JPH03232859A - Pyrazole derivative, its production and germicide - Google Patents

Abstract

NEW MATERIAL:A pyrazole derivative expressed by formula I (R1 is 1-8C alkyl or phenyl; R2 is 1-4 alkyl, phenyl or pyridyl; R3 is sulfonyl or carbonyl; R4 is phenyl, naphthyl, benzyl, styryl, quinolyl, 1-6C haloalkyl, furylethylene or 2-10C alkenyl). EXAMPLE:1,3-dimethyl-4-(4-methylbenzene sulfonyl) oxyiminopyrazole-5-one. USE:Useful as a germicide. Usable for preventing plant diseases such as downy mildew or an epidemic of vegetables, downy mildew of grapes or blast, especially effective for prevention of downy mildew of cucumber, rice blight or rust of wheat. PREPARATION:A compound expressed by formula II is subjected to a reaction with a compound expressed by formula III (X is eliminable group) in an alkaline condition to afford the compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a pyrazole derivative, a method for producing the same, and a fungicide containing the same as an active ingredient.

[Conventional technology]

Pyrazole derivatives (e.g., JP-A-60-25816)
It is known that compounds shown in Japanese Patent Application Laid-Open No. 62-114971, Japanese Patent Application Laid-open No. 62-283962, etc.) have bactericidal activity.

However, the compounds shown in (1) to (2) do not have a bactericidal effect sufficient to sufficiently suppress the onset of disease, and furthermore, no bactericidal effect can be expected at low concentrations.

[Problem that the invention seeks to solve]

An object of the present invention is to provide a novel pyrazole derivative, a method for producing the same, and a fungicide containing the same as an active ingredient.

[Means for solving problems]

As a result of intensive research to solve the above-mentioned problems, the present inventors discovered that a new pyrazole derivative has strong bactericidal activity, and completed the present invention.

That is, the present invention provides (1) the following formula: (wherein, Ro represents an alkyl group having 1 to 8 carbon atoms or an optionally substituted phenyl group; represents a group, an optionally substituted phenyl group, or an optionally substituted pyridyl group; R8
represents a sulfonyl group or a carbonyl group; R4 is an optionally substituted phenyl group, an optionally substituted naphthyl group, an optionally substituted benzyl group, an optionally substituted styryl group, an optionally substituted styryl group, represents a quinolyl group, a halogenated alkyl group having 1 to 6 carbon atoms, a furylethylene group, or an alkenyl group having 2 to 10 carbon atoms, which may be ) Compound (2) represented by the following formula: (wherein RI and R2 have the same meanings as above) and the following formula: %Formula%([[) (wherein, X represents a leaving group) (3) A method for producing a compound of the formula (1), characterized in that the formula (I) is reacted with a compound represented by the formula (iR3 and R4 have the same meanings as defined in claim 1) under alkaline conditions. The present invention relates to a disinfectant containing a compound as an active ingredient.

The present invention will be explained in detail below.

The novel pyrazole derivative 5 compound (1), which is the target compound, and (II) and (I[[), which are the raw materials for its production,
In the compound, the alkyl group having 1 to 4 carbon atoms has 1 to 4 carbon atoms.
-4 linear or branched alkyl groups (eg, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, 5ec-butyl, t-butyl, etc.).

As the alkyl group having 1 to 8 carbon atoms, 1 to 8 carbon atoms
-8 linear or branched alkyl groups (in addition to the alkyl groups exemplified above, for example, pentyl, isopentyl,
Examples include neopentyl, hexyl, 3-methylhexyl, and 2-ethylhexyl.

As a halogenated alkynyl group having 1 to 6 carbon atoms,
Mention may be made of straight-chain or branched halogenated alkynyl groups having 1 to 6 carbon atoms.

Examples of the alkoxy group having 1 to 4 carbon atoms include methoxy group, ethoxy group, propoxy group, and butoxy group.

R4 represents an alkyl group having 1 to 8 carbon atoms or a phenyl group which may be substituted with 6. Preferred alkyl groups include methyl, ethyl, propyl, and isopropyl groups.

R2 represents an alkyl group having 1 to 4 carbon atoms, an optionally substituted phenyl group, or an optionally substituted pyridyl group. Preferred alkyl groups include methyl and ethyl groups.

R3 represents a sulfonyl group or a carbonyl group.

