Silica-bonded S-sulfonic acid: an efficient and recyclable solid acid catalyst for the three-component synthesis of α-amino nitriles

Article abstract of DOI:10.1016/j.tetlet.2010.03.093

Silica-bonded S-sulfonic acid (SBSSA) is employed as a recyclable catalyst for the synthesis of α-amino nitriles. These syntheses were performed via a one-pot three-component condensation of aldehydes, amines, and trimethylsilyl cyanide under mild reaction conditions at room temperature.

Full text of DOI:10.1016/j.tetlet.2010.03.093

Tetrahedron Letters 51 (2010) 2959–2962
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Tetrahedron Letters
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Silica-bonded S-sulfonic acid: an efficient and recyclable solid acid catalyst
for the three-component synthesis of a-amino nitriles
*
Khodabakhsh Niknam , Dariush Saberi, Maryam Nouri Sefat
Chemistry Department, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Silica-bonded S-sulfonic acid (SBSSA) is employed as a recyclable catalyst for the synthesis of
a-amino
Received 26 January 2010
Revised 16 March 2010
Accepted 22 March 2010
Available online 2 April 2010
nitriles. These syntheses were performed via a one-pot three-component condensation of aldehydes,
amines, and trimethylsilyl cyanide under mild reaction conditions at room temperature.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Silica-bonded S-sulfonic acid
Aldehydes
Amines
a-Amino nitriles
One-pot synthesis
Table 1
1. Introduction
Condensation of benzaldehyde, aniline and TMSCN in the presence of different
amounts of SBSSAa
The addition of cyanide anion to imines (the Strecker reaction)1
provides one of the most important and straightforward method
Entry
Catalyst loading (g)
Time (min)
Yieldb
1
2
3
4
5
No catalyst
0.05
0.1
0.2
0.3
24 h
100
60
30
30
0
80
90
94
95
for the synthesis of
a-aminonitriles, which are useful intermedi-
ates for the synthesis of amino acids2,3 and nitrogen containing
heterocycles such as thiadiazoles and imidazoles, etc.4,5 The classi-
cal Strecker reaction usually is carried out in aqueous solution and
the work-up procedure is also tedious. Thus several modifications
of Strecker reaction have been reported using a variety of cyanide
a
Reaction conditions; benzaldehyde (1 mmol), aniline (1.2 mmol), TMSCN
(1.2 mmol), EtOH (2 ml), room temperature.
reagents,6–8 such as diethyl phosphorocyanidate and
a-trimethyl-
b
Isolated yield.
O
SH
OH
OH
(MeO)3Si
SiO2
O
O
Si
SH
SiO2
toluene, reflux, 18 h
OH
1
O
1) ClSO3H/ CHCl3 /4 h
2) wash with MeOH
O Si
S-SO3H
SiO2
O
2
Scheme 1. Preparation of silica-bonded S-sulfonic acid (SBSSA).
* Corresponding author. Tel.: +98 771 4541494; fax: +98 771 4545188.
E-mail addresses: khniknam@gmail.com, niknam@pgu.ac.ir (K. Niknam).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.03.093

