Solubility and Crystallization Studies of Picolinic Acid

Abstract

Solubility and crystallization studies of a monocarboxylic derivative of pyridine, picolinic acid (2-pyridinecarboxylic acid), were undertaken as a need for new data in the literature was identified. Moreover, comparative studies of structurally related small molecules, such as these pyridinecarboxylic acid isomers (picolinic acid (PA), nicotinic acid (NA, also known as Niacin or vitamin B3), and isonicotinic acid (IA)), can contribute to a larger goal of identifying optimal crystallization conditions. Indeed, vitamin B3 has been thoroughly explored in literature, whilst IA and, particularly, PA have received less attention. Hence, results on both the solubility (obtained through the gravimetric method) and solid-state structure (investigated by means of PXRD) of PA, at different temperatures, in three polar solvents: water, ethanol (both protic solvents) and acetonitrile (aprotic solvent) are presented in this work. These results indicate that PA is very soluble in water (for T ≈ 293 K, CPA ≈ 862.5 g·kg−1), way less soluble in ethanol (CPA ≈ 57.1 g·kg−1), and even less in acetonitrile (CPA ≈ 17.0 g·kg−1). The crystallization outcome was analyzed in comparison with its family of compounds data, revealing that two polymorphic forms were identifiable for PA, and that no hydrates or solvates were found.