Polymorphism and hydrated states in 5-nitrouracil crystallized from aqueous solution

The crystallization of 5-nitrouracil (5NU) frompure aqueous solution yields two anhydrous polymorphs and amonohydrate depending on the temperature at which theprocess is carried out. 5NU mimics true polymorphism in that,when retained in aqueous solution, both metastable (anhydrous)forms undergo solvent mediated phase transformations(SMPTs) into the more thermodynamically stable hydratedform as would be predicted by Ostwald’s rule of stages. Thephase transformations can occur either in the classical mannerof dissolution and recrystallization or, in one case, may in somecircumstances be nucleated and morphologically templated bythe original crystalline form. There is no appearance fromaqueous solution of a known third acentric anhydrous form,previously prepared from acetonitrile solutions. Preliminary experiments suggest this nonappearance may result from therelatively high solubility of this form in aqueous solution.