CN1071424A - Pyrazole derivatives and agricultural or horticultural bactericide thereof - Google Patents

Abstract

The present invention relates to pyrazole derivatives and salt, its manufacture method and agricultural or horticultural bactericide thereof with general formula [I] expression.

Description

Pyrazole derivatives and agricultural or horticultural bactericide thereof

The invention relates to new pyrazole derivatives and agricultural or horticultural bactericide thereof.

When the planting agriculture garden crop, for a lot of control medicament of disease and pest use of crop, but because its prevention effect is not good, the appearance of chemical sproof pathogenic bacteria and insect is restricted its use.In addition, in plant, produce poisoning and pollution, or for the strong toxicities of people and animals, fish.Therefore, it is believed that they differ surely satisfies the requirement of control, so shortcoming appears in urgent hope few, safe in utilization medicine.

As the compound of similar The compounds of this invention, open clear 62-404 the spy and putting down in writing following compound with fungicidal activity,

Herein, R ₁, R ₂, R ₃, R ₄, R ₅, R ₆Expression hydrogen atom, low alkyl group, lower alkyl thiazolinyl, R ₂, R ₅Also can be halogen atom, R ₁And R ₂Also can form low-grade alkylidene, R together ₂And R ₃, R ₅And R ₆Also can form Aden's dialkylene.

In addition, put down in writing following compound among the disclosed DE4023488 on January 30th, 1992 with fungicidal activity.

The object of the present invention is to provide and help synthetic, the effective and new compound safe in utilization, that be used for agricultural or horticultural bactericide of industry.

The present invention relates to the sterilant used with the pyrazole derivatives of general formula [I] expression or its salt and agriculture and garden thereof,

Y represents CR ⁶Or N,

R ¹, R ², R ³, R ⁴, R ⁶Identical or inequality, represent alkyl, the alkoxyl group of replacement, the alkene oxygen base of replacement, the alkynyloxy group of replacement, the hydroxyl of hydrogen atom, halogen atom, replacement, in addition, R ¹With R ²Also can form ring together; R ⁵The alkylthio of the alkene oxygen base of the alkyl of expression hydrogen atom, halogen atom, replacement, the alkoxyl group of replacement, replacement, the alkynyloxy group of replacement, hydroxyl, replacement, in addition, R ⁴And R ⁵Also can form ring together;

A represents the aryl that replaces, the heterocyclic radical of replacement,

B represents

In the formula, r ¹, r ², r ³, r ⁴, r ⁵, r ⁶Identical or inequality, represent the alkyl of hydrogen atom, halogen atom, hydroxyl, replacement, the alkoxyl group of replacement or the acyloxy of replacement, in addition, r ¹And r ², r ³And r ⁴Or r ⁵And r ⁶Represent carbonyl together, and then, r ¹-r ⁶And R ⁴Also can form ring together.But Q is

Time marquis, R ¹, R ², R ³, R ⁶Can not all be hydrogen atom.

The method for making of The compounds of this invention is as follows:

(1-1) R ⁵When being hydroxyl,

In the formula, R represents alkyl, Y, R ¹-R ⁴, R ⁶, A, B represent and the aforementioned identical meaning.

(1-2) R ⁴When being hydroxyl,

In the formula, R represents alkyl, Y, R ¹-R ³, R ⁵, R ⁶, A, B represent the meaning as hereinbefore.

(1-1), the reaction of (1-2), normally with formula [II] compound and formula [III] compound or formula [IV] compound and formula [V] compound or its salt, solvent-free, be preferably in the solvent, 0～150 ℃ of temperature of reaction stirred 10 minutes～24 hours and carries out.The example of spendable solvent has alcohols such as ethanol, methyl alcohol; Ethers such as diethyl ether, tetrahydrofuran (THF), diox; Cellosolve such as methylcyclohexane, ethyl cellosolve class; Benzene, toluene etc. are aromatic hydrocarbon based.These solvents can be separately or with various ratio of mixture, uses the mixed solvent more than 2 kinds or 2 kinds.This reaction is not to carry out in the presence of catalyzer, but if add acid or alkali, can promote reaction significantly.Example as acid has organic acids such as formic acid, acetic acid; Mineral acid such as hydrochloric acid, sulfuric acid; Titanium tetrachloride, lewis' acids such as boron trifluoride etc.As the example of alkali organic basess such as mineral alkalis such as sodium hydroxide, potassium hydroxide, sodium ethylate, sodium methylate and pyridine, triethylamine are arranged.

In addition, general formula [III] compound and general formula [IV] compound also can be salt or the hydrate of its HCl, HBr etc.

(2-1) R ⁵When being halogen,

In the formula, Hal represents halogen atom, Y, R ¹-R ⁴, R ⁶, A, B represent the meaning as hereinbefore.

(2-2) R ⁴When being halogen,

In the formula, Hal represents halogen atom, Y, R ¹-R ³, R ⁵, R ⁶, A, B represent the meaning as hereinbefore.

(2-1), the reaction of (2-2) normally makes the normal halogenating agent of 1-10, not necessarily needs solvent, but generally in the presence of solvent, temperature of reaction is under 20～150 ℃, the reaction times is 0.5～24 hour, synthetic halogen derivative.Example as halogenating agent has phosphorous oxychloride, thionyl chloride, phosphorus pentachloride, carbonyl chloride, phosphorus tribromide, protobromide sulfonyl etc.In addition, as solvent, can use halogenated hydrocarbons such as benzene, toluene etc. are aromatic hydrocarbon based, zellon.

(3-1) R ⁵When being hydrogen atom,

Hal represents halogen atom in the formula, Y, R ¹-R ⁴, R ⁶, A, B represent the meaning as hereinbefore.

(3-2) R ⁴When being hydrogen atom,

Hal represents halogen atom in the formula, Y, R ¹-R ³, R ⁵, R ⁶, A, B represent the meaning as hereinbefore.

(3-1), the reaction of (3-2) is by in solvent, catalyzer exists down, normal pressure or add is depressed, room temperature～50 ℃ contact with hydrogen down and carry out.

