Application of Preferential Crystallization for Different Types of Racemic Compounds

A systematic approach was developed and applied to the preferential crystallization of a racemic-conglomerate-forming system in our previous work. In this work, we extended and modified the strategy for two typical types of racemic-compound-forming systems, namely, mandelic acid and ketoprofen, taking into account the crucial different thermodynamics and crystal structure properties between a racemic compound and a conglomerate. System thermodynamic aspects such as binary melting-point phase diagram and ternary solubility phase diagram were measured. The metastable zone widths of mandelic acid with different compositions in water under different cooling rates were determined with a Lasentec focused beam reflectance (FBR) probe. The crystal nucleation and growth kinetics were measured by s -plane analysis. Based on the solubility and the metastable zone width diagram, the maximum limits of practicable operating ranges for conducting preferential crystallization to obtain enantiomerically pure products was defined. Different operating profiles were applied, and the solution supersaturation was analyzed for the crystallization processes. The optical purities, yields, and crystal size distributions of the final products were examined and compared.