JPS6047279B2 - Perhydroimidazothiazole derivatives, their production methods, and agricultural and horticultural fungicides containing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel perhydroimidazothiazole derivatives.

Specifically, hydantoin derivatives 6-(3,5-dichlorophenyl)perhydroimidazo[5,1-b]thiazole-5,7-diones or 6-(3,5-dichlorophenyl)perhydroimidazo[5, 1-b] Thiazol-5-thione-7-ones. 3
Regarding monosubstituted hydantoin derivatives, it has already been reported that some compounds have biological activities such as bactericidal and herbicidal effects. It is a hydantoin derivative.

6-(3,5-dichlorophenyl)perhydroimidazo[5,11b]thiazole-5,7-diones or 6
-(3,5-dichlorophenyl)perhydroimidazo [
5,1-b] Thiazol-5-thion-7-ones have been found to be extremely useful substances having a strong bactericidal effect against plant diseases, leading to the achievement of the present invention.

That is, the gist of the present invention is as follows: General formula (wherein R represents a hydrogen atom or a methyl group, X represents an oxygen atom or a sulfur atom, and n represents 0, 1 or 2.

6-(3,5-nodichlorophenyl)perhydroimidazo[5,11b]thiazole derivative represented by
5-dichlorophenyl) perhydroimidazo[5,1-
b] An agricultural and horticultural fungicide containing a thiazole derivative as an active ingredient. The compounds of the present invention represented by the general formula (1) are all novel compounds, and have strong bactericidal efficacy against plant diseases, and have almost no harmful effects on plants. It also has low toxicity to humans, livestock, and fish.

The compounds of the present invention are particularly effective against gray mold and sclerotium of vegetables, as well as rice blast and sesame leaf blight, as well as gray mold of grapes, black spot of pears, and leaf spot of apples. It also shows excellent efficacy against gray rot of onions. The compound of the present invention is produced using thiazolidine 2-carboxylic acid or its lower alkyl ester, which may be substituted with a methyl group at the 2-position, and 3,5-dichlorophenyl isocyanate or 3,5-dichlorophenyl isocyanate as raw materials. be able to.

The reaction formula for this is as follows. (In the formula, R.
X has the same meaning as defined in the general formula (1), R'' represents a hydrogen atom or a lower alkyl group, and m
indicates 1 or 2.

) That is, when the ester of thiazolidine-2-carboxylic acid is used as a raw material, this ester and 3,5-dichlorophenylisocyanate or 3,5-dichlorophenylisothiocyanate are mixed in a solvent such as benzene, toluene, ether, dimethylformamide, etc. By reacting, 3-(3,5-dichlorophenylcarbamoyl)thiazolidine-2-carboxylic acid esters or 3-(3,5-dichlorophenylthiocal,bamoyl)thiazolidine-2-carboxylic acid esters (the above general formula In (■), R″=lower alkyl group) is obtained.

