JPH0140833B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an industrially advantageous process for producing 2-amino-benzothiazoles, which are valuable intermediates for the production of dyes, pigments and pharmaceuticals. For more details, please refer to the formula By adding bromine or iodine as a catalyst in sulfuric acid and heating and ring-closing the phenylthioureas represented by the formula, The present invention relates to a method for producing 2-amino-benzothiazoles represented by: (In formulas (1) and (2), benzene nucleus A is an alkyl group having 1 to 4 carbon atoms, a halogen atom, a nitro group, an alkylsulfonyl group having 1 to 4 carbon atoms, or an alkyl group having 1 to 4 carbon atoms.
4 alkoxy groups, carboxyl groups, and carbalkoxy groups having 1 to 4 carbon atoms (can have 1 to 2 atoms or substituents of the same or different type) Conventionally, the method for producing benzothiazoles is as follows. There is a method like this. For example, in JP-A No. 53-9767, benzothiazoles are prepared by thermally ring-closing the compound of formula (2) using chlorine in the presence of a catalytic amount of bromine or iodine in an aprotic organic solvent. A method of manufacturing is described. Furthermore, JP-A-54-109970 describes a method for producing benzothiazoles of the formula (1) by thermally ring-closing the compound of the formula (2) in thionyl chloride. However, all of these known production methods have various drawbacks, such as the use of expensive solvents, the generation of harmful gases, and the need to dispose of waste liquids. The present inventor investigated an industrially advantageous method for producing 2-aminobenzothiazoles that does not have such drawbacks, and found that the solvent is not an organic solvent as described in the above document, but is much cheaper than these. and using sulfuric acid, which is a different inorganic acid,
It has been found that it can be obtained industrially advantageously with high yield and high purity. The present invention will be explained in more detail. The phenylthioureas of formula (2), which are the raw materials used in the present invention, can be easily obtained by reacting the corresponding mineral acid salts of anilines with rhodan salts such as rhodan potash, rhodan soda, or rhodan ammonium. Specific examples of the substituents of the benzene nucleus A of the phenylthioureas represented by formula (2) include the following. Alkyl groups having 1 to 4 carbon atoms such as methyl group, ethyl group, propyl group and butyl group, halogen atoms such as bromine atom, chlorine atom and iodine atom, nitro group, methylsulfonyl group, ethylsulfonyl group, butylsulfonyl group Alkylsulfonyl groups having 1 to 4 carbon atoms such as groups, methoxy groups, ethoxy groups, and 1 carbon atoms such as butoxy groups
A carbalkoxy group having 1 to 4 carbon atoms, such as a carboxyl group, a methoxycarbonyl group, an ethoxycarbonyl group, and a butoxycarbonyl group. Specifically, the following compounds are mentioned as examples of starting materials of the present invention. Phenylthiourea, 2-methylphenylthiourea, 4-methylphenylthiourea, 2-chlorophenylthiourea,
3,4-dichlorophenylthiourea, 4-bromphenylthiourea, 2,4-dibromphenylthiourea, 4-nitrophenylthiourea, 2-nitrophenylthiourea, 2,4-dinitro Phenylthiourea, 2-chloro-4-nitrophenylthiourea, 4-methylsulfonylphenylthiourea,
4-ethylsulfonylphenylthiourea, 2-methoxyphenylthiourea, 4-ethoxyphenylthiourea, 4-carboxyphenylthiourea, 4
-methoxycarbonylphenylthiourea, 4-ethoxycarbonylphenylthiourea, etc. According to the present invention, by heating such phenylthioureas in sulfuric acid with the addition of bromine or iodine, the ring-closing reaction proceeds in a very short time and 2-aminobenzothiazoles can be obtained. The sulfuric acid concentration should be selected so that sulfonation does not occur, and approximately 85-100% is particularly advantageous.
It is preferable to use 90-100% strength sulfuric acid. In the case of phenylthioureas having a substituent that makes sulfonation difficult, such as a nitro group, the concentration may be higher than in the case of phenylthioureas having a substituent that promotes sulfonation, such as an alkyl group or an alkoxy group. The temperature used in carrying out the present invention is 20 to 120°C, depending on the concentration of sulfuric acid, and 60 to 90°C.
A temperature of °C is preferred. The reaction time varies depending on the concentration of sulfuric acid, reaction temperature, and amount of bromine or iodine, and generally 30 minutes to 5 hours is sufficient. A catalytic amount of bromine or iodine is sufficient, but it is desirable to add bromine or iodine in an amount of 1/20 to 1/10 times the molar amount of the phenylthiourea as the raw material. The amount of sulfuric acid used should preferably be adjusted so that the raw materials dissolve, but also applies in suspensions. Usually, sulfuric acid is used in an amount 3 to 10 times the weight of the phenylthiourea. The progress of the reaction is followed by instrumental analysis such as gas chromatography. When all of the phenylthiourea starting material has disappeared, the sulfuric acid solution is cooled, poured onto ice water, and neutralized using a base such as sodium hydroxide, potassium hydroxide, soda ash or ammonia. In this case, 2-amino-benzothiazoles are obtained in high yield. This material can be isolated by separation. The 2-aminobenzothiazoles obtained by this method have sufficient purity to be used as industrial raw materials, but if necessary, they can be purified with a mineral acid such as hydrochloric acid or sulfuric acid. The present invention will be explained below with reference to Examples. Example 1 22.1 g of 3,4-dichlorophenylthiourea was added and dissolved in 60.0 g of 96% sulfuric acid at room temperature while stirring. The temperature was raised to 80°C, and 1.6g of bromine was added dropwise over 30 minutes while maintaining the temperature at 80±3°C. After the dropwise addition was completed, the reaction was carried out at the same temperature for 3 hours. After confirming that the raw materials have disappeared by gas chromatography,
The reaction solution cooled to room temperature was diluted with sodium sulfite 1.0
The mixture was gradually poured into 340 ml of water containing g. After stirring for 1 hour, the temperature was raised to 90℃, and the temperature was increased to 90-95℃ for 1 hour.
Stir for hours. After confirming that the reaction solution was sufficiently dissolved, it was filtered while maintaining the temperature at around 90°C.
The filtrate thus obtained was adjusted to pH 9-10 with an aqueous caustic soda solution at 20°C or lower. The precipitated product was collected separately, thoroughly washed with hot water, and then dried. The obtained compound was confirmed to have the structure (1) through instrumental analysis such as gas chromatography and mass spectrometry.

