Synthesis and crystal structures of 3,6-dihydroxypicolinic acid and its labile intermediate dipotassium 3-hydroxy-6-(sulfonatooxy)pyridine-2-carboxylate monohydrate

Abstract

A simplified two-step synthesis of 3,6-dihydroxypicolinic acid (3-hydroxy-6-oxo-1,6-dihydropyridine-2-carboxylic acid), C6H5NO4 (II), an intermediate in the metabolism of picolinic acid, is described. The crystal structure of II, along with that of a labile intermediate, dipotassium 3-hydroxy-6-(sulfonatooxy)pyridine-2-carboxylate monohydrate, 2K+·C6H3NO7S2−·H2O (I), is also described. Compound I comprises a pyridine ring with carboxylate, hydroxyl (connected by an intramolecular O—H...O hydrogen bond), and sulfate groups at the 2-, 3-, and 6-positions, respectively, along with two potassium cations for charge balance and one water molecule of crystallization. These components are connected into a three-dimensional network by O—H...O hydrogen bonds arising from the water molecule, C—H...O interactions and π–π stacking of pyridine rings. In II, the ring nitrogen atom is protonated, with charge balance provided by the carboxylate group (i.e., a zwitterion). The intramolecular O—H...O hydrogen bond observed in I is preserved in II. Crystals of II have unusual space-group symmetry of type Abm2 in which extended planar networks of O—H...O and N—H...O hydrogen-bonded molecules form sheets lying parallel to the ac plane, constrained to b = 0.25 (and 0.75). The structure was refined as a 50:50 inversion twin. A minor disorder component was modeled by reflection of the major component across a mirror plane perpendicular to c.