Metal-Free Nitration of Indazoles with tert-Butyl Nitrile in Air to Prepare 3-Nitroindazoles and 3-Aminoindazoles
Xin-Yue Zhang , Rong-Ting Jiang , Xiu-Qun Pan , Chun-Hua Chen , Cui Liang , Dong-Liang Mo
Chinese Journal of Chemistry ›› 2025, Vol. 43 ›› Issue (4) : 393 -398.
Metal-Free Nitration of Indazoles with tert-Butyl Nitrile in Air to Prepare 3-Nitroindazoles and 3-Aminoindazoles
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 ·NO 2 radical source in the presence of air conditions and C3-nitration of indazoles was initiated by N1-nitration and sequential migration of NO 2 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.
Nitration / Indazole / 3-Nitroindazole / 3-Aminoindazole / C-H Amination / Radical reactions / N-Heterocycles / Cleavage reactions
2024 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
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