γ-Al2O3-supported 12-tungstosilicic acid as an efficient heterogeneous catalyst for the synthesis of α-aminonitrile

Article abstract of DOI:10.1080/00397910802222571

The multicomponent Strecker reaction using trimethylsilyle cyanide was performed in very short reaction times, and α-aminonitriles were prepared in excellent yields in the presence of a catalytic amount of alumina-supported tungstosilicic acid. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802222571

This article was downloaded by: [North Carolina State University]
On: 25 August 2013, At: 08:28
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
γ-Al2O3-Supported 12-
Tungstosilicic Acid as an
Efficient Heterogeneous
Catalyst for the Synthesis of α-
Aminonitrile
Ezzat Rafiee a b , Solmaz Rashidzadeh a , Mohammad
Joshaghani a , Hadi Chalabeh a & Kambiz Afza a
a Department of Chemistry, Faculty of Science, Razi
University, Kermanshah, Iran
b Kermanshah Oil Refining Company, Kermanshah,
Iran
Published online: 25 Aug 2010.
To cite this article: Ezzat Rafiee , Solmaz Rashidzadeh , Mohammad Joshaghani ,
Hadi Chalabeh & Kambiz Afza (2008) γ-Al2O3-Supported 12-Tungstosilicic Acid as
an Efficient Heterogeneous Catalyst for the Synthesis of α-Aminonitrile, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 38:16, 2741-2747, DOI: 10.1080/00397910802222571
To link to this article: http://dx.doi.org/10.1080/00397910802222571
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.

However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communications1, 38: 2741–2747, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802222571
c-Al2O3-Supported 12-Tungstosilicic Acid as an
Efficient Heterogeneous Catalyst for the
Synthesis of a-Aminonitrile
Ezzat Rafiee,1,2 Solmaz Rashidzadeh,1 Mohammad Joshaghani,1
Hadi Chalabeh,1 and Kambiz Afza1
1Department of Chemistry, Faculty of Science, Razi University,
Kermanshah, Iran
2Kermanshah Oil Refining Company, Kermanshah, Iran
Abstract: The multicomponent Strecker reaction using trimethylsilyle cyanide
was performed in very short reaction times, and a-aminonitriles were prepared
in excellent yields in the presence of a catalytic amount of alumina-supported
tungstosilicic acid.
Keywords: Alumina, a-aminonitrile, heterogeneous catalyst, strecker reaction,
supported heteropoly acid
In the past decade, heteropoly acids (HPAs) have attracted great interest
as catalysts. Their acid–base and redox properties are widely used in het-
erogeneous catalysis.[1] Heteropoly compounds with Keggin structure are
the most studied class of polyoxometalates because they possess relatively
high thermal stability and high intrinsic acidity.[2] HPAs have low specific
area (1–10 m2=g), so it is important to increase the surface area or even
better to increase the number of accessible acid sites of the HPAs. This
can be achieved by dispersing the HPAs on a solid support with high sur-
face area.[3] Surface area enhancement, higher dispersion of acidic pro-
tons, heterogenization, and acid strength control are some of the goals
of using supported HPAs. These supported catalysts are widely studied,
and they have found useful applications in many organic reactions.[4]
Bifunctional a-aminonitriles are not only versatile intermediates for
Received in the U.K. September 18, 2007
Address correspondence to Ezzat Rafiee, Department of Chemistry, Faculty of
Science, Razi University, Kermanshah 67149, Iran. E-mail: e.rafiei@razi.ac.ir
2741

