CN1152853A - Fungicidal compositions containing 3-phenyl-pyrazole derivatives for treating propagative plant stock, 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

The Fungicidal composition based on the 3-phenylpyrazole derivatives that is used for treatment of plant propagation material, new 3-phenylpyrazole derivatives and antifungal thereof are used

The present invention relates to use 3-phenylpyrazole derivatives protective plant propagating materials to resist fungal disease; contain the composition of these derivatives and the new derivative of this type; relate to composition that contains this class new derivative and the Fungicidal composition that contains this analog derivative, and relate to these derivative methods for the treatment of plants.

Disclosed patent application EP0,538,156 and WO93/22287 some 3-phenylpyrazole derivatives have been described particularly in the superior function that prevents aspect the plant leafage fungal disease.

" plant propagation material " refers to can be used for regenerating and the procreant all sites of plant (parts) of breeding plant.For example, it can refer to seed (proper term), root, fruit, stem tuber, bulb, the rhizome of the crop except that potato, the position of plant, perhaps germinate the back or expose soil after the germination plant and the seedling of culture transferring.These seedling can carry out diseases prevention by all or part of immersion treatment before the culture transferring.In the propagation products that is fit to the inventive method processing, following material is preferably:

The seed of～dicotyledon (as pea, cucumber, muskmelon, soybean, cotton, sunflower, rape, beans, flax and beet);

The seed of～monocotyledon (as cereal, corn, rice);

～or the potato stem tuber.

Should be with 0.1-500g active substance/100kg seed, preferably the amount of 1-400g/100kg applies seed.Under the situation of stem tuber, the most handy an amount of active substance of stem tuber applies, and is equivalent to stem tuber is immersed in the composition that contains the 0.1-100g/l active substance.

Specifically, a theme of the present invention is to be used for the composition that treatment of plant propagation material is resisted fungal disease, it is characterized in that this composition contains the 3-phenylpyrazole derivatives of at least a formula I as active component:

Wherein: X ₁, X ₂, X ₃, X ₄And X ₅Can be identical or different, for:

～hydrogen or halogen atom, hydroxyl, sulfydryl, cyano group, thiocyano, nitro or nitroso, the perhaps amino that at random replaces by one or two alkyl or phenyl,

～alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkane sulfonyl; alkylthio alkyl, alkyl sulphinyl alkyl, alkyl sulphonyl alkyl, benzyl, alkenyl; alkynyl, cyano group alkyl, alkoxyl, alkene oxygen base; alkylthio group, alkyl sulphinyl, formoxyl, acetyl group; alkyl or alkoxyl (sulfo-) carbonyl, one or dialkyl amido (sulfo-) carbonyl, amino (sulfo-) carbonyl, one or ammonia diaryl base (sulfo-) carbonyl; carboxyl, carboxylate group, carbamoyl or benzoyl group

～phenyl, phenoxy group or thiophenyl,

～alkyl, alkoxyl, one or two (alkyl amino) phenyl sulfenyl (sulphenyl) or sulfinyl or sulfonyl,

～sulfo group, its salt, ester and the acid amides of deriving,

～be selected from alkyl by two, alkoxyl, alkylthio group and dialkyl amido, benzyloxy, the phosphoryl that phenoxy group or phenyl groups replace,

～trialkyl or alkyl phenyl silicyl,

The X of two vicinities ₁, X ₂, X ₃, X ₄And X ₅Group can also form the bridge with 2-4 chain member, and wherein at least one chain member is replaced by oxygen, sulphur or nitrogen-atoms, and this bridge can contain one or more following atoms or group: i.e. C, O, S, N, C=O, C=S, SO, SO ₂, CH=CH, the carbon atom on this bridge can be by at least one halogen atom and/or at least one hydroxyl, amino; alkyl, alkoxyl, alkylthio group, one or dialkyl amido; alkyl sulphinyl or sulfonyl, alkoxy carbonyl replaces or is not substituted, and moieties wherein is defined as follows

Its condition is X ₁-X ₅Can not be hydrogen atom simultaneously;

Y is hydrogen or halogen atom, or nitro, cyano group, hydroxyl, alkyl-carbonyl oxygen base, alkoxy-carbonyl oxy, amino carbonyl oxygen base, sulfydryl, carboxyl, carboxylate group, formoxyl, alkyl (sulfo-) carbonyl, aryl carbonyl, alkoxyl (sulfo-) carbonyl, carbamoyl, aminoalkyl, thiocyano or alkyl, alkenyl, alkynyl, alkoxyl or alkylthio group, alkyl sulphinyl or sulfonyl (moieties of these groups is list or many halogenations at random) they at random are the amino that one or two alkyl or phenyl replaced; Phenyl, phenoxy group, thiophenyl, aryl sulfonyl kia or sulfonyl,

Y and X ₁Or X ₅Can also form the bridge with 1-3 chain member, this bridge can contain one or more following atoms or group: i.e. C, O, S, N, C=O, C=S, SO, SO ₂, CH=CH, the carbon atom on this bridge can be by at least one halogen atom and/or at least one hydroxyl, alkoxyl, alkylthio group, one or dialkyl amido, alkyl sulphinyl or sulfonyl replace or are not substituted, and moieties wherein is defined as follows,

Z is:

～hydrogen or halogen atom, or cyano group, nitro or hydroxyl, perhaps

～alkyl, haloalkyl, hydroxyalkyl, formyloxy alkyl, alkyl or aryl (sulfo-) ketonic oxygen base alkyl, alkoxyl (sulfo-) ketonic oxygen base alkyl, amino (sulfo-) ketonic oxygen base alkyl, one or dialkyl amido (sulfo-) ketonic oxygen base alkyl, cycloalkyl or cycloalkyl-alkyl, cycloalkyl moiety can be replaced by the GR4 group that defines below

～at random by hydroxyl, alkoxyl and alkylthio group, the alkoxyl that alkyl sulphinyl or sulfonyl replaced,

～phenoxy group or thiophenyl, phenyl sulfinyl or sulfonyl,

～at random be the amino that one or two alkyl replaced,

～the alkenyl or the alkynyl that contain 3-7 carbon atom separately and replace arbitrarily,

The phenyl or the Het (heterocyclic radical) of～replacement arbitrarily,

～have a formula C (=Z ₁) Z ₂Group, wherein:

-Z ₁Be oxygen, sulphur atom or alkyl amino, alkyl imino or arylamino, aryl imino group,

-Z ₂Be:

Hydrogen or halogen atom, or hydroxyl, sulfydryl, cyano group or amino,

Alkyl, alkoxyl, halogenated alkoxy, alkylthio group,

The alkenyl or the alkynyl that contain 3-7 carbon atom respectively, or alkene oxygen base,

Phenyl, phenylalkyl, phenoxy group, the phenyl alkoxyl,

Het or Het-alkyl,

Phenyl alkenyl or phenyl alkynyl,

Het-alkenyl or Het-alkynyl,

One or dialkyl amido, one or diphenyl amino, perhaps alkyl or aryl sulfuryl amino,

～be selected from alkyl by two, alkoxyl, alkylthio group, dialkyl amido, cycloalkyl or cycloalkyl-alkyl, alkenyl or alkynyl, phenyl, phenylalkyl, the phosphoryl that the group of Het or Het-alkyl at random replaces,

～or S (=Z ₁) (=Z ₃) Z ₂Group, wherein Z ₁And Z ₂With as defined above identical, Z ₃Identical with it but may not equal Z ₁,

And the tautomerism form of formula Ia (when Z is a hydrogen atom) or isomeric forms are (when Z is formula C (=Z ₁) Z ₂Or S (=Z ₁) (=Z ₃) Z ₂),

Their salt, as hydrohalogenic acid salt, perchlorate, nitrate, sulphate, alkyl or phenyl (replacing arbitrarily) sulfonate and their metal complex and N-oxide,

With this understanding, in all above-mentioned implications:

～alkyl, alkoxyl, alkenyl and alkynyl are segment and the halogenations arbitrarily (1-8 halogen atom) that contains up to 7 carbon atoms,

～cycloalkyl contains 3-7 carbon atom, and is at random replaced by at least one substituting group that is selected from the GR4 group that defines below,

～phenyl at random is selected from halogen atom, is had the alkyl of 1-3 carbon atom or the group of alkoxyl and nitro is replaced by 1-5,

～Het is the heterocyclic group that contains one or two rings of 5-10 atom (wherein 1-4 is hetero atom, as oxygen, sulphur, nitrogen and phosphorus);

～GR4 group comprises:

-halogen atom or cyano group, nitro, one or dialkyl amido,

-alkyl, alkoxyl, alkyl sulfenyl (sulphenyl), alkyl sulphonyl, alkyl-carbonyl,

The alkylthio group carbonyl, alkoxy carbonyl, alkoxyl thiocarbonyl, one or the dialkyl amido carbonyl

Base, perhaps one or the dialkyl amido thiocarbonyl, one or dialkyl amino sulfonyl (alkyl

Group or contain 1-4 carbon atom and at random for 1-9 the sheet that halogen atom replaced

Disconnected).

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

Other preferably derivative be among the formula I, Z is hydrogen atom or C (=Z ₁) Z ₂Group (Z wherein ₁Be oxygen or sulphur atom) compound.

Other preferably derivative be among the formula I, X ₁, X ₂And X ₄Be hydrogen or halogen atom, the compound of the alkyl with 1-4 carbon atom of nitro or amino or halogenation at random.

Other preferably derivative be among the formula I, X ₃It is the compound of hydrogen or fluorine atom.

Other preferably derivative be among the formula I, X ₁And/or X ₅It is the compound of hydrogen atom.

Other preferably derivative be among the formula I, two vicinities be selected from X ₁, X ₂, X ₃, X ₄And X ₅Substituting group form the bridge comprise 3 or 4 chain members, particularly arbitrarily by the compound of methylene dioxy Ji Qiao halogenation and that preferably fluoridize.

Aryl is phenyl preferably.

Good especially derivative is respectively among the formula I:

(a) X ₁, X ₃And X ₅Be hydrogen atom, X ₂And X ₄Be respectively the chlorine atom,

(b) X ₁Be nitro, X ₂And X ₄Be respectively the chlorine atom, X ₃Be fluorine atom, X ₅Be hydrogen atom,

(c) X ₁Be fluorine atom, X ₂And X ₄Be respectively the chlorine atom, X ₃Be fluorine atom, and X ₃And X ₅It is hydrogen atom.

These derivative parts are new, are in formula I:

Y is the chlorine atom, and Z is a hydrogen atom,

X ₁Be hydrogen or halogen atom or nitro, amino, methyl,

X ₂Be halogen atom or nitro, amino or methyl,

X ₃Be hydrogen or halogen atom,

X ₄Be halogen atom or amino, nitro or methyl,

X ₅Be hydrogen or halogen atom.

New derivative is among the formula I preferably:

Y, Z, X ₁And X ₄As mentioned above,

X ₂Be the chlorine or bromine atom,

X ₃And X ₅Can be identical or different, be respectively hydrogen or fluorine atom.

Derivative of the present invention can according to method known per se (as at disclosed patent application EP0,538,156 and WO93/22287 in the method described) make.

