The thermodynamic properties, phase behavior, and kinetics of polymorphic transformations of racemic (DL-) and enantiopure (L-) menthol were studied using a combination of advanced experimental techniques, including static vapor pressure measurements, adiabatic calorimetry, Tian-Calvet calorimetry, differential scanning calorimetry (DSC), and variable-temperature X-ray powder diffraction. Several concomitant polymorphs (α, β, γ, and δ forms) were observed and studied. A continuous transformation to the stable α form was detected by DSC and monitored in detail using X-ray powder diffraction. A long-term coexistence of the stable crystalline form with the liquid phase was observed. The vapor pressure measurements of both compounds were performed using two static apparatus over a temperature range from 274 K to 363 K. Condensed-phase heat capacities were measured by adiabatic and Tian-Calvet calorimetry in the wide temperature interval from 5 K to 368 K. Experimental data of L- and DL-menthol are compared mutually as well as with available literature results. The thermodynamic functions of crystalline and liquid L-menthol between 0 K and 370 K were calculated from the calorimetric results. The thermodynamic properties in the ideal-gas state were obtained by combining statistical thermodynamics and quantum chemical calculations based on a thorough conformational analysis. Calculated ideal-gas heat capacities and experimental data on vapor pressure and condensed-phase heat capacity were treated simultaneously to obtain a consistent thermodynamic description. Based on the obtained results, the phase diagrams of L-menthol and DL-menthol were suggested.
Keywords: heat capacity; ideal gas; menthol; monoterpenoids; statistical thermodynamics; thermodynamic properties; vapor pressure; variable-temperature XRPD.