Solubility and solution thermodynamics of isobutyramide in 15 pure solvents at temperatures from 273.15 to 324.75 K

Abstract

Being an important synthetic monomer, isobutyramide (IBA) is employed as an intermediate for the synthesis of organic dyes and pharmaceuticals. It is well known that investigation of the solubility behavior of drugs and intermediates has become an extensive research topic in pharmaceutical development. In this work, the solid-liquid equilibrium (SLE) data of IBA in fifteen solvents, including methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, acetonitrile, chloroform, acetone, ethyl formate, methyl acetate, cyclohexanone, cyclopentanone, tetrahydrofuran and 2-butanone was measured with a static gravimetric method with the temperature ranging from 273.15 to 324.75 K under atmospheric pressure. The solubility of IBA increases with the rising temperature in all selected solvents. The ranking of solubility in various solvents is not in accordance with the order of solvent physicochemical properties, namely polarity index, dipole moment, dielectric constant and solubility parameter. The modified Apelblat equation, λh equation, nonrandom two-liquid (NRTL) model and the Wilson model were used to correlate the experimental data. Maximum root-mean-square deviation (RMSD) and relative average deviation (RAD) were 7.157 × 10−3 and 1.80%, respectively. The λh equation presented less effective correlating results compared with other three models. The dissolution properties of IBA, including Gibbs energy (△disG), molar enthalpy (△disH) and molar entropy (△disS) were determined based on the Wilson model and the solubility data. Positive values of the dissolution enthalpy and entropy illustrated that the dissolution process of IBA in selected solvents are endothermic and entropy-driven.