AbstractThermodynamic proton ionization constants,TpKa, of methyl trifluoroacetoacetate (HMTAA), ethyltrifluoroacetoacetate (HETAA) and ethylpentafluoropropionylacetate (HEPPA) have been determined in 10–50% dioxane‐water mixtures at 25 and 35 ± 0.1°C applying an empirical pH correction for mixed aqueous‐organic media. TheTpKavalues are calculated by subjecting the experimental data to rigorous weighted least‐squares analysis. Further, a least‐squares extrapolation technique is applied to evaluateTpKain pure water (0% dioxane). All the three ligands are weak monoprotonic acids with theirTpKabetween 6.0 and 9.0. Plots ofTpKawith the reciprocal of the dielectric constants of the medium are not linear but plots ofTpKavs. mole fraction of dioxane are linear at a given temperature. Values of standard free energy (ΔG°), enthalpy (ΔH°) and entropy (ΔS°) changes, associated with their ionization are also computed. Temperature, medium and substituent effects are