of dioxane are added while maintaining the reaction temperature below 10 ° C. The temperature of the reaction mixture was raised to room temperature while controlling the exotherm so as not to exceed + 35 ° C. After stirring for 1.5 hours at room temperature, the aqueous phase was extracted with ether, acidified to pH 1 with 1N hydrochloric acid and re-extracted with ether. The organic phase is dried over magnesium stearate and concentrated in vacuo. The solid was triturated with heptane to give 47.5 g of 3,5-dibromo-4-fluorobenzoic acid. Yield: 74%.

Melting point: 201 'C.

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

Under Argon atmosphere, at -70 ° C, 57 ml of a 1.6 M solution of n-butyllithium in hexane was added dropwise to a solution of 10.4 g, 0.090 mol of TMEDA in 40 ml of anhydrous tetrahydrofuran. A solution of 3,5-dichloro-2,4,6-trifluorobenzene (15 g, 0.075 mol) in dry tetrahydrofuran (10 ml) was added dropwise at -70 ° C. After stirring at -70 ° C for 1 hour, the mixture was poured into solid carbon dioxide (100 mL) in dry tetrahydrofuran. The reaction mixture was stirred while the temperature was allowed to rise rapidly to room temperature, then hydrolysed with water and extracted with ether. The aqueous phase was acidified with 1N hydrochloric acid and extracted with ether. The organic phase was dried over magnesium sulfate and concentrated in vacuo. The solid was recrystallized from a mixture of heptane and ether.

Yield: 54%.

Melting point: 1 - 36 ° C.

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

A 1.6 M solution in n-butyl lithium hexane (90 mL) was added to a solution of diisopropylamine (14.3 g, 0.090 mol) in dry tetrahydrofuran (100 mL) at -50 ° C under argon. After half an hour, 20 g of 0.109 mol of 3,5-dichloro-2,4-difluorobenzene in 70 ml of anhydrous tetrahydrofuran were added dropwise at -50 ° C. The reaction mixture was stirred for 1 hour at -70 ° C and then poured into solid carbon dioxide in 100 ml of anhydrous tetrahydrofuran. The mixture returns to room temperature, then hydrolysed with water and extracted with ether. The aqueous phase was acidified with 1N hydrochloric acid and extracted with ether. The organic phase is dried over magnesium sulfate and evaporated in vacuo. The solid was recrystallized from a mixture of heptane and ether.

Yield: 37%.

Melting point: 177 ° C.

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) are dissolved in 50 ml of 1,2-dichloroethane. 5 drops of dimethylformamide are added and the mixture is stirred at room temperature for 1 hour. 24 g (0.18 mol) of aluminum chloride are added and the medium is heated to 60-70 ° C. A stream of chlorine was passed through the mixture for 5 hours while maintaining the temperature at 60-70 ° C and pouring into 100 ml of 1N hydrochloric acid. The precipitate was collected by filtration, washed with water, dried under reduced pressure to give 13 g of a cream solid.

Yield: 95.6%; ¹ H and ³ C NMR).

By the above procedure, the following acids are prepared from the appropriate reagents:

- 3-fluoro-5-bromobenzoic acid (78% yield, mp 144 ° C),

- 2-nitro-3-chloro-5-methylbenzoic acid (yield 83%, mp 226 ° C),

3-fluoro-5-methoxybenzoic acid (yield: 90%, m.p. 121 ° C).

Example 2

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

- 12 From the benzoic acids obtained above, acetophenones are obtained by the following procedure:

a) 2,3-Dibromo-5-methylbenzoyl chloride

2.1 g of 2,3-dibromo-5-methylbenzoic acid (0.00714 mol) in 20 ml

Dissolve in 1,2-dichloroethane and add 0.78 ml, 0.107 mol thionyl chloride, in 5 ml 1,2-dichloroethane. The mixture was stirred at 60 ° C for 5 hours, then concentrated in vacuo to give the product

2.3-dibromo-5-methylbenzoyl chloride is obtained in the form of an oil.

b) (2,3-Dibromo-5-methylphenyl) ethanone

A mixture of 0.87 g (0.0076 mol) of magnesium ethylate and 1.17 ml (0.0076 mol) of ethyl malonate was heated to reflux in 30 ml of ether for 3 hours. The above acid chloride (2 g, 0.0064 mol) was diluted with ether (5 ml) and added to this heterogeneous solution. The reaction mixture was stirred at reflux for 3 hours, cooled, dilute sulfuric acid (10 mL) was added and the mixture was extracted with ether and washed with water. After drying over magnesium sulfate, evaporation of the solvent, the resulting oil was directly decarboxylated: diluted with a mixture of 5 ml of acetic acid, 5 ml of water and 1 ml of concentrated sulfuric acid and heated to 70 ° C for about 2 hours. The reaction mixture was then extracted with ethyl acetate, neutralized with aqueous sodium hydroxide solution, dried over magnesium sulfate, and the solvent was evaporated to give (2,3-dibromo-5-methylphenyl) ethanone oil.

The following acetophenones (see table) are similarly obtained from the above appropriately substituted benzoic acids.

«» · «4 · · · · · · · · · · · · · · · · · · · · · · · · · · ·

- 13 compounds of formula (II)

X „Χ2» X3, Χ4 »X5 Yield (%) Melting point (° C) or analysis H, Br, F, Cl, H 50 analysis F, Cl, F, Cl, F 58 analysis F, Cl, F, Cl, H 63 48.5 Me, Cl, F, Cl, H 13 62 Cl, Cl, H, NO ₂ , H 87 analysis Me, NO ₂ , H, F, H 89 50 F ₃ C, Cl, Η, Η, H 42 NMR Cl, OCF ₃ , H, Br, H 61 NMR Cl, ocf ₃ , h, no ₂ , h 82 NMR Br, OCF ₃ , Η, NO _2i H 89 NMR F, Br, F, Cl, H 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, H, Me, H 70 130 H, F, H, OMe, H 68 66 H, Cl, H, Me, H 52 NMR

Preparation of (3,5-dichlorophenyl) ethanone from 3,5-dichloroaniline (see Example 4F of WO 93/2228)

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

14 of the solution was added dropwise to 28.5 g, 0.48 mole of acetaldoxime, 25.0 g, 0.10 mole of copper sulfate pentahydrate, 20.5 g, 0.018 mole of anhydrous sodium sulfite and 121 g, 1.50 mole. sodium acetate in 250 mL water kept at 15 ° C. After stirring for 1 hour, the mixture was acidified by the addition of concentrated hydrochloric acid. Steam distillation and column chromatography of the crude product on silica gel (90:10 heptane / ethyl acetate) gave 16.6 g (30%) of (3,5-dichlorophenyl) ethanone as a colorless liquid.

Using the above procedure, starting from 3-bromo-5-trifluoromethyl-aniline gives (3-bromo-5-trifluoromethyl-phenyl) -ethanone. (Yield: 35%; NMR).

4-acetyl-2,6-dichloroaniline:

814 g of 4-mole 4-acetyl-2,6-di-dinylamine, prepared according to DD 273 435, dated November 15, 1989, are 1200 ml concentrated hydrochloric acid and 5200 ml recrystallized from a mixture of concentrated acetic acid. After cooling to 0 ° C, 290 g (4.2 mol) of sodium nitrite in 770 ml of water are added to a gentle stream. After 2.5 hours, the solution was poured into 2200 ml of a 50% aqueous solution of hypophosphorous acid at 5 ° C. After the addition was complete, the temperature was allowed to rise to room temperature, water (10 L) was added and the aqueous phase was extracted with dichloromethane. After settling, the precipitated organic phase is dried, evaporated and the crude product is distilled off. 591 g (78%) of product are obtained which boils at 91-95 ° C at 1 mm Hg. The (3,5-dichlorophenyl) ethanone was obtained as a pale yellow liquid.

• · ···· ··· · · · · · · · · ·

The above procedure gives 89% (3-bromo-5-chlorophenyl) ethanone (NMR) from 4-acetyl-6-bromo-2-chloroaniline.

The above procedure gives 3,4,5-trichloroaniline (3,4,5-trichlorophenyl) -ethanone (yield: 20%, m.p. 75 ° C).

Example 3

2-Chloroacetophenones [Chloroacetophenone is prepared by Friedel-Crafts chloroacetylation of 2-chloro-1- (2-chloro-4-fluoro-5-methylphenyl) ethanone (see WO 93/22287 4I).

