Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 1103–1106
www.elsevier.com/locate/cclet
Synthesis of a-aminonitriles using silica-bonded N-propylpiperazine
sulfamic acid as a recyclable catalyst
Tahere Rahi a, Mojtaba Baghernejad a, Khodabakhsh Niknam b,*
a
b
Department of Chemistry, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran
Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
Received 11 April 2012
Available online 23 September 2012
Abstract
a-Aminonitriles were synthesized via a one-pot three-component condensation of aldehydes, amines, and trimethylsilyl cyanide
using silica-bonded N-propylpiperazine sulfamic acid (SBPPSA) as a recyclable solid acid at room temperature. SBPPSA showed
much the same efficiency when used in consecutive reaction runs.
# 2012 Khodabakhsh Niknam. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Silica-bonded N-propylpiperazine sulfamic acid; a-Aminonitriles; Aldehydes; Amines; Catalyst; Solid acid
The addition of cyanide anion to imines (the Strecker reaction) [1] provides one of the most important and
straightforward method for the synthesis of a-aminonitriles, which are useful intermediates for the synthesis of amino
acids [2] and nitrogen containing heterocycles such as thiadiazoles and imidazoles. [3,4]. The classical 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 reagents [5], such as diethyl
phosphorocyanidate and a-trimethylsiloxy nitriles, as well as catalysts such as InCl3 [6], [bmim]BF4 [7],
montmorillonite KSF clay [8], silica sulfuric acid [9], I2 [10], Fe(Cp)2PF6 [11], xanthan sulfuric acid [12],
hydrophobic sulfonic acid based nanoreactors [13], silica-bonded S-sulfonic acid [14], and sulfamic acidfunctionalized magnetic Fe3O4 nanoparticles [15] under various reaction conditions. The use of trimethylsilyl cyanide
is a safer and more effective cyanide anion source for the nucleophillic addition reactions of imines under mild
conditions [16,17]. However, many of these methods involve the use of expensive reagents, harsh conditions, extended
reaction times, and also require tedious workup leading to the generation of a large amount of toxic waste. Furthermore
many of these catalysts are deactivated or sometimes decomposed 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 [18].
Recently we prepared silica-bonded N-propylpiperazine sulfamic acid (SBPPSA) and used as a catalyst for the
synthesis of 1,2,4,5-tetrasubstituted imidazoles [19] (Scheme 1).
* Corresponding author.
E-mail address: khniknam@gmail.com (K. Niknam).
1001-8417/$ – see front matter # 2012 Khodabakhsh Niknam. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.07.007
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T. Rahi et al. / Chinese Chemical Letters 23 (2012) 1103–1106
Scheme 1. Preparation of silica-bonded N-propylpiperazine sulfamic acid (SBPPSA).
Scheme 2. Condensation of aldehydes, amines and trimethylsilyl cyanide catalyzed by SBPPSA.
In continuation of our studies toward the preparation and applications of heterogeneous solid acid catalysts [19–
25], herein we wish to report a valid and an efficient procedure for the synthesis of a-aminonitriles via one-pot threecomponent condensation of aldehydes, amines and trimethylsilyl cyanide in the presence of SBPPSA as an
inexpensive solid acid catalyst (Scheme 2).
Initial studies were carried out on the condensation reaction between benzaldehyde and aniline with TMSCN in the
presence of catalytic amounts of SBPPSA as a model reaction (Table 1). A blank experiment without catalyst the
reaction did not proceed even after 24 h. The optimal amount of SBPPSA was 0.2 g (equal to 0.24 mmol of H+) per
1 mmol of aldehyde in ethanol at room temperature.
Next, we prepared a range of a-aminonitriles under the optimized conditions (Table 2). Both aromatic and aliphatic
aldehydes reacted with amines and TMSCN in the presence of SBPPSA in this one-pot three-component condensation
to afford excellent yields of corresponding a-aminonitriles. Moreover, aldehydes with electron-withdrawing or
electron-donating groups, i.e. 3-nitrobenzaldehyde or 4-methoxybenzaldehyde, and 3,4,5-trimethoxybenzaldehyde
were converted into the corresponding a-aminonitriles 1d–1f in high yields (Table 2, entries 4–6).
