Prediction of Enantioseparation Efficiency of Chiral Mandelic Acid in Diastereomeric Crystallization Using a Quartz Crystal Microbalance

KeyWord:chiral recognition  quartz crystal microbalance  diastereomeric crystallization  resolving agent  L phenylalanine  mandelic acid

Abstract:

      A quartz crystal microbalance(QCM) chiral recognition method was used to predict the chiral recognizability of a chiral selector for a racemate.The chiral selector of L phenylalanine(L Phe) was immobilized on the surface of a QCM sensor by a two step assembly procedure.The L Phe modified sensor surface was characterized using several techniques,including resonant frequency detection,the contact angle and X ray photoelectron spectroscopy measurements.The chiral recognizability of the L Phe modified QCM sensor for L mandelic acid(MA) was examined by the vapor diffused molecular assembly reaction technique,and the chiral discrimination factor between L and D MA was obtained to be about 8.The practical diastereomeric crystallization resolution of a MA racemic mixture was then carried out using L Phe as resolving agent.The different properties of the diastereomer crystals of L Phe-L MA and L Phe-D MA were confirmed by HPLC,morphology and DSC detection.The factors influencing the diastereomeric crystallization resolution were investigated.Under the optimal conditions,the results showed that the diastereomeric crystallization separation of racemate MA with L Phe as resolving agent matched well with that by the QCM chiral recognition method.Therefore,the proposed method using QCM chiral recognition can offer a simple solution to the challenge of screening a resolving agent for diastereomeric crystallization.