Thermodynamic Characterization of Three Polymorphic Forms of Piracetam

Combustion calorimetry, solution calorimetry, and differential scanning calorimetry (DSC) were used to determine the standard (p° = 0.1 MPa) molar enthalpies of formation of Forms I, II, and III piracetam at 298.15 K, namely, ΔfHm° (C6H10O2N2, cr I) = −520.6 ± 1.6 kJ·mol−1, ΔfHm° (C6H10O2N2, cr II) = −523.8 ± 1.6 kJ·mol−1, and ΔfHm° (C6H10O2N2, cr III) = −524.1 ± 1.6 kJ·mol−1. The enthalpy of formation of gaseous piracetam at 298.15 K was also derived as ΔfHm° (C6H10O2N2, g) = −401.3 ± 2.1 kJ·mol−1, by combining the standard molar enthalpy of formation of Form II piracetam with the corresponding enthalpy of sublimation, ΔsubHm° (C6H10O2N2, cr II) = 122.5 ± 1.4 kJ·mol−1, obtained by drop-sublimation Calvet microcalorimetry and the Knudsen effusion method. The ΔfHm° (C6H10O2N2, g) value was used to assess the corresponding predictions by the B3LYP/cc-pVTZ (−335.3 kJ·mol−1), G3MP2 (−388.7 kJ·mol−1), and CBS-QB3 (−402.8 kJ·mol−1) methods, based on the calculation of the atomization enthalpy of piracetam. Finally, the results of the solution and DSC experiments indicate that the stability hierarchy of Forms I, II, and III piracetam at 298.15 K, for which there was conflicting evidence in the literature, is III > II > I