The acid sensitive substrate thiophene-2-carbaldehyde gave the expected a-aminonitrile 1g in very good yield
(Table 2, entry 7). Aliphatic aldehydes such as 2-methylpropanal gave the corresponding product 1h in 76% yield
Table 1
The reaction of benzaldehyde, aniline and TMSCN in the presence of different amounts of SBPPSA.a
Entry
The amounts of catalyst (g)
Time (min)
Yield (%) b
1
2
3
4
5
–
0.08
0.10
0.20
0.30
24 h
140
110
5
5
<10
58
69
90
90
a
b
Reaction conditions: benzaldehyde (1 mmol), aniline (1.5 mmol), TMSCN (1.5 mmol), EtOH (2 mL), and room temperature.
Isolated yield.
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T. Rahi et al. / Chinese Chemical Letters 23 (2012) 1103–1106
Table 2
Preparation of various a-aminonitriles in the presence of SBPPSA in EtOH at room temperature.a
Entry
C6H5–
4-ClC6H4–
4-BrC6H4–
4-CH3OC6H4–
3,4,5-(MeO)3C6H2–
3-O2NC6H4–
2-Thionyl–
(CH3)2CH–
C6H5–
1
2
3
4
5
6
7
9
10
11
b
c
R2–NH2
Product
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–
C6H5–CH2–
HN
O
HN
O
3,4-(CH3O)2C6H3–
3,4,5-(MeO)3C6H2–
12
a
R1–CHO
4-Cl–C6H5–
Time (min)
Yield (%) b
90, 89, 89, 87, 85, 85
86
85
93
90
89
79
76
90
c
Mp (8C)
Lit. Mp (8C)
80–82
112–114
101–103
95–97
147–149
88–91
97–99
Colorless oil
69–71
81–83 [12]
111–112 [8]
99–100 [5]
94–95 [8]
147–149 [14]
89–92 [14]
98–100 [11]
Colorless oil [6]
68–69 [6]
1a
1b
1c
1d
1e
1f
1g
1h
1i
5
5
5
30
5
30
50
5
5
1j
5
89
88–91
–
1k
5
90
145–148
–
Reaction conditions: aldehyde (1 mmol), amine (1.5 mmol), TMSCN (1.5 mmol), SBPPSA (0.2 g), and EtOH (2 mL).
Isolated yield.
The recycled catalyst was used.
(Table 2, entry 9). Primary amines such as aniline, 4-chloroaniline, benzyl amine, and secondary amine such as
morpholine were accomplished these one-pot three-component condensation reactions in short reaction time at room
temperature and very good yields.
The condensation reaction between benzaldehyde and aniline with TMSCN was examined for the possibility of
recycling SBPPSA under the optimized conditions. Upon completion, the reaction mixture was filtered 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 reused five times without any additional treatment. SBPPSA showed
much the same efficiency when used in six consecutive reactions runs (Table 2, entry 1).
Finally, a comparative study of SBPPSA with other recently reported catalysts for condensation of benzaldehyde
and aniline with TMSCN as a model compound was made which revealed that SBPPSA is an equally efficient and
reusable catalyst (Table 3).
In conclusion, heterogeneous conditions, green solvent, easy and clean work-up, high yields and recovery of the
catalyst makes this method practical for the synthesis of a-aminonitriles.
1. General procedure, synthesis of a-aminonitriles
A mixture of aldehyde (1 mmol), amine (1.2 mmol), trimethylsilyl cyanide (1.2 mmol) and SBPPSA (0.2 g, equal
to 0.24 mmol of H+) in EtOH (2 mL) was stirred at room temperature for appropriate time (Table 2). After completion
of the reaction, as indicated by TLC, the reaction mixture was filtered and the remaining washed with warm ethanol
Table 3
Comparison of the result of condensation reaction of benzaldehyde, aniline and TMSCN in the presence of different catalysts based on silica.
