Deracemization of a Racemic Compound via Its Conglomerate-Forming Salt Using Temperature Cycling

Abstract

Salts of chiral molecules, which originally crystallize as racemic compounds, could form conglomerates. The utilization of such conglomerate salts, as intermediates for the deracemization of corresponding racemic compounds, expands the theoretical application range of Viedma Ripening by roughly 10-fold. In the present study, the use of temperature cycling on conglomerate forming salts as an alternative technique for Viedma Ripening was studied. The racemic compound Phenylalanine (Phe) was successfully deracemized via its conglomerate-forming salt with 2,5-xylenesulfonic acid (XSA) by continuous heating–cooling cycles applied to its suspension in glacial acetic acid, coupled with a solution racemization reaction. In addition, the dependence of the deracemization rate on the operational parameters was studied. Enhanced racemization reaction kinetics, either by a larger amount of free amino acid or by a higher concentration of catalyst, was shown to accelerate the deracemization process. It seems to indicate...