Method for producing 1,2-benzisothiazol-3-ones

Abstract: A method for producing a 1,2-benzisothiazol-3-one, having the steps of carrying our a reaction of a 2-halobenzonitrile with an alkanethiol in a heterogeneous solvent system in the presence of a base to give a 2-(alkylthio)benzonitrile and carrying out a reaction of the 2-(alkylthio)benzonitrile with an halogenating agent in the presence of water.

Description: BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a novel method for producing 2-(alkylthio)benzonitriles using 2-halobenzonitriles as starting materials, and to a novel method for producing 1,2-benzisothiazol-3-ones from the 2-(alkylthio)benzonitriles obtained by the method of the present invention. 1,2-benzisothiazol-3-ones are compounds useful as antibacterial agents and antifungal agents. Discussion of the Related Art The following methods are known for producing 1,2-benzisothiazol-3-ones. (A) Bull. Chem. Soc. Jpn., 55, 1183-1187 (1982) In this method, 2-(methylthio)benzamide is produced from 2-(methylthio)benzoyl chloride; oxidized with periodic acid to 2-(methylsulfinyl)benzamide; and cyclized in the presence of thionyl chloride to yield a 1,2-benzisothiazol-3-one. (B) Org. Prep. Proced. Int., 15, 315-319(1983) In this method, a 1,2-benzisothiazol-3-one is obtained in 4 steps, using thiosalicylic acid as a starting material. (C) Ger. Offen. 3500577 (1986) In this method, a desired 1,2-benzisothiazol-3-one is obtained using thiosalicylic acid as a starting material and sodium hydroxide in the final cyclization process. The present applicant have filed patent applications for the following methods as modified methods of the above known methods. (D) Japanese Patent Application No. 5-350932 titled "A method for producing 1,2-benzisothiazol-3-ones" filed on December 29, 1993. (E) Japanese Patent Application No. 6-151476 titled " A method for producing isothiazolone derivatives" filed on June 8, 1994. However, the above known conventional methods have the following drawbacks: In Method (A), the starting 2-(methylthio)benzoyl chloride has problems of high production cost and poor stability. This method also requires the use of an expensive periodic acid which is dangerous in handling and involves many reaction steps. Methods (B) and (C) require the use of expensive thiosalicylic acid as the starting material and involve many reaction steps. Therefore, this method is not satisfactory for industrial use. Methods (D) and (E) proposed by the present applicant are modifications of the above conventional methods, where a starting 2-(alkylthio)benzamide reacts with a halogenating agent. As stated above, all known methods are not satisfactory for production on an industrial scale. SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a simple and economical method for producing 1,2-benzisothiazol-3-ones on an industrial scale, without using materials which are costly and dangerous in handling. Another object of the present invention is to provide a novel method for producing 2-(alkylthio)benzonitriles which are intermediates for the production of 1,2-benzisothiazol-3-ones. In order to achieve the above objects, the present inventors made intensive studies to provide an easy and economically advantageous method for producing 1,2-benzisothiazol-3-ones without using materials which are costly and dangerous in handling. As a result, the present inventors found that a 1,2-benzisothiazol-3-one represented by the general formula (III) can be obtained in one step by treating a 2-(alkylthio)benzonitrile represented by the general formula (IV) with a halogenating agent in the presence of water as shown below, the 2-(alkylthio)benzonitrile being obtained by the reaction of a 2-halobenzonitrile represented by the general formula (V) with an alkanethiol represented by the general formula (VI) in the presence of a base in a heterogeneous solvent system. wherein R 1 represents an alkyl group having 1 to 4 carbon atoms, and R 2 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a carboxyl group or an ester thereof, or a halogen atom. Specifically, the present inventors discovered that a 2-(alkylthio)benzonitrile represented by the general formula (IV) is easily obtained by the reaction of a 2-halobenzonitrile represented by the general formula (V) with an alkanethiol represented by the general formula (VI) in the presence of a base in a heterogeneous solvent system. The present inventors also found that a 1,2-benzisothiazol-3-one represented by the general formula (III) is obtained by further treating the 2-(alkylthio)benzonitrile obtained in the above reaction and represented by the general formula (IV) with a halogenating agent in the presence of water, and that when a water-insoluble organic solvent system is used as a solvent of the above reaction, a