Silica boron sulfuric acid nanoparticles: As an efficient and reusable catalyst for the large-scale synthesis of α-amino nitriles using the strecker reaction

Article abstract of DOI:10.1002/hc.21052

A highly efficient and green procedure for the large-scale synthesis of α-amino nitriles using three-component condensation of carbonyl compounds, amines, and trimethylsilylcyanide has been developed. Silica boron sulfuric acid nanoparticles (SBSANs) are found as an efficient heterogeneous catalyst for the promotion of this process at room temperature under solvent-free conditions. This protocol offers an effective and scale-up procedure for the synthesis of various α-amino nitriles using a wide range of amines and carbonyl compounds in relatively short reaction time with the excellent isolated yields. In addition, the SBSAN catalyst is easily separated from the reaction mixture by simple filtration and can be reused several times.

Full text of DOI:10.1002/hc.21052

Heteroatom Chemistry
Volume 24, Number 1, 2013
Silica Boron Sulfuric Acid Nanoparticles: As an
Efficient and Reusable Catalyst for the
Large-Scale Synthesis of α-Amino Nitriles
Using the Strecker Reaction
Ali Khalafi-Nezhad, Habib Ollah Foroughi, and Farhad Panahi
Department of Chemistry, Shiraz University, Shiraz 71454, Islamic Republic of Iran
Received 23 November 2011; revised 13 August 2012
The development of heterogeneous catalysts and
ABSTRACT: A highly efficient and green procedure
the use of green conditions for excellent synthesis
for the large-scale synthesis of α-amino nitriles us-
of materials are two important strategies in aca-
ing three-component condensation of carbonyl com-
demic studies [3]. Solid acids as efficient hetero-
pounds, amines, and trimethylsilylcyanide has been
geneous catalysts have been extensively used in or-
developed. Silica boron sulfuric acid nanoparticles
ganic reactions, because they have several unique
(SBSANs) are found as an efficient heterogeneous cat-
characteristics [4]. Generally, by the use of these
alyst for the promotion of this process at room tem-
catalysts, acid catalyst–based processes have been
perature under solvent-free conditions. This protocol
accomplished in more environmentally sensible con-
offers an effective and scale-up procedure for the syn-
ditions [5]. Among various supports for the prepa-
thesis of various α-amino nitriles using a wide range
ration of solid acids, silica occupies one of the most
of amines and carbonyl compounds in relatively short
important positions, because it is more stable, abun-
reaction time with the excellent isolated yields. In ad-
dantly available, and can be simply functionalized
dition, the SBSAN catalyst is easily separated from the
[6]. Furthermore, when support is selected in the
reaction mixture by simple filtration and can be reused
nanometer scale [7], the dispersible capability of
ꢀC
several times.
2012 Wiley Periodicals, Inc. Het-
a catalyst in solution is improved so that it acts
as a pseudohomogeneous catalyst. Consequently,
the diffusion rate of reactants to catalyst sites is
increased and thus the reaction rate is enhanced
dramatically [8].
eroatom Chem 24:1–8, 2013; View this article online
at wileyonlinelibrary.com. DOI 10.1002/hc.21052
Recently, we have developed a new solid acid
based on the nanometer-scale silica support with
two Lewis and protic acidic sites as a silica boron
sulfuric acid nanoparticle (SBSAN) catalyst [9].
This new nanocatalyst has two Lewis and protic
acidic sites and can provide efficient and green
conditions for excellent performance of acid-based
organic reactions. The catalytic performance of
the SBSAN catalyst was evaluated in the Ritter
reaction as an acid-catalyzed process, and very ex-
cellent results have been obtained [9]. In the cur-
rent study, we present another important applica-
tion of SBSAN as an efficient heterogeneous catalyst
INTRODUCTION
Nowadays, some modifications to already existing
synthetic methodologies, considering the environ-
mental consciousness in both industrial and aca-
demic studies, have received great attention [1]. In
industries, the green chemistry approaches such as
using recyclable catalysts and less toxic materials
as solvents and reagents have been considered [2].
