Cobalt(II) chloride catalyzed one-pot synthesis of alpha-aminonitriles.
ABSTRACT A simple and efficient method has been developed for the synthesis of alpha-aminonitriles by a one-pot three- component condensation of aldehydes, amines, and potassium cyanide in acetonitrile in the presence of a catalytic amount of CoCl2 at room temperature.
- SourceAvailable from: unibielefeld.deChemical Reviews 09/2003; 103(8):2795-828. · 41.30 Impact Factor
- Journal of Medicinal Chemistry 09/1973; 16(8):901-8. · 5.61 Impact Factor
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Cobalt(II) chloride catalyzed one-pot synthesis of α-aminonitriles
Surya K De*
Address: Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Purdue Cancer Center, Purdue University,
West Lafayette, IN 47907, USA
Email: Surya K De* - firstname.lastname@example.org
* Corresponding author
A simple and efficient method has been developed for the synthesis of α-aminonitriles by a one-
pot three- component condensation of aldehydes, amines, and potassium cyanide in acetonitrile in
the presence of a catalytic amount of CoCl2 at room temperature.
The addition of cyanide to imines (the Strecker reaction) 
provides one of the most direct and viable routes for the
synthesis of α-aminonitriles, which are useful intermediates
for the synthesis of amino acids and nitrogen-containing
heterocycles such as thiadiazoles, imidazoles, etc [2,3].
They are usually prepared by the nucleophilic addition of
cyanide anion to imines. Numerous methods describing the
preparation of α-aminonitriles have been reported in the lit-
erature employing acid catalysts such as InCl3,  BiCl3, 
KSF clay,  Sc(OTf)3,  Cd(II)-salt,  Pt-salt,  and
other.  However, there are still some drawbacks in these
catalytic systems including low yields of products, long reac-
tion times, harsh reaction conditions, the requirement for
an inert atmosphere, the use of stoichiometric and/or rela-
tively expensive reagents, [4,5,7-9] and also require tedious
work-up leading to the generation of a large amount of toxic
waste. Therefore, there is a need an efficient and inexpensive
catalyst for the synthesis of α-aminonitriles.
In continuation of our work to develop new organic trans-
formations, [11-17] I report herein that cobalt(II) chlo-
ride which acts as a mild Lewis acid might be a useful and
inexpensive catalyst for the synthesis α-aminonitrile.
Although cobalt(II) chloride has been extensively used as
a mild catalyst for a plethora of organic transformations,
[18-20] there are no examples of the use of cobalt(II)
chloride as catalyst for the synthesis of α-aminonitriles.
Results and discussion
The treatment of benzaldehyde and aniline with KCN in
the presence of a catalytic amount of CoCl2 afforded the
corresponding 2-(N-anilino)-2-phenylacetonitrile in 91%
yield. Similarly, a variety of aldehydes were coupled with
a wide range of amines and potassium cyanide in a one-
pot operation in the presence of a catalytic amount of
CoCl2 at room temperature to give the corresponding α-
aminonitriles in good to excellent yields (Scheme 1). Both
aromatic and aliphatic aldehydes afforded excellent yields
whereas ketones did not give any satisfactory yields. On
the other hand, all types of primary and secondary amines
are readily coupled in good yields. Moreover, acid sensi-
tive aldehyde such as furfuraldehyde reacted in high yield.
This method does not require any additives to promote
the reaction. The results shown in Table 1 clearly indicate
the scope and generality of the reaction with respect to
various aldehydes and amines. One reaction was per-
formed for the synthesis of 2-(N-Anilino)-2-phenylace-
tonitrile (entry 1) using trimethylsilyl cyanide instead of
potassium cyanide as cyanide source to give the similar
yield. It should be mentioned that both are toxic but
potassium cyanide is cheaper than trimethylsilyl cyanide.
Published: 07 October 2005
Beilstein Journal of Organic Chemistry 2005, 1:8doi:10.1186/1860-5397-1-8
Received: 10 July 2005
Accepted: 07 October 2005
This article is available from: http://bjoc.beilstein-journals.org/content/1/1/8
© 2005 De; licensee Beilstein-Institut.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Beilstein Journal of Organic Chemistry 2005, 1:8 http://bjoc.beilstein-journals.org/content/1/1/8
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I have demonstrated a very simple, efficient, and practical
method for the synthesis of α-aminonitriles through a
one-pot three component coupling of aldehydes, amines,
and potassium cyanide using a catalytic amount of
cobalt(II) chloride. The major feature of this method is
that it is truly a one-pot protocol that does not need a sep-
arate step to synthesize an imine for subsequent use. The
advantages of this method include (a) operational sim-
plicity, (b) no need any other additive to promote the
reaction, (c) short reaction times, (d) the use of relatively
cheap commercially available reagents, and (e) high
yields of products.
1.Shfran YM, Bakulev VS, Mokrushin VS: Russ Chem Rev 1989, 5:148.
2.Wienstok LM, Davis P, Handelsman B, Tull R: J Org Chem 1967,
3. Matier WL, Owens DA, Comer WT, Deitchaman D, Ferguson HC,
Seidehamel RJ, Young JR: J Med Chem 1973, 16:901.
4.Ranu BC, Dey SS, Hajra A: Tetrahedron 2002, 58:2529.
5.De SK, Gibbs RA: Tetrahedron Lett 2004, 45:7407.
6. Yadav JS, Reddy B, Esshwaraih B, Srinivas M: Tetrahedron 2004,
7. Kobayashi S, Basujima T, Nagayama S: J Chem Soc Chem Commun
8. Ohmuri O, Fujita M: J Chem Soc Chem Commun 2004:1586.
9.Fossey JS, Richards CJ: Tetrahedron Lett 2003, 44:8773.
Grover H: Chem Rev 2003, 103:2795. and references cited therein.
De SK: Tetrahedron Lett 2004, 45:2339.
De SK: Tetrahedron Lett 2004, 45:2919.
De SK, Gibbs RA: Tetrahedron Lett 2004, 45:8141.
De SK: Tetrahedron Lett 2003, 44:9055.
De SK, Gibbs RA: Tetrahedron Lett 2005, 46:1647.
De SK, Gibbs RA: Tetrahedron Lett 2005, 46:1811.
De SK: Adv Synth Catal 2005, 347:673.
De SK: Tetrahedron Lett 2004, 45:1035.
Iqbal J, Srivastava RR: Tetrahedron Lett 1991, 32:1663.
Velusamy S, Borpuzari S, Punniyamurthy T: Tetrahedron 2005,
Table 1: Cobalt (II) chloride- catalyzed synthesis of α-amino nitriles with potassium cyanide
EntryAldehyde AmineTime (h)Yield a(%)
a Yields refer to pure isolated products and were characterized by spectral data.
Additional File 1
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RCHO + R1NH2 + KCN