Continuous enantioseparation by liquid-liquid extraction

Enantioselective Liquid-Liquid Extraction (ELLE) is a technology for chiral separation that has great potential for application on all scales, from analytical to industrial production scale. Although many chiral selectors are available for techniques such as chromatography, they are usually not applicable to ELLE. By discussing recent technological advances, it is demonstrated that the technology is moving towards maturity for commercial application. Multistage countercurrent extraction models were used for predicting extraction performances for two different systems. For the enantioseparation of phenylglycinol with an azophenolic crown ether the enantioselectivity was found to be 10, and it was predicted that for 98 percent e.e. 4 stages were sufficient. For the separation of 3, 5-dinitrobenzoyl-leucine using a cinchona alkaloid derivative the selectivity was 3.43 and 12 stages are required for 99 percent e.e. Using bench-scaled centrifugal contactor separator equipment the model predictions were experimentally validated and very stable operation for over 10hr. was proven. Extrapolation of the results shows that separation of 50 mol racemate per week with only about 0.1 mol extractant is possible in the bench scaled equipment. However, for broad application of ELLE, exploratory research to develop extensive libraries for chiral selectors is needed to speed up the development.