Monochloroacetyl chloride (14.1 g, 0.125 mol) was added dropwise to a suspension of anhydrous aluminum chloride (16.66 g, 0.125 ml) in anhydrous 1,2-dichloroethane (100 ml) kept in an ice-acetone bath at -5 ° C. 14.46 g (0.1 mol) of 4-chloro-2-fluorotoluene are added dropwise at the same temperature to the resulting solution. The reaction mixture was stirred at 5 ° C for 1 hour, allowed to stand overnight, and finally warmed to 60 ° C until gas evolution ceased. After cooling in an ice bath, 5 ml of concentrated hydrochloric acid dissolved in 100 ml of water are added dropwise. After settling, the organic phase was separated and washed successively with water (50 ml), saturated sodium bicarbonate solution (50 ml) and water (50 ml) and dried over anhydrous magnesium sulfate. After evaporation of the solvent, 22.3 g of 2-chloro-1- (2-chloro-4-fluoro-5-methylphenyl) ethanone are obtained in the form of a pale yellow oil which crystallizes on cooling (m.p. 32 '). C, 100% yield.

Similarly, 2-chloro-1- (3-methyl-4-fluoro-5-methylphenyl) ethanone (m.p. 86 ° C, 87% yield) (FG 993) and

16-2-Chloro-1- (2-fluoro-3,5-dichloro-4-fluoro-phenyl) -ethanone (NMR analysis, 75% yield).

Example 4

3,5-Dibromo-4-fluoro-acetophenone

133.5 g (1.0 mol) of aluminum chloride were added to 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 of 1,2-dichloroethane were added. The reaction mixture was heated to 55 ° C and 51 mL of bromine was added dropwise over about 1 hour. After stirring for 5 hours at 55 ° C, the reaction mixture was cooled to room temperature, poured into ice-cold slightly acidified water and extracted with dichloromethane. The organic layers were dried over magnesium sulfate and evaporated in vacuo. 6.7 g

3,5-dibromo-4-fluoroacetophenone is obtained in a yield of 23%, m.p.

Example 5

3-Methyl-4-fluoro-5-chloroacetophenone

Aluminum chloride (16.7 g, 0.123 mol) was added in 100 ml

1.2-dichloroethane, the mixture is cooled to + 10 ° C and 8.2 ml of acetyl chloride are added. After 10 hours at 10 ° C, 2-fluoro-3-chlorotoluene (15 g, 0.104 mol) was added to 10 ml.

1.2-Dissolved in dichloroethane. The reaction mixture was cooled to room temperature and then heated to 50 ° C for 3 hours. After cooling, the mixture was poured into 1N hydrochloric acid and extracted with dichloromethane. The organic layers were dried over magnesium sulfate and evaporated in vacuo. 11.6 g of 3-methyl-4-fluoro-5-chloroacetophenone are obtained.

• · • · · · · · · ·

- 17 Example 6

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

- (3,5-Dichlorophenyl) -3-dimethylamino-2-propen-1-one g, 0.053 mol of 3 ', 5'-dichloroacetophenone at room temperature and stirred in 50 ml of Ν, Ν-dimethylformamide dimethyl acetal. After stirring, the reaction mixture was heated at 90 ° C for 2 hours. The reaction mixture was evaporated to dryness under reduced pressure and the residue was taken up in 150 ml of heptane. The orange residue was filtered to give 1- (3,5-dichlorophenyl) -3-dimethylamino-2-propen-1-one (10 g, 77%), mp 100 ° C.

By a similar procedure, starting from the appropriately substituted acetophenone and using a suitable other reagent, the enaminone derivatives of formula (III) are obtained, see the following table. In formula (III), W is = N (CH ₃ ) ₂ .

Xi, x ₂ , X ₃ , X <, x ₅ Production (%) Mp (° C) or analysis H, Br, F, Cl, H 80 analysis H, Br, F, Br, H 82 143 H, 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

• ·· ·

Xi, X ₂ , X ₃ , x ₄ , X ₅ Production (%) Mp ('C) or analysis F, Me, F, Cl, H 40 RMN H, F, H, OMe, H 76 70

Example 7

Chloro enamines

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

2-Chloro-3 ', 5'-dimethyl-4'-fluoroacetophenone (6.0 g, 0.03 mol) in dimethylacetal dimethylformamide (7.15 g, 0.06 mol) in heptane (100 ml) The suspension prepared is heated to 50 ° C and stirred at this temperature for 8 hours. After cooling, the reaction mixture was filtered and the resulting crystals were washed with heptane and dried (3.2 g). The filtrate was partially evaporated to give additional crystals which were treated similarly (0.8 g). The two products were combined and chromatographed on silica gel eluting with 70% heptane / 30% ethyl acetate followed by 50% heptane / 50% ethyl acetate. 1.84 g of 2-chloro-3 ', 5'-dimethyl-4'-fluoroacetophenone and 1.55 g of 1- (3,5-dimethyl-4-fluorophenyl) -2-chloro-3-dimethyl Amino-2-propen-1-one is obtained in the form of white crystals, m.p. 177.5 DEG C. (yield: 20%).

By a similar procedure, the appropriately substituted acetophenone and another reagent (3,5-dichloro-2,4-difluorophenyl) -2-chloro-3-dimethylamino-2-propen-1-one were obtained (NMR analysis, 100%). production).

• · • · · ·

- 19 Example 8

1H-pyrazoles (see Example 7 of WO 93/22287)

3- (3,5-Dichlorophenyl) -1H-pyrazole

Hydrazine hydrate (2.4 g, 0.05 mol) was added slowly at room temperature with 9 g (0.0369 mol) of 1- (3,5-dichlorophenyl) -3-dimethylamino-2-propen-1-one in 100 ml of ethanol prepared solution. The mixture was stirred at room temperature for 2 hours, then evaporated to dryness and the residue triturated with heptane. 7.1 g (90%) of 3- (3,5-dichlorophenyl) -1H-pyrazole are obtained. Mp 156 ° C.

By a similar procedure, starting from the appropriately substituted enaminone, another pyrazole derivative of formula (Ia) is prepared according to the following table.

Compounds of formula (IA)

Xi, X ₂ , x ₃ , X4, X ₅ Production (%) Mp (° C) or analysis H, Br, F, Cl, H 77 261 H, Br, F, Br, H 86 201 H, Me, F, Cl, H 93 156 F, Cl, F, Cl, F 47 155 H, Cl, Cl, Cl, H 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 H, Cl, H, Me, H 80 analysis F, Br, F, Cl, H 88 161

• · ··· · · · ·

Xi, X2j X3> X <, X5 Production (%) Mp (° C) or analysis F, Cl, H, Cl, F 70 150 F, CF ₃ , H, Cl, H 12 NMR CF ₃ , Cl, Η, Η, H 97 NMR Cl, OCF ₃ , H, Br, H 82 NMR Cl, OCF ₃ , h, no ₂ , h 50 NMR Br, OCF ₃ , H, NO _2i H 66 NMR F, Η, H, Cl, H 75 NMR Cl, Η, H, CF ₃ , H 90 NMR H, F, H, Br, H 69 NMR NO ₂ , Cl, H, Me, H 82 175 H, F, H, OMe, H 38 83 3- (2-naphthyl) 87 162 3- (benzo [b] thien-4-yl) 60 147

Example 9

4-Chloro-pyrazoles

A) 3- (3,5-Dimethyl-4-fluorophenyl) -4-chloropyrazole (Compound 1)

While stirring at room temperature, a cold solution of 1.5 g of hydrazine hydrate in 30 ml of glacial acetic acid is added rapidly to 3.10 g of 0.0122 moles of 1- (3,5-dimethyl-4-fluorophenyl) -2-chloro-3-dimethyl -amino-2-propen-1-one in 20 ml glacial acetic acid. After stirring at room temperature for 7 hours, the reaction mixture was poured into 200 ml of water. The resulting solid was filtered, washed with water, dried in vacuo in the presence of phosphorus pentoxide, and purified by chromatography on silica gel, 70%.

Eluted with a mixture of 21 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 ° C. mining; 76%.

By a similar procedure starting from the appropriately substituted 1H-pyrazole and another reagent, 3- (3,5-difluoro-4-fluorophenyl) -4-chloropyrazole # 2 is obtained.

B) 4-Chloro-3- (3,5-dichlorophenyl) -1H-pyrazole (Compound 3) (Example 9A of WO 93/22287):

Halogenation of pyrazoles

3- (3,5-Dichlorophenyl) -1H-pyrazole (2.3 g, 0.0152 mol) was dissolved at room temperature and stirred in dichloromethane (300 ml). N-Chlorosuccinimide (2.07 g, 0.016 mol) was added and stirred for 4 days at room temperature. The reaction mixture was then evaporated and chromatographed on a silica column. The eluent was eluted with a 70:30 mixture of heptane and ethyl acetate. Yield: 1.4 g (57%), m.p. 192 ° C. 4-chloro-3- (3,5-dichlorophenyl) -1H-pyrazole was obtained.

In a similar manner, starting from the appropriately substituted 1H-pyrazole and another reagent, the 4-chloropyrazole derivatives of formula (IB) are obtained (see table below).

