GB1154570A - New Methanobenzazocine Derivatives and processes for their production - Google Patents

Abstract

1,154,570. 2,6 - Methano - 3 - benzazocine derivatives. J. R. GEIGY A.G. 5 May, 1966 [5 May, 1965], No. 19660/66. Heading C2C. Methanobenzazocines of the formula where R 1 is H, Hal, CF 3 or OH, R 2 is H, OH, C 1-4 alkoxy or C 1-6 alkanoyloxy, Y is H, C 1-5 alkyl which may be substituted by phenyl or aminophenyl, or Y is cycloalkylmethyl, and X is H or C 1-3 alkyl, and their addition salts with inorganic or organic acids are prepared from a compound having a carbonyl group in the 4- position and/or an acyl substituent on the nitrogen atom by reduction with a complex hydride. A compound where R 2 is hydroxy may subsequently be converted into an alkoxy or alkanoyloxy group by treatment with an alkylating agent, e.g. diazomethane or an acyl ating agent, e.g. an acid chloride or anhydride, and a hydroxy group at R 2 may be formed by ether cleavage or hydrolysis of an alkoxy or alkanoyloxy group, respectively. Suitable hydrides for the process are LiAlH 4 or diboran used in an ether solvent, or LiBH 4 in pyridine. The 4-carbonyl compounds used as starting materials may be prepared from, for example, 4-phenyl-1-tetralone by brominating in the 2- position with Br 2 in glacial acetic acid and reacting the resulting 2-bromo-4-phenyl-1-tetralone with benzylamine or a derivative thereof (e.g. methylbenzylamine) to form 2-methylbenzylamino - 4 - phenyl - 1 - tetralone. The carbonyl group is reduced, and the benzyl group removed, by catalytic hydrogenation in the presence of palladium on barium sulphate and perchloric and glacial acetic acid and the 2- methylamino-4-phenyl-tetralin obtained is reacted with chloroacetyl chloride to form 1- phenyl-3-(N-chloroacetyl methylamino)-tetralin, which undergoes cyclization with sodium hydride to form the required product. Other similar products are prepared analogously. The N-acyl derivatives used as starting material are formed by reacting the parent base with, e.g. an acid chloride. Exemplified products have R 1 as H, R@ as H, OH, alkoxy or alkanoyloxy, X as H or CH 3 and Y as H, CH 3 , C 2 H 5 , C 3 H 7 and cyclopropylmethyl. The Specification describes the resolution of the 8-hydroxy-3-methyl and 8- hydroxy-3,11-dimethyl derivatives. Pharmaceutical preparations which have analgesic and antitussive action, and are antagonists of morphine, contain the above compounds with conventional diluents, preferably in a sustained release preparation.