JP2013043882A - Method for producing 1,2-benzisothiazolin-3-one compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a 1,2-benzisothiazolin-3-one compound from a reaction liquid obtained by making a 2-(alkylthio)benzonitrile compound and a halogenating agent react with each other in the presence of water, with high purity and with a high yield.SOLUTION: The 1,2-benzisothiazolin-3-one compound is deposited by adding an alkali to the reaction liquid obtained by making the 2-(alkylthio)benzonitrile compound and the halogenating agent react with each other in the presence of water, and adding an acid thereto after heat treatment.

Description

  The present invention relates to a method for producing a 1,2-benzisothiazolin-3-one compound. More specifically, the present invention relates to a production method capable of obtaining a 1,2-benzisothiazolin-3-one compound useful as an antibacterial agent, an antifungal agent and the like with high purity and high yield.

  In Patent Document 1, as a method for producing a 1,2-benzisothiazolin-3-one compound in an industrially advantageous and simple and economical manner without using an expensive and highly dangerous material for handling, A method of reacting a 2- (alkylthio) benzonitrile compound and a halogenating agent in the presence of water is disclosed.

Japanese Patent Laid-Open No. 8-134051

  In the method disclosed in Patent Document 1, although a 1,2-benzisothiazolin-3-one compound can be obtained in a high yield in a shorter process than the conventional production method, a by-product generated during the reaction is generally used. Since it is difficult to remove efficiently and completely by crystallization or the like, the purity of the obtained 1,2-benzisothiazolin-3-one compound is low and there is still room for improvement.

  Thus, an object of the present invention is to provide a method for easily and economically producing a 1,2-benzisothiazolin-3-one compound with higher purity and higher yield.

  As a result of intensive studies to solve the above problems, the present inventors have found that the main by-product in the 1,2-benzisothiazolin-3-one compound obtained by the method described in Patent Document 1 is 2 It has been found that the 1,2-benzisothiazolin-3-one compound of the molecule is an N, N′-methylenebis (1,2-benzisothiazolin-3-one) compound bonded via a methylene group. The by-product is a compound that is difficult to remove by commonly used crystallization and the like, and in order to obtain a high-purity 1,2-benzisothiazolin-3-one compound, a relatively high temperature, for example, a temperature exceeding 40 ° C. It was found that it was necessary to filter with. However, it has also been found that there is a problem that the yield of the target 1,2-benzisothiazolin-3-one compound is lowered by such a simple filtration method at a high temperature.

  As a result of further intensive studies, the present inventors have found that the 1,2-benzisothiazolin-3-one compound containing the by-product N, N′-methylenebis (1,2-benzisothiazolin-3-one) is alkalinized. Is added, and the N, N′-methylenebis (1,2-benzisothiazolin-3-one) compound, which is a by-product, is decomposed and 1,2-benzisothiazoline— It is converted into an alkali salt of 3-one compound, and then acid is added for precipitation (acid precipitation) to obtain high purity 1,2-benzisothiazolin-3-one compound without reducing the yield. The present invention has been completed.

  That is, the present invention is a method for producing a 1,2-benzisothiazolin-3-one compound, which is represented by the general formula (1):

（式中、Ｒ^１は、水素原子、炭素数１〜４のアルキル基、炭素数１〜４のアルコキシ基、ニトロ基、カルボキシル基もしくはそのエステル、またはハロゲン原子を示す。）で表される１，２−ベンズイソチアゾリン−３−オン化合物および一般式（２）：

(Wherein R ¹ 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). , 2-Benzisothiazolin-3-one compounds and general formula (2):

（式中、Ｒ^１は、前記一般式（１）におけるＲ^１と同じ原子または基を示す。）で表されるＮ，Ｎ’−メチレンビス（１，２−ベンズイソチアゾリン−３−オン）化合物を含有する混合物にアルカリを添加して、１，２−ベンズイソチアゾリン−３−オン化合物のアルカリ塩を形成する工程；
前記アルカリ塩を含有する混合物を加熱処理する工程；および
前記加熱処理した混合物に酸を添加して１，２−ベンズイソチアゾリン−３−オン化合物を析出させる工程を含むことを特徴とする１，２−ベンズイソチアゾリン−３−オン化合物の製造方法に関する。

