JPH06345723A - Production of mercaptobenzamide - Google Patents

Abstract

PURPOSE:To simply obtain mercaptobenzamide useful as an intermediate for medicines, agrichemicals, etc., in good yield without using a heavy metal by reacting an o- or a p-halogenobenzamide with a sulfide in a polar solvent. CONSTITUTION:An o- or a p-halogenobenzamide expressed by formula 1 (X is Cl or Br) reacts with a sulfide in a polar solvent (an alkylamide such as N-methyl-2-pyrrolidone is especially preferred) to afford o- or p- mercaptobenzmide expressed by formula 2. Since a reducing step is absent and a heavy metal is not used, the method for production is industrially advantageous without any problems in environmental pollution due to waste liquors thereof. The mercaptobenzamide is useful as a raw material for thiosalicylic acid which is a raw material for thioindigo coloring matters.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a process for producing mercaptobenzamide which is a compound useful as an intermediate for medicines, agricultural chemicals and the like. Mercaptobenzamide is also useful as a raw material for thiosalicylic acid, which is a raw material for thioindigo dyes.

[0002]

Conventionally, as a method for producing mercaptobenzamide, thiosalicylic acid is heated and reacted with ferric chloride and concentrated hydrochloric acid to form dithiosalicylic acid, which is then halogenated to obtain dithiosalicylic acid halogenide. A method of reacting with ammonia to form 2,2'-dithiobisbenzamide, which is reduced with zinc in mineral acid (JP-A-52-108983), and chlorobenzamide is converted into dimethyl sulfoxide (DM).
SO) and N, N-dimethylformamide (DMF) in a solvent to react with sodium hydrosulfide to give 2,2′-dithiobisbenzamide, which is reduced with zinc in a mineral acid (JP-A-51- No. 131847) is known.

[0003]

In all of the above-mentioned conventionally known production methods, since mercaptobenzamide is obtained by reduction after once producing disulfide, not only the steps are complicated, but also in the case of reduction, Since heavy metals such as zinc, which are harmful to the human body, are used, there are various drawbacks such as environmental pollution caused by the waste liquid, which is a serious problem, and it cannot be said that the method is industrially excellent. The present invention solves such a problem, and an object thereof is to provide a method for easily producing mercaptobenzamide without using a heavy metal.

[0004]

In view of the above-mentioned situation, the present inventors have earnestly studied to provide a method for producing mercaptobenzamide conveniently and industrially advantageously. As a result, they have found that the desired mercaptobenzamide can be obtained by thiolating a halogenobenzamide with a sulfide in a polar solvent, and completed the present invention. In the present invention, it was peculiar that the disulfide compound obtained as a side reaction product was produced in a small amount.

[0005]

[Chemical 2]

That is, the gist of the present invention is a process for producing ortho or paramercaptobenzamide, which comprises reacting ortho or parahalogenobenzamide represented by the general formula (1) with a sulfide in a polar solvent. .

[0007]

[Chemical 3] (However, X represents a chlorine atom or a bromine atom.)

The method for producing mercaptobenzamide according to the present invention is industrially advantageous because the steps are short and the desired product can be obtained in high yield. Furthermore, since the heavy metal used in the reduction reaction in the conventional method is not used at all, there is no problem of environmental pollution due to waste liquid. The present invention will be described in detail below.

The starting halogenobenzamide used in the present invention is ortho or para-halogenobenzamide, and specific examples thereof include o-chlorobenzamide, p-chlorobenzamide, o-bromobenzamide, p-bromobenzamide and the like. Is mentioned. The halogenobenzamide is a known method, for example, chlorination of halogenobenzoic acid with a chlorinating agent such as thionyl chloride,
It can be easily obtained by amidation with ammonia.

As the sulfide used as the thiolating agent in the present invention, alkali sulfide is usually used, and sodium sulfide, sodium hydrosulfide or a hydrate thereof is particularly preferably used. The amount used is in the range of 1.0 to 10 times by mole with respect to 1 mol of halogenobenzamide,
It is preferably in the range of 1 to 3 times by mole. Usage is 1.0
If the amount is less than twice the molar amount, the amount of unreacted halogenobenzamide increases and the yield decreases. On the other hand, if the amount exceeds 10 times the molar amount, the corresponding effect cannot be obtained.

