Chiral Resolution, Kinetics And Thermodynamics In Preferential Crystallisation
Résumé
In preferential crystallization for chiral resolution, control over solubility in the racemic system plays a major role. In Figure 1, the process of preferential crystallization is demonstrated, for which the presence of a conglomerate (enantiomers crystallize independently in enantiopure crystals) is essential. At the starting point, the racemic mixture is in solution at saturation. Adding a crystalline seed of one of the pure enantiomers causes that enantiomer to supersaturate, which triggers its crystallization and through entrainment more crystal is recuperated than what has been added. Once a concentration imbalance among the enantiomers exists, adding more crystalline racemic mixture will trigger crystallization of the enantiomer that has subsequently become supersaturated. This process is fully depending on thermodynamic parameters such as solubility and supersaturation. Much less is known about the crystallization kinetics of enantiomers and racemic systems. In a paper on L-histidine, pure enantiomer appears to crystallize much faster than racemic crystals. In the photograph on the right DL-histidine racemic crystals are shown after crystallization from the racemic solution. The light-green areas obtained by SHG (second harmonic generation) demonstrate the presence of enantiopure crystallites even though the racemic crystal is thermodynamically stable. Although much work remains to be done, this may open possibilities to use kinetics to 1 steer preferential crystallization. Moreover, using achiral molecules to initiate preferential crystallization will also be discussed.