Radical, Not Ionic: The Mechanochemical Zincke Nitration of Phenols

ABSTRACT Nitrite‐mediated nitration of phenols is synthetically valuable, yet the mechanism of the classical Zincke nitration has remained insufficiently defined. Here, we show that nitrous acid, generated in situ from NaNO 2 and NaHSO 4 under liquid‐assisted vibrational mechanochemical conditions, enables both direct nitration of phenols and ipso nitration of halogenated phenols. The protocol applies to simple, substituted, electron‐rich, polycyclic and biologically relevant phenols while reproducing the halogen‐displacement reactivity historically associated with the Zincke nitration. Across 50 phenolic substrates, with isolated yields up to 98%, this mechanochemical platform extends Zincke‐type halogen‐displacement chemistry and makes phenoxyl‐radical oxidative pathways experimentally accessible under a solvent‐minimised regime. Atmosphere‐controlled experiments, NO x ‐transfer studies, anisole controls, EPR detection of phenoxyl‐type radicals and hybrid DFT‐D3 calculations support a pathway involving O ‐nitrosation, aryl nitrite fragmentation, aerobic NO‐to‐NO 2 oxidation and radical coupling. These results recast the Zincke nitration as an open‐shell nitration manifold and show that mechanochemistry can render experimentally readable mechanistic features that are difficult to resolve under conventional solution conditions.