The following example illustrates the preparation of new derivative respectively, their physico chemical property (its structure is by the NMR analysis confirmation), and they are curing derivative that fungicide performance aspect the leafage disease and the present invention collect at the fungicide performance aspect the seed treatment.Embodiment 1: benzoic acids

(a) 2,3-two chloro-5-nitrobenzoic acids

58g (0.57mol) potassium nitrate is added to 100g (0.52mol) 2 3,dichloro benzoic acid 99 that is cooled to 5 ℃ in batches to be dissolved in the solution in the 1000ml concentrated sulfuric acid.After 1 hour, reaction medium is poured in 8 liters of ice, filtered, dry then (output 63% through sintered glass; Analyze).

(b) 3-chloro-4-fluoro-5-bromobenzoic acid

In argon atmospher, make 10g (0.0265mol) 3,5-two bromo-4-fluobenzoic acids are dissolved among the anhydrous THF of 200ml.At-70 ℃ of hexane solutions that drip 37ml 1.6M n-BuLi.Stir after 1 hour, adding 25.1g (0.106mol) carbon trichloride is dissolved in the solution among the anhydrous THF of 20ml.After 2 hours, little by little make the temperature of medium rise to room temperature-70 ℃ of placements.Make reactant mixture hydrolysis in 50ml water, use extracted with diethyl ether subsequently.Add 1N HCl and make aqueous phase as acidified, use extracted with diethyl ether subsequently.Organic facies also under reduced pressure concentrates with dried over mgso.In heptane/ether mixed liquor,, obtain 1.2g 3-chloro-4-fluoro-5-bromobenzoic acid (output 18%, 184 ℃ of fusing points) with the solid recrystallization.

(c) 3,5-two bromo-4-fluobenzoic acids

60.8g sodium hydroxide piller is dissolved in the 500ml water.Add the 26ml bromine, make the temperature of reaction medium remain below 10 ℃ simultaneously.Add 50.0g (0.169mol) 3,5-two bromo-4-fluoro acetophenones are dissolved in the solution in the 50ml diox, make the temperature of reaction medium remain below 10 ℃ simultaneously.Make the temperature of reactant mixture rise to room temperature, control exothermic effect simultaneously so that temperature does not exceed 35 ℃.At room temperature continue to stir 1.5 hours.The water extracted with diethyl ether is acidified to the pH value near 1 with 1N HCl subsequently, and then uses extracted with diethyl ether.Organic facies concentrates with dried over mgso and under vacuum.Solid grinds in heptane, obtains 47.5g 3,5-two bromo-4-fluobenzoic acid (output 74%; Fusing point: 201 ℃).

(d) 3,5-two chloro-2,4,6-trifluoro-benzoic acid

In-70 ℃ and argon atmospher, the solution of 57ml 1.6M n-BuLi in hexane is splashed in the solution of 10.4g (0.090mol) TMEDA in the anhydrous THF of 40ml.At-70 ℃, drip 15.0g (0.075mol) 3,5-two chloro-2,4, the solution of 6-trifluoro-benzene in the anhydrous THF of 10ml.-70 ℃ stir 1 hour after, reactant mixture is poured in the solid carbon dioxide among the anhydrous THF of 100ml.The stirring reaction medium makes temperature go up gradually to room temperature simultaneously, and water hydrolysis is subsequently also used extracted with diethyl ether.Water is with 1N HCl acidifying and use extracted with diethyl ether.Organic facies concentrates with dried over mgso and under vacuum.In heptane/ether mixed liquor with solid recrystallization (output 54%; 136 ℃ of fusing points).

(e) 3,5-two chloro-2,4-difluoro-benzoic acid

In-50 ℃ and argon atmospher, the solution of 90ml 1.6M n-BuLi in hexane is splashed in the solution of 14.3g (0.090mol) diisopropylamine in the anhydrous THF of 100ml.-50 ℃ place half an hour after, drip 20.0g (0.109mol) 3,5-two chloro-2, the solution of 4-two fluorobenzene in the anhydrous THF of 70ml.At-70 ℃ reaction medium was stirred 1 hour, pour into subsequently in the solid carbon dioxide among the anhydrous THF of 100ml.Go up to room temperature, the hydrolysis of reactant mixture water is also used extracted with diethyl ether.Water is with 1N HCl acidifying and use extracted with diethyl ether.Organic facies concentrates with dried over mgso and under vacuum.Solid (the output 37% that in heptane/ether mixed liquor, is recrystallized; 177 ℃ of fusing points).

(f) 3,5-two chloro-2,6-difluoro-benzoic acid

With 9.5g (0.06mol) 2,6-difluoro-benzoic acid and 7.8ml (0.09mol) oxalyl chloride is dissolved in 50ml1, in the 2-dichloroethane.Adding 5 DMF also at room temperature stirs mixture 1 hour.Add 24g (0.18mol) aluminium chloride and medium is raised to 60-70 ℃.When the temperature with reaction medium remains on 60-70 ℃, fed cl gas flow 5 hours, mixture is poured among the 100ml 1N HCl then.The filtered and recycled sediment, the also drying under reduced pressure that washes with water obtains the cream-colored solid (output 95.6% of 13g; ¹H﹠amp; ¹³C NMR).

Use above-mentioned steps and suitable reactant can make following acid:

～3-fluoro-5-bromobenzoic acid (output 78%; 144 ℃ of fusing points);

～2-nitro-3-chloro-5-methyl benzoic acid (output 83%; 226 ℃ of fusing points);

～3-fluoro-5-methoxy benzoic acid (output 90%; 121 ℃ of fusing points).Embodiment 2: acetophenones

(referring to the embodiment 4D of patent application WO93/22287)

Prepare acetophenones according to the following step with the benzoic acids that makes above:

(a) 2,3-two bromo-5-methyl benzoyl chlorides

To 2.1g (0.00714mol) 2,3-two bromo-5-methyl benzoic acids are dissolved in 20ml 1, add 0.78ml (0.107mol) thionyl chloride in the solution in the 2-dichloroethane and are dissolved in 5ml 1, the solution in the 2-dichloroethane.60 ℃ of mixture stir abouts that will obtain thus 5 hours, concentrate it subsequently in a vacuum, obtain 2 of oily, 3-two bromo-5-methyl benzoyl chlorides.

(b) (2,3-two bromo-5-aminomethyl phenyls) ethyl ketone

The mixture of 0.87g (0.0076mol) magnesium ethylate and 1.17ml (0.0076mol) malonic ester added in the 30ml ether refluxed 3 hours.The acyl chlorides that 2g (0.0064mol) is obtained above (being diluted in the 5ml ether) adds in this multi-phase solution subsequently.Then reaction medium is refluxed and stirred 3 hours.After the cooling, in reaction medium, add the 10ml dilution heat of sulfuric acid, then with extracted with diethyl ether and wash with water.After the dried over mgso, boil off solvent, the grease that obtains directly carries out decarboxylation step: dilute in the mixed liquor of 5ml acetate, 5ml water and the 1ml concentrated sulfuric acid, subsequently about 2 hours of 70 ℃ of heating.Neutralize it with the ethyl acetate extraction reaction medium and with sodium hydrate aqueous solution.Boil off solvent after the dried over mgso, obtain (2,3-two bromo-5-aminomethyl phenyls) ethyl ketone of oily.

With being same as top method, can make following acetophenones (seeing the following form) by the benzoic acid of suitable replacement:

??X 1，X 2，X 3，X 4，X 5，	Output (%)	Fusing point (℃) or analyze
			??H，Br，F，Cl，H	????50	Analyze
??F，Cl，F，Cl，F	????58	Analyze
			??F，Cl，F，Cl，H	????63	????48.5
Methyl, Cl, F, Cl, H	????13	????62
			??Cl，Cl，H，NO 2，H	????87	Analyze
Methyl, NO 2，H，F，H	????89	????50
			??F 3C，Cl，H，H，H	????42	????NMR
??Cl，OCF 3，H，Br，H	????61	????NMR
			??Cl，OCF 3，H，NO 2，H	????82	????NMR
??Br，OCF 3，H，NO 2，H	????89	????NMR
			??F，Br，F，Cl，H	????50	????NMR
F, methyl, F, Cl, H	????10	????NMR
			??F，Cl，H，F，H	????46	????NMR
??H，F，H，Br，H	????54	????73
			??NO 2, Cl, H, methyl, H	????70	????130
H, F, H, methoxyl group, H	????68	????66
			H, Cl, H, methyl, H	????52	????NMR

By 3,5-dichloroaniline preparation (3, the 5-dichlorophenyl) ethyl ketone (referring to the embodiment 4F of patent application WO93/2228)

300ml water and 70ml concentrated hydrochloric acid are added to 48.6g (0.30mol) 3, in the 5-dichloroaniline.After 30 minutes, drip the solution of 27.5g (0.40mol) natrium nitrosum in 32ml water and temperature is controlled at 0-5 ℃ simultaneously.In filtered reactant mixture, add 16.2g (0.2mol) sodium acetate.The solution that obtains splashed in 28.5g (0.48mol) acetaldoxime, 25.0g (0.10mol) cupric sulfate pentahydrate, 20.5g (0.018mol) anhydrous sodium sulfite and the solution of 121g (1.50mol) sodium acetate in 250ml water and with temperature be controlled at 15 ℃.Stir after 1 hour, add this mixture of concentrated hydrochloric acid acidifying.Through steaming and with crude product with silica gel column chromatography (heptane/ethyl acetate 90: 10) purifying, be recovered to 16.6g (30%) colourless liquid shape (3, the 5-dichlorophenyl) ethyl ketone.

The use above-mentioned steps as raw material, obtains (3-bromo-5-trifluoromethyl) ethyl ketone (output 35% with 3-bromo-5-5-trifluoromethylaniline; NMR).

4-acetyl-2,6-dichloroaniline are as raw material:

814g (4mol) the 4-acetyl-2 that in the mixed liquor of 1200ml concentrated hydrochloric acid and 5200ml spirit acid, is recrystallized, 6-dichloroaniline (according to the patent DD273 on November 15th, 1989,435 make).After being cooled to 0 ℃, add the solution of 290g (4.2mol) natrium nitrosum in 770ml water of thread (fine steam) shape.After placing 2.5 hours under this temperature, this solution poured in 5 ℃ the 2200ml 50% hypophosphorous acid aqueous solution.When topple over finish after, make temperature recovery to room temperature, add 10 premium on currency and use the dichloromethane extraction water.After the clarification, separate and dry organic facies, concentrate and the distillation crude product, obtain 591g (output: 78%, boiling point (less than 1mmHg): 91-95 ℃) (3, the 5-dichlorophenyl) ethyl ketone light yellow liquid.

Use said method, as raw material, obtain (3-bromo-5-chlorphenyl) ethyl ketone (output 89% with 4-acetyl-6-bromo-2-chloroaniline; NMR).

