N-Heterocyclic Carbene-Mediated Microfluidic Oxidative Electrosynthesis of Amides from Aldehydes

Abstract

A flow process for N-Heterocyclic Carbene (NHC)-mediated anodic oxidative amidation of aldehydes is described, employing an undivided microfluidic electrolysis cell to oxidize Breslow intermediates. After electrochemical oxidation, the reaction of the intermediate N-acylated thiazolium cation with primary amines is completed by passage through a heating cell to achieve high conversion in a single pass. The flow mixing regimen circumvented the issue of competing imine formation between the aldehyde and amine substrates, which otherwise prevented formation of the desired product. High yields (71-99%), productivities (up to 2.6 g h(-1)), and current efficiencies (65-91%) were realized for 19 amides.

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

“…247 The low potential required for this process was found to be compatible with other nucleophilic species, allowing the groups of Boydston and Brown to develop methods of synthesizing amides and thioesters directly from aldehydes. 248,249 The electrochemical conversion of aldehydes into nitriles has also been reported wherein ammonium iodide served as the source of nitrogen as well as the mediator (Figure 15B). 250 …”

Modern Electrochemical Aspects for the Synthesis of Value‐Added Organic Products

“…Moreover, extension to amide formation was possible 22. Different aromatic aldehydes and aliphatic amines were tested.…”

Moderne Aspekte der Elektrochemie zur Synthese hochwertiger organischer Produkte

“…[18] Auch N-heterocyclische Carbene (NHCs) sind von besonderem Interesse füro rganokatalytische Reaktionen. [22] Verschiedene aromatische Aldehyde und aliphatische Amine wurden ge-testet. Die elektrochemische Oxidation von Aldehyden in Gegenwart von NHCs und DBUführte zur Bildung von Estern.…”