【formula】

[Formula] (Isomer mixture of 2-amino-dichlorobenzothiazole shown in the above structure, (1)-a:(1)-b
= 54:46) The amount obtained was 20.2 g (yield 92.3%), and the purity as determined by gas chromatography was 99.2%.
Moreover, the melting point was 182-202°C. Example 2 19.7 g of 4 in 60.0 g of 96% sulfuric acid at room temperature under stirring
- Nitrophenylthiourea was added and dissolved.
1.6 while increasing the temperature to 90℃ and maintaining it at 90±3℃.
g of bromine was added dropwise over 30 minutes. After the dropwise addition was completed, the reaction was continued at the same temperature for 5 hours. After confirming that the raw materials had disappeared by gas chromatography, the reaction solution was cooled to room temperature and mixed with water containing 1.0 g of sodium sulfite.
It was gradually poured into 300ml. After stirring for 1 hour, the temperature was raised to 90°C, and the mixture was stirred at 90 to 95°C for 1 hour. After confirming that the reaction solution is sufficiently dissolved
It was filtered while maintaining the temperature at around 90°C. The filtrate thus obtained was adjusted to pH 10-11 with an aqueous caustic soda solution at 20°C or lower. Separate the precipitated product,
It was collected, thoroughly washed with hot water, and then dried. The obtained compound was confirmed to have the structure (2) through instrumental analysis such as gas chromatography and mass spectrometry. The amount obtained was 17.7 g (yield 91.0%), and the purity as determined by gas chromatography was 98.4%.
Moreover, the melting point was 236-239°C. Example 3 18.2 g of 4 in 50.0 g of 96% sulfuric acid at room temperature under stirring
-Methoxyphenylthiourea was added and dissolved. Raise the temperature to 70℃ and maintain it at 70±3℃
1.0 g of bromine was added dropwise over 30 minutes. After the dropwise addition was completed, the reaction was carried out at the same temperature for 3 hours. After confirming by gas chromatography that the raw materials had disappeared, the reaction solution was cooled to room temperature and gradually poured into 300 ml of water containing 1.0 g of sodium sulfite. After continued stirring for 1 hour, the solution was filtered at below 10°C. The filtrate thus obtained was adjusted to pH 8-9 with an aqueous caustic soda solution at 10°C or lower. The precipitated product was collected separately, thoroughly washed with water, and then dried. The obtained compound was confirmed to have the structure (3) through instrumental analysis such as gas chromatography and mass spectrometry. The amount obtained was 16.7 g (yield 92.8%), and the purity as determined by gas chromatography was 97.8%.
The melting point was 159-160°C. Example 4 15.2 g of phenylthiourea was added and dissolved in 50.0 g of 96% sulfuric acid at room temperature while stirring. Raise the temperature to 60℃ and add 1.0g of bromine to 30℃ while maintaining the temperature at 60±3℃.
It was dripped over several minutes. After the dropwise addition was completed, the reaction was carried out at the same temperature for 3 hours. After confirming by gas chromatography that the raw materials had disappeared, the reaction solution cooled to room temperature was gradually poured into 340 ml of water. After continued stirring for 1 hour, the mixture was filtered. The filtrate thus obtained was adjusted to pH 7-8 with an aqueous caustic soda solution at 10°C or lower. Continued to be 10℃
After stirring for 1 hour, the precipitated product was collected separately, thoroughly washed with water, and then dried. The obtained compound was confirmed to have the structure (4) through instrumental analysis such as gas chromatography and mass spectrometry. The amount obtained was 13.4 g (yield 89.3%), and the purity as determined by gas chromatography was 98.6%. Moreover, the melting point was 126-127°C. Example 5 22.1 g of 3,4-dichlorophenylthiourea was added and dissolved in 60.0 g of 96% sulfuric acid at room temperature while stirring. The temperature was raised to 80°C, and 2.0g of iodine was added while maintaining the temperature at 80±3°C. Thereafter, the mixture was reacted at the same temperature for 4 hours. After confirming that the raw materials had disappeared by gas chromatography, the reaction solution was cooled to room temperature and gradually poured into 340 ml of water. After stirring for 1 hour, the temperature was raised to 90°C, and the mixture was stirred at 90 to 95°C for 1 hour. After confirming that the reaction solution was sufficiently dissolved, it was filtered while maintaining the temperature at around 90°C. The filtrate thus obtained was adjusted to pH 10-11 with an aqueous caustic soda solution at 20°C or lower. The precipitated product was collected separately, thoroughly washed with hot water, and then dried. The obtained compound was confirmed to have the structure of formula (5) through instrumental analysis such as gas chromatography and mass spectrometry.