Use said method, with 3,4, the 5-trichloroaniline obtains (3,4, the 5-trichlorophenyl) ethyl ketone (output 20% as raw material; M.p.:75 ℃).Embodiment 3:2-chloro-acetophenone class

Prepare chloro-acetophenone (referring to the embodiment 4I of patent application WO93/22287) by chloroacetylation (Friedel-Crafts) 2-chloro-1-(2-chloro-4-fluoro-5-aminomethyl phenyl) ethyl ketone

It is anhydrous 1 at 100ml that 14.1g (0.125mol) monochloro-acetyl chloride is splashed into 16.66g (0.125mol) anhydrous Aluminum chloride, temperature is controlled at-5 ℃ with ice/acetone bath simultaneously in the suspension in the 2-dichloroethane.Then under uniform temp, in the solution that obtains, drip 14.46g (0.1mol) 4-chloro-2-toluene fluoride.At 5 ℃ reactant mixture was stirred 1 hour, place subsequently and spend the night, and be warming up to 60 ℃ until stopping to discharge gas.After the ice bath cooling, the solution of Dropwise 5 ml concentrated hydrochloric acid in 100ml water.After the clarification, isolate organic facies, use 50ml water, 50mlNaHCO successively ₃Anhydrous magnesium sulfate drying is then used in saturated solution and 50ml water washing.After boiling off solvent, obtain 2-chloro-1-(the 2-chloro-4-fluoro-5-aminomethyl phenyl) ethyl ketone of the light yellow oily of 22.3g, and the crystallization when cooling of this oil (fusing point: 32 ℃, output: 100%).

Can make 2-chloro-1-(3-methyl-4-fluoro-5-aminomethyl phenyl) ethyl ketone (fusing point: 86 ℃, output 87%) equally (FG993) and 2-chloro-1-(2-fluoro-3,5-two chloro-4-fluorophenyls) ethyl ketone (NMR analyzes, output 75%).Embodiment 4:3,5-two bromo-4-fluoro acetophenones

133.5g (1.00mol) aluminium chloride is added to 400ml 1, in the 2-dichloroethane.Mixture is cooled to 10 ℃.Add 13.81g (0.10mol) 4-fluoro acetophenone and be dissolved in 10ml1, the solution in the 2-dichloroethane.Reaction medium is warmed to 55 ℃, and in about 1 hour Dropwise 5 1ml bromine.55 ℃ of continuous stirring 5 hours.The temperature of reaction medium is reduced to room temperature, pour into in the water of ice-cooled slight acidifying and with dichloromethane extraction it.Organic facies concentrates subsequently in a vacuum with dried over mgso.Obtain 6.7g3,5-two bromo-4-fluoro acetophenones (output: 23%, fusing point: 59 ℃).Embodiment 5:3-methyl-4-fluoro-5-chloro-acetophenone

16.7g (0.123mol) aluminium chloride is added to 100ml1, in the 2-dichloroethane.Mixture is cooled to 10 ℃ and add the 8.2ml chloroacetic chloride.10 ℃ place half an hour after, add 15.0g (0.104mol) 2-fluoro-3-chlorotoluene and be dissolved in 10ml1, the solution in the 2-dichloroethane.Make the temperature of reaction medium reduce to room temperature, subsequently 50 ℃ of heating 3 hours.After the cooling, mixture poured among the 1N HCl and with dichloromethane extraction it.Organic facies concentrates subsequently in a vacuum with dried over mgso.Obtain 11.6g3-methyl-4-fluoro-5-chloro-acetophenone.Embodiment 6: enamine ketone (enaminones)

(referring to the embodiment 5 and 6 of patent application WO93/22287)

1-(3, the 5-dichlorophenyl)-3-dimethylamino-2-propylene-1-ketone

While stirring 10g (0.053mol) 3 ', 5 '-dichloroacetophenone is dissolved in 50ml N in room temperature, in the dinethylformamide dimethyl acetal (dimethyl acetal).When stirring, heated 2 hours at 90 ℃.Under reduced pressure medium is concentrated into dried.Residue is dissolved in the 150ml heptane.Leach orange precipitation, obtain 10.0g (output: 77%, 100 ℃ of fusing points) 1-(3, the 5-dichlorophenyl)-3-dimethylamino-2-propylene-1-ketone.

Use identical step, as raw material, can make the enamine ketone derivatives (in being listed in the table below) of following formula with the acetophenone of suitable replacement and suitable second reactant:

X 1，X 2，X 3，X 4，X 5	Output (%)	Fusing point (℃) or analyze
			H，Br，F，Cl，H	????80	Analyze
H，Br，F，Br，H	????82	????143
			H, methyl, F, Cl, H	????28	????89
F，Cl，F，Cl，F	????81	????128
			H，Cl，Cl，Cl，H	????85	????143
Methyl, Cl, F, Cl, H	????69	????127
			Cl，Cl，H，NO 2，H	????60	Analyze
H, Cl, H, methyl, H	????91	Analyze
			F，Br，F，Cl，H	????87	????121
F, methyl, F, Cl, H	????40	????NMR
			H, F, H, methoxyl group, H	????76	????70

Embodiment 7: the chlorine enamine ketone

1-(3,5-dimethyl-4-fluorophenyl)-2-chloro-3-dimethylamino-2-propylene-1-ketone

6.0g (0.03mol) 2-chloro-3 ', 5 '-dimethyl-the 4 '-suspension of fluoro acetophenone in the mixed liquor of 7.15g (0.06mol) dimethyl formamide dimethyl acetal (dimethyl acetal) and 100ml heptane is warmed to 50 ℃ to be stirred 8 hours under this temperature subsequently.After the cooling, reaction medium is filtered the crystal that obtains heptane wash subsequent drying (3.2g).Filtrate is carried out the part evaporation, obtain a collection of new crystal, handle it (0.8g) with identical method.Handle the crystal of two batches of merging subsequently with silica gel chromatograph, earlier with the mixed liquor of 70% heptane and 30% ethyl acetate, use the mixed liquor wash-out of 50% heptane and 50% ethyl acetate subsequently.Obtain 1.84g raw material 2-chlorine 3 ', 5 '-dimethyl-4 '-fluoro acetophenone and 1.55g 1-(3,5-dimethyl-4-fluorophenyl)-2-chloro-3-dimethylamino-2-propylene-1-ketone white crystal, it is in 177.5 ℃ of decomposition (output 20%).

Using identical step, is raw material with the acetophenone and the second suitable reactant of suitable replacement, can make (3,5-two chloro-2,4-difluorophenyl)-2-chloro-3-dimethylamino-2-propylene-1-ketone (seeing that NMR analyzes output 100%).Embodiment 8:1H-pyrazoles

(seeing the embodiment 7 of patent application WO93/22287)

3-(3, the 5-dichlorophenyl)-1H-pyrazoles

In room temperature, 2.4g (0.05mol) hydrazine hydrate is added in 9g (0.0369mol) 1-(3, the 5-the dichlorophenyl)-3-dimethylamino-2-propylene-solution of 1-ketone in 100ml ethanol lentamente.Room temperature with reactant mixture stir concentrated then in 2 hours as for.Residue grinds in heptane, obtains 7.1g (90% output, fusing point: 156 ℃) 3-(3, the 5-dichlorophenyl)-1H-pyrazoles.

Using identical step, is raw material with the enamine ketone and the second suitable reactant of suitable replacement, can make the pyrazole derivatives (in being listed in the table below) of following formula:

????X 1，X 2，X 3，X 4，X 5	Output (%)	Fusing point (℃) or analyze
			????H，Br，F，Cl，H	????77	????261
????H，Br，F，Br，H	????86	????201
			H, methyl, F, Cl, H	????93	????156
????F，Cl，F，Cl，F	????47	????155
			????H，Cl，Cl，Cl，H	????69	????208
Methyl, Cl, F, Cl, H	????97	????130
			????Cl，Cl，H，NO 2，H	????60	Analyze
Methyl, NO 2，H，F，H	????81	????98
			H, Cl, H, methyl, H	????80	Analyze
????F，Br，F，Cl，H	????88	????161
			????F，Cl，H，Cl，F	????70	????150
????F，CF 3，H，Cl，H	????12	????NMR
			????CF 3，Cl，H，H，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 2，H	????66	????NMR
			????F，H，H，Cl，H	????75	????NMR
????Cl，H，H，CF 3，H	????90	????NMR
			????H，F，H，Br，H	????69	????NMR
????NO 2, Cl, H, methyl, H	????82	????175
			H, F, H, methoxyl group, H	????38	????83
3-(2-naphthyl)	????87	????162
			3-(benzo [b] thiophene-4-yl)	????60	????147

Embodiment 9:4-chlorine pyrazoles

(a) 3-(3,5-dimethyl-4-fluorophenyl)-4-chlorine pyrazoles (compound 1)

In room temperature, while stirring the cold soln of 1.5g hydrazine hydrate in the 30ml glacial acetic acid added to apace in 3.10g (0.0122mol) 1-(3,5-dimethyl-4-the fluorophenyl)-2-chloro-3-dimethylamino-2-propylene-suspension of 1-ketone in the 20ml glacial acetic acid., after 7 hours reaction medium is poured in the 200ml water in stirring at room, leached the solid of generation, wash with water and at P ₂O ₅Existence under vacuum drying it.Subsequently with 70% heptane and 30% ethyl acetate be eluent on silica gel chromatograph purifying it, obtain 2.09g 3-(3,5-dimethyl-4-fluorophenyl)-4-chlorine pyrazoles, be that a kind of fusing point is 144 ℃ a white solid (output: 76%).

Use identical step, as raw material, can make 3-(3,5-two fluoro-4-fluorophenyls)-4-chlorine pyrazoles (compound 2) with the 1H-pyrazoles of suitable replacement and suitable second reactant.

(b) 4-chloro-3-(3, the 5-dichlorophenyl)-1H-pyrazoles (compound 3): (referring to the embodiment 9a of patent application WO93/22287): the halogenation of pyrazoles

In room temperature, while stirring 2.3g (0.0152mol) 3-(3, the 5-dichlorophenyl)-1H-pyrazoles is dissolved in the 300ml carrene.Add 2.07g (0.016mol) N-chloro-succinimide subsequently, then stirred continuously 4 days in room temperature.Concentrated reaction mixture and with silica gel chromatograph purifying (eluent: heptane/ethyl acetate: 70: 30) then.Obtain 1.4g 4-chlorine 3-(3, the 5-dichlorophenyl)-1H-pyrazoles (output 57%, fusing point: 192 ℃).

Use identical step, as raw material, can make the 4-chlorine pyrazole derivatives (in being listed in the table below) of following formula with the 1H-pyrazoles of suitable replacement and suitable second reactant.

