Crystallization of the racemic compound and conglomerate of (RS)-2-chloromandelic acid

(RS)-2-Chloromandelic acid is a new example of chiral compounds that can exist as a racemic compound or a conglomerate depending on the crystallization conditions. Two polymorphic racemic compounds and one conglomerate were disclosed and characterized in this work. Commercially available racemic compound Form α can be prepared by crystallization from nonpolar solvents such as toluene. Freeze-drying leads to a conglomerate formation, Form γ. Crystallization from polar solvents always results in a mixture of Form α and Form γ under our experimental conditions. Thermodynamic calculation of the Gibbs free energy of racemic compound formation demonstrates that the conglomerate Form γ is slightly less stable than the racemic compound Form α. The conglomerate has a tendency to transform into racemic compound by a solid-solid transition. Another metastable racemic compound, Form β, was observed as a single crystal grown from methanol. But bulk crystals of Form β were not obtained.