(In the formula, R ¹ represents the same atom or group as R ¹ in the general formula (1).) An N, N′-methylenebis (1,2-benzisothiazolin-3-one) compound represented by Adding an alkali to the mixture containing to form an alkali salt of a 1,2-benzisothiazolin-3-one compound;
A step of heat-treating the mixture containing the alkali salt; and a step of adding an acid to the heat-treated mixture to precipitate a 1,2-benzisothiazolin-3-one compound. -It relates to a method for producing a benzisothiazolin-3-one compound.

  That is, the present invention particularly relates to a method for producing a 1,2-benzisothiazolin-3-one compound, which has the general formula (3):

（式中、Ｒ^１は、水素原子、炭素数１〜４のアルキル基、炭素数１〜４のアルコキシ基、ニトロ基、カルボキシル基もしくはそのエステル、またはハロゲン原子を示し、Ｒ^２は、炭素数１〜４のアルキル基を示す。）で表される２−（アルキルチオ）ベンゾニトリル化合物とハロゲン化剤とを水の存在下に反応させて、一般式（１）：

(In the formula, R ¹ 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, and R ² represents the number of carbon atoms. 2- (alkylthio) benzonitrile compound represented by the formula (1-4) is reacted with a halogenating agent in the presence of water to give a general formula (1):

（式中、Ｒ^１は、前記一般式（３）におけるＲ^１と同じ原子または基を示す。）で表される１，２−ベンズイソチアゾリン−３−オン化合物を含有する反応液を得る反応工程；
１，２−ベンズイソチアゾリン−３−オン化合物を含有する反応液にアルカリを添加して、１，２−ベンズイソチアゾリン−３−オン化合物のアルカリ塩を形成する工程；
前記アルカリ塩を含有する反応液を加熱処理する工程；および
前記加熱処理した反応液に酸を添加して１，２−ベンズイソチアゾリン−３−オン化合物を析出させる工程を含むことを特徴とする１，２−ベンズイソチアゾリン−３−オン化合物の製造方法に関する。

(Wherein R ¹ represents the same atom or group as R ¹ in the general formula (3)), a reaction step for obtaining a reaction solution containing a 1,2-benzisothiazolin-3-one compound represented by ;
Adding an alkali to the reaction solution containing the 1,2-benzisothiazolin-3-one compound to form an alkali salt of the 1,2-benzisothiazolin-3-one compound;
A step of heat-treating the reaction solution containing the alkali salt; and a step of adding an acid to the heat-treated reaction solution to precipitate a 1,2-benzisothiazolin-3-one compound. , 2-Benzisothiazolin-3-one compound.

  According to the present invention, as a method for producing a 1,2-benzisothiazolin-3-one compound produced by the method described in Patent Document 1 and the like, a by-product N, N′-methylenebis (1,2-benz By adding an alkali to a 1,2-benzisothiazolin-3-one compound containing an isothiazoline-3-one) compound and then heat-treating it, and then performing precipitation by adding an acid, it is simple with very high purity. In addition, a process for producing a 1,2-benzisothiazolin-3-one compound economically can be provided.

  Furthermore, according to the present invention, an alkali is added to a N, N′-methylenebis (1,2-benzisothiazolin-3-one) compound that is difficult to remove by commonly used crystallization and the like, and heat-treated. By converting to the alkali salt of the benzisothiazolin-3-one compound, the 1,2-benzisothiazolin-3-one compound is substantially increased, so that the yield of the target compound can also be improved.

  The production method according to the present invention has the general formula (1):

で表される１，２−ベンズイソチアゾリン−３−オン化合物を得ることができる。

1,2-benzisothiazolin-3-one compound represented by the following formula can be obtained.

R ¹ in the 1,2-benzisothiazolin-3-one compound represented by the general formula (1) is 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 is shown.

