Catalytic Cyanation of Aryl Halides with Electrophilic N–CN Reagent

Dedication

Dedicated to Professor S. Chandrasekaran on the occasion of his 80th birthday

Abstract

The palladium-catalyzed cyanation of aryl halides has been accomplished for the synthesis of aryl nitriles using the electrophilic N–CN reagent as a cyanating reagent. The method utilizes a mild base and a substoichiometric amount of zinc as a promotor and offers a mild cyanation that tolerates various functional groups to afford aryl nitriles in good to excellent yields. Preliminary mechanistic investigation revealed the important role of the methylene linkage and the reductant.

Keywords

CN reagent - Aryl nitriles - Cyanation - Palladium - Aryl halide

Publikationsverlauf

Eingereicht: 11. September 2025

Angenommen nach Revision: 04. November 2025

Accepted Manuscript online:
04. November 2025

Artikel online veröffentlicht:
27. November 2025

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• 15 Synthesis of p-methoxybenzonitrile 3a: In an oven dried pressure tube, 4-iodoanisole (0.30 mmol, 1.2 equiv), methylene attached N–CN reagent (0.25 mmol, 1 equiv), PdCl₂ (0.01 mmol, 5 mol%), Cy₃P·HBF₄ (0.03 mmol, 15 mol%), Na₂CO₃ (0.51 mmol, 2 equiv), Zn dust (0.12 mmol, 50 mol%), were added under argon atmosphere. Dry DME (2 mL) was added into the reaction tube using syringe. The reaction mixture was kept in a pre-heated oil bath at 120 °C and stirred at the same temperature for 16 h. The reaction mixture was cooled to room temperature, diluted with DCM and washed with water. The combined organic layer was evaporated to get the crude product, which was further purified by column chromatography using ethyl acetate: hexane (0.5:9.5) as an eluting solvent to afford the p-methoxybenzonitrile 3a in 82% yield. colourless solid; R _f = 0.5 in 5:95 ethyl acetate/hexane; FTIR (neat, cm⁻¹): 2922, 2363, 2219, 1697, 1600, 1490, 1282, 1023, 827; ¹H NMR (400 MHz, CDCl₃, 24 °C): δ 7.58 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 3.86 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃, 24 °C): δ 162.9, 134.1, 119.3, 114.8, 104.0, 55.6