JPH0625199A - Thiazole derivative - Google Patents

Abstract

PURPOSE:To obtain a new thiazole derivative having germicidal action on drug resistant microorganisms and useful for preventing and treating plant disease injuries as a germicide in agriculture and horticulture by acylating 2-amino-4trifluoromethyl-5-cyano-thiazole. CONSTITUTION:2-Chloro-4-trifluoromethyl-5-thiazole carboxylic acid is allowed to react with thionyl chloride under heating to afford a carbonyl chloride derivative, which is then treated with ammonia water to give an alkoxide derivative. The alkoxide derivative is allowed to react with phosphorus oxychloride under heating to afford 2-chloro-5-cyano-4-trifluoromethylthiazole. Then the compound is treated with an alkylamine to give an 2-alkylamino derivative expressed by formula I (R<1> is H or alkyl) and the derivative of formula I is allowed react with an acid halide compound of formula II [R<2> is (substituted)phenyl, (substituted)alkyl, etc.; X is halogen, etc.] to provide the objective new thiazole compound expressed by formula III having excellent germicidal properties.

Description

Detailed Description of the Invention

[0001]

The present invention is useful as a bactericide,
The present invention relates to a novel thiazole derivative.

[0002]

2. Description of the Related Art High productivity in today's agriculture is ensured by using fertilizers, pesticides and various agricultural materials.

[0003]

On the other hand, the emergence of drug-resistant bacteria caused by continuous application of agricultural chemicals has become a major problem, and the emergence of new compounds useful as fungicides has been awaited. is there. An object of the present invention is to provide a novel thiazole derivative having a bactericidal action.

[0004]

Means for Solving the Problems The present inventor has conducted extensive studies to develop a novel compound having a bactericidal action, and completed the present invention.

That is, the present invention has the general formula

[0006]

[Chemical 3]

(Wherein R 1 represents hydrogen or an alkyl group, R 2 represents a phenyl group, a substituted phenyl group, a benzyl group,
A substituted benzyl group, a phenylalkyl group, a naphthyl group, an alkyl group, a cycloalkyl group, a substituted alkyl group, an alkenyl group, an alkynyl group, a furyl group, a thienyl group, a 5-membered ring containing 1 to 3 nitrogen atoms in the ring, or A 6-membered ring containing 1 to 3 nitrogen atoms in the ring (when the 5-membered ring and the 6-membered ring contain 1 or 2 nitrogen atoms, the remaining atoms are only carbon atoms, or Is a heterocycle containing one oxygen atom or one sulfur atom), and has the above-mentioned furyl group, thienyl group, a 5-membered ring containing 1 to 3 nitrogen atoms in the ring, and 1 nitrogen atom in the ring. The 6-membered ring containing 3 may have 1 to 3 substituents selected from an alkyl group, an alkoxy group, a halogen atom and a haloalkyl group. ) And a [Chemical Formula 3] (in the formula, R 1
Represents hydrogen or an alkyl group, and R2 represents a phenyl group, a substituted phenyl group, a benzyl group, a substituted benzyl group, a phenylalkyl group, a naphthyl group, an alkyl group, a cycloalkyl group, a substituted alkyl group, an alkenyl group, an alkynyl group or a furyl group. , Thienyl group, containing 1-3 nitrogen atoms in the ring 5
A member ring, or a 6-membered ring containing 1 to 3 nitrogen atoms (when the 5-membered ring and the 6-membered ring contain 1 or 2 nitrogen atoms, the remaining atoms are carbon atoms) Or a heterocycle containing one oxygen atom or one sulfur atom) and is a furyl group, a thienyl group, a 5-membered ring containing 1 to 3 nitrogen atoms in the ring, or a nitrogen atom in the ring. The 6-membered ring containing 1 to 3 atoms may have 1 to 3 substituents selected from an alkyl group, an alkoxy group, a halogen atom and a haloalkyl group. And a thiazole derivative represented by the formula (1) as an active ingredient.

