Tailored Engineering of Copper on a Magnetic Fe3O4@β-CD Catalyst: Sustainable Solvent-Free Synthesis of Triazoloindoles and Preliminary Docking Insights

The synthesis of structurally fascinating 4H-1,2,3triazolo1,5-aindoles was accomplished for the first time using a novel heterogeneous magnetic nanocatalyst where copper was tailored on magnetic Fe3O4@β-CD (magnetite@β-cyclodextrin). This process involves the reaction of o-azidobenzaldehyde, secondary amines, and terminal alkynes through a sequential A3 coupling followed by 3 + 2 cycloaddition. This one-pot combinatorial reaction was optimized to obtain high yields (up to 88%) of the respective products under neat conditions at 80 °C with low complexity. The catalyst characterized by powder X-ray diffraction (PXRD), FTIR, field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HR-TEM), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and X-ray photoelectron spectroscopy (XPS) exhibited excellent stability and reusability for at least five consecutive cycles without significant yield loss. Catalyst’s substrate scope was validated via the synthesis of a library of bioactive 4H-1,2,3triazolo1,5-aindole derivatives. The structure of one of the novel molecules was confirmed by single-crystal XRD. In silico molecular docking studies suggest that the synthesized compounds are promising epidermal growth factor receptor (EGFR) inhibitors, exhibiting better scores than known references, indicating preliminary insights into potential bioactivity.