Compounds of formula (IB)

Compound number Xi »X2, X3, X4. X5 Y Yield: (%) Mp (° C) or analysis 4th H, Br, F, Cl, H cl 84 169

»· ··· · ··· · · · · · · · · · · · · · ···

Compound number Xi, ^ 2 »X3> Χ4» X5 Y Yield: (%) Mp (° C) or analysis 5th H, Br, F, Br, H cl 88 169 6th H, Me, F, Cl, H cl 69 174 7th F, Cl, F, Cl, F cl 79 143 8th H, Cl, Cl, Cl, H cl 61 208 9th F, Cl, F, Cl, H cl 30 158 10th Me, Cl, F, Cl, H cl 81 53 11th Cl, Cl, H, NO ₂ , H cl 70 172 12th Me, NO ₂ , H, F, H cl 55 126 13th H, Cl, H, Me, H cl 85 175 40th F, Br, F, Cl, H cl 92 167 41st CF ₃ , Cl, Η, Η, H cl 68 78 42nd Cl, F, H, OMe, H cl 75 156 43rd H, F, H, OMe, H cl 45 127 44th F, Me, F, Cl, H cl 20 119 45th Cl, OCF ₃ , H, Br, H cl 56 109 46th Cl, OCF ₃ , h, no ₂ , h cl 44 132 47th Br, OCF ₃ , H, no ₂ , h cl 86 150 48th H, F, H, Br, H cl 39 155 49th F, Η, H, Cl, H cl 19 116 50th Cl, Η, H, CF ₃ , H cl 71 110 51st F, Cl, H, Cl, F cl 75 152 52nd NO ₂ , Cl, H, Me, H cl 55 172

Compound number Xi, x ₂ , x ₃ , X ₄ , x ₅ Y Yield: (%) Mp (° C) or analysis 53rd 3- (2-naphthyl) cl 37 140

C) 4-Chloropyrazoles (see Example 12 of WO 93/22287)

a) Acetylation

4-Dimethylaminopyridine (0.25 g, 0.005 mol) and triethylamine (4.25 g, 0.042 mol) were added to 4-chloro-3- (2,2-difluoro-1,3-benzodioxole, 11 g, 0.046 mol). 4-yl) -1H-pyrazole in 100 ml of tetrahydrofuran (see French Patent Application No. 91/12647). A solution of acetyl chloride (3.6 g, 0.046 mol) in tetrahydrofuran (50 ml) was added dropwise to this solution at 0 ° C. After stirring for another 3 hours at room temperature, the reaction mixture was poured into water (300 ml) and extracted with ethyl acetate. The organic layer was dried, concentrated in vacuo, and the residue was triturated with heptane (50 mL), 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

6.3 g (0.063 mol) of potassium nitrate were added in small portions at 0 ° C to 12.89 g of 1-acetyl-4-chloro-3- (2,2-difluoro-1,3-benzodioxol-4-yl) - pyrazole in 21 ml of 96% sulfuric acid and 140 ml of dichloromethane. The reaction mixture was 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, washed with heptane and dried. 8.05 g of 4-chloro-3- (2,2-difluoro-5-nitro-1,3-benzodioxole-4 · * ·················································

24-yl) -pyrazole is obtained, m.p. 180 ° C in 63% yield (compound 15).

In a similar manner, the corresponding 4-chloropyrazole derivatives are obtained from the appropriately substituted 1H-pyrazole and another reagent (see table below).

Compound number X 1, X _2, X _3, X 4, xs Y Yield: (%) Mp ('C) or analysis 16th F, Cl, H, NO ₂ , H cl 74 147 17th F, Br, H, NO ₂ , H cl 34 154 18th NO _2i Cl, H, Cl H cl 55 173 54th F, NO ₂ , H, Cl, H cl 46 177 55th Cl, no ₂ , h, cf ₃ , H cl 22 128 56th NO ₂ , OMe, H, H F, 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 19)

A solution of 14.6 g (0.05 mol) of 3- (2-nitro-3,5-dichlorophenyl) -4-chloropyrazole in 200 ml of acetic acid (see Example 12b) was placed in a 500 ml three-necked round bottom flask. The solution was heated to 50 ° C and 8.4 g (0.15 mol) of iron powder was added in portions. After stirring for 5 hours at 70 ° C, the reaction mixture was cooled and poured into 800 ml of water, filtered through sintered glass, rinsed with water and dried. · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ···

25 are obtained in 90% yield, melting at 300 ° C with decomposition. The product was 3- (2-amino-3,5-dichlorophenyl) -4-chloropyrazole.

In a similar manner, the appropriately substituted 4-chloropyrazole affords the 4-chloropyrazole derivatives of formula (Ib).

Compounds of formula (IB)

Compound number Xi, X ₂ , X ₃ , x ₄ , x ₅ Y Yield: (%) Mp (° C) or analysis 20th NH ₂ , Cl, F, Cl, H cl 68 1600 21st NH ₂ , Br, H, Br, H cl 47 169 22nd Cl, Cl, H, NH ₂ , H cl 69 150 23rd F, Cl, H, NH ₂ , H cl 90 145 24th F, Br, H, NH ₂ , H cl 75 155 57th NH _2i Cl, H, Cl, F cl 85 150 58th NO ₂ , 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 25)

This compound was prepared by diazotizing 3- (2-amino-3,5-dichlorophenyl) -4-chloropyrazole and reacting with dimethyl disulfide as described in the literature. Yield: 30%; syrup.

Starting from the appropriately substituted diazonium salt and reacting with the appropriate reagent, the 3-phenyl-4-chloro- or -bromopyrazoles of formula (IB) are obtained, see the following table.

- compounds of formula (IB)

Compound number Xi, X ₂ , x ₃ , X4, x ₅ Y Yield: (%) Mp (° C) or analysis 26th F *, Cl, H, Cl, H cl 75 180 27th F *. Cl, H, Br, H cl 74 175 28th F *, Br, H, Br, H cl 70 170 29th F *, Br, H, Cl, H cl 63 176 59th F, Br, H, Cl *, H cl 64 176 60th F, Me, H, Cl *, H cl 57 136

Example 12

3- (2-Nitrophenyl) -4-chloro-pyrazoles

3- (2-Nitro-3,5-dichloro-4-fluorophenyl) -4-chloropyrazole (Example 30)

compound)

0.43 ml (0.0104 mol) of 100% fuming nitric acid was added dropwise in an ice bath to cool 2.50 g (0.00943 mol) of 3- (3,5-dichloro-4-fluorophenyl). 4-chloropyrazole (see, for example, compound 266 in WO 93/22287) in 25 ml of 100% sulfuric acid. The reaction mixture was stirred under cold conditions for 20 minutes, then stirred at room temperature for 1 hour and finally poured onto 150 g of ice. The resulting precipitate was extracted with 150 ml of ethyl acetate. The resulting solution was washed with water (100 ml), saturated sodium bicarbonate solution (100 ml) and water (100 ml), dried over magnesium sulfate and concentrated in vacuo. 2.78 g of 3- (2-nitro-3,5-dichloro-4-fluorophenyl) -4 · · • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ···., ···

27-chloropyrazole was obtained as a white solid, m.p. 196.4 ° C (95% yield).

By a similar procedure, the appropriately substituted 4-chloropyrazole gives the (IB) 3- (2-nitrophenyl) -4-chloropyrazole derivatives, which are shown in the following table.

Compounds of formula (IB)

Compound number X 1, X 2, X 3, X 4> X 5 Y Yield: (%) Mp (° C) or analysis 31st NO ₂ , Br, H, Br, H cl 25 196 32nd NO ₂ , Br, F, Br, H cl 73 221 33rd NO ₂ , Me, F, Cl, H cl 19 214 34th NO ₂ , Cl, F, Me, H cl 20 205 61st NO ₂ , Me, H, Br, H cl 13 184

Example 13

3- (5-Fluorophenyl) -4-chloropyrazole

3- (2,3-Dichloro-5-fluorophenyl) -4-chloropyrazole (Compound 35)

The diazonium tetrafluoroborate of 3- (5-amino-2,3-dichlorophenyl) -4-chloropyrazole is obtained by dropwise addition of 0.002 mole of aqueous solution of sodium nitrite (0.0021 mole) at 0 ° C. - (5-Amino-2,3-dichlorophenyl) -4-chloropyrazole in 5% aqueous solution of tetrafluoroboric acid. The reaction mixture was stirred at 0 ° C for 1 hour and then poured into water (50 ml) and ice. The resulting precipitate was rapidly evaporated in vacuo.

- dried to 28 ° C and thermally decomposed at 145 ° C in the dry state. After cooling, the reaction mixture was taken up in dichloromethane, purified by chromatography on silica gel, eluting with 25:75 ethyl acetate: heptane. Yield: 19%, m.p. 122 'C.

