Phenothiazynes: preparation of 2- and 3-tertiary aminophenothiazines

Abstract

A possible general route to 2- and 3-tertiary aminophenothiazines is described.

The reaction of 1-chloro-(3) or 2-chloro-10-methylphenothiazine (4) with sodium or lithium derivatives of secondary amines affords the same 2-tertiary amino-10-methylphenothiazine, presumably via a phenothiazyne intermediate (11). Similarly, 3-chloro-(5) or 4-chloro-10-methylphenothiazine (6) gives the same tertiary amino-10-methylphenothiazine, presumably the 3-isomer, via a different phenothiazyne (32). Demethylation of 2- and 3-tertiary amino-10-methylphenothiazines with pyridine hydrochloride at 200° affords 2- and 3-tertiary aminophenothiazines in good yield. Reaction of 2-tertiary aminophenothiazines with sodamide–3-dimethyl-aminopropyl chloride in boiling toluene gave the 10-(3-dimethylaminopropyl) derivatives.