Example as solvent has alcohols such as methyl alcohol, ethanol; Ester classes such as vinyl acetic monomer; Benzene, toluene etc. are aromatic hydrocarbon based; Ethers such as diox; Water and composition thereof etc.Example as catalyzer has palladium charcoal etc., and hydrogen-pressure is 1-10 air pressure preferably.More preferably, in the presence of dehydrohalogenating agent, react.Example as dehydrohalogenating agent has bases such as yellow soda ash, sodium-acetate, triethylamine.

(4-1) R ⁵When being the alkynyloxy group of alkene oxygen base, replacement of the alkoxyl group that replaces, replacement,

R represents the alkyl that replaces, the thiazolinyl of replacement or the alkynyl of replacement, Y, R in the formula ¹-R ⁴, R ⁶, A, B represent the meaning as hereinbefore.

(4-2) R ⁵When being the alkynyloxy group of the alkene oxygen base of substituted alkoxy, replacement or replacement,

R represents the alkyl that replaces, the thiazolinyl of replacement, the alkynyl of replacement, Y, R in the formula ¹-R ⁸, R ⁵, R ⁶, A, B represent the meaning as hereinbefore.

(4-1), the reaction of (4-2) is to make general formula [I '-1] compound or [I '-2] compound in water or pure equal solvent, in the presence of alkali such as sodium hydroxide, potassium hydroxide, sodium ethylate, under 0～50 ℃, obtain the silver salt of general formula [I '-1] compound or [I '-2] compound with the silver nitrate aqueous solution effect, then, in solvent with the r-X(formula in; X represents to break away from base, r represents the meaning as hereinbefore), ℃ following reaction is 10 minutes～24 hours in room temperature～150.Ethers such as Anaesthetie Ether, tetrahydrofuran (THF), diox are arranged as spendable solvent; Benzene, toluene etc. are aromatic hydrocarbon based etc.As the disengaging base of X, can be halogen atoms such as iodine, bromine, chlorine.

Perhaps make general formula [I '-1] compound or [I '-2] compound, in solvent, in the r-X(formula, r, X represent the meaning as hereinbefore), in the presence of silver suboxide or silver carbonate, room temperature～150 ℃, reaction 10 minutes～24 hours.Operable solvent comprises ethers such as diethyl ether, tetrahydrofuran (THF), diox; Benzene, toluene etc. are aromatic hydrocarbon based etc.

(5) R ⁶When being the alkyl that replaces,

A, B, R in the formula ¹～R ⁴, Y represents the meaning as hereinbefore, R ⁵The alkyl that expression replaces.

This reaction be by general formula [I '-3] compound and Grignard reagent, formula [VI] compound in the presence of the nickel catalyzator, under-78 ℃～100 ℃, stirring reaction 10 minutes～24 hours.

Operable solvent comprises diethyl ether, tetrahydrofuran (THF), 1, ethers such as 2-glycol dimethyl ether; Benzene, toluene etc. are aromatic hydrocarbon based.

As catalyzer, can comprise and use NiX ^' ₂L ₂(X '=halogen, L ₂=2PPh ₃, dppe, dppp, bpy etc.) the Ni(II of expression) complex compound.At this, dppe=Ph ₂P(CH ₂) ₂PPh ₂, dppp=Ph ₂P(CH ₂) ₃PPh ₂, bpy=2, the 2'-dipyridyl.

(6-1) R ⁵With the alkyl or the R that replace ⁴When forming ring together,

In the formula, A, B, R ¹～R ⁴, Y represents the meaning as hereinbefore.R ^{5 "}Alkyl or and R that expression replaces ⁴Form ring together.

(6-2) R ⁴With alkyl or R ⁵When forming ring together,

In the formula, A, B, R ¹～R ⁸, R ⁵, Y represents the meaning as hereinbefore.

R ^{4 "}Expression and the alkyl or and the R that replace ⁵The ring of Xing Chenging together.

(6-1), the reaction of (6-2), normally with general formula [VII] compound and general formula [III] compound or general formula [IV] compound and general formula [V ¹] compound or their salt, solvent-free, preferably in solvent, 0～150 ℃ of temperature of reaction stirred 10 minutes～24 hours and obtains the purpose compound.Operable solvent has: alcohols such as ethanol, methyl alcohol; Ethers such as diethyl ether, tetrahydrofuran (THF), diox; Cellosolve such as methylcyclohexane, ethyl cellosolve class; Benzene, toluene etc. are aromatic hydrocarbon based etc.These solvents can use separately, or with various ratio of mixture, use the mixed solvent more than 2 kinds or 2 kinds.This reaction can be carried out in the presence of the catalyzer not having, if add acid or alkali, can promote the carrying out that reacts significantly.As acid, can use organic acids such as formic acid, acetic acid; Mineral acid such as hydrochloric acid, sulfuric acid; Lewis' acid such as titanium tetrachloride, boron trifluoride etc.As alkali, can use organic basess such as mineral alkalis such as sodium hydroxide, potassium hydroxide, sodium ethylate, sodium methylate and pyridine, triethylamine.

（7）

In the formula, A ' represents nitrogen heterocyclic ring, and L represents halogen atom, or mesyloxy etc. breaks away from base, R ¹～R ⁵, Y represents the meaning as hereinbefore.

Originally be reflected at solvent-free, preferably in solvent, in the presence of the alkali,, reacted 10 minutes～24 hours and obtain the purpose compound at 0～150 ℃.

As solvent, can use DMF, DMSO, benzene, toluene etc. aromatic hydrocarbon based; Ethers such as diox, tetrahydrofuran (THF); Acetonitrile; Pyridine; Water etc. or their mixture.

As alkali, can use alkalimetal hydrides such as sodium hydride; Lithium alkylides such as n-Butyl Lithium; Basic metal alkyl oxides such as sodium methylate; Mineral alkali such as salt of wormwood, sodium hydroxide; Organic bases such as triethylamine, pyridine.In addition, according to nitrogenous heterocyclic kind, it can double as solvent and alkali.