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K. Niknam et al. / Tetrahedron Letters 51 (2010) 2959–2962
Table 2
SBSSA
Condensation of benzaldehyde, aniline and TMSCN in different solvents and under
solvent-free conditions in the presence of SBSSA (0.2 g)
R-CHO + R-NH2 + TMSCN
R-C-NH-R
CN
EtOH, rt
Entry
Solventa
Time (min)
Yieldb
4
3
5
1
2
3
4
5
6
EtOH
H2O
CH2Cl2
n-Hexane
MeCN
30
120
120
120
60
94
75
70
30
90
90
R = aliphatic, aromatic
R = primary, secondary
Scheme 2. Synthesis of a-amino nitrile derivatives catalyzed by SBSSA.
Solvent-free
120
a
The reaction was carried out in 2 mL of solvent at rt.
Isolated yield.
b
Table 3
Preparation of various
a
-amino nitriles in the presence of SBSSA in EtOH at room temperaturea
Entry
R
R0
Product (5)
Time (min)
30
Yield (%)b
94
Mp (°C)
Lit. Mp (°C)
H
C
H
N
a
C6H5–
C6H5–
80–82
81–8322
CN
H
C
H
F
N
b
c
4-F–C6H4–
C6H5–
40
90
25
90
92
93
99–101
85–87
95–97
98–10015
84–858
CN
H
C
H
N
Me
Cl
4-Cl–C6H4–
4-MeO–C6H4
4-Me–C6H4–
C6H5–
CN
H
C
H
94–9511
N
MeO
d
CN
H
C
H
e
C6H5–
3,4-(Me)2–C6H3–
25
88
92–94
—
N
CN
H
H
C
N
Br
MeS
f
4-MeS–C6H4–
C6H5–
4-Br–C6H4–
4-Br–C6H4–
30
40
91
85
122–124
91–93
—
—
CN
H
C
H
N
Br
g
CN
MeO
MeO
MeO
H
C
CN
H
N
h
i
3,4,5-(MeO)3–C6H2–
2,4-(Cl)2–C6H3
C6H5–
C6H5–
25
80
95
78
147–149
115–117
—
—
Cl
H
C
H
N
Cl
CN
H
C
H
N
MeS
j
4-MeS–C6H4–
3-O2N–C6H4–
4-Me–C6H4–
C6H5–
40
80
86
91
102–104
89–92
—
—
CN
H
H
N
C
k
CN
O2N
F
H
C
H
N
l
4-F–C6H4–
C6H5–
4-Me–C6H4–
4-Me–C6H4–
60
25
94
90
101–103
102–104
—
—
CN
H
C
H
N
m
CN
NH
n
2-Thienyl–
C6H5–
60
81
100–102
98–10015
S
CN
H
C
O
N
O
HN
o
p
q
C6H5–
C6H5–
180
90
82
78
80
69–71
68–699
CN
H2
C
H
H
Colorless oil22
Colorless oil9
C
N
Ph-CH2–
Ph-CH2–
Colorless oil
Colorless oil
CN
H2
C
H
C
H
N
i-C3H7–
100
CN
CHO
NH
r
C6H5–
100
78
55–57
56–5817
NC
a
Reaction conditions: aldehyde (1 mmol), aniline (1.2 mmol), TMSCN (1.2 mmol), SBSSA (0.2 g), room temperature, EtOH.
Isolated yield.
b

