Abstract
A simplified two-step synthesis of 3,6-di-hydroxy-picolinic acid (3-hy-droxy-6-oxo-1,6-di-hydro-pyridine-2-carb-oxy-lic acid), C6H5NO4 (II), an inter-mediate in the metabolism of picolinic acid, is described. The crystal structure of II, along with that of a labile inter-mediate, dipotassium 3-hy-droxy-6-(sulfonato-oxy)pyridine-2-carboxyl-ate monohydrate, 2K+·C6H3NO7S2-·H2O (I), is also described. Compound I comprises a pyridine ring with carboxyl-ate, hydroxyl (connected by an intra-molecular 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 mol-ecule of crystallization. These components are connected into a three-dimensional network by O-H⋯O hydrogen bonds arising from the water mol-ecule, C-H⋯O inter-actions and π-π stacking of pyridine rings. In II, the ring nitro-gen atom is protonated, with charge balance provided by the carboxyl-ate group (i.e., a zwitterion). The intra-molecular 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 mol-ecules 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.
Highlights
A simplified two-step synthesis of 3,6-dihydroxypicolinic acid (3-hydroxy-6-oxo1,6-dihydropyridine-2-carboxylic acid), C6H5NO4 (II), an intermediate in the metabolism of picolinic acid, is described
Compound I comprises a pyridine ring with carboxylate, hydroxyl, 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—HÁ Á ÁO hydrogen bonds arising from the water molecule, C—HÁ Á ÁO interactions and – stacking of pyridine rings
We report here a two-step synthesis starting with 3-hydroxypicolinic acid by an Elbs oxidation (Behrman, 1988; 2021) and crystal structures of both the intermediate sulfate ester (I) and of 3,6-dihydroxypicolinic acid (II)
Summary
3,6-Dihydroxypicolinic acid (3-hydroxy-6-pyridone-2-carboxylic acid), C6H5NO4, is an intermediate in the metabolism of picolinic acid by several microorganisms (Shukla & Kaul, 1973; Shukla et al, 1977; Qiu et al, 2019). Both give the desired product but we chose the pathway from 3-hydroxypicolinic acid because in the first step, the dipotassium salt of the 6-sulfate ester precipitates from the mixture in an almost pure state. This sulfate ester is extraordinarily sensitive to acid-catalyzed hydrolysis; acidification at room temperature (RT) gives complete hydrolysis in a few minutes. The ester was crystallized from water and 3,6-dihydroxypicolinic acid obtained by hydrolysis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
