Department of Pharmaceutical Technology (Process Chemistry), National Institute of Pharmaceutical Education and Research, S. A. S. Nagar, Punjab 160062, India.
Org Lett. 2023 May 19;25(19):3402-3406. doi: 10.1021/acs.orglett.3c00927. Epub 2023 May 9.
Unlike conventional amide synthesis, a decarboxylative amidation of aryl/heteroarylacetic acids by reaction with NHS and -butyl nitrite has been reported to afford both aliphatic and (hetero)aromatic amides in satisfactory yields. Mechanistic studies revealed a previously unexplored pathway for the formation of an activated ester through the generation and subsequent reactions of traceless α-functionalized benzylic radicals, which upon subsequent one-pot reaction with amines form the amides. A gram-scale synthesis of Moclobemide indicates the practical applicability.
与传统的酰胺合成不同，通过 NHS 和 -丁基亚硝酸酯与芳基/杂芳基乙酸的脱羧酰胺化反应，可以以令人满意的收率得到脂肪族和（杂）芳族酰胺。机理研究表明，通过生成和随后的无痕迹α-功能化苄基自由基的反应，形成活化酯的途径以前未被探索，随后与胺进行一锅反应形成酰胺。莫鲁比胺的克级合成表明了其实用性。