The compounds of the present invention are all novel compounds and can be produced by the following reaction. That is, the general formula

[0009]

[Chemical 4]

(Wherein R 1 represents hydrogen or an alkyl group), and a compound of the general formula

[0011]

[Chemical 5]

(Wherein R 2 is a phenyl group, a substituted phenyl group, a benzyl group, a substituted benzyl group, a phenylalkyl group, a naphthyl group, an alkyl group, a cycloalkyl group, a substituted alkyl group, an alkenyl group, an alkynyl group, a furyl group,
A thienyl group, a 5-membered ring containing 1 to 3 nitrogen atoms in the ring, or a 6-membered ring containing 1 to 3 nitrogen atoms in the ring.
Member ring and said 6-membered ring, when containing one or two nitrogen atoms, are the remaining atoms are only carbon atoms, or are heterocycles containing one oxygen atom or one sulfur atom), One of the above furyl groups, thienyl groups, and nitrogen atoms in the ring
A 5-membered ring containing 3 to 3, a 6-membered ring containing 1 to 3 nitrogen atoms in the ring have 1 to 3 substituents selected from an alkyl group, an alkoxy group, a halogen atom and a haloalkyl group. Is also good. ) A known acid halide compound represented by

[0013]

[Chemical 6]

(Wherein R 2 is a phenyl group, a substituted phenyl group, a benzyl group, a substituted benzyl group, a phenylalkyl group, a naphthyl group, an alkyl group, a cycloalkyl group, a substituted alkyl group, an alkenyl group, an alkynyl group, a furyl group,
A thienyl group, a 5-membered ring containing 1 to 3 nitrogen atoms in the ring, or a 6-membered ring containing 1 to 3 nitrogen atoms in the ring.
Member ring and said 6-membered ring, when containing one or two nitrogen atoms, are the remaining atoms are only carbon atoms, or are heterocycles containing one oxygen atom or one sulfur atom), One of the above furyl groups, thienyl groups, and nitrogen atoms in the ring
A 5-membered ring containing 3 to 3, a 6-membered ring containing 1 to 3 nitrogen atoms in the ring have 1 to 3 substituents selected from an alkyl group, an alkoxy group, a halogen atom and a haloalkyl group. Is also good. ) It can manufacture by making it react with the well-known acid anhydride compound represented by this.

In the above production method, the reaction is usually carried out in the presence of a suitable base. Examples of the base include organic bases such as triethylamine and pyridine, and inorganic bases such as sodium methoxide, sodium hydride, potassium hydroxide, potassium carbonate and sodium hydrogencarbonate.

Further, in the above-mentioned production method, the reaction is carried out in the presence of no solvent or an inert solvent. Examples of usable solvents include hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as chloroform and dichloroethane, ketones such as acetone and methyl ethyl ketone,
Examples thereof include ethers such as diethyl ether, tetrahydrofuran and dioxane, and polar solvents such as N, N-dimethylformamide, dimethyl sulfoxide and acetonitrile.

The reaction temperature in the above production method is usually from room temperature to the reflux temperature of the solvent. Furthermore, when it is necessary to shorten the reaction time, it is preferable to heat.

When producing the compound of the present invention, the compound represented by the general formula [Chemical Formula 4] which is an intermediate is also a novel compound and can be produced by the following method.

That is, 2-chloro-4-trifluoromethyl-5-thiazolecarboxylic acid [I] (J. Heterocyclic Chem., 22 1621) which can be synthesized by a known method.
(1985)) with thionyl chloride [II]
Then, the amide derivative [III] is obtained by reacting with ammonia water. Next, this [III] is reacted with a suitable dehydrating agent such as phosphorus oxychloride to obtain 2-chloro-5-cyano-4-trifluoromethylthiazole [IV]. A novel compound [Chemical Formula 4] is obtained by reacting this compound [IV] with aqueous ammonia or various alkylamines in a solvent such as dioxane, tetrahydrofuran, N, N-dimethylformamide, dimethylsulfoxide and acetonitrile. You can

The fungicide of the present invention contains a thiazole derivative represented by the general formula [Chemical Formula 3] as an active ingredient. These thiazole derivatives are novel compounds and are expected to have an effect on drug-resistant bacteria. When the fungicide of the present invention is used for agriculture, depending on its purpose, by a general pesticide production technique, the compound is mixed with various carriers and additives, a wettable powder, an emulsion, a powder, Granules, flowable agents, etc.
It can be used in various forms. Furthermore, the compound of the present invention is also useful as an industrial bactericide. For example, it exhibits excellent antibacterial activity against Bacillus, Pseudomonas, Aspergillus, Penicillium, Saccharomyces and the like.

