School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Arch Pharm Res. 2021 Nov;44(11):1012-1023. doi: 10.1007/s12272-021-01351-5. Epub 2021 Oct 18.
The site-selective and metal-free C-H nitration reaction of quinoxalinones and pyrazinones as biologically important N-heterocycles with t-butyl nitrite is described. A wide range of quinoxalinones were efficiently applied in this transformation, providing C7-nitrated quinoxalinones without undergoing C3-nitration. From the view of mechanistic point, the radical addition reaction exclusively occurred at the electron-rich aromatic region beyond electron-deficient N-heterocycle ring. This is a first report on the C7-H functionalization of quinoxalinones under metal-free conditions. In contrast, the nitration reaction readily takes place at the C3-position of pyrazinones. This transformation is characterized by the scale-up compatibility, mild reaction conditions, and excellent functional group tolerance. The applicability of the developed method is showcased by the selective reduction of NO functionality on the C7-nitrated quinoxalinone product, providing aniline derivatives. Combined mechanistic investigations aided the elucidation of a plausible reaction mechanism.
本文描述了生物重要的 N-杂环喹喔啉酮和哒嗪酮与叔丁基亚硝酸酯的位点选择性和无金属 C-H 硝化反应。该转化可高效应用于多种喹喔啉酮，且未发生 C3-硝化反应，即可得到 C7-硝化喹喔啉酮。从机理角度来看，自由基加成反应仅发生在富电子芳环区域，而不是缺电子的杂环环上。这是首例在无金属条件下喹喔啉酮 C7-H 官能化的报道。相比之下，硝化反应容易发生在哒嗪酮的 C3-位。该转化具有规模兼容性、温和的反应条件和优异的官能团耐受性。通过对 C7-硝化喹喔啉酮产物上的 NO 功能基的选择性还原，展示了所开发方法的适用性，得到了苯胺衍生物。结合机理研究有助于阐明合理的反应机理。
