A Green and Scalable Protocol for Oxidative Cyclization of N-Acylamidines with Oxone-Halide.

Oxidative cyclization of N-acylamidines is one of the most widely used approaches to yield 1,2,4-oxadiazoles, which are prevalent in many bioactive molecules and drugs. Herein, we report a scalable and green protocol using oxone and halide to achieve this transformation, affording the desired 1,2,4-oxadiazoles (32 examples, up to 93% yield) with readily removable inorganic salts as byproducts. This method offers distinct advantages over previous procedures, including operational simplicity, tolerance to air and moisture, ambient temperature, and no requirement for specialized equipment or expensive reagents. Notably, three oxadiazole-based agents were efficiently synthesized from the corresponding N-acylamidines via this protocol. Given its practical scalability and environmental friendliness, this approach is expected to find broad applications in organic synthesis and process chemistry.