Modelling studies of enantioselective extraction of an amino acid derivative in slug flow capillary microreactors

This work shows that enantioselective liquid-liquid extraction in microreactors is attractive for chiral separation. A precise control over the residence time in microreactors results in high enantiopurities and low host inventories. Mathematical modelling has been presented to describe the experimental results on the enantioselective extraction of an aqueous racemic amino acid derivative (3,5-dinitrobenzoyl-(R,S)-leucine) with a cinchona alkaloid chiral host in 1-octanol using a slug flow capillary microreactor (at an aqueous to organic flow ratio of 1:1). A good agreement between the model predictions and experimental results was obtained by taking the enhancement of the mass transfer rates due to the reactions in the aqueous and organic phases into account. An enantiomeric excess of the (S)-enantiomer higher than the equilibrium value was observed especially at shorter residence times due to kinetic effects. The observed phenomena could be explained by an instantaneous rate of the complexation of the (S)-enantiomer with the host and a finite rate of the complexation of the (R)-enantiomer. The developed model was used to determine guidelines for multi-stage operation in microreactors in order to increase yield and enantiopurity.