Entry
Catalyst
Catalyst loading (g)
Conditions
Time (min)
Yield (%)a
Ref.
1
2
3
4
5
6
7
Montmorillonite KSF clay
Silica sulfuric acid
Xanthene sulfuric acid
SBA-15 supported sulfonic acid
SBSSA
Sulfamic acid Fe3O4 nanoparticles
SBPPSA
1.0
0.095 (0.25 mmol)
0.1 (0.06 mmol)
0.031 (0.017 mmol)
0.2 (0.066 mmol)
0.02 (0.006 mmol)
0.2 (0.24 mmol)
rt
rt
rt
50 8C
rt
rt
rt
210
360
65
5
30
10
5
90
88
97
100
94
97
90
[8]
[9]
[12]
[13]
[14]
[15]
Present work
a
Isolated yield.
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T. Rahi et al. / Chinese Chemical Letters 23 (2012) 1103–1106
(3 5 mL). After cooling, the corresponding a-aminonitrile products were obtained which purified by
recrystallization from hot ethanol. The recovered catalyst was dried and reused for subsequent runs.
All the products were characterized by comparison of their IR, 1H NMR and 13C NMR spectroscopic data and their
melting points with reported values [5–18,26]. Silica-bonded N-propylpiperazine sulfamic acid (SBPPSA) was
prepared according to our previously reported procedure [19].
Acknowledgment
We are thankful to the Islamic Azad University Research Council for the partial support of this work.
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Data for new compounds. (3,4-Dimethoxyphenyl)-morpholin-4-yl-acetonitrile 1j: white solid; recrystallized from ethanol; mp: 88–91 8C; IR
(KBr, cm 1): 2925 (s), 2810 (s), 2320 (m), 1610 (m), 1585 (m), 1510 (vs), 1465 (s), 1418 (s), 1340 (s), 1320 (s), 1279 (s), 1250 (s), 1235 (vs),
1158 (s), 1140 (s), 1115 (vs), 1020 (s), 1000 (s), 865 (vs), 779 (s). 1H NMR (400 MHz, CDCl3): d 2.46–2.55 (m, 4H), 3.60–3.70 (m, 4H), 3.82 (s,
3H), 3.84 (s, 3H), 4.69 (s, 1H), 6.80 (d, 1H, J = 8.3 Hz), 6.94 (d, 1H, J = 2.0 Hz), 7.03 (dd, 1H, J1 = 8.0 Hz, J2 = 2.0 Hz). 13C NMR (100 MHz,
CDCl3): d 49.91, 55.97, 56.02, 62.10, 66.69, 110.72, 110.83, 115.40, 120.47, 124.81, 149.28, 149.56. Elemental analysis: calcd: C, 64.10; H,
6.92; N, 10.68. Found: C, 63.89; H, 6.88; N, 10.51. (4-chlorophenylamino)-(3,4,5-trimethoxyphenyl)-acetonitrile 1k: white solid; recrystallized from ethanol; mp: 145–148 8C; IR (KBr, cm 1): 3380 (vs), 2950 (m), 2910 (s), 2807 (m), 2340 (m), 1590 (vs), 1500 (vs), 1458 (s), 1418
(s), 1338 (s), 1310 (s), 1279 (s), 1240 (s), 1230 (vs), 1180 (m), 1081 (m), 999 (s), 810 (s), 720 (s). 1H NMR (400 MHz, CDCl3): d 3.87 (s, 3H),
3.88 (s, 6H), 4.12 (d, 1H, J = 8.4 Hz), 5.32 (d, 1H, J = 8.0 Hz), 6.72 (d, 2H, J = 8.8 Hz), 6.78 (s, 2H), 7.24 (d, 2H, J = 8.8 Hz). 13C NMR
(100 MHz, CDCl3): d 50.42, 56.23, 60.89, 104.22, 115.35, 117.97, 125.05, 128.94, 129.45, 138.64, 143.33, 153.77. Elemental analysis: calcd.
C, 61.36; H, 5.15; N, 8.42. Found: C, 61.13; H, 5.12; N, 8.28.