In this reaction, depending on the reaction conditions, condensation can be achieved by continuing the reaction after forming the 3-monosubstituted thiazolidine-2-carboxylic acid ester (in the general formula (■), R'' = lower alkyl group). 6-(3,5-dichlorophenyl)perhydroimidazo[5,1-b]thiazole 5, which is reduced and represented by the general formula (1a),
7-diones or 6-(3,5-dichlorophenyl)
Perhydroimidazo[5,11b]thiazole-5-thione-7-ones can be obtained. In addition, when thiazolidine-2-carboxylic acid is used as a raw material, it is suspended or dissolved in a mixed solvent of water and an organic solvent such as benzene, chlorobenzene, ether, or dimethylformamide. In the presence of alkali, 3,5-dichlorophenylisocyanate or 3
, 5-dichlorophenylthioisocyanate, and then neutralized with an acid such as hydrochloric acid or sulfuric acid.
(3,5-dichlorophenylcarbamoyl)thiazolidine-2-carboxylic acid or 3-(3,5-dichlorophenylthiocarbamoyl)thiazolidine-2-carboxylic acids (in the general formula (■), R″=hydrogen atom) is obtained. Then, this When compound (■) is condensed and cyclized by heating in the presence of an acid such as hydrochloric acid or sulfuric acid or in acetic anhydride in the presence of sodium acetate, the desired 6
-(3,5-dichlorophenyl)perhydroimidazo [
5,1-b]thiazole-5,7-diones or 6-
(3,5-dichlorophenyl)perhydroimidazo[5
, 11b] Thiazol-5-thione-7-ones (1a
) is obtained. These compounds are purified by conventional methods such as recrystallization and chromatography. Also, 6-(3,5
-dichlorophenyl) perhydroimidaso[5,1-b
] Thiazol-5,7-dione-1-oxide or -1,1-dioxides or 6-(3,5-dichlorophenyl)perhydroimidaso[5,1-b]thiazole-5-thione-7-one-1- The oxide or -1,1-dioxide (Ib) is the compound (
It can be obtained by dissolving 1a) in a solvent such as methylene chloride and oxidizing it with an oxidizing agent such as m-chloroperbenzoic acid or peracetic acid. When using the compound of the present invention as a fungicide for agriculture and horticulture, it may be used as is, or an adjuvant may be added according to a conventional method to enable effective dispersion of the active ingredient at the time of application. It is preferable to use it in the form of , emulsion, wettable powder, powder, or the like.

Examples of solvents that are one of the auxiliary agents in the agricultural and horticultural fungicides of the present invention include water, alcohols (methyl alcohol, ethyl alcohol, ethylene glycol, etc.), ketones (acetone, methyl ethyl ketone, cyclohexanone, etc.), ethers) (ethyl ether, dioxane, cellosolve, etc.), aliphatic hydrocarbons (kerosene, kerosene, fuel oil, etc.), aromatic hydrocarbons (benzene, toluene, xylene, solvent naphtha, methylnaphthalene, etc.), halogenated hydrocarbons ( (dichloroethane, trichlorobenzene, carbon tetrachloride, etc.), acid amides (dimethylformamide, etc.), esters (ethyl acetate, butyl acetate, fatty acid glycerin ester, etc.), nitriles (acetonitrile, etc.), and the like are suitable. Species or mixtures of two or more species are used.

In addition, as fillers, mineral powders such as clays such as kaolin and bentonite, talcs such as talc and pyrophyllite, oxides such as diatomaceous earth and white carbon, tize powder, and CMC are used.
Vegetable powders such as these are suitable, and one or two of these
Mixtures of more than one species are used.

Surfactants are also used as spreading agents, dispersants, emulsifiers, and penetrants.

Examples of the surfactant include nonionic surfactants (polyoxyethylene alkylaryl ether, polyoxyethylene sorbitan monolaurate, etc.), cationic surfactants (alkyldimethylbenzylammonium chloride, alkylpyridinium chloride, etc.) , anionic surfactants (alkylbenzene sulfonates, lignin sulfonates, higher alcohol sulfates),
Examples include amphoteric surfactants (alkyldimethylbetaine, dodecylaminoethylglycine, etc.). These surfactants are used singly or as a mixture of two or more depending on the purpose. When applying the agricultural and horticultural fungicide of the present invention in the form of an emulsion, 10 to 50 parts of the compound of the present invention, 10 to 10 parts of a solvent, and 5 to 5 parts of a surfactant are mixed in appropriate proportions. Prepare the product as a undiluted solution, and add water before use. The solution is diluted to a predetermined concentration and applied by spraying or other methods.

In addition, when used in the form of a wettable powder, the compound 10 of the present invention
~50 parts, 10~10 parts of an extender, and 5~5 parts of a surfactant are mixed in appropriate proportions, and the mixture is made into an emulsion! Dilute with water, etc., and use.

