Functionalization of Phenols Using a Biomimetic Couple of Sodium Nitrite/Hydrogen Peroxide in an Acidic Medium

Sodium nitrite and hydrogen peroxide are ubiquitous in bioorganic and environmental chemistry, and their role has been exceptionally important and under continuous investigation. Sodium nitrite is a potential source of cytotoxic peroxynitrite in biological systems, while in a tandem with hydrogen peroxide it may serve as a precursor of mutagenic aromatic nitro compounds in the environment. A biomimetic couple of sodium nitrite and an aqueous solution of hydrogen peroxide was utilized for the transformation of phenols in an acidic medium. Phenols were regioselectively converted into the corresponding nitro derivatives; the sterically hindered phenols of vitamin E type were oxidized into the quinone derivatives. This is an indication that vitamin E and its derivatives can be good nitrite scavengers. Cresols were transformed to the mixture of mono- and dinitro derivatives; the o-substitution was substantial. Regioselectivity of nitration of 3,4-dialkyl substituted phenols was in accordance with the Mills-Nixon effect; estrone was converted into a mixture of its 2- and 4-nitro analogues. Nitration of phenols obviously encountered a single electron transfer, because the transformation was completely suppressed in the presence of a free radical TEMPO. The most likely nitrating agent was nitronium ion derived from nitrogen dioxide. The NaNO2/H2O2/H2SO4 system differs from the 'classic' HNO3/H2SO4 system, since a considerably different selectivity was established.