Regioselective Ortho-Azidation of Anilines via Quinone Imine Ketals: A One-Pot Approach to Proton Pump Inhibitors

Here, we demonstrated a metal-free, Brønsted acid-catalyzed, regioselective nondirected C-H activation reaction that efficiently achieves ortho-functionalization of p-anisidines via quinone imine ketals. Besides streamlining the synthesis of ortho-azidated anilines, our method is scalable and exhibits a high tolerance to various functional groups. Control experiments and comprehensive 2D NMR analysis confirmed the ortho-selectivity. The protocol was also adapted to synthesize difficult diaminated arenes and successfully used to produce marketed proton-pump inhibitors, Ufiprazole and Omeprazole.