KR890001701B1 - New process for preparing 3,4-disubstituted-benzothiazole-2-on derivatives - Google Patents

Abstract

A method of the production for the title compds. (I)[R1= halogen atom (Cl, Br, F) or methyl; R2=C1-4 of alkyl) comprises (a) dissolving 18.47g of 2-amino-4-chloro-benzothiazol in 20ml of dimethylformamide and adding to 16.83g of KOH, (b) adding 37.84g of dimethylsulfate to the mixture having KOH and heating at 153≰C for 8hr, (c) extracting the mixture with 50ml of ethylacetate, (d) neutralizing a saturated aqueous soln. of sodium bicarbonate.

Description

New preparation of 3,4-disubstituted-benzothiazol-2-one derivatives

The present invention relates to a new process for the preparation of 3,4-disubstituted-benzothiazol-2-one derivatives of the following formula (I) (hereinafter referred to as "benzothiazolone derivatives").

Wherein R ₁ is a halogen atom (eg Cl, Br, F) or a methyl group, and R ₂ is an alkyl group of C ₁ -C ₄ . Benzothiazolone derivatives are particularly effective in preventing rice blast (pyrichloria orizae) and rot (Helmintosporium sigmide) and have the characteristics that can be applied by either leaf or root soil. In addition, it has a very strong effect, which is faster to control and longer lasting than conventional antimicrobial agents, and has extremely low toxicity to warm-blooded animals (e.g. mice, mice, chicks) and fish (e.g. carp, small fishes of North America). There is little toxicity left. As a method for preparing a benzothiazolone derivative known so far, German Patent Application Publication No. 2924712 discloses diazotizing 4-substituted-2-amino benzothiazole of the following general formula (III) to 4-substituted general formula (IV)- 2-halobenzothiazole was prepared, followed by reaction in the presence of a lower alcohol and a basic condensate to form 4-substituted-2-alkoxy benzothiazole of general formula (V), followed by thermal dislocation with a catalyst to formula (I). A benzothiazolone derivative is synthesized.

R ₁ , R ₂ are as defined above and X is Cl or Br. In addition, Japanese Patent Application Laid-Open Nos. 82-6935 and 82-6972 disclose 2-substituted-N-alkylanilines of the following general formula (VI) in the presence of a tertiary base. And a phenylthiazole derivative of the following general formula (VIII) to form a phenylthiazole derivative of the general formula (I) by ring closing the reaction in aluminum chloride or concentrated sulfuric acid.

These methods are a multi-stage reaction, not only takes a long reaction time, but also is difficult to operate and the yield is low to 70-80%, making it difficult to carry out on an industrial scale.

The present inventors earnestly studied to solve the above problems, and react the 4-substituted-2-aminobenzothiazole derivative of the general formula (II) with an alkylating agent in the presence of an alkali metal hydroxide in a one-step reaction. The present invention was completed to know that can be obtained in high purity (more than 96%), high yield (more than 90%). That is, the present invention reacts the 4-substituted-2-aminobenzothiazole derivative of formula (II) with an alkylating agent in the presence of an alkali metal hydroxide to form a quaternary salt of formula (IX) or formula (X), A method for producing a 3,4-disubstituted-benzothiazol-2-one derivative of formula (I) characterized by decomposition.

Wherein R ₁ is a fluorine, chlorine, bromine or methyl group, R ₂ is an alkyl group of C ₁ -C ₄ and R ₃ and R ₄ are differently or identically an alkyl group of hydrogen, C ₁ -C ₈ , or C ₄ -C A cycloalkyl group of ₁₂ or a cycloalkyl group containing oxygen, nitrogen and Y is iodine, bromine, chlorine or an alkylating ion. Hereinafter, the present invention will be described in detail. The 4-substituted-2-aminobenzothiazole derivative, which is a compound of formula (II), which is a starting material of the present invention, can be prepared by the following method. (J. Heterocyclic Chem. 17, 1325 (1980))

Examples of alkali metal hydroxides used in the present invention are KOH, NaOH, K ₂ CO ₃ , NaHCO ₃ , Na ₂ CO ₃ , Mg (OH) ₂ , Ca (OH) ₂ , and the amount of the alkali metal hydroxide is 1 per compound of formula (II). More than one mole, preferably 3-8 moles. In addition, examples of the alkylating agent are dialkyl sulfate, alkyl halide and trialkyl phosphate, and the amount of the alkylating agent is 1 mole or more, preferably 3-8 moles per compound of formula (II). The reaction can be carried out in the presence or absence of a solvent and solvents include toluene, benzene, xylene, chloroform, diglyme dimethylsulfoxide, dimethylsulfate dimethylformamide, water and the like. Reaction temperature is 0 degreeC or more, Preferably it is made to react at room temperature to the reflux temperature of a solvent. It will be described in detail by the following examples.