In a similar manner starting from the appropriately substituted 4-chloropyrazole, 3- (3-chloro-2,5-difluorophenyl) -4-chloropyrazole 36 is obtained. Yield: 17%, m.p. 150 'C.

Example 14

3- (3-Chloro-5-hydroxyphenyl) -4-chloropyrazole (Reference Derivative)

In a 1000 ml three-necked round-bottomed flask according to WO 93/22287. 49.5 g (2 mol) of 4-chloro-3- (3,5-dichlorophenyl) -pyrazolo 11 (Example 9) are added to 500 ml of N-methylpyrrolidone. Sodium methylate (43.2 g, 0.8 mol) was added and the mixture heated at 140 ° C for 50 hours. After cooling, the reaction mixture was poured into water (500 mL), acidified and extracted with ethyl acetate. The organic phase was dried, concentrated in vacuo and purified by column chromatography on silica gel. The eluent was eluted with a 60:40 mixture of heptane and ethyl acetate. 28 g (0.12 mol, 61%) of 4-chloro-3- (3-chloro-5-hydroxyphenyl) pyrazole, m.p. 222 DEG C., are obtained.

Example 15

3- (3-Chloro-5-fluorophenyl) -4-chloropyrazole (Compound 37)

In a 500 ml three-necked flask at 0 'C, WO 93/22287. 4-Chloro-3- (3-amino-5-chloro-phenyl) -pyrazole (150 ml, 1.20 mol, 50%) was added. · * · · · ·········

- 29 for aqueous fluoroboric acid. Sodium nitrite (5.7 g, 0.826 mol) was dissolved in water (10 mL) dropwise while maintaining the temperature at 0-5 ° C. After stirring for another hour at room temperature, the resulting solid was filtered through a sintered glass filter, washed with water and then with pentane. The dry material decomposes at 150 ° C to give a brown oil which is taken up in isopropanol when heated. Chromatography on a silica gel column using heptane / ethyl acetate (70:30) as eluent. Yield: 4.9 g (0.0342 mol) of 4-chloro-3- (3-chloro-5-fluorophenyl) pyrazole (45.6%), m.p. 150 ° C.

Example 16

N-substituted pyrazoles (according to Example 19D of WO 93/22287)

-Acetoxymethyl-4-chloro-3- (3,5-dichlorophenyl) -pyrazole (# 38).

compound)

0.15 ml of 1,8-diazabicyclo [5.4.0] undecen-7-ene are added at room temperature with 2.55 g, 0.01 mol of 4-chloro-3- (3,5-dichlorophenyl) -pyrazole and 0 Paraformaldehyde (90 g, 0.030 mol) in tetrahydrofuran (70 ml). The reaction mixture was stirred at room temperature for 4 hours, added dropwise at 0 ° C with 1.20 g (0.015 mol) of acetyl chloride in 10 ml of tetrahydrofuran and stirred for 6 hours at room temperature. The reaction mixture was evaporated to dryness and the residue was taken up in heptane (15 mL) and dried. 3.05 g of 1-acetoxymethyl-4-chloro-3- (3,5-dichlorophenyl) pyrazole are obtained, m.p. 95 ° C.

Starting from a similar procedure substituted 1 Η-4-chloropyrazole, the following derivatives of formula (I) are obtained.

• ·· · ····· · · ·

30 compounds of formula (I)

Compound number Xi, X ₂ , x ₃ , X4, x ₅ Y z Yield: (%) Mp (° C) obsession analysis 39th NO ₂ , Cl, F, Cl, H cl CH2OAC 97 100 40th F, Cl, H, Cl, H cl CH ₂ OAc 95 90

Example 17

4-Chloro-3- (5-chloro-3-cyano-2-fluoro-phenyl) -pyrazole (Compound 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) in dimethylformamide (10 ml) and the mixture was heated at 180 ° C for 8 hours. After cooling to room temperature, it was poured into 50 ml of 14% ammonium hydroxide solution, extracted with 2 x 50 ml of ethyl acetate, dried over magnesium sulfate and concentrated in vacuo. The oily residue was purified on anhydrous silica column. Elution with 30% ethyl acetate in heptane gave 0.1 g of a yellow solid (mp 128 ° C, 28%).

Example 18

4-Chloro-1- (4-methylphenylsulfonyl) -pyrazole (Compound 63) g, 0.5 mol of pyrazole is dissolved in 350 ml of dichloromethane at 10 ° C and 77.6 g, 0.575 are added dropwise. moles of sulfuryl chloride in 150 ml of dichloromethane. After dosing is complete, the

The mixture was heated under reflux for 18 hours, dichloromethane was removed in vacuo, the residue was suspended in pyridine (200 mL) and para-toluenesulfonyl chloride (95.33 g, 0.5 mol) was added portionwise. This mixture was heated to reflux, allowed to cool to room temperature, cooled in an ice bath, and water (800 mL) was added with vigorous stirring. After 1 hour a solid formed which was filtered, washed with water, recrystallized from ethanol to give 102 g of 4-chloro-1- (4-methylphenylsulfonyl) pyrazole as a white powder in 80% yield. Melting point: 96-97 ° C.

Example 19

4-Chloro-5- (3-fluoro-phenyl) -1- (4-methyl-phenylsulfonyl) -pyrazole (Compound 64)

4-Chloro-1- (methylphenylsulfonyl) -pyrazole (2.4 g, 0.0093 mol) was dissolved in tetrahydrofuran (20 mL) and cooled to -78 ° C under argon. 3.92 ml (0.0098 mol) of a 2.5 molar solution of n-butyllithium are added dropwise over 10 minutes, and the mixture is stirred at -78 ° C for 1.25 hours. Zinc chloride (10 mL, 0.01 mol) in tetrahydrofuran was added dropwise over 10 minutes and the mixture was stirred at -78 ° C for half an hour and then at room temperature for 2 hours. Then 0.35 g (0.0003 mol) of tetrakis (triphenylphosphine) palladium (Pd (PPh ₃ ) ₄ ) are added, followed by 1.4 g (0.0062 mol) of 3-fluoroiodobenzene in 15 ml of tetrahydrofuran. The mixture was heated at reflux for 18 hours, allowed to cool to room temperature, diluted with 50 mL of EDTA solution and extracted with ether (3.times.50 mL), the organic extract was washed with water, dried over magnesium sulfate, filtered, and concentrated to a Purified on anhydrous silica column • ·· · ····

32 µl, eluting with 10% ethyl acetate in heptane, 1.05 g of 4-chloro-5- (3-fluorophenyl) -1- (4-methylphenyl) sulfonitrile. m.p. 110-111 ° C.

The above procedure provides 4-chloro-1- (methylphenylsulfonyl) pyrazole and the appropriate reagent to give the following compounds of formula IV.

Compounds of formula IV

Compound number R Yield: (%) Mp (° C) 65th benzo [b] thien-4-yl 56 133 66th 2-carbomethoxy benzo [b] thien-4-yl 69 170 67th benzo [b] furan-4-yl 67 102

The appropriate intermediates are obtained by the following procedures:

a) 2-Carbomethoxy-4-iodo-benzo [b] thiophene

2-Fluoro-6-iodobenzaldehyde (30.0 g, 0.012 mol) was dissolved in anhydrous dimethyl sulfoxide (150 mL) at room temperature under argon. 14.05 g (0.0119 mole) of methylthioglycolate was added dropwise over 1 minute followed by 25.85 g (0.255 mole) of triethylamine. The mixture was heated at 60 ° C for 2 hours, cooled to room temperature and poured into 1,000 ml of water / ice with stirring. The yellow precipitate was collected by filtration, air-dried, slurried in 300 ml of methanol and refluxed for 10 minutes. The solution was cooled to 0 ° C and then a

- 33 ·· ········· »· · · · · * ···· ···

: .. · .. · ... ·:. The precipitate was filtered off and dried in vacuo to give 30.2 g of 2-carbomethoxy-4-iodobenzo [b] thiophene as a cream colored solid in 79% yield. Melting point: 123-124 ° C.

b) 2-Carbomethoxy-4-iodo-benzo [b] furan

Sodium hydride (4.36 g, 0.0109 mol, 60% in oil) was suspended in tetrahydrofuran (100 ml) under argon. The reaction mixture was cooled to 5-10 ° C and a solution of methylthioglycolate (10.3 g, 0.115 mol) in tetrahydrofuran (50 ml) was added dropwise over 30 minutes on an ice-cold water bath. After stirring at this temperature for 5 minutes, 2-fluoro-6-iodobenzaldehyde (21 g, 0.084 mol) dissolved in tetrahydrofuran (50 ml) was added dropwise over 30 minutes. The temperature of the reaction mixture spontaneously rises to 40 ° C. After stirring for another 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 was washed with water, triturated with methanol in the cold state, and dried under reduced pressure. 14.3 g of a white solid are obtained in 45% yield. Melting point: 141-143 ° C.

c) 2-Carboxy-4-iodo-benzo [b] thiophene

A solution of 5.8 ml of 10 M aqueous sodium hydroxide was added to a mixture of 17.0 g of 0.053 mol of 2-carbomethoxy-4-iodobenzo [b] thiophene in 150 ml of ethanol. The mixture was heated under reflux for 1 hour and then evaporated to dryness under reduced pressure. The residue was dissolved in water (300 mL) and washed with ethyl acetate (100 mL). The aqueous phase was acidified to pH 1 with 36% hydrochloric acid. The precipitate was filtered off, washed with water, washed also with diisopropyl ether and then dried under reduced pressure at 70 ° C to give 15 g.

