Direct Amidation of Alkynes with Nitroarenes via Heterogeneous Semiconductor TiO₂ Nanotubes.

Amides, which are crucial in pharmaceuticals and materials science, are traditionally synthesized via unsustainable condensation reactions. While direct amidation has long been pursued as an atom-economical route, it still relies on toxic reagents and harsh conditions. This work presents a light-driven photocatalytic process that explores a rarely investigated transformation of alkynes and nitroarenes, enabling amide synthesis with excellent yields (up to 95%) using heterogeneous TiO₂ nanotubes. This sustainable approach enables C-N bond formation with a wide range of alkynes and diverse nitroarenes under mild reaction conditions. This method is suitable for the direct synthesis of pharmaceutically relevant amides and offers broad applicability for the late-stage modification of bioactive molecules. A tentative coupling mechanism is proposed based on controlled, mechanistic experiments. Overall, the combination of operational simplicity, ambient-air compatibility, and catalyst recyclability positions this method as a promising tool for green, practical synthesis in pharmaceutical and chemical applications.