Ring-Closure Mechanisms Mediated by Laccase to Synthesize Phenothiazines, Phenoxazines, and Phenazines.

The green and environmentally friendly synthesis of highly valuable organic substances is one possibility for the utilization of laccases (EC 1.10.3.2). As reactants for the herein described syntheses, different o-substituted arylamines or arylthiols and 2,5-dihydroxybenzoic acid and its derivatives were used. In this way, the formation of phenothiazines, phenoxazines, and phenazines was achieved in aqueous solution mediated by the laccase of Pycnoporus cinnabarinus in the presence of oxygen. Two types of phenothiazines (3-hydroxy- and 3-oxo-phenothiazines) formed in one reaction assay were described for the first time. The cyclization reactions yielded C-N, C-S, or C-O bonds. The syntheses were investigated with regard to the substitution pattern of the reaction partners. Differences in C-S and C-N bond formations without cyclization are discussed.