When used in the form of a powder, a mixture of 1 to 5 parts of the compound of the present invention and 95 to 95 parts of a bulking agent such as carrion, bentonite, or talc is usually used.

Furthermore, the agricultural and horticultural fungicide of the present invention can be used in combination with other active ingredients that do not inhibit the bactericidal effect of the active ingredient, such as fungicides, insecticides, and mites. The amount of the agricultural and horticultural fungicide of the present invention used is 250 to 1500 in the case of foliage treatment.
ppm of solution is about 50 to 500 e per 10 are.

Next, the present invention will be explained in more detail by giving examples of the production of the compound of the present invention, formulation examples of agricultural and horticultural fungicides containing the same, and examples of pest control tests using the present fungicide. It is not limited to what is illustrated.

Note that parts indicate parts by weight. Production Example 1 Cysteamine hydrochloride 56.8g, triethylamine 50g
．． 6y was dissolved in 500ml of ethanol, and 14ml of a 25% aqueous solution of heglyoxylic acid was added thereto.

The reaction mixture was heated under reflux for 1.5 hours, cooled, and the precipitated crystals were separated to obtain 41.6y (yield: 62.5%) of thiazolidine-2-carboxylic acid.

Melting point 187-9di (decomposition). Obtained thiazolidine-2
- 6.66y of carboxylic acid and 2.0V of caustic soda at 100%
ml of water, and into this, 9.40"q of 3,5-dichlorophenylisocyanate and 50 nL of chlorobenzene.
A solution of t was added thereto, and the reaction was carried out by stirring at room temperature for 2 hours.

After the reaction, the mixture was extracted with ether and the aqueous phase was neutralized with concentrated hydrochloric acid. The precipitated crystals were separated, washed with water, and dried to give 14.4y (yield: 89.
5%) of 3-(3,5-dichlorophenylcarbamoyl)thiazolidine-2-carboxylic acid was obtained. Melting point 175.
5-7.0℃. Elemental analysis value (calculated value in parentheses) C4O.
88% (41.14%), H3. ll% (3.14%)
, N8.86% (8.72%), Cl22.24% (2
2.08%). Obtained 3-(3,5-dichlorophenylcarbamoyl)thiazolidine-2-carboxylic acid 13.
Add 0q to 50TLL of concentrated hydrochloric acid and heat to 120°C for 2 hours.
The reaction was carried out by heating and stirring for hours. After the reaction was cooled, the precipitated crystals were separated and recrystallized from a mixed solvent of ethyl acetate and hexane to give 10.7 g (yield 86.9%) of 6-(3,
5-dichlorophenyl) perhydroimidazo[5,1-
b] Thiazole-5,7-dione (compound No. 1) was obtained. Melting point 141~2℃, elemental analysis values (calculated values in parentheses) C43.4O% (43.58%), H2.73% (2
．． 66%), N9. 18% (9.24%), Cl23.
25% (23.39%). Production Example 2 Thiazolidine-2-carboxylic acid obtained in Production Example 1 20.0
Add y to 20% hydrochloric acid ethanol solution of 200Tn1,
After heating under reflux for 2 hours, the solvent was distilled off under reduced pressure, water was added, and the mixture was neutralized with saturated aqueous sodium bicarbonate.

After extraction with ethyl acetate, the extract was vacuum distilled.19.
Thiazolidine-2-carboxylic acid ethyl ester of 1f (yield 79.8%) was obtained. Boiling point 104~5℃/5.5T
! RmHyO 1.61y of the obtained thiazolidine-2-carboxylic acid ethyl ester and 2.04y of 3,5-dichlorophenylisothiocyanate were mixed at 20m. The mixture was added to Z in toluene and heated to 90°C for 1 hour to carry out a reaction. After the reaction, it was cooled and the precipitated crystals were separated to give 3.11y (yield: 8
6.1%) of 3-(3,5-dichlorophenylthiocarbamoyl)thiazolidine-2-carboxylic acid ethyl ester was obtained. Melting point 170.5-1.5℃, elemental analysis value (calculated value in brackets) C42.68% (42.74%), H3
．． 93% (3.86%), N7.7O% (7.67%)
, Cll9.32% (19.41%). The obtained 3-(
20 mL of 2.19q of 3,5-dichlorophenylcarbamoyl)thiazolidine-2-carboxylic acid ethyl ester
of concentrated hydrochloric acid, and the mixture was heated and stirred at 120° C. for 1.5 hours to carry out a reaction.