series of the above reactions to yield a 1,2-benzisothiazol-3-one from a 2-halobenzonitrile can be carried out in a one-pot process. Based upon the above findings, the present inventors made further studies and have completed the present invention. In brief, the present invention is concerned with: (1) A method for producing a 1,2-benzisothiazol-3-one represented by the general formula (III), comprising carrying out a reaction of a 2-(alkylthio)benzonitrile represented by the following general formula (IV): wherein R 1 represents an alkyl group having 1 to 4 carbon atoms, and R 2 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a carboxyl group or an ester thereof, or a halogen atom, with a halogenating agent in the presence of water to give a 1,2-benzisothiazol-3-one represented by the following general formula (III): wherein R 2 is defined as above; (2) A method for producing a 2-(alkylthio)benzonitrile represented by the general formula (IV), comprising carrying out a reaction of a 2-halobenzonitrile represented by the following general formula (V): wherein X represents a chlorine atom or a bromine atom, and R 2 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a carboxyl group or an ester thereof, or a halogen atom, with an alkanethiol represented by the following general formula (VI): R 1 SH wherein R 1 represents an alkyl group having 1 to 4 carbon atoms, in a heterogeneous solvent system in the presence of a base to give a 2-(alkylthio)benzonitrile represented by the following general formula (IV): wherein R 1 and R 2 are defined as above; and (3) A method for producing a 1,2-benzisothiazol-3-one represented by the general formula (III), comprising carrying out a reaction of a 2-halobenzonitrile represented by the following general formula (V): wherein X represents a chlorine atom or a bromine atom, and R 2 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a carboxyl group or an ester thereof, or a halogen atom, with an alkanethiol represented by the following general formula (VI): R 1 SH wherein R 1 represents an alkyl group having 1 to 4 carbon atoms, in a heterogeneous solvent system in the presence of a base to give a 2-(alkylthio)benzonitrile represented by the following general formula (IV): wherein R 1 and R 2 are defined as above; and carrying out a reaction of said 2-(alkylthio)benzonitrile with a halogenating agent in the presence of water to give a 1,2-benzisothiazol-3-one represented by the following general formula (III): wherein R 2 is defined as above. According to the process of the present invention, 1,2-benzisothiazol-3-ones, compounds useful as antibacterial or antifungal agents, can easily be produced in high yield in short process without using expensive starting materials. DETAILED DESCRIPTION OF THE INVENTION The present invention will be explained in detail below. The present invention discloses a method for producing a 1,2-benzisothialzol-3-one, wherein a 2-(alkylthio)benzonitrile represented by the general formula (IV) is treated with a halogenating agent in the presence of water in one step to yield a 1,2-benzisothiazol-3-one, the 2-(alkylthio)benzonitrile being obtained by the reaction of a 2-halobenzonitrile represented by the general formula (V) with an alkanethiol represented by the general formula (VI) in the presence of a base in a heterogeneous solvent system. The method of the present invention is characterized in that a 1,2-benzisothiazol-3-one can easily be produced by cyclizing a 2-(alkylthio)benzonitrile, readily being obtained from a 2-halobenzonitrile, with a halogenating agent in the presence of water. The method is also characterized by producing a 1,2-benzisothiazol-3-one in a one-pot process by the steps of carrying out a reaction between a 2-halobenzonitrile and an alkanethiol in the presence of a base in a heterogeneous solvent system containing a water-insoluble solvent to yield a 2-(alkylthio)benzonitrile separating oil layer containing the 2-(alkylthio)benzonitrile from water layer, treating the 2-(alkylthio)benzonitrile in the oil layer with a halogenating agent in the presence of water to yield a 1,2-benzisothiazol-3-one. R 1 in the above general formulas (IV) and (VI) stands for an alkyl group having 1 to 4 carbon atoms. Alkyl groups represented by R 1 are exemplified by methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and sec-butyl, tert-butyl groups, with a preference given to methyl, ethyl, n-propyl, and tert-butyl groups. R 2 in the general formulas (IV), (III), and (V) stands for a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a carboxyl group or an ester thereof, or a halogen atom. Alkyl groups represented by R 2 are exemplified by methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl groups. Alkoxy groups represented by R 2 are exemplified by