34 white solid melting at 260 ° C are obtained. Yield: 93%.

d) 4-Iodobenzo [b] thiophene

4.3 g of barium-contaminated copper chromite are suspended in 70 ml of quinoline and the mixture is heated to 200 ° C. 2-Carboxy-4-iodo-benzo [b] thiophene (13.0 g, 0.043 mol) was added in portions. After about 15 minutes after the evolution of gas had ceased, the reaction mixture was cooled to room temperature and poured into 100 ml of 36% HCl in ice and filtered through Celite. The Celite was rinsed with 200 mL water and 100 mL ethyl acetate. The filtrate was re-extracted with ethyl acetate (2 x 150 mL), washed with water (400 mL), dried over magnesium sulfate. Concentration under reduced pressure gave 11.65 g of a brown oil. Purification on a silica column eluting with pure heptane gave 9.6 g of a yellow solid in 86% yield. Melting point: 37-39 'C.

Example 20

4-Chloro-3- (benzo [b] thien-4-yl) -pyrazole (Compound 68)

5- (Benzo [b] thien-4-yl) -4-chloro-1- (4-methylphenylsulfonyl) -pyrazole (3.3 g, 0.00844 mol) was dissolved in dimethylformamide (25 mL) and stirred for 18 hours. length is heated to 110 ° C. After cooling to room temperature and pouring into ice with stirring, an oily product was obtained which was extracted with ethyl acetate (2 x 50 ml), washed with water (3 x 100 ml) and dried. Elution with anhydrous silica column eluting with 20% ethyl acetate in heptane gave 1.4 g of a yellow solid after grinding in 70% yield, mp 123'C.

·· «· ····

• · • · · ·

The above procedure yields 4-chloro-3- (benzo [b] furan-4-yl) -pyrazole from the appropriate reagent in 64% yield. 122 DEG C. (Compound 69).

Example 21

4-Chloro-3- (5-chloro-2-fluoro-3-phenyl-thiophenyl) -pyrazole (Compound 70)

3- (3-Bromo-5-chloro-2-fluoro-phenyl) -pyrazole (1.100 g, 0.035 mol) was dissolved in tetrahydrofuran (20 ml) and cooled to -78 ° C under argon. 5.5 ml of 1.6 molar n-butyllithium (0.088 mol) was added dropwise over 10 minutes and the mixture was stirred at -78 ° C for half an hour. Subsequently, 1.53 g of diphenyl disulphide (0 ^ 007 mole) was dissolved in 10 ml of tetrahydrofuran in a tile and stirred at -78 ° C for 1 hour and then at room temperature the following day. Water (100 ml) was added and the mixture was extracted with ethyl acetate (2 x 50 ml), dried over magnesium sulfate and evaporated in vacuo to give an oily residue. This was purified on a silica column eluting with 30% ethyl acetate in heptane to give 0.45 g of 4-chloro-3- (5-chloro-2-fluoro-3-phenyl-thiophenyl) -pyrazole in 38% yield. ¹ H and ¹³ C NMR).

The above procedure, starting from 4-chloro-3- (3-bromo-5-chloro-2-fluorophenyl) pyrazole and the appropriate reagent, provides compounds of formula (I). See the table below, where introduced substituents are denoted by *.

- 36 compounds of formula (I)

Compound number Xi »X _2> X ₃ , Xo Xs Y Yield: (%) Mp (° C) or analysis 71st F, CO ₂ H ', H, Cl, H cl 37 184 72nd F, CHO *, H, Cl, H cl 26 NMR 73rd F, CO ₂ Et *. H, Cl, H cl 51 100

Example 22

Metal complex of 4-chloro-3- (3 _J, 5-dichlorophenyl) pyrazole and copper chloride (Compound 74)

Copper chloride dihydrate (1.70 g, 0.071 mol) was dissolved in anhydrous ethanol (10 ml) and triethyl ortho formic acid (1 ml) was added. The mixture was stirred for half an hour at room temperature and 4.95 g (0.02 mol) of 4-chloro-3- (3,5-di-dichlorophenyl) pyrazole (11) was dissolved in 10 ml of anhydrous ethanol. added. This mixture was stirred at room temperature for half an hour until the following 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 in quantitative yield. Melting point: 288 DEG C. (with decomposition).

Starting from the corresponding pyrazole and metal salt, the above procedure gives the compounds of formula I - L 'M ⁺ - I in quantitative yield, as shown in the table below.

- 37 - • · • · • ··· ·· . ··· · · · * · · · · · · ··· ·· · The compound Xi, X ₂ , X ₃ , X ₄ , M ⁺ L ' Color Mp number x ₅ (° C) 75th H, Cl, H, Cl, H Cu Br greenish 264 (decomposes) 76th H, Cl, H, Cl, H Cu from ₃ 190 (decomposes) 77th H, Cl, H, Cl, H Zn cl white 195 (decomposes) 78th H, Cl, H, Cl, H Zn AcO white > 300 79th H, Cl, H, Cl, H Ni cl cream- > 300 coloured 80th NO _2l Cl, F, cl Cu cl blue 255 (decomposes) H 81st F, Cl, H, Cl, H Cu cl green 287 (decomposes) Further Of formula (I) Compounds which a

European Patent Application 538,156, also examined:

Compound 82: 4-Chloro-3- (2 ', 2'-difluoro-1', 3'-benzodioxolyl) -pyrazole (Compound 25 of European Patent Application 0 538 156)

Compound 83: 4-Chloro-3- (2,3-dichlorophenyl) pyrazole (a

European Patent Application Serial No. 12, No. 538,156; compound)

Compound 84: 4-Chloro-3- (2-nitro-3-chlorophenyl) pyrazole (a)

European Patent Application Serial No. 120, No. 538,156; compound)

The present invention also relates to the treatment of fungal diseases of crop plants, which comprises applying an effective amount of a compound of formula I, a salt, a metal complex or an N-oxide thereof to the propagation material of these plants. An effective dose is an amount sufficient to effect

- Kill or control fungi on 38 vine plants. The doses used can vary within wide limits, depending on the type of crop, the climatic conditions and the compound used.

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

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

The compounds of the present invention are useful in the fungicidal treatment of rice, cereals, especially wheat and barley, and vegetables. Preferably, the compound of the present invention is a rice fungicide.

Example 23

In vivo testing of seed disinfection

Two protocols are used, depending on whether they are naturally infected seeds (Drechslera graminea / Drechslera teres barley) or artificially infected seeds (Cochliobolus sativus / Fusarium culmorum / Fusarium nivale / Septoria nodorum).

g seed is treated with the active compounds of the invention in the form of an aqueous suspension concentrate at a concentration of 1.5 liters / 100 kg in a HEGE pan. In 7x7x8 cm pots, 30 seeds are sown in pots containing peat / tuff mixture and 3 pots are prepared per treatment. A contaminated untreated control and an unpolluted control in the case of artificial impurities

- We sow between 39. In the case of artificial contamination, the treated healthy seeds are discarded and a spore suspension is applied per pot to 10 ml of aqueous suspension base. The concentration of suspension varies according to the pathogen tested as follows:

pathogen utility Plant Number of spores Cochliobolus sativus barley 200,000 Fusarium culmorum / wheat, barley 400,000 Fusarium nivale Septoria nodorum wheat 250,000

The pots were placed in a controlled ambient cabinet at 5 ° C and kept at saturated relative humidity for a period depending on the assay performed, i.e. for 3 weeks for Drechslera graminea / Drechslera teres and Cochliobolus sativus and 2 weeks for Fusarium culmorum / Fusarium nivale / Septoria nodorum.

The pots are then transferred to a controlled ambient cabinet at 10 ° C (photoperiod: 8 hours and 16 hours at night) at 80% relative humidity until symptoms develop.

Evaluation is performed visually against contaminated untreated control.