The present invention is characterized in that the above-mentioned reaction of halogenobenzamide and sulfide is carried out in a polar solvent. The polar solvent used is an alkylamide, which is usually an alkylamide having a C _{1 to} C ₄ alkyl group, such as N-methyl-2-pyrrolidone (hereinafter, referred to as N-methyl-2-pyrrolidone).
Examples thereof include MP), dimethylformamide (hereinafter abbreviated as DMF), dimethylacetamide, and the like. Among them, good results are obtained by using NMP. The amount of solvent used is
Usually, 2 to 20 parts by weight, preferably 5 to 10 parts by weight, is used with respect to 1 part by weight of halogenobenzamide. If the amount of the solvent used is less than 2 parts by weight, dissolution of the sulfide will be insufficient and the yield will decrease, and if used in excess of 20 parts by weight, it will be disadvantageous in terms of volumetric efficiency.

The reaction temperature is usually in the range of 80 to 200 ° C, preferably 120 to 180 ° C. Reaction temperature is 8
If the temperature is lower than 0 ° C, the reaction rate becomes slow, and if the temperature exceeds 200 ° C, a side reaction occurs, so that the yield of the target substance decreases. The progress of the reaction can be confirmed by a decrease in the raw material and an increase in the product by an appropriate analytical means such as high performance liquid chromatography. The reaction time depends on the reaction conditions such as the reaction temperature and the molar ratio of the raw materials charged, but the reaction is usually completed in 1 to 15 hours. After completion of the reaction, the solvent is distilled off, water is added, and the product is acidified by acidifying the system with a mineral acid such as hydrochloric acid, and the product is filtered to obtain the desired product, mercaptobenzamide. be able to.

[0013]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

EXAMPLE 1 15.6 g (0.10 g) of o-chlorobenzamide was placed in a 200 ml three-necked flask equipped with a stirrer, a thermometer and a condenser.
mol), 60% sodium sulfide 16.0 g (0.12 mo)
1) and 100 g of NMP were charged, and the mixture was stirred at 160 ° C. for 4 hours. After the reaction, NMP was distilled off under reduced pressure, and then water 100 was added.
The mixture was diluted with g and concentrated hydrochloric acid was added to acidify the system. The precipitated crystals were collected by filtration and dried to obtain 13.0 g of o-mercaptobenzamide. The yield based on the raw material o-chlorobenzamide was 85%.

Example 2 The reaction was carried out in the same manner as in Example 1 except that 20.0 g (0.10 mol) of o-bromobenzamide was used instead of o-chlorobenzamide. The yield of o-mercaptobenzamide was 13.7 g, and the yield based on o-bromobenzamide was 90%.

Example 3 20.0 g (0.10 mol) of o-bromobenzamide was used instead of o-chlorobenzamide, and 9.6 g of 70% sodium hydrosulfide was used instead of 60% sodium sulfide.
The reaction was performed in the same manner as in Example 1 except that 1) was used. The yield of o-mercaptobenzamide was 12.3 g.
And the yield based on o-bromobenzamide is 81%.
Met.

Example 4 The reaction was carried out in the same manner as in Example 1 except that 15.5 g (0.10 mol) of p-chlorobenzamide was used instead of o-chlorobenzamide. The yield of p-mercaptobenzamide was 11.4 g, and the yield based on p-chlorobenzamide was 75%.

Example 5 A reaction was carried out in the same manner as in Example 1 except that 100 g of DMF was used instead of NMP as the solvent and the reaction conditions were 130 ° C. and 7 hours. The yield of o-mercaptobenzamide was 10.5 g, and the yield based on o-chlorobenzamide was 69%.

[0019]

INDUSTRIAL APPLICABILITY According to the present invention, the desired ortho or paramercaptobenzamide can be produced in good yield by a simple method of reacting ortho or parahalogenobenzamide with a sulfide in a polar solvent. Unlike the conventionally known method, there is no reduction step and no heavy metal is used. Therefore, mercaptobenzamide can be industrially produced without any problem of environmental pollution due to the waste liquid.

Claims (3)

[Claims] 1. A method for producing ortho or paramercaptobenzamide, which comprises reacting ortho or parahalogenobenzamide represented by the general formula (1) with a sulfide in a polar solvent. [Chemical 1] (However, X represents a chlorine atom or a bromine atom.) 2. The method according to claim 1, wherein the polar solvent is an alkylamide. 3. The method according to claim 2, wherein the alkylamide is N-methyl-2-pyrrolidone.