After the reaction was cooled and the precipitate was separated, it was recrystallized from a mixed solvent of ethyl acetate and n-hexane to give 1.43y (yield 74.
7%) of 6-(3,5-dichlorophenyl)perhydroimidazo[5,1-b]thiazo-5-thione-7-
(Compound No. 2) was obtained. Melting point 149.5-50
．． 5℃. Elemental analysis value (calculated value in parentheses) C4l. 33%
(41.39%), H2.59% (2.53%), N8
．． 6O% (8.78%), Cl22.5l% (22.2
1%). Production example 3 Cysteamine hydrochloride 36.6y1 Triethylamine 32.6y1 Pyruvate methyl ester 3
2.99 was added to 500 ml of ethanol, and the reaction was carried out by heating under reflux for 2 hours.

After the reaction, the solvent was distilled off under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The extract was vacuum distilled to yield 36.6 g (yield 7
0.4%) of 2-methylthiazolidine-2-carboxylic acid methyl ester was obtained. Boiling point 76℃/2TnmHy0 3.22y of the obtained 2-methylthiazolidine-2-carboxylic acid methyl ester was mixed with 0.80y of caustic soda and 20m of water.
Add to the solution of 1 and stir at room temperature to make a sodium salt aqueous solution of 2-methylthiazolidine-2-carboxylic acid.
, 5-dichloroisocyanate 3.76y1 A solution of 20 mt of chlorobenzene was added thereto, and the reaction was carried out with stirring for 1S at room temperature.

After the reaction, the mixture was extracted with ether, and the aqueous phase was neutralized with concentrated hydrochloric acid. The precipitated crystals were separated, washed with water, and dried to give 5.22V (yield 77.
9%) of 2-methyl-3-(3,5-dichlorophenylcarbamoyl)thiazolidine-2-carboxylic acid was obtained.
Melting point 164-166°C. Elemental analysis values (calculated values in parentheses)
C43.2l% (43.00%), H3.58% (3,
61%), N8.28% (8.36%), Cl2l. 2
8% (21.15%). The obtained 2-methyl-3-(3
, 5-dichlorophenylcarbamoyl) thiazolidine-2-carboxylic acid 5.0y and sodium acetate 5m9 to 30ml
of acetic anhydride and heated to 90° C. for 2 hours to carry out a reaction. After the reaction, the mixture was concentrated under reduced pressure and water was added. The precipitated crystals were recrystallized from a mixed solvent of ethyl acetate and n-hexane to give 3.9
2q 7a-methyl-6-(3,5-dichlorophenyl)perhydroimidazo[5,1-b]thiazol-5,
7-dione (compound NO, 3) was obtained. Melting point 110-2
℃. Elemental analysis value (calculated value in parentheses) C45.56% (4
5.44%), H3. O9% (3.18%), N8.7
2% (8.83%), Cl22.2O% (22.35%
). Production Example 4 1.61 g of 2-methylthiazolidine-2-carboxylic acid methyl ester obtained in Production Example 3 and 2.04 da of 3,5-dichlorophenylisocyanate were added to 30 ml of toluene, and the mixture was heated and stirred at 90°C for 2 hours. The reaction was carried out.