Compound	????X 1，X 2，X 3，X 4，X 5	????Y	Output (%)	Fusing point (℃) or analyze
					????4	????H，Br，F，Cl，H	????Cl	????84	????169
????5	????H，Br，F，Br，H	????Cl	????88	????169
					????6	H, methyl, F, Cl, H	????Cl	????69	????174
????7	????F，Cl，F，Cl，F	????Cl	????79	????143
					????8	????H，Cl，Cl，Cl，H	????Cl	????61	????208
????9	????F，Cl，F，Cl，H	????Cl	????30	????158
					????10	Methyl, Cl, F, Cl, H	????Cl	????81	????53
????11	????Cl，Cl，H，NO 2，H	????Cl	????70	????172
					????12	Methyl, NO 2，H，F，H	????Cl	????55	????126
????13	H, Cl, H, methyl, H	????Cl	????85	????175
					????40	????F，Br，F，Cl，H	????Cl	????92	????167
????41	????CF 3，Cl，H，H，H	????Cl	????68	????78
					????42	Cl, F, H, methoxyl group, H	????Cl	????75	????156
????43	H, F, H, methoxyl group, H	????Cl	????45	????127
					????44	F, methyl, F, Cl, H	????Cl	????20	????119
????45	????Cl，OCF 3，H，Br，H	????Cl	????56	????109
					????46	????Cl，OCF 3，H，NO 2，H	????Cl	????44	????132
????47	????Br，OCF 3，H，NO 2，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 2, Cl, H, methyl, H	????Cl	????55	????172
????53	3-(2-naphthyl)	????Cl	????37	????140

(c) 4-chlorine pyrazoles (referring to patent application WO93/22287 embodiment 12)

The a-acetylization

0.25g (0.005mol) 4-dimethylaminopyridine and 4.25g (0.042mol) triethylamine are added to 11.0g (0.046mol) 4-chloro-3-(2,2-two fluoro-1,3-benzodioxole-4-yl)-1H-pyrazoles (making as the method for describing among the french patent application No.91/12647) is dissolved in the solution among the 100mlTHF.In this solution, splash into the solution of 3.6g (0.046mol) chloroacetic chloride in 50mlTHF at 0 ℃.Room temperature continuous stirring 3 hours.Reactant mixture poured in the 300ml water and with ethyl acetate extraction it.After the organic facies drying also concentrated in a vacuum, residue ground in the 50ml heptane, leached and drying, obtained 12.8g 1-acetyl-4-chloro-3-(2,2-two fluoro-1,3-benzodioxole-4-yl) pyrazoles (compound 14), 131 ℃ of fusing points.

B-is nitrated

In small batches 6.3g (0.063mol) potassium nitrate being added to 12.8g 1-acetyl-4-chloro-3-(2,2-two fluoro-1,3-benzodioxole-4-yl) pyrazoles at 0 ℃ of branch is dissolved in the solution in 21ml sulfuric acid (96%) and the 140ml carrene.At 0 ℃ reaction medium is stirred 3 hours subsequently to 300cm ³On ice.Filtered and recycled precipitation, successively water and heptane wash it, obtain 8.05g4-chloro-3-(2,2-two fluoro-5-nitros-1,3-benzodioxole-4-yl) pyrazoles after the drying, 180 ℃ of (output: 63%) (compound 15) of fusing point.

Use identical step, as raw material, can make following formula 4-chlorine pyrazole derivatives (in being listed in the table below) with the 1H-pyrazoles of suitable replacement and suitable second reactant.

Compound	??X 1，X 2，X 3，X 4，X 5	??Y	Output (%)	Fusing point (℃) or analyze
					????16	??F，Cl，H，NO 2，H	??Cl	????74	??????147
????17	??F，Br，H，NO 2，H	??Cl	????34	??????154
					????18	??NO 2，Cl，H，Cl，H	??Cl	????55	??????173
????54	??F，NO 2，H，Cl，H	??Cl	????46	??????177
					????55	??Cl，NO 2，H，CF 3，H	??Cl	????22	??????128
????56	??NO 2, methoxyl group, H, F, H	??Cl	????50	??????158

Embodiment 10:3-(2-aminophenyl)-4-chlorine pyrazoles

(seeing the embodiment 14 of patent application WO93/22287)

3-(2-amino-3,5-dichloro) phenyl-4-chlorine pyrazoles (compound 19)

The solution that 3-(2-nitro-3,5-dichlorophenyl)-4-chlorine pyrazoles that 14.6g (0.05mol) embodiment 12b is made is dissolved in the 200ml acetate adds in the 500ml three neck round-bottomed flasks.This solution is warmed to 50 ℃, adds 8.4g (0.15mol) iron powder in batches.Subsequently reaction medium was stirred 5 hours at 70 ℃.After the cooling, reaction medium is poured in the 800ml water, is filtered it, wash with water and dry through sintered glass, obtain 3-(2-amino-3,5-dichlorophenyl)-4-chlorine pyrazoles white solid (output: 90%, fusing point: 300 ℃ of decomposition).

Use identical step, as raw material, can make following formula 4-chlorine pyrazole derivatives (in being listed in the table below) with the 4-chlorine pyrazoles of suitable replacement, wherein the substituting group of Yin Ruing indicates asterisk.

Compound	??X 1，X 2，X 3，X 4，X 5	??Y	Output (%)	Fusing point (℃) or analyze
					????20	??NH 2，Cl，F，Cl，H	??Cl	????68	?????160
????21	??NH 2，Br，H，Br，H	??Cl	????47	?????169
					????22	??Cl，Cl，H，NH 2，H	??Cl	????69	?????150
????23	??F，Cl，H，NH 2，H	??Cl	????90	?????145
					????24	??F，Br，H，NH 2，H	??Cl	????75	?????155
????57	??NH 2，Cl，H，Cl，F	??Cl	????85	?????150
					????58	??NO 2，Cl，H，NH 2，H	??Cl	????26	?????198

Embodiment 11:4-chlorine pyrazoles

(seeing the embodiment 15 of patent application WO93/22287)

3-(2-methyl mercapto-3,5-dichlorophenyl)-4-chlorine pyrazoles (compound 25)

This compound can make by the diazotising of 3-(2-amino-3,5-dichlorophenyl)-4-chlorine pyrazoles and with Methyl disulfide (dimethyl disulphide) reaction: output 30% according to the method for describing in the document; Pulpous state.

With the diazol of suitable replacement be raw material and with suitable reaction reagent reaction, can make following formula 3-phenyl-4-chlorine or bromine pyrazoles (in being listed in the table below), wherein the group of Yin Ruing has asterisk:

Compound	??X 1，X 2，X 3，X 4，X 5	????Y	Output (%)	Fusing point (℃) or analyze
					????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, methyl H, Cl *，H	????Cl	????57	?????136

Embodiment 12:3-(2-nitrobenzophenone)-4-chlorine pyrazoles

3-(2-nitro-3,5-two chloro-4-fluorophenyls)-4-chlorine pyrazoles (compound 30)

0.43ml (0.0104mol) (100%) nitric acid of being fuming is splashed into 2.50g (0.00943mol) 3-(3,5-two chloro-4-fluorophenyls)-solution of 4-chlorine pyrazoles (making compound 266 according to the method for describing among the patent application WO93/22287) in 25ml 100% sulfuric acid in simultaneously with temperature cooling at about 5 ℃ (ice-water baths).Under the state of cooling, reaction medium stirred 20 minutes subsequently stirring at room 1 hour, then with its to 150g on ice.The precipitation 150ml ethyl acetate extraction that forms.The solution that obtains is used 100ml water, 100ml saturated solution of sodium bicarbonate and 100ml water washing successively, dried over mgso and evaporation in a vacuum.Obtain 2.78g3-(2-nitro-3,5-two chloro-4-fluorophenyls)-4-chlorine pyrazoles white solid, 196.4 ℃ of (output: 95%) of fusing point.

Using identical step, is raw material with the 4-chlorine pyrazoles of suitable replacement, can make following formula 3-(2-nitrobenzophenone)-4-chlorine pyrazole derivatives (in being listed in the table below):

Compound	X 1，X 2，X 3，X 4，X 5	?????Y	Output (%)	Fusing point (℃) or analyze
					????31	NO 2，Br，H，Br，H	?????Cl	????25	????196
????32	NO 2，Br，F，Br，H	?????Cl	????73	????221
					????33	NO 2, methyl, F, Cl, H	????Cl	????19	????214
????34	NO 2, Cl, F, methyl, H	????Cl	????20	????205
					????61	NO 2, methyl, H, Br, H	????Cl	????13	????184

Embodiment 13:3-(5-fluorophenyl)-4-chlorine pyrazoles

3-(2,3-two chloro-5-fluorophenyls)-4-chlorine pyrazoles (compound 35)

At 0 ℃ natrium nitrosum (0.0021mol) aqueous solution splashed into and to contain 0.002mol 3-(5-amino-2, the 3-dichlorophenyl)-solution of 4-chlorine pyrazoles and 5ml 50% tetrafluoroborate solution, make the diazonium tetrafluoroborate of 3-(5-amino-2,3-dichlorophenyl)-4-chlorine pyrazoles.Reaction medium was poured in 50ml water and the ice 0 ℃ of stirring in 1 hour subsequently.The precipitation that obtains rapid draing in a vacuum, then at 145 ℃ in the drying regime thermolysis.After the cooling, reaction medium is dissolved in the carrene, and uses the silica gel chromatograph purifying, with ethyl acetate/heptane (25: 75) as wash-out mixed liquor (output: 19%, 122 ℃ of fusing points).

Using identical step, is raw material with the 4-chlorine pyrazoles of suitable replacement, can make 3-(3-chloro-2,5-difluorophenyl)-4-chlorine pyrazoles (compound 36, output: 17%, 150 ℃ of fusing points).Embodiment 14:3-(3-chloro-5-hydroxy phenyl)-4-chlorine pyrazoles (with reference to derivative A)

In the 1000ml three-neck flask, 49.5g (2mol) 4-chloro-3-(3, the 5-dichlorophenyl) pyrazoles (method of describing as embodiment among the patent application WO93/22287 9 makes) is added among the 500ml NMP (N-Methyl pyrrolidone).Add 43.2g (0.8mol) sodium methoxide and with mixture 140 ℃ of heating 50 hours.After the cooling, reactant mixture is poured in the 500ml water, acidifying and with ethyl acetate extraction it.Behind the dry and vacuum concentration of organic facies, with silica gel column chromatography (eluent: heptane/ethyl acetate: 60: 40) purifying it.Obtain 28g (0.12mol; Output 61%; 222 ℃ of fusing points) 4-chloro-3-(3-chloro-5-hydroxy phenyl) pyrazoles.Embodiment 15:3-(3-chloro-5-fluorophenyl)-4-chlorine pyrazoles (compound 37)

0 ℃ in the 500ml three-neck flask, 17.4g (0.075mol) 4-chloro-3-(3-amino-5-chlorphenyl) pyrazoles (method of describing as the embodiment 14 of patent application WO93/22287 makes) is added in 150ml (1.20mol) fluoboric acid (50% the aqueous solution).The solution that Dropwise 5 .7g (0.826mol) natrium nitrosum is dissolved in the 10ml water is controlled at temperature 0-5 ℃ simultaneously.Room temperature continuous stirring 1 hour.Also water and pentane wash it successively to leach the solid that obtains through sintered glass.After the drying, this solid is decomposed at 150 ℃ produce brown oil, this oil is dissolved in the isopropyl alcohol.Through silica gel column chromatography (eluent: heptane/ethyl acetate 70: 30) behind the purifying, obtain 7.9g (0.0342mol; Output: 45.6%; Fusing point: 150 ℃) 4-chloro-3-(3-chloro-5-fluorophenyl) pyrazoles.The pyrazoles that embodiment 16:N-replaces

(the embodiment 19D of patent application WO93/22287)

1-acetoxy-methyl-4-chloro-3-(3, the 5-dichlorophenyl) pyrazoles (compound 38)

With 0.15ml1,8-diazabicylo [5.4.0] endecatylene-7 adds in 2.55g (0.01mol) 4-chloro-3-(3, the 5-dichlorophenyl)-pyrazoles and the solution of 0.90g (0.030mol) paraformaldehyde in 70mlTHF in room temperature.In room temperature reactant mixture was stirred 4 hours.Drip the solution of 1.20g (0.015mol) chloroacetic chloride in 10mlTHF at 0 ℃, and room temperature continuous stirring 6 hours.Reaction medium is concentrated into dried.Residue is dissolved in subsequent drying in the 15ml heptane.Obtain 3.05g1-acetoxy-methyl-4-chloro-3-(3, the 5-dichlorophenyl) pyrazoles, 95 ℃ of fusing points.

