Solvates with anomalous low melting points

Abstract

Single crystals of the N,N-dimethylformamide (DMF) solvate (1:1) of flurbiprofen (FBP) were grown for the first time and characterised by X-ray diffraction, IR spectrophotometry, DSC and solution calorimetric methods. The structure may be characterised as a layer-structure, where DMF double-sheets are arranged between FBP double-sheets. The FBP and DMF molecules are linked to each other by a hydrogen bond, which is formed between the hydroxyl group of FBP and the carbonyl group of DMF. The conformation of FBP molecules in the DMF solvate differs from analogous enantiomers in the unsolvated form. The differences are discussed from the point of view of the influence of the nature of the solvent on selective crystallisation of the enantiomers. A peculiarity of the solvate is its low melting point, 37.3±0.2°C, with respect to the unsolvated phase, 113.5±0.2°C. Based on solution enthalpies of the solvated and unsolvated phases dissolved in DMF, the difference in crystal lattice energies, 9.8 kJ mol^-1, was calculated and the difference in entropies, 33 J mol^-1 K^-1 estimated. A possible mechanism explaining the low melting point of the solvate is discussed.