Aqueous solubility study of salts of benzylamine derivatives and p-substituted benzoic acid derivatives using X-ray crystallographic analysis

Twenty two p-substituted benzoic acid derivates were used to prepare salts of N-methylbenzylamine (II) and NN-dimethylbenzylamine (III), respectively. Only five salts of (II) and two salts of (III) were obtained in a crystalline state. The solubility of these salts was orders of magnitude higher than those reported for the corresponding salts of benzylamine (I). Thermal analysis indicated that the increased solubility was caused by reduced crystal lattice energy, which was most likely due to the reduced number of strong hydrogen bonds of the salt of (II) and (III). X-ray crystallographic analysis of p-hydroxybenzoic acid salt of (I), (II) and (III) suggested that the reduced number of hydrogen bonds caused the apparent higher solubility. Further analyses of seven salts of (I) were performed. It was not possible to identify any relationship between the number of hydrogen bonds and the corresponding solubility of the salts. (C) 2003 Elsevier B.V. All rights reserved.