Direct observation of α- to β-glycine transformation during the ionic liquid-mediated crystallization process

Abstract

The application of in situ powder X-ray diffraction (XRD) to monitor the polymorphic transformation and crystallization of glycine from an ionic liquid–water system is introduced. We compared the polymorphic crystallization processes of glycine in pure water, a hydrophilic ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate ([Emim]BF₄)- and a hydrophobic ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([Bmim]PF₆)-water system. In these three cases, the mixture was predominantly composed of the metastable α-glycine, while the least stable β-glycine was only observed during the growth of crystals at room temperature and 32% humidity. The phase transformation from α- to β-glycine was clearly observed through the change in the intensity of characteristic peaks at 29.9° and 18.0° (2 theta) in the XRD patterns. In addition, the effect of the ionic liquid [Bmim]PF₆ as an anti-solvent on the re-crystallization process of glycine from three commercially available brands was estimated. Also, the satisfactory reproducibility was obtained from glycine crystallization in the ionic liquid [Emim]BF₄-water system in four independent experiments. Therefore, laboratory-based powder XRD analysis can not only provide dynamic information about phase transformation in situ, but can also discover the unstable or transition state in the polymorphic design and control crystallization processes by adding ionic liquids or other additives.