The pressure-temperature phase diagram of dimorphic caffeine: experiment versus topology

The pressure-temperature behavior of anhydrous caffeine's two polymorphs-form II (monoclinic) and form I (trigonal)-was characterized by high-resolution powder diffraction, electron microscopy, differential scanning calorimetry and high-pressure thermal analysis. Measured transition enthalpies are 19 J g⁻¹ for the solid-solid conversion and 109 J g⁻¹ for melting of form I. Direct application of the Clapeyron equation to these state functions yields linear equilibrium relations with slopes of dP/dT = 4.15 MPa K⁻¹ for the I-II equilibrium and 2.6 MPa K⁻¹ for the I-L equilibrium, values that match the direct measurements at different pressures and temperatures in this study and in the literature. The resulting phase diagram shows divergent I-II and I-L lines with increasing pressure, placing caffeine in Bakhuis-Roozeboom's case 2 (overall enantiotropy) and locating the I-II-L triple point at negative pressure, thus metastable. Form I consistently has a larger specific volume than form II, and the volume change on melting follows the typical V_L/V_S ratio of about 1.11 for organic solids. The close agreement between experiment and Clapeyron-based (topological) predictions demonstrates that the topological method correctly captures polymorphic stability across broad pressure and temperature ranges.