Sonochemical N-nitrosation of secondary amines under mild conditions

N-Nitrosamines are a structurally important class of compounds that have attracted considerable attention owing to their classification as a regulatory "cohort of concern" and their diverse applications in pharmaceutical chemistry and organic synthesis; however, their preparation often relies on harsh reaction conditions and hazardous nitrosating reagents. Herein, we report a rapid and environmentally benign sonochemical protocol for the synthesis of N-nitrosamines using readily available iron(III) nitrate nonahydrate as an inexpensive nitroso source. The transformation proceeds under exceptionally mild conditions without the need for strong acids, oxidants, or specialized nitrosating agents. A broad range of secondary amines, including aliphatic, benzylic, cyclic, heterocyclic, amino acid-derived, and pharmaceutically relevant substrates, undergo efficient nitrosation in good to excellent yields with excellent functional-group tolerance. The methodology also enables the late-stage nitrosation of drug molecules and is readily scalable. Mechanistic studies, including radical-trapping experiments, HRMS, and EPR spectroscopy, provide evidence for the in situ generation of reactive nitrogen oxide species under ultrasonic irradiation. The results support both nitrosonium-ion- and radical-mediated pathways and reveal an acoustic-cavitation-driven nitrate-activation process. This operationally simple and sustainable protocol provides a practical platform for N-nitrosamine synthesis and highlights the potential of sonochemistry in nitrogen-oxide transformations under mild conditions.