N-Formyl compounds have a broad utility, especially as pharmaceuticals and as synthetic precursors for other organic molecules, such as isocyanates and nitriles. The Wenzel group previously characterized a silver-catalyzed N-formylation reaction that utilizes oligomeric ethylene dioxides as formylation agents. Our model reaction, which uses silver hexafluoroantimonate (V) as the catalyst and 1,4-dioxane as the formylating agent, was found to react with several secondary and primary amines. Herein, we present a mechanistic study of this formylation reaction. Kinetic studies using aniline suggest a first-order dependence on the amine. A Hammett plot constructed using a series of para-substituted anilines revealed that electron-donating groups promote the reaction rate. Although the reaction is usually performed under anhydrous conditions with argon gas, it was found to also perform equally well in air-exposed or hyperoxygenated environments. Stoichiometric amounts of TEMPO in the presence of the silver catalyst and substrates 1-benzylimidazolidin-2-one or aniline showed the formation of a TEMPO-dioxane adduct, detectable by GC-MS and FAB. The presence of oxetane was also detectable by GC-MS and APCI-MS. These results suggest a radical-based mechanism initiated by the homolysis of a C-H bond on the 1,4-dioxane by the silver catalyst, followed by dioxane decomposition to formylate the amine substrate and release oxetane.

Kinetic and mechanistic investigations of a silver-catalyzed N-formylation reaction

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.