Correspondence to: Ali Khalafi-Nezhad; e-mail: khalafi@chem
.susc.ac.ir. Farhad Panahi; e-mail: panahi@shirazu.ac.ir.
ꢀC
2012 Wiley Periodicals, Inc.
1

2
Khalafi-Nezhad, Ollah Foroughi, and Panahi
for the preparation of α-amino nitriles under mild
conditions.
Alpha-amino nitriles are classified as a main cat-
egory of compounds, because of their beneficial syn-
thetic applications in medicinal chemistry and nat-
ural products [10]. The synthesis of α-amino acids
and nitrogen-containing heterocycles (such as imi-
dazoles and thiadiazoles) is too significant in organic
synthesis [11]. The Strecker reaction is one of the
most important synthetic strategies for the prepa-
ration of α-amino nitriles [12]. Moreover, α-amino
nitriles can be synthesized from the catalytic cya-
nation of imines [13]. In modern organic synthetic
reactions, they have been synthesized using the one-
pot three-component reaction of amines, carbonyl
compounds, and trimethylsilylcyanide (TMSCN) in
the presence of an acid catalyst [14]. So far, this reac-
tion has been studied with different homogeneous,
heterogeneous, and Lewis acid catalysts. Although
these methods are suitable for this process, but
some of them have one or more deficiencies such as
low yield, prolonged reaction time, tedious workup
processes, hazardous reaction conditions, and lack
of scalability [15–18]. Herein, we report that the
SBSAN catalyst is efficient in mild conditions with a
safe and clean procedure for the large-scale synthe-
sis of α-amino nitriles.
FIGURE 1 Proposed chemical structure for SBSAN.
tures that are predictable for the SBSAN catalyst and
we have shown all of these possible structures in
Fig. 1.
In accordance with Fig. 1, a number of possi-
bilities of the structure of the SBSAN catalyst as a
result of, during the generation of SBAN, boric acid
can be connected to the silica surface with differ-
ent modes. In addition, the boron atoms having the
empty orbital (as Lewis acid) can interact with hy-
droxy groups on the substrate (silica and boric acid),
and this resulted in additional complexities in the
structure of the SBSAN catalyst. Furthermore, the
sulfonation of some of the silica hydroxyl groups
with ClSO3H should also be considered. Based on
the proposed structure for the SBSAN catalyst, the
Lewis acidity in the catalyst is resulted from the tri-
coordinated boron atoms. Perhaps this is the reason
why the SBSAN catalyst is effectively catalyzed the
reactions under solvent-free conditions. Overall, in
the structure of the SBSAN catalyst two acidic cat-
alytic sites including the proton of sulfuric groups
(protic acid) and boron atoms (Lewis acid) are lo-
cated on a silica nanostructure support. It seems
that these two acidic catalytic sites have a syner-
gistic effect, so that they can provide an efficient cat-
alytic activity for reactions to accomplish under mild
conditions.
RESULTS AND DISCUSSION
Silica Boron Sulfuric Acid Nanoparticles
Silica boron sulfuric acid nanoparticles were pre-
pared in a two-steps process (Scheme 1). First, silica
boron acid nanoparticles (SBANs) were synthesized
during the modification of the silica support by boric
acid [B(OH)3] using the chemical vapor deposition
(CVD) process. Then SBAN was reacted with chloro-
sulfonic acid (ClSO3H) to obtain the SBSAN catalyst.
This catalyst has been fully characterized us-
ing some different microscopic and spectroscopic
techniques [9]. Our studies show that activity of the
SBSAN catalyst is decreased in donor solvents. As
a result, the boron atoms should have a key role in
the reactivity of this catalyst. On the other hand, we
know that the boron atom can be only considered as
a Lewis acid if it is tricoordinated. According to this
point of view, we considered all of the possible struc-
Synthesis of α-Amino Nitriles Using the SBSAN
Catalyst
The reaction between benzaldehyde (1), aniline (2),
and TMSCN (3) was selected as a simple model to
find optimum conditions for the preparation of the
α-amino nitrile derivatives using the SBSAN cata-
lyst. The results of optimization study are presented
in Table 1.
