Resolution of Zopiclone enantiomers by biphasic recognition chiral extraction

This paper reports a new chiral separation technology—biphasic recognition chiral extraction for the racemic separation of zopiclone, which was selected, as a case study, due to its enantiomers diverse properties.The studies performed involve an enantioselective extraction in a biphasic system, where zopiclone complexes with β-cyclodextrin derivative in aqueous phase and complexes with d(l)-tartaric acid esters present in organic phase, respectively. Factors affecting the extraction mechanism were analysed, namely the influence of the concentrations of the extractants and zopiclone enantiomers, the types of the extractants, pH and temperature.Experimental results show that, in the biphasic recognition chiral extraction system containing hydroxypropyl-β-cyclodextrin and l-isobutyl tartrate, the maximum enantioselectivity is 1.51, which is larger than that in the monophasic recognition chiral extraction system containing only l-isobutyl tartrate in organic phase. Biphasic recognition chiral extraction is of strong chiral separation ability, and has great significance for preparative separation of racemic compounds. It may also be very helpful to optimize the extraction systems and realize the large-scale production of enantiomer.