Among the carriers to be added when used for agriculture, the liquid carrier is a usual organic solvent. Usual clay minerals, pumice, etc. are used as the solid carrier. Further, a surfactant can be added in order to impart emulsifiability, dispersibility, spreadability and the like to the formulation. Furthermore, it can be used by mixing with agricultural chemicals such as fertilizers, herbicides, insecticides and other fungicides.

In order to be used as a bactericide, it is necessary to apply the active ingredient compound sufficiently so that the desired effect is exhibited. The application amount can be applied in the range of 20 to 2000 g / ha, but generally 100
A range of up to 1000 g / ha is suitable. It is used by formulating it in the form of a wettable powder, an emulsion, a powder, a granule and a flowable agent with the content of the active ingredient being 0.1 to 50%.

The emulsion can be prepared by dissolving the active ingredient in an agriculturally usable organic solvent and adding a solvent-soluble emulsifier. As the solvent, xylene, orthochlorotoluene, cyclohexanone, isophorone, N, N
-Dimethylformamide, dimethylsulfoxide, or mixtures thereof can be used. A particularly suitable solvent is a mixed solvent of an aromatic hydrocarbon, a ketone and a polar solvent. The surfactant used as an emulsifier is used in an amount of 1 to 20% by weight of the emulsion. Further, as the type, any of anionic, cationic and nonionic can be used. The concentration of active ingredient is 0.5-50
A range of 5% by weight, preferably 5 to 30% by weight is suitable.

Specific examples of the above-mentioned surfactant are as follows. Examples of the anionic surfactant include alkyl sulfate ester, alkyl diphenyl ether disulfonate, naphthyl methane sulfonate, lignin sulfonate, alkyl sulfosuccinate, alkyl benzene sulfonate and alkyl phosphate. Examples of cationic surfactants include alkylamine salts and quaternary ammonium salts. Examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene alkyl allyl ether, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, glycerin fatty acid ester, and polyoxyethylene fatty acid ester. To be

The wettable powder is prepared by adding an active ingredient to an inert finely divided solid carrier and a surfactant. The active ingredient is in the range of 2 to 50% by weight, and the surfactant is 1 to 20%.
It is common to mix in wt%. As inert finely divided solid carriers, naturally occurring clay, silicates, silica and carbonates of alkaline earth metals can be used. Representative examples of these are kaolin, sieglite, talc, diatomaceous earth, magnesium carbonate, calcium carbonate and dolomite. As the emulsifier, the spreading agent, and the dispersant, generally used anionic surfactants, nonionic surfactants, and mixtures thereof can be used. As the system of each surfactant, the same system as that used for the emulsion can be used.

Dusts include talc, finely divided clay, pyrophyllite,
Formulation is carried out by incorporating the active ingredient into an inert carrier commonly used for the production of powders such as diatomaceous earth and magnesium carbonate. The concentration of the active ingredient is 0.1 to 20% by weight
In particular, the range of 0.5 to 5% by weight is suitable.

Granules are prepared by mixing the active ingredient with an inert finely divided carrier such as bentonite, diatomaceous earth, kaolin clay or talc, kneading with water and using a granulator. Alternatively, granulate in advance to a particle size range of 15
~ 30 mesh granular carrier, natural pumice stone,
It can also be prepared by adhering a solution in which the active ingredient and the spreading agent are dissolved to a granular mineral in which the acid clay and zeolite are crushed to adjust the particle size range. The active ingredient concentration of such granules is 0.2 to 20% by weight, especially 1
The range of 10 to 10% by weight is suitable.

The flowable agent is obtained by pulverizing the active ingredient into a fine powder and mixing it with a surfactant and water. The surfactant used here is an anionic surfactant or cationic surfactant listed for the emulsion. Both the agent and the nonionic surfactant are used alone or in combination. The amount used is generally 1 to 20% by weight. The active ingredient is suitably in the range of 1 to 50% by weight, preferably 2 to 20% by weight.