According to Table 1, the reactivity of the
SBSAN catalyst is decreased in donor solvents to
some extent. The yield of products under both room
SCHEME 1 Synthetic routes for the preparation of SBANs
and SBSAN catalyst.
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Silica Boron Sulfuric Acid Nanoparticles As an Efficient and Reusable Catalyst
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TABLE 1 Optimization of Reaction Condition between Benzaldehyde, Aniline and TMSCN for Preparation of the α-Amino
Nitrile Derivatives Using SBSAN Catalysta
Entry
1
Catalyst
SBSAN
Catalyst Loading
4.5 (mol%)
Solvent
DCM
Temperature (◦C)
Time (min)
Yield (%)b
r.t.
Reflux
r.t.
Reflux
r.t.
r.t.
r.t.
r.t.
80
r.t.
30
30
30
30
5
84
88
71
76
96
97
75
53
68
0
Trace
0
24
0
2
SBSAN
4.5 (mol%)
EtOH
3
4
5
6
SBSAN
SBSAN
SBSAN
SBAN
4.5 (mol%)
6.75 (mol%)
2.25 (mol%)
0.1 g
None
None
None
None
5
30
120
120
5
120
5
720
5
720
5
7
Silica
B(OH)3
0.1 g
50 (mol%)
(0.1/0.1) g
0.1 g
None
None
None
None
8
r.t.
r.t.
r.t.
9
Silica/ B(OH)3
SSA
29
38
79
0
10
360
720
720
11
12
None
None
None
None
None
None
r.t.
80
Trace
Abbreviations: DCM, dichloromethane; r.t., room temperature; SBAN, silica boron acid nanoparticle; SBSAN, silica boron sulfuric acid nanopar-
ticle; SSA, silica sulfuric acid.
aAmount of reagents in all reactions: aniline (1 mmol), benzaldehyde (1 mmol), and TMSCN (1.1 mmol).
bIsolated yield.
temperature
dichloromethane as
and
reflux
conditions
in
strong evidence that the catalytic sites of SBAN
are different from the silica and boric acid. This
catalytic activity can result from the nanostructure
nature of silica boric acid nanoparticles. Silica
sulfuric acid [19] did not show activity similar to
SBSAN in this multicomponent reaction. This test
confirmed that the catalytic activity of SBSAN is
not resulted from only SO3H groups (Table 1,
entry 10). At the end of our optimizing studies, we
also carried out the blind-probe experiments and
the results show that, for the promotion of this
protocol at room temperature and heat conditions,
the existence of a catalyst is unavoidable and the
SBSAN catalyst has a significant effect on the
progress of this reaction (Table 1, entries 11 and
12). As shown in Table 1, the best results for this
protocol were obtained with catalyst loading of
4.5 mol% of SBSAN at room temperature and under
solvent-free conditions.
a
noncoordinating solvent
is more than in ethanol as a donor solvent (Table 1,
entries 1 and 2). It is noteworthy that, in solvent-free
conditions, the SBSAN catalyst shows high activity,
and the expected product was obtained in a high
isolated yield (96%) after a very short reaction time
(Table 1, entry 3). These results also confirm that the
boron atoms as Lewis acid play an important role
in the catalytic activity of the SBSAN catalyst. With
a decrease in the catalyst loading to 2.25 mol%,
the yield of the product significantly decreased, but
its increase to 6.75 mol% did not have any effect
on the reaction yield. To clarify the synergistic
effect between the SBSAN catalytic sites, SBAN,
silica, and boric acid were applied separately under
the same reaction conditions. The SBAN showed
a good reactivity for this reaction in solvent-free
conditions at 80◦C (Table 1, entry 6), whereas a low
isolated yield for the corresponding product was
obtained in the presence of silica and boric acid
(Table 1, entries 7 and 8). Moreover, in the presence
of a mixture of silica and boric acid the yield of
product did not changed even after a more reaction
time (Table 1, entry 9). This experiment provides
To determine the scope of the designed protocol
for the preparation of α-amino nitrile derivatives,
a number of commercially available aldehydes and
amines were reacted with TMSCN under optimized
reaction conditions and the results are summarized
in Table 2.