  Examples of the alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. it can. Examples of the alkoxy group having 1 to 4 carbon atoms include methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group and tert-butoxy group. Can do. Examples of the carboxyl group ester include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, and a butoxycarbonyl group. As said halogen atom, a chlorine atom, a bromine atom, etc. can be mentioned, for example.

  Specific examples of the 1,2-benzisothiazolin-3-one compound represented by the general formula (1) include 1,2-benzisothiazolin-3-one, 7-methyl-1,2-benzisothiazoline- 3-one, 5-tert-butyl-1,2-benzisothiazolin-3-one, 6-methoxy-1,2-benzisothiazolin-3-one, 7-nitro-1,2-benzisothiazolin-3-one , 6-chloro-1,2-benzisothiazolin-3-one, 6-carboxy-1,2-benzisothiazolin-3-one, 6-methoxycarbonyl-1,2-benzisothiazolin-3-one, and the like Can do.

  The 1,2-benzisothiazolin-3-one compound according to the present invention has a general formula (2) as a by-product:

で表されるＮ，Ｎ’−メチレンビス（１，２−ベンズイソチアゾリン−３−オン）化合物を含む。

N, N′-methylenebis (1,2-benzisothiazolin-3-one) compound represented by the formula:

R ¹ in the N, N′-methylenebis (1,2-benzisothiazolin-3-one) compound represented by the general formula (2) represents the same atom or group as R ¹ in the general formula (1). .

  The 1,2-benzisothiazolin-3-one compound represented by the above general formula (1) and the N, N′-methylenebis (1,2-benzisothiazoline- represented by the above general formula (2) according to the present invention The mixture containing a 3-one) compound is, for example, the general formula (3):

（式中、Ｒ^１は、水素原子、炭素数１〜４のアルキル基、炭素数１〜４のアルコキシ基、ニトロ基、カルボキシル基もしくはそのエステル、またはハロゲン原子を示し、Ｒ^２は、炭素数１〜４のアルキル基を示す。）で表される２−（アルキルチオ）ベンゾニトリル化合物とハロゲン化剤とを水の存在下に反応させて得られる反応液に含まれる。

(In the formula, R ¹ 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, and R ² represents the number of carbon atoms. 1 to 4 alkyl groups) are included in a reaction solution obtained by reacting a 2- (alkylthio) benzonitrile compound represented by (2) with a halogenating agent in the presence of water.

R ¹ in the 2- (alkylthio) benzonitrile compound represented by the general formula (3) represents the same atom or group as R ¹ in the general formula (1), and is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms. Represents an alkoxy group having 1 to 4 carbon atoms, a nitro group, a carboxyl group or an ester thereof, or a halogen atom. Examples of the alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. it can. Examples of the alkoxy group having 1 to 4 carbon atoms include methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group and tert-butoxy group. Can do. Examples of the carboxyl group ester include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, and a butoxycarbonyl group. As said halogen atom, a chlorine atom, a bromine atom, etc. can be mentioned, for example. Among these, a hydrogen atom, a methyl group, an ethyl group, a tert-butyl group, a methoxy group, a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, a chlorine atom and a nitro group are preferable.

R ² in the 2- (alkylthio) benzonitrile compound represented by the general formula (3) represents an alkyl group having 1 to 4 carbon atoms. Examples of the alkyl group having 1 to 4 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. it can. Among these, a methyl group, an ethyl group, an n-propyl group, and a tert-butyl group are preferable.

  Specific examples of the 2- (alkylthio) benzonitrile compound represented by the general formula (3) include, for example, 2- (methylthio) benzonitrile, 2- (ethylthio) benzonitrile, 2- (n-propylthio) benzonitrile. 2- (tert-butylthio) benzonitrile, 3-methyl-2- (methylthio) benzonitrile, 5-tert-butyl-2- (methylthio) benzonitrile, 4-methoxy-2- (methylthio) benzonitrile, 3 -Nitro-2- (methylthio) benzonitrile, 3-nitro-2- (tert-butylthio) benzonitrile, 4-chloro-2- (methylthio) benzonitrile, 4-carboxy-2- (methylthio) benzonitrile, and Examples include 4-methoxycarbonyl-2- (methylthio) benzonitrile. Kill. Among these, 2- (methylthio) benzonitrile, 3-methyl-2- (methylthio) benzonitrile, 5-tert-butyl-2- (methylthio) are easily available and have excellent antibacterial properties. ) Benzonitrile, 4-methoxy-2- (methylthio) benzonitrile, 3-nitro-2- (tert-butylthio) benzonitrile, 4-chloro-2- (methylthio) benzonitrile and 4-methoxycarbonyl-2- ( Methylthio) benzonitrile is preferably used.

