Theoretical Study of O-CH3 Bond Dissociation Enthalpy in Anisole Systems


Understanding ubiquitous methyl transfer reactions requires a systematic study of thermodynamical parameters that could reveal valuable information about the nature of the chemical bond and the feasibility of those processes. In the present study, the O-CH3 bond dissociation enthalpies (BDEs) of 67 compounds belonging to phenol/anisole systems were calculated employing the Gaussian-4 (G4) method. Those compounds contain different substituents including alkyl groups, electron-donating groups (EDGs), and electron-withdrawing groups (EWGs). The results show that the bigger branched alkyl groups and EDGs will destabilize the O-CH3 bond, while EWGs have the opposite effect. A combination of different effects including steric effects, hydrogen bonds, and substituents and their position can achieve around 20 kcal/mol difference compared to the basic phenyl frame. Also, the linear correlation between σp+ and O-CH3 BDE can provide a reference for the O-CH3 BDE prediction. The present study represents a step forward to establish a comprehensive O-CH3 BDE database to understand the substituent effect and make its contribution to the rational design of inhibitors and drugs.


© 2021 The Authors. Published by American Chemical Society. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.


Alkyls, Bond Cleavage, Enthalpy, Molecules, Substituents


Li, R., Du, T., Liu, J., Aquino, A. J. A., & Zhang, J. (2021). Theoretical Study of O-CH3 Bond Dissociation Enthalpy in Anisole Systems. ACS Omega, 6(34), 21952-21959.