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

Jia-Liang Zhu; Fa-Yen Lee; Jen-Dar Wu; Chun-Wei Kuo; Kak-Shan Shia

doi:10.1055/s-2007-980338

LETTER

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

Jia-Liang Zhu*^a, Fa-Yen Lee^a, Jen-Dar Wu^b, Chun-Wei Kuo^b, 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;

Abstract

All articles of this category

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

Full Text

References

References and Notes

<A NAME="RW02107ST-1">1</A> Friedrich K. Wallensfels K. The Chemistry of the Cyano Group Rappoport Z. Wiley-Interscience; New York: 1970.

<A NAME="RW02107ST-2">2</A> Coskun N. Arikan N. Tetrahedron 1999, 55: 11943

<A NAME="RW02107ST-3">3</A> Boruah M. Knowar D. J. Org. Chem. 2002, 67: 7138

<A NAME="RW02107ST-4A">4a</A> Erman MB. Snow JW. Williams MJ. Tetrahedron Lett. 2000, 41: 6749

<A NAME="RW02107ST-4B">4b</A> Talukar S. Hsu JL. Chou TC. Fang JM. Tetrahedron Lett. 2001, 42: 1103

<A NAME="RW02107ST-5">5</A> Foley PJ. J. Org. Chem. 1969, 34: 2805

For examples, see:

<A NAME="RW02107ST-6A">6a</A> Sandnya A. Synthesis 1982, 190

<A NAME="RW02107ST-6B">6b</A> Feng JC. Lin G. Dia L. Bian NS. Synth. Commun. 1998, 28: 3765

<A NAME="RW02107ST-6C">6c</A> Das B. Madhusudhan P. Venkataiah B. Synlett 1999, 1569

<A NAME="RW02107ST-6D">6d</A> Kumar HMS. Reddy BVS. Deddy PT. Yadav JS. Synthesis 1999, 586

<A NAME="RW02107ST-6E">6e</A> Sharghi H. Sarvari MH. Tetrahedron 2002, 58: 10323

<A NAME="RW02107ST-6F">6f</A> Koshima H. Hamada M. Tani M. Iwasaki S. Sato F. Heterocycles 2002, 57: 2145

<A NAME="RW02107ST-6G">6g</A> Srinivas KVNS. Mahender I. Das B. Chem. Lett. 2003, 32: 738

<A NAME="RW02107ST-6H">6h</A> Ballini R. Fiorini D. Palmieri A. Synlett 2003, 1841

<A NAME="RW02107ST-6I">6i</A> Sharghi H. Sarvari MH. Synthesis 2003, 243 ; and references cited therein

<A NAME="RW02107ST-7">7</A> Kuo CW. Zhu JL. Wu JD. Chu CM. Yao CF. Shia KS. Chem. Commun. 2007, 301

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

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).

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.

<A NAME="RW02107ST-11">11</A> For the preparation of compound 3, see: Falorni M. Giacomelli G. Porcheddu A. Teddei M. J. Org. Chem. 1999, 64: 8962

<A NAME="RW02107ST-12">12</A> Monica CD. Randazzo A. Bifulco G. Cimino P. Aquino M. Izzo I. Riccardis F. Luigi GP. Tetrahedron Lett. 2002, 43: 5707

<A NAME="RW02107ST-13">13</A> Costello GF. James R. Shaw JS. Slater AM. Stutchbury NCJ. J. Med. Chem. 1991, 34: 181

<A NAME="RW02107ST-14">14</A> Liskamp R. M. J., Boiejen A.; Eur. J. Org. Chem.; 1999, 2127

<A NAME="RW02107ST-15">15</A> Kohrt A., Hartke K.; Liebigs Ann. Chem.; 1992, 6: 595

<A NAME="RW02107ST-16">16</A> 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)}