Intermittent Simulated Moving Bed Processes for Chromatographic Three-Fraction Separation

Simulated moving bed (SMB) chromatography is a well-established technique to resolve racemic mixtures into pure enantiomers. However, the conventional SMB process is restricted to binary separations, and its applicability is therefore limited when impurities are present. In this contribution we address this issue by considering impurities as a third fraction which is separated from the two product streams, i.e. the pure enantiomers, by two novel intermittent SMB (I-SMB) concepts. The process schemes studied consist of four sections, each section comprising only one column, and are straightforward extensions of the original I-SMB process; therefore, the switch time is also divided into two substeps. Substep I is characterized by feed and withdrawal of two product streams, whereas in substep II only pure solvent is introduced to the unit in order to recover the third product stream and to adjust the relative positions of the concentration fronts along the column train. The two concepts presented in this contribution differ in the column configuration and in the withdrawal of the product streams. One process is characterized by withdrawal of the most retained component during substep II, whereas in the other process the least retained species is recovered in the second substep. Consequently, these processes are termed 3S-ISMB and 3W-ISMB, respectively. These process schemes are analyzed in the frame of equilibrium theory under the assumption of linear chromatographic conditions, thus yielding a graphical representation of the region of complete ternary separation similar to classical triangle theory. Furthermore, an experimental study of the 3W-ISMB concept is presented in which a ternary system consisting of a mixture of the enantiomers of gamma-phenyl-gamma-butyrolactone and of the (-)-Troger's Base enantiomer (the impurity in this context) is separated in pure ethanol on the chiral stationary phase Chiralpak AD. These experiments are carried out under linear chromatographic conditions, namely the concentration of each solute is kept constant at 0.5 g/L. A purity of at least 94% for all product streams is achieved, which demonstrates successfully the potential of this novel, three-fraction SMB-like process.