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.For a review of previous work see N. I,. \Yeinberg, ' 'I'ecliniques of Electro-organic Synthesis,' P a r t I , 1' . 2 3 7 ; vol. \ r .of ' Technique5 of Organic Chemistry,' ed. :I. \Vt.issbc.rger,

Anodic methoxylation of cinnamate esters

“…If the electrolyses were conducted without base, black polymeric materials were obtained, suggesting that the presence of methoxy radicals formed during the oxidation play an important role in the methoxylation of the intermediate like radical cations as pointed out previously 10 . Without base the intermediates seem to react with each other leading to compounds with higher molecular weight.…”

A Century of Organic Electrochemistry

“…114,115 Methoxylation of alkylbenzenes may take place in the side chain or in the nucleus; 4-methylanisole can thus form methoxybenzyl methyl ether or 1,1,4-trimethoxy-4-methylcyclohexa-2,5-diene depending on the medium; when the electrolysis is conducted under conditions where formation of methoxy radicals also takes place, nuclear methoxylation dominates. 116 The methoxylation of methylbenzenes is of industrial importance; BASF oxidizes substituted toluenes in methanolic solution at a carbon anode in a capillary-gap cell to the substituted benzaldehyde dimethylacetal.…”

Bromide‐Assisted Oxidation of Substituted Phenols with Hydrogen Peroxide to the Corresponding p‐Quinol and p‐Quinol Ethers over WO42−‐Exchanged Layered Double Hydroxides

“…The selective oxidation of substituted phenols to yield 4‐hydroxycyclohexa‐2,5‐dienones ( p ‐quinols) and their ethers has been intensely investigated in view of their applications as antioxidants, antibiotics, and antitumor agents 1. 2 Besides electrolytic3 and photosensitized4 approaches, procedures for quinol preparation require stoichiometric amounts of oxidants, such as Bi III or Tl III salts,5, 6 oxygen at high pressure,7 hydrogen peroxide,8 or particularly electrophilic halogens,9 such as I III reagents, chlorine, or bromine. In view of the risks associated with handling such reactive species, much attention has recently been devoted to the in situ generation of halonium species from harmless halides by using oxygen or hydrogen peroxide 10.…”