The curious case of the colored crystals of N-substituted 2-oxo-1,2-dihydropyridinyl-3-yl amines and amides: Self-association in the solid state

Abstract

During a previous investigation of pyridone derivatives as inhibitors of glycogen phosphorylase, we observed that some N-substituted 2-oxo-1,2-dihydropyridinyl-3-yl amines and amides exhibited different colors, ranging from red to green to blue to teal. Remarkably, one compound (compound 8) could be crystallized in both a red form and a green form. To try to understand these observations, we have carried out further spectroscopic studies in the solid state and in solution employing UV-visible spectroscopy, NMR spectroscopy, and X-ray crystallography, along with molecular mechanics and DFT calculations on selected compounds. Evidence was obtained in the solid state for the self-association of pyridones into dimeric complexes or near-planar dimers induced by intermolecular hydrogen bonding and possible π-stacking, whereas monomeric structures for two compounds were proposed in chloroform, in agreement with the DFT calculated chemical shifts. In this study, it was determined that the colors observed could not be attributed to hydrogen bonding or possible π-bond stacking in the novel relatively unconjugated pyridone derivatives. A possible explanation for the colors is suggested: a contaminant formed by aerial oxidation of trace amounts of the 3-aminopyridone starting material. This result contrasts with existing literature reports of UV and fluorescence spectra, which indicated distinct coloration for conjugated 2-pyridone compounds. The spectroscopic results, including X-ray structural data for five pyridones, contribute to a deeper understanding of structural interactions in pyridone derivatives.