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Khalafi-Nezhad, Ollah Foroughi, and Panahi
TABLE 2 Three Components Reaction between Different
Amines and Aldehydes with TMSCN in the Presence of
SBSAN Catalysta
excellent yields of corresponding α-amino nitriles
were obtained. Another important feature of this
method is the use of sensitive acid aldehyde such
as thiophene-2-carbaldehyde to generate the corre-
sponding α-amino nitrile derivatives in the excellent
isolated yield (Table 2, entry 9).
Moreover, the SBSAN-catalyzed Strecker reac-
tion between morpholine as a secondary amine
and benzaldehyde led to the formation of the
2-morpholino-2-phenylacetonitrile product in 91%
yield after only 15 min (Scheme 2).
The synthetic efficiency of this reaction was
highlighted by the reaction of piperazine with ben-
zaldehyde and TMSCN to give a structurally complex
α-amino nitrile derivative (Scheme 3).
In addition, acetophenone as a ketone was con-
verted into the corresponding α-amino nitriles with
the excellent isolated yields (Scheme 4). As we know,
few methods for the Strecker reaction of ketones are
reported in the literature [17b] therefore our con-
venient procedure for the synthesis of this class of
compounds may have synthetic significance.
Entry
R1
R2
Time (min) Yield (%)b
1
2
3
4
5
6
7
8
Ph
4-SMe-Ph
Ph
2,4-Cl-Ph
4-Cl-Ph
4-OMe-Ph
4-F-Ph
3-NO2-Ph
Thiophenyl
Ph
Ph
4-Br-Ph
4-Br-Ph
Ph
4-Me-Ph
Ph
4-Me-Ph
Ph
Ph
3,4-Me-Ph
Ph
5
10
10
10
5
96
95
93
97
96
95
94
95
90
93
91
10
5
10
15
10
20
9
10
11
C4H9
aAmount of reagents in all reactions: aniline (1 mmol), aldehyde
(1 mmol), TMSCN (1.1 mmol), and catalyst (0.05 g, 4.5 mol%).
bIsolated yield.
According to Table 2 and aforementioned reac-
tions, the SBSAN catalyst can provide a suitable con-
dition for the three-component coupling reaction be-
tween aldehydes/ketones, amine, and TMSCN to ac-
complish in solvent-free conditions at room temper-
ature. Hence, SBSAN was introduced as an efficient
and green catalyst for the facile synthesis of α-amino
nitriles under mild conditions.
We also propose the following mechanism for
this reaction in the presence of the SBSAN catalyst
(Scheme 5). In the proposed mechanism, we tried
to show that both active sites of the SBSAN cata-
lyst are engaged in the Strecker reaction. As shown
in Scheme 5, the aldehyde can be protonated to be-
come active for the reaction with an amine compo-
nent, producing the imine intermediate. Then, the
intermediate subsequently reacts with a trapped
SCHEME 2 The Strecker reaction between morpholine
(as secondary amine) and benzaldehyde in the presence
of the SBSAN catalyst. Reaction conditions: benzaldehyde
(1 mmol), morpholine (1 mmol), and TMSCN (1.1 mmol).
We applied optimized conditions for the synthe-
sis of α-amino nitriles by a reaction between some
of the commercial aldehydes, amines, and TMSCN,
and a range of α-amino nitriles were synthesized. As
clearly shown in Table 2, both aromatic and aliphatic
(entry 11) aldehydes reacted with amines and TM-
SCN in the presence of the SBSAN catalyst and the
SCHEME 3 SBSAN-catalyzed Strecker reaction between piperazine (as bifunctionalized amine) and benzaldehyde.
SCHEME 4 SBSAN-catalyzed Strecker reaction between acetophenone and aniline. Reaction conditions: acetophenone
(1 mmol), aniline (1 mmol), and TMSCN (1.1 mmol).
