Ketoprofen And Mandelic Acid Enantiomers Of A Chiral Separation

In this paper, ketoprofen enantiomers and mandelic acid enantiomers were separated, respectively. The main contents can be summarized as follows:1. Synthesis of the chiral selector of tartrate:A series of chiral selectors of L/D-tartaric esters were synthesized with L/D-tartaric acid and fatty alcohols as material. And the structure of aimed products were studied by Infrared Spectrum. Taking the synthesis of isobutyl tartrate as an example, the effects of mole ratio, solvent, types of catalysts and concentration of catalyst on the esterification were investigated. The experimental results indicated that the optimum reaction conditions were that the molar ratio of L/D-tartaric acid to alcohol was 1:2.8, p-toluene sulfonic acid as catalyst was 1.0 g and the amount of toluene as dehydrating agent was 45 mL.2. Study on chiral separation of ketoprofen enantiomers by two-phase(W/O) recognition chiral extraction:The distribution behavior of ketoprofen enantiomers was performed in the extraction system, which was established by adding hydrophobic tartrates in organic phase and hydrophilicβ-cyclodextrin (β-CD) derivatives in aqueous phase. Parameters such as the types of the organic solvent,β-CD derivatives and tartaric derivatives, the concentrations of the optimum extractants, and pH of the buffer were studied to determine their influence on enantioseparation. The results indicated thatβ-CD derivatives preferentially recognized not R-ketoprofen but S-ketoprofen, whereas L-tartrates had reverse recognition of ketoprofen enantiomers; 1,2-dichloroethane as solvent, trimethyl-β-CD and L-(+)-isobutyl tartrate as chiral extractants were the best choice; the concentrations of the extractants and pH had obvious effect on the enantioselectivity; high enantioselectivity for ketoprofen enantiomers was obtained in the buffer consisted of 0.2 mol/L L-(+)-isobutyl tartrate and 0.1 mol/L trimethyl-β-CD at pH≤2.5.3. The distribution behavior of MA acid enantiomers was examined in a two-phase aqueous-organic solventmixture containing D2EHPA and tartaric acid derivatives as co-extractants.The influence of tartaric acid derivative's species and it's initial concentration, the initial concentration of D2EHPA and D, L-MA on distribution ratio and enantioselectivity were studied.The results showed that both the distribution ratio and enantioselectivity are greatly improved by using D2EHPA and tartaric acid derivatives as co-extractants than using tartaric acid derivatives individually. The influence of the intial concentration of D,L-MA and the chiral selector on k and a were insignificant.4. Study on chiral separation of mandelic acid enantiomers by high-speed countercurrent chromatography:The different two-phase solvent systems were consisted of hexane-ethyl acetate-isopropanol, and L-DBTA and D-isobutyltartrate were as chiral selectors. The experimental results indicated that the retention of the stationary phase of the two-phase solvent system used reached 50%, but the enantiomers failed to be separated. The reasons caused the above results could be as follows:the composion or propotion of two-phase solvent system was unsuitable; the selective differences between different configurations of chiral selector was not visible, or the amount of chiral selector was too little; the chiral selector was not adequately disolved in the stationary phase; high-speed countcurrent chromatography had inferior separation efficiency.