【formula】

[Formula] (Isomer compound of 2-amino-dichlorobenzothiazole shown in the above structure, (1)-a:(1)-b
= 54:46) The amount obtained was 20.0 g (yield 91.3%), and the purity as determined by gas chromatography was 98.8%. Moreover, the melting point was 181-202°C. Example 6 18.6 g of 2-chlorophenylthiourea was added and dissolved in 60.0 g of 98% sulfuric acid at room temperature while stirring. Raise the temperature to 80℃ and maintain it at 80±3℃
1.6 g of bromine was added dropwise over 30 minutes. After finishing dropping,
The reaction was carried out at the same temperature for 3 hours. After confirming that the raw materials had disappeared by gas chromatography, the reaction solution cooled to room temperature was gradually poured into 340 ml of water containing 1.0 g of sodium sulfite. After stirring for 1 hour, the temperature was raised to 90°C, and the mixture was stirred at 90 to 95°C for 1 hour. After confirming that the reaction solution was sufficiently dissolved, it was filtered while maintaining the temperature at around 90°C. The filtrate thus obtained was adjusted to pH 9-10 with an aqueous caustic soda solution at 20°C or lower. The precipitated product was collected separately, thoroughly washed with hot water, and then dried. The obtained compound was confirmed to have the structure (6) through instrumental analysis such as gas chromatography and mass spectrometry. The amount obtained was 16.6 g (yield 90.2%), and the purity as determined by gas chromatography was 99.5%.
Moreover, the melting point was 198-202°C. As shown in Table 1 below, instead of 2-chlorophenylthiourea, a similar reaction was attempted using various phenylthioureas of formula (7), and the corresponding 2-chlorophenylthiourea of formula (8) was used. Amino-benzothiazoles were obtained in good yield and their structures were confirmed.

【table】

Claims (1)

[Claims] 1 formula In producing 2-amino-benzothiazoles represented by the formula A method for producing 2-amino-benzothiazoles, which comprises heating and ring-closing phenylthioureas represented by the formula in sulfuric acid with the addition of bromine or iodine as a catalyst. (In formulas (1) and (2), benzene ring A is an alkyl group having 1 to 4 carbon atoms, a halogen atom, a nitro group, an alkylsulfonyl group having 1 to 4 carbon atoms, or an alkyl group having 1 to 4 carbon atoms.
(can have 1 to 2 atoms or substituents of the same or different type selected from 4 alkoxy groups, carboxyl groups, and carbalkoxy groups having 1 to 4 carbon atoms)