Batch Cooling Crystallization
Access to enantiopure feedstocks of chiral molecules remains a challenge in both the fine chemical and pharmaceutical industries. Strategies involving asymmetric synthesis have dominated recent efforts. However, broader application of physical techniques, such as preferential crystallization, could dramatically augment currently available methods. From the perspective of the typical synthetic organic chemist, preferential crystallization is considered a technique only suitable for experts. This perspective is partly reinforced by the needs for detailed analysis of the solubility behavior and thermodynamic stability of what can be a multitude of crystal phases for any one compound. Even with this information, successfully executing a traditional preferential crystallization process separation can be challenging to the non-expert.
During this presentation, Jason Hein discusses applying an alternative method: continuous preferential crystallization (CPC).
During continuous preferential crystallization (CPC), the separation of racemic mixtures is accomplished by coupling multiple, parallel crystallizer and dissolving reactors which are linked by continuous circulation of the crystal-free solution phase. The continuous preferential crystallization approach provides superior control, allowing challenging systems to be resolved by utilizing only a small perturbation from equilibrium solubility. The result is a far more facile separation. In addition, the continuous preferential crystallization approach allows for efficient separation of crystalline material which are not suitable for classical preferential crystallization. These include samples with low degrees of entrainment, crystals prone to epitaxial growth and partial solid solutions. Coupling inline automated analysis with a synthesis reactor provides a benchtop prototype that can produce enantiopure crystalline material in fully continuous operation.
Jason Hein received his B.Sc. in biochemistry and Ph.D. in synthetic organic chemistry at the University of Manitoba. He then moved to the Scripps Research Institute as an NSERC postdoctoral fellow supervised by Professors K. Barry Sharpless and Valery V. Fokin. In 2010, he became a senior research associate with Professor Donna G. Blackmond at Scripps. He began his independent career at the University of California, Merced in 2011. His work focused on employing in situ kinetic reaction analysis as a means to rapidly profile and study complex networks of reactions. In 2015, he moved to the University of British Columbia to continue the development of reaction analytical techniques to further mechanistic organic chemistry.
Research in the Hein lab is aimed at solving a diverse set of lingering problems in modern organic chemistry, with primary focus towards understanding mechanisms of catalyst induction and deactivation as well as developing techniques to resolve racemic mixtures using coupled preferential crystallization.