A New Synthesis of 1-Chlorophenothiazine

Abstract

Derivatives of 1-chlorophenothiazine, possessing different basic side chains on the nitrogen atom, have attracted the attention of medicinal chemists in the past.^1–5 Our interest in the title compound 1 stems from reports that 1-chloropromazine 2⁵ and the corresponding trans-2-(l-chloro- lo-phenothiazinyl)-N,N-dimethylcyclopropane methylamine derivative (314 exhibit antidepressant (but not antipsychotic activity) in experimental animals. A literature survey revealed that multistep syntheses were required for the preparation of I-chlorophenothiazine (1)6-9. It has however been

obtained in a single step procedure by heating a complex of phenothiazine with cupric chloride, but the yield was very low, 1.5%¹⁰.