Synthesis of 1,4-thiazino- and benzo-1,4-thiazinomorphinans: their acid-catalyzed rearrangement and study of the formation of unexpected oxidation products

The formation of 1,4-thiazine and benzo-1,4-thiazine rings was performed at the 6,7-positions of the morphinan backbone in order to synthesize systems annulated with a new six-membered ring providing potential pharmacological activity and the opportunity of easy functionalization. An unexpected oxidation of cyclic sulfur was observed in both cases affording either sulfones or open-ringed bis-morphinan-type by-product. These phenomena are in conformity with the observations and mechanistic explanations made by several research groups in the past in connection with the photosensitized oxidation of cyclic sulfides.

Graphical abstractThe formation of 1,4-thiazine and benzo-1,4-thiazine rings was performed at the 6,7-positions of the morphinan backbone in order to synthesize systems annulated with a new six-membered ring providing potential pharmacological activity and the opportunity of easy functionalization. An unexpected oxidation of cyclic sulfur was observed in both cases affording either sulfones or open-ringed bis-morphinan-type by-product.Download full-size image