Example 1

4-Chloro-3-methyl-benzothiazol-2-one

18.47 g (0.1 mol) of 2-amino-4-chloro-benzothiazole is dissolved in 20 cc of dimethylformamide, and 16.83 g (0.3 mol) of KOH is dissolved in a small amount of water and mixed. 37.84 g (0.3 mol) of dimethyl sulfate was added to the mixture and heated to reflux at 153 ° C. for 8 hours to complete the reaction. After the reaction, the mixture was cooled, extracted with 50 cc of ethyl acetate, washed with saturated aqueous sodium bicarbonate solution, and the vessel solvent was distilled under reduced pressure to obtain 19.16 g of the target compound as a white solid.

Yield: 94.2%, purity: 98.0%

Example 2-14

4-Chloro-3-methyl-benzothiazol-2-one

Next, the results of Table 1 were obtained in the same manner as in Example 1, using the materials listed in Table 1 as starting materials.

TABLE 1

Example 15

4-Chloro-3-ethyl-benzothiazol-2-one

18.47 g (0.1 mol) of 2-amino-4-chlorobenzothiazole was dissolved in 20 cc of diglyme, and 41.46 g (0.3 mol) of K ₂ CO _3, 1.8 cc of water and 46.25 g (0.3 mol) of diethyl sulfate were added thereto. Heat. After refluxing at 162 ° C. for 12 hours, the mixture was cooled and extracted with 50 cc of ethyl acetate. The organic layer was washed with saturated aqueous sodium carbonate solution and distilled under reduced pressure to remove the organic solvent to obtain 19.88 g of the target compound.

Yield: 91.1%, Purity: 97.8%

[Example 16-31]

4-Chloro-3-ethyl-benzothiazol-2-one

Next, the result of Table 2 was obtained by performing the same method as Example 15 using the material of Table 2 as a starting material.

TABLE 2

Example 32

4-bromo-3-methyl-benzothiazol-2-one

22.97 g (0.1 mol) of 2-amino-4-bromobenzothiazole was dissolved in 20 cc of dimethylformamide (DMF), 41.46 g (0.3 mol) of K ₂ CO _{3 and} 1.8 cc of water and 28.02 g of trimethylsulfate ( 0.2 mol) was added thereto, heated to reflux at 153 ° C. for 10 hours, cooled, extracted with 50 cc of ethyl acetate, and washed with saturated aqueous sodium bicarbonate solution. The organic solvent is then removed to give 22.91 g of the desired compound.

Yield: 92.1%, Purity: 98.4%

Example 33-42

4-bromo-3-methyl-benzothiazol-2-one

Next, the result of Table 1 was obtained in the same manner as in Example 32, using the material of Table 3 as a starting material.

TABLE 3

Example 43

3,4-dimethyl-benzothiazol-2-one

Dissolve 16.42 g (0.1 mol) of 2-amino-4-methyl-benzothiazole, add KOH 16,83 (0.3 mol), 1.8 cc water, and 28.02 g (0.2 mol) of trimethylphosphate, and heat. The mixture was refluxed at 153 ° C. for 14 hours, cooled, extracted with 50 cc of ethyl acetate, and washed with saturated aqueous sodium bicarbonate solution. Thereafter, the organic solvent is removed to obtain 16.84 g of the target compound.

Yield: 91.1%, Purity: 97.4%

Example 44-53

3,4-dimethyl-benzothiazol-2-one

Next, the result of Table 1 was obtained in the same manner as in Example 43, using the material of Table 4 as a starting material.

TABLE 4

Example 54

4-fluoro-3-methyl-benzothiazol-2-one

16.88 g (0.1 mol) of 2-amino-4-fluoro-benzothianol was dissolved in 20 cc DMF, followed by 41.46 g (0.3 mol) of K ₂ CO _3, 1.8 cc of water, and 37.84 g (0.3 mol) of dimethyl sulfate. 17.60 g of the target compound are obtained in the same manner as in (1).

Example 55-62

4-fluoro-3-methyl-benzothiazol-2-one

Next, the result of Table 1 was obtained by performing the same method as Example 1 using the material of Table 5 as a starting material.

TABLE 5

Claims (3)

The 4-substituted-2-aminobenzothiazole derivative represented by formula (II) is reacted with an alkylating agent in the presence of an alkali metal hydroxide to form a quaternary salt represented by formula (IX) or formula (X), A method for producing a 3,4-disubstituted-benzothiazol-2-one derivative represented by general formula (I), which is obtained by hydrolyzing this.

(Wherein R ₁ is a fluorine, chlorine, bromine or methyl group, R ₂ is an alkyl group of C ₁ -C ₄ , R ₃ and R ₄ are different or identical hydrogen, an alkyl group of C ₁ -C ₈ , or C _4- C ₁₂ is an alkyl group or a cycloalkyl group containing oxygen and nitrogen, and Y represents iodine, bromine, chlorine or alkylating ion.) The 3,4-disubstituted-benzothiazol-2-one derivative according to claim 1, wherein the alkali metal hydroxide is KOH, NaOH, K2CO3, Na2CO3, NaHCO3, Mg (OH) 2, Ca (OH) 2. Manufacturing method. 3.4-Di-substituted according to claim 1, wherein the alkylating agent is dimethylsulfate, diethylsulfate, iodinemethane, bromomethane, chloromethane, iodineethane, bromoethane, chloroethane, trimethylphosphate, triethyl phosphate. Process for the preparation of benzothiazol-2-one derivatives.