Effective Control of Liquid-Liquid Phase Separation and Nucleation of Vanillin Single Crystals through a Vapor Diffusion Crystallization Process in Selected Solvent Environments

摘要

An effective way of controlling the occurrence of liquid-liquid phase separation (LLPS) and nucleation of vanillin from aqueous solution was achieved through a vapor diffusion crystallization process in selected solvent environments. Dimethyl sulfoxide and sulfuric acid solvent environments generate a sufficient level of supersaturation due to their significant hygroscopic and water absorbing capabilities and induce crystal nucleation within shorter periods well before the occurrence of LLPS, whereas in the case without any solvent environment, nucleation occurs only at longer periods. Also, in the case of ethyl acetate as the solvent environment, due to its non-hygroscopic nature and high vapor pressure when compared to water molecules, no crystal nucleation was attained even after a month period owing to the dominance of LLPS in the solution. A powder X-ray diffraction study reveals that the nucleated plate-like crystals belong to monoclinic Form-I polymorph of vanillin, and differential scanning calorimetry and Fourier transform infrared spectroscopic analyses reveal that the diffusion processes have no effect on the thermal stability and chemical purity of the grown vanillin single crystals. This method proves to be an effective means of controlling the occurrence of unwanted LLPS prior to the crystal nucleation and to promote the crystallization of a stable polymorph of vanillin from aqueous solution.