Insight into solid-liquid and liquid-liquid phase equilibrium behavior of vanillin and ethyl vanillin.

• Lower polarity and stronger hydrophobicity leading to lower solubility of EVA. • The relative contribution of enthalpy decreases with increasing n -propanol content. • LLPS is mainly dependent on solute and solvent properties but not temperature. • EVA is more prone to LLPS due to greater steric hindrance and hydrophobicity. • Water and oil phase satisfies optimal and suboptimal stable ratio, respectively. How different solute affects solid-liquid equilibrium and the underlying mechanisms of how solutes are partitioned in the liquid-liquid two phases during crystallization are not well understood, which setting up obstacles to better control of the crystallization and purification process. Thus, firstly, we uncover how the solvent composition and solute structure affect the phase equilibrium of vanillin (VA) and ethyl vanillin (EVA) in n -propanol-water mixed solvent. The results show that both the solubility of VA and EVA show significant co-solvency phenomenon. Besides, stronger hydrophobicity of EVA leading to lower solubility than that of VA. Furthermore, we found that the ratio of relative contribution of enthalpy and entropy decreases with increasing n -propanol content. Secondly, ternary phase diagrams indicate that EVA is more prone to liquid-liquid phase separation (LLPS) than VA, since EVA possesses greater steric hindrance and stronger hydrophobicity. Interestingly, the LLPS curves are mainly dependent on solute and solvent properties but almost independent of temperature in both systems. Meanwhile, the tie lines are found to be not strictly parallel to each other, which suggest that solute clusters exist in the lean solute phase satisfying the optimal stable ratio and the rich solute phase satisfying the suboptimal stable ratio. Finally, molecular simulation showed that the energy of the LLPS system is always lower than that of the homogeneous solution system. These contributions provide in-depth understanding of the solid-liquid and liquid-liquid phase behavior, which is expected to provide theoretical guidance for breaking through the bottleneck of crystallization control. [ABSTRACT FROM AUTHOR]