Catalyst‐ and Solvent‐Free Thioamidation of Aromatic Aldehydes through a Willgerodt‐Kindler Reaction

• Published in: ChemistrySelect (Weinheim) 2022-12, Vol.7 (48), p.n/a
• Main Authors: Kale, Arun D., Dalal, Dipak S.
• Format: Article
• Language: English
• Subjects: Amines; Aromatic aldehydes; Catalyst-free; Solvent-free; Thioamide synthesis; Willgerodt-Kindler reaction
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202203497

A simple, straightforward, and highly efficient approach has been developed to synthesize thioamide derivatives under catalyst‐ and solvent‐free conditions at 100 °C/room temperature. Total 51 thioamides were synthesized via a one‐pot multicomponent Willgerodt‐Kindler reaction between substituted aromatic aldehydes, elemental sulfur powder and amines with 70–98 % yield within 20–70 min using cyclic secondary amines and 1.5–24 h using aliphatic primary and secondary amines. The cyclic secondary amines react faster than aliphatic amines. Twenty‐one newer compounds were prepared and characterized by 1H NMR, 13C NMR, HRMS. Mild reaction conditions, good yields, and a wide range of reactions demonstrate the excellent synthetic utility of this method. The developed protocol showed that there is no need to collect, purify, recycle, and remove the solvent after the reaction is complete. Reaction rates are generally high due to the high availability of reactants, i. e., shortens the reaction time, is environmentally friendly, and which makes the overall process more sustainable and economical. A convenient, greener, and highly efficient approach for the synthesis of thioamide derivatives under catalyst‐ and solvent‐free conditions at 100 °C / room temperature has been developed. Total 51 thioamides were synthesized with 70‐98% yield within 20‐70 min using cyclic secondary amines and 1.5‐24 h using aliphatic primary and secondary amines. On gram‐scale, the reaction is successfully attempted with good yields.