Using identical step, is the common derivative (coderivatives) that raw material can make following formula I with the 1H-4-chlorine pyrazoles that replaces.

Compound	X 1，X 2，X 3，X 4，X 5	??Y	????Z	Output (%)	Fusing point (℃) or analyze
						????39	NO 2，Cl，F，Cl，H	??Cl	?CH 2OAc	????97	????100
????40	F，Cl，H，Cl，H	??Cl	?CH 2OAc	????95	????90

Embodiment 17:4-chloro-3-(5-chloro-3-cyano group-2-fluorophenyl) pyrazoles (compound 62)

With 3-(3-bromo-5-chloro-2-fluorophenyl)-4-chlorine pyrazoles (0.45g; 0.0014mol) and copper cyanider (0.14g; 0.0015mol) be dissolved in dimethyl formamide (DMF, 10ml) in, with mixture 180 ℃ the heating 8 hours.After being cooled to room temperature, pour mixture into 14%NH ₄In the OH solution (50ml), use ethyl acetate (2 * 50ml) extractions, dried over mgso and evaporation in a vacuum subsequently.This oily residue of purifying on a dried silica column (with the eluant solution of 30% ethyl acetate in heptane) obtains 0.1g yellow solid (output: 28%; Fusing point: 128 ℃).Embodiment 18:4-chloro-1-(4-Methyl benzenesulfonyl) pyrazoles (compound 63)

At 10 ℃ with pyrazoles (34g; 0.5mol) be dissolved in the carrene (350ml), drip sulfonic acid chloride (77.6g; 0.575mol) solution in carrene (150ml).After reinforced the finishing, mixture was added hot reflux 18 hours.Remove carrene subsequently in a vacuum, residue is suspended in the pyridine (200ml), adds paratoluensulfonyl chloride (95.33g in batches; 0.5mol).Then this mixture is added hot reflux, be cooled to room temperature.This mixture is cooled off the powerful Bian Jiajia water (800ml) that stirs in limit in ice bath.There is solid to form after 1 hour, filters collection, wash with water and in ethanol, be recrystallized, obtain 102g white powder 4-chloro-1-(4-Methyl benzenesulfonyl) pyrazoles (output: 80%; Fusing point 96-97 ℃).Embodiment 19:4-chloro-5-(3-fluorophenyl)-1-(4-Methyl benzenesulfonyl) pyrazoles (compound 64)

In argon atmospher, 2.4g (0.0093mol) 4-chloro-1-(Methyl benzenesulfonyl) pyrazoles is dissolved in oxolane (THF) (20ml) in and be cooled to-78 ℃.In 10 minutes, drip the 2.5M n-BuLi (3.92ml, 0.0098mol) and at-78 ℃ with this mixture continuous stirring 1.25 hours.In 10 minutes, drip the solution (10ml of zinc chloride in THF; 0.01mol).At-78 ℃ with this mixture continuous stirring 0.5 hour, subsequently stirring at room 2 hours.Then add four (triphenyl phasphine) palladium (Pd (PPh ₃) ₄) (0.35g; 0.0003mol) and 3-fluorine iodobenzene (1.4g; 0.0062mol) solution in 15mlTHF.Then this mixture was refluxed 18 hours, be cooled to room temperature, with EDTA solution (50ml) dilution, then with ether (3 * 50ml) extractions.Organic extract liquid washes with water, and dried over mgso is filtered and evaporation, obtains yellow oil (4.1g).Purifying on dried silica column (eluant solution of 10% ethyl acetate in heptane) obtains 1.05g4-chloro-5-(3-fluorophenyl)-1-(4-Methyl benzenesulfonyl) pyrazoles (output: 48%; Fusing point: 110-111 ℃).

Using above-mentioned steps, is raw material with 4-chloro-1-(Methyl benzenesulfonyl) pyrazoles and suitable reaction reagent, can make following formula and be listed in the table below in compound:

Compound	????R	Output (%)	Fusing point (℃)
				????65	Benzo [b] thiophene-4-base	????56	????133
????66	2-methoxycarbonyl group benzo [b] thiophene-4-base	????69	????170
				????67	Benzo [b] furans-4-base	????67	????102

Can make suitable intermediate according to the following step:

(a) 2-methoxycarbonyl group (carbomethoxy)-4-iodobenzene [b] thiophene also:

In room temperature and argon atmospher, 30.0g (0.012mol) 2-fluoro-6-benzaldehyde iodine is dissolved in the dry methyl-sulfoxide (150ml).In 1 minute, drip 14.05g (0.0119mol) methyl thioglycolate and 25.85g (0.255mol) triethylamine.Mixture is cooled to room temperature 60 ℃ of heating 2 hours, is poured into while stirring in the mixture (1000ml) of water and ice.The filtered and recycled yellow mercury oxide, air drying, and it is suspended in the 300ml methyl alcohol, added hot reflux then 10 minutes.Solution is cooled to 0 ℃, and filtered and recycled precipitation and drying in a vacuum obtain also [b] thiophene (output: 79% of the solid-state 2-methoxycarbonyl group of 30.2g cream color-4-iodobenzene; Fusing point: 123-124 ℃).

(b) 2-methoxycarbonyl group-4-iodobenzene [b] furans also:

In argon atmospher, 4.36g (0.0109mol) sodium hydride (60% suspension in oil) is suspended in the 100ml oxolane.Use ice-water bath that this suspension is cooled to 5-10 ℃.In 30 minutes, drip the solution of 10.3g (0.115mol) methyl thioglycolate in 50mlTHF.In this temperature mixture was stirred 5 minutes.In 30 minutes, drip the solution of 21g (0.084mol) 2-fluoro-6-benzaldehyde iodine in 50mlTHF.The temperature of medium is increased to 40 ℃ naturally.Room temperature continuous stirring 1 hour,, under reduced pressure concentrate it subsequently with 2ml methyl alcohol and this medium of 50ml water treatment.Solid residue washes with water, grinds and drying under reduced pressure with methyl alcohol under the state of cooling, obtains 11.3g white solid (output: 45%; Fusing point: 141-143 ℃).

(c) 2-carboxyl-4-iodobenzene [b] thiophene also:

10M sodium hydrate aqueous solution (5.8ml) is added to 17.0g (0.053mol) 2-methoxycarbonyl group-4-iodobenzene also in the mixture of [b] thiophene in 150ml ethanol, the mixture that obtains is added hot reflux under reduced pressure be concentrated into dried subsequently in 1 hour.Residue is dissolved in the water (300ml) and with ethyl acetate (100ml) and washs.Hydrochloric acid with 36% with aqueous phase as acidified to pH be 1.Filtered and recycled precipitation, water and diisopropyl ether washing successively, dry under 70 ℃ and decompression subsequently, obtain 15.0g white solid (output: 93%; Fusing point: 260 ℃).

(d) 4-iodobenzene [b] thiophene also:

The copper chromite that 4.3g is applied barium is suspended in the 70ml quinoline and with the mixture that obtains and is heated to 200 ℃.Add also [b] thiophene of 13.0g (0.043mol) 2-carboxyl-4-iodobenzene in batches.Stop to discharge (about 15 minutes) behind the gas, the temperature of medium is reduced to room temperature, and be poured in the mixture of 36%HCl (100ml)-ice, and through diatomite filtration.Water (200ml) and ethyl acetate (100ml) wash diatomite successively.(dried over mgso also under reduced pressure concentrates, and obtains the 11.65g brown oil for 2 * 150ml) extraction filtrates, water (400ml) washing to use ethyl acetate again.Purifying it (with pure heptane wash-out) obtains 9.6g yellow solid (output: 86% on silica column; Fusing point: 37-39 ℃).Embodiment 20:4-chloro-3-(benzo [b] thiophene-4-yl) pyrazoles (compound 68)

With 5-(benzo [b] thiophene-4-yl)-4-chloro-1-(4-Methyl benzenesulfonyl) pyrazoles (3.3g; 0.00844mol) be dissolved among the DMF (25ml), subsequently this mixture was heated 18 hours at 110 ℃.After being cooled to room temperature, while stirring mixture is poured in the ice, generated the oily product.(2 * 50ml) extractions, (3 * 100ml) washings are also dry for water with ethyl acetate for this product.Purifying on dried silica column (eluant solution of 20% ethyl acetate in heptane) obtains 1.4g yellow solid (output: 70% after the grinding; Fusing point: 123 ℃).

Using said method, is raw material with suitable reaction reagent, can make 4-chloro-3-(benzo [b] furans-4-yl) pyrazoles (output: 64%; Fusing point: 122 ℃) (compound 69).Embodiment 21 (metallization): 4-chloro-3-(5-chloro-2-fluoro-3-thiophenyl phenyl) pyrazoles (compound 70)

In argon atmospher with 3-(3-bromo-5-chloro-2-fluorophenyl) pyrazoles (1.10g; 0.0035mol) be dissolved in oxolane (THF, 20ml) in and be cooled to-78 ℃.In 10 minutes, drip 1.6M n-BuLi (5.5ml; 0.088mol) and at-78 ℃ with mixture continuous stirring 0.5 hour.Drip diphenyl two sulphur (1.53g; 0.007mol) being dissolved in the solution among the THF (10ml), the mixture that obtains is placed to second day in room temperature subsequently-78 ℃ of continuous stirring 1 hour.Then add 100ml water.With the mixture that 2 * 50ml ethyl acetate extraction obtains, dried over mgso is also evaporated in a vacuum, obtains the residue of oily.Purifying on dried silica column (with the eluant solution of 30% ethyl acetate in heptane) obtains 0.45g4-chloro-3-(5-chloro-2-fluoro-3-thiophenyl phenyl) pyrazoles (38%; ¹H﹠amp; ¹³C NMR).

