Willgerodt-Kindler conditions

The yields of trifluoropyruvic thioamides 6 with common secondary amines are mostly fair and do not exceed 65 %. The reduction products - trifluorolactic thioamides 7 are formed in certain cases as by-products (about 5 %). Trifluoroacetone yields under the Willgerodt-Kindler conditions only 7 (30-35 %), besides other products. These lactic products 7 are therefore formed more expediently by reduction of 6 using ammonium formate at 100°C. 

Synthesis of 2-aminobenzothiophene derivatives were achieved via a modified Gewald aminobenzothiophene synthesis under the Willgerodt-Kindler conditions." This procedure produced the desired 2-aminobenzothiophenes, such as A-methyl-5-nitrobenzo[b]thiophen-2-amine shown below, in moderate to good yields. 

Example 3, A domino annulation reaction under Willgerodt-Kindler conditions ... 

Other Type B Syntheses.— The interaction of 2-picoline with 3-substituted anilines in the presence of sulphur under Willgerodt-Kindler conditions, reported... 

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. 

Prediction of Optimum Conditions for New Substrates in the Willgerodt-Kindler Reaction [19]... 

Table 15. Optimum conditions in the Willgerodt-Kindler reaction of substituted acetophenones...

Various condensations of 3-acetyl-l,2,5-thiadiazole (83) have been carried out which indicate a high degree of reactivity of both the carbonyl and the methyl group. The reactions investigated include the aldol condensation of 88, the Mannich reaction to 89, triscyano-ethylation to 90, and the Willgerodt-Kindler reaction to 91. The reactions proceeded under mild conditions and the normal products were obtained in good yield in each case. ... 

Table 16.1 Optimum conditions and optimum yield in the Willgerodt-Kindler rection with different...

The reaction space linked to the experimental space and the response space, illustrated by prediction of optimum conditions for new substrates in the Willgerodt-Kindler reaction. 

Diphenylguanidine was successfully used as starting material for the Willgerodt-Kindler reaction, giving polythioamides. Carbon disulphide reacted with triethylamine and DMF to give A /Z-diethyl- and i W-dimethyl-thioformamide. Under the same conditions, dithiocarbamates decompose to give iViV-dialkyl-thioformamide and sulphur. HMPT and sulphur have been shown to be a useful system for the oxidation of a variety of aromatic and heteroaromatic compounds to the corresponding A -methyl- and JVAT-dimethyl-thioamides in the case of phenyl benzyl ketone, /mn -stilbene and the heterocyclic compounds (114) and (115) have been obtained as by-products. Whereas the benzylic... 

Moghaddam and Ghaffarzadeh (2001) have successfully transformed aldehydes and aryl alkyl ketones to thioamides with the same number of carbon atoms via Willgerodt-Kindler reaction under microwave irradiation in solvent-free conditions. 

Aryl-substituted olefins and acetylenes are transformed into amides under the conditions of both the Willgerodt and Kindler procedures. ... 

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. 

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