Structure and intermolecular interactions of the rare amide–pyridine synthon: a cocrystal of nicotinamide and 2-chloro-3-hydroxypyridine

Abstract

Nicotinamide (Nico) and derivatives of pyridine are important materials in both the pharmaceutical and agrochemical industries. In the 21st century, pyridine-based agrochemical products achieved commercial success because of their structural diversity and different modes of action that can be explored to improve the effectiveness of the compounds. In this article, we explore the cocrystallization of nicotinamide/isonicotinamide and substituted pyridines and their synthons to understand their ease of formation. A cocrystal of Nico and 2-chloro-3-hydroxypyridine (2Cl3OHPY) was synthesized using solution and mechanochemical methods, and characterized by X-ray diffraction. The structural stability and intermolecular interaction of the (Nico)·(2Cl3OHPY) cocrystal were investigated using differential scanning calorimetry (DSC) and density functional theory (DFT). The cocrystal has strong chain (N—H...N), dimer (N—H...O) and discrete (N—H...O) hydrogen bonds with energy strengths of −31.21, −66.99 and −36.82 kJ mol −1 , respectively, and a short C—H...π bond that builds a twisted three-dimensional structure (viewed along the c axis) and stabilizes the crystal packing. The results show that the compound is chemically stable, and the two dominating interactions are electrostatic and dispersion energies. An analysis of the aromatic amide and pyridine synthon in the CSD reveals the presence of close supporting interactions that strengthen the N—H...N hydrogen bond. The understanding of the structural properties and intermolecular interactions in the (Nico)·(2Cl3OHPY) cocrystal and NH 2 ...N py synthon provided in this study could be used to design materials for different applications, including pigments, explosives, drugs, agrochemicals and food additives.