2742
E. Rafiee et al.
the synthesis of a-aminoacids[5] and various nitrogen-containing hetero-
cycles such as imidazoles and thiadiazoles, but they also exhibit a valu-
able dual reactivity, which has been utilized in a broad range of
synthetic applications.[6]
They are often synthesized by the Strecker reaction[7] and are highly
useful synthons for the synthesis of biologically useful molecules such as
saframycin A, a natural product with antitumor activity or phthalascidi,
a synthetic analog that exhibits even greater potency.[8] The classical pro-
cedure involves the treatment of an aldehyde or a ketone with alkaline
cyanides and salts of amines, and was discovered a century and a half
ago.[7] Numerous modifications have been made to the original Strecker
reaction using a variety of cyanating agents such as hydrogen cyanide,
sodium or potassium cyanide, Bu3SnCN, bis(dialkylamino)cyanobor-
anes,
diethylphosphorocyanidate,
and
trimethylsilyle
cyanide
(TMSCN).[9] TMSCN is a safer, more effective, and more easily handled
anion source than others.[10] The efficiency of the reaction has also been
increased by the use of catalysts.[9-11]
In continuation of our ongoing work on solid acid catalysts for
developing new synthetic methodologies,[4a,4b] herein we introduce sup-
ported HPAs as catalysts for synthesis of a-aminonitriles (Scheme 1).
Initially, the primary structures of supported HPAs were identified
by comparing their Fourier transform infrared spectroscopy (FTIR)
absorbtion bands to those of bulk HPAs. Keggin tungstosilicic acid
(SiW) consists of an SiO4 tetrahedron surrounded by four W3O13 groups
formed by edge-sharing octahedral. These groups are connected to each
other by corner-sharing oxygens,[12] and this arrangement gives rise to
four types of oxygen bands between 1200 and 700 cmꢀ1, a fingerprint
region for these compounds. Bulk SiW shows the characteristic IR bands
at ca. 982 cmꢀ1 (terminal W¼O), 928 cmꢀ1 (Si-O in central tetrahedral),
and 880 and 786 cmꢀ1 (W-O-W) associated with the asymmetric vibra-
tions in the Keggin polyanions. FTIR of the supported SiW indicates
that the primary Keggin structure is preserved after supporting SiW on
alumina. It should be emphasized that some bands overlapped with those
of the supports.
Scheme 1. Synthesis of a-amino nitrile.

Strecker Reaction in the Presence of Alumina-Supported HPA
2743
Table 1. Effect of different catalysts under different reaction conditions for
condensation of benzaldehyde, aniline, and TMSCN
Entry
Catalyst
Solvent
Yield (%)a
Time (min)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
PMo (2.7 mol%)
PW (2.7 mol%)
SiW (2.7 mol%)
Al2O3 (1.0 g)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2Cl2
C6H6
98
98
98
80
98
94
98
92
98
94
98
76
43
67
3
2
5
100
1
5
1
5
2
5
40%PMo=Al2O3 (0.2 g)
40%PW= Al2O3 (0.2 g)
40%SiW=Al2O3 (0.2 g)
20%SiW=Al2O3 (0.2 g)
60%SiW=Al2O3 (0.2 g)
40%SiW=Al2O3 (0.1 g)
40%SiW=Al2O3 (0.4 g)
40%SiW=Al2O3 (0.2 g)
40%SiW=Al2O3 (0.2 g)
40%SiW=Al2O3 (0.2 g)
1
30
15
15
THF
aIsolated yield.
Although the three-component Strecker reaction involving benzal-
dehyde, aniline, and TMSCN in the presence of catalytic amounts of
the different HPAs shows excellent yield (Table 1, entries 1–3), it is a
homogeneous reaction and recovery of catalyst is tedious. Thus, optimi-
zation experiments for the model reaction in the presence of a catalytic
amount of HPA=c-Al2O3 were carried out. After some experimentation
with respect to the different HPAs, molar ratios, and catalyst loadings,
the best results were obtained in the presence of 40 wt% of SiW=
c-Al2 O3 with 2.5 mol% catalyst loading (Table 1, entries 4–11). It seems
that acetonitrile is a much better solvent than all other tested solvents
(such as dichloromethane, tetrahydrofuran, and toluene) (Table 1, entries
7, 12–14). It is striking to note that no improvements in the reaction rates
and yields were observed by increasing the temperature to 90 ꢁC.
The reaction was applied to other aliphatic, heterocyclic, and aromatic
aldehydes carrying either electron-donating or electron-withdrawing
substitutions and aromatic, benzylic, and aliphatic (both primary and
secondary) amines (Table 2). To our knowledge, only a few reports of
Strecker reactions with ketones were found in the literature,[10–12] but as
evidenced in Table 2, entries 16–19, ketones gave excellent yields at longer
reaction times in this report.

