CS264496B1 - Process for the pH adjustment of 2-chlorobenzthioamide - Google Patents

Abstract

2-Chlorobenzthioamide is prepared by thioamidation of 2-chlorobenzonitrile, which reacts with an aqueous solution of ammonium sulfide. The reaction is carried out in a medium of dimethylformamide and ethanol at a temperature range of 20 to 40 °C. An aqueous solution of ammonia is used to complete the reaction of the starting material. The product is then isolated by filtration from the aqueous medium.

Description

(57) 2-Chlorobenzthioamide is prepared by thioamidation of 2-chlorobenzonitrile, which is reacted with an aqueous solution of ammonium sulfide. The reaction is carried out in a medium of dimethylformamide and ethanol at a temperature range of 20 to 40 ° C. An aqueous ammonia solution was used to react the starting material. Further, the product is isolated by filtration from an aqueous medium.

The invention relates to a process for the preparation of 2-chlorobenzthioamide from o-chlorobenzonitrile. The procedure for the preparation of this compound having tuberculostatic effects (see CA 102, 112 577, 1985) is not disclosed in commonly available literature such as in Beilsteins Handbuch, CA and the like, although in Beilsteins Handbuch II, 9, 292, reported preparation of 4-chlorobenzthioamide from p-chlorobenzonitrile by reaction with hydrogen sulfide in a medium of sodium ethylate, at a temperature of 60.6 ° C and at a pressure of 0.177 MPa.

It has now been found that the 2-chlorobenzthioamide formula

are prepared very advantageously according to the invention.

•

The process for the preparation of 2-chlorobenzthioaraid consists in carrying out the thioamidation of o-chlorobenzonitrile in dimethylformamide and ethanol with an aqueous solution of ammonium sulfide at a temperature of 20 to 40 [deg.] C.

The actual synthesis of 2-chlorobenzthioamide is carried out by dissolving o-chlorobenzonitrile with stirring at room temperature in the present dimethylformamide and ethanol, then adding a portion of the aqueous ammonia solution and first adding a portion of the aqueous ammonium sulfide solution and reacting for 2.5 h. Stir at 25-30 ° C. The remaining amount of aqueous ammonia and ammonium sulfide solution was then charged and the reaction mixture was stirred at 30-35 ° C for 2 h. The progress of the reaction was monitored by thin-layer chromatography in benzene-acetone (6: 1) and the conversion of o-chlorobenzonitrile to the desired thioamide was adjusted as necessary by addition of ammonium sulfide solution. After completion of the reaction, the reaction mixture was poured into ice water. The resulting white precipitate was stirred and then filtered. The product was washed with water and dried at room temperature in a vacuum oven. The solvents are regenerated by rectification under normal pressure or under vacuum.

Compared to the available thioamidation methods which have been applied to p-chlorobenzonitrile, the novel process is characterized in a simple manner, without special equipment requirements, operating under pressure at normal or slightly elevated temperature, and using a more technologically advantageous aqueous ammonium sulfide solution.

The disadvantage of the process is higher demands on the rectification of solvents. The process is particularly suitable where post-treatment of the 2-chlorobenzthioamide thus produced, for example to o-chlorophenyliminohydrazine and the like, respectively, is envisaged. in cases where any moisture in the product does not matter.

The preparation of 2-chlorobenzthioamide can be carried out in conventional batch reactors equipped with a duplicator. Filtration and washing of the product on the flint does not cause problems.

The following example illustrates an embodiment of the invention.

Example

80 ml of dimethylformamide, 120 ml of ethanol, 60 g of o-chlorobenzonitrile and 35 ml of 26% aqueous ammonia and 200 ml of aqueous ammonium sulfide (containing 458 g / l) are introduced successively into the reactor and the mixture is stirred at 25 DEG C. for 2.5 h. to 30 ° C.

100 ml of the same ammonium sulphide and 20 ml of 26% aqueous ammonia are then introduced and the reaction is completed within 2 hours at 30-35 [deg.] C. with stirring.

After checking by thin-layer chromatography, the reaction mixture is poured into 1500 ml of ice-water and the white to yellowish suspension of 2-chlorobenzthioamide is filtered off under suction. The filter cake is washed twice with 400 ml of cold water, i.e. a total of 800 ml of water, and then at least 30 mingts are sieved or purged with air to remove water from the cake. The product is dried in a rotary vacuum dryer at room temperature as required. This gave 60 g of 2-chlorobenzthioamide of m.p. 29-35 [deg.] C, which contained only traces of o-chlorobenzonitrile by NMR.

Claims (1)

OBJECT OF THE INVENTION A process for the preparation of 2-chlorobenzthioamide characterized in that the thioamidation of o-chlorobenzonitrile is carried out in a medium of dimethylformamide and ethanol with an aqueous solution of ammonium sulfide at a temperature of 20 to 40 ° C and by addition of aqueous ammonia solution. aqueous environment.