Determination of polymorphic forms of hydroxy-2-naphthoic acid and the corresponding solubility in twelve mono-solvents

Abstract

The polymorphs of 1‑hydroxy-2-naphthoic acid (HNA) were screened in twelve organic solvents. Five aprotic solvents – acetone, acetonitrile, methyl acetate, ethyl acetate, and n-propyl acetate – along with n-butanol crystalized HNA in Form II. Meanwhile, HNA in Form I was obtained from methanol, ethanol, n-propanol, isopropanol, 2-butanol, and isobutanol. Solubility data of the two polymorphs was determined with static method, and fitted with λh equation, van't Hoff equation, Apelblat model, NRTL, and Wilson model, with Apelblat the most accurate based on ARD and RMSD. The dissolving process was affected significantly by hydrogen bond propensity and cohesive energy density. Moreover, Hansen solubility parameters analyses indicate that the smaller $\Delta \overline{{\delta }_t}$, the better solubility of HNA. Additionally, the intermolecular interactions imply that both the van der Waals interaction and hydrogen bonding interaction take the leading role in affecting the solubility. The thermodynamic parameters suggest that the dissolving process is spontaneous and entropy increasing.