Solvent-free and eco-friendly green protocol for N-Boc Protection of amines using picric acid as a catalyst

Abstract

We have developed an environmentally conscious green protocol to protect amine functional groups in drug discovery and the total synthesis of biologically active natural products. This method utilizes di-tert-butyl dicarbonate ((Boc)₂O) to protect aromatic and aliphatic amines, with readily available picric acid (2 mol%) serving as a Brønsted acid catalyst. This approach enables rapid and high-yield (up to 98 %) protection of amines under completely solvent-free and eco-friendly conditions, thereby promoting a cleaner and more sustainable synthetic process.