（8）

In the formula, L, Y, R ¹～R ⁶, A, B represent the meaning as hereinbefore.

This reaction is with general formula [X] compound and general formula [X IV] compound, and solvent-free, preferably in solvent, in the presence of de-acidying agents such as alkali, 0～150 ℃ of temperature of reaction stirred 10 minutes～24 hours and obtains the purpose compound.Operable solvent comprises ketones such as acetone, 2-butanone; Ethers such as ether, tetrahydrofuran (THF); Arene such as benzene, toluene; Acetonitrile; N, dinethylformamide; Dimethyl sulfoxide (DMSO); Tetramethylene sulfone etc.

As alkali, comprise organic basess such as pyridine, triethylamine, xylidine, DBU (these materials according to circumstances, also can be used as solvent and use); Mineral alkalis such as sodium hydroxide, potassium hydroxide, salt of wormwood, yellow soda ash, sodium hydride.

In addition, initial compounds is general formula [X IV] compound, for example can synthesize in order to following method:

R ⁴The time marquis of=H,

In the formula, A, R ¹～R ⁵, Y, r ¹, r ²The expression meaning as hereinbefore.

This reaction is in water solvent, in the presence of potassium permanganate, under 20～100 ℃, stirs 10 minutes～24 hours.

In addition, this reaction also can be used ACS Monograph 186 " Oxidations in Organic Chemistry " 1990, oxygenants such as the tin anhydride of 103-104 record, Manganse Dioxide, anhydrous chromic acid.

In addition, the carbonyl by compound that this reaction is obtained carries out suitable change, can obtain having alcohol derivate, halogen derivative of different functional groups etc.

Among the present invention,, can use the salt of hydrochloric acid, Hydrogen bromide etc. as salt.

In any case, after reaction ends, by carrying out common aftertreatment, and can obtain product.

The structure of The compounds of this invention is waited to determine by infrared, nuclear-magnetism, mass spectrum.

When on the pyrazoles ring hydroxyl substituent being arranged, there is the such tautomer of following formula in The compounds of this invention.

Enumerate embodiment below, specify the present invention.

Embodiment 1

3-(4-benzyl chloride base)-and 5-hydroxyl-1-(6-methyl-2-pyridyl) pyrazoles (compound number I-133)

(6-methyl-2-pyridyl) hydrazine with 3.0g is dissolved in the 50ml dehydrated alcohol, again to the 4-chloro-phenyl-methyl aceto acetate that wherein adds 5.9g, reflux 5 hours.Behind the reaction solution cool to room temperature,, at room temperature, stirred 3 hours to wherein adding by the ethanol of 15ml, the alcohol sodium alcohol solution of 0.56g sodium Metal 99.5 preparation.Reaction solution is poured in the frozen water,, neutralizes to wherein adding acetic acid.The crystallization that filtration is separated out, cold water washing with the normal hexane washing, with after the ether washing, obtains 5.5g product (mp.103-104 ℃) again.

Embodiment 2

3-(4-benzyl chloride base)-and 5-methoxyl group-1-(6-methyl-2-pyridyl) pyrazoles (compound number I-13)

At the 3-(4-of 2.86g benzyl chloride base)-5-hydroxyl-1-(6-methyl-2-pyridyl) in the pyrazoles, adding 15ml contains the aqueous solution and the 15ml methyl alcohol of the sodium hydroxide of 0.38g, make its dissolving, in room temperature, stir under, contain the aqueous solution of the Silver Nitrate of 1.70g to wherein dripping 15ml.Will be at room temperature, after stirring silver salt after 30 minutes and filtering, wash, thorough drying.It is suspended in the 400ml tetrahydrofuran (THF) (THF), adds the methyl-iodide of 2.0g, reflux 4 hours.After filtering out insolubles, filtrate decompression is concentrated, at (elutriant: hexane: vinyl acetic monomer=1: 1(V/V)) behind the refining oily residue that obtains, obtain 1.87g product (n on the silica gel chromatographic column ²⁶ _D1.5863).

Embodiment 3

5-chloro-3-(4-benzyl chloride base)-and 1-(6-methyl-2-pyridyl) pyrazoles (compound number I-155)

At the 3-(4-of 4.4g benzyl chloride base)-5-hydroxyl-1-(6-methyl-2-pyridyl) in the pyrazoles, add the 9.0g phosphorous oxychloride, add the N of 1.8g again, accelerine, reflux 6 hours.After placing cooling, cool off reaction solution with frozen water again,, add the 1N aqueous sodium hydroxide solution again to wherein adding frozen water, chloroform, be 9 to pH after, make its layering.After chloroform layer water, saturated common salt water washing, carry out drying with anhydrous magnesium sulfate.With its concentrating under reduced pressure, obtain crude product, with silica gel column chromatography (elutriant: hexane: vinyl acetic monomer=3: 1(V/V)) make with extra care, obtain product 2.6g(n ²⁵ _D1.6059).

Embodiment 4

3-(4-benzyl chloride base)-and 1-(4,6-dimethyl-2-pyrimidyl) pyrazoles (compound number I-178)

5-chloro-3-(4-benzyl chloride base with 0.6g)-and 1-(4,6-dimethyl-2-pyrimidyl) pyrazoles, be dissolved in 5ml ethanol, the 10ml toluene.Contain the aqueous solution of the yellow soda ash of 0.2g to wherein adding 2ml, add the 10% palladium charcoal of 0.1g again, at room temperature, contact 2.5 hours with hydrogen.After falling catalyzer with diatomite filtration, in filtrate, add toluene, water after, carry out layering, after the water washing of toluene layer usefulness saturated common salt, carry out drying with anhydrous magnesium sulfate, with its concentrating under reduced pressure, the white crystals that obtains is washed with normal hexane, obtain product 0.56g(mp.109-111 ℃).

