A One-Pot, Three-Component Synthesis of β,γ-Unsaturated α-Aminonitriles Using TMSCN as the Cyanide Source

Pengxian Niu; Fei Wen; Guangyuan Chen; Tujun Liu; Zhe Ding

doi:10.1055/a-2526-0446

Synlett, Table of Contents

Synlett 2025; 36(10): 1363-1366
DOI: 10.1055/a-2526-0446

letter

A One-Pot, Three-Component Synthesis of β,γ-Unsaturated α-Aminonitriles Using TMSCN as the Cyanide Source

Pengxian Niu

^aSchool of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, Gansu 730000, P. R. China

,

Fei Wen∗

^bYellow River Basin Ecotope Integration of Industry and Education Research Institute, Lanzhou Resources & Environment Voc-Tech University, Lanzhou, Gansu 730022, P. R. China

,

Guangyuan Chen

^bYellow River Basin Ecotope Integration of Industry and Education Research Institute, Lanzhou Resources & Environment Voc-Tech University, Lanzhou, Gansu 730022, P. R. China

,

Tujun Liu

^bYellow River Basin Ecotope Integration of Industry and Education Research Institute, Lanzhou Resources & Environment Voc-Tech University, Lanzhou, Gansu 730022, P. R. China

,

Zhe Ding

^cNorthwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou, Gansu 730000, P. R. China

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Abstract

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We thank Prof. Zheng Li of Northwestern Normal University (China) for his support and celebrate his 60^th birthday.

Abstract

An efficient method for synthesizing β,γ-unsaturated α-aminonitriles via a one-pot procedure using cinnamaldehydes, anilines and trimethylsilyl cyanide (TMSCN) as starting materials under catalyst-free conditions is reported. This one-pot, three-component reaction proceeds efficiently with a broad range of substrates and tolerates a wide variety of functional groups. Notably, the process features a simple work-up procedure and does not require transition-metal catalysts. Additionally, the reaction can be performed on gram scale without loss of efficiency.

Key words

α-aminonitriles - trimethylsilyl cyanide - cyanide source - catalyst-free - cinnamaldehyde

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References

References and Notes

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12 β,γ-Unsaturated α-Aminonitriles 3; General Procedure A reaction tube (15 mL) containing a magnetic stir bar was charged with cinnamaldehyde 1 (1.0 mmol), aniline 2 (1.0 mmol), TMSCN (1.2 mmol) and EtOH (5 mL) under air. The reaction mixture was stirred at room temperature for 24 h. Upon completion the mixture was concentrated under reduced pressure. The residue was purified by column chromatography (petroleum ether/EtOAc as eluent) to give the target product 3.
13 (E)-4-Phenyl-2-(o-tolylamino)but-3-enenitrile (3b) ¹H NMR (600 MHz, CDCl₃): δ = 7.44 (d, J = 7.2 Hz, 2 H), 7.37 (t, J = 7.0 Hz, 2 H), 7.32 (t, J = 7.1 Hz, 1 H), 7.20 (t, J = 7.3 Hz, 1 H), 7.12 (d, J = 7.4 Hz, 1 H), 7.06 (dd, J = 15.9, 1.3 Hz, 1 H), 6.84 (t, J = 7.4 Hz, 1 H), 6.81 (d, J = 8.0 Hz, 1 H), 6.31 (dd, J = 15.9, 5.2 Hz, 1 H), 5.06 (dd, J = 5.2, 1.3 Hz, 1 H), 3.75 (s, 1 H), 2.18 (s, 3 H). ¹³C NMR (151 MHz, CDCl₃): δ = 142.5, 135.1, 135.0, 130.8, 129.0, 128.9, 127.4, 127.0, 123.7, 121.2, 120.0, 117.8, 111.7, 47.6, 17.5. HRMS (ESI): m/z [M – H]⁺ calcd for C₁₇H₁₅N₂: 247.12407; found: 247.12410.

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