Iodine-Promoted N-Acylation of Amines with Hydrazide: An Efficient Metal-Free Amidation

Abstract

An efficient protocol for the amidation of hydrazide with amine has been developed by utilizing I2 as an oxidant under metal and base-free conditions at room temperature. N-acylation products of amines were obtained in good to excellent yield without using toxic reagents. This method is operationally straightforward and tolerates aliphatic/aromatic and primary/secondary amines with different hydrazides.

One-Pot Oxidative Amidation of Aldehydes via the Generation of Nitrile Imine Intermediates

“…To investigate the role of hydrazide 4 as an intermediate in the process, it was independently prepared and then subjected to the oxidative conditions with KBr/Oxone which afforded amide 2a in 71% yield. Previous protocols have been reported that involve the oxidative coupling of acyl hydrazides with amines . It was reasoned that the NI was rapidly hydrolyzed to provide a hydrazide intermediate 4 which was oxidized to diazene intermediate 3 in situ .…”

“…Previous protocols have been reported that involve the oxidative coupling of acyl hydrazides with amines. 20 It was reasoned that the NI was rapidly hydrolyzed to provide a hydrazide intermediate 4 which was oxidized to diazene intermediate 3 in situ . In our manifold, acyl diazene 3 is a reactive acylating agent and reacts with the requisite amine to form the amide products, with loss of nitrogen and concomitant formation of nitrobenzene as a byproduct which was detected by LC analysis ( Scheme 5 ), and confirmed via gas chromatography–MS (GC–MS).…”