Embodiment 5

1-benzyl-5-hydroxyl-3-(6-methyl-2-pyridyl) pyrazoles (compound number VI-2)

With the benzyl hydrazine dihydrochloride of 4.4g, 3-(6-methyl-2-pyridyl of 4.7g)-sodium acetate, anhydrous of 3-oxo ethyl propionate and 3.7g, be dissolved in the 30ml acetic acid, at room temperature, stirred 2 hours.Reaction solution is poured in the frozen water, add vinyl acetic monomer, neutralize with sodium bicarbonate aqueous solution again, with its layering, behind saturated common salt water washing vinyl acetic monomer layer, carry out drying with anhydrous magnesium sulfate, with its concentrating under reduced pressure, crystallization with the normal hexane washing obtains obtains 3.4g product (mp.163-165 ℃).

Embodiment 6

1-benzyl-5-methoxyl group-3-(6-methyl-2-pyridyl) pyrazoles (compound number VI-3)

1-benzyl-5-hydroxyl-3-(6-methyl-2-pyridyl with 1.0g) pyrazoles is dissolved in 5ml and contains in the aqueous solution of sodium hydroxide of 0.15g, in room temperature and under stirring, contains the aqueous solution of the Silver Nitrate of 0.67g to Dropwise 5 ml wherein.At room temperature, stirred 30 minutes, after the silver salt of separating out filtered, washes, thorough drying was suspended in it in tetrahydrofuran (THF) of 15ml, the methyl-iodide that adds 0.8g, reflux 2 hours, filter out insolubles after, concentrating under reduced pressure filtrate, with silica gel column chromatography (elutriant: hexane: vinyl acetic monomer=4: 1(V/V) make with extra care, obtain the product (n of 0.82g ²⁵ _D1.5902).

Reference example 1

4-methoxyl group-3-(6-methyl-2-pyridyl) pyrazoles

3-(N with 0.5g, the N-dimethylamino)-2-methoxyl group-1-(6-methyl-2-pyridyl)-2-propylene-1-ketone is dissolved in the 10ml ethanol, add the 0.17g hydrazine hydrate, reflux 2 hours is behind the reaction solution concentrating under reduced pressure, adding chloroform, water carry out layering, chloroform layer carries out drying with anhydrous magnesium sulfate, with its drying under reduced pressure after using the saturated common salt water washing, with the crystallisate hexane wash that obtains, obtain 0.37g product (mp.171-173 ℃).

¹HNMR（CDCl ₃）δ.ppm

2.53（s，3H），3.92（s，3H），7.01（d，1H），7.43（s，1H），7.60（t，1H），7.72（d，1H）

Reference example 2

3-(N, the N-dimethylamino)-2-methoxyl group-1-(6-methyl-2-pyridyl)-2-propylene-1-ketone

2-(methoxymethyl with 1.0g) N of carbonyl-6-picoline and 1.8g, the dinethylformamide dimethyl-acetal is dissolved in the toluene of 10ml, reflux 7 hours, after placing cooling, the concentrating under reduced pressure reaction solution, with enriched material with silica gel column chromatography (elutriant: vinyl acetic monomer: methyl alcohol=9: 1(V/V)) handle, obtain the product of 0.5g.

¹HNMR（CDCl ₃）δ，ppm

2.58（s，3H），3.14（s，6H），3.72（d，3H），7.17（d，1H），7.47（s，1H），7.58（d，1H），7.65（t，1H）

Embodiment 7

1-(4-benzyl chloride base)-and 4-methoxyl group-3-(6-methyl-2-pyridyl) pyrazoles (compound number VI-17)

4-methoxyl group-3-(6-methyl-2-pyridyl with 0.37g) pyrazoles is dissolved in the N of 5ml, in the dinethylformamide, adds 0.41g salt of wormwood, and the 4-benzyl chloride base bromamide of 0.44g at room temperature, stirred 17 hours.Reaction solution is poured in the frozen water, use ethyl acetate extraction, after its usefulness saturated common salt water washing, use anhydrous magnesium sulfate drying, concentrating under reduced pressure, with the thick resultant that obtains, with silica gel column chromatography (elutriant: hexane: vinyl acetic monomer=7: 3～1: 4(V/V)) refining, obtain 0.28g product (mp.110～112 ℃).

¹HNMR（CDCl ₃）δppm

2.64（s，3H），3.78（s，3H），5.31（s，2H），7.00（s，1H），7.03（d，1H，J＝7.5Hz），7.19（d，2H，J＝8.5Hz），7.31（d，2H，J＝8.5Hz），7.59（t，1H，J＝7.5Hz），7.77（d，1H，J＝7.5Hz）

Embodiment 8

5-methoxyl group-3-(3-methoxy-benzyl)-and 1-(6-methyl-2-pyridyl) pyrazoles (compound number I-47)

5-hydroxyl-3-(3-methoxy-benzyl with 4.0g)-and 1-(6-methyl-2-pyridyl) pyrazoles, be dissolved in the tetrahydrofuran (THF) of 30ml, add the methyl-iodide of 3.04g, then, the silver suboxide that adds 2.36g, at room temperature stirred 3 hours, and filtered insolubles, wash with tetrahydrofuran (THF), concentrating under reduced pressure behind merging filtrate and the washings, with the oily matter that obtains, with silica gel column chromatography (elutriant: hexane: vinyl acetic monomer=1: 1(V/V) make with extra care, obtain 3.28g product (n ^23.9 _D1.5944).

Embodiment 9

5-methoxyl group-1-(6-methyl-2-pyridyl)-and 3-(4-oil of mirbane formyl) pyrazoles (compound number II-7)

5-methoxyl group-1-(6-methyl-2-pyridyl with 4.6g)-and 3-(4-oil of mirbane formyl) pyrazoles is suspended in the 70ml water, adds 6.8g potassium permanganate, under 70～80 ℃, heated and stirred 20 hours.

Filter out insolubles, and with its water, chloroform washing.Merging filtrate and washings carry out layering, and chloroform layer with after the saturated common salt water washing, use anhydrous magnesium sulfate drying, and concentrating under reduced pressure with the crystallisate that obtains, washs with vinyl acetic monomer, obtains 4.2g(mp.173-174 ℃) product.

