Wallach rearrangement

The Wallach rearrangement is an organic reaction and a rearrangement reaction converting an aromatic azoxy compound with sulfuric acid to an azo compound with one arene ring substituted by an hydroxyl group in the aromatic para position.^[1][2]

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60% to 100% sulfuric acid is required.

Conceptually related reactions are the Fries rearrangement, the Fischer-Hepp rearrangement, the Bamberger rearrangement, the benzidine rearrangement and the Hofmann-Martius rearrangement.

Reaction mechanism

The reaction mechanism for this reaction is not known with great precision despite experimental evidence:

• The primary kinetic isotope effect for the arene proton is close to one excluding the corresponding C-H bond from breaking in the rate-determining step
• The chemical kinetics of the reaction point to involvement of two protons in the reaction: the reaction rate of the rearrangement continues to increase beyond the stage of complete monoprotonation of the substrate.
• Other kinetic evidence identifies the second proton donation as the rate-determining step
• The phenolic oxygen atom in the product is not the oxygen atom in the reactant but provided by solvent, based on isotopic scrambling experiments.
• Furthermore isotope labeling of the N-O nitrogen atom in azoxybenzene gives the azo compound with the ¹⁵N isotope distributed over over both nitrogen atoms indicating a symmetrical intermediate.

A mechanism not inconsistent with these findings is depicted below:

In the first part of the reaction two equivalents of acid tease the oxygen atom away from the azoxy group. The resulting dicationic intermediate 3 with an unusual R-N⁺:::N⁺-R motif in this scheme has been observed by proton NMR in a system of fluoroantimonic acid and azoxybenzene at -50°C ^[3]. In the second part of the reaction the HSO₄^- anion is a nucleophile in a nucleophilic aromatic substitution to 5 followed by hydrolysis to 6.

References