Subscribe to RSS
DOI: 10.1055/s-2007-980338
An Efficient New Procedure for the One-Pot Conversion of Aldehydes into the Corresponding Nitriles
Publication History
Publication Date:
08 May 2007 (online)
![](https://www.thieme-connect.de/media/synlett/200708/lookinside/thumbnails/10.1055-s-2007-980338-1.jpg)
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
- 1
Friedrich K.Wallensfels K. The Chemistry of the Cyano GroupRappoport Z. Wiley-Interscience; New York: 1970. - 2
Coskun N.Arikan N. Tetrahedron 1999, 55: 11943 - 3
Boruah M.Knowar D. J. Org. Chem. 2002, 67: 7138 -
4a
Erman MB.Snow JW.Williams MJ. Tetrahedron Lett. 2000, 41: 6749 -
4b
Talukar S.Hsu JL.Chou TC.Fang JM. Tetrahedron Lett. 2001, 42: 1103 - 5
Foley PJ. J. Org. Chem. 1969, 34: 2805 - For examples, see:
-
6a
Sandnya A. Synthesis 1982, 190 -
6b
Feng JC.Lin G.Dia L.Bian NS. Synth. Commun. 1998, 28: 3765 -
6c
Das B.Madhusudhan P.Venkataiah B. Synlett 1999, 1569 -
6d
Kumar HMS.Reddy BVS.Deddy PT.Yadav JS. Synthesis 1999, 586 -
6e
Sharghi H.Sarvari MH. Tetrahedron 2002, 58: 10323 -
6f
Koshima H.Hamada M.Tani M.Iwasaki S.Sato F. Heterocycles 2002, 57: 2145 -
6g
Srinivas KVNS.Mahender I.Das B. Chem. Lett. 2003, 32: 738 -
6h
Ballini R.Fiorini D.Palmieri A. Synlett 2003, 1841 -
6i
Sharghi H.Sarvari MH. Synthesis 2003, 243 ; and references cited therein - 7
Kuo CW.Zhu JL.Wu JD.Chu CM.Yao CF.Shia KS. Chem. Commun. 2007, 301 - 11 For the preparation of compound 3, see:
Falorni M.Giacomelli G.Porcheddu A.Teddei M. J. Org. Chem. 1999, 64: 8962 - 12
Monica CD.Randazzo A.Bifulco G.Cimino P.Aquino M.Izzo I.Riccardis F.Luigi GP. Tetrahedron Lett. 2002, 43: 5707 - 13
Costello GF.James R.Shaw JS.Slater AM.Stutchbury NCJ. J. Med. Chem. 1991, 34: 181 - 14 Liskamp R. M. J., Boiejen A.; Eur. J. Org. Chem.; 1999, 2127
- 15 Kohrt A., Hartke K.; Liebigs Ann. Chem.; 1992, 6: 595
- 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)}
References and Notes
Both PhCH=NOPO(OEt)2 and PhCH=NOH were obtained as the single stereoisomers. The stereochemistry remains to be determined.
9An 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).
10Satisfactory 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.