Symmetry-Adapted Perturbation Theory Decomposition of the Reaction Force: Insights into Substituent Effects Involved in Hemiacetal Formation Mechanisms.

The decomposition of the reaction force based on symmetry-adapted perturbation theory (SAPT) has been proposed. This approach was used to investigate the substituent effects along the reaction coordinate pathway for the hemiacetal formation mechanism between methanol and substituted aldehydes of the form CXCHO (X = H, F, Cl, and Br), providing a quantitative evaluation of the reaction-driving and reaction-retarding force components. Our results highlight the importance of more favorable electrostatic and induction effects in the reactions involving halogenated aldehydes that leads to lower activation energy barriers. These substituent effects are further elucidated by applying the functional-group partition of symmetry-adapted perturbation theory (F-SAPT). The results show that the reaction is largely driven by favorable direct noncovalent interactions between the CX group on the aldehyde and the OH group on methanol.