methoxy, ethoxy, propoxy, and butoxy groups. Esters of carboxyl group represented by R 2 are exemplified by methoxy carbonyl, ethoxy carbonyl, propoxy carbonyl, and butoxy carboxyl. Halogen atoms represented by R 2 are exemplified by a chlorine atom and a bromine atom. Preferred examples of R 2 include a hydrogen atom, a methyl group, an ethyl group, a tert-butyl group, a methoxy group, a methoxy carbonyl group, an ethoxy carbonyl group, a propoxy carbonyl group, a chlorine atom, and a nitro group. Examples of 2-(alkylthio)benzonitrile represented by the general formula (IV) include: 2-(methylthio)benzonitrile, 2-(ethylthio)benzonitrile, 2-(n-propylthio)benzonitrile, 2-(tert-butylthio)benzonitrile, 3-methyl-2-(methylthio)benzonitrile, 5-butyl-2-(methylthio)benzonitrile, 4-methoxy-2-(methylthio)benzonitrile, 2-methylthio-3-nitrobenzonitrile, 4-chloro-2-(methylthio)benzonitrile, 4-carboxy-2-(methylthio)benzonitrile, and 4-methoxycarbonyl-2-(methylthio)benzonitrile. Of the above examples, 2-(methylthio)benzonitrile, 2-(ethylthio)benzonitrile, 2-(n-propylthio)benzonitrile, and 2-(tert-butylthio)benzonitrile are preferably used because they are readily available and can give products with high antibacterial activity. Although the method for producing 2-(alkylthio)benzonitriles represented by the general formula (IV) is not limited, it is advantageous to use the method of the present invention. Specifically, a 2-(alkylthio)benzonitrile represented by the general formula (IV) is produced by the reaction of a 2-halobenzonitrile represented by the general formula (V) with an alkanethiol represented by the general formula (VI) in the presence of a base in a heterogeneous solvent system. In the general formula (V), X stands for a chlorine atom or a bromine; and R 2 stands for the same substituents as R 2 in the general formula (IV). R 1 in the general formula (VI) stands for the same substituents as R 1 in the general formula (IV). Examples of 2-halobenzonitriles represented by the general formula (V) include 2-chlorobenzonitrile, 2-bromobenzonitrile, 3-methyl-2-chlorobenzonitrile, 5-butyl-2-chlorobenzonitrile, 4-methoxy-2-chlorobenzonitrile, 2-chloro-3-nitrobenzonitrile, and 4-methoxycarbonyl-2-chlorobenzonitrile. Alkanethiols represented by the general formula (VI) are exemplified by methanethiol, ethanethiol, 1-propanethiol, and 2-butanethiol. The alkanethiol is used normally in an amount of 0.8 to 3.0 moles, preferably 1.0 to 2.0 moles, per mole of 2-halobenzonitrile used. When the amount of alkanethiol used is less than 0.8 moles, unchanged 2-halobenzonitrile increases. Even though the amount of alkanethiol exceeds 3.0 moles, additional effects cannot be expected, and, therefore, it is economically disadvantageous. Bases which can be used in the reaction of a 2-halobenzonitrile with an alkanethiol include alkali metal hydroxides, such as sodium hydroxide and potassium hydroxide; alkali metal carbonates, such as sodium carbonate and potassium carbonate; and metal alcoholates, such as sodium methylate and sodium ethylate. From the economic viewpoint, sodium hydroxide is preferably used. The base is used normally in an amount of 0.8 to 3.5 moles, preferably 1.0 to 2.5 moles, per mole of 2-halobenzonitrile used. When the amount of a base used is less than 0.8 moles, unchanged 2-halobenzonitrile increases. Even when the amount of base used exceeds 3.5 moles, additional effects cannot be expected, and, therefore, it is economically disadvantageous. The present method for producing an 2-(alkylthio)benzonitrile is characterized in that the reaction is carried out in a heterogeneous solvent system in the presence of a base. The reaction of a starting 2-halobenzonitrile with an alkanethiol is carried out in a two-phase solvent system, because a 2-halobenzonitrile is insoluble in water. In this case, a phase-transfer catalyst is preferably added to the solvent system to promote the reaction. Phase-transfer catalysts which can be used for this purpose include quaternary ammonium salts, such as benzyltriethylammonium bromide, benzyltrimethylammonium chloride, hexadecyltriethylammonium bromide, hexadecyltrimethylammonium chloride, dodecyltrimethylammonium chloride, octyltriethylammonium bromide, tetra-n-butylammonium bromide, tetra-n-butylammonium chloride, tetraethylammonium chloride and trioctylmethylammonium chloride; quaternary phosphonium salts, such as hexadecyltriethylphosphonium bromide, hexadecyltributylphosphonium chloride, tetra-n-butylphosphonium bromide, tetra-n-butylphosphonium chloride, trioctylethylphosphonium bromide and tetraphenylphosphonium bromide; and crown ethers, such as 18-crown-6, dibenzo-18-crown-6 and dicyclohexyl-18-crown-6. From the economic viewpoint, quaternary ammonium salts, such as tetra-n-butylammonium bromide and tetra-n-butylammonium