Embodiment 10

3-[1-hydroxyl-1-(4-nitrophenyl) methyl)]-and 5-methoxyl group-1-(6-picolyl) pyrazoles (compound number II-8)

5-methoxyl group-1-(6-methyl-2-pyridyl with 3.2g)-and 3-(4-oil of mirbane formyl) pyrazoles, be dissolved in the 40ml methyl alcohol, under 5～10 ℃, add the 0.20g sodium borohydride, and then, at room temperature, stirred 2 hours, after the degree with reaction solution concentrating under reduced pressure to 1/3, add salt solution, use chloroform extraction, behind the washing chloroform layer, carry out drying with anhydrous magnesium sulfate.Concentrating under reduced pressure with the thick resultant that normal hexane washing obtains, obtains 2.8g(mp.128～129 ℃) product.

Embodiment 11

3-(1-benzoglyoxaline ylmethyl)-and 5-methoxyl group-1-(6-methyl-2-pyridyl) pyrazoles (compound number VI-14)

The 0.25g benzoglyoxaline is dissolved in the N of 20ml, in the dinethylformamide, the salt of wormwood that adds 0.29g, 3-chloromethyl-5-methoxyl group-1-(6-methyl-2-the pyridyl that adds 0.5g again) pyrazoles, under 70 ℃, heated and stirred 5 hours, after placing cooling, reaction solution is poured in the frozen water, uses ethyl acetate extraction, and then, after the saturated common salt water washing, carry out drying with anhydrous magnesium sulfate, with its concentrating under reduced pressure, the resultant that obtains silica gel column chromatography (elutriant: chloroform: ethanol=19: 1(V/V) refining, obtain 0.41g(n ^24.1 _D1.6006) product.

Embodiment 12

3-(4-benzyl chloride base)-and 1-(6-methyl-2-pyridyl)-4,5,6,7-tetrahydrochysene-1H-indazole (compound number I-229)

2-(4-chloro-phenyl-ethanoyl with 1.5g)-and pimelinketone, (6-methyl-2-pyridyl) hydrazine of 0.9g is dissolved in the ethanol of 15ml, at room temperature, stirs 3 hours, behind the concentrating under reduced pressure reaction solution, adds vinyl acetic monomer, water, carries out layering.After the vinyl acetic monomer layer is used the saturated common salt water washing, carry out drying with anhydrous magnesium sulfate, concentrating under reduced pressure, with the thick resultant that obtains with silica gel column chromatography (elutriant: hexane: acetone=9: 1(V/V) separate, refining, obtain the 3-(4-benzyl chloride base of 0.6g)-2-(6-methyl-2-pyridyl)-4,5,6,7-tetrahydrochysene-2H-indazole (n ^22.1 _D1.5880) target product.

Embodiment 13

3-benzyl-5-ethyl-1-(6-methyl-2-pyridyl) pyrazoles (compound number I-230)

At monobromoethane by 1.2g, 0.24g MAGNESIUM METAL, in the Ge Liya solution of the magnesium ethide bromamide that the ether of 10ml makes, the diphenylphosphine methane chlorination nickel of dissolving 10ml, below 0 ℃, drip 3-benzyl-5-chloro-1-(6-methyl-2-pyridyl of 0.9g at leisure) ethereal solution (5ml) of pyrazoles, at room temperature, stirred 2 hours, and then, reflux 2 hours, after putting cold reaction solution, add frozen water, carry out layering, behind saturated common salt water washing ether layer, carry out drying with anhydrous magnesium sulfate, concentrating under reduced pressure is with silica gel column chromatography (elutriant: hexane: after vinyl acetic monomer=9: 1) refining, obtain purpose product 0.45g(n ^25.0 _D1.5913).

List the typical example of The compounds of this invention in table 1-1, table 1-2, table 2, table 3, table 4, table 5, the table 6, wherein also comprised the compound that obtains in the previous embodiment of the present invention.

The compounds of this invention because wide spectrum wire bacterium is had good sterilizing power, can be used to prevent and treat all diseases that comprise generation when flowers, lawn, herbage, agriculture and garden crop etc. are cultivated.The brown spot of beet (Cercospora beticola) for example, the brown spot of Semen arachidis hypogaeae (Mycosphaerella arachidis), the black disease (Mycosphaerella berkeleyi) that relates to, the Powdery Mildew of cucumber (sphaerotheca fuliginea), climing rot (Moycosphaerella melonis), sclerotium disease (Sclerotinia sclerotiorum), grey mildew (Botrytis cinerea), black spot (Cladosporium cucumerinum), the grey mildew of tomato (Botrytis cinerea), leaf mold (Cladosporium fulvum), the grey mildew of eggplant (Botrytis cinerea), bacterial blight (Corynespora melongenae), Powdery Mildew (Erysiphe cichoracearum), the grey mildew of strawberry (Bortytis cinerea), Powdery Mildew (Sphaerotheca humuli), the gray spoilage disease of onion (Botrytis allii), grey mildew (Botrytis cinerea), the sclerotium disease of Kidney bean (Sclerotinia sclerotiorum), grey mildew (Botrytis cinerea), apple mildew (Podosphaera leucotricha), black spot (Venturia inaequalis), the Powdery Mildew (Phyllactinia kakicola) of apple brown rot (Monilinia mali) Fei, anthrax (Gloeosporium kaki), angle spot defoliation disease (Cercospora kaki), peach, the grey scab of cherry (Monilinia fructicola), the grey mildew of grape (Botrytis cinerea), Powdery Mildew (Uncinula necator), late blight (Glomerella cingulata), the black spot of eggplant (Venturia nashicola), red-star like disease (Gymnosporangium asiaticum), black spot (Alternaria Kikuchiana), the zonate spot of tea (Pestalotia theae), anthrax (Colletotrichum theae-sinensis), fruit disease morning of citrus (Elsinoe fawcetti), penicilliosis (Penicillium italicum), green mould (Penicillium digitatum), grey mildew (Botrytis cinerea), the Powdery Mildew of barley (Erysiphe graminisf.sp.hordei), naked smut (Ustilago nuda), the red mildew of wheat (Gibberella zeae), red rust disease (Puccinia recondita), spot disease (Cochliobolus sativus), eyeprint disease (Pseudocercosporella herpotrichoides), spot blight (Leptosphaeria nodorum), Powdery Mildew (Erysiphe graminis f.sp.tritici), snow red rot (Micronectriella nivalis), the rice blast of rice (Pyricularia oryzae), banded sclerotial blight (Rhizoctonia solani), red mould seedling diseases (Gibberella fujikuroi), sesame leaf rot (Cochliobolus miyabeanus), the sclerotium disease of tobacco leaf (Sclerotinia sclerotiorum), Powdery Mildew (Erysiphe cichoracearum), the grey mildew of turmeric (Brtrytis cinerea), the snow big grain sclerotinia rot (Sclerotinia borealis) of moderately well-off grass, the Powdery Mildew of orchard grass (Erysiphe graminis), the anaphylactoid purpura of soybean (Cercospora kikuchii), the eqpidemic disease of pomato (Phytophthorainfestans), the oidium of cucumber (Pseudoperonospora cubensis), the oidium of grape (Plasmopara viticoia) etc.

