Three-component solventless Strecker synthesis of α-aminonitriles catalysed by a renewable sulfonated nanoporous carbon catalyst (CMK-5-SO3H)

Article abstract of DOI:10.1002/aoc.4422

The one-pot three-component synthesis of a variety of α-aminonitriles has been studied using a catalytic amount of a sulfonic acid-functionalized ordered nanoporous carbon catalyst, CMK-5-SO₃H, at room temperature under solvent-free reaction co

Full text of DOI:10.1002/aoc.4422

Received: 16 February 2018
DOI: 10.1002/aoc.4422
Revised: 5 April 2018
Accepted: 18 April 2018
C O M M U N I C A T I O N
Three‐component solventless Strecker synthesis of α‐
aminonitriles catalysed by a renewable sulfonated
nanoporous carbon catalyst (CMK‐5‐SO3H)
Daryoush Zareyee1
| Ali Shokuhi Rad2
| Zahra Ataei1 | Sayed Hossein Javadi1 |
Mohammad A. Khalilzadeh1
1 Department of Chemistry, Qaemshahr
Branch, Islamic Azad University,
Qaemshahr, Iran
2 Department of Chemical Engineering,
Qaemshahr Branch, Islamic Azad
University, Qaemshahr, Iran
The one‐pot three‐component synthesis of a variety of α‐aminonitriles has been
studied using a catalytic amount of a sulfonic acid‐functionalized ordered
nanoporous carbon catalyst, CMK‐5‐SO3H, at room temperature under
solvent‐free reaction conditions. The heterogeneous catalyst could be readily
isolated from the reaction mixture and reused at least ten times without signif-
icant loss in activity. A clean, rapid and simple method for the preparation of
α‐aminonitriles using the recoverable CMK‐5‐SO3H catalyst is described.
Correspondence
Daryoush Zareyee, Department of
Chemistry, Qaemshahr Branch, Islamic
Azad University, Qaemshahr, Iran.
Email: zareyee@gmail.com
KEYWORDS
α‐aminonitriles, CMK‐5, solid sulfonic acid, Strecker, three components
1 | INTRODUCTION
heterocycles.[6–8] However, the Strecker reaction has
drawbacks, in particular due to the volatile and highly
Multi‐component reactions have become an area of prime
interest due to their ability to convert more than two compo-
nents in a single step in the synthesis of pharmacologically
and biologically important targets, without isolation of
intermediates in minimal time with maximum selectivity,
high atom economy, high purity and excellent yields.[1–3]
Consequently, the design of multi‐component reactions
has attracted great attention from research groups working
in medicinal chemistry and drug discovery. Moreover,
in recent years, considerable attention has been paid to
solvent‐free reactions because of their high efficiency, oper-
ational simplicity and environmental benignity. Therefore,
the possibility of performing multi‐component reactions[4]
such as the Strecker reaction[5] under green conditions with
a heterogeneous catalyst could enhance their utility from
economic as well as from ecological points of view.
toxic nature of HCN. Among various cyanide sources
such as HCN, KCN, NaCN, Bu3SnCN, K4[Fe (CN)6] and
trimethylsilyl cyanide (TMSCN),[9–43] TMSCN is a desir-
able cyanide reagent, due to its safety, efficiency and
availability. It is also noteworthy that TMSCN cannot
transfer to electrophiles by itself and needs a catalyst for
its activation. Accordingly, enormous efforts have been
devoted to the development of catalysts to effect the
Strecker reaction. While acknowledging the pioneering
advances in this area, some of these methods suffer from
disadvantages such as the use of hazardous organic
solvents, harsh reaction conditions, low yields, tedious
work‐up and effluent pollution. Therefore, the develop-
ment of efficient, recyclable and environmentally benign
catalytic methods for these transformations using
non‐polluting reagents and solvents is desirable.
The three‐component one‐pot Strecker reaction
employs an aldehyde/ketone, amine and cyanide to gen-
erate α‐aminonitriles which are versatile intermediates
for the synthesis of various building blocks such as α‐
amino acids, 1,2‐diamines and nitrogen‐containing
The efficiency of heterogeneous catalysis in organic syn-
thesis can be improved by employing nanosized catalysts
because of their extremely small size, large surface to vol-
ume ratio, simplified recovery, reusability and potential
for incorporation in continuous reactors, which can lead
Appl Organometal Chem. 2018;e4422.
wileyonlinelibrary.com/journal/aoc
Copyright © 2018 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4422