Using above-mentioned steps, is raw material with 4-chloro-3-(3-bromo-5-chloro-2-fluorophenyl) pyrazoles and suitable reaction reagent, the compound in can making following formula and being listed in the table below, and wherein the substituting group of Yin Ruing indicates asterisk:

Compound	X 1，X 2，X 3，X 4，X 5	??Y	Output (%)	Fusing point (℃)
					???71	F，CO 2H *，H，Cl，H	??Cl	????37	????184
???72	F，CHO *，H，Cl，H	??Cl	????26	????NMR
					???73	F，CO 2Et *，H，Cl，H	??Cl	????51	????100

The metal complex (compound 74) of embodiment 22:4-chloro-3-(3, the 5-dichlorophenyl) pyrazoles and copper chloride

With copper chloride dihydrate (1.70g; 0.01mol) be dissolved in the absolute ethyl alcohol (10ml), add triethyl orthoformate (1ml).With mixture continuous stirring 0.5 hour, add 4-chloro-3-(3, the 5-dichlorophenyl) pyrazoles (4.95g in room temperature; 0.02mol) be dissolved in the solution in the absolute ethyl alcohol (10ml).In room temperature with the mixture continuous stirring 0.5 hour that obtains and be placed to second day.Filter collecting precipitation,, obtain 11.8g light green color solid (output: quantitatively with the also drying under reduced pressure of ether washing; Fusing point: 288 ℃ (decomposition)).

Using above-mentioned steps, is raw material with suitable pyrazoles and slaine, can quantitative output make formula I--L ^-M ⁺--I and be listed in the table below in compound:

Compound	X 1，X 2，X 3，X 4，X 5	??M +	??L-	Color	Fusing point (℃)
						??75	H，Cl，H，Cl，H	??Cu	??Br	Light green color	264 (decomposition)
??76	H，Cl，H，Cl，H	??Cu	??NO 3	Blue	190 (decomposition)
						??77	H，Cl，H，Cl，H	??Zn	??Cl	White	195 (decomposition)
??78	H，Cl，H，Cl，H	??Zn	??AcO	White	??＞300
						??79	H，Cl，H，Cl，H	??Ni	??Cl	Cream-colored	??＞300
??80	NO 2，Cl，F，Cl，H	??Cu	??Cl	Blue	255 (decomposition)
						??81	F，Cl，H，Cl，H	??Cu	??Cl	Green	287 (decomposition)

Also tested other formula I compound and from european patent application 0,538, the compound of learning in 156:

Compound 82:4-chloro-3-(2 ', 2 '-two fluoro-, 1 ', 3 '-benzodioxole base) pyrazoles (european patent application 0,538,156 compound 25);

Compound 83:4-chloro-3-(2, the 3-dichlorophenyl) pyrazoles (european patent application 0,538,156 compound 12);

Compound 84:4-chloro-3-(2-nitro-3 chlorphenyl) pyrazoles (european patent application 0,538,156 compound 120).

The invention still further relates to the processing method of the crops plant that suffers or suffer easily fungal disease, formula I compound or its salt, metal complex or the N-oxide that it is characterized in that effective dose is to be applied on the propagating materialss of these plants.Effective dose is interpreted as being meant is enough to control or kill the dosage that is present in the fungi on these plants.But this dosage can change with weather conditions and according to the different of compound of using within a large range according to the fungi of desire control, the type of crop.

In practice, the application dosage of compound is preferably per 100 kilograms of seeds and uses the 0.1-500g active substance, is preferably/100 kilograms of 1-400 grams.

Fungal disease is meant by fungi, the particularly fungus-caused disease of those Oomycetes, Ascomycetes and Basidiomycetes that plant is caused a disease.

Can use The compounds of this invention to carry out in the crop of antifungal processing rice, cereal, particularly wheat and barley and leguminous plant being arranged.Rice is to use The compounds of this invention to carry out the crop that antifungal is handled preferably.Embodiment 23: (in vivo) formula is tested in the body of seed disinfection

According to the difference that is the seed (the Drechslera graminea/Drechslera teres of barley) or artificial infection's the seed (standing grain revolves mould (Cochliobolus the sativus)/machete sickle of spore spore (Fusarium culmorum)/snow mold sickle spore (Fusarium nivale)/clever withered septoria musiva (Septoria nodorum)) of natural infection, use two kinds of methods:

In the HEGE cup, use active substance of the present invention, to contain the form of aqueous suspension concentrate, handle the 30g seed with 1.5 liters/100 kilograms concentration.With the 30g planting seed basin (on peat in 7 * 7 * 8cm)/volcanic ash matrix, planting seed 3 basins of every kind of processing.Sow under the same conditions that a basin infects and control group (under artificial infection's situation) that a undressed control group and a basin do not infect.

Under artificial infection's situation, sow treated healthy seed and use the suspension (every basin 10ml aqueous suspension) of roe deer (spore).

The concentration of this suspension is different with the difference of the pathogen of being studied:

Pathogen	Crop	Spore count
			It is mould that standing grain revolves spore	Barley	????200,000
Machete sickle spore/snow mold sickle spore	Wheat, barley	????400,000
			The withered septoria musiva of grain husk	Wheat	????250,000

Place the controlled environment case under 5 ℃ and saturated relative moisture, to place a period of time in each basin, this time is depended on the test of being carried out, promptly revolving spore mould to Drechslera graminea/Drechslera teres and standing grain was 3 weeks, was 2 weeks to machete sickle spore/snow mold sickle spore/clever withered septoria musiva.

Subsequently each basin is moved into 10 ℃ of (periodicity of illuminations: 8 hour daytime; 16 hour night), the controlled environment case of 80% relative moisture is interior until demonstrating symptom.

Control group range estimation untreated with infection relatively marked.

Under these conditions, under the dosage of 100g/100kg, can be observed good prophylaxis effect (at least 75% or whole):

～to Drechslera graminea: use following derivative: 3,4,5,7,10,18,26,30,68,69;

～to Drechslera teres: use following derivative: 3,26,30,82,83,84;

～that standing grain is revolved spore is mould: use following derivative: 3,26,30;

～to machete sickle spore: use following derivative: 3,26,30,82,83,84;

～to snow mold sickle spore: use following derivative: 1,3,4,7,8,9,12,20,26,27,28,30,37,82,83,84;

～to the withered septoria musiva of grain husk: use following derivative: 3,26,30,82,83,84.

The invention still further relates to the processing method of the crops plant that suffers or suffer easily fungal disease, the noval chemical compound that it is characterized in that the above-mentioned formula I of effective dose is the acrial part that is applied to these plants.Effective dose is interpreted as being meant is enough to control or kill the dosage that is present in fungi on these plants.But this dosage can change with weather conditions and according to the different of compound of using within a large range according to the fungi of desire control, the type of crop.

In practice, the application dosage of compound is preferably 0.002-5kg/ha, is preferably 0.005-1kg/ha.

Fungal disease is meant by fungi, the particularly fungus-caused disease of those Oomycetes, Ascomycetes and Basidiomycetes that plant is caused a disease.

Can use The compounds of this invention to carry out in the crop of antifungal processing rice, cereal, particularly wheat and barley and leguminous plant being arranged.Rice is to use The compounds of this invention to carry out the crop that antifungal is handled preferably.Embodiment 24: on the tomato blade of cutting off to the in vivo studies (to benzimidazole sensitive strain and antibody-resistant bacterium) of gray botrytis (Botrytis cinerea):

Make the aqueous suspension of test active substance with following ingredients through fine gtinding:

～active substance: 60mg

～be diluted with water to 10% Tween 80 surfactants (oleate of the sorbitan derivatives of polyoxyethyleneization): 0.3ml

～mixture adds water to 60ml.

This aqueous suspension of dilute with water is until the active material concentration that obtains requiring subsequently.

By the above-mentioned aqueous suspension that sprays various concentration test compounds the 30 day age tomato of cultivation in greenhouse (Marmande kind) handled.

After 24 hours, cut off blade and place a training Ti Shi culture dish (diameter 14cm), the bottom of this culture dish is lined with the wet filter paper (each culture dish is put 10 vanelets) of a slice circle in advance.

Using syringe to drip (every leaf 3) subsequently (cultivated subsequently with 150,000 units/cm through 15 days the gray botrytis spore benzimidazole sensitivity or resistance ³Ratio suspend) suspension is with the coating culture.

Infecting after 6 days the untreated control group of contrast observes.

Under these conditions; under the dosage of 1g/l following compounds, on Botrytis, observe good (at least 75%) or protective effect completely: 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 to the benzimidazole sensitivity.Embodiment 25: to the in vivo studies of the Pyricularia oryzae of the piriculariosis that causes rice

Make the aqueous suspension of test active substance with following ingredients through fine gtinding:

～active substance: 60mg

～be diluted to 10% Tween 80 surfactants (oleate of the sorbitan derivatives of polyoxyethyleneization): 0.3ml with water

Add water to 60ml in the～mixture.

This aqueous suspension of dilute with water is until the active material concentration that obtains requiring subsequently.

By spraying above-mentioned aqueous suspension the rice in the sowing stage that the 10cm in 50: 50 fertile peat and the volcanic ash is high in basin is handled.

After 24 hours, Pyricularia oryzae spore (was cultivated through 15 days, subsequently with 100,000 units/cm ³Ratio suspend) aqueous suspension be applied on the blade.

This rice crops was placed 24 hours in insulating box (25 ℃, 100% relative moisture), in inspection box, placed 5 days under the same conditions subsequently.

Infect and mark after 6 days.

Under these conditions; under the dosage of the following compounds of 1g/l, can be observed good (at least 75%) or protective effect completely: 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.Embodiment 26: the in vivo studies of grape being given birth to single shaft mould (Plasmopara viticola):

Make the aqueous suspension of test active substance with following ingredients through fine gtinding:

～active substance: 60mg

～be diluted to 10% Tween 80 surfactants (oleate of the sorbitan derivatives of polyoxyethyleneization): 0.3ml with water

～mixture adds water to 60ml.

This aqueous suspension of dilute with water is until the active material concentration that obtains requiring subsequently.

The cutting (Chardonnay kind) of grape (vine, Vitis vinifera) is cultivated in basin.When these plants reach 2 monthly ages (8-10 leaf stage, 10-15cm height), it is sprayed above-mentioned aqueous suspension handle.

With the aqueous solution that does not contain active substance plant is in contrast handled.

After dry 24 hours, each plant species is sprayed grape give birth to single shaft mould (Plasmopara viticola) spore (through cultivation in 7 days, subsequently with 100,000 units/cm ³Ratio suspend) aqueous suspension infect.

Subsequently with the insulation 2 days in about 18 ℃ of atmosphere with saturated humidity of the plant that infects, then in about 20-22 ℃, the relative moisture of 90-100%, be incubated 5 days.

Infecting after 7 days the contrast check plant marks.

Under these conditions; under the dosage of 1g/l following compounds, can be observed good (at least 75%) or protective effect completely: 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.Embodiment 27: to Puccinia recondita (Puccinia recondita) in vivo studies of (or claiming the wheat rust bacterium)

Make the aqueous suspension of test active substance with following ingredients through fine gtinding:

～active substance: 60mg

～be diluted to 10% Tween 80 surfactants (oleate of the sorbitan derivatives of polyoxyethyleneization): 0.3ml with water

～mixture adds water to 60ml, generates the suspension/solution that contains 1g/l.

The active material concentration of this aqueous suspension of dilute with water randomly subsequently to obtain requiring.

With above-mentioned aqueous suspension to the sowing wheat of 10cm high-stage processing of spraying in 50: 50 peat/volcanic ash soil matrix in basin.