Under these conditions, a good protective effect is observed at a dose of at least 75% or 100 g / q:

- Drechslera gramineane: with the following derivatives: 3, 4,

5, 7, 10, 18, 26, 30, 68, 69;

Drechslera tereres: with the following derivatives: 3, 26, 30, 82, 893, 84;

- Cochliobolus sativuson: with the following derivatives: 3, 26, 30;

- Fusarium culmorumon: with the following derivatives: 3, 26, 30, 82, 83, 84;

Fusarium nivalen: with the following derivatives: 1, 3, 4, 7, 8, 9, 12, 20, 26, 27, 28, 30, 37, 82, 83, 84;

- Septoria nodorumon: with the following derivatives: 3, 26, 30, 82, 83, 84.

The present invention also encompasses the treatment of crop plants suffering from or exposed to a fungal disease by applying an effective dose of a novel compound of formula I to the above-ground parts of these plants. An effective dose is an amount sufficient to kill or control the fungi present in the crop plants. Dosages may vary within wide limits, depending on the fungus, the crop, the climatic conditions and the compound used.

In practice, the compounds are preferably applied at a dose of 0.002 to 5 kg / ha, preferably 0.005 to 1 kg / ha.

Example 24

In vivo test on tomato leaf exposed to Botrytis cinere (susceptible strains and strains resistant to benzimidazoles):

An aqueous suspension of the test compound is prepared by finely grinding:

- active ingredient: 60 mg »· ♦ · · - - • 9 · · ·

- 41 - Tween 80 surfactant (polyoxyethylated sorbitan derivative oleate) diluted 10% in water: 0.3 ml

make up to 60 ml with water.

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

A 30-day tomato of the Marmande variety is grown in a greenhouse and sprayed with various concentrations of the test compound in aqueous suspensions as defined above. At the end of the 24th hour, the leaves were cut off and placed in a 14 cm diameter petri dish, the bottom of which was lined with wet filter paper (10 leaves per dish).

The vaccine is then administered using a syringe. Three drops of Botrytis cinerea spore suspension, benzimidazole-sensitive or benzimidazole-resistant, obtained from a 15-day culture are placed on each leaf and resuspended in 150,000 units / cm ³ . Six days after contamination, it is monitored and compared to untreated control.

Under these conditions, a good effect or total protection of at least 75% is observed at a dose of 1 g / l for the following compounds: 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 benzimidazole-sensitive Botrytisen.

Example 25

In-vehicle test with Pyricularia oryzae, responsible for the pyriculariosis of rice

The composition of the aqueous suspension of the test compound is as follows:

- 42 to 60 mg of active ingredient,

- Tween 80 surfactant (ploxyethylene sorbitan oleate) diluted to 10% with water: 0.3 ml

- make up to 60 ml with water.

The mixture is finely ground and the aqueous suspension diluted with water to give the desired concentration of the active ingredient.

The rice is sown in pots containing a 50:50 mixture of peat and tuff and treated at a height of 10 cm by spraying the aqueous suspension.

At the end of 24 hours, an aqueous suspension of Pyricularia orazye spores, obtained from a 15-day culture, was suspended in 100,000 units to 1 cm ³ and applied to the leaves.

The rice seedlings were placed in an incubator at 25 ° C and 100% relative humidity for 24 hours and then placed in an observation cell for 5 days under the same conditions.

The scan is performed 6 days after infection. Under these conditions, at least 75% good efficacy or total protection is observed at a dose of 1 g / l for the following compounds: 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 on Plasmospara viticola

An aqueous suspension of the test compound of the following composition is prepared by fine grinding:

- active ingredient: 60 mg

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

make up to 60 ml with water.

· · · · · · · · · · · · · · · · · · · · ···

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

Chardonnay grape cuttings (Vitis vinifera) are grown in pots. When the pots are 2 months old (8-10 leaf height, 10-15 cm height), the plants are sprayed with the above aqueous suspension.

Control plants were treated with an aqueous solution of the active ingredient. 24 hours after drying, each plant is inoculated by spraying with an aqueous suspension of Plasmospara viticola spores obtained from a 7-day culture and resuspending at 100,000 units / cm ³ .

The infected plants are then incubated for 2 days in a humidified atmosphere and then for 5 days at 20-22 ° C and 90-100% relative humidity.

Readings are performed 7 days after infection compared to control plants.

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

Example 27

In-Carrier Test on Puccinia recondita (Wheat Rust)

An aqueous suspension of the test compound of the following composition is prepared by fine grinding:

- active ingredient: 60mg · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

- 44 - Tween 80 surfactant (polyoxyethylene sorbitan derivative oleate) diluted with water 10%: 0.3 ml

make up to 60 ml with water to give a suspension / solution of 1 g / l.

This aqueous suspension is optionally diluted with water to give the desired concentration of active ingredient.

Wheat was planted in pots at a ratio of 50-50 and sprayed at a height of 10 cm with the above suspension.

The control plants were treated with an aqueous solution containing no active ingredient as a control.

After 24 hours, 100,000 spores / cm ^{3 of} spore suspension were sprayed onto the wheat and this suspension was obtained from the infected plants. The wheat is then placed in an incubation cell for 24 hours at 20 ° C and 100% relative humidity and then for 7-14 days at 60% relative humidity. The condition of the plants was observed between 8 and 15 days post-infection by comparison with untreated control.

Under these conditions, a good protective effect of at least 75% or full at a dose of 1 g / liter is observed for the following compounds: 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 invention also relates to compositions which can be used as fungicides and which contain as active ingredient one or more of the compounds of the formula I described above in admixture with solid or liquid carriers which are agriculturally acceptable and surfactants which are also agriculturally acceptable.

Standard inert carriers and surfactants are particularly useful.

These compositions may also contain other active ingredients such as protective colloid, adhesive, thickener, thixotropic agent, penetrating agent, stabilizing agent, sequestering agent, and the like. More generally, the compositions of the invention may be admixed with any solid or liquid excipient which conforms to conventional formulation techniques.

In general, the compositions of the invention will contain from 0.05% to 95% by weight of the compound of the invention, i.e., the active ingredient, together with one or more solid or liquid carriers and optionally one or more surfactants.

The term carrier, as used herein, refers to a natural or synthetic, organic or inorganic material that can be mixed with a compound to facilitate application to soil, plants or seeds. Since this carrier is generally inert, it should be agriculturally acceptable, especially on the crop to be treated. The carrier can be solid (clay, natural or synthetic silicates, silica, resin, wax, solid manure, etc.) or liquid (water, alcohols, especially butanol, etc.).

The surfactant may be an emulsifying, dispersing or wetting agent, of the ionic or nonionic type, or a mixture of these surfactants. It may also be mentioned that polyacrylic acid salts, lignin sulfonic acid salts, phenolsulfonic or naphthalenesulfonic acid salts, polycondensates of ethylene oxide and fatty alcohols or fatty acids or fatty amines, substituted phenols, in particular alkylphenols or esters of aryls, «· # ········ * ·•••••••••••••••••••••••••••••

46 taurine derivatives, in particular alkyl taurates, polyoxyethylated phosphorus esters of alcohols or phenols, esters of fatty acids and polyols, and sulfates, sulfonates and phosphates of the above compounds. Generally, it is essential that at least one surfactant is present when the substance and / or the inert carrier are insoluble in water and if the solvent is water when used.

The agricultural compositions of the invention may thus contain the active compounds of the invention within a broad range of 0.05 to 95% by weight. The surfactant content is preferably between 5 and 40% by weight.

The compositions of the present invention may be prepared in a solid or liquid form which is sufficiently variable.

Solid forms according to the invention include dusting powders (up to 100% active ingredient), granules, in particular those obtained by extrusion, compression, impregnation of a granular carrier or granulation from a powder (content of these granules is 0.5%). 80%) and the tablets may be effervescent.

The compounds of formula (I) may also be used in the form of dusts; a composition comprising 50 grams of active ingredient and 950 grams of talc, or 20 grams of active ingredient, 10 grams of finely divided silica and 970 grams of talc; the components are mixed, ground and the mixture is powdered.

Liquid forms or formulations which are intended to be converted into liquid preparations by application may include solutions, in particular water-soluble concentrates.

47 concentrates, emulsifiable concentrates, emulsions, suspension concentrates, aerosols, wettable powders or spray powders, pastes and gels.

Emulsifiable and soluble concentrates usually contain from 10 to 80% by weight of the active ingredient, and emulsions or ready-to-use solutions contain from 0.001 to 20% by weight of the active ingredient.

In addition to the solvent, the emulsifiable concentrate may contain from 2% to 20%, if necessary, of a stabilizer, a surfactant, a penetrating agent, an anticorrosive agent, a dye and an adhesive.

An emulsion of any concentration can be obtained from these concentrates by dilution with water and is particularly suitable for use in crop plants.

