Vitamin E Chemistry. Nitration of Non-α-tocopherols: Products and Mechanistic Considerations

In contrast to the α-form permethylated at the aromatic ring, non-α-tocopherols possess free aromatic
ring positions which enable them to act as potent scavengers of electrophiles in vivo and in vitro. In
preparation of enzymatic studies involving peroxynitrite and other nitrating systems, the behavior of
non-α-tocopherols under nitration conditions was studied. The nitration products of β-, γ-, and δ-tocopherol
were identified, comprehensively analytically characterized, and their structure was supported by X-ray
crystal structure analysis on truncated model compounds. Even under more drastic nitration conditions,
no erosion of the stereochemistry at 2-C occurred. The nitrosation of γ-tocopherol and δ-tocopherol was
re-examined, showing the slow oxidation of the initial nitroso products to the corresponding nitro
derivatives by air to be superimposed by a fast equilibrium with the tautomeric ortho-quinone monoxime,
which only in the case of γ-tocopherol released hydroxyl amine at elevated temperatures to afford the
stable ortho-quinone. Mononitration of δ-tocopherol selectively proceeded at position 5. This selectivity
can be explained by the theory of strain-induced bond localization (SIBL) to the quinoid nitration
intermediates. Bisnitration was only insignificantly disfavored by the first nitro group, so that under
normal nitration conditions offering an excess of nitrating species only the bisnitration product was found.