With the aqueous solution that does not contain active substance plant is in contrast handled.

After dry 24 hours, with aqueous suspension (100,000 spores/cm of spore ³) be sprayed on the wheat the next plant that oneself infects of this suspension.Subsequently wheat was placed 24 hours in about 20 ℃, the incubator of 100% relative moisture, then in about 60% relative moisture, placed 7-14 days.

Observed to contrasting untreated check plant between the fortnight at the 8th day that infects.

Under these conditions; under the dosage of 1g/l following compounds, can be observed good (at least 75%) or protective effect completely: 1,2,3,4,5,6,7,8,9,10,12,13,20,21,26,27,28,30,31,32,33,35,37,40.

Theme of the present invention also comprises the composition as fungicide, it contains (as active substance) one or more above-mentioned formula I compounds, is mixed with in this active substance that agricultural goes up acceptable solid-state or liquid carrier and is that agricultural goes up acceptable surfactant equally.Can use the inert carrier of standard and the surfactant of standard especially.

These compositions also can contain the composition of any other type, as protecting colloid, adhesive, thickener, thixotropic agent, bleeding agent, stabilizing agent, chelating agent etc.Usually, the composition that uses of the present invention all solid-state or liquid additives that can be adopted with the conventional formulation technology mix mutually.

Generally speaking, the present composition often contains the 0.05-95% that has an appointment (weight) The compounds of this invention (below be referred to as active substance), one or more solid-state or liquid carrier and one or more optional surfactants.

In this manual, term " carrier " refers to material natural or synthetic, organic or inorganic, and it is in order to simplify to plant, to the use of seed or soil that compound mixes with it.In this this carrier inertia normally, and must be that the plant of particularly desire being handled on the agricultural is acceptable.Carrier can be solid (clay, natural or synthetic silicate, silica, resin, wax, solid fertilizer etc.) or liquid (water, alcohol is butanols etc. particularly).

Surfactant can be ion or nonionic emulsifier, dispersant or wetting agent, perhaps these surfactant mixtures.Phosphate, fatty acid ester and polyalcohol that the polyoxyethyleneization of condensation polymer, substituted phenol (particularly alkyl phenol or aryl phenol), sulfosuccinate ester salt, taurine derivatives (particularly alkyl taurine ester), alcohol or the phenol of polyacrylate, lignosulphonates, hydroxy benzene sulfonic acid or naphthalene sulfonate, oxirane and fatty alcohol, fatty acid or fatty amine is for example arranged that can exemplify and the derivative that contains the above-claimed cpd of sulfuric ester, sulphonic acid ester and phosphate functional group.When compound and/or inert carrier is water insoluble and when the excipient that uses is water, add a kind of surfactant usually at least.

Agriculturally useful compositions of the present invention can contain the active substance of the present invention of wide range (0.05-95% (weight)).The content of surfactant is preferably 5-40% (weight).

These compositions of the present invention itself can be various solid-state or liquid formulations.

With regard to the solid forms of composition; but can exemplify the powder (can contain compound) and the particle of dust formation up to 100%; those solid composites that form by extruding, compression, dipping or powder granulation by the granulating carrier (under these situations of back in the particle content of compound be 0.5-80%) particularly, and tablet comprises effervescent tablet.

But the Powdered use that formula I compound also can dust formation; Also can use and contain 50g active substance and the talcous composition of 950g; Also can use the silica and the talcous composition of 970g that contain 20g active substance, 10g pulverizing; These compositions are mixed and grinding, use this mixture by dusting.

To make with regard to the liquid form of composition or when using with regard to the form of fluid composition, can exemplify solution, particularly water-soluble concentrate, emulsible concentrate, emulsion, suspending concentrate, aerosol, wetting powder (or the pulvis that is used to spray), paste and gel.

But emulsification or solubility concentrate the active substance that thing often contains 10-80%, and emulsion or the solution of preparing to use contains the active substance of (by its umber) 0.001-20%.

If necessary, outside desolventizing, emulsible concentrate can contain the above-mentioned suitable additive of 2-20%, as stabilizing agent, surfactant, bleeding agent, anticorrosive, colouring agent or adhesive.

The emulsion that is particularly suitable for being applied to any concentration on the crop can obtain by these concentrates of dilute with water.

As embodiment, the composition of following several emulsifiable concentrates: embodiment E C1 is arranged:

～active substance 400g/l

～DBSA alkali metal salt 24g/l

～contain the oxygen of 10 ethylene oxide molecules

The nonyl phenol 16g/l of vinylation

～cyclohexanone 200g/l

～aromatic solvent adds to 11

According to another kind of emulsifiable concentrate preparation, can use following prescription: embodiment E C2:

～active substance 250g

～epoxidized vegetable oil 25g

～alkylaryl sulfonate and poly-second two

The mixture 100g of alcohol ether and fatty alcohol

～dimethyl formamide 50g

～dimethylbenzene 575g

Preparation also can be sprayed the suspending concentrate of using, with the stable fluid product that obtains can not precipitate, they often contain the suitable additive of 10-75% active substance, 0.5-15% surfactant, 0.1-10% thixotropic agent, 0-10%, as defoamer, anticorrosive, stabilizing agent, bleeding agent and adhesive and as the active substance of carrier only slightly soluble or insoluble water or organic liquid, some solid-state organic substances or mineral salt may be dissolved in the carrier to help prevent precipitation or anti-sealing to freeze.

As embodiment, the composition of following suspending concentrate is arranged: embodiment SC1:

～active substance 500g

The tricresyl phosphate styryl phenol ester 50g of～polyethoxylated

The alkyl phenol 50g of～polyethoxylated

～polycarboxylic acids sodium 20g

～ethylene glycol 50g

～organopolysiloxane oil (defoamer) 1g

～polysaccharide 1.5g

～water 316.5g

Normal preparation wettable powder (or the powder that is used to spray) makes it to contain the 20-95% active substance, except solid-state carrier, they often contain the wetting agent of 0-30%, the dispersant of 3-20%, also can add one or more stabilizing agents and/or other additive such as bleeding agent, adhesive or anticaking agent, the colouring agent etc. of 0.1-10% if necessary.

For powder or the wettable powder that preparation is used to spray, in suitable blender, active substance is mixed up hill and dale with additive, and use grinder or suitable cracker milled mixtures.Thereby obtain the powder that is used to spray, wettable and can to suspend be its advantage; They can any requirement concentration be suspended in the water, can use this suspension easily, particularly be applied on the blade of plant.

Can prepare paste and replace wettable powder.Preparation and use the condition of this paste and step similar in appearance to the conditioned disjunction step of the powder that is used for wettable powder or is used to spray.

As embodiment, the composition of following various wettable powder (or the powder that is used to spray) is arranged: embodiment WP1:

～active substance 50%

The fatty alcohol of～ethoxylation

(wetting agent) 2.5%

The phenylethyl phenol of～ethoxylation

(dispersant) 5%

～chalk (inert carrier) 42.5% embodiment WP2:

～active substance 10%

～synthetic with 8-10 ethylene oxide unit

The branched chain type C13 oxo alcohol (wetting agent) 0.75% of ethoxylation

～neutral Lignosite (dispersant) 12%

～calcium carbonate (inert filler) adds to 100% embodiment WP3:

This wettable powder contains the composition identical with top embodiment, and its ratio is as follows:

～active substance 75%

～wetting agent 1.50%

～dispersant 8%

～calcium carbonate (inert filler) adds to 100% embodiment WP4:

～active substance 90%

The fatty alcohol of～ethoxylation (wetting agent) 4%

Phenylethyl phenol (dispersant) the 6% embodiment WP5 of～ethoxylation:

～active substance 50%

The mixture of～anionic and nonionic surface active agent

(wetting agent) 2.5%

～sodium lignosulfonate (dispersant) 5%

～kaolin (inert carrier) 42.5%

Aqueous dispersion and emulsion (as the composition that makes by dilute with water wettable powder of the present invention or emulsible concentrate) are included within the total size of the present invention.Emulsion can be Water-In-Oil or oil-in-water type, and they can resemble and have thick denseness " mayonnaise ".

Compound of the present invention can be made into the water-dispersible granule form, and this preparation is also included within the scope of the present invention.

The apparent density Chang Weiyue 0.3-0.6 of these dispersibility particles, particle diameter often is about 150-2000, is preferably the 300-1500 micron.

At the activity substance content Chang Weiyue of these particles 1-90%, be preferably 25-90%.

Other composition of particle comprises that mainly solid-state filler and the optional particle of giving are with surfactant dispersed in the water.These particles can mainly be divided into two types, depend on the water-soluble or water-insoluble of selected filler.When the filler tool was water-soluble, it can be inorganic, or preferably organic.Use urea to obtain good result.Under the situation of water-insoluble filler, this filler is preferably inorganic, for example kaolin or bentonite.Preferably contain surfactant (accounting for the 2-20% of particle weight) this moment, the over half of this surfactant mainly is made up of for example at least a anionic dispersing agent (as poly-naphthalene sulfonic acids alkali metal or alkali salt or lignosulphonic acid alkali metal or alkali salt) institute, and remaining is made up of nonionic or anionic wetting agent (as alkyl naphthalene sulfonic acid alkali metal or alkali salt).

In addition, although be not absolutely necessary, also can add other auxiliary agent, as defoamer.

By mixing essential composition, can make particle of the present invention according to several technology granulations known per se (ball nodulizer, fluid bed, sprayer, extruding etc.) subsequently.Preparation process is often to pulverize, to sieve with the particle diameter of selecting in the above-mentioned scope subsequently and to come to an end.Can also use the particle that as above makes, flood it with the composition that contains active substance subsequently.

The step of describing among the embodiment below preferably using makes particle embodiment DG1 by extruding: dispersible granules

The urea that in a blender, mixes globular 90% (weight) active substance and 10%.In toothed roll crusher, grind this mixture subsequently.With the moistening powder that obtains of the water of about 8% (weight).This moistening powder of extruding on the flow roll extruder.The particle that drying obtains is pulverized subsequently and is sieved to keep the particle of 150-2000 micron grain size respectively.Embodiment DG2: dispersible granules

In blender, mix following ingredients:

～active substance 75%

～wetting agent (Negel) 2%

～dispersant (poly-sodium naphthalene sulfonate) 8%

～water-soluble inert filler (kaolin) 15%

In the presence of water in fluid bed with mixture pelleting, subsequent drying, pulverize and sieve to obtain 0.15～0.80mm size particles.

These particles can use or be used for the aqueous solution or the dosage of water dispersant to obtain to require separately.They also can make compound with other composition (particularly fungicide, active substance), and active component can be wettable powder, particle or aqueous suspension.

With regard to the composition that is suitable for storing and transporting, it preferably contains 0.5-95% (weight) active substance.

