Sulfated tungstate: A green catalyst for Strecker reaction

Article abstract of DOI:10.1016/j.tetlet.2011.12.027

A straightforward, mild, efficient, and general method has been developed for the synthesis of α-aminonitriles via Strecker reaction starting from aldehydes or ketones, amines, and trimethylsilyl cyanide in the presence of sulfated tungstate as a heterogeneous mild solid acid catalyst at room temperature and solvent free condition. The developed method has been successfully applied for the synthesis of a wide range of α-aminonitriles with variable functionality.

Full text of DOI:10.1016/j.tetlet.2011.12.027

Tetrahedron Letters 53 (2012) 871–875
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Tetrahedron Letters
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Sulfated tungstate: a green catalyst for Strecker reaction
⇑
Sagar P. Pathare, Krishnacharya G. Akamanchi
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400 019, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A straightforward, mild, efficient, and general method has been developed for the synthesis of a-amino-
Received 12 October 2011
Revised 6 December 2011
Accepted 8 December 2011
Available online 13 December 2011
nitriles via Strecker reaction starting from aldehydes or ketones, amines, and trimethylsilyl cyanide in the
presence of sulfated tungstate as a heterogeneous mild solid acid catalyst at room temperature and sol-
vent free condition. The developed method has been successfully applied for the synthesis of a wide range
of a-aminonitriles with variable functionality.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Sulfated tungstate
Strecker reaction
a-Aminonitriles
TMSCN
Recently we have synthesized and characterized sulfated tung-
state and demonstrated its effectiveness as green catalyst in ami-
dation,1 Ritter,2 Biginelli,3 and Willgerodt4 reactions. Attributes of
sulfated tungstate such as easy preparation, mild acidity, stability,
and reusability have caught our attention for further exploration
and expanded its applications. In this Letter one such exploration
toward its potential as catalyst in Strecker reaction, a multicompo-
nent reaction of an aldehyde, an amine, and a cyanating agent for
production, have also been employed for the reaction. The exam-
ples include polymer-supported Sc(OTf)3,18a montmorillonite
KSF-clay,18b silica–H2SO4,18c,d heteropoly acid,18e–g NH2SO3H,18h,i
and poly(4-vinylpyridine)–SO2 complex.5c One of the major short
comings of all of these methods with some exceptions is that start-
ing carbonyl compounds are mostly limited to aldehydes. Attempts
toward further improvements to over-come this limitation have
led to methods suitable for ketones or both aldehydes and ketones,
and these include, Jung et al. modification to affect Strecker
synthesis of a-aminonitriles, is presented.
Strecker reaction5,6 is one of the most important multicompo-
nent reactions in organic chemistry for direct one-pot synthesis
O
CN
of
a-aminonitriles. a-Aminonitriles find wide applications in or-
Sulfated
H2N
H
tungstate
N
ganic synthesis. They serve as efficient precursors, for the synthesis
TMSCN
H
of natural and unnatural a-amino acids, different nitrogen contain-
ing heterocycles like imidazoles, thiadiazoles7,8 bioactive mole-
cules like clopidogrel, prasugrel, saframycin A,9 manzacidin A,
Scheme 1. Strecker reaction of benzaldehyde, aniline, and TMSCN.
and short-acting opioid analgesics.10
a-Aminonitriles are generally
prepared by nucleophilic addition of cyanide anion to imines using
a variety of cyanating agents such as HCN,5 KCN,11 Et2AlCN,12
(EtO)2P(O)CN,13 Bu3SnCN,14 and Me3SiCN11 under Strecker-type
reaction conditions.15 Trimethylsilyl cyanide (TMSCN) is an effec-
tive and safe source of cyanide anions16 and is most commonly em-
ployed as cyanide source in the presence of various Lewis acids
such as Yb(OTf)3,17a Pr(OTf)3,17b Cu(OTf)2,17c LiClO4,17d BiCl3,17e
NiCl2,17f RuCl3,17g CeCl3,17h InCl3,17i InI3,17j RhI3,17k La(NO3)3Á
6H2O or GdCl3Á 6H2O,17l I2,17m and (bromodimethyl)sulfonium bro-
mide.17n Several heterogeneous catalysts which are more advanta-
geous in terms of catalyst/product separation and continuous
Table 1
Results of optimization studiesa
Entry Solvent
Sulfated tungstate (wt %) Time (min) Yieldb (%)
1
2
3
4
5
6
7
8
9
Neat
Neat
Neat
Neat
—
1
720
60
60
10
10
10
60
60
60
—
18
67
99
99
97
93
90
64
5
10
20
10
10
Neat
Water
Ethanol
Ethyl acetate 10
Toluene 10
a
Reaction conditions: benzaldehyde (1 g, 9.4 mmol), aniline (0.88 g, 9.4 mmol),
and TMSCN (0.94 g, 9.4 mmol) at rt.
⇑
Corresponding author. Tel.: +91 22 33612214; fax: +91 22 24145614.
E-mail address: kgap@rediffmail.com (K.G. Akamanchi).
b
Isolated yield.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.12.027