In addition, The compounds of this invention is effective equally to benzimidazole germicide (for example thiophanate methyl F-1991, derosal etc.) the demonstration mould germ of chemical sproof grey (Botrytis cinerea) and sweet bud brown patch germ (Cercospora beticola), apple black star bacteria (Venturia inaegualis), pear cucumerinum (Venturia nashicola) and sensitive strain.

And then The compounds of this invention is effective equally to dicarboxylic acid imido series bactericidal agent (for example Vinclozolin, sterilization profit, isoprothiolane) demonstration mould germ of chemical sproof grey and sensitive strain.

The compounds of this invention is more suitable in the following disease of control: the rice blast of the brown spot of sweet bud, the Powdery Mildew of wheat, rice, the black spot of apple, the grey mildew of cucumber, the brown spot of Semen arachidis hypogaeae etc.

The compounds of this invention can also use as stain control agent, is used for preventing that hydrobiont is attached on the contactant in the water such as hull bottom, fishnet.

The The compounds of this invention that obtains like this when using actually, can not add other compositions, use with pure form, or when being used for agricultural chemicals, the form that can adopt general agricultural chemicals to adopt, i.e. forms such as hydrating agents, granula, pulvis, emulsion, water solvent, clouding agent.When the solid-state agricultural chemicals of preparation, can use vegetalitas powder, diatomite, combustion lime stone, gypsum, talcum powder, agalmatolite, clay, mineral oil, plant wet goods mineral micropowders such as big beans, wheat-flour as additive and carrier.When the preparation liquid pesticide, can use kerosene, Dormant oils, oil, solvent petroleum naphtha, dimethylbenzene, hexanaphthene, pimelinketone, dimethyl formamide, dimethyl sulfoxide (DMSO), ethanol, acetone, mineral oil, vegetables oil, water etc. as solvent.In order to make these preparations uniform and stable, can add tensio-active agent in case of necessity.The hydrating agents that obtains like this, emulsion are diluted with water to the concentration of regulation, use with suspension liquid or emulsion.Pulvis, granula can directly be spread fertilizer over the fields on plant.

Below, represented some embodiment of the present composition, but additive and adding proportion thereof not being limited by these embodiment, can in wide scope, change.Part in the example of formulations is a weight part.

Embodiment 14 hydrating agents

40 parts of The compounds of this invention

53 parts in diatomite

4 parts of higher alcohol sulfates

3 parts of sulfonated alkyl naphathalenes

Above uniform ingredients is mixed, after the fine pulverizing, just can obtain effective constituent and be 40% hydrating agents.

Embodiment 15 emulsions

30 parts of The compounds of this invention

33 parts of dimethylbenzene

30 parts of dimethyl formamides

7 parts of polyxyethylated allyl ethers

Behind above composition mixed dissolution, obtain effective ingredient and be 30% emulsion.

Embodiment 16 pulvis

10 parts of The compounds of this invention

89 parts of talcum powder

1 part of polyxyethylated allyl ether

With above composition uniform mixing, after the fine pulverizing, obtain effective ingredient and be 10% pulvis.

Embodiment 17 granulas

5 parts of The compounds of this invention

73 parts of clays

20 parts of wilkinites

1 part of dioctyl sulphur Succinic Acid sodium salt

1 part of sodium phosphate

Above composition is mixed, after fully pulverizing, add entry, fully mixing again, behind the granulating and drying, obtain effective ingredient and be 5% granula.

Embodiment 18 clouding agents

10 parts of The compounds of this invention

4 parts of sodium lignosulfonates

1 part of Sodium dodecylbenzene sulfonate

Xanthogenic acid 0.2

84.8 parts in water

Above composition is mixed, and case of wet attrition is below 1 micron to granularity, obtains effective ingredient and be 10% suspension liquid.

In addition, need not wait to say that the independent use of The compounds of this invention also is highly effective.But insufficient or render a service low disease or harmful insect, mite for action effect, the back of mixing more than a kind or 2 kinds of various sterilant, Insecticidal and acaricidal agent can be used.

Can be as follows with the typical example of The compounds of this invention blended sterilant, sterilant, miticide, plant-growth regulator:

[sterilant]

Vancide 89, Phaltan, autumn is blue female, zineb, maneb, enemy's snout moth's larva pine, propineb, polycarbamate, chlorine titanium sieve saccharic acid, quintozene, Difolatan, iprodione, the sterilization profit, vinclozolin, the fluorine imide, cymoxanil, mepronil, plutonium Ni Laer, pencycuron, oxycarboxin, fosetylalaluminum, propamocarb, cycloheximide triazole, Triabimeno I, propiconazole, dichlobutrazol, bitertanol, hexaconzole, microbutanil, flusilazole, etaconazole, the spirit of bacterium azoles, flutiafen, penconazole, diniconazole, cyproconazole, fenarimol, triflumizole, Prochloraz, IMAZALIL, pefrazoate, cyclomorpholine, fenpropimorph, triforine, buthiobate, pyrifenox, anilazine, Polyoxin, matalaxyl, oxadixyl, Furalaxyl, isoprothiolane, thiophene bacterium alkene, thiabendazole, it pest element, spring mycomycin-S, validamycin, dihydrostreptomycin sulfate, F-1991, derosal, thiophanate methyl, hymexazol, the alkalescence cupric chloride, basic cupric sulfate, fentinacetate, the hydroxide triphenyltin, diethofencarb, metasulfocarb, chinomethionate, Niagara 9044, Yelkin TTS, sodium bicarbonate, the Delan, dinocap, fenaminosulf, diclomedin, Guanoctine, dodine, IBP, Hinosan, mepanipirim, ferimzon, three end acid amides, metasulfocarb, fluazinam, 1,2,3, the acid of 4-benzene tetraketone, dimethomorph, pyroquilon, Bai Ye subtracts, phthalide.

