Dissociation Constant and Solubility of (S)‑2-Hydroxy-4-phenylbutyric Acid

The dissociation constant (pK a) of (S)-2-hydroxy-4-phenylbutyric acid ((S)-HPBA) was determined at 298.2 K by potentiometric titration. (S)-HPBA exhibits a pK a value of 3.81. The solubility of (S)-HPBA in toluene from (288.2 to 343.2) K, in water from (283.2 to 333.2) K, and in ethyl acetate from (278.2 to 313.2) K was measured by the steady-state method. The solubility in all selected solvents increases with the increase of temperature. The solubility of (S)-HPBA in ethyl acetate is much greater than that in water or toluene. Water was found to be a fine alternative to toluene for crystallizing (S)-HPBA and ethyl acetate to be a suitable extraction solvent of (S)-HPBA in the pharmaceutical industry. The experimental solubility data were correlated with the modified Apelblat, Redlich–Kister, Wilson, and universal quasichemical activity coefficient (UNIQUAC) equations, respectively. The Wilson, Redlich–Kister, and modified Apelblat equations show better agreement with the experimental solubility data of (S)-HPBA in toluene, water, and ethyl acetate, respectively. The solubility of (S)-HPBA in aqueous solutions over the pH range from 1.48 to 5.45 at 298.2 K was also determined by the steady-state method, and the corresponding solubility data were separately fitted well with a semi-Henderson–Hasselbalch equation (pH ≤ 4.0) and a linear equation (pH > 4.0).