872
S. P. Pathare, K. G. Akamanchi / Tetrahedron Letters 53 (2012) 871–875
Table 2
Strecker reaction of various aldehyde and amines in the presence of sulfated tungstatea
O
CN
R2
R2
HN
R3
TMSCN
R1
H
R1
N
R3
Entry
1
Aldehyde R1
C6H5
Amine R2
C6H5
R3
H
Productb
Yieldc
99
CN
CN
N
H
OCH3
2
3
4
5
C6H5
4-MeOC6H4
H
H
H
H
99
99
95
97
N
H
CN
4-MeOC6H4
C6H5
N
H
H3CO
Cl
CN
C6H5
4-ClC6H4
N
H
CN
4-ClC6H4
C6H5
N
H
Cl
NO2
CN
6
7
C6H5
4-NO2C6H4
H
H
78
94
N
H
CN
2-Napthyl
C6H5
N
H
CN
8
Cinnamyl
2-Furyl
C6H5
C6H5
C6H5
H
H
H
99
85
89
N
H
CN
9
N
H
O
S
CN
10
2-Thienyl
N
H
CN
CN
11
12
C6H5
2-Pyridyl
C6H5CH2
H
H
90
96
N
H
N
C6H5
N
H
CN
13
14
C6H5
c-Hex
H
H
85
84
N
H
CN
Isobutyl
C6H5
N
H

