Willgerodt‐Kindler Reaction

Abstract

The preparation of thionamide from the reaction of an organic molecule (from acetophenone and anhydrous primary or secondary amines) with sulfur and amine is generally called the Willgerodt–Kindler reaction. Occasionally, this reaction is also termed as the Willgerodt–Kindler redox amidation. The resulting thionamides are further converted into carbonamides by hot aqueous ammonia under the Willgerodt condition. The high boiling point of morpholine, an intrinsic feature, allows the Willgerodt–Kindler reaction to take place in an open vessel instead of an autoclave or a sealed tube. For comparison, under the condition of Willgerodt reaction, it has been found that the presence of pyridine is beneficial to the reaction by lowering the reaction temperature from 210°C to 165°C and raising the yield of phenylacetamide from 49% to 64%. It has been reported that the ketones with a straight chain usually give much better yields of amides than the branched ketones with the same number of carbon atoms at the main chains under comparable reaction conditions. Furthermore, the yields of amide from ketones decrease inversely with the increase of chain length of the alkyl groups. Moreover, the amount of sulfur has also been found to be critical. This reaction has very broad application in the preparation of thionamides and carboxylic acids.