JP2552846B2 - Substituted thiazolecarboxylic acid derivatives and agricultural and horticultural fungicides containing the same as active ingredients - Google Patents

Description

The present invention relates to a substituted thiazole carboxylic acid derivative and a fungicide for agricultural and horticultural use containing the same as an active ingredient.

<Prior Art> The fact that certain substituted thiazolecarboxylic acid derivatives have bactericidal activity is found in Chem Abstr. 70 87799j (S. African 6
7 06,681 Uniroyal, Inc), GA White et al. Pesticide Bioc
hemistry and Physiology 5,380-895 (1975) and M.
Shell et al. Phytopatholoy 60 , 1164-1169 (1970).

<Problems to be Solved by the Invention> However, the compounds exemplified in these documents are insufficient in potency and the like, and it cannot be said that they are necessarily satisfactory. Therefore, development of a drug with few such defects is desired.

<Means for Solving Problems> In view of the above situation, the present inventors have made various studies to develop a compound having excellent bactericidal activity, and as a result, have shown the substituted thiazole represented by the following general formula [I]. The present invention has been found out that a carboxylic acid derivative, particularly a substituted indanylamine derivative thereof, has excellent bactericidal activity with few defects as described above.

That is, the present invention has the general formula [In the formula, R ₁ represents a methyl group, an ethyl group or a trifluoromethyl group, X represents an amino group, a methyl group or a chlorine atom, Y represents an oxygen atom or a sulfur atom, and R ₂
Represents a hydrogen atom or a methyl group. ] A substituted thiazolecarboxylic acid derivative represented by the following (hereinafter referred to as the compound of the present invention) and an agricultural and horticultural fungicide containing the same as an active ingredient are provided.

The compound of the present invention is prophylactic against various plant pathogens, especially plant diseases caused by microorganisms belonging to basidiomycetes, and is curative.
It is an excellent active ingredient of a bactericidal agent because it has a systemic migration bactericidal effect and has little effect on the environment.

Examples of plant diseases in which the compound of the present invention has excellent efficacy include, for example, rice blight (Rhizoctonia solani), pseudo-blight blight (Rhizoctonia oryzae, R.solani III B type),
Rust of wheat (Puccinia striiformis, P. graminis, P.
recondita, P.hordei), snow rot (Typhula incarrata, T.
ishikariensis), naked smut (Ustilago tritici, V.nud
a), damping-off of various crops (Rhizoctonia solani), white silkworm (Corticiumolfsii), potato and beet rhizoctonia (Rhizoctonia solani), pear scab (Gymn)
osporangium haraeanum), apple scab (Venturia)
inaequaris), grass and lawn leaf rot (Rhizoctoniasol)
ani), White silkworm (Corticium rolfsii), Leaf rust (Urom)
ycestifolii), snow rot (Typhula incarnata, T.ishikar
iensis) and the like.

 Next, the method for producing the compound of the present invention will be described in detail.

[Production method (a)]

General formula of the compound of the present invention Wherein R ₁ , R ₂ and X have the same meaning as described above. ] The substituted thiazolecarboxylic acid derivative represented by [In the formula, R ₁ and X have the same meanings as described above. ] A substituted thiazole carboxylic acid represented by the formula [Wherein, R ₂ has the same meaning as described above. ] It can manufacture by making it react with the substituted amino indane derivative shown by these.

In the reaction, a reaction solvent is not necessarily required, but generally, the reaction is carried out in the presence of a solvent.

Examples of the solvent used in the above reaction include hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as chlorobenzene, methylene chloride, chloroform and carbon tetrachloride, diisopropyl ether, tetrahydrofuran and dioxane. Ethers such as
Examples include ketones such as acetone and methyl ethyl ketone, esters such as ethyl acetate, nitriles such as acetonitrile, dimethylsulfoxide, dimethylformamide, and water, and preferably tetrahydrofuran.

The amount of the reagent used in the above reaction is 0.4 to 1.5 for the substituted thiazolecarboxylic acid represented by the general formula [III] or its reactive derivative with respect to 1 equivalent of the substituted aminoindan derivative represented by the general formula [IV]. Equivalent, preferably 0.5
The range is to 1.1 equivalents.

