Work

Electrochemical N-Formylation of Amines: Mechanistic Insights and Sustainable Synthesis of Formamides via a Methylisocyanide Intermediate

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Electrochemical methodologies offer a transformative approach to sustainable chemical synthesis by enabling precise, energy-efficient transformations. Here, we report the selective electrochemical N-formylation of methylamine using methanol as both reagent and solvent, facilitated by a simple glassy carbon electrode. Under optimized conditions, we achieve a faradaic efficiency (FE) of 34% for methylformamide synthesis in a neutral NaClO 4 electrolyte. Mechanistic insights from in situ Fourier-transform infrared spectroscopy (FTIR) and complementary synthetic experiments reveal two distinct reaction pathways: the direct oxidation of a hemiaminal intermediate and a novel route involving the formation of methylisocyanide, which subsequently hydrates to yield methylformamide. The presence of methylisocyanide was confirmed through mass spectrometry analysis following a successful Ugi multicomponent reaction, demonstrating the ability to safely utilize reactive intermediates within an electrochemical framework. This work underscores the potential of electrosynthesis to unlock metal-free, sustainable pathways to produce value-added nitrogen-containing compounds, paving the way for greener approaches in chemical manufacturing and catalysis.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.4c16725

Authors: Pim J. L. Broersen, Lars Wielhouwer, Gadi Rothenberg, Amanda C. Garcia

Institution: University of Amsterdam

Language: English

Topic: Radical Photochemical Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funder: Nederlandse Organisatie voor Wetenschappelijk Onderzoek