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

• Published in: ACS omega 2021-08, Vol.6 (34), p.21952-21959
• Main Authors: Li, Rui, Du, Tianshu, Liu, Jingxing, Aquino, Adelia J. A, Zhang, Jianyu
• Format: Article
• Language: English
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.1c02310

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.