Molecular electrostatic potential as a tool for evaluating the etherification rate constant

Area of Science:

• Computational chemistry
• Physical organic chemistry

Background:

• Understanding substituent effects on reaction kinetics is crucial in organic chemistry.
• Quantitative structure-activity relationships (QSAR) often employ local quantum descriptors.

Purpose of the Study:

• To investigate the utility of molecular electrostatic potential (MEP) as a descriptor for substituent effects on etherification reaction rate constants.
• To establish a theoretical relationship between MEP and etherification reaction rates.
• To compare MEP with the Atoms-in-Molecules (AIM) charge scheme for predicting kinetic variations.

Main Methods:

• Utilizing density functional theory (DFT) to calculate MEP at atomic sites.
• Employing MEP and AIM charge as local quantum descriptors.
• Correlating descriptor values with experimental rate constants for 30 substituted phenols.

Main Results:

• A direct proportionality was established between etherification rate constants and MEP at atomic sites.
• MEP effectively estimated reaction rate constant variations due to substituent effects.
• Both MEP and AIM charge showed strong correlations with experimental kinetic data.
• The proposed method offers a simple and effective way to compute rate constants.

Conclusions:

• MEP is a valid and effective quantum descriptor for substituent effects in etherification reactions.
• The correlation between MEP, AIM charge, and experimental rate constants validates the proposed computational approach.
• This study provides a simplified method for predicting etherification reaction rates of substituted phenols.