The above reaction is carried out at any temperature from the freezing point to the boiling point of the solvent, but preferably at a temperature from 0 ° C. to the boiling point of the solvent.

Examples of the substituted thiazolecarboxylic acid represented by the general formula [III] or its reactive derivative to be used include corresponding carboxylic acids, acid anhydrides, acid chlorides, acid bromides, carboxylic acid esters and the like.

The above reaction can be carried out in the presence of a suitable reaction aid depending on the substituted thiazolecarboxylic acid represented by the general formula [III] or the reactive derivative thereof.
For example, when a carboxylic acid is used, dicyclohexylcarbodiimide, phosphorus pentachloride and the like can be used, and when a carboxylic acid ester is used, sodium methylate, sodium ethylate and the like can be used. Further, when an acid halogen compound or an acid anhydride is used, sodium hydroxide, potassium hydroxide, triethylamine, N-methylmorpholine and the like can be used.

These reaction auxiliaries are usually used in the range of a catalyst amount to 2 equivalents, but preferably the reaction can be carried out in an amount of 0.95 to 1.1 equivalents.

After completion of the reaction, the reaction solution is filtered, washed with water and the like, and then the solvent is distilled off and, if necessary, subjected to an operation such as recrystallization to obtain the target compound.

[Production method (b)]

Among the compounds of the present invention, the general formula [In the formula, R ₁ and R ₂ have the same meanings as described above, and Z is
Represents an amino group or a methyl group. ] The substituted thiazolecarboxylic acid derivative represented by [In the formula, R ₁ and R ₂ have the same meanings as described above. ] The substituted aminoindan derivative represented by [In the formula, Z represents the same meaning as described above. And a thioamide derivative represented by the following formula:

In the reaction, a reaction solvent is not necessarily required, but generally, the reaction is carried out in the presence of a solvent. Examples of the solvent used include hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as chlorobenzene, diisopropyl ether, tetrahydrofuran,
Examples thereof include ethers such as dioxane, esters such as ethyl acetate, alcohols such as methanol and ethanol, dimethyl sulfoxide, dimethylformamide, water and the like.

The amount of the reagent used in the above reaction is not particularly limited, but usually the thioamide derivative represented by the general formula [VII] is added to 1 equivalent of the substituted aminoindan derivative represented by the general formula [VI]. , 0.5 to 10 equivalents, preferably 1 to 3 equivalents.

The above reaction can be carried out at any temperature between the freezing point and the boiling point of the solvent, preferably at a temperature between 0 ° C. and the boiling point of the solvent.

In the above reaction, a base can also be used as a reaction aid if necessary.
Examples thereof include aqueous ammonia, amines such as triethylamine and N-methylmorpholine, and inorganic bases such as potassium carbonate and sodium carbonate.

After completion of the reaction, the reaction solution is filtered, washed with water, etc., the solvent is distilled off, and if necessary, subjected to operations such as recrystallization and chromatography to obtain the target compound.

[Production method (c)]

Of the compounds of the present invention, the general formula Wherein R ₁ , R ₂ and X have the same meaning as described above. The substituted thiazolecarboxylic acid derivative represented by the above formula can be produced by reacting the substituted thiazolecarboxylic acid derivative represented by the general formula [II] with a thionation reaction reagent.

Examples of the thionation reaction reagent used in the above reaction include phosphorus pentasulfide, 2,4-bis (methylthio) -1,3,2,4-dithiadiphosphetan-2,4-disulfide and 2,4-bissulfide. (P-Methoxyphenyl) -1,3,2,4-dithiadiphosphatane-
2,4-disulfide and the like can be mentioned.

In the above reaction, a reaction solvent is not always necessary, but it is generally carried out in the presence of a solvent.

The amount of the reagent used in the above reaction is not particularly limited, but usually the thionation reagent is 0.5 to 20 equivalents, preferably 1 to 1 equivalent of the substituted thiazolecarboxylic acid derivative represented by the general formula [II]. Is in the range of 1 to 10 equivalents.

