Wallach rearrangement

The Wallach rearrangement, named after Otto Wallach, 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. [Otto Wallach and E. Belli, Chem. Ber., 13, 525 (1880) DOI|10.1002/cber.188001301153] ["Catalysis in strongly acidic media and the Wallach rearrangement" Erwin Buncel Acc. Chem. Res.; 1975; 8(4) pp 132 - 139; DOI|10.1021/ar50088a004]

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:

NOTE The curly arrows in intermediate 4 go in the wrong direction.

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 ["Stable carbocations. CXXIX. Mechanism of the benzidine and Wallach rearrangements based on direct observation of dicationic reaction intermediates and related model compounds" George A. Olah, Kenneth Dunne, David P. Kelly, Y. K. Mo J. Am. Chem. Soc.; 1972; 94(21); 7438-7447.DOI| 10.1021/ja00776a029] . 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