An improved approach to the synthesis of tetrahydroindeno[1,2-d] imidazoles: DFT (FT-IR, NMR, NBO, FMO), ADMET, and drug-likeness studies

A new entry into the synthesis of tetrahydroindeno[1,2-d]imidazole compounds 4a-c is based on the reactions isothiocyanate benzene 1 and substituted aniline 2 via condensation with 1H-indene-1,2,3-trione in a one-pot three-component. A wide variety of relevant tetrahydroindeno[1,2-d]imidazole derivatives were obtained with high yields ranging from 97 to 98 % with excellent yields. The synthesized compounds were determined using FT-IR, 1H NMR, 13C NMR, and elemental analysis methods. Moreover, the DFT calculations performed on 4a-c provide additional validations to the experimentally obtained data of the compounds, as well as useful insights on topics such as reactivity trends and physicochemical properties. In this context, in the initial stage, the conformational study was performed and minimum energy structures were determined for 4a-c. The subsequent stage included a comparative analysis of the electronic properties, reactivity tendencies, possible donor–acceptor interactions, and electrostatic surface properties of the mentioned compounds in gas, CHCl3, and DMSO environments. All FT-IR and NMR computations were performed at B3LYP/6–311++G** level for confirmation purposes. The ADMET “Adsorption-Distribution-Metabolism-Excretion-Toxicity”, drug-likeness, and physicochemical characteristics of compounds were evaluated to explore possible suitability for early-stage-drug-design research. © 2025 Elsevier B.V.