R4 is an optionally substituted phenyl group, an optionally substituted naphthyl group, an optionally substituted benzyl group, an optionally substituted styryl group, an optionally substituted quinolyl group, the number of carbon atoms It represents a halogenated alkyl group having 1 to 6 atoms, a furylethylene group, or an alkenyl group having 2 to 10 carbon atoms. Preferred substituents for the phenyl group include a halogen atom, a nitro group, an alkoxy group having 1 to 4 carbon atoms, and an alkyl group having 1 to 4 carbon atoms. As a quinolyl group, 2-
Examples include quinolyl group, 4-quinolyl group, 8-quinolyl group, and 8-quinolyl group is preferred. Examples of the naphthyl group include α-naphthyl group and β-naphthyl group. Preferred substituents for the styryl group include a halogenated alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, and more preferably a trifluoromethyl group among the halogenated alkyl groups. , among the alkoxy groups, a methoxy group is more preferred. As a halogenated alkyl group,
Those having 1 to 3 carbon atoms are preferred. The alkenyl group preferably has 4 to 7 carbon atoms.

X is a leaving group, and is not particularly limited, such as a halogen atom (chlorine, bromine, or iodine, etc.), an alkylthio group (methylthio, ethylthio, propylthio, butylthio, etc.), or an alkanesulfonyl optionally substituted with halogen. Examples include oxy groups (methanesulfonyloxy, ethanesulfonyloxy, trifluoromethanesulfonyloxy, etc.), arylsulfonyloxy groups (benzenesulfonyloxy, p-toluenesulfonyloxy, etc.), hydroxyl groups, etc., but halogen atoms are preferred. , more preferably a chlorine atom.

The novel pyrazole derivative, which is the target compound, can include a mixture of geometric isomers based on >c=N- of the oxime, and can be separated into individual isomers if necessary.

That is, the most preferred target compound (I) of the present invention is: 1-2 alkyl group, optionally substituted 9-substituted phenyl group, or optionally substituted pyridyl group; R3 represents a sulfonyl group or carbonyl group; R4 represents a halogen atom, a nitro group , an alkoxy group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms
4. Phenyl group optionally substituted with alkyl group, naphthyl group optionally substituted, benzyl group optionally substituted, styryl group optionally substituted with trifluoromethyl group or methoxy group, substituted represents a quinolyl group, a halogenated alkyl group having 1 to 3 carbon atoms, a furylethylene group, or an alkenyl group having 4 to 7 carbon atoms, which may be ) can be mentioned.

A preferable example of the raw material compound (II) is 2 [wherein R and R2 have the same meanings as described in (1-A). ] 10- can be mentioned, and the starting compound (I
As a preferable example of II), X R3R4(III
A) [In the formula, X represents a halogen atom and iR3 and R4 are (I
- It has the same meaning as described in A). ] Compounds represented by these can be mentioned.

The raw material compound (II) used in the present invention can be obtained by producing pyrazolone from an alkaloyl or aryloyl acetate and an alkyl or aryl hydrazine, for example, according to the method described in JP-A-62-283962. It can be easily produced by treatment with an appropriate nitrite in the presence of an acid.

The raw material compound (I[[) used in the present invention can be easily produced, for example, by treating a sodium salt of an alkyl or arylsulfonic acid with thionyl chloride according to the method described in Shin Jikken Kagaku Koza volume 14. be able to.

The target compound (I) can be produced by reacting the starting compound (It) and the starting compound (nI) in an organic solvent in the presence of a salt 11- group.

Examples of organic solvents that can be used in the production method include aprotic solvents (acetonitrile, dimethylformamide, dimethyl sulfoxide, etc.), ethereal solvents (tetrahydrofuran, diethyl ether, dioxane, etc.), polar solvents (acetone, etc.), etc. However, it is preferable to use an aprotic solvent, and examples of the base include inorganic bases (potassium carbonate, sodium carbonate, sodium hydride, etc.), organic bases (pyridine, triethylamine, etc.), etc. However, it is preferable to use an organic base.

The method for producing the target compound (1) requires a reaction concentration of 0.5 to 40
It can be done in %.

In the manufacturing method, the raw material compound (n) and (■) may be added at a ratio of 0.1 to 3 moles of the raw material compound (I[[) per 1 mole of the raw material compound (■). However, it is preferably 0.5 to 1.512 mol.

