Visible-Light Photocatalytic Oxidative Dehydrogenation toward Midazolam under Continuous Flow

Midazolam is a widely used benzodiazepine whose pharmacological activity depends on a conjugated heteroaromatic system formed during the final oxidative dehydrogenation step. Conventional synthesis employs stoichiometric oxidants, such as manganese dioxide, generating waste and limiting sustainability and continuous-flow implementation. In this work, organic photocatalysts, including eosin Y, methylene blue, rose bengal, and 2,4,6-triphenylpyrylium tetrafluoroborate (TPPT), were evaluated under different reaction conditions. HPLC analysis identified TPPT as the most efficient photocatalyst, affording midazolam with 90% purity and a 63% isolated yield after 24 h in batch mode. The optimized conditions were translated to a continuous-flow photoreactor, where HPLC confirmed precursor conversion to midazolam base. The continuous-flow process provided high-purity product at a residence time of 3 h. Although the isolated yield was lower than in batch, the results demonstrate the potential of visible-light photocatalysis as a more sustainable strategy for continuous pharmaceutical manufacturing while indicating the need for further optimization.