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Silica Boron Sulfuric Acid Nanoparticles As an Efficient and Reusable Catalyst
5
SCHEME 5 Proposed mechanism for the Strecker reaction of aldehydes/ketones, amines, and TMSCN for the synthesis of
α-amino nitriles in the presence of the SBSAN catalyst.
CN anion to produce the corresponding product.
It seems that the Lewis and protic acidic sites of
the SBSAN catalyst are fully involved in the reactive
substrate and intermediates for the progress of the
reaction.
For practical applications of heterogeneous cat-
alysts in the industrial scale, the level of reusability
and scale-up of the reaction catalyst are very impor-
tant factors.
is less efficient when the reaction is performed with
a higher volume of vessel [20].
Recyclability of the SBSAN Catalyst in the
Strecker Reaction
The possibility of recycling of the catalyst was exam-
ined using the reaction of benzaldehyde and aniline
with TMSCN under optimized reaction conditions.
When the reaction was complete, the reaction mix-
ture was washed with hot EtOH and catalyst was
separated by simple filtration, and the recycled cat-
alyst was saved for the next operation. The recycled
Scalability of the Strecker Reaction in the
Presence of the SBSAN Catalyst
The reaction between benzaldehyde, aniline, and
TMSCN was evaluated using some different
amounts of the SBSAN catalyst to optimize the cata-
lyst loading for the scale-up procedure. The obtained
results have shown that the optimum catalyst load-
ing for this process can be 2.0 g of the SBSAN cata-
lyst (Table 3).
In comparison to the small-scale experiment (Ta-
ble 2, entry 1), approximately 1 additional h was re-
quired to achieve the desired isolated yield of prod-
uct using the SBSAN catalyst. The slight decrease
in the efficiency and an unimportant increase in the
time could be due to the fact that the orbital shaking
TABLE 3 Optimization of Catalyst Loading for the Large-
Scale Synthesis of α-Amino Nitriles Using SBSAN Catalysta
Entry
Catalyst Loading (g)
Time (h)
Yield (%)b
1
2
3
4
5
5
3
2.5
2
1.5
1
1
1
1
5
92
91
91
91
78
79
12
aReaction condition: benzaldehyde (0.1 mol), aniline (0.1 mol),
TMSCN (0.11 mol), r.t., and solvent-free condition.
bIsolated yield.
Heteroatom Chemistry DOI 10.1002/hc

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Khalafi-Nezhad, Ollah Foroughi, and Panahi
TABLE 4 Reusability of the SBSAN Catalyst in the Reaction
Preparation of SBSANs
between Benzaldehyde, Aniline, and TMSCNa
The SBSAN catalyst was synthesized on the basis of
the previous procedure [9]. According to this proce-
dure, first SBANs were prepared and then this mate-
rial was reacted with chlorosulfonic acid to produce
the SBSAN catalyst. For the preparation of SBANs,
the CVD process was applied for doping of boron
species on a silica support. In this way, a mixture of
Ar, O2, and the aerosols of the aqueous solution of
boric acid (2.0 g mL−1) was injected into the solid
silica supports positioned inside a quartz tube lo-
cated in a tubing furnace at 600◦C. Then, SBANs
were transferred into a flask and chlorosulfonic acid
was added to it dropwise at room temperature. After
completion of acid addition, the mixture was stirred
for 30 min under vacuum pressure. Therefore, the
SBSAN catalyst was obtained as a white solid.
A representative example of the large-scale
preparation of α-amino nitriles using the SBSAN
catalyst is 2-phenyl-2-(phenylamino)acetonitrile
(Table 2, entry 1). Into a canonical flask (500 mL),
a mixture of benzaldehyde (0.1 mol), aniline (0.1
mol), TMSCN (0.11 mol), and SBSAN (2.0 g) was
stirred at room temperature for 1 h. Then, the
reaction mixture was washed with hot ethanol
(100 mL) and the SBSAN catalyst was separated
by simple filtration. The α-amino product was
precipitated following the cooling of ethanol, and
pure 2-phenyl-2-(phenylamino)acetonitrile was
obtained by its recrystallization in ethanol (18.9 g,
91%). White solid; mp 80–81◦C; 1H NMR (300 MHz,
DCl3/TMS): δ = 4.04 (brs, 1H, NH), 5.46 (s, 1H),
6.79–6.93 (m, 3H), 7.28–7.65 (m, 7H); 13C NMR (75
MHz, CDCl3/TMS): δ = 50.3, 114.2, 118.2, 120.4,
127.3, 129.4, 129.6, 131.3, 34.0, 144.7; Anal. Calcd
for C14H12N2 (208.2): C, 80.74; H, 5.81; N, 13.45.
