Qian Min, Qin Bowen, Yuan Haiyan, Li Wenliang, Zhang Jingping
Department of Chemistry, Northeast Normal University, Changchun 130024, China.
J Comput Chem. 2018 Oct 15;39(27):2324-2332. doi: 10.1002/jcc.25564. Epub 2018 Sep 20.
The mechanism of N-Bromosuccinimide (NBS) promoted synthesis of imidazo[1,2-a]pyridine in water as well as the effective activation modes of NBS was investigated by Density Functional Theory (DFT) calculations. Two main mechanisms that differ in the reaction sequence of substrate were explored: styrene with NBS then followed by 2-aminopyridine (M1) or simultaneously with NBS and 2-aminopyridine (M2), and water-assisted M2 is the more favored one. We found that the adding sequence of 2-aminopyridine affects profoundly on the title reaction. Moreover, upon the assistance of water and NBS, the preferential mechanistic scenario involves three major processes: nucleophilic addition, stepwise H-shift and intramolecular cyclization, three-step deprotonation, rather than a classical bromonium ion species. Specifically, the cooperative interaction of NBS and water plays a critical role in the title reaction. Water acts as solvent, reactant, anchoring, stabilizer, and catalyst. NBS promotes the above three processes by the effective forms of Br /Br , succinimide, and its ethanol isomer. Furthermore, noncovalent interactions between catalysts and substrates are responsible for the different reactive activities of M1 and M2. Our results indicate that simultaneous adding of all reactants is recommended toward economical synthesis. © 2018 Wiley Periodicals, Inc.
通过密度泛函理论（DFT）计算研究了N-溴代琥珀酰亚胺（NBS）促进在水中合成咪唑并[1,2-a]吡啶的机理以及NBS的有效活化模式。探索了两种在底物反应顺序上不同的主要机理：苯乙烯先与NBS反应，然后与2-氨基吡啶反应（M1），或者与NBS和2-氨基吡啶同时反应（M2），并且水辅助的M2是更有利的一种。我们发现2-氨基吡啶的添加顺序对该反应有深远影响。此外，在水和NBS的辅助下，优先的机理方案涉及三个主要过程：亲核加成、逐步氢转移和分子内环化、三步去质子化，而不是经典的溴鎓离子物种。具体而言，NBS和水的协同相互作用在该反应中起关键作用。水充当溶剂、反应物、锚定剂、稳定剂和催化剂。NBS通过Br/Br、琥珀酰亚胺及其乙醇异构体的有效形式促进上述三个过程。此外，催化剂与底物之间的非共价相互作用导致了M1和M2不同的反应活性。我们的结果表明，为了经济合成，建议同时加入所有反应物。©2018威利期刊公司。