The above reaction can be carried out at any temperature between the freezing point and the boiling point of the solvent, preferably at a temperature between 0 ° C. and the boiling point of the solvent.

After completion of the reaction, the reaction solution is concentrated or extracted, washed with water, and optionally subjected to an operation such as recrystallization to obtain the substituted thiazolecarboxylic acid derivative represented by the general formula [VIII].

When the compound of the present invention is used as an active ingredient of a fungicide, it may be used as it is without adding any other components.
Usually, it is mixed with a solid carrier, a liquid carrier, a surfactant, and other formulation auxiliaries to be formulated into emulsions, wettable powders, suspensions, granules, powders, liquids and the like.

These preparations contain the compound of the present invention as an active ingredient in a weight ratio of 0.1 to 99.9%, preferably 0.2 to 80%.

As a solid carrier, kaolin clay, attapulgite clay, bentonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite, corn cob powder, walnut shell powder, urea, ammonium sulfate, fine powder of synthetic hydrous silicon dioxide, etc. Alternatively, a granular material may be used, and examples of the liquid carrier include aromatic hydrocarbons such as xylene and methylnaphthalene, alcohols such as isopropanol, ethylene glycol and cellosolve, ketones such as acetone, cyclohexanone and isophorone, soybean oil and cottonseed oil. Vegetable oil, dimethyl sulfoxide, acetonitrile, water and the like.

Surfactants used for emulsification, dispersion, wet spreading, etc. include alkyl sulfates, alkyl (aryl) sulfonates, dialkyl sulfosuccinates, polyoxyethylene alkyl aryl ether phosphates, and naphthalene sulfones. Examples include anionic surfactants such as acid formalin condensates, and nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene polyoxypropylene block copolymers, sorbitan fatty acid esters, and polyoxyethylene sorbitan fatty acid esters. Pharmaceutical adjuvants include lignin sulfonate, alginate, polyvinyl alcohol, gum arabic, CMC (carboxymethylcellulose), PAP
(Acid isopropyl phosphate) and the like.

These preparations are applied undiluted or directly to plants, for example, diluted with water, or applied to soil.

More specifically, it can be used in various forms such as by spraying or dusting the above-mentioned formulation on plants, spraying, dusting or granulating on the surface of soil, or if necessary, further gentle treatment with soil. When used as a seed treatment agent, seed dressing treatment, seed dipping treatment and the like can be used. In addition, it can be expected to enhance the bactericidal effect by mixing with other bactericides. In addition, insecticides,
Acaricide, nematicide, herbicide, plant growth regulator, fertilizer,
It can also be used as a mixture with a soil conditioner.

The compound of the present invention can be used as an active ingredient of a fungicide for paddy fields, fields, orchards, pastures, lawns, and the like.

When the compound of the present invention is used as an active ingredient of a fungicide,
The application rate is meteorological conditions, formulation form, application time, method,
Although it varies depending on the place, target disease, target crop, etc., it is usually 0.5 g to 100 g, preferably 1 g to 50 g per are, and the emulsion, wettable powder, suspension, liquid, etc. are diluted with water before application. In this case, the application concentration is 0.001% to 1%, preferably 0.005% to 0.5%, and granules, powders, etc. are applied as they are without any dilution.

<Examples> The present invention will be described in more detail below with reference to manufacturing agents, reference examples, formulation examples and test examples.

 First, a production example is shown.

Production Example 1 (Synthesis of Compound (5) by Production Method (a)) 0.82 g (5.07 mmo) of 1,1-dimethyl-4-aminoindane
l), pyridine 0.48 g (6.08 mmol) and tetrahydrofuran 10 ml while stirring under ice-cooling at an internal temperature of 5 ° C. or lower, while stirring 2-chloro-4-methylthiazole-5-carboxylic acid chloride 0.99 g (5.07 mmol). Tetrahydrofuran 3
The solution dissolved in ml was dropped. After completion of dropping, the mixture was stirred overnight at room temperature, and then water and ethyl acetate were added to separate the layers.
The organic layer was washed with 5% hydrochloric acid and water in this order and then dried over anhydrous sodium sulfate. The crystals obtained by distilling off the solvent were washed with n-hexane and dried to give 1.51 g of N- (1,1-dimethyl-4-indanyl) -2.
-Chloro-4-methylthiazole-5-carboxylic acid amide was obtained (yield 93%).

