W0236

When Can Fractional Crystallization be Expected to Fail? Carolyn P. Brock, Dept. of Chemistry, Univ. of Kentucky, Lexington, KY 40506-0055, USA.

Fractional crystallization is the method of choice for purification of chemicals produced on a commercial scale. The possibility that impurities might be included in the recrystallized material is a serious concern.

If fractional crystallization fails then at least some of the crystals in the batch may be disordered mixed crystals (or, solid solutions) or ordered stoichiometric compounds (or, cocrystals). Solvates are a special kind of cocrystal.

Searches of the Cambridge Structural Database show that ordered compounds (other than solvates and racemic compounds) are rare unless there is complete or partial transfer of a proton or electron between the two components. Many of the known compounds that are formed from isomers and near isomers are quasiracemates in which the two components are related by an approximate inversion center. Another set of compounds is formed from relatively rigid molecules that have substituents (e.g., hydroxyl groups) that are expected to form good hydrogen bonds.

Disordered mixed crystals are more common than ordered compounds, and these solid solutions probably occur much more often than they are recognized. If two different molecules can occupy about the same space the possibility of a solid solution must be considered.

It seems likely that the probability of compound formation is related to the probability of structures having Z'>1 because in most crystals the size of asymmetric unit is minimized. The relationship of solid-state compound formation to the occurrence of Z'>1 structures in which the independent molecules are different tautomers or conformers will be considered.