Syntheses of 1,2-N-alkylimino-1,2,3,4-tetrahydronaphthalene derivatives and preparation of ring closed analog of salbutamol as a new beta-adrenoceptor agent.

Abstract

A method for preparing 5-substituted 2-tertiary-alkylamino-6-hydroxy-1, 2, 3, 4-tetrahydro-1-naphthalenols was described. The method involves the preparation of 1-alkylamino-2-hydroxy-1, 2, 3, 4-tetrahydronaphthalenes from 2-bromo-1-hydroxy derivatives via 1, 2-epoxides followed by the transposition of 1-alkylamino and 2-hydroxy groups via the ring closure to 1, 2-aziridines. Formation of the epoxides and aziridines and the reaction of epoxides with amines were examined in detail. The ring-opening reaction of epoxides was regioselective and the attacking position of a nucleophile was not affected by the electronic effects of substituents on the benzene ring. Cyclization into aziridine rings was best accomplished by the Wenker method using a sulfur trioxide-triethylamine adduct as the sulfating agent. Using our process, trans-2-tert-butylamino-6-hydroxy-5-hydroxymethyl-1, 2, 3, 4-tetrahydro-1-naphthalenol (70) was synthesized as conformationally fixed analog of salbutamol.