By way of example, the following are some emulsifiable concentrate formulations:

Example EC1

- active ingredient 400 g / 1 - alkali metal dodecyl benzenesulfonate 24 g / L - oxyethylated nonylphenol which is 10 16 g / L molecule contains ethylene oxide - cyclohexanone 200 g / L - aromatic solvent optionally Up to 1 liter

Alternatively, the following emulsifiable concentrate may be prepared:

• · ·

- 48 EC2. example

- active ingredient

- epoxidized vegetable oil

- alkylaryl sulphonate and a mixture of polyglycol ether and fatty alcohols - dimethylformamide

- xylene

250g / 1 25g

100 g g 575 g

The suspension concentrates may also be applied by spraying. It is prepared by obtaining a stable fluid product which does not precipitate and is usually 10 to 75% active ingredient, 0.5 to 15% surfactant, 0.1 to 10% thixotropic agent, 0 to 10% suitable additive such as antifoam. , corrosion inhibitor, stabilizer, penetrating agent, adhesive, and the carrier may be water or an organic liquid in which the active ingredient is only partially soluble or insoluble, and solid organic substances or inorganic salts which may be dissolved in the carrier to prevent sedimentation or water antifreeze In the case.

For example, a suspension concentrate having the following composition may be prepared:

SC1. example

- active ingredient 500 g

- polyethoxylated tristyryl phenol phosphate 50 g

- polyethoxylated alkyl phenol 50 g

poly (sodium carboxylate) 20 g

- ethylene glycol 50 g

- Organopolysiloxane oil (antifoam)

- polysaccharide g 1.5 g ·· ········· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

- 49 - water 316.5 g

Wettable powders or spray powders are usually formulated to contain from 20% to 95% of the active ingredient, and usually contain from 0% to 30% of a wetting agent, from 3 to 20% of a dispersant and from 0.1 to 10% of one or more of the solid carrier. a number of stabilizers and / or other additives such as penetrating agents, adhesives or anti-caking agents, dyes, etc.

To form sprays or wettable powders, the active ingredient is thoroughly mixed in a suitable mixer with the other materials, milled in a mill or suitable milling equipment. The powders thus obtained have a wettability and suspendability, and can be suspended in water at the desired concentration, and these suspensions are preferably applied especially to the leaves of the plants.

Pulp may be used instead of wettable powders. The conditions and processes for producing these pastes are similar to those for wettable powders or spray powders.

Wettable powders or spray powders may be prepared as follows:

Example 1 WP

- active ingredient 50%

- ethoxylated fatty alcohol (wetting agent) 2.5%

- ethoxylated phenylmethylphenyl 5% (dispersant)

- chalk 42.5% • ·

- 50. Example 2 of WP

- active ingredient

- ethoxylated with 8-10 ethylene oxide units synthetic type branched C ₃ oxo alcohol (wetting agent)

- Neutral calcium lignosulfonate (dispersant)

- calcium carbonate (inert filler)% 0,75%

qs 100%

Example 3 of WP

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

- active ingredient

- wetting agent

dispersant

- inert filler

Example 4 WP

- active ingredient

- wetting agent

- dispersant% 1,50% 8%

qs 100%

%%

Example 5 WP

- active ingredient 50%

- Mixture of anionic and nonionic surfactant 2.5% (wetting agent)

- Sodium lignin sulphonate (dispersant)%

- 51 - kaolin clay (inert support) 42.5%

Aqueous dispersions and emulsions are prepared by diluting them with water-wettable powders or emulsifiable concentrates and may have a water-in-oil or oil-in-water consistency and a mayonnaise-like consistency.

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

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

The active ingredient content of these granules is generally from 1 to 90%, preferably from 25 to 90%.

The remainder of the granulate is generally a solid filler, optionally a surfactant, which imparts to the granulate the properties of dispersibility in water. These granules can be of essentially two types, depending on whether the filler is soluble or insoluble in water. If the filler is water soluble, it may be inorganic or preferably organic. Excellent results were obtained with urea. In the case of an insoluble filler, the latter is preferably inorganic, for example kaolin or bentonite. In this case, it is preferable to use a surfactant in an amount of from 2% to 20% by weight of the granulate, of which more than half consists, for example, of at least one substantially anionic dispersant, for example alkali or alkaline a wetting agent such as an alkali metal or alkaline earth metal alkyl naphthalene sulfonate.

While not essential, other additives, such as antifoaming agents, may be used.

The granules of the present invention can be prepared by mixing the components and then granulating using a number of known techniques (tray granulator, fluid bed, atomizer, extruder, etc.). The process is generally carried out by grinding and screening the mixture to a selected particle size within the limits mentioned above. The granules obtained above may also be used and impregnated with the active ingredient formulation.

Preferably, it is prepared by extrusion according to the procedure described in the Examples below.

DG Example 1

Dispersible granules are mixed in weight of active ingredient and 10% of urea in the form of beads in a mixer. The mixture is then comminuted in a toothed roller crusher, the resulting powder is moistened with about 8% by weight of water, the wet powder is extruded in a perforated roller extruder, the resulting granulate is dried and screened to retain granules of 150 to 2000 microns.

DG Example 2

Dispersible granules

Mix the following components in a blender:

- active ingredient 45%

- wetting agent (sodium alkyl naphthalene 2%)

- 53 sulfonate)

- dispersant (sodium polynaphthalene- 8%

sulfonate)

- water-insoluble inert filler 15% (kaolin)

The mixture is granulated in a fluid bed in the presence of water, dried, crushed, sieved to give granules of 0.15-0.80 mm.

These granules are used alone or in aqueous solution or dispersion to achieve the desired dosage. They may also be used in combination with other, particularly fungicidal, active compounds in the form of wettable powders, granules or aqueous suspensions.

For storage and transport it is advantageous if the active ingredient content is between 0.5 and 95% by weight.

Claims (16)