[Insecticidal and acaricidal agent]

G-23922, chloropropylate, encircle third chlorfenethol, bromopropylate, Mitigan, zineb ketone, chlordimeform, amine three nitrogen mites, propargite, kelthane, benzoximate, hexythiazox, the oxidation fenbutatin oxide, polynactin, thioquinox, Ovotran, tedion karphos, avermectin, many nitric sulfids, clofenetzine, fulbenzimin, fulfenoxuron, Ovotran, cyhexatin, pyridaben, fenpyroximate, Tiguvon, Sumithion, diazinon, Chlorpyrifos 94, different sulfone sulphur phosphorus, vamidothion, rice Feng Jing, Rogor, the peace fruit, the Malathion, Trichlorphon, thiometon, R-1504, menazon, SD-1750, acephate, she is than sulphur phosphorus, Fac, parathion-methyl, sulfone is inhaled sulphur phosphorus, Nialate, pyrachlofos, ventilation breather, methomyl, Aldicarb, Propoxur; Osbac; Lian Gengwei; SevinCarbaryl; Padan; Carbosulran; benfaracarb; go out and decide prestige; benzene worm prestige; phenoxycarb; permethrin; Cypermethrin; first chrysanthemum ester; kill the chrysanthemum ester; divide and pounce on the chrysanthemum ester; fenson; Pynamin; tetramethyl chrysanthemum ester; resmethrin; dimethirn; proparthrin; bifenthrin; PH; fluralinate; cyfluthrin; cyhalothrin; flucythrinate; ethfenoprox; encircle the third chrysanthemum ester; tralomethrin; silaneophane; diflubenzuron; chlorfluazuron; triflumuron; teflubenzuron; bupnrotezin and machine oil.

[plant-growth regulator]

The Plant hormones regulators,gibberellins class is (as Plant hormones regulators,gibberellins A ₃, Plant hormones regulators,gibberellins A ₄, Plant hormones regulators,gibberellins A ₇) methyl ethyl diketone (IAA), toluylic acid (NAA).

Be the test agent that The compounds of this invention is used as the effective constituent of the various Plant diseasess of treatment below.Prevention effect is the morbidity state with the test plant of visual inspection investigation, the i.e. scab that on leaf, stem etc., occurs and the extent of growth of bacterium layer, when not observing fully, bacterium layer, scab be [5], compare with the check plot observe 10% for [4], 25% be [3], 50 be [2], 75% degree be [1], during with the morbidity state indifference of check plot is [0], be divided into 0～5, six stages evaluations, with 0,1,2,3,4,5 expressions.

The control test of test example 1 sweet bud brown spot

On the sweet bud seedling of in watt flowerpot of 9cm, cultivating (kind バ-レ ス ス ト リ-ネ, 5～6 leaf phases), the hydrating agents (its concentration is shown in Table 7) of spraying The compounds of this invention, after making leaf air-dry, the mitogenetic sporozoite suspension liquid of spray inoculation sugar beet leaf spot bacteria (Cercospora beticola), at 24～28 ℃, high-temperature kept one day down, in 23～30 ℃ greenhouse, kept 12 days, the investigation morbidity state draws prevention effect.It the results are shown in table 7.

The 2 sweet bud brown spot control tests (therapeutic test) of test example

Give the mitogenetic sporozoite suspension liquid of cultivating sweet bud seedling (kind バ-レ ス ス ト リ-ネ, 5～6 leaf phases) the sweet bud brown patch germ of spray inoculation (Cercospora beticola) in 9cm watt of flowerpot, under 24～28 ℃, high humidity, cultivated 1 day, and then in 23～30 ℃ of greenhouses, cultivated 2 days, then spray the hydrating agents (concentration is shown in the table 8) of The compounds of this invention, after leaf is air-dry, cultivated 10 days in the greenhouse, the situation of investigation morbidity draws prevention effect.Its result is as shown in table 8.

Test example 3 wheat powdery mildews control tests (prophylactic tria)

Give with watt wheat seedling (No. 61, kind agricultural, 1.0～1.2 leaf phases) of flowerpot cultivation and spray The compounds of this invention hydrating agents (concentration sees Table 9), after leaf is air-dry, the mitogenetic sporozoite of jolting inoculation wheat powdery mildew germ (Erysiphe graminis f.sp.trtici), in 22～25 ℃ of greenhouses, cultivated the investigation prevention effect 7 days.Its result is as shown in table 9.

The control test (prophylactic tria) of test example 4 rice blasts

On paddy rice (fine, 3.0 leaf phases of the kind Japan) seedling to the plastic flowerpot cultivation, spray The compounds of this invention hydrating agents (concentration sees Table 10), after at room temperature air-dry, spray inoculation is cultivated the mitogenetic sporozoite suspension liquid of the rice Pyricularia grisea (Pyriculavia oryzae) that obtains.Under 25 ℃, dark, carry out 48 hours high humidity and cultivate, then, with plant, at 25～27 ℃, the constant temperature indoor cultivation of humidity more than 70%.Inoculate after 7 days, the investigation onset state is obtained prevention effect.Its result is as shown in table 10.

