JPH0357898B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel 3-hydroxyisoxazole derivative and a method for producing the same. The compounds of the invention have the formula (In the formula, R ¹ represents a hydrogen atom or a halogen atom, and R ² represents a hydrogen atom, an alkyl group, a lower alkenyl group, a lower alkynyl group, a cycloalkyl group, an aralkyl group that may have a substituent, or a substituent. Indicates an optional aryl group, A is a sulfur atom,
Indicates a sulfinyl group or a sulfonyl group. ) is a 3-hydroxyisoxazole derivative. In the above formula (), the halogen atom of R ¹ is:
Examples include chlorine, bromine, iodine or fluorine atoms, with chlorine and bromine atoms being preferred. The alkyl group of R ² may be linear or branched, and may be a C _1-8 alkyl group, such as methyl, ethyl n
-propyl, isopropyl, n-butyl, t-butyl, n-pentyl, and n-octyl. Examples of the lower alkenyl group for R ² include allyl and methallyl. Examples of the lower alkynyl group for R ² include 1-propynyl and 2-propynyl. Examples of the cycloalkyl group for R ² include cyclohexyl. The optionally substituted aralkyl group for R ² includes, for example, benzyl or phenethyl with or without substituents such as halogen, lower alkyl, lower alkoxy, trifluoromethyl, nitro or carboxyl. ^R2
Examples of the aryl group which may have a substituent include halogen, lower alkyl, lower alkoxy,
Mention may be made of phenyl or naphthyl with or without substituents such as trifluoromethyl or carboxyl. Examples of the salt of the compound of formula () include alkali metal salts and alkaline earth metal salts. The compound of formula () is effective for controlling rice seedlings, and preferred compounds are those in which R ¹ is a hydrogen atom or a chlorine atom, particularly a hydrogen atom, and R ² is a linear lower alkyl group or a lower alkenyl group, A
is a compound that is a sulfur atom. The compound of formula () is also useful as an intermediate for the synthesis of compounds of formula () and formula (), which are useful as insecticides and acaricides for controlling two-spotted spider mites and aphids, by the method shown below. (In the formula, R ¹ , R ² and A are the same as described above.
Y represents a halogen atom. ) Preferred compounds as such synthetic intermediates include R ¹ being a hydrogen atom, chlorine atom, or bromine atom, R ² being a linear lower alkyl group or lower alkenyl group, and A being a sulfur atom, a sulfinyl group, or a sulfinyl group. This is a compound that is a sulfonyl group. The compounds of formula () of the present invention are illustrated in the following table.
Note that compound numbers are referred to in the following description.

