A Novel One-Pot Three-Component Approach to Orthoaminocarbonitrile Tetrahydronaphthalenes Using Triethylamine (Et3N) as a Highly Efficient and Homogeneous Catalyst under Mild Conditions and Investigating its Anti-Cancer Properties through Molecular Docking Studies and Calculations

An efficient and environmentally friendly method for the one-pot synthesis of ortho-aminocarbonitrile tetrahydronaphthalenes has been developed in the presence of triethylamine (Et3N) as a homogeneous catalyst. The multicomponent reactions of benzaldehydes, cyclohexanone, and malononitrile were carried out under mild conditions to obtain some ortho-aminocarbonitrile tetrahydronaphthalene derivatives. A broad range of structurally diverse benzaldehydes was applied successfully, and the corresponding products (4A-L) were obtained in good to excellent yields (87-98%) in very short times (10-25 minutes). The present approach provides several advantages, including simple workup, high yields, very mild reaction conditions, short reaction times, little catalyst loading, and not requiring specialized equipment. Furthermore, with the help of computational chemistry and drug design methods, the anti-cancer properties of these compounds were studied and investigated. All the synthesized compounds bind to an agonist at the active site of the 3A8P protein, which leads to the inactivation of this protein and produces beneficial effects during cancer treatment. In the synthesized compounds, the ligands establish hydrogen bonds with leucine A:728 residues through nitrogen, which has a very special and vital role in biological sciences and pharmaceutical connections. In this study, it was found that these compounds have the potential to become an oral anti-cancer drug.