chloride, are preferably used. In the case where a phase-transfer catalyst is used, the amount of the phase-transfer catalyst used is normally 0.005 to 0.5 times, preferably 0.01 to 0.2 times the weight of 2-halobenzonitrile. When the amount of a phase-transfer catalyst used is less than 0.005 times the weight of 2-halobenzonitrile, adequate catalytic effecte cannot be obtained. Even when the amount of a phase-transfer catalyst used exceeds 0.5 times the weight of 2-halobenzonitrile used, additional expected effect cannot be obtained, and, therefore, it is economically disadvantageous. In this method, a reaction solvent is not always necessary. However, in order to facilitate the reaction and the separation of the product from the reaction mixture, the use of mixed solvent composed of 0.5 to 10 parts by weight of a water-insoluble organic solvent based on 1 part by weight of water is preferred in the present invention. In many cases, better results can be obtained by the use of the mixed solvent. Water-insoluble organic solvents are not particularly limited and include hydrocarbons, such as n-hexane, n-heptane, cyclohexane, methylcyclohexane, benzene, toluene and xylene; and halogenated hydrocarbons, such as methylene chloride, 1,2-dichloroethane and chlorobenzene. The amount of the solvent used is normally 1 to 30 times the weight of 2-halobenzonitrile. The reaction temperature for the above reaction is normally in the range of from 0 to 150°C, preferably 20 to 120°C. Reaction temperatures higher than 150°C cause side reactions. On the other hand, the reaction rate unfavorably lowers to an impractical level when the reaction temperature is less than 0°C. The reaction time varies with the reaction temperature and the types of phase-transfer catalyst and reaction solvent and cannot be generalized, but it is normally in the range between 1 and 40 hours. After completion of the reaction, a 2-(alkylthio)benzonitrile can be isolated and purified from the separated organic solvent layer by an ordinary procedure, such as crystallization. Since the water layer separated contains a phase-transfer catalyst, it can repeatedly be used in subsequent reactions. Therefore, almost no aqueous waste is discharged out of the solvent system. The separated organic solvent layer containing an 2-(alkylthio)benzonitrile can also directly be used for the reaction to yield a 1,2-benzisothiazol-3-one. Next, the process in which 1,2-benzisothiazol-3-ones are obtained from 2-(alkylthio)benzonitriles will be described. Examples of halogenating agents usable in the process include chlorine, bromine, sulfuryl chloride and sulfuryl bromide, with a preference given to sulfuryl chloride and chlorine in view of reaction selectivity. The halogenating agent is used normally in an amount of 0.8 to 3.0 moles, preferably 1.0 to 2.0 moles, per mole of 2-(alkylthio)benzonitrile. When the amount of the halogenating agent is less than 0.8 moles of 2-(alkylthio)benzonitrile, the amount of unchanged 2-(alkylthio)benzonitrile tends to increase. On the other hand, the amount of halogen used exceeds 3.0 moles, side reactions occur and lower the yield. The water is added in the process to yield a 1,2-benzisothiazol-3-one normally in an amount of 0.8 to 5.0 moles, preferably 1.0 to 3.0 moles, per mole of 2-(alkylthio)benzonitrile. When the amount of water is less than 0.8 moles or more than 5.0 moles, side reactions occur to lower the yield. Solvents used in the process to yield a 1,2-benzisothiazol-3-one are not particularly limited as long as they are inert to the reaction. Examples of solvents usable in the reaction include hydrocarbons, such as n-hexane, n-heptane, cyclohexane, methylcyclohexane, benzene, toluene and xylene; and halogenated hydrocarbons, such as methylene chloride, 1,2-dichloroethane and chlorobenzene. When the same solvent as used in the reaction of 2-halobenzonitrile with an alkanethiol to yield a 2-(alkylthio)benzonitrile is used in the process, a series of reactions, i.e., the reaction to obtain a 2-(alkylthio)benzonitrile and the reaction to obtain a 1,2-benzisothiazol-3-one from the 2-(alkylthio)benzonitrile, can be carried out in a one-pot process. Therefor, the production efficiency can markedly be increased. The amount of the solvent used is normally 1 to 30 times the weight of 2-(alkylthio)benzonitrile. The reaction temperature for the process is normally in the range of from -20 to 170°C, preferably 0 to 150°C. Reaction temperature higher than 170°C causes side reactions. On the other hand, the reaction rate unfavorably lowers to an impractical level when the reaction temperature is less than -20°C. The reaction time varies with the reaction temperature and reaction solvent, and it is normally in the range between 1 and 40 hours. The isolation of 1,2-benzisothiazol-3-one