Determination of pKa for substituted benzoic acids in mixed solvent using density functional theory and QSPR

Abstract

The pKa of some substituted benzoic acid were calculated using three different methods in 50% ethanol/water at 273.15 K with B3LYP/6-31G(d,p) level of calculations. The calculated pKas were compared with the experimental values. The quantitative structure property relationship was found to give good results compared with the first principle methods. The solution-phase quantum chemical descriptors were found to give more accurate pKas than the gas-phase descriptors. The participation of quantum chemical descriptors as bond lengths and charge density mainly affects the acidity constant of studied compounds as represented by high correlation coefficient factors for the obtained equations. The obtained equations were applied to predict the acidity constant of some related structures to benzoic acid.

Experimental Quantum Chemistry: A Hammett‐inspired Fingerprinting of Substituent Effects

“…Hammett parameters have been predicted using theory and can also be used as experimental benchmarks to valid descriptors produced by theory. One approach for evaluating σ from first principles is to calculate the Δ G of benzoic acid dissociation to obtain p K a values [12–14] . However, because of the intricacies of modeling solvation effects accurately, computational prediction of p K a is both challenging and costly [12] .…”

Conformation/Tautomerization effect on the pKa values of lumazine and 6‐thienyllumazine

“…pK a values are related to a number of properties such as solubility, scope of binding, and rate of absorption. A number of methods, both experimental and theoretical, have been employed to calculate pK a values . The correlation of theoretical and experimental data allows for the development of models to determine the pK a of compounds for which no experimental data are yet available.…”