Two-phase (o / W) Recognition Chiral Extraction Separation Of The Enantiomers

In this paper,naproxen(NAP)enantiomers and zopiclone enantiomers were separated by a new chiral separation technique—two-phase(O/W)recognition chiral extraction.The main contents can be summarized as follows:(1)Separation extraction of naproxen(NAP)enantiomers and zopiclone(ZPC)enantiomers:the influence of the kind organic solute,the kind and concentration of extractant(tartrate derivatives andβ-CD derivatives),pH value and temperture on extraction performance was investigated.The experimental results indicate that two-phase(O/W) recognition chiral extraction is of strong chiral separation ability. HP-β-CD,HE-β-CD and Me-β-CD have higher recognition ability for one-isomer than that for other-isomer,among which HP-β-CD has the strongest ability.But tartrate derivatives have reversed recognition ability for them.In the extraction system containing HP-β-CD and L-isobutyl tartrate,the extraction effect ofα-CHMA is optimum by one stage extraction,and the distribution ratio for R-NAP(K_R)and for S-NAP(K_S) and separation factor(α)are 8.91,5.40 and 1.65,respectively.Meanwhile, pH value and concentration of extractants have great effects on chiral separation ability.In the extraction system containing HP-β-CD and L-isobutyl tartrate,the extraction effect of ZPC is optimum by one stage extraction,and the distribution ratio for R-ZPC(K_R)and for S-ZPC(K_S) and separation factor(α)are 0.97,1.47 and 1.51,respectively.(2)The inclusion stability constants of naproxen withβ-cyclodextrin derivatives(HPCD,HECD,MECD)in aqueous solution was studied by UV and HPLC.Thermodynamic parameters for the binding of NAP and HPCD was investigated.The effects of alcohol and ionic strength on inclusion behavior had been further investigated.Stable inclusion complex in solid state was characterized by IR spectra.The experimental results indicate:host-guest complexs with 1:1 molar ratio is formed.Three hosts all have weak binding ability with NAP in aqueous solution;The solubility of naproxen increase with increasing pH and the concentration of HPCD,but the apparent stability constants decrease with increasing pH.△G,AH and AS are all less than 0,so the inclusion process is a spontaneous and exothermic process.Binding ability of HPCD increased with the rise of ionic strength;β-cyclodextrin derivatives have chiral recognition ability for R- and S-naproxen.(3)The inclusion complex formation of zopiclone withβ-cyclodextrin was studied by using phase solubility method,and the formation constant for zopiclone -β-cyclodextrin was determined,the solubility of zopiclone and the formation constant was enhanced with the increase ofβ-cyclodextrin concentration and increase of pH value.The effect of temperature on the reaction was studied through thermodynamics,and the change of entropy AS,enthalpy△H and free energy△G of the reaction were all negative,suggesting that the inclusion complexation is exothermic and can spontaneously occur by the balance of enthalpy driving and entropy opposing.The inclusion complex of zopiclone andβ-cyclodextrin prepared by a method of solidgrinding. Stable inclusion complex in solid state was characterized by IR spectra and DTA.Results showed and zopiclone-β-cyclodextrin conclusion complex could be formed,β-cyclodextrin is a desirable solubilizer for zopiclone.