2744
E. Rafiee et al.
Table 2. Alumina-supported H4SiW12O40-catalyzed synthesis of a-aminonitriles
Entry Aldehyde=ketone
Amine
Time (min) Yield (%)a Ref.b
1
2
3
4
5
6
7
8
9
10
11
12
13
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
3-Methoxybenzaldehyde Aniline
3-Methoxybenzaldehyde Benzylamine
3-Methoxybenzaldehyde Butylamine
4-Chlorobenzaldehyde
4-Methylbenzaldehyde
Furfural
Aniline
1
1
8
8
2
8
5
8
6
2
3
6
10
98
98
95
94
98
98
98
92
96
98
94
94
91
10g
10d
10g
9a
9a
9a
Benzylamine
Butylamine
Isobutylamine
9a
Aniline
Aniline
Aniline
Benzylamine
Aniline
Benzylamine
10g
10g
10a
10g
10g
10d
Furfural
Cinamaldehyde
Thiophene-2-
carboxaldehyde
Decanal
Benzaldehyde
Cyclohexanone
Cyclohexanone
14
15
16
17
18
19
Aniline
1
2
30
45
30
30
98
94
90
92
95
89
10d
9a
9a
9a
9a
9a
Morpholine
Benzylamine
Butylamine
3-Methyl cyclohexanone Benzylamine
3-Methyl cyclohexanone Morpholine
aIsolated yield
bProducts were characterized by comparison of their spectroscopic data with
those reported in the literature.
Acid-sensitive aldehydes such as furfural and cinnamaldehyde
worked well without the formation of any side products (Table 2, entries
10–12). Furthermore, the reaction conditions are mild enough to perform
in the presence of enolizable aldehydes such as decanal (Table 2, entry
14). These three-component coupling reactions proceeded efficiently at
ambient temperature with high selectivity.
In addition, SiW=Al2O3 could be recovered and subsequently reused
several times simply by filtering the catalyst, washing with acetonitrile,
and drying in an oven at 120ꢁC for 2 h, to remove the adsorbed reactants
or product. It showed a slightly loss of activity after four successive
runs: the yield of the product for the model reaction was 85% after the
fourth run. Also, the reaction mixture was filtered 30 s after the first
run. Then the reaction was resumed with the filtrate, in the absence of

Strecker Reaction in the Presence of Alumina-Supported HPA
2745
any externally added catalyst. No increase in conversion was observed
after 10 min, which proves it is a real heterogenic catalyst.
In conclusion, the results presented in this article demonstrate that
alumina can be regarded as a good support for HPAs. SiW=Al2O3 is
an efficient, environmentally friendly, cheap, and nontoxic catalyst with
very easy workup. Also, the present procedure represents a clean, practi-
cal, simple, mild, and time-saving method for synthesis of a-aminonitriles
in short reaction times and excellent yields with 100% selectivity.
EXPERIMENTAL
Catalyst based on HPA supported on c-Al2O3 was prepared by the
impregnation method. The solution of HPA was prepared by dissolving
an appropriate amount of HPA (with concentrations depending upon the
loading required to support 20, 40, and 60 wt% HPA to alumina) in
25 mL of aqueous solution. Then 5.0 g of c-Al2O3 was dropped into this
solution under vigorous stirring, and the resulting solution was impreg-
nated for 24 h. After that, catalyst was dried at room temperature for
24 h and calcined at 200ꢁC for 3 h.
Typical Procedure for the Synthesis of a-Aminonitriles
A mixture of aldehyde (1 mmol), amine (1.1 mmol), TMSCN (1.5 mmol),
and SiW=Al2O3(2.7 mol%) in acetonitrile (3 mL) was stirred at room
temperature for an appropriate time (Table 2). After completion of the
reaction, as indicated by thin-layer chromatography (TLC), the reaction
mixture was filtered and washed with acetonitrile (2 ꢂ 10 mL). The com-
bined organic layers were dried over anhydrous Na2SO4, concentrated
in vacuo, and purified by column chromatography on silica gel (ethyl
acetate=n-hexane, 1:9) to afford pure a-aminonitrile. All products were
identified by comparison of their spectral data with those of the authentic
samples.[9a,10a,10d,10g]
ACKNOWLEDGMENT
The authors thank the Razi University Research Council and
Kermanshah Oil Refining Company for support of this work.
REFERENCES
1. (a) Holderich, W. F. In Comprehensive Supramolecular Chemistry; J. L.
Atwood, J. E. P. Davies, D. D. MacNicol, F. Vo¨gtle, (Eds.); Pergamon Press:

