2-pyridones are an important class of compounds among the N-heterocycles due to the abundant presence of their structural derivatives in many biologically active compounds. The synthesis of 2-pyridone derivatives (compounds 3A-3C) involves the condensation of aldehyde, malononitrile, and ethyl acetoacetate by a base-catalyzed reaction. Heterocyclic ring rearrangements were carried out using the simplest acid as a catalyst to produce hydroaromatic compounds, followed by dehydrogenation to yield the corresponding aromatic analogues. A sample of the crystals obtained from the synthesized compounds 3A-3C were studied to explore the types of hydrogen bonding and other intermolecular interactions involved in the supramolecular assemblies. Hirsheld surface analyses were also conducted to support the weak interactions and investigate their contributions within the supramolecular assemblies. In silico studies were also performed on the molecular recognition and ADMET properties of the compounds to reveal the most promising compounds for drug development.