The reaction temperature in the production method can be carried out at 0 to 100°C, but preferably 10 to 70°C.

The manufacturing method varies depending on the concentration and temperature mentioned above, but
It can usually be carried out in 0.5 to 8 hours.

The target compound (I) can be isolated by simply removing the solvent from the reaction mixture after the completion of the reaction to obtain the crude target compound (1), which is further subjected to conventional methods such as recrystallization and chromatography. High purity target compound (I) can be obtained by the purification method.

The object compound (1) of the present invention can be used to treat downy mildew, late blight,
It can be used to prevent plant diseases such as grape mildew, rice blast, and wheat rust, and has a particularly remarkable bactericidal effect in preventing cucumber mildew, rice blast, and wheat rust.

The fungicide of the present invention contains one or more types of compound (I) as an active ingredient.

Compound (1) can be used alone, but is usually mixed with a carrier, a surfactant, a dispersant, or an auxiliary agent (e.g., powder, emulsion, fine granule, etc.) by a conventional method.
It is preferable to use the composition as a granule, a wettable powder, an oily suspension, an aerosol, or the like.

Examples of carriers include solid carriers such as talc, bentonite, clay, kaolin, diatomaceous earth, white carbon, vermiculite, slaked lime, silica sand, ammonium sulfate, and urea; hydrocarbons (kerosene, mineral oil, etc.), aromatic hydrocarbons (
benzene, toluene, xylene, etc.), chlorinated hydrocarbons (chloroform, carbon tetrachloride, etc.), ethers (dioxane, tetrahydrofuran, etc.), ketones (acetone, cyclohexanone, isophorone, etc.), esters (ethyl acetate, ethylene glycol acetate, etc.) , dibutyl maleate, etc.), alcohols (methanol, n-
hexanol, ethylene glycol, etc.), polar solvents (
liquid carriers such as dimethylformamide, dimethylsulfoxide, etc.) or water; gaseous carriers such as air, nitrogen, carbon dioxide, freon, etc. (in this case, mixed injection can be performed).

Examples of surfactants and dispersants that can be used to improve properties such as adhesion to animals and plants, absorption, dispersion, emulsification, and spreading of drugs include alcohol sulfate esters, alkyl sulfonates, lignin sulfonate,
Examples include polyoxyethylene glycol ether.

In order to improve the properties of the preparation, carboxymethyl cellulose, polyethylene glycol, gum arabic, etc. can be used as adjuvants.

In the basic production method, the carrier, surfactant, dispersant, and auxiliary agent described above can be used individually or in appropriate combinations depending on the purpose.

When the compound (I) of the present invention is formulated, the active ingredient concentration is usually 1 to 50% by weight in an emulsion and usually 0.3.
For ~25% weight additives, it is usually 0.5~5% by weight for 1~90% weight additives, for oil agents it is usually 0.5~5% by weight, and for aerosols it is usually 0゜1~5% by weight. be.

These preparations can be diluted to an appropriate concentration and sprayed on plant foliage, soil, or the water surface of paddy fields, depending on the purpose.
Alternatively, it can be applied directly for various purposes.

〔Example〕

Hereinafter, the present invention will be illustrated by reference examples and examples.

Note that these Examples do not limit the scope of the present invention.

Reference Example 1 [Synthesis of raw material compound (II)] Ethyl acetoacetate (13 g) and methylhydrazine (4,
6g) was dissolved in ethanol (50mA) and stirred under reflux for 3 hours.

This was concentrated under reduced pressure, and the resulting oil was converted into ethanol (
It was dissolved in 50mj.

6N hydrochloric acid (60 mI!,) was added to this, and water-cooled sodium nitrite (14 g) dissolved in water (20 mI!,) was added dropwise, followed by stirring at the same temperature as above for 1 hour.

This was extracted with ethyl acetate, dried over anhydrous magnesium sulfate, and then the solvent was distilled off.

By washing the obtained crystals with hexane, the yellow crystals of 4-hydroxyimino-
12 g of 1,3-dimethyl and lab-ru-5-one were obtained.

Reference Example 2 [Synthesis of raw material compound (III)] Sodium 4-methylbenzenesulfonate (19 g) was suspended in 30 mJ of DMF, and the internal temperature was adjusted to 10 to 12 mJ.
Thionyl chloride (8 mA) was added dropwise while maintaining the temperature at °C.

