One pot copper catalyzed conversion of oximes to thioamides

Abstract

Thioamides are important structural motifs found in many biologically active molecules and precursors for the synthesis of various fine chemicals, heterocycles etc. In view to the wide use of thioamides, development of a simple and practical method toward their synthesis is an active area of research. The classical methods for the preparation of thioamides usually involve the generation of amides followed by subsequent thionation using the thionating agents such as P4S10, Lawesson’s reagent, etc. Beckmann rearrangement is one of the most practised methods to produce amides. However, Beckmann rearrangement has some limitations such as the requirement of high reaction temperatures and the use of large amounts of strong Brønsted acids and dehydrating media followed by production of large amounts of byproducts. It has been observed that when aldoximes undergoing acid catalysed Beckmann rearrangement, it leads to nitriles, whereas in the presence of metal catalysts, primary amides are obtained. Usually, the transition metal-catalyzed reactions are proceeding through a dehydration/rehydration route via the formation of a discrete nitrile intermediate. A number of important transition metal (i.e. Rh, Ru, Ir, Pd, and Au/Ag) catalysts were successfully used to synthesize primary amides from aldoximes. Now, considering the low cost, low catalyst concentration, milder reaction condition and high abundance of Cu catalyst, makes it an attractive choice for reaction. Recently, Panda et.al from NIT Rourkela developed a Cu-catalyzed protocol for the regioselective synthesis of N-aryl amides from the reaction of aldoxime with aryl halide in moderate to good yield. In line with this work, we attempted and successfully developed a simple Cu-catalyzed direct synthesis of thioamides from aldoximes in one-pot in the presence of thionating agent. Here, this report discusses the simple Cu-catalysed protocol to synthesize thioamides from aldoximes in moderate to good yield.