Syrris in Publications - Syrris
N‑Heterocyclic Carbene-Mediated Microfluidic Oxidative Electrosynthesis of Amides from Aldehydes
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- Category: Publications
Organic Letters, 2016, 18 (5), pp 1198–1201
Robert A. Green†, Derek Pletcher†, Stuart G. Leach‡, and Richard C. D. Brown*†
†Department of Chemistry, University of Southampton, Southampton, Hampshire SO17 1BJ, U.K. ‡ GlaxoSmithKline, Stevenage, Herts SG1 2NY, U.K.
Using a Syrris flow system and the FLUX continuous electrochemistry module, researchers at the University of Southampton and GlaxoSmithKline have demonstrated a flow process for the N-Heterocyclic carbene-mediated continuous oxidative electrosynthesis of amides from aldehydes.
The use of N-Heterocyclic carbenes (NHCs) as organic catalysts for a range of reactions including the oxidative conversion from aldehydes to amides is well known but requires a stoichiometric amount of chemical oxidant. The electrochemical oxidation of the Breslow intermediate offers an attractive, greener alternative.
After electrochemical oxidation, the reqaction of the intermediateN-acylated thiazolium cation with primary amines is carried out in a heated microreactor to achieve a high conversion in a single pass. Using this methodology high yields (71–99%), productivities (up to 2.6 g h–1), and current efficiencies (65–91%) were realized for 19 amides.
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.