Modeling multiple chemical equilibrium in chiral extraction of metoprolol enantiomers from single-stage extraction to fractional extraction

Enantioselective extraction of metoprolol (MT) enantiomers with di-cyclohexyl (D)-tartrate (DT) and boric acid (BA) as chiral extractant was performed. The process involving multiple chemical equilibrium is very complicated and the process optimization is difficult. On the basis of an interfacial reaction mechanism, a single-stage extraction model was established. The operation conditions of pH and DT to BA ratio were obtained through simulation and optimization of the equilibrium of the two phase extraction system. Based on the single-stage extraction model and the law of mass conservation, a fractional extraction model was established to simulate and optimize the fractional extraction process. To pursue a high productivity and reduce the required stages, a high feed to aqueous phase ratio (F/W = 1) and an asymmetric separation mode were applied. By asymmetric separation where the optical purity of the product in extract phase and raffiniate phase is not equal, enantiomeric excess (ee) value for the eutomer of MT can reach up to 98.64% and yield can reach up to 64.68% with 20 extraction stages.