2746
E. Rafiee et al.
Oxford, 1996. vol. 7, p. 671; (b) Pope, M. T.; In Comprehensive Coordination
Chemistry II; A. G. Wedd (Ed.); Elsevier: Oxford, U.K., 2004; vol. 4, p. 635;
(c) Hill, C. L. In Comprehensive Coordination Chemistry II; A. G. Wedd
(Ed.); Elsevier: Oxford, U.K., 2004; vol. 4, p. 679.
2. (a) Drago, R. S.; Dias, J. A.; Maier, T. O. An acidity scale for Brønsted acids
including H3PW12O40. J. Am. Chem. Soc. 1997, 119, 7702–7710; (b) Dias, J.
A.; Dias, S. C. L.; Kob, N. E. Dehydration of 1-propanol using H3PW12O40
as catalyst. J. Chem. Soc., Dalton Trans. 2001, 3, 228–231.
3. (a) Kozhevnikov, I. V.; Sinnema, A.; Jansen, R. J. J.; Pamin, K.; Van Bekkum,
H. New acid catalyst comprising heteropoly acid on a mesoporous molecular
sieve MCM-41. Catal. Lett. 1995, 30, 241–252; (b) Moffat, J. B. Metal–Oxygen
Cluster—The Surface and Catalytic Properties of Heteropoly Oxometalates;
Kluwer: New York, 2001; p. 25; (c) Kozhevnikov, I. V.; Kloetstra, K. R.;
Sinnema, A.; Zandbergen, H. W.; van Bekkum, H. The study of catalysts
comprising heteropoly acid H3PW12O40 supported on MCM-41 molecular sieve
and amorphous silica. J. Mol. Catal. A: Chem. 1996, 114, 287–298.
4. (a) Rafiee, E.; Shahbazi, F. One-pot synthesis of dihydropyrimidones using
silica-supported heteropoly acid as an efficient and reusable catalyst:
Improved protocol conditions for the Biginelli reaction. J. Mol. Catal. A:
Chem. 2006, 250, 57–61; (b) Rafiee, E.; Rashidzadeh, S.; Azad, A. Silica-
supported heteropoly acids: Highly efficient catalysts for synthesis of
a-aminonitriles, using trimethylsilyl cyanide or potassium cyanide. J. Mol.
Catal. A: Chem. 2006, 261, 49–52; (c) Izumi, Y.; Hisano, K.; Hida, T. Acid
catalysis of silica-included heteropolyacid in polar reaction media. Appl.
Catal. A 1999, 181, 277–282.
5. (a) Enders, D.; Shilvock, J. P. Some recent application of a-aminonitrile
chemistry. Chem. Soc. Rev. 2000, 29, 359–373; (b) Shafran, Y. M.; Bakulev,
V. A.; Mokrushin, V. S. Synthesis and properties of a-aminonitriles. Russ.
Chem. Rev. 1989, 58, 148–162; (c) March, J. Advanced Organic Chemistry,
´
4th ed.; Wiley: New York, 1999; p. 965; (d) Gonzalez-Vera, J. A.; Garcıa-
Lopez, M. T.; Herranz, R. Molecular diversity via amino acid derived
´
´
a-aminonitriles: Synthesis of spirocyclic 2,6-dioxopiperazine derivatives. J.
Org. Chem. 2005, 70, 3660–3666; (e) Dyker, G. Amino acid derivatives by
multicomponent reactions. Angew. Chem., Int. Ed. 1997, 36, 1700–1702.
6. (a) Weinstock, L. M.; Davis, P.; Handelsman, B.; Tull, R. A. General synthetic
system for 1,2,5-thiadiazoles. J. Org. Chem. 1967, 32, 2823–2829; (b) Matier,
W. L.; Owens, D. A.; Comer, W. T.; Deitchman, D.; Ferguson, H. C.;
Seidehamel, R. J.; Young, J. R. Antihypertensive Agents: Synthesis and
biological properties of 2-amino-4-aryl-2-imidazolines. J. Med. Chem. 1973,
16, 901–908.
7. Strecker, A. Ueber die Kunstliche Bildung der Milchsa¨ure und einen neuen,
¨
dem Glycocoll homologen Ko¨rper. Ann. Chem. Pharm. 1850, 75, 27–45.
8. (a) Duthaler, R. O. Recent developments in the stereoselective synthesis of
a-aminoacids. Tetrahedron 1994, 50, 1539–1650; (b) Martinez, E. J.; Corey,
E. J. Enantioselective synthesis of saframycin A and evaluation of antitumor
activity relative to ecteinascidin=saframycin hybrids. Org. Lett. 1999, 1, 75–78.

