126.9, 129.3, 129.4, 133.4, 154.2; EIMS: m/z 255 (M + 23); mp 120.5–
121.3 uC; [a]2D4 + 1.83 (c = 1.09, CHCl3).
benzonitrile as a typical pathway. It is highly conceivable that the
carboxamido group is initially coupled with ethyl dichloropho-
sphate to form an active intermediate which in turn undergoes
elimination rapidly with DBU to give the corresponding cyano
group.
1 L. N. Mander and M. M. McLachlan, J. Am. Chem. Soc., 2003, 125,
2400.
2 B. R. Lahue, S. M. Lo, Z. K. Wan, G. H. C. Woo and J. K. Snyder,
J. Org. Chem., 2004, 69, 7171.
3 (a) A. V. Narsaiah and K. Nagaiah, Adv. Synth. Catal., 2004, 346, 1271;
(b) D. S. Bose and A. V. Narsaiah, Synthesis, 2001, 373; (c) K. Ishihara,
Y. Furuya and H. Yamamoto, Angew. Chem., Int. Ed., 2002, 41, 2983;
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D. S. Bose and B. Jayalakshmi, J. Org. Chem., 1999, 64, 1713; (f)
S. V. Ley, A. G. Leach and R. I. Storer, J. Chem. Soc., Perkin Trans. 1,
2001, 358; (g) E. C. Wang, K. S. Huang, H. M. Chen, C. C. Wu and
G. J. Lin, J. Chin. Chem. Soc., 2004, 51, 619.
As described above, the EtOPOCl2/DBU system presents itself
as a mild, highly effective dehydrating agent for the conversion of
primary amides to the corresponding nitriles. In addition to high
yields, enhanced reaction rates and operational simplicity, this
newly developed process is expected to have broad synthetic utility,
particularly for the preparation of thermodynamically labile
nitriles.
4 E. Yamto and S. Sugasawa, Tetrahedron Lett., 1970, 4383.
5 W. Lehnert, Tetrahedron Lett., 1971, 1501.
6 C. Ressler, G. R. Nagarajan, M. Kirisawa and D. V. Kashelikar, J. Org.
Chem., 1971, 36, 3960.
We are grateful to the National Health Research Institutes and
National Science Council of the Republic of China for financial
support.
7 T. Sodeyama, M. Kodomari and K. Itabashi, Chem. Lett., 1973, 577.
8 T. Saraie, T. Ishiguro, K. Kawashima and K. Morita, Tetrahedron Lett.,
1973, 2121.
Notes and references
9 J. B. Hendrickson and S. M. Schwartzman, Tetrahedron Lett., 1975,
277.
10 F. Campagna, A. Carotti and G. Casini, Tetrahedron Lett., 1977,
1813.
11 D. Cooper and S. Trippett, Tetrahedron Lett., 1979, 1725.
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1980, 657.
13 T. M. Bargar and C. M. Riley, Synth. Commun., 1980, 10, 479.
14 T. Imamoto, T. Takaoka and M. Yokoyama, Synthesis, 1983, 142.
15 A. Saednya, Synthesis, 1985, 184.
{ EtOPOCl2, C6H5OPOCl2, (CH3)2NPOCl2 and (CH3)2NPCl2 were
obtained from Aldrich or Acros and used without further purification.
{ Satisfactory spectral and elemental or LC-MS analytical data were
obtained for all new compounds; all known nitriles showed physical and
spectral properties identical to those reported in the literature.
§ (R)-2-N-tert-butoxycabonylamino-2-phenylethanenitrile (3): 1H NMR
(400 MHz, CDCl3): d 1.47 (s, 9H), 5.23 (br s, 1H), 5.78 (br s, 1H), 7.41–
7.48 (m, 5H, ArH); 13C NMR (100 MHz, CDCl3): d 28.2, 46.0, 81.5, 177.7,
126.8, 129.2, 129.4, 133.5, 154.2; EIMS: m/z 255 (M + 23); mp 119.5–
120.2 uC; [a]2D4 21.82 (c = 1.1, CHCl3) {Lit.18 [a]D22 21.9 (c = 1.1, CHCl3)}.
(S)-2-N-tert-butoxycabonylamino-2-phenylethanenitrile (4): 1H NMR
(400 MHz, CDCl3): d 1.46 (s, 9H), 5.21 (br s, 1H), 5.77 (br s, 1H), 7.41–
7.48 (m, 5H, ArH); 13C NMR (100 MHz, CDCl3): d 28.2, 46.1, 81.5, 177.6,
16 D. M. Ketcha and G. W. Gribble, J. Org. Chem., 1985, 50, 5451.
17 K. Mai and G. Patil, Tetrahedron Lett., 1986, 27, 2203.
18 N. Noriyuki, S. Miho and U. Makoto, Tetrahedron, 2002, 58, 3561.
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