Maharana Rajat Rajiv, Bhanja Rosalin, Mal Prasenjit, Samanta Kousik
School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Argul, Odisha 752050, India.
School of Chemical Sciences, National Institute of Science Education and Research (NISER), An OCC of Homi Bhabha National Institute, Bhubaneswar, PO Bhimpur-Padanpur, Via Jatni, District Khurda, Odisha 752050, India.
ACS Omega. 2023 Sep 1;8(37):33785-33793. doi: 10.1021/acsomega.3c04207. eCollection 2023 Sep 19.
It has been recognized that CBr can give rise to a noncovalent interaction known as halogen bond (XB). CBr was found to catalyze, in terms of XB formation, the transformation of 2'-aminochalcone to aza-flavanone through an intramolecular Michael addition reaction. The impact of XB and the resulting yield of aza-flavanone exhibited a pronounced dependence on the characteristics of the solvent. Notably, yields of 88% in ethanol and 33% in DMSO were achieved, while merely a trace amount of the product was detected in benzene. In this work, we use a computational modeling study to understand this variance in yield. The reaction is modeled at the level of density functional theory (based on the M06-2X exchange-correlation functional) with all-electron basis sets of triple-ζ quality. Grimme's dispersion correction is incorporated to account for the noncovalent interactions accurately. Harmonic frequency calculations are carried out to establish the character of the optimized structures (minimum or saddle point). Our calculations confirm the formation of an XB between CBr and the reacting species and its role in lowering the activation energy barrier. Stronger orbital interactions and significant lowering of the steric repulsion were found to be important in lowering the activation barrier. The negligible yield in the nonpolar solvent benzene may be attributed to the high activation energy as well as the inadequate stabilization of the zwitterionic intermediate. In ethanol, a protic solvent, additional H-bonding contributes to further lowering of the activation barrier and better stabilization of the zwitterionic intermediate. The combined effects of solvent polarity, XB, and H-bond are likely to give rise to an excellent yield of aza-flavanone in ethanol.
人们已经认识到，CBr 能够引发一种被称为卤键（XB）的非共价相互作用。研究发现，就 XB 的形成而言，CBr 可通过分子内迈克尔加成反应催化 2'-氨基查尔酮转化为氮杂黄烷酮。XB 的影响以及由此产生的氮杂黄烷酮产率对溶剂特性表现出显著的依赖性。值得注意的是，在乙醇中产率达到 88%，在二甲基亚砜（DMSO）中为 33%，而在苯中仅检测到痕量产物。在这项工作中，我们通过计算建模研究来理解产率的这种差异。该反应在密度泛函理论水平（基于 M06 - 2X 交换相关泛函）上进行建模，采用全电子三ζ质量基组。纳入了 Grimme 的色散校正以准确考虑非共价相互作用。进行了谐波频率计算以确定优化结构的性质（极小值或鞍点）。我们的计算证实了 CBr 与反应物种之间形成了 XB 及其在降低活化能垒方面的作用。发现更强的轨道相互作用和空间排斥力的显著降低对于降低活化能垒很重要。在非极性溶剂苯中产率可忽略不计可能归因于高活化能以及两性离子中间体的稳定性不足。在质子溶剂乙醇中，额外的氢键有助于进一步降低活化能垒并更好地稳定两性离子中间体。溶剂极性、XB 和氢键的综合作用可能导致乙醇中氮杂黄烷酮的产率极高。
