Oxidative Synthesis of Amides and Imides

The oxidative synthesis of amides and imides has emerged as a cornerstone of modern organic chemistry, uniting principles of green chemistry with the demand for efficient bond formation. In this approach, simple amines or existing amide substrates undergo controlled oxidation to deliver amide or imide functions, often with high atom economy and minimal waste. Mechanistic pathways range from radical‐mediated dehydrogenation and oxidative cyclisation to photocatalytic and transition‐metal‐catalysed processes. Key oxidants include molecular oxygen, peroxides and hypervalent metal oxides, which in concert with tailored catalysts enable selective C–N bond formation or C–H activation under mild conditions. These advances underpin the streamlined manufacture of pharmaceuticals, agrochemicals and polymer precursors by offering direct access to peptide mimics, lactams and cyclic imides. Ongoing innovations focus on recyclable heterogeneous catalysts, visible-light activation and solvent-free protocols, all in pursuit of sustainability. The global significance of these methods lies in their potential to replace multistep sequences, reduce hazardous reagents and meet stringent regulatory standards in active-ingredient synthesis.

Research from Nature Portfolio

A heterogeneous manganese-oxide catalyst has been shown to mediate the selective oxidation of secondary amides to cyclic imides in a single step. By employing Cs-promoted Mn₂O₃ and a benign peroxide source, air serves as the terminal oxidant and no external ligands are required. The system exhibits broad substrate scope across aromatic and aliphatic amides, achieving high turnover numbers and excellent chemoselectivity to the imide products. Its heterogeneous nature allows simple catalyst recovery and reuse, marking a significant advance in sustainable imide synthesis.

Oxidative Synthesis of Amides and Imides publication trend

The graph below shows the total number of articles in oxidative synthesis of amides and imides across all publications each year (not limited to Nature Index journals).

Technical terms

Amide: A functional group featuring a carbonyl bonded to a nitrogen atom (–CONR₂).

Imide: A nitrogen centre flanked by two acyl groups (–CO–NR–CO–), often forming five- or six-membered rings.

Heterogeneous catalysis: Catalytic reactions in which the catalyst exists in a different phase from the reactants, enabling easy separation.

Photocatalysis: Acceleration of a chemical reaction by light in the presence of a photosensitiser or photocatalyst.

Radical mechanism: A pathway involving discrete radical intermediates, commonly initiated by oxidants such as peroxides.

References

1. Radical-mediated dehydrative preparation of cyclic imides using (NH4)2S2O8–DMSO: application to the synthesis of vernakalant. Beilstein Journal of Organic Chemistry (2015).
2. Heterogeneous Catalytic Oxidation of Amides to Imides by Manganese Oxides. Scientific Reports (2018).
3. Synthesis of new imides and imidoamides of citraconopimaric acid. Proceedings of the National Academy of Sciences of Belarus Chemical Series (2023).
4. RuO4-mediated oxidation of secondary amines 2. imines as main reaction intermediates. Journal of the Serbian Chemical Society (2017).