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LETTER
Res. 2001, 34, 563. (c) Fatiadi, A. J. In Preparation and
Synthetic Applications of Cyano Compounds; Patai, S.;
Rappaport, Z., Eds.; Wiley: New York, 1983, 1057.
(2) (a) North, M. In Comprehensive Organic Functional Group
Transformations; Katrizky, A. R.; Meth-Cohn, O.; Rees, C.
W., Eds.; Pergamon: Oxford, 1995, 617. (b) Mowry, D. T.
Chem. Rev. 1948, 42, 250.
OH
CN
PyrH+Cl– (0.5 equiv)
DMSO, 90 °C, 4 h
N
Br
Br
1a
2a
98%
Scheme 2 Reaction of aldoxime with pyridinium chlororide in
DMSO
(3) (a) Desai, D. G.; Swami, S. S.; Mahale, G. D. Synth.
Commun. 2000, 30, 1623. (b) Katritzky, A. R.; Zhang, G. F.;
Fan, W. Q. Org. Prep. Proced. Int. 1993, 25, 315.
(c) Forey, H. G.; Datlon, D. R. J. Chem. Soc., Chem.
Commun. 1973, 628. (d) Kukhar, V. P.; Pasternak, V. I.
Synthesis 1974, 563. (e) Shinozaki, H.; Imaizumi, M.;
Tajima, M. Chem. Lett. 1983, 929. (f) Meshram, H. M.
Synthesis 1992, 943. (g) Findlay, J. A.; Tang, C. S. Can. J.
Chem. 1967, 45, 1014.
(4) (a) Brackman, W.; Smit, P. J. Recl. Trav. Chim. Pays-Bas
1963, 82, 757. (b) Sato, R.; Itoh, Y.; Itep, K.; Nihina, H.;
Goto, T.; Saito, M. Chem. Lett. 1984, 1913. (c) Erman, M.
B.; Snow, J. W.; Williams, M. J. Tetrahedron Lett. 2000, 41,
6749. (d) Talukdar, S.; Hsu, J. L.; Chou, T. C.; Fang, J. M.
Tetrahedron Lett. 2001, 42, 1103. (e) Bandgar, B. P.;
Makone, S. S. Synth. Commun. 2006, 36, 1347. (f) Arote,
N. D.; Bhalerao, D. S.; Akamanchi, K. G. Tetrahedron Lett.
2007, 48, 3651. (g) Telvekar, V. N.; Patel, K. N.; Kundaikar,
H. S.; Chaudhari, H. K. Tetrahedron Lett. 2008, 49, 2213.
(5) (a) Kumar, H. M. S.; Reddy, B. V. S.; Reddy, P. T.; Yadav,
J. S. Synthesis 1999, 586. (b) Karmarkar, S. N.; Kelkar, S.
L.; Wadia, M. S. Synthesis 1985, 510. (c) Blatter, H. M.;
Lukaszewski, H.; de Stevens, G. J. Am. Chem. Soc. 1961, 83,
2203. (d) Olah, G. A.; Keumi, T. Synthesis 1979, 112; and
references cited therein. (e) Dauzonne, D.; Demerseman, P.;
Royer, R. Synthesis 1981, 739. (f) Saednya, A. Synthesis
1982, 190. (g) Ganboa, I.; Palomo, C. Synth. Commun.
1983, 13, 219. (h) Capdevielle, P.; Lavigne, A.; Maumy, M.
Synthesis 1989, 451. (i) Bose, D. S.; Narsaiah, A. V.
Tetrahedron Lett. 1998, 39, 6533.
with substoichiometric amount of PyrH+Cl– indicates the
catalytic role of HCl in the process.
