SO₂F₂-Promoted Dehydration of Aldoximes: A Rapid and Simple Access to Nitriles

Abstract

A rapid, simple and mild process for the dehydration of aldoximes to give the corresponding nitriles, which utilizes SO₂F₂ as an efficient reagent, has been developed. A variety of (hetero)arene, alkene, alkyne and aliphatic aldoximes proceeded with high efficiency to afford nitriles in excellent to quantitative yields with great functional group compatibilities in acetonitrile under ambient conditions. Furthermore, an eco-friendly synthetic protocol to access nitriles from aldehydes with ortho-, meta- and para-nitrile groups was also described in aqueous methanol by using inorganic base Na₂CO₃, and a one-pot synthetic strategy to generate nitriles from aldehydes was proved to be feasible.

Key words

SO₂F₂ - aldoxime - nitrile - dehydration - CH₃CN - aqueous methanol

• References and Notes

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• 15 Converting Aldoximes into the Corresponding Nitriles in Acetonitrile; Typical Procedure: 4-Chlorobenzaldoxime 2e (0.137 g, 1.0 mmol), CH₃CN (2.0 mL) and Et₃N (278 μL, 2.0 mmol) were added into a 25 mL Schlenk flask equipped with magnetic stirrer and rubber stopper. Then the SO₂F₂ gas was introduced into the stirring reaction mixture by slow bubbling from a SO₂F₂ balloon, and the reaction mixture was stirred at room temperature for 15 min. After the reaction, the mixture was diluted with water and extracted with ethyl acetate (3 × 10 mL). The combined organic layers were then washed with brine, dried over anhydrous Na₂SO₄ and concentrated to dryness. The residue was purified by column chromatography on silica gel (300–400 mesh) with hexane and ethyl acetate to give 4-chlorobenzonitrile 3e. ¹H NMR (500 MHz, CDCl₃): δ = 7.62 (d, J = 8.7 Hz, 2 H), 7.49 (d, J = 8.7 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 139.6, 133.4, 129.7, 117.9, 110.9.
• 16 Converting Nitrobenzaldoximes into Nitrobenzonitriles in Aqueous Methanol; Method a: 4-Nitrobenzaldoxime 2g (166 mg, 1.0 mmol), CH₃OH (2.0 mL), H₂O (0.5 mL) and Na₂CO₃ (159 mg, 1.5 mmol) were added into a 25 mL Schlenk flask equipped with magnetic stirrer and rubber stopper. The SO₂F₂ gas was introduced into the stirring reaction mixture by slow bubbling from a SO₂F₂ balloon, and the reaction mixture was stirred at room temperature for 30 min. After the reaction, the mixture was diluted with water and extracted with ethyl acetate (3 × 10 mL). The combined organic layers were then washed with brine, dried over anhydrous Na₂SO₄ and concentrated to dryness. The residue was purified by column chromatography on silica gel (300–400 mesh) with hexane and ethyl acetate to give the 4-nitrobenzonitriles 3g. ¹H NMR (500 MHz, CDCl₃): δ = 8.38 (d, J = 8.9 Hz, 2 H), 7.90 (d, J = 8.9 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 150.1, 133.5, 124.3, 118.4, 116.7.