  The 2- (alkylthio) benzonitrile compound used for obtaining the 1,2-benzisothiazolin-3-one compound may be one produced by any method. For example, it is described in Patent Document 1. As general formula (4):

（式中、Ｒ^１は、一般式（３）におけるＲ^１と同じ原子または基を示し、Ｘは塩素または臭素原子を示す。）で表される２−ハロベンゾニトリル化合物と一般式（５）：

(Wherein, R ¹ represents the same atom or group as R ¹ in general formula (3), X represents a chlorine or bromine atom.) 2-halo benzonitrile compound represented by the general formula (5) :

（式中、Ｒ^２は、一般式（３）におけるＲ^２と同じ基を示す。）で表されるアルカンチオールとを、塩基の存在下、不均一系で反応させることにより製造することができる。

(Wherein R ² represents the same group as R ² in formula (3)), and can be produced by reacting in a heterogeneous system in the presence of a base. .

  Examples of the halogenating agent used in the method for producing a 1,2-benzisothiazolin-3-one compound according to the present invention include chlorine, bromine, sulfuryl chloride, and sulfuryl bromide. Among these, chlorine or sulfuryl chloride is preferably used from the economical viewpoint.

  The proportion of the halogenating agent used is preferably 0.8 to 3 mol, more preferably 1 to 2 mol, relative to 1 mol of the 2- (alkylthio) benzonitrile compound. When the use ratio of the halogenating agent is less than 0.8 mol, the amount of unreacted 2- (alkylthio) benzonitrile compound increases, and the yield may decrease. Moreover, when the usage-amount of a halogenating agent exceeds 3 mol, a side reaction tends to occur and there exists a possibility that a yield may fall.

  In the method for producing a 1,2-benzisothiazolin-3-one compound according to the present invention, a 2- (alkylthio) benzonitrile compound represented by the general formula (3) and a halogenating agent are reacted in the presence of water. At this time, the proportion of water used is preferably 0.8 to 5 mol, and more preferably 1 to 3 mol, relative to 1 mol of the 2- (alkylthio) benzonitrile compound. When the proportion of water used is less than 0.8 mol and exceeds 5 mol, side reactions may occur and the yield may be reduced.

In the method for producing the 1,2-benzisothiazolin-3-one compound according to the present invention, the 2- (alkylthio) benzonitrile compound represented by the general formula (3) and the halogenating agent are reacted in the presence of water. In this case, a mineral acid may be added to water and used as a mineral acid aqueous solution. By adding a mineral acid to water, the selectivity at the time of reaction improves and the production | generation of a by-product can be suppressed.
Examples of the mineral acid include hydrochloric acid, sulfuric acid, and nitric acid.
The concentration of the aqueous mineral acid solution is not particularly limited, but usually 10% by mass to saturated concentration in the case of hydrochloric acid and 10 to 50% by mass in the case of sulfuric acid or nitric acid is preferably used.
The use ratio of the mineral acid varies depending on the kind and concentration of the mineral acid to be used, but is 0.01 to 2 mol, preferably 0.1 to 1. mol per mol of the 2- (alkylthio) benzonitrile compound. 5 moles. However, it is preferable that the amount of water contained in the mineral acid is 5 mol or less with respect to 1 mol of the 2- (alkylthio) benzonitrile compound.