Due to its excellent antibacterial activity, the compound of the present invention represented by the general formula [Chemical Formula 3] exerts an effect as an agricultural and horticultural fungicide against plant diseases caused by a wide range of microorganisms. For example, tomato late blight, downy mildew, various powdery mildew, apple scab, wheat rust, wheat rot, rice blast, rice blight, various gray molds, rice wilt, cucumber. It shows an excellent control effect against spotted bacterial diseases. Further, since the compound of the present invention has not only an excellent preventive effect but also an excellent therapeutic effect, it is possible to control diseases by treatment after infection.

Representative compounds relating to the present invention are shown in [Table 1] to
The results are shown in [Table 9]. In the following, the compound Nos. In [Table 1] to [Table 9] are used to represent individual compounds.

[0031]

[Table 1]

[0032]

[Table 2]

[0033]

[Table 3]

[0034]

[Table 4]

[0035]

[Table 5]

[0036]

[Table 6]

[0037]

[Table 7]

[0038]

[Table 8]

[0039]

[Table 9]

[0040]

EXAMPLES The present invention will be specifically described below with reference to Examples (Synthesis Examples, Formulation Examples and Test Examples), but the present invention is not limited to these. Hereinafter, representative synthetic examples relating to the present invention will be shown.

[Synthesis Example 1] Synthesis of 2-chloro-4-trifluoromethyl-5-thiazolecarbonyl chloride 117.3 g of 2-chloro-4-trifluoromethyl-5-thiazolecarboxylic acid was dissolved in 1.1 l of dioxane. Then, 185 ml of thionyl chloride and a catalytic amount of N, N-dimethylformamide were added, and the mixture was heated under reflux for 2.5 hours. The solvent was distilled off from the reaction solution under reduced pressure to obtain the target product 1 as a colorless oily substance.
24.1 g was obtained. Yield 98%.

[Synthesis Example 2] Synthesis of 2-chloro-4-trifluoromethyl-5-thiazolecarboxamide 124.1 g of 2-chloro-4-trifluoromethyl-5-thiazolecarbonyl chloride was added to 1.1 l of dioxane.
Was added dropwise to 290 ml of 28% aqueous ammonia at room temperature, and the mixture was stirred for 1 hour at room temperature. After completion of the reaction, the reaction solution was neutralized with diluted hydrochloric acid, extracted with ethyl acetate, washed with water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was recrystallized with a toluene-hexane mixed solvent to obtain 98.5 g of the desired product. Yield 86.1
%, Melting point 89-90 ° C.

[Synthesis Example 3] 2-chloro-5-cyano-4
-Synthesis of trifluoromethylthiazole 2-chloro-4-trifluoromethyl-5-thiazolecarboxamide (43.3 g) was dissolved in 160 ml of N, N-dimethylformamide, and 120 ml of phosphorus oxychloride.
Was added dropwise at 40 ° C or lower, and after completion of the addition, the mixture was stirred at 70 ° C for 3 hours. After completion of the reaction, the reaction solution was put into ice water, neutralized with sodium carbonate, and extracted with ethyl acetate. Extract the water,
The extract was washed with brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give the desired product (38.2 g) as a colorless oil. Yield 95.7%.

[Synthesis Example 4] 2-amino-5-cyano-4
-Synthesis of trifluoromethylthiazole Dissolve 1.0 g of 2-chloro-5-cyano-4-trifluoromethylthiazole in 40 ml of tetrahydrofuran,
To this, 9 ml of 28% ammonia water was added dropwise.
Stir at room temperature for 8 hours. After completion of the reaction, the reaction solution was put into water, neutralized with diluted hydrochloric acid, and extracted with ethyl acetate. The extract was washed with water and brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was recrystallized from a toluene-hexane mixed solvent to obtain 0.82 g of the desired product. Yield 90.3%, melting point 166-167 ° C.

