Patent GB-1170561-A (GB)
Title: 5-Nitrothiazole Derivatives and their production
Inventor: DAEBRITZ ERICH
IPC: C07D295/16
Filed: 1968-01-24
Abstract: 1,170,561. 5-Nitrothiazoles. FARBENFABRIKEN BAYER A.G. 24 Jan., 1968 [24 Jan., 1967], No. 3692/68. Heading C2C. Novel compounds I wherein X signifies -O- or -SO 2 - and each of the substituents R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP> and R<SP>4</SP>, which may be the same or different, is a hydrogen atom, or a substituted or unsubstituted, saturated or unsaturated aliphatic (includes cycloaliphatic), aralkyl or aryl group, or R<SP>1</SP> together with R<SP>2</SP> and R<SP>3</SP> together with R<SP>4</SP> are constituents of a carbocyclic 6-membered ring, are prepared by reacting a compound II either with (a) a 2-substituted-5-nitrothiazole (the 2-substituent being halogen or the group -SO 2 .CH 3 ); or (b) in succession with cyanogen chloride, hydrogen sulphide in the presence of ammonia, monochloro-acetaldehyde semihydrate and finally with a nitrating agent. 3 - Methyl (also separated as the laevorotatory form using tartaric acid), -ethyl-, -(2- methoxy - ethoxy) - methyl - and - n - butoxymethyltetrahydro - 1,4 - thiazine - dioxides - (1,1) are obtained by reacting 3-methyl- or -ethyl- 1,4 - thioxan - dioxide (1,1) with ammonia and 2 - hydroxyethyl - 21 - hydroxy - 3<SP>1</SP> - butoxy -, or - (2 - methoxyethoxy), - propyl sulphone with ammonia respectively. 3 - Methyl - and - ethyl - 4 - {thiazolyl - (2)}- tetrdhydro - 1,4 - thiazine - dioxide - (1,1) are prepared, via the hydrochlorides, by reacting 3- methyl - or - ethyl - tetrahydro - 1,4 - thiazine- 1,1 - dioxide - 4 - thiocarboxamide (obtained by reacting the corresponding 4-cyano compound with hydrogen sulphide in the presence of ammonia) with chloro-acetaldehyde semihydrate; 4 - {thiazolyl - (2)} - tetrahydro - 1,4- thiazine - dioxide - (1,1) is similarly obtained, via the hydrochloride from tetrahydro - 1,4- thiazine - 1,1 - dioxide - 4 - thiocarboxamide. 3 - Methyl - and - ethyl - 4 - cyano - tetrahydro - 1,4 - thiazine - dioxide - (1,1) are prepared by the interaction of 2-methyl- or -ethyl-tetrahydro - 1,4 - thiazine - dioxide - (1,1) and cyanogen chloride; 4 - cyano - tetrahydro - 1,4- thiazine-dioxide- (1,1) is similarly prepared. 2 - Methylsulphonyl - 5 - nitrothiazole is obtained by the interaction of 2-bromo-5-nitrothiazole and sodium methylsulphinate. 4 - {Thiazolyl - (2)} - morpholine, which is also described as the hydrochloride dihydrate, is prepared by the interaction of morpholinothiocarboxamide and chloro-acetaldehyde semihydrate. 2 - Hydroxyethyl - 2<SP>1</SP> - hydroxypropyl -, 2<SP>1</SP> - hydroxybutyl -, - 2<SP>1 </SP>- hydroxy - 3<SP>1</SP> - butoxy - propyl - and - 21 - hydroxy - 3<SP>1</SP> - (2 - methoxy - ethoxy) - propyl - sulphide are obtained by the reaction of mercapto-ethanol with propylene oxide, 1,2-epoxybutane, glycide-butyl ether and 1,2 - epoxy - 3 - (2<SP>1</SP> - methoxy - ethoxy) - propane respectively; the sulphones corresponding to the foregoing sulphides are obtained utilizing hydrogen peroxide oxidation. 3-Methyl- and - ethyl - 1, 4- thioxan - dioxide - (1,1) are obtained by cyclizing, in the presence of alkali, the appropriate sulphone. Pharmaceutical preparations capable of destroying the organisms causing Entamoeba histolytica, Trichomonas vaginalis and lambliae contain as active ingredient compounds I; administration may be orally or parenterally.