On the microwave-assisted synthesis of acylphenothiazine derivatives — Experiment versus theory synergism

The microwave-assisted synthesis of a series of acylphenothiazine derivatives is described. 10H-Phenothiazine-3-carbaldehyde derivatives were obtained in moderate yields by the Duff formylation reaction, and 10-acetyl-phenothiazine derivatives were obtained in excellent yields by acetylating phenothiazine derivatives with acetic anhydride. A theoretical explanation for the chemoselectivity and regioselectivity of these acylation reactions applied to phenothiazine substrates was attempted by molecular-modeling analyses based on molecular mechanics, and semi-empirical and DFT calculations.