DE1042591B - Process for the preparation of 2-amino-1,3,4-thiadiazoles substituted in the 5-position - Google Patents

Description

A process for preparing a 5-substituted 2-amino - 1,3,4 - thiadiazoles The invention relates to methods for the preparation of new 5-substituted 2-Arnino-1,3,4-thiadiazol # s of the general formula in which R = 2-thienyl, o-chlorophenyl or o-tolyl.

These compounds have a central paralyzing effect and are particularly effective as ataractics for anxiety and excitement states as well as for nervous tension. This is a primary effect, since neither the muscle tension, nor the polysnaptic medullary reflexes, nor the neuro-vegetative system are influenced. The compounds can be administered in daily doses of 200 to 1000 and, if appropriate, in even higher doses. In some cases, e.g. B. 25 m tablets three to nine times a day and in other cases 10 mg tablets three to six times a day. Considerable successes against anxiety, insomnia and restlessness have always been achieved.

The basic substances obtainable according to the invention can be used as those or in the form of their salts with inorganic acids, such as hydrochloric or sulfuric acid be used. In this case, of course, the doses must be set in such a way that that the desired amount of free base is always administered.

If z. B. 2-Amino-5- (2-thienyl) -1,3,4-th-iadiazole hydrochloride instead of the free base is used, the doses must be increased by around 20 11 / o-.

The compounds according to the invention can be prepared by two different methods. According to the first process, carboxylic acid chlorides of the formula R-COCI in which R = 2-thienyl, o-chlorophenyl or o-tolyl are treated with thiosernicarbazide in a solvent, e.g. B. acetic acid or pyridine, and the resulting NI-acylthiosemicarbazide of the formula R-CONHNHCSNH, treated for a few minutes with around 2 parts by volume of concentrated sulfuric acid. The mixture is then poured into water and any insoluble material is filtered off. The end products are then precipitated up to pH 8 by adding ammonia. In the second process, a thiosemicarbazone of the formula RC H = t: = N-NH-C S -NH2, in which R has the above meaning, is suspended in water and heated to 80 ° C. with iron III chloride. The resulting solution is then concentrated to dryness and the thiadiazole formed is recrystallized from hydrochloric acid to form the hydrochloride. The free thiadiazoles can be obtained from the hydrochloride by adding an alkali.

They can be converted into other salts with inorganic acids, by treating them with an equivalent amount of the desired acid, e.g. B. sulfur, Nitric, phosphoric, hydrochloric acid, iodic or hydrobromic acid, added.

Example 1 A mixture of 18.2 g of thiosemicarbazide and 150 cc of pyridine is cooled to 0 'C. Then 31 g of o-methylbenzoyl chloride are gradually added with constant stirring. The mixture obtained is stirred for a further 2 hours, then poured into 350 cc of cold water, a rich precipitate separating out, which is filtered off with suction and dried. Yield: 37 o - methylbenzoyltbiosernicarbazide (88 111c, of theory). 100 cc of sulfuric acid are added dropwise with stirring to 20.9 g of this product. The reaction is exothermic. After everything has gone into solution, the mixture is cooled and gradually diluted with 2000 cc of water while stirring. The solution is then filtered, adjusted to pH 8 with concentrated ammonia and cooled. The precipitate is filtered off and recrystallized from ethyl alcohol. Yield: 16g (8411N) 2-amino-5- (o-tolyl) -1,3-, 4-thiadiazole. Melting point 128 to 129 ° C.

Example 2 197-2 -Thenaldehydthiosemicarl) azon are heated with 121 water and 540 iron III chloride for 30 minutes to 80.degree . A small crystalline fraction is filtered off with suction, the filtered solution is decolorized with sodium hydroxide, concentrated in vacuo until the crystals begin to separate and cooled in an ice bath. The crystals are filtered off with suction and recrystallized from 10% hydrochloric acid. Yield: 132 g (56 oe, theory) of 2-amino-5- (2-thienyl) -1,3,4-thiadiazole hydrochloride; melting point 241 to 43 ° C . example 3 a mixture of 25 g o-Chlorbenzaldehydthiosemicarbazon, 1250ccm water and 60g EisenIII chloride is heated 45 minutes at 80 'C, a small amount of undissolved crystals is filtered off with suction, decolorized the solution with sodium hydrosulfite and concentrated in vacuo, until the onset of crystal deposition concentrated. The mixture is cooled in an ice bath, the product is filtered off with suction and recrystallized from 10 11/9 hydrochloric acid. Yield: 15.5 - (53 11 / c- of theory) 2-amino-5- (o-chlorophenyl) -1.3, 4-thiadiazole-hydochloride, melting point 184 to 1860 C. Example 4 A mixture of 193 g of o-tolualdehyde thiosemicarbazone, 15 l of water and 500 g of ferric chloride is heated for around 30 minutes to 80 ° C. A small portion of undissolved crystals is filtered off with suction , the solution with sodium hydrosulfite decolorized and in the vacuum concentrated to the beginning of crystal deposition. After cooling in an ice bath, the product is filtered off with suction and recrystallized from 10 1 / o hydrochloric acid. Yield: 125 g (55 % of theory) of 2-amino-5- (o-tolyl) -1,3,4-thiadiazole; Melting point 128 to 30 ° C.

Claims (1)

PATENT CLAIM: Process for the preparation of 2-amino-1,3,4-thiadiazoles of the general formula which are substituted in the 5-position in which R is a 2-thienyl, o-chlorophenyl or o-tolyl radical, and salts thereof with mineral acids, characterized in that a.) a carboxylic acid chloride of the formula RC 0 CI, in which R has the above meaning , treated with thiosemicarbazide and dehydrated the resulting acylthiosemicarbazide of the formula R-CONH-NHCSNH2 with concentrated sulfuric acid, or b) a thiosemicarbazone of the formula R-CH = N-NH-CS-NH2 in whichever R has the above meaning, in aqueous The suspension with ferric chloride in water is heated to 80 ° C., the solution is concentrated to dryness and the residue is recrystallized from dilute hydrochloric acid, and the salts obtained are optionally converted into the free bases with alkalis. Documents considered: German Patent No. 827 948; Patent writing No. 6789 of the Office for Invention and Patents in the Soviet zone of occupation in Germany. When the registration was announced, three pages of the test report were laid out.