  When the 2- (alkylthio) benzonitrile compound and the halogenating agent are reacted in the presence of water, it is not always necessary to use a solvent, but a solvent can be used as necessary. By using a solvent, the reaction can often proceed smoothly. Examples of the solvent include, but are not limited to, hydrocarbons such as n-hexane, cyclohexane, and n-heptane; halogenated hydrocarbons such as dichloroethane, dichloromethane, and chloroform; aromatics such as benzene, toluene, xylene, and monochlorobenzene. Group hydrocarbons; N, N-dimethylformamide, dimethyl sulfoxide, and the like. Among these, toluene and monochlorobenzene are preferably used.

  When using a solvent, the amount of its use is 20-3000 mass parts normally with respect to 100 mass parts of 2- (alkylthio) benzonitrile compounds. When the usage-amount of a solvent is less than 20 mass parts, there exists a possibility that reaction may become difficult to advance smoothly. Moreover, when the usage-amount of a solvent exceeds 3000 mass parts, there exists a possibility that volumetric efficiency may deteriorate.

  The reaction temperature in the reaction is usually -20 to 170 ° C, preferably 0 to 150 ° C. When reaction temperature is less than -20 degreeC, reaction rate is slow and there exists a possibility that reaction may require a long time. Moreover, when reaction temperature exceeds 170 degreeC, there exists a possibility that a side reaction may occur easily. The reaction time varies depending on the reaction temperature and the like, but is usually 1 to 40 hours.

  An alkali is added to the mixture containing the 1,2-benzisothiazolin-3-one compound thus obtained to form an alkali salt of the 1,2-benzisothiazolin-3-one compound, and the alkali salt 1,2-benzisothiazolin-3-one compound is obtained by filtration after heat-treating the mixture and adding acid to cause precipitation (acid precipitation).

  In addition, in the manufacturing method concerning this invention, in order to advance each process smoothly, the mixture containing a 1, 2- benzisothiazolin-3-one compound can also be dissolved in a solvent etc. and it can also carry out as a solution. Moreover, in the case of a reaction liquid, each process can be performed as it is.

  Examples of the alkali used in the present invention include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, magnesium hydroxide, and calcium hydroxide. Examples thereof include alkaline earth metal hydroxides, metal alcoholates such as sodium methylate and sodium ethylate. Among these, an alkali metal hydroxide is preferable, and sodium hydroxide is more preferably used. Moreover, these alkalis may be used alone or in combination of two or more. The alkali may be mixed with water and used as an aqueous solution.

  The amount of the alkali used is preferably such that the pH of the mixture containing the 1,2-benzisothiazolin-3-one compound exceeds 7, more preferably 8 or more, and even more preferably 9 or more. Add amount. When the pH is 7 or less, the 1,2-benzisothiazolin-3-one compound does not become an alkali salt, and the N, N′-methylenebis (1,2-benzisothiazolin-3-one) compound during the heat treatment May not decompose into a 1,2-benzisothiazolin-3-one compound.

  For example, in the case of a reaction solution obtained by reacting a 2- (alkylthio) benzonitrile compound and a halogenating agent, the alkali is used at a preferable pH. ) 0.5 to 5 moles per mole of benzonitrile compound.

  Here, the basis of the proportion of alkali used is the amount of 2- (alkylthio) benzonitrile compound because all 2- (alkylthio) benzonitrile compounds are ideally 1,2-benzisothiazolin-3-one compounds This is because it is assumed to be converted to Thus, for a mixture containing 1,2-benzisothiazolin-3-one compound and N, N′-methylenebis (1,2-benzisothiazolin-3-one compound, 1,2-benzisothiazolin-3-one ON compound and N, N′-methylenebis (1,2-benzisothiazolin-3-one compound into two molecules of 1,2-benzisothiazolin-3-one compound, 1,2-benzisothiazoline-3 -The total amount of on-compound is used as a reference for the proportion of alkali used.

In the manufacturing method concerning this invention, the temperature of heat processing is 30-100 degreeC, Preferably it is 50-100 degreeC.
The heat treatment time is determined depending on the temperature of the heat treatment and by-products such as N, N′-methylenebis (1,2-benzisothiazolin-3-one) compound contained in the 1,2-benzisothiazolin-3-one compound. Although it varies depending on the amount, it is usually 0.5 to 24 hours.

