Discovery of New Metastable Polymorphs in a Family of Urea Co-Crystals by Solid-State Mechanochemistry

Members of a homologous family of 1:2 co-crystals comprising even-chain α,ω-dihydroxyalkanes and urea have been reported previously to fall into three well-defined structure types, although surprisingly polymorphism was not observed for any member of this series. Here we report the discovery of the first examples of polymorphism within this family of materials, specifically for 1,6-dihydroxyhexane-(urea)₂ and 1,8-dihydroxyoctane-(urea)₂. The new polymorphs have been prepared by mechanochemical milling, and the crystal structures have been determined directly from powder X-ray diffraction data. On the basis of periodic density functional theory calculations, the new polymorphs are assigned as metastable with respect to the polymorphs reported previously. Under ambient conditions, the new polymorph of 1,6-dihydroxyhexane-(urea)₂ transforms to the previously known polymorph over a matter of days. However, the new polymorph of 1,8-dihydroxyoctane-(urea)₂ has significantly greater kinetic stability, which can be rationalized on the basis of the specific structural reorganization required to transform to the previously known polymorph.