[Synthesis Example 5] Synthesis of 5-cyano-2-methylamino-4-trifluoromethylthiazole 1.2 g of 2-chloro-5-cyano-4-trifluoromethylthiazole was dissolved in 40 ml of tetrahydrofuran,
1.32 g of 40% methylamine aqueous solution was added dropwise at 10 ° C or lower. After completion of dropping, the mixture was stirred at room temperature for 2 hours, after completion of the reaction, the reaction solution was put into water, neutralized with diluted hydrochloric acid, and extracted with ethyl acetate. The extract was washed with water and brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was recrystallized with a toluene-hexane mixed solvent to obtain 1.11 g of the desired product. Yield 90.3%, melting point 125-
126 ° C.

[Synthesis Example 6] Synthesis of N- (5-cyano-4-trifluoromethylthiazol-2-yl) -4-chlorobenzamide (Compound No. 15) 2-Amino-5-cyano-4-tri 0.2 g of fluoromethylthiazole was dissolved in 30 ml of acetone, 0.2 g of 4-chlorobenzoyl chloride and 0.3 g of potassium carbonate were added, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, the reaction solution was put into ice water, extracted with ethyl acetate, washed with an aqueous solution of sodium carbonate, diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography to obtain 0.21 g of the desired product. Yield 63.5%, melting point 1
28-129 ° C.

Synthesis Example 7 Synthesis of N- (5-cyano-4-trifluoromethylthiazol-2-yl) -propionamide (Compound No. 55) 2-Amino-5-cyano-4-trifluoromethyl 0.8 g of thiazole was dissolved in 50 ml of dioxane, 0.8 ml of propionyl chloride and 1.2 ml of triethylamine were added, and the mixture was stirred at 60 ° C. for 6 hours. After the reaction was completed, the reaction solution was put into ice water, extracted with ethyl acetate, washed with an aqueous solution of sodium carbonate, diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. After purifying the obtained crude product by silica gel column chromatography,
0.68 g of the target product was obtained. Yield 74.6%, melting point 102
-10 3 ° C.

[Synthesis Example 8] Synthesis of N- (5-cyano-4-trifluoromethylthiazol-2-yl) -trifluoroacetamide (Compound No. 67) 2-Amino-5-cyano-4-trifluoro 0.8 g of methyl thiazole was dissolved in 50 ml of dioxane, 0.7 ml of trifluoroacetic anhydride and 0.7 ml of triethylamine were added, and the mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was put into ice water, extracted with ethyl acetate, washed with an aqueous solution of sodium carbonate, diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was recrystallized with a mixed solvent of ethyl acetate-hexane to obtain 1.03 g of the desired product. Yield 86.0%, decomposed at 260 ° C.

[Synthesis Example 9] N- (5-cyano-4-trifluoromethylthiazol-2-yl) -N-methyl-
4-trifluoromethylbenzamide (Compound No. 4
Synthesis of 8) 5-cyano-2-methylamino-4-trifluoromethylthiazole 1.1 g was dissolved in dioxane 50 ml and 4
-1.6 ml of trifluoromethylbenzoyl chloride and 1.5 ml of triethylamine were added, and the mixture was stirred at 60 ° C for 2 hours. After completion of the reaction, the reaction solution was put in ice water, extracted with ethyl acetate, washed with an aqueous solution of sodium carbonate, diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was recrystallized with a toluene-hexane mixed solvent to obtain 1.10 g of the desired product. Yield 5
4.1%, melting point 98-99 ° C.

[Synthesis Example 10] Synthesis of N- (5-cyano-4-trifluoromethylthiazol-2-yl) -cyclopentanecarboxamide (Compound No. 66) 2-Amino-5-cyano-4-trifluoro 0.8 g of methylthiazole was dissolved in 50 ml of dioxane, 1.2 g of cyclopentanecarbonyl chloride and 1.5 ml of triethylamine were added, and the mixture was stirred at 60 ° C. for 6 hours. After completion of the reaction, the reaction solution was put in ice water, extracted with ethyl acetate, washed with an aqueous solution of sodium carbonate, diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography to obtain 0.78 g of the desired product. Yield 65.1%,
Melting point 179-181 [deg.] C.

