A Novel Approach to the Synthesis of α-Aminonitriles Using Triphenyl-
phosphine Dibromide under Solvent-Free Conditions

Devdutt Chaturvedi; Amit K. Chaturvedi; Parmesh K. Dwivedi; Nisha Mishra

doi:10.1055/s-0032-1317690

Synlett, Inhaltsverzeichnis

Synlett 2013; 24(1): 33-36
DOI: 10.1055/s-0032-1317690

letter

A Novel Approach to the Synthesis of α-Aminonitriles Using Triphenyl- phosphine Dibromide under Solvent-Free Conditions

Devdutt Chaturvedi*

^aLaboratory of Medicinal Chemistry, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Campus, Lucknow 226028, U. P., India Fax: +91(522)2399610 eMail: devduttchaturvedi@gmail.com eMail: dchaturvedi@lko.amity.edu

,

Amit K. Chaturvedi

^bSynthetic Research Laboratory, Department of Chemistry, B. S. A. P. G. College, Mathura 281004, U. P., India

,

Parmesh K. Dwivedi

^aLaboratory of Medicinal Chemistry, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Campus, Lucknow 226028, U. P., India Fax: +91(522)2399610 eMail: devduttchaturvedi@gmail.com eMail: dchaturvedi@lko.amity.edu

,

Nisha Mishra

^bSynthetic Research Laboratory, Department of Chemistry, B. S. A. P. G. College, Mathura 281004, U. P., India

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Abstract

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Abstract

A quick and highly efficient, one-pot, three-component, solvent-free method for the synthesis of α-aminonitriles starting from the corresponding carbonyl compounds, amines, and trimethylisocyanide using triphenylphosphine dibromide, has been developed. Diverse α-aminonitriles have been synthesized in good to excellent yields (80–99%) using a range of aldehydes, ketones and amines.

Key words

multicomponent reactions - Strecker synthesis - aminonitriles - carbonyl compounds

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Referenzen

References and Notes

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12 Synthesis of α-Aminonitriles; Typical Procedure: A mixture of aldehyde (1 mmol), amine (1 mmol), triphenylphosphine dibromide (10 mol%), and trimethylsilylcyanide (1.2 mmol) was stirred at room temperature until the reaction was complete (monitored by TLC). The reaction mixture was then extracted with EtOAc (×3), dried over anhydrous Na₂SO₄, filtered, and concentrated. Purification of the crude product by chromatography on silica gel (60–120 mesh; petroleum ether–EtOAc, 5:1) gave the pure product. 2-Anilino-2-phenylacetonitrile (Table 3, Entry 1): Light-yellow solid; mp 85–86 °C; IR (CHCl₃): 3368, 3055, 2233, 1602, 1502 cm^–1; ¹H NMR (300 MHz, CDCl₃): δ = 4.03 (d, J = 9 Hz, 1 H), 5.41 (d, J = 9 Hz, 1 H), 6.76 (d, J = 9 Hz, 2 H), 6.90 (t, J = 6 Hz, 1 H), 7.30 (t, J = 9 Hz, 2 H), 7.44 (m, 3 H), 7.59 (m, 2 H); ¹³C NMR (75 MHz, CDCl₃): δ = 49.8, 114.0, 118.1, 119.9, 127.0, 128.3, 129.4, 129.8, 133.6, 144.6; MS (ESI): m/z = 208.2 [M]⁺; Anal. Calcd for C₁₄H₁₂N₂: C, 80.74; H, 5.81; N, 13.45. Found: C, 80.80; H, 5.76; N, 13.47. 2-Anilino-2-(4-chlorophenyl)acetonitrile (Table 3, Entry 2): White solid; mp 96–98 °C; IR (CHCl₃): 3365, 3055, 2235, 1603, 1504 cm^–1; ¹H NMR (300 MHz, CDCl₃): δ = 4.02 (d, J = 6 Hz, 1 H), 5.41 (d, J = 9 Hz, 1 H), 6.75 (d, J = 9 Hz, 2 H), 6.92 (t, J = 6 Hz, 1 H), 7.28 (m, 2 H), 7.42 (d, J = 9 Hz, 2 H), 7.53 (d, J = 6 Hz, 2 H); ¹³C NMR (75 MHz, CDCl₃): δ = 49.5, 114.2, 117.8, 120.4, 128.4, 129.2, 129.6, 132.8, 135.4, 144.3; MS (ESI): m/z = 242.1 [M]⁺; Anal. Calcd for C₁₄H₁₁ClN₂: C, 69.28; H, 4.57; N, 11.54; Found: C, 69.19; H, 4.63; N, 11.56. 2-Anilino-2-(4-nitrophenyl)acetonitrile (Table 3, Entry 3): Gummy solid; IR (CHCl₃): 3381, 3063, 2225, 1601, 1550, 1502 cm^–1; ¹H NMR (300 MHz, CDCl₃): δ = 4.08 (d, J = 9 Hz, 1 H), 5.57 (d, J = 9 Hz, 1 H), 6.68 (d, J = 9 Hz, 2 H), 6.78 (t, J = 8 Hz, 1 H), 7.29 (t, J = 9 Hz, 2 H), 7.8 (d, J = 9 Hz, 2 H), 8.1 (d, J = 9 Hz, 2 H); ¹³C NMR (75 MHz, CDCl₃): δ = 49.8, 115.3, 118.0, 127.0, 127.7, 127.8, 128.6, 129.0, 133.8, 144.1, 145.0; MS (ESI): m/z = 276.2 [M + Na]⁺; Anal. Calcd for C₁₄H₁₁N₃O₂: C, 66.40; H, 4.38; N, 16.59; Found: C, 66.46; H, 4.40; N, 16.51.