Palladium-Catalyzed Synthesis of Aryl Nitriles: Using α-Imino­nitrile as Cyano Source for Aryl Halide Cyanations

Abstract

An efficient and ligand-free palladium-catalyzed exchange reaction to synthesize aryl nitriles by using α-iminonitrile as a starting reagent has been developed. This methodology provides an optional method for the synthesis of aryl nitriles with moderate to good yields. At the same time, this approach is adaptable for many substrates.

Key words

α-iminonitrile - palladium catalyst - aryl halide - aryl nitrile - exchange reaction

• References and Notes

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• 20 General Procedure for the Synthesis of α-Iminonitrile: t-Butyl isocyanide (1.5 mmol), iodobenzene (0.5 mmol), PdCl₂ (0.05 mmol), PCy₃ (0.1 mmol), Cs₂CO₃ (1.0 mmol), and 4 Å MS (100 mg) were added into a 15 mL sealed tube equipped with a magnetic stirring bar and stirred in DMF (2 mL) under argon at 135 °C for 18 h. After completion of the reaction as detected by TLC, it was poured into water (30 mL) and extracted with ethyl acetate (3 × 30 mL). The combined organic layers were dried (Na₂SO₄) and evaporated. The residue was purified on a silica gel column using petroleum ether/EtOAc as the eluent to give the pure target product. N-(tert-Butyl)benzimidoyl Cyanide: Yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.00–7.97 (m, 2 H), 7.52–7.40 (m, 3 H), 1.53 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 136.8 (s), 131.8 (s), 128.8 (s), 127.3 (s), 111.8 (s), 58.5 (s), 29.5 (s). HRMS (CI): m/z [M + H]⁺ calcd for C₁₂H₁₄N₂: 186.1157; found: 186.1154.
• 21 General Procedure for the Synthesis of the Cyanate Product: Aryl halide (0.5 mmol), α-iminonitrile (0.6 mmol), Cu(TFA)₂ (1.0 mmol), Pd(OAc)₂ (0.1 mmol) and DMF (2 mL)were added to a 15 mL sealed tube containing a magnetic stirring bar, and the mixture was stirred under air at 120 °C for 24 h (the progress of the reaction was monitored by TLC). The mixture was poured into water (10 mL) and extracted with ethyl acetate (3 × 10 mL). The organic phase was dried with Na₂SO₄, evaporated, and purified by by silica gel column chromatography. 4-Methoxy-benzonitrile (2a): See ref 19. White solid; mp 59–61 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.55 (d, J = 8.8 Hz, 2 H), 6.92 (d, J = 8.8 Hz, 2 H), 3.83 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 162.8 (s), 133.9 (s), 119.2 (s), 114.8 (s), 103.9 (s), 77.5 (s), 77.2 (s), 76.8 (s), 55.5 (s).