Simultaneous biphasic enantioselective liquid-liquid extraction for racemic separation pantoprazole.

Obtaining optically-pure enantiopure in a cost-efficient and eco-friendly manner is of high importance to human health and environmental sustainability. Currently, enantioselective liquid-liquid extraction (ELLE) is one of the promising processes because of its green production and advantages in scaling up. Nonetheless, the ELLE method for enantioseparation is still unsatisfactory due to the poor efficiency. Herein we present, using pantoprazole (PAN) as a case study, simultaneously employing chiral ionic liquids (CILs) and tartaric acids (TA) derivatives as hydrophilic and hydrophobic chiral additives in biphasic recognition chiral extraction (BRCE) process to enhance the performance. (92) RESULTS: The types of CILs and TA derivatives configurations, concentration of chiral additives and initial PAN, extraction temperature, aqueous pH value have been systematically investigated. The excellent enantioselectivity (α) and enantiomeric excess (e.e.%) values of 3.83 and 13.3 % were achieved at the pH of 8.0, temperature of 25 °C, the initial PAN concentration of 0.3 mg/mL, and the ratio of 1:10 of [Bmim][L-Phe] to [D-di-isopropyl-tartrate], which is significantly better than other available ELLE systems in previous works. Furthermore, the equilibrium and mechanism of stereoselective capacity in BRCE was discussed. And isolated interaction between hydrophobic and hydrophilic chiral additives toward PAN enantiomer was simulated by DFT calculations. As a result, comprehensive efficiency for BRCE was improved greatly while comparing with monophasic recognition chiral extraction (MRCE). Theoretically, in terms of enantioselective capacity, BRCE technology was stronger than MRCE. (135) SIGNIFICANCE: We propose that the improvement of performance was attributed to the simultaneous biphasic recognition of oppositely R- and S-enantiomers. This work provides guidance for construction of an enhanced BRCE system in combination with multistage countercurrent cascade technology a fierce rival in the field of new enantioselective separation technologies. In addition, it is also foreseeable that different stereochemical preferences under thermodynamic and kinetic conditions may be exploited to increase by consecutive BRCE technology. (72).