  After the heat treatment, an acid is added for precipitation (acid precipitation), and then a 1,2-benzisothiazolin-3-one compound is obtained by filtration. Examples of the acid used for acid precipitation include mineral acids such as hydrochloric acid, sulfuric acid, and nitric acid, and organic acids such as formic acid, acetic acid, citric acid, oxalic acid, and methanesulfonic acid. Among these, mineral acids are preferable, and hydrochloric acid, sulfuric acid, and acetic acid are preferably used. These acids may be used alone or in combination of two or more.

  The acid is preferably used in such an amount that the pH of the mixture containing the 1,2-benzisothiazolin-3-one compound subjected to heat treatment with addition of alkali is 7 or less. If the pH is higher than 7, the alkali salt of 1,2-benzisothiazolin-3-one compound may not be converted to 1,2-benzisothiazolin-3-one compound.

  For example, in the case of a reaction solution obtained by reacting a 2- (alkylthio) benzonitrile compound with a halogenating agent, the ratio of the acid used when the pH is adjusted is preferably the 2- (alkylthio) used in the reaction step. ) It is preferable that it is 0.5-5 mol with respect to 1 mol of benzonitrile compounds, and it is more preferable that it is 0.8-3 mol. When the amount of the acid used is less than 0.5 mol, the alkali salt of the 1,2-benzisothiazolin-3-one compound may not be converted to the 1,2-benzisothiazolin-3-one compound. When it exceeds, there is no effect corresponding to the amount of use and it is not economical.

  Here, the amount of the 2- (alkylthio) benzonitrile compound is used as the basis for the ratio of the acid used. All of the 2- (alkylthio) benzonitrile compounds are ideally 1,2-benzisothiazolin-3-one compounds. This is because it is assumed to be converted to Thus, for a mixture containing 1,2-benzisothiazolin-3-one compound and N, N′-methylenebis (1,2-benzisothiazolin-3-one compound, 1,2-benzisothiazolin-3-one ON compound and N, N′-methylenebis (1,2-benzisothiazolin-3-one compound into two molecules of 1,2-benzisothiazolin-3-one compound, 1,2-benzisothiazoline-3 -The total amount of ON compound is used as a reference for the proportion of acid used.

  In the present invention, addition of an alkali and an acid produces a salt accompanying neutralization. Therefore, water is usually added to dissolve the salt. Although it does not specifically limit as a method to add water, Usually, water can be mixed with the alkali and / or acid to add.

  The amount of water used varies depending on the alkali and / or acid used and is not particularly limited. The amount used is, for example, a reaction solution obtained by reacting a 2- (alkylthio) benzonitrile compound with a halogenating agent. In the case of, it is usually 100 to 3000 parts by mass with respect to 100 parts by mass of the 2- (alkylthio) benzonitrile compound used in the reaction step. When the usage-amount of water is less than 100 mass parts, there exists a possibility that salt may not fully melt | dissolve. Moreover, when the usage-amount of water exceeds 3000 mass parts, there exists a possibility that volumetric efficiency may deteriorate.

  About the filtration temperature at the time of obtaining a 1, 2- benzisothiazolin-3-one compound by filtration after adding an acid and making it precipitate (acid precipitation), -20-40 degreeC normally, Preferably it is -10-30 degreeC More preferably, it is -10-25 degreeC. When the filtration temperature exceeds 40 ° C., the 1,2-benzisothiazolin-3-one compound may be lost to the filtrate and the yield may be reduced. When the filtration temperature is less than −20 ° C., an effect corresponding to the filtration temperature is not obtained, which is economically disadvantageous.

  The present invention will be described in more detail with reference to production examples and examples. However, the present invention is not limited to these examples and the like.

