Separation of nonracemic mixtures of enantiomers by achiral simulated moving bed chromatography

A continuous process for isolating pure enantiomers from nonracemic mixtures by achiral multicolumn chromatography has been developed. The mechanism of the separation was based on self-disproportionation of enantiomers (SDE). This phenomenon relies on the formation of homochiral and heterochiral associates that differ in adsorption behavior. A standard four-zone simulated moving bed (SMB) unit was exploited for process realization, in which the target enantiomer was collected in the raffinate outlet, and the unresolved fraction of both enantiomers was collected in the extract outlet. Separation was performed in silica gel columns for a model mixture of methyl p-tolyl sulfoxide enantiomers, in which S-methyl p-tolyl sulfoxide was the target enantiomer. Systematic experiments were performed to assess the influence of the operating conditions on the process performance, including the flowrates in the SMB zones, the switching time, the feed concentration, and the enantiomeric excess of the feed mixture. The product yield obtained in the experimental runs varied from 14 to 73%, the purity from 81% to 100%, and the productivity from 15 to 99 g per liter of the total column volume per day. The process design was supported by a mathematical model that accounted for the specificity of the SDE-driven separation. The process was found to be feasible, reproducible, and predictable. It can be applied in industrial production to isolate the target enantiomer from nonracemic mixtures obtained from asymmetric synthesis and is seen as an attractive alternative to enantioselective chromatography using expensive chiral stationary phases.