After stirring at the above internal temperature for 10 minutes, the reaction solution was poured into ice water.
This was extracted with ether. After washing the organic layer with water,
It was dried with anhydrous magnesium sulfate.

By distilling off the solvent, 19 g of colorless crystal 4-methylbenzenesulfonyl chloride, which was the starting compound (■), was obtained.

Furthermore, substituents (R, and R4) as shown in Table 1
It was possible to obtain each raw material compound (I[[) 17 Cf R3R4 (I[[) ) having the following.

Example 1 [1,3-dimethyl-4-(4-methylbenzenesulfonyl)oximinopyrazol-5-one (compound 1)
[Synthesis] Raw material compound (II) of Reference Example 1 (0.71 g, 5 mmo
Il) and 4- which is the starting compound (II[) of Reference Example 2
Methylbenzenesulfonyl chloride (0.96g, 5
．． Dissolve 0 mmoj in methylene chloride (10 mm,
Lysine (0.43 g, 5.5 mmoi!) was added to this, and the mixture was stirred at room temperature for 2 hours. This was washed with dilute hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and then the solvent was distilled off.

The resulting residue was subjected to silica gel column chromatography (
Wakogel C-200,) Luene: Ethyl acetate = 2
= 1), and the target compound (I) was isolated as orange crystals (shown as Compound 1 in Table 1).
1.4 g of the product was obtained (yield: 9518-%).

(syn-1,3-dimethyl-4-cinnamoyloxyiminopyrazole”5-one (compound 22) and ant
Synthesis of i-1,3-dimethyl-4-cinnamoyloxyiminopyrazol-5-one (Compound 23) Raw material compound (I[) of Reference Example 1 (0.71 g, 5 mmo
f) and cinnamoyl chloride (0.83 g, 5.0 mm), which is the raw material compound (DI) of Reference Example 2.

1) was dissolved in methylene chloride (10 ml), pyridine (0.43 g, 5.5 mmol) was added thereto, and 2
Stirred at room temperature for an hour. This was washed with dilute hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and then the solvent was distilled off.

The resulting residue was subjected to silica gel column chromatography (
Wakogel C-200, toluene: ethyl acetate = 2:
The geometric isomers were each isolated by purification in step 1), and the target compound (■) in the form of orange crystals [Table 1 shows 5yn
-1,3-dimethyl 4-cinnamoyloxyiminopyrazol-5one (compound 22), anti-1,3-
Dimethyl-4-cinnamoyloxyiminopyrazole-
5-one was shown as (compound 23). ]1.4g
was obtained (yield: 95%).

[Synthesis of compounds 2 to 21 and 24 to 48 in Table 1] Starting compound (II) and each starting compound in Reference Example 2 (
Each target compound (I) as shown in Table 1 (shown as Compounds 2-21.24-48 in Table 1) was synthesized using the same synthesis method as Compound 1.22 or 23 using In). ) was able to be obtained.

Example 2 [Preparation of emulsion] 50 parts by weight of Compound 1, 30 parts by weight of xylene, 10 parts by weight of Agelisil P-300 (trade name; manufactured by Kao Atlas), 5 parts by weight of Emulgen A-90 (trade name; manufactured by Kao Atlas). Part, Rheosol 460 (product name; manufactured by Kao Atlas) 5
Parts by weight were mixed and dissolved to obtain an emulsion.

Example 3 [Preparation of finely powdered wettable powder] 10 parts by weight of compound 22, 69.75 parts by weight of Kaolin', 18 parts by weight of white carbon, 1.8 parts by weight of Neoperex powder (trade name; manufactured by Kao Atlas) and 0.45 parts by weight of Demol EP (trade name; manufactured by Kao Atlas Co., Ltd.) were uniformly mixed and ground to obtain a finely powdered wettable powder.

Example 4 [Control efficacy test (preventive effect) against cucumber and disease] One cucumber (variety: Sumo Hanshiro) per pot was grown in a plastic flower pot with a diameter of 6 cm, and the seedlings were grown at the 1.5-leaf stage. A wettable powder prepared from the target compound (I) shown in Table 1 according to Example 3 was diluted to 500 ppm with water containing a surfactant (0.01%), and 20 mJ per pot was prepared.
2 was sprayed.

