Research On Enantioseparation Of Phenylsuccinic Acid By Solvent Sublation

In this paper, solvent sublation, a new analysis method of separation and enrichment, was firstly introduced into the chiral separation field by using phenylsuccinic acid (H2A) as the model enantiomers. The separation effects of two chiral solvent sublations were investigated. Besides, a preliminary investigation has also been carried out on the enantioselectivities and the theory of the separation. The main contents can be summarized as follows:(1) A co-technology of solvent sublation and biphasic recognition chiral extraction (BRCE) was firstly reported. Combining the advantages of both, the co-technology was used to separate racemic H2A. In this method, hydrophilic hydroxypropyl-β-cyclodextrin (HP-β-CD), hydrophobic dibenzoyl-L-tartaric acid (L-DBTA) and n-octanol were used as chiral co-extractants and organic solvent. Several important parameters influencing the separation performances, such as the pH in the aqueous phase, the concentrations of phenylsuccinic acid (H2A), L-DBTA, and hydroxypropyl-β-cyclodextrin (HP-β-CD), the flow rate of air and the sublation time were investigated. Under the optimal operating conditions, that was obtained with the concentration of H2A of1.0g/L, pH value of2.5, HP-β-CD of0.015mol/L, L-DBTA of0.70mol/L and the air flow rate of30mL/min, flotation time of2h, the enantiomeric excess (e.e.%) and separation factor (a) were29.50%and2.47respectively. Meanwhile, the possible mechanisms of chiral selectors and H2A in the two phases for reaction in the separation process was discussed.(2) Aqueous two-phase flotation (ATPF), a co-technology of solvent sublation and aqueous two-phase system, is often used in bioseparation. In this work, it was used in the chiral separation field by using rac-H2A as model enantiomers. Based on polyethyleneglycol (PEG)/salts system, a series of ATPF systems were employed and their contributions to the enantiosepatation were investigated. Furthermore, using HP-β-CD as chiral selector, many factors such as the composition of phases, pH in bottom phase, air flow rate and flotation time were studied. The results showed that α was1.99and e.e.%was23.49%with the (NH4)2SO4of20%, PEG of40%, HP-β-CD concentration of0.015mol/L, pH value of2.5in the bottom phase, air flow rate of20mL/min and flotation time of1h. Finally, the most reasonable mechanisms for H2A enantioseparation in ATPF system were proposed.(3) Herein, the bubble fractionation was developed for the enantioseparation of rac-H2A. In current work, L-DBTA, sodium lauryl sulfate (SDS) and n-octanol was used as chiral selector, foamer and organic solvent respectively. Here it is shown that the efficiency of the enantioseparation depends strongly on a number of process conditions, including the types and concentrations of chiral selectors, the concentrations of the SDS, pH, air flow rate and reflux time. Under the selected optimal conditions:Concentration of H2A of1.0g/L, SDS of0.40mg/mL, L-DBTA of0.50mol/L, pH value of2.5in the aqueous phase, air flow rate of50mL/min and reflux time of3h, α and e.e.%reached3.16and38.45%, respectively. Finally, the differences between three technologies were discussed.