Uncovering the solid-liquid equilibrium behavior of 6-Chloronicotinic acid in eleven pure solvents by thermodynamic analysis and molecular dynamic simulation

Abstract

The structure and properties of 6-Chloronicotinic acid (6-CNA) were investigated both in solid and solution phases. Hirshfeld surface analysis has been employed to analyze the intermolecular contacts with the crystal structure. The dipole moment of 6-CNA was calculated to judge the strength of polarity. The solid-liquid equilibrium behavior of 6-CNA in eleven pure solvents (methanol, 1-propanol, isopropyl alcohol, 2-butanol, isobutyl alcohol, methyl acetate, ethyl acetate, acetone, 2-butanone, acetonitrile and 1,4-dioxane) was determined at temperature from 283.15 to 323.15 K by gravimetric method. The modified Apelblat equation, van't Hoff equation, NRTL equation and λh equation were applied to mathematically describe the relationship between temperature and solubility and the ARD% was used to test the accuracy of the four equations. In addition, the mixing thermodynamic properties calculated based on the NRTL model shows that the mixing process is spontaneous and endothermic. Besides, multiple factors including solvent polarity, hydrogen bond donor propensity and hydrogen bond acceptor propensity were applied to analyze the solubility of 6-CNA in different solvents. In the last, molecular dynamic simulation including solvation free energy and radial distribution function (RDF) analysis have been furthermore employed to analyze the solute-solvent interactions and the results show that solute-solvent interaction plays important role in solid-liquid phase equilibrium.