Production Example 2 (Synthesis of Compound (6) by Production Method (a)) 2-Chloro-4-methylthiazole-5-carboxylic acid
252 mg (1.42 mmol) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide methodide 422 m
After dissolving g (1.42 mmol) in 10 ml of methylene chloride and stirring at room temperature for 1 hour, 249 mg (1.42 mmol) of 1,1,3-trimethyl-4-aminoindan was added thereto and reacted for 6 hours under reflux. Then, methylene chloride and water were added to the reaction solution to separate the layers, and the organic layer was concentrated and purified by column chromatography (developing solution; n-hexane: ethyl acetate = 50: 50) to give 204 mg of N- (1, 1,3-Trimethyl-4-indanyl) -2-chloro-4-methylthiazole-5-carboxylic acid amide was obtained (yield 43%).

Production Example 3 (Synthesis of Compound (4) by Production Method (b)) N- (1,1-dimethyl-4-indanyl) acetoacetamide 1.00 g (4.08 mmol) and thiourea 0.62 g (8.16 mm)
ol) was dissolved in 10 ml of benzene, and a solution of 0.55 g (4.08 mmol) of sulfuryl chloride in 5 ml of benzene was added dropwise at room temperature. After reacting for 2 hours at the same temperature, the mixture was reacted under reflux for 1 hour and left overnight. Next, the reaction solution was concentrated, dissolved in hot water, and then neutralized with 28% aqueous ammonia to precipitate crystals. The crystals formed were filtered while hot, washed with water and dried to give 1.00 g of N- (1,1-dimethyl-4-indanyl)-
2-Amino-4-methylthiazole-5-carboxylic acid amide was obtained (yield 81%).

Production Example 4 (Synthesis of Compound (3) by Production Method (b)) N- (1,1-Dimethyl-4-indanyl) -2-chloroacetoacetamide 1,14 g (4.08 mmol) and thioacetamide 0.30 g (4.08) mmol) was dissolved in 10 ml of tetrahydrofuran, and the mixture was reacted under reflux for 3 hours. 0.56 g (4.08 mmol) of anhydrous potassium carbonate was added to the resulting reaction solution, and the mixture was reacted under reflux for 4 hours. Ethyl acetate and water were added to the resulting reaction solution, the layers were separated, and the organic layer was concentrated and purified by column chromatography (developing solution n-hexane-ethyl acetate 50:50) to give 0.52 g of N- (1, 1-Dimethyl-4-indanyl) -2,4-dimethylthiazole-5-carboxylic acid amide was obtained (yield 43%).

Production Example 5 (Synthesis of Compound (12) by Production Method (c)) N- (1,1,3-trimethyl-4-indanyl) -2-
0.20 g of methyl-4-trifluoromethyl-5-carboxylic acid amide and 0.18 g of 2,4-bis (methylthio) -1,3,2,4-dithiadiphosphetane-2,4-disulfide in 5 ml of tetrahydrofuran. The mixture was melted and reacted under reflux for 10 hours. After the reaction, the reaction solution was concentrated, and the residue was treated by column chromatography packed with silica gel (developing solution; n-hexane: chloroform: tetrahydrofuran = 6: 2: 1) to give 0.1.
4 g of N- (1,1,3-trimethyl-4-indanyl) -2
-Methyl-4-trifluoromethyl-5-carboxylic acid thioamide was obtained. (Yield 65%) The compounds of the present invention which can be produced by such a production method are summarized in Table 1.

Of the raw material compounds used in the synthesis of the compound of the present invention,
2-methyl-4-trifluoromethylthiazole-5-
The method for producing the carboxylic acid derivative will be described in detail below.

Reference Example 1 Synthesis of ethyl 2-methyl-4-trifluoromethylthiazole-5-carboxylate Ethyl 2-chloro-4,4,4-trifluoroacetoacetate
6.00 g and 2.06 g of thioacetic acid amide were dissolved in 30 ml of acetic acid and reacted under reflux with stirring for 6 hours. After the reaction, the reaction solution was neutralized with an aqueous sodium hydrogen carbonate solution, extracted with ethyl acetate, and concentrated.

