Enantioselective resolution of 4-chloromandelic acid by liquid-liquid extraction using 2-chloro-N-carbobenzyloxy-L-amino acid.

A liquid-liquid extraction resolution of 4-chloro-mandelic acid (4-ClMA) was studied by using 2-chloro-N-carbobenzyloxy-L-amino acid (2-Cl-Z-AA) as a chiral extractant. Important factors affecting the extraction efficiency were investigated, including the type of chiral extractant, pH value of aqueous phase, initial concentration of chiral extractant in organic phase, initial concentration of 4-ClMA in aqueous phase, and resolution temperature. It was observed that the concentration of (R)-4-ClMA was much higher than that of (S)-4-ClMA in organic phase due to a higher stability of the complex formed between (R)-4-ClMA and 2-Cl-Z-AA. A separation factor (α) of 3.05 was obtained at 0.02 mol/L 2-Cl-Z-Valine dissolved in dichloromethane, pH of 2.0, concentration of 4-ClMA of 0.11 mmol/Land T of 296.7K.