Synthesis of Pyrazoles Utilizing the Ambiphilic Reactivity of Hydrazones

A Bronsted acid-mediated synthesis of pyrazoles from conjugated hydrazones through a beta-protonation/nucleophilic addition/cyclization/aromatization sequence was developed. This protocol utilizing the ambiphilic reactivity of hydrazones enables not only self-condensation but also cross-condensation, affording multisubstituted pyrazoles in high yields, with a broad substrate scope. This sequential reaction proceeds under mild conditions via a simple operation. Moreover, the method can be applied to the synthesis of a nonsteroidal anti-inflammatory drug, Lonazolac.