Kindler thioamide synthesis

Another frequently used multicomponent reaction is the Kindler thioamide synthesis (the condensation of an aldehyde, an amine, and sulfur). The Kappe group has described a microwave-assisted protocol utilizing a diverse selection of 13 aldehyde and 12 amine precursors in the construction of a representative 34-member library of substituted thioamides (Scheme 6.114) [226]. The three-component con-... 

DMF is recommended as diluent in the Ullmann synthesis of diaryls from aryl halides and as solvent for the Beckmann rearrangement of steroidal enone oximes. The Willgerodt-Kindler reaction (a carbonyl compound with a secondary amine and sulfur to give a thioamide) can be carried out in good yield at 50-60 if DMF is... 

Reichardt (2003, p. 504) presents a table of solvents recommended as replacements for more hazardous ones. Total avoidance of solvent is sometimes a possibility. An example was mentioned in Chapter 1. Scott (2003) discusses the scope of solvent-free methods and considerations of mutual solubility of reactants and of control, including exothermic reactions. A recent application is the solvent-free synthesis by Valdez-Rojas et al. (2012) of thioamides and alpha-ketothioamides through the Willgerodt-Kindler reaction. Scheme B. 

The Kindler variation, - which promises to be more useful than the original Willgerodt procedure, consists in heating the ketone with approximately equimolecular amounts of sulfur and a dry amine instead of aqueous ammonium polysulfide. A thioamide is formed as the principal product and on hydrolysis with acid or alkali affords the carboxylic acid, usually in good yield. Generally a secondary aliphatic amine but sometimes a primary amine or even anhydrous ammonia is used the development of a method for the electrolytic reduction of the thioamides to amines extended the usefulness of the reaction as a new route to the synthesis of many important nitrogen bases. Early descriptions of this... 

Several papers have reported on the application of the Willgerodt-Kindler reaction in the synthesis of thioamides. In an investigation of a modified form of this reaction, Ried and his co-workers treated some 2,4,6-trimethylphenyl alkyl ketones with dimorpholinodisul-phide (215). Only the methyl ketone afforded a normal Willgerodt-Kindler product (216), but otherwise a clear relationship between the nature of the product and the nature of the ketone alkyl group, Le. the number of... 

---