Efficient Synthesis of N-phenethylarylthioamides by Kindler Reaction

In recent years, the thioamides are often appeared in the literature as intermediates in medicinal chemistry and biological, but also in organic synthesis for the preparation of heterocycles containing sulphur.1 Thioamides are traditionally prepared by thionation of the corresponding amides with phosphorus pentasulfide or Lawesson's reagent as thionating agent. Because sulfur is nontoxic, stable under ambient conditions, easy to handle, and readily available, its use in the preparation of thioamides is highly desirable as exemplified by the Kindler reaction, starting from aldehydes, elemental sulfur and amines.2 This reaction has found in the past a bad reputation because of long reaction time, difficult conditions of reaction and formation of hydrogen sulfide toxic to humans and the environment. In the quest to find methods of catalytic synthesis responding to the new requirements of green chemistry, optimization conditions have made the Kindler reaction more attractive.3 Therefore, the establishment of an effective, practical and green strategy for the formation of thioamides remains highly desirable. For this purpose, we have used an easy synthetic green approach to prepare N-phenethylarylthioamides (3a-p) by Kindler reaction (Scheme 1). In this work we used the Kindler reaction under microwave irradiation using aryl aldehydes (1a-p), 2- phenylethylamine (2), sulfur, Na2S.9H2O as catalyst and N-methylpyrrolidone (NMP) as solvent at 150°C for 6 minutes.3 On average, aryl aldehydes substituted with electron-rich, neutral and deficient groups generated N-phenethylarylthioamides (3a-p) in 58-91% yields after recrystallization from boiling ethanol. Structures were confirmed by IR and NMR analysis. In summary, sixteen N-phenethylarylthioamides have been prepared with good to excellent yields. The protocol features broad substrate scope, nice yields, operability and commercially available and inexpensive raw materials, showing its practical synthetic value in organic synthesis.