Development of a novel Enantioselective Crystal Floatation (ECF) Process for the separation of industrially relevant chiral compounds

Chiral separation is crucial in the pharmaceutical and agrochemical industries, making high-purity separation essential. Innovative technologies that enhance efficiency, scalability, and versatility for diverse chiral compounds are necessary. This PhD project will focus on a novel Enantioselective Crystal Floatation process first conceived in collaboration with BASF SE, aiming to evaluate and extend its application to other chiral systems. This separation is based on the remarkable discovery that the racemic crystals and enantiopure crystals of chiral compounds have different surface energies due to the arrangement of enantiomers within the crystal lattice. A significant challenge of this technique is that it can only separate pre-enriched enantiomer solutions near the eutectic point of the ternary mixture. To address this, a Continuous Annular Chromatography (CAC) system will serve as the pre-enrichment step for partial enrichment, facilitating the initial separation of enantiomers before crystallization. A key objective is to merge the novel ECF process with known CAC technology to create a unified process for complete chiral separation of racemic mixtures. 

Key questions to be addressed during the PhD will be: 

The main limitation of ECF technology is its requirement for a pre-enantiomer-enriched solution, necessitating an additional enrichment step that restricts its applicability. While chromatography can provide this pre-enrichment, High-Performance Liquid Chromatography (HPLC) can be costly and complex. A cost-benefit analysis reveals diminishing returns at >90% enrichment, as similar construction is needed for final purification and polishing. In contrast, Continuous Annular Chromatography can manage higher throughput and be adapted for partial enrichment without the high costs of HPLC. However, integrating this with the ECF process presents challenges due to differing unit operations and conditions. The floatation process must be further developed to become more adaptable to other chiral systems. Understanding how these two systems can be optimized and integrated, including effective solvent exchange and recovery, is crucial. Efficient solvent management is essential for maintaining system performance, and a complete unit can be designed to incorporate both techniques, ultimately enhancing the efficiency of chiral compound purification. 

To apply, please complete an application form Application process nearmejobs.eu Study nearmejobs.eu Imperial College London.   Informal enquiries about the post and the application process can be made to Bhavna Patel (iconic-pp@imperial.ac.uk)