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Synlett 2007(8): 1317-1319  
DOI: 10.1055/s-2007-980338
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient New Procedure for the One-Pot Conversion of Aldehydes into the Corresponding Nitriles

Jia-Liang Zhu*a, Fa-Yen Leea, Jen-Dar Wub, Chun-Wei Kuob, Kak-Shan Shia*b
a Department of Chemistry, National Dong-Hwa University, Hualien 974, Taiwan, R.O.C.
Fax: +886(38)633570; e-Mail: jlzhu@mail.ndhu.edu.tw;
b Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 350, Taiwan, R.O.C.
Fax: +886(37)586456; e-Mail: ksshia@nhri.org.tw;
Further Information

Publication History

Received 30 January 2007
Publication Date:
08 May 2007 (online)

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Abstract

A new and efficient procedure for the one-pot conversion of various aldehydes into the corresponding nitriles under mild reaction conditions has been developed. The ethyl dichlorophosphate/DBU-mediated dehydration of aldoxime intermediates was utilized as a key operation to effect the transformation.

Key words

aldehydes - nitriles - ethyl dichlorophosphate - DBU - ­dehydration

    References and Notes

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  • 16 A representative experimental procedure is described for the preparation of benzonitrile (2). To a solution of benzaldehyde (1, 0.2 g, 1.88 mmol) in CH2Cl2 (8 mL), powdered 3 Å MS (120 mg), 1.2 equiv of NH2OH·HCl (0.157 g, 2.26 mmol) and 5 equiv of DBU (1.43 g, 9.42 mmol) were successively added in one portion. The reaction mixture was stirred at r.t. for 10 h, cooled in an ice-water bath to 5 °C, and 1.5 equiv of EtOPOCl2 (0.46 g, 2.83 mmol) were added. Then, stirring at r.t. was continued for an additional 5 h. The mixture was then quenched with aq NH4Cl, extracted with CH2Cl2 and subjected to chromatographic purification on silica gel (15% EtOAc in hexane) to afford 2 in 96% yield (0.186 g), whose spectral data (IR, 1H NMR and 13C NMR) were identical to those of the authentic sample.Benzonitrile(2): IR (KBr): 2228, 1701, 1597, 1583, 1489, 1447 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.56-7.46 (m, 3 H), 7.43-7.32 (tm, J = 7.5 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 132.8, 132.0, 129.1, 118.8, 112.2. GC-MS: m/z = 103.5 [M]+.(S)-2-(tert-Butoxycarbonylamino)propanenitrile (4): IR (KBr): 3317, 2979, 2260, 1680 cm- 1. 1H NMR (400 MHz, CDCl3): δ = 1.46 (s, 9 H), 1.53 (d, J = 7.2 Hz, 3 H), 4.61 (br s, 1 H), 4.99 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 19.6, 28.2, 37.6, 81.2, 119.6, 154.1. LC-MS (ES): m/z = 193 [M + 23]+; mp 105-106 °C; [α]D 2 5 -24.5 (c 2.5, CHCl3) {Lit.15 [α]D 2 0 -24.6 (c 2.5, CHCl3)}.(S)-2-(tert-Butoxycarbonylamino)-3-phenylpropanenitrile (6): IR (KBr): 3353, 3065, 2248, 1691 cm- 1. 1H NMR (400 MHz, CDCl3): δ = 1.45 (s, 9 H), 3.08 (m, 2 H), 4.84 (m, 1 H), 4.95 (m, 1 H), 7.25-7.40 (m, 5 H). 13C NMR (100 MHz, CDCl3): δ = 28.2, 39.2, 43.4, 81.3, 118.4, 127.9, 129.0, 129.5, 133.9, 154.1. LC-MS (ES): m/z 246 [M]+; mp 114-115 °C; [α]D 2 5 -16.4 (c 0.98, dioxane) {Lit.14 [α]D 2 5 -16.4 (c 0.98, dioxane)}
8

Both PhCH=NOPO(OEt)2 and PhCH=NOH were obtained as the single stereoisomers. The stereochemistry remains to be determined.

9

An optimized amount of 3 Å MS was used. It was found that at least 120 mg of 3 Å MS was required for a quantitative conversion of 1.50 mmol of benzaldehyde (1) into benzonitrile (2).

10

Satisfactory spectral and LC-MS analytical data were obtained for all products; all known nitriles showed physical and spectral properties identical to those reported in the literature.