It has been recognized that CBr4 can give rise to a noncovalent interaction known as halogen bond (XB). CBr4 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 CBr4 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.
© 2023 The Authors. Published by American Chemical Society.