Racemic Compound, Conglomerate, or Solid Solution: Phase Diagram Screening of Chiral Compounds

Crystallization in racemic solutions usually results in a racemic compound, a conglomerate or a solid solution. Resolution of a chiral compound strongly depends on the kind of solid state that it forms. Solid−liquid equilibria are related to the prevailing solid state of the chiral compound. A phase diagram screening of enantiomer mixtures in solution can therefore give important indications on the possibility of chiral resolution through crystallization. We describe a new simple and straightforward phase diagram screening method for chiral compounds in solution. Rather than determining the saturation concentration at a certain temperature, we more conveniently determined the saturation temperature of a certain solution composition. A number of chiral compounds were tested with the new method. Asparagine in water behaves as a conglomerate system, ibuprofen in hexane shows racemic compound/enantiopure compound formation, and atenolol shows solid solution behavior, consistent with observations elsewhere. Additionally, the method results in the ternary phase diagram of both enantiomers in a solution which may enable separation methods to be identified and designed.