Willgerodt reaction mechanism

It has been tentatively suggested that one mechanism underlies the Willgerodt reaction and the Kindler modification of it. A labile intermediate is first formed which has a carbon—carbon bond in the side chain. The scheme is indicated below it postulates a series of steps involving the addition of ammonia or amine (R = H or alkyl), elimination of water, re addition and eUmination of ammonia or amine until the unsaturation appears at the end of the chain then an irreversible oxidation between sulphur and the nitrogen compound may occur to produce a thioamide. 

The Willgerodt reaction starts with the formation of an enamine 4 from the ketone, e.g. from acetophenone 3. The further course of the reaction cannot be described by a single mechanism that would apply to all examples known. For aryl methyl ketones 3 the mechanism for the Kindler variant is formulated as follows ... 

The mechanism of the Willgerodt reaction is not completely known, but some conceivable mechanisms can be excluded. Thus, one might suppose that the alkyl group becomes completely detached from the ring and then attacks it with its other end. However, this possibility is ruled out by experiments such as the following When isobutyl phenyl ketone (42) is subjected to the Willgerodt reaction, the product is 43, not 44, which would arise if the end carbon of the ketone became bonded to the ring in the product ... 

The Willgerodt reaction allows amide synthesis from aromatic aldehydes or ketones, using a secondary amine and a thiating agent. The mechanism of the more convenient Kindler modification, employing sulfur and morpholine, has been reviewed.281... 

The Willgerodt Reaction allows the synthesis of amides from aryl ketones under the influence of a secondary amine and a thiating agent. The mechanism involves the formation of an enamine which undergoes thiation, and the carbonyl group migrates to the end of the chain via a cascade of thio-substituted iminium-aziridinium rearrangements. 

The mechanism of the Willgerodt reaction is not completely known, but some conceivable mechanisms can be excluded. Thus, one might suppose that the alkyl group becomes completely detached from the ring, and then attacks it with its other... 

The mechanism of the Willgerodt reaction is not entirely clear [439], Most likely it does not proceed by a skeletal rearrangement, but involves a series of consecutive oxidations and reductions along the carbon chain. A thorough understanding of this reaction is still to be established. 

Enamines are sufficiently basic and nucleophilic to activate elemental sulfur and undergo thiolation at room temperature to give very high yields of the thioamides (Scheme 8). This step would appear to hold the key to the mechanism of the Willgerodt-Kindler reaction. 

Acetophenones - methyl phenylacetates, ArCOCH3 -- ArCH2COOCH, Treatment of an acetophenone with thallium(Ill) nitrate in methanol containing a trace of perchloric acid at room temperature for 2-18 hr. results in formation of a methyl arylacetate in 60-95 % yield. The mechanism suggested for this transformation is shown in the formulation. The reaction provides an alternative to the Willgerodt-Kindler reaction."... 

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