Polymorphism in 4'-Hydroxyacetophenone: Structure and Energetics

Abstract

A new polymorph of 4′-hydroxyacetophenone (form I, monoclinic, P2₁/c, Z′ = 1) was isolated and characterized. The structural differences between this phase and the previously known one (form II, orthorhombic, P2₁2₁2₁, 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)CH3 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_fG_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_trsH_m^o(II→I) = 0.49 ± 0.13 kJ/mol. Despite this small enthalpy difference compared to the thermal energy at 298.15 K (RT = 2.5 kJ/mol), 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.

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