S. P. Pathare, K. G. Akamanchi / Tetrahedron Letters 53 (2012) 871–875
873
Table 2 (continued)
Entry
Aldehyde R1
C6H5
Amine R2
n-butyl
R3
H
Productb
Yieldc
CN
CN
CN
15
16
80
87
86
N
H
C6H5
C6H5
-(CH2)5-
N
N
17
-(CH2)2-O-(CH2)2-
O
a
Reaction conditions: aldehyde (1 equiv), amine (1 equiv), TMSCN (1 equiv), and sulfated tungstate (10 wt %) at rt under solvent-free conditions.
All products are known compounds and were identified by their melting point, IR and 1H NMR spectra according to the literature.
Isolated yields.
b
c
reaction of ketones using palladium catalyst,19 Matsumoto et al.
which is prone to polymerization under acidic conditions was
stable and furfural gave very good yield of the corresponding a-
aminonitrile (Table 2, entry 9). Furthermore, a combination of ali-
protocol under high pressure conditions,20 Olah’s combination of
TMSCN with Ga(OTf)3,21,22 and Khan’s combination of TMSCN with
Fe(Cp)2PF6,23 and a recent method by Rao et al. using b-cyclodex-
trins as a medium.24 Suginome and co-workers have used bis(dial-
kylamino)cyanoborane as a new cyanide source and found suitable
for Strecker reaction of acyclic and cyclic aliphatic ketones.25 In
spite of several modifications there exists scope especially, for
green and efficient heterogeneous catalyst methods, because many
of the present methods require expensive reagents, harsh condi-
tions, extended reaction times, and tedious work-up procedure
leading to the generation of large amounts of toxic waste.
We investigated Strecker reaction in the presence of sulfated
tungstate as catalyst and the results are presented here. Prelimin-
ary investigations were carried out using benzaldehyde and aniline
as building blocks (Scheme 1) to find the suitability of sulfated
tungstate as a catalyst and optimize reaction conditions and details
are given in Table 1.
phatic/aromatic aldehydes and amines was investigated and was
found to react readily giving the corresponding
a-aminonitriles
in good yields (Table 2, entries 12–15). As expected, cyclic sec-
ondary amines viz. piperidine, morpholine also reacted smoothly
and gave high yields (Table 2, entries 16 and 17). It is to be noted
that with respect to yields, variations were in the range of 78–
99%. With the exception of p-nitroaniline, yield of a-aminonitriles
was very high (above 90%) in all cases of aromatic substrates
(Table 2, entries 1–8 and 12). In cases of aliphatic aldehyde or
amines as substrates, the yields were comparatively on the lower
side and were between 80% and 87% (Table 2, entries 13–17).
Encouraged by these promising results, studies were extended
to aromatic and aliphatic ketones, and different amines and the
results are given in Table 3. In general, compared to aldehydes,
reactions were very slow and took 6 h to complete. Substrate with
both electron-donating and electron withdrawing substituents on
the phenyl moiety of aromatic ketones underwent reaction
smoothly and gave excellent yield (Table 3, entries 2–7). In case
of halogenated acetophenones, halogen remained intact and no
side products were observed arising from nucleophilic displace-
ment of halogen under these conditions (Table 3, entries 4 and
5). Heteroaryl ketones, such as 2-acetylthiophene and 2-acetylpyr-
idine reacted equally well as demonstrated by using aniline as
Thus, when
a mixture of benzaldehyde (1 equiv), aniline
(1 equiv), TMSCN (1 equiv), and sulfated tungstate (10 wt %) was
stirred at rt, a fast reaction ensued and got completed in just
10 min to give 99% yield of 2-phenyl-2-(phenylamino)acetonitrile
(Table 1, entry 4). A control experiment was performed in the
absence of catalyst and the reaction did not occur (Table 1, entry
1) thus proving the catalytic role of sulfated tungstate. Next, exper-
iments were conducted to optimize the quantity of sulfated tung-
state and found that use of just 10 wt % of catalyst is sufficient to
produce an excellent yield of the product (Table 1, entries 2–5).
As regards use of solvent, water was found to be most suitable
and as good as neat system with respect to both yields and reaction
time (Table 1, entry 6), where-as other solvents such as ethanol,
ethyl acetate, and toluene were found to be relatively inferior
(Table 1, entries 7–9).
To assess substrate scope a number of structurally diverse
aldehydes, ketones, and amines have been screened for studying
the generality as well as the efficacy of the present procedure26
and results are as follows. Different aldehydes, aliphatic, aromatic,
and heteroaromatics were found to undergo these reactions and
the results are given in Table 2. Benzaldehyde and substituted
benzaldehydes containing electron-donating or electron-with-
drawing functionalities (Table 2, entries 1–6), naphthaldehyde
(Table 2, entry 7), and cinnamaldehyde (Table 2, entry 8) under-
went facile reactions giving very good to excellent yields. Reac-
tion proceeded equally smooth in the case of heterocyclic
aldehydes and amine (Table 2, entry 9–11). Even the furan ring
amine and gave
a-aminonitriles in high yields (Table 3, entries 8
and 9). Interestingly, the reaction of aliphatic ketones such as ethyl
methyl ketone, acetone, and cyclohexanone with aliphatic as well
as aromatic amines showed good yield under similar set of
conditions (Table 3, entries 10–14).
The work-up procedure is simple, catalyst is filtered off by
diluting the reaction mixture with ethyl acetate, and organic layer
was concentrated after giving water washes. The products
obtained in many cases were of high purity and do not require
any further purification.
Reusability study results summarized in Table 4, indicate that
the catalyst was stable and reusable four times without any signif-
icant loss of activity. It is noteworthy that the catalyst was
recovered simply by filtration without any acidic or basic workup
even after its fourth use.
Sulfated tungstate was found to be an efficient, clean, green cat-
alyst for Strecker reaction of both aldehydes and ketones under
solvent-free conditions. Operational simplicity, high yield, room
temperature, and reusability of the catalyst are the striking

