Ketones Willgerodt reaction

The conversion of a carbonyl compound by ammonium polysulphide solution into an amide with the same number of carbon atoms is known as the Willgerodt reaction. The procedure has been improved by the addition of about 40 per cent, of dioxan or of pyridine to increase the mutual solubility of the ketone and aqueous ammonium polysulphide the requisite temperature is lowered to about and the yield is generally better. 

A further improvement is embodied in the Klndler variation of the Willgerodt reaction this consists in heating the ketone with approximately equal amounts of sulphur and a dry amine instead of aqueous ammonium polysulphide. The principal product is a thioamide, and hydrolysis with acid or alkali affords the carboxylic acid, usually in good yield. 

An aryl alkyl ketone 1 can be converted into an tn-arylalkane carboxylic amide 2 by employing the Willgerodt reaction The number of carbon centers is retained. The reaction is carried out by treating the ketone with an aqueous solution of ammonium polysulfide. A variant that has been developed by Kindler, and which is called the Willgerodt-Kindler reaction, uses a mixture of sulfur and a secondary amine instead of the ammonium polysulfide. 

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 Willgerodt reaction is usually carried out under high pressure, thus requiring special laboratory equipment, while with the Kindler variant this is not necessary. The Kindler variant is of wider scope, and yields are generally better. In addition aromatic compounds with vinyl substituents may be employed as substrates instead of the ketone, e.g. styrene 7 ... 

The Willgerodt reaction also works with hetaryl alkyl ketones, but often gives unsatisfactory yields. Yields generally decrease with increasing chain length of the alkyl group. 

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 ... 

WILLGERODT REACTION, This reaction, discovered in 1887, is conducted by heating a ketone, for example ArCOCHi, with an aqueous solution of yellow ammonium sulfide (sulfur dissolved in ammonium sulfide), and results in formation of an amide derivative of an arylacetic add and in some reduction of the ketone. The dark reaction mixture usually is refluxed with... 

These are usually prepared by the following methods (a) the Willgerodt reaction on the corresponding methyl ketone,82,98,337,485, 557 (6) hydrolysis of the corresponding cyanomethyl compound,77,337, 485,499,517,521,568 cyclization reactions (Section IV, C) (for 3-acetic acids only),143,209,310,311,313,351 or (d) the Arndt-Eistert reaction on the corresponding carbonyl chloride, which may lead directly to the acetic acid 689 or its amide.337, 568... 

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 most useful application of sulfur is the Willgerodt reaction—the conversion of ketones into acids having the same number of carbon atoms [498]. The conversion is accomplished by heating ketones with sulfur and ammonium sulfide [499, 500, 501, 502] at 160-210 °C under pressure. The Kindler modification avoids operation under pressure by using sulfur and high-boiling secondary amines such as morpholine, instead of ammonium sulfide [503, 504]. Such a reaction carried out at reflux gives the thio-morpholides, which are subsequently hydrolyzed to acids. 

The Willgerodt reaction, which involves heating ketones with ammonium polysulfide, is the most important route to carboxylic acids without degradation of the carbon chain. It applies especially to methyl and alkyl... 

The uniqueness of the Willgerodt reaction lies in the ultimate formation of acids from ketones regardless of the position of the carbonyl group in the chain. 

The Willgerodt reaction of isobutyl methyl ketone with ammonium polysulfide at 200 °C gives an 88% yield of isocapronamide after 4 h of heating [1169. Yields of other aliphatic ketones are not nearly as high [1161, 1169 (equation 415). 

The Willgerodt reaction is frequently used to convert alkyl aryl ketones, which are synthesized easily by the Friedel-Crafts reaction, into aryl alkanoic acids with or without isolation of the intermediate thiomor-pholides [499, 504, 1170] (equation 416). 

The Kindler modification of the Willgerodt reaction uses sulfur and dry amines, ammonia, primary amines or secondary amines, which leads to the formation of thioamides (conversion of thioamides to amides cf Section 2.3.1.7). This reaction can also be extended to aldehydes, hydrocarbons and heterocyclic ketones. Due to the usually low to moderate yields this reaction has not found general application. 

Willgerodt reaction. In its original form this reaction involved heating an aryl alkyl ketone in a sealed tube at 210-230° with an aqueous solution of yellow ammonium polysulfide, prepared by dissolving sulfur in ammonium sulfide solution. The product is an aryl substituted aliphatic aciil amide, together with some of the corresponding carboxylic acid and often the hydrocarbon. An example is the... 

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