One-Pot, Catalyst-Free Synthesis of Nitriles from Aldehydes Using Aminating Reagent MsONH3OTf

Tharcisse Gatera; Daijiao Zhuang; Rulong Yan

doi:10.1055/s-0041-1737293

Synlett, Table of Contents

Synlett 2022; 33(02): 182-186
DOI: 10.1055/s-0041-1737293

letter

One-Pot, Catalyst-Free Synthesis of Nitriles from Aldehydes Using Aminating Reagent MsONH₃OTf

Tharcisse Gatera‡

,

Daijiao Zhuang‡

,

Rulong Yan∗

Abstract

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Abstract

An eco-friendly protocol to synthesize nitriles from their corresponding aromatic and aliphatic aldehydes in excellent yields has been developed. This is a catalyst-free protocol which employs an aminating reagent (MsONH₃OTf) under mild conditions. The hydroxylamine triflic acid salts (MsONH₃OTf) acted as the N source for this protocol. Our protocol proved to be easy to perform and presented good functional group tolerance.

Key words

aldehydes - nitriles - hydroxylamine triflic acid salts - catalyst-free

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References

References and Notes

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18 General Procedure for the Synthesis of Nitriles from AldehydesA solution of aldehyde (0.4 mmol) and MsONH₃OTf (0.6 mmol, 1.5 equiv) was mixed in MeCN (4 mL), then the reaction mixture was placed in a preheated oil bath and stirred at 60 °C for the mentioned period while checking the reaction progress (TLC monitored). After completion, the solvent was removed by rotary evaporator, and the crude product was purified by column chromatography on silica gel, using petroleum ether/EtOAc (10:1) as eluent to afford the pure nitriles. The synthesis of both aliphatic and aromatic nitriles obeyed the above workup procedure, except for the compound 2-aminobenzonitrile (2u). After completion, the reaction mixture was extracted with EtOAc and washed with saturated K₂CO₃ solution, the organic layers were combined and dried with anhydrous Na₂SO₄. The solvent was evaporated under reduced pressure, and the crude product was purified by column chromatography on silica gel, using petroleum ether/EtOAc (10:1) as eluent to afford 2u.Benzonitrile (2a)Colorless oil (37.1 mg, 90% yield). ¹H NMR (400 MHz, CDCl₃): δ = 7.66–7.59 (m, 3 H), 7.50–7.46 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 132.6, 132.0, 129.0, 118.7, 112.2. HRMS: m/z calcd for C₇H₆N [M + H]⁺: 104.0495; found: 104.0491.2-Aminobenzonitrile (2u)Colorless solid (34.0 mg, 72% yield), mp 45–47 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.38–7.30 (m, 2 H), 6.75–6.71(m, 2 H), 4.45 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 149.6, 133.9, 132.2, 117.8, 117.6, 115.1, 95.7. HRMS: m/z calcd for C₇H₇N₂ [M + H]⁺: 119.0604; found: 119.0601.Heptanenitrile (4a)Colorless oil (32.0 mg, 72% yield). ¹H NMR (400 MHz, CDCl₃): δ = 2.36–2.33 (m, 2 H), 1.70–1.62 (m, 2 H), 1.49–1.42 (m, 2 H), 1.34–1.28 (m, 4 H), 0.92–0.89 (m, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 119.9, 30.9, 28.3, 25.3, 22.3, 17.1, 13.9 ppm. HRMS: m/z calcd for C₇H₁₄N [M + H]⁺: 112.1121; found: 112.1117.

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