After the reaction, it was concentrated under reduced pressure and recrystallized from a toluene-n-hexane mixed solvent to give 2.50 Da (yield 75.0%) of 7.
a-Methyl-6-(3,5-dichlorophenyl)perhydroimidazo[5,1-b]thiazol-5-thion-7-one (Compound No. 4) was obtained. Melting point: 160°C~
1℃. Elemental analysis value (calculated value in brackets) C43.36%
(43.25%), H2.95% (3.02%), N8
．． 36% (8.41%), Cl2l. 4l% (21.2
8%). Production Example 5 3,5-dichlorophenylisocyanate 1.88y instead of 3,5-dichlorophenylisothiocyanate 7
The reaction was carried out in the same manner as in Production Example 4 using 1.8
4g (yield 58.0%) of compound NO. I got 3.

Production Example 6 9 Compound NO. obtained in Production Example 1. ll. 52y was dissolved in 10 mt of methylene chloride, to which was added a solution of 1.04y1 m-chloroperbenzoic acid and 12.5 mt of methylene chloride under ice cooling, and the mixture was heated under reflux for 1 hour.

Then, a solution of 1.04y1 m-chloroperbenzoic acid and 12.5ml methylene chloride was added again, and the mixture was heated under reflux for 1 hour to complete the reaction. After the reaction, it was washed with dilute caustic soda, concentrated, and purified by column chromatography using ethyl acetate as a developing solvent to obtain 0.50y (yield 29.8%) of 6-(3
,5-dichlorophenyl)perhydroimidazo[5,1
-b] Thiazole-5,7-dione-1,1-dioxide (Compound No. 5) was obtained. Melting point: 176-8°C. Elemental analysis value (calculated value in parentheses) C4O. Ol% (39.4
2%), H2.36% (2.41%), N8.27% (
8.36%), Cl2l. 35% (21.16%). Production Example 7 Compound No. Compound N obtained in Production Example 3 instead of l
O. 3l. The reaction was carried out in the same manner as in Production Example 6 except that 52y was used.

After the reaction, the product was washed with dilute caustic soda solution, concentrated, and recrystallized from a mixed solvent of ethyl acetate and n-hexane.
(yield 67.6%) of 7a-methyl-6-(3,5-dichlorophenyl)perhydroimidazo[5,1-b]thiazole-5,7-dione-1,1-dioxide (compound No. 6). Obtained. Melting point: 190-1°C. Elemental analysis value (calculated binary values in parentheses) C4l. 35% (41.28%)
, H2.95% (2.89%), N7.89% (8.0
2%), Cl2O. l3% (20.31%). Formulation example 1
Compound No. L-marked part, 45 parts of talc, Solpol 807
A disinfectant (wettable powder) was obtained by uniformly pulverizing and mixing 5 parts of 0 (trademark, surfactant having two main components of higher alcohol sulfate ester).

Formulation Example 2 Compound No. A disinfectant (water) was prepared by uniformly pulverizing and mixing 3 parts of 3 parts, 2 parts of white carbon, 47 parts of diatomaceous earth, and 3 parts of Solbol 5039 (trademark, a surfactant whose main components are polyoxy 3, cyethylene alkylaryl ether sulfonate). (Japanese preparation) was obtained.

Formulation Example 3 Compound No. 2 (9) parts, Solpol 3005X (Trademark, 3! Mixture of nonionic surfactants with anionic surfactants) 15 parts, xylene 25 parts, dimethylformamide 3? A bactericide (emulsion) was obtained by mixing and dissolving.

Formulation Example 4 Compound No. A fungicide (powder) was obtained by mixing and pulverizing 42 parts of N,N-kaolin clay 4C (manufactured by Tsuchiya Kaolin Co., Ltd.) and 98 parts of N,N-kaolin clay 4C (manufactured by Tsuchiya Kaolin Co., Ltd.).

Test Example 1 Test for the control effect of cucumber gray rot A hydrating powder containing compounds No. 2 to 6 as active ingredients obtained in the same manner as in Formulation Example 1, and a comparative drug containing tetrachloroisophthalonitrile as an active ingredient in the same manner as in Formulation Example 1. Dilute the hydrating agent) with water and add 10ml per pot.
The mixture was sprayed in small portions and air-dried for 5 hours.

