Willgerodt-Kindler reaction at room temperature: Synthesis of thioamides from aromatic aldehydes and cyclic secondary amines

• Published in: Tetrahedron 2019-10, Vol.75 (41), p.130575, Article 130575
• Main Authors: Kale, Arun D., Tayade, Yogesh A., Mahale, Sachin D., Patil, Rahul D., Dalal, Dipak S.
• Format: Article
• Language: English
• Subjects: Aromatic aldehydes; Catalyst-free; Cyclic secondary amines; Room temperature; Thioamide synthesis; Willgerodt-Kindler reaction
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2019.130575

A simple method for the synthesis of thioamide derivatives in DMSO at room temperature and at 120 °C has been developed. Total 27 compounds were prepared under both conditions via a one-pot, three component reaction between substituted aromatic aldehydes, elemental sulfur powder, and cyclic secondary amines. By optimizing the mole ratio of sulfur powder and amines, we have successfully carried out Willgerodt-Kindler reaction of aromatic aldehydes at room temperature. At 120 °C, it is catalyst free reaction with lower reaction time whereas at room temperature, due to the additional amine molecule, Willgerodt-Kindler reaction of aromatic aldehydes is successfully carried out at room temperature. On gram-scale, the reaction is successfully attempted under both conditions with good yields. [Display omitted] •First time we are reporting Willgerodt-Kindler reaction of aromatic aldehydes at room temperature.•On gram-scale, the reaction is successfully attempted under both conditions with good yields.•Catalyst free method for the synthesis of thioamides in DMSO at 120 °C with short reaction time has been developed.•Total 27 compounds were prepared under both conditions via a one-pot multicomponent reaction.