Found: C, 80.65; H, 5.78; N, 13.37. The recovered
SBSAN catalyst was washed with water (2 × 20 mL)
and ethanol (2 × 20 mL), dried at 100◦C in an oven
(for 5 h), and reused catalyst was saved for the next
operation without any treatment.
Entry
Yield of Product (%)
Recovery of SBSAN (%)
Fresh
96
96
95
94
94
93
>99
99
98
98
98
1
2
3
4
5
97
aReaction conditions: SBSAN (0.05 g, 4.5 mol%), aniline (1.0 mmol),
benzaldehyde (1.0 mmol), and TMSCN (1.1 mmol). Reaction time is
5 min.
catalyst could be reused more than five times with-
out any treatment (Table 4).
To confirm this point, the catalyst activity of
SBSAN did not change remarkably during the re-
action process, we checked the sulfur content of the
SBSAN catalyst using elemental analysis after six
times of reusability and the results have shown that
only 0.7% of sulfur was lost. These results are in
good agreement with catalyst activity of the SBSAN
catalyst after each recovery and we did not observed
any appreciable loss in the catalytic activity of the
SBSAN catalyst.
CONCLUSIONS
In summary, SBSANs as a dual Lewis/protic solid
acid catalyst are introduced for the large-scale syn-
thesis of α-amino nitriles under green conditions
using the Strecker reaction. The one-pot three-
component condensation of aldehydes/ketones,
amines, and TMSCN is catalyzed by SBSAN at room
temperature under solvent-free conditions. This new
approach was preceded by the excellent isolated
yields, and the target products were obtained in short
reaction time. Reusability and easy workup were
two other advantages of the SBSAN catalyst for this
process.
EXPERIMENTAL
General Procedure for the Preparation of
α-Amino Nitriles Using the SBSAN Catalyst
on a 1 mmol Scale
Chemicals were purchased from Fluka (Neu-Ulm,
Germany) and Aldrich (Gillingham, UK). H NMR
1
and 13C NMR were run on a Brucker Avance DRX
(300 and 400 MHz) in a pure deuterated CDCl3 sol-
vent with tetramethylsilane (TMS) as internal stan-
dards. Melting points were determined in open cap-
illary tubes in a Barnstead Electrothermal 9100 BZ
circulating oil melting point apparatus. The reac-
tion monitoring was accomplished by thin layer
chromatography (TLC) on silica gel Poly Gram
SILG/UV254 plates.
Into a canonical flask (50 mL), a mixture of alde-
hyde/ketone (1.0 mmol), amine (1.0 mmol), TMSCN
(1.1 mmol), and SBSAN (0.05 g) was stirred at room
temperature for an appropriate time, as specified in
Table 2. After completion of the reaction, as indi-
cated by TLC, the reaction mixture was washed with
hot ethanol (10 mL) and catalyst separated by sim-
ple filtration. After cooling of ethanol, the α-amino
Heteroatom Chemistry DOI 10.1002/hc

Silica Boron Sulfuric Acid Nanoparticles As an Efficient and Reusable Catalyst
7
product was precipitated and pure product was ob-
tained by its recrystallization in ethanol.
129.7, 129.8, 130.5, 133.0, 136.2, 143.9; Anal. Calcd
for C14H11N3O2 (253.2): C, 66.40; H, 4.38; N, 16.59.
Found: C, 66.38; H, 4.34; N, 16.52.