874
S. P. Pathare, K. G. Akamanchi / Tetrahedron Letters 53 (2012) 871–875
Table 3
Strecker reaction of various Ketones and Amines in the presence of sulfated tungstatea
Sulfated
tungstate
O
CN
R2
R3 NH2
+
R3
+
TMSCN
R2
R1
R1
N
H
solvent free, rt
6h
Entry
1
Ketones R1
C6H5
R2
Amines R3
Productb
Yieldc
96
NC
CH3
CH3
CH3
C6H5
N
H
NC
CH3
2
3
4-MeC6H4
C6H5
96
93
N
H
NC
CH3
4-MeOC6H4
CH3
CH3
C6H5
N
H
H3CO
NC
CH3
4
4-ClC6H4
C6H5
91
N
H
Cl
NC
CH3
5
6
4-BrC6H4
CH3
CH3
C6H5
89
76
N
H
Br
NC
CH3
4-NO2C6H4
C6H5
N
H
O2N
NC
CH3
7
8
2-Napthyl
2-Thienyl
CH3
CH3
C6H5
C6H5
85
87
N
H
NC
CH3
N
H
S
N
NC
CH3
9
3-Pyridyl
CH3
C6H5
84
N
H
NC CH3
10
11
C6H5
C2H5
CH3
CH3
C6H5CH2
80
86
N
H
CH3
NC
C6H5
N
H
CH3
NC
12
13
14
CH3
CH3
CH3
C6H5
89
67
88
N
H
CH3
NC
CH3
n-C4H9
C6H5
N
H
CN
–CH2–(CH2)3–CH2–
N
H
a
b
c
Reaction conditions: ketones (1 equiv), amines (1 equiv), TMSCN (1 equiv), and catalyst (10 wt %) at rt under solvent-free conditions.
All products are known and were identified by their melting point, IR and 1H NMR spectra according to the literature.
Isolated yield.

S. P. Pathare, K. G. Akamanchi / Tetrahedron Letters 53 (2012) 871–875
875
Table 4
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S. K. J. Mol. Catal. A: Chem. 2005, 225, 169; (g) De, S. K. Synth. Commun. 2005, 35,
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Reusability studya
Run no.b
% Yield 2-phenyl-2-(phenylamino)acetonitrile
Fresh
99
97
97
96
93
First recycle
Second recycle
Third recycle
Fourth recycle
a
Reaction condition: benzaldehyde (1 g, 9.4 mmol), aniline (0.88 g, 9.4 mmol),
and TMSCN (0.94 g, 9.4 mmol) at rt.
b
Loss of catalyst (<5%) during handling.
features of this methodology. This new combination of TMSCN/sul-
fated tungstate might open up new vistas for applications.
Acknowledgments
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The authors thank the University Grants Commission of India
for financial support and Ms. Punit Bansal Globe Chemie Ltd Pune,
India for providing a gift sample of TMSCN.
22. Prakash, G. K. S.; Panja, C.; Do, C.; Mathew, T.; Olah, G. A. Synlett 2007, 2395.
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;
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