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ZAREYEE ET AL.
FIGURE 1 Strecker synthesis of α‐aminonitriles using CMK‐5‐SO3H under solvent‐free conditions at ambient temperature
to novel and environmentally benign chemical procedures
for academia and industry.[44] The application of solid acid
catalysts to replace the traditional mineral acids, such as
sulfuric acid, is a rapidly growing field in organic syntheses,
because these species have many advantages such as sim-
plicity in handling, reduced reactor and plant corrosion
problems and more environmentally safe disposal.[45,46]
In this sense, very recently, we used a heterogeneous
sulfonic acid catalyst (CMK‐5‐SO3H) in various organic
transformations.[47–49] Herein, in the light of growing
interest in developing green reaction conditions in a
one‐pot three‐component Strecker reaction, we report
the use of heterogeneous CMK‐5‐SO3H[50–53] as an effi-
cient and recyclable catalyst which delivers excellent
yields of α‐aminonitriles and with the added advantage
of catalyst recyclability (Figure 1).
solvent‐free reaction conditions. The resulting mixture
was stirred at room temperature until completion of
the reaction with monitoring by TLC (n‐hexane–ethyl
acetate, 4:1). After completion of the reaction, hot EtOAc
was added to the reaction mixture and the resulting
mixture filtered. Then, the reaction solution was concen-
trated under vacuum. If it was necessary, the crude prod-
ucts were further purified by column chromatography.
3 | RESULTS AND DISCUSSION
As part of our interest in heterogeneous acid‐catalysed
reactions,[39–41] we anticipated that CMK‐5‐SO3H can be
used as an efficient catalyst for the promotion of reactions
that need the use of an acidic catalyst to speed them up.
Fourier transform infrared (FT‐IR) spectroscopy
provided clear evidence for organo‐sulfonic acid
functionalization of the catalyst. In the spectrum of
CMK‐5‐SO3H, the bands for C═ C, methylene and SO3─
H stretching vibrations are observed at 1440–1630, 2923
and 3430 cm−1, respectively (Figure 2). These results con-
firm the integrity of the phenethyl sulfonic acid groups
within the support samples. Additionally, according to
2 | EXPERIMENTAL
The general procedure for the Strecker synthesis of α‐
aminonitriles was as follows. CMK‐5‐SO3H (0.046 g,
2 mol%) was added to a mixture of aldehyde (1 mmol),
aniline (1 mmol) and TMSCN (0.157 ml, 2 mmol) under
FIGURE 2 FT‐IR spectrum of CMK‐5‐
SO3H

ZAREYEE ET AL.
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TABLE 1 Synthesis of α‐aminonitriles from aldehydes, aniline and TMSCN using 2 mol% of CMK‐5‐SO3H at room temperature under
solvent‐free conditions
M.p. (°C)
Time
(min)
Yield
(%)a
Entry
Aldehyde
Product
Found
Reported
1
45
96
80–82
80–82[35]
2
3
60
91
Oil
Oil
50
91
52–55
56–58[54]
4
5
6
7
60
50
45
40
90
92
91
93
Oil
Oil
94–95
84–86
Oil
94–97[55]
86–88[56]
Oil
8
40
50
80
92
80
70
107–110
118–120
90–92
110–112[32]
120–122[57]
89–92[58]
9
10
11
70
70
78
75
Oil
Oil
12
112–114
109–111[35]
aIsolated yield.
Barrett–Joyner–Halenda diagrams of CMK‐5 and CMK‐5‐
SO3H, average pore diameter of CMK‐5 decreases from
3.27 to 2.82 nm after sulfonation. Consequently, surface
area decreases from 695 to 395 m2 g−1. These results con-
firm the attachment of organo‐sulfonic group to ordered
nanoporous carbon (supporting information).