The residue was treated by column chromatography packed with silica gel (developing solution; n-hexane / chloroform / tetrahydrofuran = 6: 2: 1) to give 3.7 g of 2-methyl-4-trifluoromethylthiazole-5-carboxylic acid. Ethyl was obtained (yield 56%).

PMR (CDCl ₃ ) δ4.33 (2H, q, J = 7.0Hz), 2.72 (3H, s,
1.36 (3H, t, J = 7.0Hz), F-NMR (CDCl ₃ / CF ₃ COOH) δ + 17.0 (3F, s) Reference Example 2 of 2-methyl-4-trifluoromethylthiazole-5-carboxylic acid Synthesis 2-methyl-4-trifluoromethylthiazole-5
-Ethyl carboxylate (1.3 g) and potassium hydroxide (0.4 g) were dissolved in water and ethanol (5 ml each), and the mixture was reacted overnight at room temperature. After the reaction, the reaction solution was concentrated, acidified with diluted hydrochloric acid, and extracted with ethyl acetate. By concentrating the extract, 0.89 g of 2-methyl-4-trifluoromethylthiazole-5-carboxylic acid was obtained.

Reference Example 3 Synthesis of 2-methyl-4-trifluoromethylthiazole-5-carbonyl chloride 2-Methyl-4-trifluoromethylthiazole-5
-0.50 g of carboxylic acid was added to 5 ml of thionyl chloride and reacted under reflux for 2 hours. After reaction, by concentrating the reaction solution
Obtained 0.54 g of 2-methyl-4-trifluoromethylthiazole-5-carbonyl chloride. Formulation examples are shown below. The compounds of the present invention are shown by the compound numbers in Table 1.
Parts are parts by weight.

Formulation Example 1 50 parts of each of the compounds (1) to (12) of the present invention, 3 parts of calcium ligninsulfonate, 2 parts of sodium lauryl sulfate and 45 parts of synthetic hydrous silicon oxide are well pulverized and mixed to obtain a wettable powder.

Formulation Example 2 10 parts of each of the compounds (1) to (12) of the present invention, 14 parts of polyoxyethylene styryl phenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 70 parts of xylene are mixed well to obtain an emulsion.

Formulation Example 3 2 parts of each of the compounds (1) to (12) of the present invention, 1 part of synthetic hydrous silicon oxide, 2 parts of calcium lignin sulfonate, 80 parts of bentonite and 65 parts of kaolin clay are well pulverized and mixed, and water is added. After kneading well, it is granulated and dried to obtain granules.

Formulation Example 4 25 parts each of the compounds (1) to (12) of the present invention, 8 parts polyoxyethylene sorbitan monooleate, 3 parts CMC, 69 water
Parts are mixed and wet milled until the particle size is 5 microns or less to obtain a suspending agent.

Formulation Example 5 2 parts of each of the compounds (1) to (12) of the present invention, 88 parts of kaolin clay and 10 parts of talc are well pulverized and mixed to obtain a powder.

Formulation Example 6 10 parts of each of the compounds (1) to (12) of the present invention, 1 part of polyoxyethylene styryl phenyl ether, and 89 parts of water are mixed to obtain a liquid preparation.

Next, Test Examples show that the compound of the present invention is useful as an active ingredient of a fungicide. The compounds of the present invention are indicated by the compound numbers in Table 1, and the compounds used for comparison are indicated by the compound symbols in Table 2.

Moreover, the control efficacy is "5", about 10% if the disease state of the test plant at the time of the survey, that is, the flora of leaves, stems, etc. If it is admitted, "4, 30% is admitted to be" 3 ", 50% is admitted to be" 2 ", 70% is admitted to be" 1 ", and there is a difference from the onset state when the compound is not tested. If not, it is evaluated as 6 levels from 0 to 5, 0, 1, 2,
Shown as 3, 4, and 5.

