Gradual Changes in the Aromaticity in a Series of Hydroxypyridine-Carboxylic Acid Derivatives and Their Effect on Tautomerism and Crystal Packing

Abstract

The keto−enol tautomerism of hydroxypyridinecarboxylic acid (HPC) derivatives with proton transfer between the hydroxyl or carboxyl oxygen atoms was investigated in the case of three 3-hydroxy-4-pyridine-carboxylic acid (3HPC) and eight 4hydroxy-3-pyridine-carboxylic acid (4HPC) derivatives containing altered pyridine ring substituents. Due to the vicinal position of hydroxyl and carboxylate groups, the hydroxyl proton is involved in an intramolecular H-bond and can very easily transform into the keto or enol tautomer. The proton position was found to correlate with the aromaticity of the pyridine ring, which was described by the Bird index, calculated on the basis of the measured atomic distances. Due to the planar shape of the molecules, π•••π stacking and/or C−O•••π interactions were found in all investigated compounds. The molecular properties along with their main supramolecular interactions were compared. Packing arrangements and the main hydrogen-bonding schemes were further compared by using Hirshfeld surface analysis. In the case of the four N-methyl-substituted 4HPC derivatives, the synthon consisting of hydrogen bonds was preserved in the plane of the molecules despite the presence of the various ring substituents. Pairing the 3HPC and 4HPC derivatives, the corresponding compounds exhibited the same molecular shape but different nitrogen positions in the pyridine ring. This gave us the opportunity to examine how the difference in the electron distribution affects only and exclusively the secondary interactions and the arrangement of the molecules in the crystals. The electrostatic potential was calculated and mapped over the Hirshfeld surface, and the calculations of pairwise interaction energies and total energy frameworks were performed using the B3LYP/6-31G(d,p) energy model.