Determination of l-Tryptophan Methyl Ester Hydrochloride Solubility in 12 Pure Solvent Systems from 283.15 to 323.15 K

Abstract

Research on the solubility behavior of l-tryptophan methyl ester hydrochloride, an important pharmaceutical intermediate, is necessary for the design of its crystallization and separation processes. The solubility data of l-tryptophan methyl ester hydrochloride were measured by the static gravimetric method in 12 pure solvents (methanol, water, ethanol, n-propanol, n-butanol, isobutanol, sec-butanol, isopropanol, propanone, 2-butanone, ethyl acetate, and acetonitrile) at 283.2–323.2 K and 101.2 kPa. The solubility of l-tryptophan methyl ester hydrochloride in all studied solvents increases with the increase of temperature. In addition, the solubility sequence of l-tryptophan methyl ester hydrochloride at 298.2 K is methanol (0.033403 mol/mol) > water (0.011939 mol/mol) > ethanol (0.007368 mol/mol) > n-propanol (0.003708 mol/mol) > n-butanol (0.002632 mol/mol) > isobutanol (0.001716 mol/mol) > sec-butanol (0.001651 mol/mol) > isopropanol (0.001573 mol/mol) > propanone (0.000605 mol/mol) > 2-butanone (0.000401 mol/mol) > ethyl acetate (0.000074 mol/mol) > acetonitrile (0.000065 mol/mol). Methanol had the highest solubility of 0.033403 mol/mol, while acetonitrile had the lowest solubility of 0.000065 mol/mol. The main factors influencing the solubility behavior include the empirical solvent polarity parameters (ET(30)), hydrogen bonding, and cohesive energy density. Three solubility fitting models were used to correlate the experimental mole fraction solubility data, including the modified Apelblat model, the nonrandom two liquid (NRTL) model, and the Margules model. Furthermore, mixing thermodynamic characteristics of l-tryptophan methyl ester hydrochloride in selected solvents were calculated by the NRTL model, and the results indicated that the mixing process was spontaneous and driven by entropy. In order to choose the best model for l-tryptophan methyl ester hydrochloride, the relative applicability of these models was evaluated by the Akaike Information Criterion (AIC). The study of the solubility of l-tryptophan methyl ester hydrochloride not only enriches the solubility database and provides guidance and basis for crystallization but also provides rich solubility data for machine learning models.