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

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 dipolemoment of 6-CNA was calculated to judge the strength of polarity. The solid-liquid equilibriumbehavior 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 lambda h 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 solutesolvent interaction plays important role in solid-liquid phase equilibrium. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The research investigated the structure and properties of 6-Chloronicotinic acid (6-CNA) in both solid and solution phases, as well as its solid-liquid equilibrium behavior in various solvents. Mathematical equations were applied to describe the relationship between temperature and solubility, with mixing thermodynamic properties showing the process to be spontaneous and endothermic. Factors such as solvent polarity and hydrogen bonding tendencies were analyzed to understand 6-CNA solubility. Molecular dynamic simulations were further employed to study solute-solvent interactions, highlighting their importance in solid-liquid phase equilibrium.