After spraying, cultivation was carried out in a glass greenhouse for 2 days, and then cucumbers and diseased bacteria (Pseudoperonospora cu
bensiS) zoosporangial suspension (7X10' spores/
M! ! , ) was spray-inoculated uniformly on the underside of the plant leaves.

After inoculation, the cucumbers were kept in the dark at 20°C for 1 day, and then grown in a glass greenhouse for 5 days, and the extent of cucumbers and lesions that appeared on the first leaves was examined.

The drug effect was determined by comparing the degree of lesions in the untreated plot.

The evaluation is given on a 6-level scale of 5.4.3.2.1.0, with 5 being no lesions and 10% of the lesion area compared to the untreated area.
Below, approximately 4.20%, 3.40%, and 2.60% were indicated as 1, and cases where the entire population was affected were indicated as O. In addition, the control compound is 4-(4-chlorobenzoyloxyimino) 1<3-dimethyl-2-pyranolin 5-one CH shown in the following formula (A).

was used at 500 ppm.

The results are shown in Table 2. show.

(Hereinafter, blank space) 26 Table 4 Example 5 [Control efficacy test against rice blast (preventive effect)] Ten rice plants (variety: Nipponbare) were grown per pot in plastic flower pots with a diameter of 6 cm, and 1.5 A wettable powder prepared according to Example 3 containing the target compound (I) shown in Table 1 was diluted to 500 ppm with water containing a surfactant (0.01%) to a young plant at the leaf stage. In short, 20m1 per pot! , was scattered.

After spraying, the rice blast fungus (Pyricularia
oryzae) conidial suspension (7X 10' spores/
mI! , ) was evenly spray inoculated onto the plant leaves.

After inoculation, the plants were grown in a humid room at 28°C for 5 days, and the extent of rice blast lesions that appeared on the leaves was examined.

The drug effect was determined by comparing the degree of lesions in the untreated plot.

The results are shown in Table 3 using the same evaluation method as in Example 5. Note that the control compound includes the compound shown in Example 5 (
A) was used at 500 ppm.

(Hereinafter, blank spaces) Table Example 6 [Control efficacy test (preventive effect) against wheat rust] Ten wheat plants (variety: Kaffirella trifoliata) were grown per pot in plastic flower pots with a diameter of 6 cm, and the wheat was grown at the 1.5-leaf stage. A hydrating agent prepared according to Example 3 containing the target compound (I) shown in Table 1 was added to a seedling of a surfactant (0.01%).
) diluted to 500 ppm with water containing 20 per pot.
mI! , was scattered.

After spraying, the plants were cultivated in a glass greenhouse for 2 days, and then a spore suspension of Puccinia dispersa (7 x 10' spores/m2) was uniformly spray-inoculated onto the plants.

After inoculation, the plants were grown in a glass greenhouse for one week, and the extent of wheat rust lesions that appeared on the first leaves was examined.

The drug effect was determined by comparing the degree of lesions in the untreated plot.

The results are shown in Table 4 using the same evaluation method as in Example 4. Note that the control compound includes the compound shown in Example 4 (
A) was used at 500 ppm.

Table 4 30 - The present invention can provide pyrazole derivatives having excellent bactericidal effects.

Claims (3)

[Claims] (1) The following formula: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) (In the formula, R_1 represents an alkyl group having 1 to 8 carbon atoms or a phenyl group that may be substituted; represents an alkyl group having 1 to 4 atoms, an optionally substituted phenyl group, or an optionally substituted pyridyl group;
R_3 represents a sulfonyl group or a carbonyl group; R_
4 is an optionally substituted phenyl group, an optionally substituted naphthyl group, an optionally substituted benzyl group,
It represents an optionally substituted styryl group, an optionally substituted quinolyl group, a halogenated alkyl group having 1 to 6 carbon atoms, a furylethylene group, or an alkenyl group having 2 to 10 carbon atoms. ). (2) The following formula: ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (II) (In the formula, R_1 and R_2 have the same meanings as in claim 1) and the following formula: X-R_3-R_4 ( III) (wherein, X represents a leaving group; R_3 and R_4 have the same meanings as in claim 1) under alkaline conditions. (I) Method for producing the compound. (3) A fungicide containing the compound of formula (I) according to claim 1 as an active ingredient.