Synthesis of New Coumarin-3-carboxamides and Theoretical Study of the Synthesized Compounds

Abstract

Coumarin derivatives exhibit significant biological and pharmacological activities, motivating the design of new coumarin-based compounds. This study aimed to synthesize novel coumarin-3-carboxamides using a simple and efficient multicomponent reaction, and to investigate their structural and electronic properties through theoretical calculations. Quantum theoretical studies on compounds 4a, 4b, and 4c were performed at the B3LYP level of theory with the 6-311+G** basis set. The optimized geometric parameters were compared with experimental data. The structure of the compounds was confirmed by IR, 1 H NMR, 13C NMR, and elemental analysis. Further computational analyses were conducted to predict the IR spectra, 1 H NMR, and 13C NMR chemical shifts in the ground state. The study also included an examination of the frontier molecular orbitals (FMOs), total density of states (DOS), and thermodynamic parameters. The theoretical and experimental results demonstrated excellent agreement, confirming the reliability of the computational models used. The target coumarin-3-carboxamides were synthesized via a three-component condensation of salicylaldehyde derivatives, dimethyl malonate, and N-aminophthalimide in refluxing ethanol, catalyzed by iodine and piperidine. The structures of the synthesized compounds were confirmed using IR spectroscopy, 1 H and ¹³C NMR, and elemental analysis. Quantum chemical calculations were performed at the B3LYP/6-311+G** level to optimize geometric parameters, predict IR and NMR spectra, and analyze frontier molecular orbitals (FMOs), density of states (DOS), and thermodynamic properties. The synthesis proceeded with good yields, and experimental characterization confirmed the proposed structures. Theoretical calculations showed excellent agreement with experimental data, validating the computational models. FMOs and DOS analyses provided insight into electronic distributions and stability, while predicted spectroscopic properties closely matched the measured spectra. The combination of experimental and computational results allowed a comprehensive understanding of the structural and electronic characteristics of the synthesized coumarin-3- carboxamides. These findings highlight the reliability of the chosen theoretical methods and suggest potential applicability of these compounds in further chemical and pharmaceutical research. A convenient method for synthesizing coumarin-3-carboxamides was established, and theoretical studies successfully complemented experimental findings. The integrated approach confirms the structural integrity and electronic features of the compounds, providing a foundation for future exploration of their properties and applications.