Reaction of 2-methoxy-3H-azepine with NBS: efficient synthesis of 2-substituted 2H-azepines

[reaction: see text] The reaction of 2-methoxy-3H-azepines, in the presence or absence of a nucleophile, with N-bromosuccinimide (NBS) gave a regioselective 1,4-adduct from which the corresponding 2H-azepine derivatives were formed via base-promoted hydrogen bromide elimination, generally in moderate to quantitative yield. Competitive formation of 4-bromo-2-methoxy-3H-azepine by electrophilic substitutuion or 3H-azepin-2-yl 2H-azepin-2-yl ether by transetherification was minimized at lower reaction temperatures. Quantitative substitution of 2-(2',4',6'-trichlorophenoxy)-2H-azepine derivatives, formed in moderate yield from the respective 3H-azepine and NBS in the presence of 2,4,6-trichlorophenol (TCP), by various nucleophiles gave the corresponding 2-substituted 2H-azepine. Among these nucleophiles were alkanethiol and alkylamine that are not tolerated in the reaction of 3H-azepine and NBS.