Kindler modification of Willgerodt reaction

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. 

Willgerodt reaction, 923, 924J, 925, Kindler modification of, 923 Williamson synthesis, 309, 665, 670, 671 Witt plate, 51... 

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. 

The original Willgerodt Reaction conditions required high temperature and pressure, with use of ammonium poly sulfide fNHihS, and H20 to give either an amide or the ammonium salt of the corresponding acid. Kindler s modification, shown above, eliminated these problems and substituted S8 and a dry amine, most commonly morpholine. 

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 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. 

Time and Temperature. Earlier experiments were usually carried out at temperatures above 200°. More recently, in runs with added dioxane, temperatures in the range 150-160° have been generally employed. The time required for complete reaction is dependent upon the temperature. It appears likely, however, that the reaction periods of twelve to twenty-four hours which frequently have been used are longer than necessary, and that most reactions are complete in three to four hours at 160°. For a relatively unreactive ketone like pinacolone, a temperature above 200° may be required to obtain a satisfactory yield in a convenient time. The conditions in the Kindler modification with amines have been approximately the same as those in the Willgerodt reaction in aqueous solution, usually four to six hours of heating at 140-160° occasionally reaction times have been longer— up to fifteen hours. When morpholine is employed the reaction mixture is simply heated to boiling under reflux. 

The Willgerodt reaction is useful in the preparation of arylacetic acids and amides from substituted methyl aryl ketones or vinyl aromatic compounds. The aliphatics and acetylenes give lower yields. The conversion is effected by heating aromatic compounds at 160°-200°C in an aqueous solution under pressure using ammonium polysulfide. In the Kindler modification, the ketone or styrene is refluxed with a mixture of sulfur and an amine, usually morpholine, to give a thioamide, ArCHjCSNRj. 

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