Claims (15)

1. be used for treatment of plant propagation material to prevent the composition of fungal disease, it is characterized in that it contains the active component of the 3-phenylpyrazole derivatives of a kind of formula I at least:

Wherein: X ₁, X ₂, X ₃, X ₄And X ₅Can be identical or different, for:

～hydrogen or halogen atom, hydroxyl, sulfydryl, cyano group, thiocyano, nitro or nitroso, the perhaps amino that at random replaces by one or two alkyl or phenyl,

～alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkane sulfonyl; alkylthio alkyl, alkyl sulphinyl alkyl, alkyl sulphonyl alkyl, benzyl, alkenyl; alkynyl, cyano group alkyl, alkoxyl, alkene oxygen base; alkylthio group, alkyl sulphinyl, formoxyl, acetyl group; alkyl or alkoxyl (sulfo-) carbonyl, one or dialkyl amido (sulfo-) carbonyl, amino (sulfo-) carbonyl, one or ammonia diaryl base (sulfo-) carbonyl; carboxyl, carboxylate group, carbamoyl or benzoyl group

～phenyl, phenoxy group or thiophenyl,

～alkyl, alkoxyl, one or two (alkyl amino) thiophenyl (sulphenyl) or sulfinyl or sulfonyl,

～sulfo group, its salt, ester and the acid amides of deriving,

～be selected from alkyl by two, alkoxyl, alkylthio group and dialkyl amido, benzyloxy, the phosphoryl that phenoxy group or phenyl groups replace,

～trialkyl or alkyl phenyl silicyl,

Two adjacent X ₁, X ₂, X ₃, X ₄And X ₅Group can also form the bridge with 2-4 chain member, and wherein at least one chain member is replaced by oxygen, sulphur or nitrogen-atoms, and this bridge can contain one or more following atoms or group: i.e. C, O, S, N, C=O, C=S, SO, SO ₂, CH=CH, the carbon atom on this bridge can be by at least one halogen atom and/or at least one hydroxyl, amino; alkyl, alkoxyl, alkylthio group, one or dialkyl amido; alkyl sulphinyl or sulfonyl, alkoxy carbonyl replaces or is not substituted, and moieties wherein is defined as follows

Its condition is X ₁-X ₅Can not be hydrogen atom simultaneously;

Y is hydrogen or halogen atom, or nitro, cyano group, hydroxyl, alkyl-carbonyl oxygen base, alkoxy-carbonyl oxy, amino carbonyl oxygen base, sulfydryl, carboxyl, carboxylate group, formoxyl, alkyl (sulfo-) carbonyl, aryl carbonyl, alkoxyl (sulfo-) carbonyl, carbamoyl, aminoalkyl, thiocyano or alkyl, alkenyl, alkynyl, alkoxyl or alkylthio group, alkyl sulphinyl or sulfonyl (moieties of these groups is list or many halogenations at random) they at random are the amino that one or two alkyl or phenyl replaced; Phenyl, phenoxy group, thiophenyl, aryl sulfonyl kia or sulfonyl,

Y and X ₁Or X ₅Can also form the bridge with 1-3 chain member, this bridge can contain one or more following atoms or group: i.e. C, O, S, N, C=O, C=S, SO, SO ₂, CH=CH, the carbon atom on this bridge can be by at least one halogen atom and/or at least one hydroxyl, alkoxyl, alkylthio group, one or dialkyl amido, alkyl sulphinyl or sulfonyl replace or are not substituted, and moieties wherein is defined as follows,

Z is:

～hydrogen or halogen atom, or cyano group, nitro or hydroxyl, perhaps

～alkyl, haloalkyl, hydroxyalkyl, formyloxy alkyl, alkyl or aryl (sulfo-) ketonic oxygen base alkyl, alkoxyl (sulfo-) ketonic oxygen base alkyl, amino (sulfo-) ketonic oxygen base alkyl, one or dialkyl amido (sulfo-) ketonic oxygen base alkyl, cycloalkyl or cycloalkyl-alkyl, cycloalkyl moiety can be replaced by the GR4 group that defines below

～at random by hydroxyl, alkoxyl, alkylthio group, the alkoxyl that alkyl sulphinyl or sulfonyl replaced,

～phenoxy group or thiophenyl, phenyl sulfinyl or sulfonyl,

～at random be the amino that one or two alkyl replaced,

～the alkenyl or the alkynyl that contain 3-7 carbon atom separately and replace arbitrarily,

The phenyl or the Het of～replacement arbitrarily,

～have a formula C (=Z ₁) Z ₂Group, wherein:

-Z ₁Be oxygen, sulphur atom or alkyl amino, alkyl imino or arylamino, aryl imino group,

-Z ₂Be:

Hydrogen or halogen atom, or hydroxyl, sulfydryl, cyano group or amino,

Alkyl, alkoxyl, halogenated alkoxy, alkylthio group,

The alkenyl or the alkynyl that contain 3-7 carbon atom respectively, or alkene oxygen base,

Phenyl, phenylalkyl, phenoxy group, the phenyl alkoxyl,

Het or Het-alkyl,

Phenyl alkenyl or phenyl alkynyl,

Het-alkenyl or Het-alkynyl,

One or dialkyl amido, one or diphenyl amino, perhaps alkyl or aryl sulfuryl amino,

～be selected from alkyl by two, alkoxyl, alkylthio group, dialkyl amido, cycloalkyl or cycloalkyl-alkyl, alkenyl or alkynyl, phenyl, phenylalkyl, the phosphoryl that the group of Het or Het-alkyl at random replaces,

～or S (=Z ₁) (=Z ₃) Z ₂Group, wherein Z ₁And Z ₂With as defined above identical, Z ₃Identical with it but needn't equal Z ₁,

And the tautomerism form of formula Ia, when Z is hydrogen atom or C (=Z ₁) Z ₂Or S (=Z ₁) (=Z ₃) Z ₂The time,

Or their salt, metal complex or N-oxide,

With this understanding, in all above-mentioned implications:

～alkyl, alkenyl and alkynyl are to contain the nearly segment and the halogenation at random (1-8 halogen atom) of 7 carbon atoms,

～cycloalkyl contains 3-7 carbon atom, and is at random replaced by at least one substituting group that is selected from the GR4 group that defines below,

～phenyl at random is selected from halogen atom, is had the alkyl of 1-3 carbon atom or the substituting group of alkoxyl and nitro is replaced by 1-5,

～Het is the heterocyclic group that contains one or two rings of 5-10 atom (wherein 1-4 is hetero atom, as oxygen, sulphur, nitrogen and phosphorus);

～GR4 group comprises:

-halogen atom or cyano group, nitro, one or dialkyl amido,

-alkyl; alkoxyl; alkylthio group (sulphenyl), alkyl sulphonyl, alkyl-carbonyl; the alkylthio group carbonyl; alkoxy carbonyl, alkoxyl thiocarbonyl, one or dialkyl amino carbonyl; perhaps one or the dialkyl amido thiocarbonyl, one or dialkyl amino sulfonyl (alkyl group and contain 1-4 carbon atom and at random be 1-9 the segment that halogen atom replaced).

2. composition as claimed in claim 1 is characterized in that in formula I Y is the chlorine or bromine atom.

3. as any one described composition in claim 1 and 2, it is characterized in that in formula I that Z is hydrogen atom or C (=Z ₁) Z ₂Group, wherein Z ₁Be oxygen or sulphur atom.

4. as any one described composition among the claim 1-3, it is characterized in that in formula I X ₁, X ₂And X ₄Be hydrogen or halogen atom, the amino or optional haloalkyl of nitro with 1-4 carbon atom.

5. as any one described composition among the claim 1-3, it is characterized in that in formula I X ₃Be hydrogen or fluorine atom.

6. as any one described composition among the claim 1-3, it is characterized in that in formula I X ₁And/or X ₅It is hydrogen atom.

7. as any one described composition among the claim 1-3, it is characterized in that in formula I two adjacent X that are selected from ₁, X ₂, X ₃, X ₄And X ₅Substituting group form contain 3 or 4 chain members bridge particularly arbitrarily halo and the methylene dioxy Ji Qiao of fluoro preferably.

8. as any one described composition among the claim 1-3, it is characterized in that in formula I X ₁, X ₃And X ₅Be hydrogen atom, X ₂And X ₄It is respectively the chlorine atom.

9. as any one described composition among the claim 1-3, it is characterized in that in formula I X ₁Be nitro, X ₂And X ₄Be respectively the chlorine atom, X ₃Be fluorine atom, X ₅It is hydrogen atom.

10. composition as claimed in claim 7 is characterized in that in formula I X ₁Be fluorine atom, X ₂And X ₄Be respectively the chlorine atom, X ₃Be fluorine atom, X ₃And X ₅It is hydrogen atom.

11. treatment of plant propagation material is resisted the method for disease, it is characterized in that using as propagating materials as described in the 3-phenylpyrazole derivatives of the defined formula I of claim 1 or their salt, metal complex or the N-oxide process.

12. the new 3-phenylpyrazole derivatives of formula I:

Wherein:

Y is the chlorine atom, and Z is a hydrogen atom,

X ₁Be hydrogen or halogen atom or nitro, amino, methyl,

X ₂Be halogen atom or nitro, amino or methyl,

X ₃Be hydrogen or halogen atom,

X ₄Be halogen atom or amino, nitro or methyl,

X ₅Be hydrogen or halogen atom;

Perhaps their salt, metal complex or N-oxide.

13. compound as claimed in claim 12 is characterized in that in formula I,

X ₂It is the chlorine or bromine atom;

X ₃Or X ₅Can be identical or different, be respectively hydrogen or fluorine atom.

14. derivative as claimed in claim 12, it is selected from the derivative that comprises one group of formula I, wherein:

X ₁＝H；X ₂＝CH ₃；X ₃＝F；X ₄＝CH ₃；X ₅＝H；

X ₁＝NO2；??X ₂＝Cl；????X ₃＝F；????X ₄＝Cl；??X ₅＝H；

X ₁＝NH ₂；??X ₂＝Cl；????X ₃＝F；????X ₄＝Cl；??X ₅＝H；

X ₁＝F；????X ₂＝Cl；????X ₃＝F；????X ₄＝Cl；??X ₅＝F；

X ₁＝H；????X ₂＝Cl；????X ₃＝H；????X ₄＝F；???X ₅＝H；

X ₁＝F；????X ₂＝Cl；????X ₃＝H；????X ₄＝Cl；??X ₅＝H；

X ₁＝F；????X ₂＝Br；????X ₃＝H；????X ₄＝Br；??X ₅＝H；

X ₁＝CH ₃；??X ₂＝NO ₂；???X ₃＝H；????X ₄＝F；???X ₅＝H；

X ₁＝F；????X ₂＝Cl；????X ₃＝F；????X ₄＝Cl；??X ₅＝H；

X ₁＝F；????X ₂＝Cl；????X ₃＝H；????X ₁＝F；???X ₂＝Cl；??X ₃＝H；

X ₁＝H；????X ₂＝Cl；????X ₃＝F；????X ₄＝Cl；??X ₅＝H。

15. be used to handle the composition that plant leaf blade is resisted fungal disease, it is characterized in that they contain at least a as active substance as any one described 3-phenylpyrazole derivatives among the claim 11-13, or their salt, metal complex or N-oxide.

16. handle the method that plant leaf blade is resisted fungal disease, it is characterized in that with at least a as any one described 3-phenylpyrazole derivatives or their salt, metal complex or N-oxide process plant among the claim 11-13.