Wang Yong, Lin Xueying, Ying Xianyu, Hu Shan, Zhu Hongjun
School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, 211816, China.
Chempluschem. 2024 Nov;89(11):e202400397. doi: 10.1002/cplu.202400397. Epub 2024 Sep 12.
A facile C-H amination of quinazoline employing N-fluorobenzenesulfonimide (NFSI) as the amination source has been disclosed in the absence of any metal, oxidant or additive. The methodology shows a board range of quinazolines with different functional groups in moderate to good yields up to 87 %. Furthermore, gram-scale reaction, desulfonylation to amine and synthesis of pharmaceutical intermediate were also investigated, which demonstrates potential applications in medicinal chemistry. A plausible amination mechanism is proposed via F transfer accompanied by the removal of one molecule of PhSOF. DFT studies with experimental work suggest that the mechanism via F transfer is more favorable than the free radical one.
已公开了一种在不存在任何金属、氧化剂或添加剂的情况下，使用N-氟苯磺酰亚胺（NFSI）作为胺化源对喹唑啉进行简便的C-H胺化反应。该方法适用于一系列具有不同官能团的喹唑啉，产率适中至良好，最高可达87%。此外，还研究了克级反应、脱磺酰化制胺以及药物中间体的合成，这表明该方法在药物化学中具有潜在应用。通过氟转移伴随一分子苯磺酰氟的去除，提出了一种合理的胺化机理。结合实验工作的密度泛函理论研究表明，氟转移机理比自由基机理更有利。
