Willgerodt rearrangement

The Willgerodt rearrangement or Willgerodt reaction is an organic reaction converting an aryl alkyl ketone to the corresponding amide by reaction with ammonium polysulfide.^[1] The formation of the corresponding carboxylic acid is a side reaction. When the alkyl group is an aliphatic chain (n typically 0 to 5), multiple reactions take place with the amide group always ending up at the terminal end.

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An example with modified reagents (sulfur, concentrated ammonium hydroxide and pyridine) is the conversion of acetophenone to phenylacetamide and phenylacetic acid:^[2]

Willgerodt-Kindler reaction

The related Willgerodt-Kindler reaction^[3] takes place with elemental sulfur and an amine like morpholine. The initial product is a thioacetamide for example that of benzophenone ^[4] which can again be hydrolyzed to the amide.

Reaction mechanism

A possible reaction mechanism for the Kindler variation ^[5] is depicted below:

The first stage of the reaction is basic imine formation by the ketone group and the amine group of morpholine to the enamine 4 which reacts in a conjugate addition (see Stork enamine alkylation for a related step) with sulfur to the sulfide 6. The actual rearrangement reaction takes place when the amine group attacks thiocarbonyl 7 in a nucleophilic addition temporarily forming an aziridine ring (8) and the amine group moving along the central C-C bond to 9 and after proton exchange to 10 and further on to the thioacetamide 11 by tautomerization.

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