Production Example [Synthesis of 2- (methylthio) benzonitrile]
In a four-necked flask with an internal volume of 500 ml equipped with a stirrer, thermometer, dropping funnel and condenser, in a nitrogen atmosphere, 27.5 g (0.2 mol) of 2-chlorobenzonitrile, 30.0 g of monochlorobenzene, A 50 mass% tetra-n-butylammonium bromide aqueous solution 1.0 g was charged, and 51.4 g (0.22 mol) of a 30 mass% methanethiol aqueous sodium salt solution was stirred at 60 to 65 ° C. for 5 hours while stirring. After completion of the dropwise addition, the mixture was further reacted at the same temperature for 12 hours.
After completion of the reaction, the reaction solution was cooled to room temperature, the solvent was distilled off, and then distilled under reduced pressure to obtain 29.5 g of 2- (methylthio) benzonitrile (boiling point 139 to 140 ° C./931 Pa). The yield based on 2-chlorobenzonitrile was 99%.

Example 1
29.8 g (0.2 mol) of 2- (methylthio) benzonitrile obtained by the same method as in Production Example, monochlorobenzene, in a 500-ml four-necked flask equipped with a stirrer, thermometer and condenser 50.0 g and 6.6 g of 35 mass% hydrochloric acid (hydrochloric acid 0.06 mol, water 0.24 mol) were charged at 45 to 50 ° C. with stirring, and 15.6 g (0.22 mol) of chlorine was required for 2 hours. And then heated to 65-70 ° C. and reacted for 1 hour.

  After the reaction was completed, 82.0 g (0.41 mol) of a 20 mass% sodium hydroxide aqueous solution was added at the same temperature to adjust to pH 9, and the mixture was stirred at 100 ° C. for 2 hours. Thereafter, 22.0 g (0.21 mol) of 35 mass% hydrochloric acid was added to adjust the pH to 6, and the mixture was cooled to 0 ° C. The precipitated crystals were separated by filtration, washed with monochlorobenzene and dried to obtain 30.1 g (0.199 mol) of 1,2-benzisothiazol-3-one. The yield based on 2- (methylthio) benzonitrile was 99.5%.

  The purity of the obtained 1,2-benzisothiazol-3-one was 99.9% as measured by high performance liquid chromatography, and N, N′-methylenebis (1,2-benzisothiazolin-3-one ) Was not detected.

Example 2
29.8 g (0.2 mol) of 2- (methylthio) benzonitrile obtained by the same method as in Production Example, monochlorobenzene, in a 500-ml four-necked flask equipped with a stirrer, thermometer and condenser 50.0 g and 6.6 g of 35 mass% hydrochloric acid (hydrochloric acid 0.06 mol, water 0.24 mol) were charged at 45 to 50 ° C. with stirring, and 15.6 g (0.22 mol) of chlorine was required for 2 hours. And then heated to 65-70 ° C. and reacted for 1 hour.

  After completion of the reaction, 82.0 g (0.41 mol) of a 20 mass% sodium hydroxide aqueous solution was added at the same temperature to adjust to pH 9, and the mixture was stirred at 50 ° C. for 10 hours. Thereafter, 22.0 g (0.21 mol) of 35 mass% hydrochloric acid was added to adjust the pH to 6, and the mixture was cooled to 0 ° C. The precipitated crystals were separated by filtration, washed with monochlorobenzene and dried to obtain 30.1 g (0.199 mol) of 1,2-benzisothiazol-3-one. The yield based on 2- (methylthio) benzonitrile was 99.5%.

  The purity of the obtained 1,2-benzisothiazol-3-one was 99.9% as measured by high performance liquid chromatography, and N, N′-methylenebis (1,2-benzisothiazolin-3-one ) Was not detected.

Comparative Example 29.8 g (0.2 mol) of 2- (methylthio) benzonitrile obtained in the same manner as in Production Example, in a four-necked flask having an internal volume of 500 ml equipped with a stirrer, a thermometer and a condenser tube, Monochlorobenzene (50.0 g) and 35 mass% hydrochloric acid (6.6 g) (hydrochloric acid (0.06 mol), water (0.24 mol)) were charged and stirred at 45 to 50 ° C. with 15.6 g (0.22 mol) of chlorine. It took time to blow, and the mixture was further heated to 65 to 70 ° C. and reacted for 1 hour.