Next, the gray and diseased bacterium Botrytis cinerea was cultured with shaking in a yeast glucose liquid medium.
inerea) and kept at a humid temperature of 23° C. for 4 days after inoculation, and then the disease state was investigated. The investigation method was as follows. In other words, the disease severity is calculated by calculating the percentage of diseased area of the investigated leaves and dividing it into 0, 1, 2, 3, 4, 5 depending on the degree.
Number of leaves N corresponding to each disease index. ,nl
, n2, n3, rl4, rv. was investigated and calculated using the following formula. (n is the total number of leaves examined) The disease severity control value was calculated using the following formula.

The results are shown in Table 1.

Test Example 2 Test for the control effect of green bean sclerotium disease The compounds shown in Table 2 below were used on green beans (variety: Kintoki) at the third true leaf stage grown in vinyl pots with a diameter of 15 cm, and the same procedure as in Formulation Example 1 was carried out. The prepared test and control drugs in the form of wettable powders were diluted with water, sprayed in 10 mL per pot, air-dried for 5 hours, and then cultured with shaking in a yeast glucose liquid medium. ScierOt
Iniascier OtiOrum) was spray-inoculated and kept at a humid temperature of 23° C. for 4 days after inoculation, and then the disease state was investigated.

The investigation method is the same as Test Example-1. The results are shown in Table 2. Control drug: 2,6-dichloro-4-nitroaniline Test Example 3 Rice sesame leaf blight prevention effect test Hydrogenated rice seedlings (variety: Kinnanpu) at the 3rd to 4th leaf stage grown in clay pots with a diameter of 10 cm agent (compound N obtained according to Formulation Example 1)
O. A hydrating powder containing as an active ingredient a hydrating powder containing as an active ingredient a compound shown in Table 3 obtained in the same manner as in Formulation Example 1, and a hydrating powder containing as an active ingredient a compound shown in Table 3 obtained in the same manner as in Formulation Example 1; Wettable powder containing dimethylthiocarbamoyl (dimethylthiocarbamoyl) disulfide as an active ingredient is diluted with water and 10mt per pot.
After spraying and air drying for 5 hours, moist temperature (temperature 27℃,
The humidity is 100%), and the pre-prepared Sesame gall fungi (
A spore suspension of COchllObO] (cultivated in Usmjyabeanusl rice hull medium at 25°C for 5 days) was inoculated by spraying.

After leaving it in a damp room for an extended period of time, we investigated the onset of the disease.
The control effect was calculated. The results are shown in Table 3.

Table 3 Results of rice sesame leaf blight control test 1 Control agent: Bis(dimethylthiocarbamoyl)
1) Disulfide Test Example 4 Antibacterial Test 5 A chemical solution containing the compounds shown in Table 4 below is mixed to a predetermined concentration in a PDA medium, and poured into a 9 cm diameter Peel dish and allowed to solidify.

Claims (1)

[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R represents a hydrogen atom or a methyl group, X represents an oxygen atom or a sulfur atom, and n is 0, 1 or 2 6-(3,5-dichlorophenyl)perhydroimidazo[5,1-b]thiazole derivative represented by 2
General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R represents a hydrogen atom or a methyl group, X represents an oxygen atom or a sulfur atom, and n represents 0, 1 or 2.) An agricultural and horticultural fungicide containing a 6-(3,5-dichlorophenyl)perhydroimidazo[5,1-b]thiazole derivative as an active ingredient. 3 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ... (II) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R represents a hydrogen atom or a methyl group, and X represents an oxygen atom or a sulfur atom. and R' represents a hydrogen atom or a lower alkyl group. General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ ... (I) (In the formula, R and X have the same meaning as defined in the above general formula (II).) 6- A method for producing a (3,5-dichlorophenyl)perhydroimidazo[5,1-b]thiazole derivative.