Temperature- and moisture-dependent phase changes in crystal forms of barbituric acid

The dihydrate of barbituric acid (BAc) and its dehydration product, form II were investigated by means of moisture sorption analysis, hot-stage microscopy, differential scanning calorimetry, thermogravimetry, solution calorimetry, IR- and Raman-spectroscopy as well as powder X-ray diffraction. The dihydrate desolvates already at and below 50% relative humidity (RH) at 25 °C whereas form II is stable up to 80% RH, where it transforms back to the dihydrate. The thermal dehydration of barbituric acid dihydrate (BAc-H2) is a single step, nucleation controlled process. The peritectic reaction of the hydrate was measured at 77 °C and a transformation enthalpy of ΔtrsHH2-II = 17.3 kJ mol−1 was calculated for the interconversion between the hydrate and form II. An almost identical value of 17.0 kJ mol−1 was obtained from solution calorimetry in water as solvent (ΔsolHH2 = 41.5, ΔsolHII = 24.5 kJ mol−1). Additionally a high-temperature form (HT-form) of BAc, which is enantiotropically related to form II and unstable at ambient conditions has been characterized. Furthermore, we observed that grinding of BAc with potassium bromide (KBr) induces a tautomeric change. Therefore, IR-spectra recorded with KBr-discs usually display a mixture of tautomers, whereas the IR-spectra of the pure trioxo-form of BAc are obtained if alternative preparation techniques are used.