Determination of the solubilities of crystalline solids in solvent media that induce phase changes: Solubilities of 1,2-dialkyl-3-hydroxy-4-pyridones and their formic acid solvates in formic acid and water

Abstract

Problems associated with the determination of the solubilities of solvates and of nonsolvates which undergo phase transformation in the presence of an interacting solvent are discussed. When determining the solubility of a nonsolvate in an interacting solvent, a solvate may be formed resulting in a reduced equilibrium solubility corresponding to that of the solvate. Similarly, when determining the solubility of a solvate in a different solvent, a new solvate or the nonsolvate may be formed resulting in a reduced equilibrium solubility corresponding to that of the new phase. A useful extrapolation technique is developed to overcome the problems resulting from the solvation of nonsolvates in the solvent of crystallization and from the desolvation of solvates in water, often observed during the measurement of equilibrium solubilities by the equilibration method. A thermodynamic cycle analogous to Hess's law but based on free energies is used to predict the theoretical solubility of the solvates in water, especially those which are inaccessible by both the equilibration and the extrapolation methods. The model systems employed are 1,2-dialkyl-3-hydroxy-4-pyridones which form 1:1 formic acid solvates in the presence of formic acid and the 1:1 formic acid solvates which produce the corresponding unsolvated compound in the presence of water. There is good agreement between the solubility values measured by equilibration and derived from the extrapolation method and between those derived from the extrapolation method and calculated by means of the thermodynamic cycle.