These results support the mechanism described in
Scheme 3. The interaction of HCl (associated with hy-
droxylamine hydrochloride) with DMSO yields an oxy-
sulfonium salt 3. The intermediate 3 instantaneously
reacts with aldoxime 1 to produce 4 via electrophilic ad-
dition. Subsequent expulsion of nitrile from 4 regenerates
DMSO and HCl. The process is mechanistically related to
oxidation of aldoximes to nitriles using bromodimethyl-
sulfonium bromide.17
R
NH2OH⋅HCl
N
R
CHO
HCl + H2O +
H
OH
1
OH
S+
Cl–
Me
Me
3
H2O
O
S
HCl
+
Me
Me
R
H
Me
S+
N
Cl–
O
4
Me
(6) (a) Olah, G. A.; Vankar, Y. D. Synthesis 1978, 702.
(b) Olah, G. A.; Narang, S. C.; Garcia, L. A. Synthesis 1980,
659.
R
CN
2
(7) Georg, G. I.; Pfeifer, S. A.; Haake, M. Tetrahedron Lett.
1985, 26, 2739.
(8) (a) Stankovic, S.; Espenson, H. Chem. Commun. 1998,
1579. (b) Rudler, H.; Denise, B. Chem. Commun. 1998,
2145.
(9) (a) Fernandez, R.; Gasch, C.; Lassaleta, J.; Llera, J.;
Vazquezz, J. Tetrahedron Lett. 1993, 34, 141. (b) Said, S.
B.; Skarzewski, J.; Mlochowski, J. Synthesis 1989, 223.
(c) Mlochowski, J.; Kloc, K.; Kubicz, E. J. Prakt. Chem.
1994, 336, 467.
Scheme 3 Probable pathway of nitrile generation from aldehydes
involving ‘activated DMSO’
In conclusion, we have demonstrated a practical and cost
efficient one-pot transformation of aldehydes to nitriles
mediated by ‘activated DMSO’. A variety of aromatic,
heterocyclic, and aliphatic aldehydes are converted into
respective nitriles, in which only water is a byproduct.18
The reaction tolerates a wide scope of functional groups,
and the method is simple to conduct. As established by us,
this protocol can be readily applied to multigram-scale
processes with high efficiency and selectivity, making it
an economical and a convenient process for the prepara-
tion of nitriles.
(10) Murahashi, S. I.; Shiota, T.; Imada, Y. Org. Synth. 1991, 70,
265.
(11) For various methods of DMSO activation, see: Tidwell, T. T.
Synthesis 1990, 857; and references cited therein.
(12) (a) Epstein, W. W.; Sweat, F. W. Chem. Rev. 1967, 67, 247.
(b) De Luca, L.; Giampaolo, G.; Porcheddu, A. J. Org.
Chem. 2001, 66, 7907. (c) Liu, Y.; Vederas, J. C. J. Org.
Chem. 1996, 61, 7856. (d) Murray, R. W.; Gu, D. J. Chem.
Soc., Perkin Trans. 2 1994, 451. (e) Pfitzner, K. E.; Moffatt,
J. G. J. Am. Chem. Soc. 1963, 85, 3027. (f) Taber, D. F.;
Amedio, J. C. Jr.; Jung, K. J. Org. Chem. 1987, 52, 5621.
(g) Marx, M.; Tidwell, T. T. J. Org. Chem. 1984, 49, 788.
(h) Albright, J. D. J. Org. Chem. 1974, 39, 1977.
(i) Albright, J. D.; Goldman, L. J. Org. Chem. 1967, 32,
2416. (j) Omura, K.; Swern, D. Tetrahedron 1978, 34,
1651. (k) Mancuso, A. J.; Brownfain, D. S.; Swern, D.
J. Org. Chem. 1979, 44, 4148. (l) Mancuso, A. J.; Huang,
Supporting Information for this article is available online at
References and Notes
(1) (a) Friedrich, K.; Wallenfels, K. In The Chemistry of the
Cyano Group; Rappaport, Z., Ed.; Wiley-Interscience: New
York, 1970, 67. (b) Miller, J. S.; Manson, J. L. Acc. Chem.
Synlett 2011, No. 15, 2223–2227 © Thieme Stuttgart · New York