Synthesis Example 11 Synthesis of N- (5-cyano-4-trifluoromethylthiazol-2-yl) -1-naphthamide (Compound No. 53) 5-Cyano-2-methylamino-4-tri Dissolve 0.7 g of fluoromethylthiazole in 40 ml of dioxane,
-Naphthoyl chloride 1.4 g, triethylamine 1.
3 ml was added, and the mixture was stirred at 60 ° C. for 4 hours. After the reaction,
The reaction mixture was put into ice water, extracted with ethyl acetate, washed with aqueous sodium carbonate solution, diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained crude product was recrystallized with a toluene-hexane mixed solvent to obtain 0.78 g of the desired product. Yield 62.0%, melting point 1
35-136 ° C.

Synthesis Example 12 Synthesis of N- (5-cyano-4-trifluoromethylthiazol-2-yl) -2-thiophenecarboxamide (Compound No. 74) 2-amino-5-cyano-4-tri 0.7 g of fluoromethylthiazole was dissolved in 40 ml of dioxane, 1.1 g of 2-thiophenecarbonyl chloride and 1.3 ml of triethylamine were added, and the mixture was stirred at 60 ° C. for 4 hours. After completion of the reaction, the reaction solution was put in ice water, extracted with ethyl acetate, washed with an aqueous solution of sodium carbonate, diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography to obtain 1.13 g of the desired product. Yield 81.3%,
Melting point 194-195 [deg.] C.

Synthesis Example 13 N- (5-cyano-4-trifluoromethylthiazol-2-yl) -4-chloro-1-methyl-3-trifluoromethyl-5-pyrazolecarboxamide (Compound No. 79 ) Synthesis of 2-amino-5-cyano-4-trifluoromethylthiazole (1.5 g) is dissolved in 40 ml of pyridine and 4-chloro-1-methyl-3-trifluoromethyl-5-pyrazolecarbonyl chloride (3.8 g) is added. In addition, the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction solution was put in ice water, extracted with ethyl acetate, washed with an aqueous solution of sodium carbonate, diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography to obtain 1.86 g of the desired product. Yield 70.5%, melting point 128-129 ° C.

Synthesis Example 14 Synthesis of N- (5-cyano-4-trifluoromethylthiazol-2-yl) -2-pyridinecarboxamide (Compound No. 83) 2-Amino-5-cyano-4-tri Fluoromethylthiazole (1.6 g) was dissolved in pyridine (30 ml), 2-pyridinecarbonyl chloride (3.5 g) was added, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction solution was put into ice water, extracted with ethyl acetate, washed with diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography to obtain 1.42 g of the desired product. Yield 57.5%, melting point 205-206 ° C.

[Synthesis Example 15] Synthesis of N- (5-cyano-4-trifluoromethylthiazol-2-yl) -3-chloro-5-trifluoromethyl-2-pyridinecarboxamide (Compound No. 90) 2 0.8 g of -amino-5-cyano-4-trifluoromethylthiazole was dissolved in 30 ml of dioxane, 1.0 g of 3-chloro-5-trifluoromethyl-2-pyridinecarbonyl chloride and 0.6 ml of triethylamine were added,
The mixture was stirred at 60 ° C for 3 hours. After completion of the reaction, the reaction solution was put into ice water, extracted with ethyl acetate, washed with diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography to obtain 0.98 g of the desired product. Yield 5
9.0%, melting point 93-94 ° C.

[Synthesis Example 16] Synthesis of N- (5-cyano-4-trifluoromethylthiazol-2-yl) -2-pyrazinecarboxamide (Compound No. 92) 2-amino-5-cyano-4-tri Fluoromethylthiazole (1.2 g) was dissolved in pyridine (30 ml), 2-pyrazinecarbonyl chloride (1.8 g) was added, and the mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction solution was put into ice water, extracted with ethyl acetate, washed with diluted hydrochloric acid, water and brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography to obtain 1.56 g of the desired product. Yield 83.9%, melting point 183-184 ° C.

The compositions of the present invention will be specifically shown below as formulation examples according to dosage forms.

[Formulation Example 1 (Emulsion)] Compound No. 12 20 parts Orthochlorotoluene 40 parts Cyclohexanone 35 parts Solpol 900B 5 parts "Solpol": trademark of Toho Chemical Industry Co., Ltd. An emulsion of was obtained.

