Patent GB-1152486-A (GB)
Title: Benzoxazine and Benzothiazine Compounds and process for preparing them
IPC: C07D219/14
Filed: 1966-06-03
Abstract: 1,152,486. Benzoxazine and benzothiazine compounds. FARBWERKE HOECHST A.G. 3 June, 1966 [3 June, 1965; 18 March, 1966; 22 March, 1966; 23 March, 1966 (2)], No. 24865/66. Heading C2C. Novel compounds of the formula (wherein A is O or S; R is H, alkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, aralkyl or dialkylamino-alkyl, wherein the alkyl groups of the dialkylamino radical may form a ring which may be closed through an oxygen or sulphur atom or a methyl-imino or benzyl-imino group; R 1  is H, halogen, methoxy, CF 3  or NO 2 ; and R 2  is alkyl, aryl or aralkyl which may be aromatically substituted by halogen, methoxy, CF 3  or NO 2  groups) and salts thereof are prepared (a) by reacting a compound of the formula (wherein X is chlorine, bromine, OH, SH, alkoxy, alkylthio, or alkanoyloxy) with a compound (NHR) 2 CS, or RNCS or, when X is halogen, OH, O alkyl, or alkanoyloxy, with RNCO, or compounds which form the isocyanates or isothiocyanates; or (b) by treating a compound of the formula or a functional derivative thereof (1) if A is O, with H 2 S or an inorganic sulphide to give a benzothiazine; or (2) if A is oxygen and X is SH, with a water separating agent to give a benzothiazine; or (3) if A is O and X is other than SH, with a water separating agent to give a benzoxazine; or (4) if A is S with an agent capable of splitting off sulphur to give a benzoxazine; or (c) reacting a compound of Formula (I) which contains in the 2-position a halogen, amino, SH or S alkyl group instead of the group NHR with the amine NH 2 R<SP>1</SP> or a salt thereof (where R<SP>1</SP> is the same as R but is not H); or (d) reacting a free 2-amino compound of the invention with a reactive derivative of the alcohol R<SP>1</SP>OH; or (e) reducing with a complex metal hydride a compound of the formula (wherein R 4  is alkyl, alkenyl, aryl, aralkyl, halogeno alkyl or dialkylamino alkyl as hereinbefore defined) and, if required, reacting the haloalkyl compound before or after reduction with the appropriate dialkylamine or heterocyclic amine; or (f) reacting a compound (II) wherein X is not S-containing with a halogen cyanide; or (g) converting benzoxazines of the invention to benzothiazines with H 2 S or an inorganic sulphide. Some of these processes may require the presence of an acid or waterseparating agent. Starting materials (II) wherein X is OH are prepared (when R 2  is aryl) by reduction of the appropriate benzophenones, or, for 2-aminoalpha - methyl - benzyl alcohol, by reduction of the 2-nitro compound, and are converted to compounds of Formula (IV) by reaction with RNCO or RNCS. Starting materials (VIII) are prepared by acylation of the free amines. 2 - Methylmercapto - 4 - phenyl - 6 - chloro- 4H-3,1-benzothiazine is prepared by methylation of 2 - mercapto - 4 - phenyl - 6 - chloro - 4H - 3,1- benzothiazine, itself prepared by heating 5- chloro-2-aminobenzhydrol with H 2 S, KOH and ethanol. The benzoxazines and benzothiazines of the invention, which are stated to have a centrally depressive as well as a stimulating, tranquillizing, noradrenalin activating, anaesthesia prolonging, analgesic and spasmolytic activity, may be made up into pharmaceutical compositions with suitable carriers.