Synthesis of the N-Oxides of Phenothiazine Antipsychotic Agents

Abstract

Chlorpromazine N-oxide, fluphenazine N4’-oxide, prochlor-perazine N4’-oxide, sulforidazine N-oxide, and trifluoperazine N4’-oxide were synthesized by oxidation of the designated nitrogen atom in the N-10 side chain of the respective parent drug with 3-chloroperoxybenzoic acid. In the case of trifluoperazine, a stepwise increase in the amount of oxidant yielded the N1,N4 -dioxide and N1’,N4’,S-trioxide. The N’,S-dioxides of chlorpromazine and sulforidazine were obtained by hydrogen peroxide oxidation of the appropriate parent drug.