NBS-promoted reactions of symmetrically hindered methylphenols via p-benzoquinone methide

Symmetrically hindered methylphenols 1 react smoothly with NBS to form tran sient intermediates, p-benzoquinone methides (BM), which can be further pro cessed to give hydroxybenzaldehydes in the presence of DMSO. This reaction is initiated by the formation of the phenoxy radical, followed by dispropor tionation to afford BM. None of the side-chain-brominated product is observ ed. The existence of BM is supported by the following observations: the for mation of BM in solution can be monitored by GC and GC-MS; the electrophili c methine part participates in electrophilic aromatic substitution with ani soles to give hydroxybenzylated products 15; and the double bond character of the exocyclic methine plays a role in [4 + 2] cycloaddition with diene t o afford Diels-Alder adducts. In contrast, unsymmetrically hindered or simp le methylphenol (p-cresol) with NBS gives the nuclear brominated products, as usual. The energies of symmetrically hindered BMs, unsymmetrically hinde red BM, and simple BM were calculated using density functional theories. Re lative stabilization energies calculated at the B3LYP/G-31G*//B3LYP/6-31G* level by an isodesmic equation are enhanced 3-6 kcal/mol for symmetrically hindered BMs.