Incorporating Morpholine and Oxetane into Benzimidazolequinone Antitumor Agents: The Discovery of 1,4,6,9-Tetramethoxyphenazine from Hydrogen Peroxide and Hydroiodic Acid-Mediated Oxidative Cyclizations

The reactivity of hydrogen peroxide
and catalytic hydroiodic acid
toward 3,6-dimethoxy-2-(cycloamino)­anilines is tunable to give ring-fused
benzimidazoles or 1,4,6,9-tetramethoxyphenazine in high yield. Mechanisms
via a detected nitroso-intermediate are proposed for oxidative cyclization
and the unexpected intermolecular displacement of the oxazine. An
aqueous solution of molecular iodine is capable of the same transformations.
Oxidative demethylation gave targeted benzimidazolequinones, including
without cleavage of the incorporated oxetane.