K. Niknam et al. / Tetrahedron Letters 51 (2010) 2959–2962
2961
Table 4
Comparison of the result of condensation reaction of benzaldehyde and aniline with TMSCN in the presence of different catalysts based on silica
Entry
Catalyst
Catalyst loading (g)
Conditions
Time (min)
Yielda
Ref.
1
2
3
4
4
5
SBSSA
0.2 (0.066 mmol)
1.0
0.1 (0.03 mmol)
0.1 (0.06 mmol)
0.095 (0.25 mmol)
0.031 (0.017 mmol)
rt
rt
rt
rt
rt
50 °C
30
210
840
65
360
5
94
90
94
97
88
Present work
Montmorillonite KSF clay
Silica-based scandium(III)
Xanthene sulfuric acid
Silica sulfuric acid
11
12
22
24
25
SBA-15 supported sulfonic acid
100
a
Isolated yield.
100
90
80
70
60
50
40
30
20
10
0
siloxy nitriles, as well as catalysts such as InCl3,9 BiCl3,10 montmo-
rillonite KSF clay,11 silica-based scandium(III),12 SO42ꢀ/ZrO2, fer-
13
ric perchlorate,14 Fe(Cp)2PF6,15 InI3,16 I2,17 K5CoW12O40ꢁ3H2O,18
vanadyl triflate,19 Fe3O4,20 guanidine hydrochloride,21 xanthan sul-
furic acid,22 [bmim]BF4,23 silica sulfuric acid,24 hydrophobic sul-
fonic acid based nanoreactors25 under various reaction
conditions. The use of trimethylsilyl cyanide is a safer and more
effective cyanide anion source for the nucleophilic addition reac-
tions of imines under mild conditions.26–28 However, many of
these methods involve the use of expensive reagents, harsh condi-
tions, extended reaction times, and also require tedious workup
leading to the generation of a large amount of toxic waste. Further
more many of these catalysts are deactivated or sometimes decom-
posed by amines and water that exist during imine formation. In
order to overcome these problems, recently one-pot procedures
have been developed for this transformation.29–31
1
2
3
Run
4
5
Figure 1. Recyclability of SBSSA (0.2 g) in the reaction of benzaldehyde (1 mmol)
and aniline (1.2 mmol) with TMSCN (1.2 mmol) in 2 mL EtOH at room temperature.
Reaction time = 30 min.
In continuation of our work to develop new catalysts for organic
transformations, here we report mild, efficient and environmen-
and 5k in high yields. The acid sensitive substrate thiophene-2-
tally benign catalyst for the preparation of
a-aminonitriles from
carbaldehyde 3n gave the expected a-amino nitrile 5n in very good
aldehydes, amines and trimethylsilyl cyanide in the presence of
silica bonded S-sulfonic acid (SBSSA) in ethanol at room
temperature.
yield (Table 3, entry n). Most of primary and secondary amines are
easily reacted in these condensations (Table 3).
To show the efficiency of the SBSSA in comparison with previ-
ously reported procedures in the literature, Table 4 compares some
of our results with montmorillonite KSF clay,11 silica-based scan-
dium(III),12 xanthan sulfuric acid,22 silica sulfuric acid,24 and
hydrophobic sulfonic acid based nanoreactors25 with respect to
reaction times, yields of obtained products. It is clear from the re-
sults shown in Table 4, which condensation reaction carried out
with SBSSA requires shorter reaction time and higher yield.
The possibility of recycling the catalyst was examined using the
reaction of benzaldehyde and aniline with TMSCN under the opti-
mized conditions. Upon completion, the reaction mixture was fil-
tered and washed with warm ethanol. The product was
recrystallized from hot ethanol. The recovered catalyst was dried
and reused for subsequent runs. The recycled catalyst could be re-
used five times without any additional treatment. No observation
of any appreciable loss in the catalytic activity of SBSSA was ob-
served (Fig. 1).
Recently, we have reported the preparation of silica-bonded
S-sulfonic acid (SBSSA) and used it as a catalyst for the synthesis
of 1,1-diacetates,32 quinoxaline,33 coumarin derivatives,34 4,40-
(arylmethylene)bis(1H-pyrazol-5-ols),35
and
silyl
ethers36
(Scheme 1).
To study the effect of catalyst loading on the condensation of
aldehydes, amines, and trimethylsilyl cyanide as the corresponding
a-amino nitriles, the reaction of benzaldehyde and aniline with
TMSCN was chosen as a model reaction (Table 1). To illustrate
the need of SBSSA for this condensation we examined the model
reaction in the absence of SBBSA. In this case the reaction did not
proceed even after 24 h (Table 1, entry 1). Obviously, SBSSA is an
important component of the reaction.
The model reaction was also examined in various solvents as
well as under solvent-free conditions in the presence of 0.2 g
(0.066 mmol/g) of SBSSA (Table 2).
The results showed that the efficiency and the yield of the reac-
tion in EtOH were higher than those obtained in other solvents or
under solvent-free conditions. Therefore, we employed the opti-
mized conditions [aldehyde (1 mmol), amine (1.2 mmol), TMSCN
(1.2 mmol), SBSSA (0.2 g) and EtOH (2 mL)] for the synthesis of
In conclusion, we have shown that silica-bonded S-sulfonic acid
catalyzed efficiently the synthesis of a-amino nitriles by a one-pot
three-component condensation of aldehydes, amines, and trimeth-
ylsilyl cyanide. The mild reaction conditions, simplicity of the pro-
cedure and the recovery of the catalyst are the advantages of this
method.
All the products were characterized by comparison of their IR,
1H NMR and 13C NMR spectroscopic data and their melting points
with reported values.37 Silica-bonded S-sulfonic acid (SBSSA) was
prepared according to our previously reported procedure.32–36
a
-amino nitriles in this one-pot three-component condensation
(Scheme 2).
Next, we prepared a range of
a-amino nitriles under the opti-
mized conditions (Table 3). Both aromatic and aliphatic aldehydes
reacted with amines and TMSCN in the presence of SBSSA in this
one-pot condensation to afford excellent yields of corresponding
a-amino nitriles. Moreover, aldehydes with electron-donating or
Acknowledgment
electron-withdrawing groups, that is, 4-methoxybenzaldehyde
3d, and 3,4,5-trimethoxybenzaldehyde 3h, or 3-nitrobenzaldehyde
3k, were converted into the corresponding a-amino nitriles 5d, 5h
We are thankful to Persian Gulf University Research Council for
partial support of this work.

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K. Niknam et al. / Tetrahedron Letters 51 (2010) 2959–2962
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General procedure:
A mixture of aldehyde (1 mmol), amine (1.2 mmol),
trimethylsilyl cyanid (1.2 mmol), and SBSSA (0.2 g) in EtOH (2 mL) was
stirred at room temperature for appropriate time (Table 3). After completion
of the reaction, as indicated by TLC, the reaction mixture was filtered and the
remaining washed with warm ethanol (3 ꢂ 5 mL). After cooling, the
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corresponding
a-amino nitrile products were obtained which were purified
by recrystallization from hot ethanol. The recovered catalyst was dried and
reused for subsequent runs.
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