CLAIMS 1. A composition for the treatment of fungal diseases of plant reproductive organs, comprising as active ingredient at least one 3-phenylpyrazole derivative of formula (I), wherein X ₁ , X ₂ , X ₃ , X ₄ and X ₅ may be the same or different and have the meaning - hydrogen or halogen, hydroxy, mercapto, cyano, thiocyanato, nitro or nitroso groups or optionally substituted one or two alkyl or phenyl groups, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkylsulfonyl, alkyl 1-thioalkyl, alkylsulfinylalkyl, alkylsulfon-1-yl i-alkyl, benzyl, alkenyl, alkynyl, cyanoalkyl, alkoxy, alkenyloxy, alkylthio, i-sulfonyl, formyl, acetyl, alkyl or alkoxy (thio) -carbonyl, mono- or dialkylamino (thio) carbonyl, amino (thio) carbonyl, mono- or diarylamino (thio) carbonyl, carboxyl, carboxylate, carbamoyl or benzoyl, - phenyl, phenoxy or phenylthio, - alkyl, alkoxy or mono- or di (alkylamino) phenylsulfenyl or sulfinyl or sulfonyl, - sulfone group, its salts, esters and amides, - a phosphoryl group substituted by two alkyl, alkoxy, alkylthio and / or dialkylamino, benzyloxy, phenyloxy or phenyl groups, - a trialkyl or alkylphenylsilyl group, two adjacent groups X _{1 (} X ₂ , X ₃ , X ₄ and X ₅₎ can form a bridge consisting of 2 to 4 chain members, of which air • · ·· * ····· · · • · · · · · · · · · ···· • • · · · · · · · · · · ···· ···· · · - 55 may be replaced by one of oxygen, sulfur or nitrogen below and which may contain one or more of the following atoms or groups: carbon, oxygen, nitrogen, sulfur, C = O, C = S, SO, SO ₂ , CH = CH, and the carbon atoms of this bridge may be unsubstituted or at least one halogen and / or at least one hydroxy, amino, alkyl, alkoxy, alkylthio, mono or dialkylamino, alkylsulfinyl or sulfonyl or alkoxy substituted with a carbonyl group, the alkyl moiety is as defined below, with the proviso that X _{1 to} X ₅ cannot be simultaneously hydrogen; Y is hydrogen or halogen, or nitro, cyano, hydroxy, alkylcarbonyloxy, alkoxycarbonyloxy, aminocarbonyloxy, mercapto, carboxyl, carboxylate, formyl, alkyl (thio) carbonyl -, aryl 1-carbonyl, alkoxy (thio) carbonyl, carbamoyl, aminoalkyl, thiocyanato or alkyl, alkenyl, alkynyl, alkoxy or alkylthio, alkylsulfinyl or - a sulfonyl group wherein the alkyl moiety in these groups may be optionally mono- or polyhalogenated, an amino group optionally substituted by one or two alkyl or phenyl groups; phenyl, phenoxy, phenylthio, arylsulfinyl or sulfonyl, X 1 to X ₅ and Y may also form a bridge having 1 to 3 chain members and which may contain one or more of the following atoms or groups: carbon, oxygen, sulfur, nitrogen, C = O, C = S, SO , SO ₂ , CH = CH, and the carbon atoms of this bridge may be unsubstituted or substituted with at least one halogen atom and / or at least one hydroxy, alkoxy, alkylthio, mono. · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·; - 56 or a dialkylamino, alkylsulfinyl or sulfonyl group, and the alkyl moiety is defined as follows: Z is hydrogen, halogen, cyano, nitro or hydroxy, or - alkyl, haloalkyl, hydroxyalkyl, formyloxyalkyl, alkyl or aryl (thio) carbonyloxyalkyl, alkoxy (thio) carbonyloxyalkyl, amino (thio) carbonyloxyalkyl, mono- or dialkylamino (thio) -carbonyloxyalkyl, cycloalkyl or cycloalkylalkyl, and wherein the cycloalkyl moiety may be substituted by GR4 as defined below, - alkoxy optionally substituted by hydroxy, alkoxy, alkylthio, alkylsulfinyl or sulfonyl, - phenyloxy or phenylthio, phenylsulfinyl or sulfonyl, - amino optionally substituted by one or two alkyl groups, - alkenyl or alkynyl, each of which contains from 3 to 7 carbon atoms and is optionally substituted, - phenyl or a group of Seven optionally substituted, a group of the formula wherein Z 1 is oxygen or sulfur or alkylamino, alkylimino or arylamino or arylimino, and Z ₂ is hydrogen, halogen, hydroxy, mercapto, cyano or amino, - alkyl, alkoxy, haloalkoxy, alkylthio, - or alkenyl or alkynyl or alkenyloxy groups, each of which contains from 3 to 7 carbon atoms, · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · fr • · · · ····· · ···· · * ··· · »* - 57 - phenyl, phenylalkyl, phenoxy, phenylalkoxy, - Seven or Het-alkyl, - phenylalkenyl or phenylalkynyl; Het-alkenyl or Het-alkynyl, - mono or dialkylamino, mono or diphenylamino or alkyl or arylsulfonylamino, - phosphoryl substituted twice with alkyl, alkoxy, alkylthio, dialkylamino, cycloalkyl or cycloalkylalkyl, alkenyl or alkynyl, phenyl, phenylalkyl, Seven or Hetalkyl, wherein the substituents may also be optionally substituted; - S (= Zi) (= Z ₃ ) Z ₂ , where Z ₁ and Z ₂ are as defined above, and Z ₃ is the same without necessarily being Ζ, and the tautomeric forms of formula (Ia), wherein Z is a hydrogen atom or an isomeric form thereof, when Z is C (= Z ₁ ) Z ₂ or S (= Z ₁ ) (= Z ₃ ) Z ₂ , salts of the compounds, e.g. salts, metal complexes and N-oxides thereof with phenylsulfonic acid, and in the above reports - alkyl, alkoxy, alkenyl and alkynyl groups, and groups containing these, having up to 7 carbon atoms and optionally halogenated with from 1 to 8 halogens, - the cycloalkyl groups contain from 3 to 7 carbon atoms and are optionally substituted with at least one GR4 group, -, -, -, -, -, - - - - - - - - - - - - - - - - - - - - - ·· · * ·· ··· »· * · · - 58 - phenyl groups optionally having 1 to 5 halogens, Substituted with C 1-3 alkyl or alkoxy or nitro, - Sev is a C 5 -C 10 monocyclic or bicyclic heterocyclic group, of which 1 to 4 heteroatoms, for example oxygen, sulfur, nitrogen or phosphorus; - meaning of group GR4 - halogen, cyano, nitro, mono or dialkylamino, alkyl, alkoxy, alkylsulfonyl, alkylsulfonyl, alkylcarbonyl, alkylthiocarbonyl, alkoxycarbonyl, alkoxythiocarbonyl, mono- or dialkylaminocarbonyl; or mono- or dialkylaminothiocarbonyl, mono- or dialkylaminosulfonyl (alkyl groups and groups containing 1 to 4 carbon atoms and optionally substituted with 1 to 9 halogens). Compositions according to Claim 1, characterized in that in the formula (I) Y comprises an active ingredient of the formula I containing a chlorine or bromine atom. Compositions according to any one of claims 1 and 2, characterized in that Z contains a hydrogen atom or a compound of the formula I having the formula C (= Z ₁ ) Z _2, wherein Z _{1 is} oxygen or sulfur. 4. Compositions according to any one of the preceding claims, characterized in that Xi, X ₂ and X ₄ is hydrogen, halogen, nitro, amino or optionally substituted with 1 - 4 carbon atoms include compounds of general formula (I) with a halogenated alkyl. · · · · · · · · · · · · · · · · · · · · · · · · · · ··· 5. Formulations according to any one of claims 1 to ₃ , characterized in that X contains an active ingredient of the formula I in which X ₃ is hydrogen or fluorine. 6. Compositions according to any one of claims 1 to 3, characterized in that the active ingredient of the formula (I) containing X ₁ and / or X ₅ is hydrogen. 7. Formulations according to any one of claims 1 to 3, characterized in that they contain as active ingredient a compound of formula (I), wherein two adjacent X _1t X ₂ , X ₃ , X ₄ and / or X ₅ 3 - 4 linkage bridges, in particular optionally halogenated and preferably fluorinated methylene dioxide bridge. 8. Formulations according to any one of claims 1 to 4, characterized in that X 1, X ₃ and X _{5 are} hydrogen and X ₂ and X _{4 are} chlorine. 9. Compositions according to any one of claims 1 to 3, characterized in that they contain an active ingredient of the formula I, wherein X _{1 is} nitro, X ₂ and X _{4 are} chlorine, X _{3 is} fluorine, X _{5 is} hydrogen. 10. A composition according to claim 7, characterized in that they comprise an active compound, wherein the Xi (I), R is fluoro, X ₂ and X ₄ Cl, X ₃ is fluoro, X ₃ and X 5 are hydrogen. 11. A method of treating a plant reproductive system against a fungal disease, comprising treating the material with a 3-phenylpyrazole derivative of the Formula I according to claim 1, a salt thereof, a metal complex thereof or an N-oxide thereof. 12. The 3-phenylpyrazole derivatives represented by the general formula (I) wherein: • V · · · · · · · · · · · · · · · · · · · »· * *» ··· · - 60 Υ is chlorine and Z is hydrogen, Χί is hydrogen or halogen, nitro, amino or methyl, X ₂ is halogen or nitro, amino or methyl, X ₃ is hydrogen or halogen, X ₄ is halogen or amino, nitro or methyl, X ₅ is hydrogen or halogen or a salt, metal complex or N-oxide thereof. The compound of claim 12, wherein, in formula (I), X ₂ is chlorine or bromine; X ₃ and X _{5 are the} same or different and are hydrogen or fluorine. Derivatives according to claim 12, wherein in the formula (I): χ ₁ = H; X ₂ = CH; X ₃ = F; X ₄ = CH ₃ ; and X ₅ = H; X 1 = NO ₂ ; X ₂ = Cl; X ₃ = F; X ₄ = Cl; and X ₅ = H; X 1 = NH ₂ ; X ₂ = Cl; X ₃ = F; X ₄ = Cl; and X ₅ = H; X! = F; X ₂ = Cl; X ₃ = F; X ₄ = Cl; and X ₅ = F; X 1 = H; X ₂ = Cl; X ₃ = H; X ₄ = F; and X ₅ = H; X 1 = F; X ₂ = Cl; X ₃ = H; X ₄ = Cl; and X ₅ = H; X 1 = F; X ₂ = Br; X ₃ = H; X ₄ = Br; and X _s = H; X 1 = CH ₃ ; X ₂ = NO ₂ ; X ₃ = H; X ₄ = F; and X ₅ = H; X 1 = F; X ₂ = Cl; X ₃ = F; X ₄ = Cl; and X ₅ = H; X 1 = F; X ₂ = Cl; X ₃ = Η; X! = F; X ₂ = Cl; X ₃ = H; X 1 = H; X ₂ = Cl; X ₃ = F; X ₄ = Cl; and X ₅ = H. A composition for treating foliage of plants against fungal diseases, characterized in that it is an active ingredient 61 at least one of 11-13; A 3-phenylpyrazole derivative according to any one of claims 1 to 3, a salt, a metal complex or an N-oxide thereof. 16. A method of treating a foliage of plants against fungal diseases, wherein the plants are at least one of 11 to 13. The compound of claim 1 is treated with a 3-phenylpyrazole derivative, a salt, a metal complex or an N-oxide thereof.