Diazaphenoxazines and Diazaphenothiazines: Synthesis of the "Correct" Isomers Reveals They Are Highly Reactive Radical-Trapping Antioxidants.

The preparation of 2,4-diazaphenothiazines and 2,4-diazaphenoxazines via a copper-catalyzed intramolecular amination is described. Literature approaches which utilize easily accessed (2'-aminophenyl) 4-pyri(mi)dyl sulfides undergo a Smiles rearrangement that gives rise to the 1,3-diaza derivatives instead, confirmed by X-ray crystallography. Inversion of the polarity of the cyclization avoids the rearrangement and affords the desired products. Preliminary kinetic studies suggest that 2,4-diazaphenothiazines and diazaphenoxazines, but not the 1,3-diaza isomers, are remarkably potent radical-trapping antioxidants.