Shortcut Model for Describing Isothermal Batch Preferential Crystallization of Conglomerates and Estimating the Productivity

[Image: see text] Preferential crystallization (PC) is a powerful method to separate the enantiomers of chiral molecules that crystallize as conglomerates. The kinetically controlled separation method works in a typically narrow metastable zone. Currently, there are no simple models available that allow estimating the productivity of PC and, thus, the comparison with rivalling resolution techniques. In this Article, we suggest a simple shortcut model (SCM) capable of describing the main features of batch-wise operated PC using three ordinary differential equations originating from the mass balance of the target enantiomer and solvent in the liquid and solid phases. Compared to population balance models, the basis of the SCM is the assumption that the crystals for each enantiomer have the same size, which increases continuously from prespecified initial values. The goal of the model is to describe the initial period of the batch, during which the purity is within the specification required. It is accepted that after reaching this border, the precision of predictions can drop. This Article also illustrates a simple strategy how to parametrize the model based on a few experimental runs of PC. At first, for demonstration purposes, theoretical transients generated using the more rigorous PBE model is analyzed using SCM considering the separation of the enantiomers of dl-threonine. Subsequently, results of an experimental study with the enantiomers of asparagine monohydrate are presented to validate the shortcut model, which is seen as a new valuable tool to quantify more rapidly the productivity of PC and to further promote this elegant technique capable to resolve enantiomers of conglomerate forming chiral systems.