Anodic functionalisation in synthesis. Part 1. Methoxylation of methyl-substituted benzene and anisole derivatives, and the synthesis of aromatic aldehydes by anodic oxidation

Abstract

The anodic oxidation in methanol of a series of alkylanisoles and hydroquinone ethers, and of p-xylene has been studied. It was established that the initial step in the product formation always involves direct anodic oxidation of the aromatic compound to the corresponding cation radical. If the electrolysis is conducted under conditions where formation of methoxyl radicals also takes place (platinum anode, supporting electrolyte NaOMe) nuclear methoxylation dominates. Substitution in the nucleus of the aromatic compound presumably occurs either by nucleophilic attack of a methoxide ion on the anodically generated cation radical or by a coupling reaction between the latter and an anodically generated methoxyl radical. If the electrolysis is conducted under conditions where formation of methoxyl radicals does not take place (carbon or platinum anode with supporting electrolyte LiBF4) side-chain oxidation of p-alkylanisoles and p-xylene, with the formation of benzyl ethers, benzaldehyde dimethyl acetals, or ortho-esters of benzoic acids becomes important. This side-chain oxidation occurs via nucleophilic attack of methanol on a benzyl cation formed by deprotonation–anodic oxidation of the initially formed cation radical. Phenol ether cation radicals without p-alkyl substituents under these conditions either dimerise or undergo nuclear methoxylation via nucleophilic attack of methanol on the cation radical.