Test Example 1 Rice Sheath Blight Preventive Effect Test Plastic pots were filled with sandy loam and rice (Kinki 33
No.) and cultivated in a greenhouse for 60 days. The test compound in the form of an emulsion according to Formulation Example 2 was diluted with water to a predetermined concentration of rice seedlings having developed 6 to 7 leaves and sprayed so as to adhere sufficiently to the leaves. Four hours after spraying, agar-containing agar pieces of rice sheath blight were pasted and inoculated. After inoculation, it was grown at 28 ° C. in high humidity for 4 days, and the dehumidifying effect was investigated. The results are shown in Table 3.

Test Example 2 Permeation transfer effect test of rice blight disease A 130 ml plastic pot was filled with sandy loam soil, and rice (Kinki No. 38) was sown and grown in a greenhouse for 8 weeks. 6 ~
A test compound prepared as a wettable powder according to Formulation Example 1 was diluted with water on rice with seven leaves developed, and a predetermined amount of the compound was irrigated into soil and grown for 7 days in a greenhouse. The bacteria-containing agar pieces were stuck and inoculated. After inoculation, they were grown for 4 days at 28 ° C. and in a high humidity, and their control efficacy was investigated. Table 4 shows the results.

Test Example 3 Test for preventive effect of bean white silk disease A 250 ml plastic pot was mixed well with sandy loam with white silk pathogens previously cultured in a bran medium. Green beans were sown on them. A test compound made into a wettable powder according to Formulation Example 1 was diluted with water, and a predetermined amount thereof was irrigated into the soil. After the irrigation, the plants were grown in a greenhouse for 3 weeks, and the control efficacy was investigated according to the degree of disease of the stem at the edge. Table 5 shows the results.

Test Example 4 Wheat Bunting Bunting Seed Treatment Test A test compound hydrated according to Formulation Example 1 was diluted with water to a predetermined concentration, and the drug solution was diluted with wheat Bunting blight fungus (Us
tilago tritici) inoculated and infected wheat seeds (Agriculture and Forestry 61)
No.) and immersion treatment for 24 hours. Thereafter, the seeds were sown and cultivated in a field, and after heading, the controlling effect was examined according to the disease state of the ear. The results are shown in Table 6.

Test Example 5 Wheat leaf rust therapeutic effect test A plastic pot was filled with sandy loam soil, and wheat (Agriculture 78
No.) and bred in a greenhouse for 10 days. The spores of the wheat leaf rust fungus developed on the second to third leaves were inoculated. 23 after vaccination
The test compound, which had been grown for 1 day at 37 ° C. and high humidity and made into an emulsion according to Formulation Example 2, was diluted with water to a predetermined concentration and sprayed on foliage so that it adhered sufficiently to the leaf surface. After spraying, they were grown for 7 days under illumination at 23 ° C., and their control efficacy was investigated. The results are shown in Table 7.

<Effects of the Invention> The compound of the present invention exhibits excellent efficacy against plant diseases caused by various plant pathogenic fungi, particularly microorganisms belonging to basidiomycetes, and thus can be used for various purposes as an active ingredient of a fungicide.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Kiyoto Maeda 4-2-1 Takashi Takarazuka-shi, Hyogo Sumitomo Chemical Co., Ltd. (72) Inventor Tadashi Oishi 4-2-1 Takashi Takarazuka-shi, Hyogo Sumitomo Chemical Co., Ltd.

Claims (2)

(57) [Claims] 1. A general formula [In the formula, R ₁ represents a methyl group, an ethyl group or a trifluoromethyl group, X represents an amino group, a methyl group or a chlorine atom, Y represents an oxygen atom or a sulfur atom, and R ₂
Represents a hydrogen atom or a methyl group. ] The substituted thiazole carboxylic acid derivative represented by these. 2. General formula [In the formula, R ₁ represents a methyl group, an ethyl group or a trifluoromethyl group, X represents an amino group, a methyl group or a chlorine atom, Y represents an oxygen atom or a sulfur atom, and R ₂
Represents a hydrogen atom or a methyl group. ] A fungicide for agricultural and horticultural use, which comprises a substituted thiazolecarboxylic acid derivative represented by the following as an active ingredient.