(139c) Designing Rules for Continuous Separation of Enantiomers By Orthogonal Electrochromatography

The separation of enantiomers in a continuous manner represents a nontrivial task. Identical physical properties of an enantiomeric pair render the standard separation methods unusable, and its separation traditionally relies on the use of a chiral environment. Here, we focus on the method of continuous steady-state separation of enantiomers of mandelic acid in a chromatography column packed by a chiral sorbent. We consider the orthogonal orientation of the pressure and electric field gradients, i.e., the driving forces of the separation process. The transport of solutes in a mobile phase and a porous stationary phase is analyzed. We describe the behavior of mandelic acid inside porous particles by introducing a pseudo-homogeneous model in which the solute binding to the solid phase effectively decreases the diffusivity of the solute. For simplicity, the mandelic acid partitioning between the liquid and solid phase was described by a linear isotherm. However, the mathematical model can be modified using nonlinear adsorption isotherms. The model only requires the knowledge about the equilibrium relationship between the solute concentrations in the solid and liquid phases. Two local balances coupled through the overall mass transport coefficient model the mandelic acid transport inside both pseudo-homogeneous environment and mobile phase. The model equations are numerically analyzed in spatially two- and three-dimensional domains and the separation efficiency of mandelic acid is determined in the parametric space of the control and other parameters. More importantly, we derived simplified algebraic expressions determining the concentration trajectories of mandelic acid under the assumptions of phase equilibrium and neglected diffusion/dispersion transport. These expressions may assist in optimizing the geometry of an orthogonally operating electrochromatographic device and setting the control parameters such as the applied voltage or pressure difference. The predictions based on the simplified expressions are in good agreement with both available experimental observations and numerical simulations of the full model. Finally, we show that orthogonal electrochromatography can separate enantiomers continuously in a steady-state regime under optimized operating conditions. The separation efficiency strongly depends on the enantioselectivity of the stationary phase. Our results offer basic designing rules for orthogonal electrochromatographic devices that can be integrated in continuously operating micro- or milli-plants for the continuous synthesis and separation of pharmaceuticals and other special chemicals.

References

• PÅ™ibyl, M.; Izák, P.; Slouka, Z.: A mathematical model of a lateral electrochromatography device for continuous chiral separation, Separation and Purification Technology 2022, 282, 120033.

Acknowledgement: The author thanks for the support by the grant of the Czech Science Foundation (grant no. 20-09980S).