[Formulation Example 2 (wettable powder)] Compound No. 4 25 parts Kaolin clay 57 parts Solpol 5039 9 parts Solpol 5060 9 parts The above components were mixed and ground to obtain a wettable powder of the present invention.

[Formulation Example 3 (powder)] Compound No. 19 5 parts Kaolin clay 95 parts The above components were mixed and pulverized to obtain the powder of the present invention.

[Formulation Example 4 (Granule)] Compound No. 46 6 parts Bentonite 44 parts Talc 44 parts Lignin sulfonate soda 6 parts The above components are uniformly mixed and pulverized, and water is added to the mixture to knead and granulate. It was dried to obtain the granule of the present invention.

[Formulation Example 5 (flowable agent)] Compound No. 24 10 parts Ethylene glycol 6 parts Solpol 3078 6 parts Solpol 7512 1 part Water 77 parts The above ingredients were uniformly mixed and pulverized to obtain the flowable agent of the present invention.

Formulation Example 6 (Emulsion) Compound No. 38 10 parts Isophorone 22 parts Orthochlorotoluene 28 parts Xylene 22 parts Sorpol 900A 9 parts Solpol 900B 9 parts The above ingredients are uniformly mixed and dissolved to obtain an emulsion of the present invention. It was

The control effect of the compound of the present invention against filamentous fungi will be specifically described below with reference to test examples.

[Test Example 1] Rice blast prevention effect test Rice (variety: Koshihikari) was cultivated in a plastic cup having a diameter of 7 cm, and when the two-leaf stage was reached, each test prepared according to Formulation Example 1 The compound was adjusted to 100 ppm, and 10 ml of the test compound drug solution was sprayed using a spray gun. For each test compound, 10 plants in 1 group were treated in duplicate. One day after the drug treatment, each plant had Pyricularia oryza (Pyricularia oryza), which causes rice blast disease.
The conidia suspension of e) was inoculated. After this inoculation, the rice plant was cultivated for 24 hours at 25 ° C. in a dark place under water-saturated condition, and then for 6 days at 25 ° C. for 12 hours. Seven days after the inoculation, the lesion rates of the first and second leaves were investigated. At the same time, the test was conducted under the same conditions for the control without drug treatment. The control value was determined by the formula of [Equation 1], and the results are shown in [Table 10].

[0066]

[Equation 1]

[0067]

[Table 10]

[Test Example 2] Wheat powdery mildew prevention effect test Wheat (variety: Norin 6
No. 1) was cultivated, and when reaching the 2-leaf stage, each test compound prepared according to Formulation Example 2 was prepared at 100 ppm, and 10 ml of the test compound drug solution was sprayed using a spray gun. With respect to each test compound, 13 plants in 1 group were treated in duplicate. One day after the drug treatment, each plant was treated with Erysiphe graminis, which causes wheat powdery mildew.
minis) conidia suspension was inoculated. After this inoculation, the wheat plants were cultivated at 20 ° C in the dark for 12 hours, then at 20 ° C,
It was cultured for 6 days with a 12-hour photoperiod. Seven days after the inoculation, the lesion rates of the first and second leaves were investigated. At the same time, the test was conducted under the same conditions for the control without drug treatment. The control value was determined by the formula of [Equation 1], and the results are shown in [Table 11].

[0069]

[Table 11]

[Test Example 3] Wheat leaf rust prevention effect test Wheat (variety: Norin 6
No. 1) was cultivated, and when reaching the 2-leaf stage, each test compound prepared according to Formulation Example 6 was prepared to 100 ppm, and 10 ml of the test compound drug solution was sprayed using a spray gun.
For each test compound, 13 plants in 1 group were treated in duplicate. One day after the chemical treatment, each plant was infected with Puccinia reco
ndita) conidial suspension. After this inoculation, the wheat plants were cultivated in a water-saturated condition at 20 ° C. in the dark for 24 hours, and then cultivated at 20 ° C. for 12 hours and a photoperiod of 6 days.
Seven days after the inoculation, the lesion rates of the first and second leaves were investigated. At the same time, the test was conducted under the same conditions for the control without drug treatment. The control value was determined by the formula of [Equation 1], and the results are shown in [Table 12].

