ORGANIC
LETTERS
2001
Vol. 3, No. 26
4209-4211
Highly Efficient and Catalytic
Conversion of Aldoximes to Nitriles
Soon Ha Yang and Sukbok Chang*
Department of Chemistry, Ewha Womans UniVersity, Seoul 120-750, Korea
Received October 8, 2001
ABSTRACT
Catalytic dehydration of aldoximes can be performed highly efficiently with a catalyst system of [RuCl2(p-cymene)]2/molecular sieves under
essentially neutral and mild conditions, and various types of cyano compounds are produced in good to excellent yields.
Nitrile is a key constituent in numerous natural products,
and it also serves as an important synthetic intermediate for
pharmaceuticals, agricultural chemicals, dyes, and material
sciences.1 One of the most general methods for synthesis of
alkylnitriles is a direct nucleophilic substitution of alkyl
halides with inorganic cyanides although the reaction is
frequently accompanied by elimination of hydrogen halides
especially with bulky alkyl halides.2 R,â-Unsaturated nitriles
can be prepared via a Wittig reaction of the corresponding
aldehyde with cyanoalkyl phosphonate. However, it fre-
quently results in an unbiased mixture of E- and Z-isomeric
nitriles.3 Nitrile synthesis by means of dehydration of amides
or aldoximes with an appropriate nonmetal dehydrating agent
would be an alternative method.4 However, it suffers from
some disadvantages such as inconvenient preparation of the
reagents, limited substrate scope, or incompatibility of
sensitive groups to the reaction conditions. Recently, there
have been several reports describing dehydration methods
of aldoximes with the use of stoichiometric amounts of
certain main or transition metal complexes.5 Despite the
recent progress, there is still a strong need for a preparatiVe
method of highly efficient and catalytic conVersion of
aldoximes to nitriles.6 In continuation of our studies directed
toward the development of metal-catalyzed efficient reac-
tions,7 described herein is a realization of this goal with a
Ru catalyst.
Conversion of 4-bromobenzaldoxime to 4-bromobenzo-
nitrile was first examined as a test reaction under various
conditions (Table 1). Whereas no conversion of the oxime
to cyano was observed in the absence of catalyst, some Rh
or Ru complexes exhibited noticeable catalytic activities on
the transformation. While Rh complexes displayed moderate
to low reactivity, use of certain Ru catalysts led to higher
conversion and better selectivity in general. For example,
addition of Ru3(CO)12 catalyst provided good conversion
albeit with modest selectivity for the formation of nitrile
(1) (a) Friedrich, K.; Wallenfels, K. In The Chemistry of the Cyano
Group; Rappaport, Z., Ed.; Wiley-Interscience Publishers: New York, 1970;
p 67. (b) Fatiadi, A. J. In Preparation and synthetic applications of cyano
compounds; Patai, S., Rappaport, Z., Eds.; Wiley: New York, 1983; p 1057.
(c) Miller, J. S.; Manson, J. L. Acc. Chem. Res. 2001, 34, 563.
(2) (a) Kiefel, M. J. In ComprehensiVe Organic Functional Group
Transformations; Katrizky, A. R., Meth-Cohn, O., Rees, C. W., Eds.;
Pergamon: Cambridge, UK, 1995; pp 641-676. (b) Kukushkin, V. Y.;
Tudela, D.; Pombeiro, A. J. L. Coord. Chem. ReV. 1996, 156, 333.
(3) For example, see: Magnus, P.; Scott, D. A.; Fielding, M. R.
Tetrahedron Lett. 2001, 42, 4127.
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J. B.; Hussoin, M. S. J. Org. Chem. 1987, 52, 4139. (e) Fukuzawa, S.-i.;
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A. J.; Prajapati. D.; Sandhu, J. S. Chem. Lett. 2000, 1196.
(6) For some previously reported examples of metal-catalyzed reactions,
see: (a) Attanasi, O.; Palma, P.; Serra-Zanetti, F. Synthesis 1983, 741. (b)
Hart-Davis, J.; Battioni, P.; Boucher, J.-L.; Mansuy, D. J. Am. Chem. Soc.
1998, 120, 12524.
(7) (a) Na, Y.; Chang, S. Org. Lett. 2000, 2, 1887. (b) Lee, M.; Chang,
S. Tetrahedron Lett. 2000, 41, 7507. (c) Lee, M.; Ko, S.; Chang, S. J. Am.
Chem. Soc. 2000, 122, 12011. (d) Chang, S.; Na, Y.; Choi, E.; Kim, S.
Org. Lett. 2001, 3, 2089. (d) Chang, S.; Yang, S. H.; Lee, P. H. Tetrahedron
Lett. 2001, 42, 4833.
10.1021/ol0168768 CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/29/2001