  After completion of the reaction, 41.0 g (0.21 mol) of a 20 mass% aqueous sodium hydroxide solution was added at the same temperature to adjust the pH to 6, and the mixture was cooled to 0 ° C. The precipitated crystals were separated by filtration, washed with monochlorobenzene, and dried to obtain 29.9 g (0.198 mol) of 1,2-benzisothiazol-3-one. The yield based on 2- (methylthio) benzonitrile was 99%.

  To 10 g of the obtained 1,2-benzisothiazol-3-one, 28 g of dipropylene glycol and 3.7 g of water were mixed. While the mixture was stirred, 8.7 g of a 30% by mass aqueous sodium hydroxide solution was added to obtain a white insoluble material. The obtained insoluble material was filtered off, washed with methanol and water, and dried to obtain white crystals. NMR measurement was performed on the obtained crystals. From the measurement result, the general formula (6):

で表されるＮ，Ｎ’−メチレンビス（１，２−ベンズイソチアゾリン−３−オン）であると同定された。

N, N′-methylenebis (1,2-benzisothiazolin-3-one) represented by

¹ H-NMR (400 MHz, (D ₃ C) ₂ S═O) δ (ppm): 5.88 (s, 2H), 7.46 (dd, J = 8 Hz, 2H), 7.70 (dd, J = 8 Hz, 2H), 7.93 (d, J = 8 Hz, 2H), 7.96 (d, J = 8 Hz, 2H).

  The purity of the obtained 1,2-benzisothiazol-3-one was 98.5% as measured by high performance liquid chromatography, and N, N′-methylenebis (1,2-benzisothiazoline-3- ON) was 1.5%.

Claims (6)

A method for producing a 1,2-benzisothiazolin-3-one compound comprising a compound represented by the general formula (1):

(Wherein R ¹ 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). , 2-Benzisothiazolin-3-one compounds and general formula (2):

(In the formula, R ¹ represents the same atom or group as R ¹ in the general formula (1).) An N, N′-methylenebis (1,2-benzisothiazolin-3-one) compound represented by Adding an alkali to the mixture containing to form an alkali salt of a 1,2-benzisothiazolin-3-one compound;
A step of heat-treating the mixture containing the alkali salt; and a step of adding an acid to the heat-treated mixture to precipitate a 1,2-benzisothiazolin-3-one compound. -Method for producing benzisothiazolin-3-one compound. A method for producing a 1,2-benzisothiazolin-3-one compound comprising a compound represented by the general formula (3):

(In the formula, R ¹ 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, and R ² represents the number of carbon atoms. 2- (alkylthio) benzonitrile compound represented by the formula (1-4) is reacted with a halogenating agent in the presence of water to give a general formula (1):

(Wherein R ¹ represents the same atom or group as R ¹ in the general formula (3)), a reaction step for obtaining a reaction solution containing a 1,2-benzisothiazolin-3-one compound represented by ;
Adding an alkali to the reaction solution containing the 1,2-benzisothiazolin-3-one compound to form an alkali salt of the 1,2-benzisothiazolin-3-one compound;
A step of heat-treating the reaction solution containing the alkali salt; and a step of adding an acid to the heat-treated reaction solution to precipitate a 1,2-benzisothiazolin-3-one compound. , 2-Benzisothiazolin-3-one compound production method.   The method for producing a 1,2-benzisothiazolin-3-one compound according to claim 1 or 2, wherein the alkali is an alkali metal hydroxide.   The method for producing a 1,2-benzisothiazolin-3-one compound according to claim 1 or 2, wherein an alkali is added so that the pH exceeds 7.   The method for producing a 1,2-benzisothiazolin-3-one compound according to claim 1 or 2, wherein the heat treatment step is performed at 30 to 100 ° C.   The production of 1,2-benzisothiazolin-3-one compound according to claim 1 or 2, wherein the acid is selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, formic acid, acetic acid, citric acid, oxalic acid and methanesulfonic acid. Method.