Strecker Reaction in the Presence of Alumina-Supported HPA
2747
9. (a) Ranu, B. C.; Dey, S. S.; Hajra, A. Indium trichloride catalyzed one-pot
synthesis of a-aminonitriles by a three-component condensation of carbonyl
compounds, amines, and potassium cyanide. Tetrahedron 2002, 58, 2529–
2532; (b) Harusawa, S.; Hamada, Y.; Shioiri, T. Diethyl phosphorocyanidate
(DEPC), a novel reagent for the classical Strecker’s a-aminonitriles synthesis.
Tetrahedron Lett. 1979, 48, 4663–4666; (c) Royer, L.; De, S. K.; Gibbs, R. A.
Iodine as a novel efficient reagent for the synthesis of a-aminonitriles by a
three-component condensation of carbonyl compounds, amines, and tri-
methylsilyl cyanide. Tetrahedron Lett. 2005, 46, 4595–4597; (d) Suginome,
M.; Yamamoto, A.; Ito, Y. Bis(dialkylamino)cyanoboranse: Highly efficient
reagents for the Strecker–type aminative cyanation of aldehydes and ketones.
Chem. Commun. 2002, 1392–1393; (e) Kobayashi, S.; Busujima, T.;
Nagayama, S. Scandium triflate–catalyzed Strecker-type reactions of alde-
hydes, amines, and tributyltin cyanide in both organic and aqueous solutions:
Achievement of complete recovery of the tin compounds toward environmen-
tally friendly chemical processes. Chem. Commun. 1998, 981–982.
10. (a) Yadav, J. S.; Reddy, B. V. S.; Eeshwaraiah, B.; Srinivas, M. Montmorillo-
nite KSF clay catalyzed one-pot synthesis of a-aminonitriles. Tetrahedron
2004, 60, 1767–1771; (b) Fetterly, B. M.; Jana, N. K.; Verkade, J. G.
[HP(HNCH2)3N]NO3: An efficient homogeneous and solid-supported promoter
for aza and thia-Michael reactions and for Strecker reactions. Tetrahedron 2005,
61, 1–18; (c) Kobayashi, S.; Nagayama, S.; Busujima, T. Polymer scandium-
catalyzed three-component reactions leading to diverse amino ketone, amino
ester, and amino nitrile derivatives. Tetrahedron Lett. 1996, 37, 9221; (d) Yadav,
J. S.; Reddy, B. V. S.; Eshwaraiah, B.; Srinivas, M.; Vishnumurthy, P. Three-
component coupling reactions in ionic liquids: A facile synthesis of a-aminoni-
triles. New J. Chem. 2003, 27, 462–465; (e) De, S. K.; Gibbs, R. A. Bismuth
trichloride–catalyzed synthesis of a-aminonitriles. Tetrahedron Lett. 2004, 45,
7407–7408; (f) Heydari, A.; Fatemi, P.; Alizadeh, A. Lithium perchlora-
te=diethylether–catalyzed aminocyanation of aldehydes. Tetrahedron Lett.
1998, 39, 3049–3050; (g) De, S. K. Nickel(II) chloride–catalyzed one-pot
synthesis of a-aminonitriles. J. Mol. Catal. A: Chem. 2005, 225, 169–171.
11. (a) De, S. K. RuCl3-catalyzed one-pot synthesis of a-aminonitriles. Synth.
Commun. 2005, 35, 653–656; (b) De, S. K.; Gibbs, R. A. Praseodynium
trifluromethylsulfonate as an efficient and recyclable catalyst for the syn-
thesis of a-aminonitriles. Synth. Commun. 2005, 35, 961–966; (c) Kobayashi,
S.; Ishitani, H.; Ueno, M. Facile synthesis of a-aminonitriles using lanthanide
triflate as a Lewis acid catalyst. Synlett 1997, 115–116.
12. Kozhevnikov, I. V. Catalysis for Fine Chemical Syntheses—Catalysis by
Polyoxometalates; John Wiley & Sons: Chichester, 2002; p. 50.