Metal-Free Nitration of Indazoles with tert-Butyl Nitrile in Air to Prepare 3-Nitroindazoles and 3-Aminoindazoles

Abstract

A variety of 3-nitroindazoles and 3-aminoindazoles were prepared in good to excellent yields with high regioselectivity through TBN-mediated nitration at the C3-position of indazoles under the air conditions and sequential reduction. Mechanistic studies revealed that TBN played crucial roles to produce •NO₂ radical source in the presence of air conditions and C3-nitration of indazoles was initiated by N1-nitration and sequential migration of NO₂ group to C3-position. Moreover, this method could be easily applied in the gram scalable synthesis of ibuprofen and ciprofibrate-derived 3-aminoindazoles. The present method highlights air as mild oxidant, metal-free radical nitration of indazole, N—N bond formation and cleavage, and late-stage modification of drugs.