Direct Oxidative Conversion of Alkyl Halides into Nitriles with Molecular Iodine in Aqueous Ammonia

Shinpei Iida; Hideo Togo

doi:10.1055/s-2008-1078491

LETTER

Direct Oxidative Conversion of Alkyl Halides into Nitriles with Molecular Iodine in Aqueous Ammonia

Shinpei Iida, Hideo Togo*
Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chia 263-8522, Japan
Fax: +81(43)2902792; e-Mail: togo@faculty.chiba-u.jp;

Abstract

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Abstract

The direct oxidative conversion of various benzylic alkyl halides and primary alkyl halides into corresponding nitriles was efficiently and simply carried out using molecular iodine in aqueous ammonia. This novel reaction converts alkyl halides into corresponding nitriles without changing the number of carbon atoms.

Key words

iodine - ammonia - nitrile - halide

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References

References and Notes

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Typical Procedure for Oxidative Conversion of Benzyl Halides into Nitriles with I ₂
To a mixture of 4-methylbenzyl chloride (140.6 mg, 1 mmol) and aq NH₃ (3.0 mL, 45 mmol) was added I₂ (533.0 mg, 2.1 mmol) at r.t. under an empty balloon. The obtained mixture was stirred at 60 °C. After 4 h at the same temperature, the reaction mixture was quenched with H₂O (10 mL) and sat. aq Na₂SO₃ (2 mL) at 0 °C and was extracted with Et₂O (3 × 15 mL). The organic layer was washed with brine and dried over Na₂SO₄ to provide p-tolunitrile in 82% yield in an almost pure state. If necessary, the product was purified by a column chromatography (SiO₂; hexane-EtOAc, 4:1) to give pure p-tolunitrile as a colorless solid; mp 25 °C. IR (NaCl): 2230 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.55 (2 H, d, J = 7.9 Hz), 7.27 (2 H, d, J = 7.9 Hz), 2.42 (3 H, s).

Typical Procedure for Oxidative Conversion of Alkyl Halides into Nitriles with I ₂
A mixture of 3-phenylpropyl bromide (199.1 mg, 1 mmol) and aq NH₃ (5.0 mL, 75 mmol) in a screw-capped glass vial (10 mL) was stirred at 60 °C for 24 h. Then, aq NH₃ (3.0 mL, 45 mmol) and I₂ (761.4 mg, 3.0 mmol) were added. After 4 h at the same temperature, the reaction mixture was quenched with H₂O (10 mL) and sat. aq Na₂SO₃ (2 mL) at 0 °C and was extracted with Et₂O (3 × 15 mL). The organic layer was washed with brine and dried over Na₂SO₄ to provide 3-phenylpropionitrile in 73% yield in an almost pure state. If necessary, the product was purified by column chromatography (SiO₂; hexane-EtOAc, 4:1) to give pure 3-phenylpropionitrile as a colorless oil. IR (NaCl): 2250 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.34 (2 H, t, J = 8.2 Hz), 7.28 (1 H, t, J = 8.2 Hz), 7.23 (2 H, d, J = 8.2 Hz), 2.96 (2 H, d, J = 7.9 Hz), 2.62 (2 H, d, J = 7.9 Hz).
All nitrile products mentioned in this work, except 10-cyanodecanoic acid, were identified with commercially available authentic samples.
10-Cyanodecanoic Acid
Mp 42-44 °C. IR (neat): 2243, 1690 cm^-1. ¹H NMR (400 MHz, CDCl₃): d = 2.35 (t, J = 7.4 Hz, 2 H), 7.34 (t, J = 7.2 Hz, 1 H), 1.64 (m, 4 H), 1.44 (br, 2 H) 1.32 (br, 9 H). ¹³C NMR (100 MHz, CDCl₃): d = 179.7, 119.9, 34.0, 29.1, 29.0, 28.72, 28.66, 25.4, 24.7, 17.2. HRMS: m/z calcd for C₁₁H₁₉O₂N: 198.1494; found: 198.1484.