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[Table] The present invention also relates to a method for producing the compound of formula (), which is produced by the following various methods. (In the formula, R ¹ and R ² are the same as above,
and Y represents a halogen atom, M represents an alkali metal, and n represents 1 or 2. ) (1) In the formula (), A is a sulfur atom (-
The compound of 1) can be prepared by reacting the compound of formula (a) with mercaptide (R ² SM) or by reacting the compound of formula (b) with formula ().
The compound of formula () obtained by reacting the compound with thiourea is reacted with a halide (R ² Y), or the compound of formula (c) is reacted with sulfuric diester ((R ² ) ₂ SO ₄ ). Obtained by reaction. In the method (a), the mercaptide can be used as a previously produced mercaptide, or can be generated in the reaction solvent. The above methods (a), (b) and (c) are carried out in the presence of a base such as an alkali hydroxide or an alkali carbonate.
Water; alcohols such as methanol and ethanol; ethers such as tetrahydrofuran, dioxane, and diglyme; ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; dimethylformamide; dimethyl sulfoxide; hexamethylphosphoramide and mixed solvents thereof Particularly suitable solvents are water and methanol. The reaction temperature is 0° C. or higher and the reaction is carried out under reflux of the solvent, preferably 0° C. or higher and room temperature. Since the compound of formula (-1) is produced as an alkali metal salt, the desired product can be obtained by neutralizing it with an acid such as hydrochloric acid or sulfuric acid. (2) A compound of formula (-2) in which A is a sulfinyl group or a sulfonyl group can be obtained by reacting a compound of formula (-1) with a peroxide. Examples of the peroxide include hydrogen peroxide, benzoyl peroxide, and methachloroperbenzoic acid, with methachloroperbenzoic acid being particularly preferred. It is preferable to use hydrogen peroxide in an equimolar amount, and the reaction temperature is preferably in the range of 5 to 25°C. It is usually preferable to use molar or more of methachloroperbenzoic acid, and the reaction temperature is 0.
The reaction is completed in several hours at a temperature ranging from .degree. C. to room temperature or lower, but it can also be carried out under reflux of the solvent if necessary. As reaction solvents, aliphatic carboxylic acids, especially acetic acid, are used when hydrogen peroxide is used, and substantially inert organic solvents are used when methachloroperbenzoic acid is used, but in particular halogenated hydrocarbons are used. such as methylene chloride, carbon tetrachloride, chloroform, chlorobenzene or o-
Dichlorobenzene is preferred. (3) The raw material compound having the formula () is new and is produced by reacting the 5-halogenomethylisoxazole derivative of the formula () with thiourea. Examples of the reaction solvent include ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone; and alcohols such as methanol, ethanol, and propanol, with acetone and ethanol being particularly preferred. It is preferable to use equimolar amounts of thiourea. The reaction temperature is 0° C. or higher and the solvent is refluxed, preferably room temperature or higher than the reflux temperature of the solvent. After the reaction is complete, the reaction mixture is cooled to below room temperature and vortexed.
If the crystals are washed with acetone, methanol or ethanol and then dried, a substantially pure compound of formula () can be obtained. In addition, among the compounds of formula () which are raw material compounds, the compound in which R ¹ is a hydrogen atom and X is a halogen atom is Tetrahedron Letters No. 25.
2077 (1965), the compound in which R ¹ and
It is manufactured according to the method described in the publication. In addition, the compound of formula () is useful as a synthetic intermediate, and is also used as a control agent for rice seedlings, and is also effective against rice blast, sesame flaking disease, and tomato leaf blight. In order to use the compound of formula () as a rice seedling control agent, 0.01 to 1 g of the active ingredient is sprinkled or mixed into the soil per seedling raising box (wooden box 60 cm long, 30 cm wide, 3 cm deep). Methods include coating seeds with powder or soaking rice seeds, and any of these methods can be effective. To prepare rice seedling control agent, formula ()
The compound can be mixed with a carrier and formulated into powders, wettable powders, tablets, powder coatings, emulsions, etc.
Of course, other plant growth regulators, fungicides, insecticides, fertilizers, etc. can also be used in combination. Example 1 A 15% aqueous solution of the sodium salt of methyl mercaptan in a solution of 3.2 g of caustic soda dissolved in 16 ml of water.
32 ml was added to this mixed solution at room temperature with stirring.
10.6 g of hydroxy-5-chloromethylisoxazole was added, and the mixture was further stirred at room temperature for 30 minutes. After adding about 50 ml of 2N sulfuric acid to the reaction mixture to make it acidic,
The precipitated crystals were vortexed, washed with about 100 ml of water, and air-dried to form 3-hydroxy-5-methylthiomethylisoxazole with a melting point of 90-91°C.
7.05g (yield 61.1%) was obtained. Furthermore, the combined solution and washing solution was extracted three times with 50 ml of diethyl ether, the extracts were combined and dried with sodium sulfate, the solvent was distilled off, and the residue was chromatographed on silica gel to obtain hexane:diethyl ether=
Purification was carried out by elution at a ratio of 1:1, and the solvent was distilled off from the eluate to obtain a pure target compound. Example 2 3-Hydroxy-4-chloro-5-amidinothiomethylisoxazole hydrobromide 2.88
30 ml of water and a solution of 1.7 g of caustic soda dissolved in 10 ml of water were added to the mixture and stirred. After the crystals were dissolved, 1.44 ml of diethyl sulfate was added and the mixture was further stirred at room temperature for 1 hour and 15 minutes. After adjusting the pH to around 3 by adding 2N sulfuric acid to the reaction mixture, it was extracted twice with 20 ml of diethyl ether, the ether extracts were combined and dried over Glauber's salt, the solvent was distilled off, and the residue was purified with silica gel. It was purified by column chromatography by elution with hexane:diethyl ether = 1:1, the solvent was distilled off from the eluate, and the residue was recrystallized from hexane to give 3-hydroxy-4 with a melting point of 49-51°C. 1.70 g (yield: 87.6%) of crystals of -chloro-5-ethylthiomethylisoxazole were obtained. Example 3 Dissolve 1.2 g of caustic soda in 10 ml of water, and add 1.44 g of 5-amidinothiomethyl-4-chloro 3-hydroxyisoxazole hydrobromide to this solution.
g was added and heated to 60°C to dissolve. After cooling to room temperature, it was made acidic with 2N sulfuric acid, extracted five times with 10 ml of diethyl ether, the ether extracts were combined and dried over Glauber's salt, the solvent was distilled off, and the residue was chromatographed on silica gel using hexane: Elution was carried out with diethyl ether = 1:1, and the solvent was distilled off from the eluate to obtain 3-hydroxy-4 with a melting point of 104-105°C.
0.71 g (yield: 85.5%) of crystals of -chloro-5-mercaptomethylisoxazole was obtained. Example 4 Dissolve 0.36g of carbonated soda in 20ml of methanol,
To this solution, 419 mg of 5-amidinothiomethyl-3-hydroxy)isoxazole hydrochloride was added and dissolved, and then 190 mg of methallyl chloride was added and stirred at room temperature for 1 hour. Distill the solvent and collect 30ml of the residue.
After dissolving in water, adjusting the pH to about 2 with 2N sulfuric acid, extracting twice with 10 ml of diethyl ether,
The ether extracts were combined, dried over Glauber's salt, the solvent was distilled off, and the residue was purified through a silica gel column eluting with hexane:diethyl ether = 1:1. When the solvent was distilled off from the eluate, the melting point was 88-89. 332 mg (yield: 89.7%) of crystals of 3-hydroxy-5-methallylthiomethylisoxazole were obtained. Example 5 To a solution of 0.73 g of 3-hydroxy-5-methylthiomethylisoxazole in 15 ml of methylene chloride, a solution of 1.02 g of 85% methachloroperbenzoic acid in 10 ml of methylene chloride was added over 10 minutes while stirring on ice, and the mixture was further heated to room temperature. The mixture was stirred for 3 hours. 5 g of chromatographic silica gel was added to the reaction mixture, the solvent was distilled off, and the residue was loaded onto a silica gel column and first eluted with diethyl ether to remove methachlorobenzoic acid, then acetone, and the solvent was removed from the eluate. is distilled off, a brown oil is obtained, which is crystallized by adding a mixed solvent of benzene:acetone = 10:1, and then recrystallized from the same mixed solvent to give a slightly yellow needle with a melting point of 96-97℃. 0.66 g (yield: 81.9%) of 3-hydroxy-5-methylsulfinylmethylisoxazole crystals were obtained. Reference example 1 0.8 g of thiourea was dissolved in 30 ml of acetone, and 1.96 g of 5-bromomethyl-4-chloro-3-hydroxyisoxazole was added to this solution, followed by stirring at room temperature for 4.5 hours. The precipitated crystals were vortexed, washed with 30 ml of acetone, and dried to give 2.66 g (yield) of the desired product with a melting point of 171°C (decomposition).
100%) was obtained. According to the method of Reference Example 1, the following compound was produced.