from the reaction mixture obtained by the above method can normally be carried out by conventional crystallization technique or by recrystallization after extraction, but other technique may be used. Examples of 1,2-benzisothiazol-3-ones represented by the general formula (III) obtained by the method of the present invention include: 1,2-benzisothiazol-3-one, 7-methyl-1,2-benzisothiazol-3-one, 5-butyl-1,2-benzisothiazol-3-one, 6-methoxy-1,2-benzisothiazol-3-one, 7-nitro-1,2-benzisothiazol-3-one, 6-chloro-1,2-benzisothiazol-3-one, 6-carboxy-1,2-benzisothiazol-3-one, and 6-methoxycarbonyl-1,2-benzisothiazol-3-one. EXAMPLES The present invention will be further described by means of the following working examples, without intending to restrict the scope of the present invention thereto. Incidentally, the obtained product is confirmed by nuclear magnetic resonance method ( 1 H-NMR) or mass spectroscopy in order to determine whether a desired product is obtained. Example 1: Synthesis of 2-(methylthio)benzonitrile To a 500 ml four-necked flask equipped with a stirrer, a thermometer, and a condenser, 27.5 g (0.2 mol) of 2-chlorobenzonitrile, 100 g of monochlorobenzene, and 5.5 g of 50% by weight aqueous solution of tetra-n-butylammonium bromide were placed under nitrogen atmosphere. Separately, 9.6 g (0.24 mol) of sodium hydroxide and 35.0 g of water were placed in a vessel under nitrogen atmosphere, to which 11.5 g (0.24 mol) of methanethiol was added at room temperature for 1 hour. 56.1 g (0.24 mol) of the resulting 30% by weight aqueous solution of sodium methylmercaptide was added to the above four-necked flask with stirring and refluxed for 2 hours. After the completion of the reaction, the reaction mixture was cooled to room temperature. After the solvent was distilled off, the reaction mixture was evaporated to dryness under a reduced pressure to give 29.2 g of 2-(methylthio)benzonitrile (boiling point:139 to 140°C/7mmHg). The yield against 2-chlorobenzonitrile was 98%. Example 2: Synthesis of 1,2-benzisothiazol-3-one To a 500 ml four-necked flask equipped with a stirrer, a thermometer, and a condenser, 29.8 g (0.2 mol) of 2-(methylthio)benzonitrile, 100 g of monochlorobenzene, and 4.32 g (0.24 mol) of water were added. To the flask, 29.7 g (0.22 mol) of sulfuryl chloride was added with stirring at a temperature of from 5 to 15°C, heated to a temperature of from 70 to 80°C, and allowed to react for 1 hour. After the completion of the reaction, the reaction mixture was cooled to room temperature to precipitate white crystals. The white crystals were washed with monochlorobenzene, and dried to give 29.0 g of 1,2-benzisothiazol-3-one (melting point: 157 to 158°C). The yield of the product was 96% against the starting 2-(methylthio)benzonitrile. Example 3: Synthesis of 1,2-benzisothiazol-3-one (one-pot process) To a 500 ml four-necked flask equipped with a stirrer, a thermometer, and a condenser, 27.5 g (0.2 mol) of 2-chlorobenzonitrile, 100 g of monochlorobenzene, and 2.25 g of 50% by weight aqueous solution of tetra-n-butylammonium bromide were placed under nitrogen atmosphere. Separately, 9.6 g (0.24 mol) of sodium hydroxide and 35.0 g of water were placed in a vessel under nitrogen atmosphere, to which 11.5 g (0.24 mol) of methanethiol was added at room temperature for 1 hour. 56.1 g (0.24 mol) of the resulting 30% by weight aqueous solution of sodium methylmercaptide was added to the above four-necked flask with stirring and refluxed for 2 hours. After the completion of the reaction, the reaction mixture was separated to water (lower) layer and oil (upper) layer at 40 to 50°C. To the oil layer, 100 g of monochlorobenzene, and 3.6 g (0.2 mol) of water were added. To the flask, 27.0 g (0.2 mol) of sulfuryl chloride was added with stirring at a temperature of from 5 to 15°C, heated to a temperature of from 70 to 80°C, and allowed to react for 1 hour. After the completion of the reaction, the reaction mixture was cooled to room temperature to precipitate white crystals. The white crystals were washed with monochlorobenzene, and dried to give 29.3 g of 1,2-benzisothiazol-3-one (melting point: 157 to 158°C). The yield of the product was 97% against the starting 2-chlorobenzonitrile. Example 4: Synthesis of 1,2-benzisothiazol-3-one (one-pot process) 25.7 g of 1,2-benzisothiazol-3-one was obtained by the same procedures as in Example 3 except that 14.2 g (0.2 mol) of chlorine was introduced into the reaction mixture instead of adding sulfuryl chloride. The yield of the product was 85% against the starting 2-chlorobenzonitrile. Examples 5 to 10: Syntheses of 1,2-benzisothiazol-3-ones 1,2-benzisothiazol-3-ones were obtained in the same manner as in Example 2 except that 2-(alkylthio)benzonitriles listed in Table 1 were used as starting materials.

