Understanding the solid-liquid phase equilibrium of 3,5-dimethoxybenzoic acid in thirteen pure solvents by thermodynamic analysis and molecular simulation

Abstract

The solubility of 3,5-dimethoxybenzoic acid in 13 pure solvents range from 283.15 K to 323.15 K was investigated by the experiments and molecular simulations. Interestingly, its solubility in ethanol shows a particularity that is larger than that in n-butanol, which may be different from the expectation. This phenomenon was analyzed by molecular electrostatic potential surface (MEPs), Hirschfeld surface (HS), and radial distribution function (RDF) simulated by molecular dynamics (MD). The results indicate that the higher solubility of 3,5-dimethoxybenzoic acid in ethanol is due to the solute-solvent and solvent-solvent intermolecular hydrogen bonds. While in the investigation of the solubility in the esters, the relevant results of solvation free energy demonstrate that the solute-solvent interaction is dominant. The experimental data were further correlated with the van't Hoff model, λh model, the modified Apelblat equation and the NRTL model. All the overall ARD values are less than 4%. The modified Apelblat equation presents the best fitting effect. Furthermore, based on the NRTL model, the order of the obtained mixing Gibbs energy is consistent with the solubility order. Besides, its negative value indicates that the mixing process is spontaneous. The solubility of 3,5-dimethoxybenzoic acid in different solvents increases from 2-folds to 5-folds with the increasing temperature, which provides favorable conditions for the separation and purification of 3,5-dimethoxybenzoic acid in industrial production.