1,2-Didehydrophenothiazines: preparation of 1-alkyl and 1-aryl-substituted phenothiazines by lithium-directed alkylation

Abstract

A general route to 1-alkyl substituted phenothiazines is described. Reactions of 2-chlorophenothiazine with an excess of methyl-, n-butyl-, s-butyl, t-butyl-or phenyl-lithiums give the corresponding 1-substituted phenothiazines via 10-lithio-1,2-dehydrophenothiazine. Attempts to trap the presumed 1,10-dilithio intermediate failed. The reaction of 1-chlorophenothiazine with s-butyl-lithium results in preferential metallation of the 9-position. 2-Chlorophenothiazine reacts with nitrogen nucleophiles (lithium dialkylamides) to give 2-substituted products.