Polymorphism and Hydrated States in 5‑Nitrouracil Crystallized from Aqueous Solution

The crystallization of 5-nitrouracil (5NU) from pure
aqueous solution
yields two anhydrous polymorphs and a monohydrate depending on the
temperature at which the process 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 hydrated form as would be predicted
by Ostwald’s rule of stages. The phase transformations can
occur either in the classical manner of dissolution and recrystallization
or, in one case, may in some circumstances be nucleated and morphologically
templated by the original crystalline form. There is no appearance
from aqueous solution of a known third acentric anhydrous form, previously
prepared from acetonitrile solutions. Preliminary experiments suggest
this nonappearance may result from the relatively high solubility
of this form in aqueous solution.