Polymorphism in 4′-Hydroxyacetophenone: Structure and Energetics

A new polymorph of 4′-hydroxyacetophenone (form I, monoclinic, P 2 1 / c, Z ′ = 1) was isolated and characterized. The structural differences between this phase and the previously known one (form II, orthorhombic, P 2 1 2 1 2 1, Z ′ = 2) were investigated by X-ray diffraction. The two polymorphs exhibit distinct packing features and, at the molecular level, they seem to differ by the relative conformations of the OH and C(O)CH 3 groups. The stability domains of the two phases from 298.15 K to the fusion temperature were also studied by a variety of thermodynamic methods and by density functional theory calculations. On the basis of the obtained results, p − T and Δ f G m o − T phase diagrams for 4′-hydroxyacetophenone were defined. Differential scanning calorimetry experiments indicated that the system is enantiotropic, with form II first transforming into form I at 351.2 ± 2.7 K, followed by fusion of form I at 381.9 ± 0.1 K. Solution calorimetry demonstrated that form II is more stable than form I at 298.15 K, with Δ trs H m o (II→I) = 0.49 ± 0.13 kJ mol −1 . Despite this small enthalpy difference compared to the thermal energy at 298.15 K ( RT = 2.5 kJ mol −1 ), a sample of form I could be stored at ambient temperature, for at least 1 year, without change. Results of B3LYP/6–31G(d,p) calculations indicated that the most stable conformation of the isolated molecule is also that corresponding to the most stable polymorph of 4′-hydroxyacetophenone at ambient temperature (form II). The computations further suggest that the occurrence of the II → I transition through a simple rotation of the OH group is unlikely. Finally, the fact that the more stable form II has a greater Z′ than the less stable form I contrasts with the recent proposal that high Z ′ polymorphs are metastable precursors of lower Z ′ forms along the crystallization pathway.