A Bifunctional Phosphoramidic Acid Functionalized Magnetic Nanocatalyst for One-Pot Synthesis of 1H-Naphtho[1,2-e][1,3]oxazine

Abstract

A bifunctional magnetic nanocatalyst, Fe₃O₄-L-proline-PO₃H₂, was developed and applied for the efficient one-pot synthesis of 1H-naphtho[1,2-e][1,3]oxazine derivatives through a multicomponent reaction of β-naphthol, pyrazin-2-amine, aromatic aldehydes, and formaldehyde. The catalyst was designed to combine accessible Brønsted acidic phosphoramidic acid sites with the organocatalytic functionality of L-proline, providing a cooperative acidic-basic environment for substrate activation. Structural and morphological characterization confirmed the successful functionalization of the Fe₃O₄ magnetic core and the formation of nanoscale particles. Under optimized solvent-free conditions, the catalyst afforded the desired naphthooxazine derivatives in good to excellent yields (80%–93%) without isolation of the Betti base intermediate. The magnetic catalyst was readily recovered by external magnetic separation and reused for four consecutive cycles with acceptable retention of catalytic activity. The combination of one-pot synthesis, operational simplicity, catalyst recyclability, and reduced solvent consumption highlights the potential of this bifunctional magnetic catalyst as a sustainable approach for the synthesis of biologically relevant naphthooxazine scaffolds.