Catalytic Synthesis of Nitriles in Organic Reactions

Nitriles, characterised by the carbon–nitrogen triple bond (–C≡N), are ubiquitous motifs in pharmaceuticals, agrochemicals, polymers and functional materials. Traditional routes to nitriles have often relied on stoichiometric metal cyanides, posing significant safety and environmental concerns. In recent years, catalytic strategies have emerged to enable the direct formation of C–N bonds under mild, sustainable conditions. These include oxidative cyanations of C–H or C–X bonds using benign oxidants such as molecular oxygen, reductive cyanations that employ non-toxic precursors like carbon dioxide and ammonia, transition-metal-mediated C–H activation processes, and metal-free photoredox approaches. Heterogeneous catalysts and recyclable ligated complexes have broadened substrate scope and improved functional-group tolerance. Together, these advances offer versatile platforms for the late-stage functionalisation of complex molecules, safer cyanide-free protocols and scalable methodologies aligned with green chemistry principles.

Research from Nature Portfolio

A novel heterogeneous cobalt catalyst comprising graphene-encapsulated nanoparticles and atomically dispersed Co–Nₓ sites has been developed for oxidative cleavage and cyanation of organosulfur compounds. Under an oxygen atmosphere with ammonia as nitrogen source, a wide array of thiols, sulfides and sulfonyl derivatives is transformed into nitriles without external cyanide, displaying excellent functional-group tolerance, catalyst recyclability and mechanistic evidence of synergistic Co nanoparticle–Co–Nₓ cooperation.
A complementary strategy uses a nickel-Triphos system to achieve reductive cyanation of aryl and aliphatic chlorides with carbon dioxide and ammonia as combined CN source. The protocol proceeds under mild conditions, tolerates diverse substituents and can employ urea as a bench-stable surrogate. Mechanistic studies indicate the key role of Ni(I) intermediates and isocyanate formation in effecting safe, cyanide-free C–C coupling to furnish nitriles with high efficiency.

Catalytic Synthesis of Nitriles in Organic Reactions publication trend

The graph below shows the total number of articles in catalytic synthesis of nitriles in organic reactions across all publications each year (not limited to Nature Index journals).

Technical terms

Nitrile: Organic functional group featuring a carbon–nitrogen triple bond (–C≡N).

Cyanation: Catalytic introduction of a cyano (–C≡N) unit into an organic substrate.

C–H activation: Direct cleavage of a carbon–hydrogen bond by a catalyst to enable new bond formation.

Oxidative cyanation: Cyanation process that simultaneously oxidises a substrate, often employing O₂ or other benign oxidants.

Reductive cyanation: Formation of a cyano group via reductive coupling, typically using CO₂, NH₃ or related precursors under metal catalysis.

Heterogeneous catalysis: Catalytic reactions in which the catalyst resides in a different phase (usually solid) from the reactants, facilitating separation and reuse.

Photoredox catalysis: Use of light-absorbing catalysts to drive redox transformations via radical or electron-transfer pathways.

References

1. Oxidative cleavage and ammoxidation of organosulfur compounds via synergistic Co-Nx sites and Co nanoparticles catalysis. Nature Communications (2023).
2. Reductive cyanation of organic chlorides using CO2 and NH3 via Triphos–Ni(I) species. Nature Communications (2020).
3. Copper/TEMPO catalysed synthesis of nitriles from aldehydes or alcohols using aqueous ammonia and with air as the oxidant. Chemical Communications (2013).
4. Visible‐Light‐Promoted Metal‐Free Synthesis of (Hetero)Aromatic Nitriles from C(sp3)−H Bonds**. Angewandte Chemie International Edition (2020).
5. Aerobic dehydrogenation of amines to nitriles catalyzed by triazolylidene ruthenium complexes with O 2 as terminal oxidant. Dalton Transactions (2020).