Claims: A method for producing a 1,2-benzisothiazol-3-one represented by the following general formula (III): wherein R 2 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a carboxyl group or an ester thereof, or a halogen atom, comprising carrying out a reaction of a 2-(alkylthio)benzonitrile represented by the following general formula (IV): wherein R 1 represents an alkyl group having 1 to 4 carbon atoms, and R 2 is defined as above, with a halogenating agent in the presence of water to give a 1,2-benzisothiazol-3-one represented by the following general formula (III): wherein R 2 is defined as above. The method according to claim 1, wherein said halogenating agent is chlorine. The method according to claim 1, wherein said halogenating agent is sulfuryl chloride. The method according to any one of claims 1 to 3, wherein the compound represented by the general formula (IV) is selected from the group consisting of 2-(methylthio)benzonitrile, 2-(ethylthio)benzonitrile, 2-(n-propylthio)benzonitrile, 2-(tert-butylthio)benzonitrile, 3-methyl-2-(methylthio)benzonitrile, 5-butyl-2-(methylthio)benzonitrile, 4-methoxy-2-(methylthio)benzonitrile, 2-methylthio-3-nitrobenzonitrile, 4-chloro-2-(methylthio)benzonitrile, 4-carboxy-2(methylthio)benzonitrile, and 4-methoxycarbonyl-2-(methylthio)benzonitrile. A method for producing a 1,2-benzisothiazol-3-one represented by the following general formula (III): wherein R 2 represents a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a carboxyl group or an ester thereof, or a halogen atom, comprising carrying out a reaction of a 2-halobenzonitrile represented by the following general formula (V): wherein X represents a chlorine atom or a bromine atom, and R 2 is defined as above, with an alkanethiol represented by the following general formula (VI): R 1 SH wherein R 1 represents an alkyl group having 1 to 4 carbon atoms, in a heterogeneous solvent system in the presence of a base to give a 2-(alkylthio)benzonitrile represented by the following general formula (IV): wherein R 1 and R 2 are defined as above; and carrying out a reaction of said 2-(alkylthio)benzonitrile with an halogenating agent in the presence of water to give a 1,2-benzisothiazol-3-one represented by the following general formula (III): wherein R 2 is defined as above.

Inventors: GODA HIROSHI, KAGANO HIROKAZU, SAKAUE SHIGEKI, YAMAMOTO MIKIO, YOSHIDA KATSUHIKO, GODA, HIROSHI, SAKAUE, SHIGEKI, YAMAMOTO, MIKIO, YOSHIDA, KATSUHIKO, Goda, Hiroshi, c/o Sumitomo Seika Chem. Co. Ltd., Kagano Hirokazu, Sumitomo Seika Chem. Co. Ltd., Sakaue, Shigeki, c/o Sumitomo Seika Chem. Co. Ltd., Yamamoto, Mikio, c/o Sumitomo Seika Chem. Co. Ltd., Yoshida, Katsuhiko, Sumitomo Seika Chem. Co. Ltd.
Applicants: SUMITOMO SEIKA CHEMICALS, SUMITOMO SEIKA CHEMICALS CO., LTD.
Application year: 1995
Main classification: C07D275
IPC codes: C07D275