[Table] Reference example 2 3.59 g of 3-hydroxy-5-methylthiomethylisoxazole and 2.2 g of dimethylcarbamoyl chloride were dissolved in 55 ml of benzene, and a solution of 2.5 g of triethylenediamine in 40 ml of benzene was added dropwise to this solution over 3 minutes while stirring at room temperature. The mixture was further stirred at room temperature for 1 hour. The triethylenediamine hydrochloride was removed by vortexing, the solvent was distilled off from the solution, the residue was purified by eluting with benzene:acetone=10:1 through a silica gel column, and the solvent was distilled off from the eluate. ²¹ _D 1.5221 3-dimethylcarbamoyloxy-4-chloro-5-methylthiomethylisoxazole 4.67 g colorless oil (yield
93.2%) was obtained. According to the method of Reference Example 2, the following compound was produced.

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[Table] Test example Rice seedling control test The test compound was prepared as a 2% powder and applied as an active ingredient to diluvial volcanic ash soil (Kuroboku) with a pH of 6.0.
It was mixed to a concentration of 40 ppm. Separately, rice seeds (variety Nihonbare) were soaked in running water for 5 days, and then
The seeds were left at ℃ overnight to germinate. The soil mixed with the above test compound was placed in a seedling box (60 cm vertically, 30 cm horizontally, 3 cm deep).
cm), and 120 g (in terms of dry seeds) of germinated seeds were sown per box. After sowing and covering with soil, seedlings were placed in a room at 32℃ for 2 days to allow them to germinate, then raised in a greenhouse at 10℃ to 25℃ for 5 days, then in a plastic greenhouse at 0℃ (nighttime) to 35℃ (daytime) for 28 days. The area where stuffy seedlings appeared was investigated. In addition, the growth suppression system for rice seedlings was investigated 3 weeks after sowing.

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Claims (1)

[Claims] 1 formula (In the formula, R ¹ represents a hydrogen atom or a halogen atom, and R ² represents a hydrogen atom, an alkyl group, a lower alkenyl group, a lower alkynyl group, a cycloalkyl group, an aralkyl group that may have a substituent, or a substituent. Indicates an optional aryl group, A is a sulfur atom,
Indicates a sulfinyl group or a sulfonyl group. ) or a salt thereof. 2 formulas (In the formula, R ¹ represents a hydrogen atom or a halogen atom.) In the presence of a base, an acid addition salt of a 5-amidinothiomethylisoxazole derivative having the formula R ² Y or (R ² ) ₂ SO ₄ ( In the formula, ^R2 represents a hydrogen atom, an alkyl group, a lower alkenyl group, a lower alkynyl group, a cycloalkyl group, an aralkyl group that may have a substituent or an aryl group that may have a substituent, and Y is (representing a halogen atom), characterized by reacting a halide or sulfuric acid diester with (In the formula, R ¹ and R ² are the same as those described above.) A method for producing an isoxazole derivative or a salt thereof.