Developing a Sustainable Mechanochemical Route to Bio-Relevant 2-Amino-Indeno-Pyrimidinone Scaffolds

This work demonstrates a highly efficient and environmentally benign synthesis of novel 2-amino-indeno-pyrimidinone analogues via a one-pot, three-component reaction of substituted aldehydes, indane-1,3-dione, and guanidinium hydrochloride. The reaction was conducted under solvent-free conditions using a mortar and pestle grinding technique at room temperature, affording the target compounds in excellent yields (91–97%). All synthesized derivatives were thoroughly characterized by spectroscopic methods, including 1 H NMR, 13 C NMR, and high-resolution mass spectrometry (HRMS). The present methodology offers notable advantages such as mild reaction conditions, catalyst-free operation, simple grinding, short reaction time, exceptional yields, minimal environmental impact, and straightforward workup procedures.