Structural Landscape of 2-Aminopyridine Derivatives: Chains or Dimers?

This study examines the structural landscape of 14 crystal structures across two acetylated series of 2-aminopyridine derivatives (5-NO2 and 3-Cl, 5-CF3), which often display diverse solid-state interactions that complicate the prediction of supramolecular self-assembly. Comparative analysis of the NO2 series revealed that sterics alone has a significant impact on the formation of supramolecular assemblies in this family of compounds, as increasing steric demand shifts the bonding pattern from N–H···C═O chains to N–H···N(pyridine) dimers. In contrast, in the second series (3-Cl, 5-CF3), infinite N–H···O═C chains were present in all structures, indicating that increasing the steric factor does not affect the molecular assemblies in this series. Rather, this series demonstrated that the charge of pyridine nitrogen has a significant influence on the formation of supramolecular assemblies. Overall, these two series indicated that both sterics and charge have a great impact on the determination of final supramolecular assembly, and subtle changes in the structure were found to have a significant impact on solid-state assembly. In addition, infrared (IR) spectroscopy was shown to be a reliable tool for distinguishing between different hydrogen-bonding modes in the solid-state acetylated derivatives of 2-aminopyridines.