Partial Miscibility of Organic Compounds in the Solid State : The Case of Two Epimers of a Diastereoisomer

The purification that can be attained via crystallisation is on one side governed by kinetic factors such as the growth rate and can on the other hand be limited by thermodynamic factors such as the formation of a solid solution of the impurity with the product. For organic substances, these solid solubilities are difficult to establish, especially for low partial solubilities in the solid state. For the case of the crystallisation of two epimers of a diastereoisomer the formation of partial solid solutions with a solubility limited to approximately 5% and 3% respectively has been shown using both DSC and XRPD measurements. The enthalpies of fusion of the solids are a strong function of the content of the opposite epimer. This can be interpreted with a disruption of bonds in the lattice, a disruption index of di~8 is found. First determinations of the crystal structure of one of the epimers suggest the formation of a solid solution to occur via the replacement of dimers of molecules that are bound by two hydrogen bonds involving the epimeric OH- group and a vicinal phenoxy- group. By replacing dimers, the lattice distortion might be limited. Copyright © 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim [accessed 2013 November 27th