Synthesis of 3-Substituted Benzoxazoline-2-thiones

Several methods for the preparations of 3-substituted benzoxazoline-2-thiones (1) were examined. Method B via the thiation of 3-substituted benzoxazolin-2-one (5) with phosphorus pentasulfide was found to be applicable to the preparation of most analogs of 1, with a few exceptions. Method C via the cyclization of 2-(alkylamino)phenol (7) with potassium O-methyldithiocarbonate was suitable for the preparation of analogs with a group sensitive to high temperature or with an aryl- (including aromatic hetero-cyclic ring) methyl group. In addition, the reaction of benzoxazoline-2-thione (2) with acetals such as 1-ethoxy-isochroman, 2-ethoxytetrahydrofuran, and 2-ethoxytetrahydropyran, or with Michael acceptors such as 2,3-dihydrofuran and 2H-3,4-dihydropyran, gave 3-substituted benzoxazoline-2-thione (1d—f).