[0071]

[Table 12]

[Test Example 4] Wheat rot prevention effect test Wheat (variety: Norin 6
No. 1) was cultivated, and when reaching the 2-leaf stage, each test compound prepared according to Formulation Example 5 was prepared to 200 ppm, and 10 ml of the test compound drug solution was sprayed using a spray gun.
For each test compound, 13 plants in 1 group were treated in duplicate. One day after the chemical treatment, Leptosphaerinodrum (Leptospha), which causes wheat rot, was planted on each plant.
eria nodorum) was inoculated with a conidia suspension. After this inoculation, the wheat plants were cultivated in a water-saturated condition at 20 ° C. in the dark for 48 hours, and then cultivated at 20 ° C. for 12 hours with a photoperiod of 6 days. Seven days after the inoculation, the lesion rate of the first and second leaves was investigated. At the same time, the test was conducted under the same conditions for the control without drug treatment. The control value was obtained by the calculation formula of [Equation 1], and the results are shown in [Table 13].

[0073]

[Table 13]

[0074]

INDUSTRIAL APPLICABILITY The compound of the present invention is a novel compound and is suitable as an agricultural / horticultural fungicide and an industrial fungicide.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Reference number in the agency FI Technical indication location C07D 417/12 333 (72) Inventor Hiroshi Kawada 45 Miyukigaoka, Tsukuba, Ibaraki Prefecture Hodogaya Kagaku Industry Co., Ltd. Tsukuba Research Institute (72) Inventor Chieko Inayoshi 45 Miyukigaoka, Tsukuba City, Ibaraki Prefecture Hodogaya Chemical Industry Co., Ltd. Tsukuba Research Institute (72) Inventor Iku Kasahara 45 Miyukigaoka, Tsukuba City, Ibaraki Hodogaya Chemical Industry Co., Ltd. Tsukuba Research Center

Claims (2)

[Claims] 1. A general formula: (In the formula, R1 represents hydrogen or an alkyl group, R2 represents a phenyl group, a substituted phenyl group, a benzyl group, a substituted benzyl group, a phenylalkyl group, a naphthyl group, an alkyl group, a cycloalkyl group, a substituted alkyl group, an alkenyl group, Alkynyl group, furyl group, thienyl group, 1 nitrogen atom in the ring
A 5-membered ring containing 3 to 3 members, or a 6-membered ring containing 1 to 3 nitrogen atoms in the ring (when the 5-membered ring and the 6-membered ring contain 1 or 2 nitrogen atoms, the remaining Is a heterocycle containing only one carbon atom or one oxygen atom or one sulfur atom, and is a 5-membered ring containing 1 to 3 nitrogen atoms in the above furyl group, thienyl group, or ring. The 6-membered ring containing 1 to 3 nitrogen atoms in the ring is 1 to 3 selected from an alkyl group, an alkoxy group, a halogen atom and a haloalkyl group.
It may have one substituent. ) A thiazole derivative represented by: 2. The general formula of claim 1. (In the formula, R1 represents hydrogen or an alkyl group, R2 represents a phenyl group, a substituted phenyl group, a benzyl group, a substituted benzyl group, a phenylalkyl group, a naphthyl group, an alkyl group, a cycloalkyl group, a substituted alkyl group, an alkenyl group, Alkynyl group, furyl group, thienyl group, 1 nitrogen atom in the ring
A 5-membered ring containing 3 to 3 members, or a 6-membered ring containing 1 to 3 nitrogen atoms in the ring (when the 5-membered ring and the 6-membered ring contain 1 or 2 nitrogen atoms, the remaining Is a heterocycle containing only one carbon atom or one oxygen atom or one sulfur atom, and is a 5-membered ring containing 1 to 3 nitrogen atoms in the above furyl group, thienyl group, or ring. The 6-membered ring containing 1 to 3 nitrogen atoms in the ring is 1 to 3 selected from an alkyl group, an alkoxy group, a halogen atom and a haloalkyl group.
It may have one substituent. ) A thiazole derivative represented by the formula (1) is contained as an active ingredient.