Test example 5 scabs of apple control tests (prophylactic tria)

Give the hydrating agents (concentration sees Table 11) that sprays The compounds of this invention with (kind state light, 3～4 leaf phases) on watt apple seedling of flowerpot cultivation, after making it air-dry, the mitogenetic sporozoite of inoculation apple black star bacteria (Venturia inaegualis), illumination is (bright, alternately dark) down, 20 ℃, high humidity indoor, after cultivating for 2 weeks, the investigation prevention effect, its result is as shown in table 11.

Test example 6 cucumber grey mildews control test

Give the hydrating agents (concentration sees Table 12) that sprays The compounds of this invention with watt cucumber seedling of flowerpot cultivation (half white, 1.0 leaf phases of kind phase mould), after the sprinkling, after plant is at room temperature air-dry, (Botrytis cinerea is to benzimidazoles medicament and dicarboxylic acid imines class medicament sensitive organism, to call the medicament sensitive organism in the following text to drip the mould germ of grey that kind of cultivation obtains for this leaf of cucumber.Two class medicaments are shown drug-fast bacterium, to call resistant organism in the following text) the suspension liquid (containing glucose and yeast extract) of sporozoite.Under 20 ℃, dark, high humidity, cultivate.Inoculate after 4 days, the investigation onset state is obtained prevention effect, and its result is as shown in table 12.

Test example 7 Semen arachidis hypogaeae brown spots control test

Give the hydrating agents (concentration sees Table 13) of seedling (kind NAKATUTAKA, 4.0 compound leaf phases) the sprinkling The compounds of this invention of the Semen arachidis hypogaeae of cultivating with watt flowerpot.After the sprinkling, at room temperature air-dry plant, spray inoculation is cultivated the sporozoite suspension liquid of the Semen arachidis hypogaeae brown patch germ (Mycosphaerlla arachidis) that obtains, at 24～28 ℃, cultivated 1 day under the high humidity, cultivated 12 days in 23～30 ℃ the room temperature, the investigation onset state is obtained prevention effect.Its result is as shown in table 13.

* 1 NMR data (CDCl ₃), δ (ppm)

2.62（s，3H），3.04（s，3H），3.89（s，3H）4.09（s，2H），5.40（s，1H），7.09（d，1H，J＝7.5Hz），7.28（s，1H），7.42（d，1H，J＝7.5Hz），7.51（d，2H，J＝8.5Hz），7.68（t，1H，J＝7.5Hz），7.88（d，2H，J＝8.5Hz）

* 2 NMR data (CDCl ₃), δ (ppm)

2.33（s，3H），2.52（s，3H），3.87（s，3H）5.33（s，1H），6.9～7.3（m，5H），7.7～7.8（m，2H），1.31（brs.1H）

Claims (6)

1, pyrazole derivatives or its salt of representing with logical formula I,

Y represents CR ⁶Or N

R ¹, R ², R ³, R ⁴, R ⁶Identical or different, expression hydrogen atom, halogen atom, also can be the alkyl that replaces, also can be the alkoxyl group that replaces, also can be the alkene oxygen base that replaces, also can be alkynyloxy group, the hydroxyl that replaces, in addition, R ¹And R ²Also can form ring together,

R ⁵Expression hydrogen atom, halogen atom, also can be the alkyl that replaces, also can be the alkoxyl group that replaces, also can be the alkene oxygen base that replaces, also can be the alkynyloxy group that replaces, hydroxyl, also can be the alkylthio that replaces, in addition, R ⁴And R ⁵Also can form ring together,

A represents the aryl that replaces, the heterocyclic radical of replacement,

B represents

In the formula, r ¹, r ², r ³, r ⁴, r ⁵, r ⁶Identical or different, expression hydrogen, halogen atom, hydroxyl, also can be the alkyl that replaces, also can be the alkoxyl group that replaces or also can be the acyloxy that replaces, or r ¹And r ², r ³And r ⁴Or r ⁵And r ⁶Form carbonyl together, and then, r ¹-r ⁶And R ⁴Also can form ring together, but Q is

The time, R ¹, R ², R ³, R ⁶Can not be hydrogen atom entirely.

2, the preparation method of general formula [I '-1] compound,

In the formula, A, B, R ¹, R ², R ³, R ⁴, Y represents the meaning as hereinbefore, the compound that it is characterized in that making compound that logical formula II represents and logical formula III to represent reacts and obtains,

In the formula, R represents alkyl, A, B, R ⁴The expression meaning as hereinbefore,

In the formula, R ¹, R ², R ³, Y represents the meaning as hereinbefore.

3, the preparation method of general formula [I '-2] compound,

In the formula, A, B, R ¹, R ², R ³, R ⁵, Y represents the meaning as hereinbefore, it is characterized in that making the compound of the compound of general formula [IV] expression and general formula [V] expression to react and obtain:

In the formula, A, B represent the meaning as hereinbefore,

R, R in the formula ¹, R ², R ³, Y represents the meaning as hereinbefore.

4, the preparation method of general formula [I '-7] compound,

In the formula, A, B, R ¹, R ², R ⁴, r, Y represent the meaning as hereinbefore, it is characterized in that making in the compound and general formula r-X[formula of general formula [I '-1] expression, r represents that the alkyl that replaces, alkane thiazolinyl or alkane alkynyl, the X of replacement of replacement represent to break away from base] react,

A, B, R in the formula ¹, R ², R ³, R ⁴, Y represents the meaning as hereinbefore.

5, the preparation method of general formula [I '-8] compound,

A, B, R in the formula ¹, R ², R ³, R ⁵, r, Y represent the meaning as hereinbefore,

It is characterized in that r, x represent the meaning as hereinbefore in the compound and general formula r-X[formula of general formula [I '-2] expression] compound of expression reacts,

In the formula, A, B, R ¹, R ², R ³, R ⁵The expression meaning as hereinbefore.

6, a kind of agricultural or horticultural bactericide, one or two or more kinds that it is characterized in that containing the pyrazole derivatives of useful general formula [I] expression or its salt be as effective constituent,

In the formula, Q, Y, R ¹～R ⁶, r ¹-r ⁶, A, B, n represent the meaning as hereinbefore.