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ZAREYEE ET AL.
SCHEME 1 Plausible catalytic cycle for
synthesis of α‐aminonitriles through
Strecker reaction
Acid capacity of CMK‐5‐SO3H (0.87 mmol g−1) was
was definitely identified. Further studies showed that
increasing the amount of CMK‐5‐SO3H (3 mol%,
0.069 g) did not improve the reaction significantly. It is
evident that the best result was obtained by the applica-
tion of 2 mol% of CMK‐5‐SO3H under solvent‐free
reaction conditions at ambient temperature.
determined by titration with NaOH aqueous solution.
Briefly, 50 mg of CMK‐5‐SO3H was dispersed in 15 g of
an aqueous solution of NaCl (2 M) with stirring at room
temperature overnight. The dispersion was then titrated
potentiometrically with 0.1 M NaOH.
In the efforts to develop an efficient and environmen-
tally benign methodology for the synthesis of α‐
aminonitriles via Strecker reaction, our initial work
started with screening of catalyst loading to identify the
optimal reaction conditions. We initiated our studies by
subjecting 1 mol% (0.023 g) of CMK‐5‐SO3H to a mixture
of benzaldehyde, aniline and TMSCN under solvent‐free
reaction conditions at room temperature. It was found
that the reaction took a considerably long time and low
yield was obtained (100 min, 60% yield). When the con-
centration of catalyst was increased to 2 mol% (0.046 g)
under the same reaction conditions, the reaction was
greatly accelerated and completed within 45 min to give
the expected product in 96% yield. The same reaction
without CMK‐5‐SO3H gave product in 10% yield after
360 min. Thus the catalytic efficiency of CMK‐5‐SO3H
With the optimized reaction conditions in hand, we
investigated the substrate scope using the CMK‐5‐SO3H
catalyst. To explore the generality of this reaction, we
applied CMK‐5‐SO3H in the solventless reaction of
various aldehydes with aniline and TMSCN under opti-
mized conditions (Table 1). We were pleased to find that
moderate to high yields were obtained for the reaction of
virtually all aryl aldehydes examined. We investigated
aldehydes containing both electron‐withdrawing and
electron‐donating groups. The results show that being
electron‐withdrawing or electron‐donating does not
determine the general trend of the reactivity (Table 1,
entries 1–12). In all cases, the reaction proceeded effi-
ciently at room temperature without the formation of
any by‐products.
FIGURE 3 Recyclability of CMK‐5‐SO3H for the Strecker
FIGURE 4 TEM image of CMK‐5‐SO3H after tenth reaction
reaction of benzaldehyde, aniline and TMSCN
cycle

ZAREYEE ET AL.
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The mechanism of the CMK‐5‐SO3H‐catalysed
ORCID
reaction is believed to involve the formation of imine,
so that addition of CN− is facilitated to afford the
α‐aminonitrile (Scheme 1).[39,59] The acidic hydrogen
of CMK‐5‐SO3H activates the carbonyl group of the
aldehyde through hydrogen bonding for nucleophilic
attack of amine to produce the corresponding imine,
which is in equilibrium with the starting materials. In
the next step, the CN− group of TMSCN transfers to
imine to afford α‐aminonitrile with regeneration of
CMK‐5‐SO3H.
The reusability of a catalyst is one of the most
important benefits, making it useful for commercial
applications. Recycling experiments were conducted
to determine the recovery of the catalyst after the
reaction, through a series of sequential syntheses of
α‐aminonitrile from benzaldehyde, aniline and TMSCN
as model substrates. Upon completion, hot EtOAc was
added and the reaction mixture was filtered and washed
with hot EtOAc. CMK‐5‐SO3H showed excellent recov-
erability and reusability over ten successive runs under
the same conditions as the first run (Figure 3).
Moreover, the uniformity of the highly ordered structure
of CMK‐5‐SO3H after ten recoveries is confirmed from
the transmission electron microscopy (TEM) image
(Figure 4).
Daryoush Zareyee http://orcid.org/0000-0001-9405-5683
Ali Shokuhi Rad http://orcid.org/0000-0002-2426-0339
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How to cite this article: Zareyee D, Rad AS,
Ataei Z, Javadi SH, Khalilzadeh MA. Three‐
component solventless Strecker synthesis of α‐
aminonitriles catalysed by a renewable sulfonated
nanoporous carbon catalyst (CMK‐5‐SO3H). Appl
Organometal Chem. 2018;e4422. https://doi.org/
10.1002/aoc.4422
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