Copper/l-Proline-Catalyzed Synthesis of Phenothiazines

Significance

Reported here is the copper-catalyzed synthesis of phenothiazines from the reaction of 2-iodoanilines with 2-bromobenzenethiols. After optimization, the best results were obtained using CuI as a catalyst and l-proline as a ligand in 2-methoxyethanol as the solvent. After a certain time at 90 ˚C to produce the S-arylated product (isolated in 90% yield in the case of R^¹ = R^² = H), it was necessary to increase the temperature to 110 ˚C to afford the phenothiazines in moderate to good yields. The reaction proved to be efficient for anilines and benzenethiols with both electron-donating and -withdrawing groups, although the nature of the substituents has an effect on the ­reaction rate of the S- and N-arylation steps.