2-Morpholino-2-phenylacetonitrile. Yield; 91%;
white solid; mp 68–70◦C; 1H NMR (300 MHz,
CDCl3/TMS): δ = 2.61 (t, J = 4.7 Hz, 4H), 3.69–3.81
(m, 4H), 4.85 (s, 1H), 7.41–7.57 (m, 5H); 13C NMR
(75 MHz, CDCl3/TMS): δ = 50, 62.5, 66.7, 115.2,
128.0, 128.9, 129.1, 132.5; Anal. Calcd for C12H14N2O
(202.2): C, 71.26; H, 6.98; N, 13.85. Found: C, 71.19;
H, 6.91; N, 13.78.
ACKNOWLEDGMENT
We acknowledge Shiraz University for partial sup-
port of this work.
2-(2,4-Dichlorophenyl)-2-(phenylamino) acetoni-
trile (Table 2, entry 4). Yield: 97%; pale yellow solid;
mp 116–118◦C; 1H NMR (300 MHz, CDCl3/TMS): δ =
4.05 (brs, 1H, NH), 5.7 (s, 1H), 6.77–7.71 (m, 8H); 13C
NMR (75 MHz, CDCl3/TMS): δ = 47.7, 114.4, 117.4,
120.8, 128.1, 129.7, 129.9, 130.4, 134.3, 136.5; Anal.
Calcd for C14H10Cl2N2 (277.1): C, 60.67; H, 3.64; N,
10.11. Found: C, 60.61; H, 3.59; N, 10.05.
2-(p-Tolylamino)-2-(4-chlorophenyl)acetonitrile
(Table 2, entry 5). Yield: 96%, yellow solid; mp
86–88◦C; 1H NMR (300 MHz, CDCl3/TMS): δ =
2.31 (s, 3H), 3.97 (brs, 1H, NH), 5.4 (s, 1H), 6.7
(d, J = 8.0 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 7.44
(d, J = 8.6 Hz, 2H), 7.56 (d, J = 8.3 Hz, 2H); 13C
NMR (75 MHz, CDCl3/TMS): δ = 20.6, 50.2, 114.7,
118.0, 128.6, 129.5, 130.1, 132.7, 142.1; Anal. Calcd
for C15H13ClN2 (256.7): C, 70.18; H, 5.10; N, 10.91.
Found: C, 70.11; H, 5.02; N, 10.86.
2-(4-Methoxyphenyl)-2-(phenylamino) acetoni-
trile (Table 2, entry 6). Yield: 95%; pale yellow solid;
mp 96–97◦C; 1H NMR (300 MHz, CDCl3/TMS): δ
= 3.85 (s, 3H), 4.01 (brs, 1H, NH), 5.38 (s, 1H),
6.8 (d, J = 8.0 Hz, 2H), 6.90–7.00 (m, 3H), 7.27–
7.33 (m, 2H), 7.53 (d, J = 8.0 Hz, 2H); 13C NMR
(75 MHz, CDCl3/TMS): δ = 49.7, 55.5, 114.2, 114.7,
118.4, 120.2, 126.0, 128.6, 129.6, 144.8, 160.5; Anal.
Calcd for C14H10Cl2N2 (238.3): C, 75.61; H, 5.92; N,
11.76. Found: C, 75.55; H, 5.84; N, 11.71.
2-(p-Tolylamino)-2-(4-fluorophenyl)acetonitrile
(Table 2, entry 7). Yield: 94%; white solid; mp
100–102◦C; 1H NMR (300 MHz, CDCl3/TMS): δ =
2.20 (s, 3H), 3.82 (brs, 1H, NH), 5.30 (s, 1H), 6.61
(d, J = 8.4 Hz, 2H), 6.9–7.09 (m, 4H), 7.48–7.53 (m,
2H); 13C NMR (75 MHz, CDCl3/TMS): δ = 20.5, 50.1,
114.7, 116.2, 116.5, 118.2, 129.1, 126.0, 130.1, 142.2,
161.6; Anal. Calcd for C15H13FN2 (240.3): C, 74.98;
H, 5.45; N, 11.66. Found: C, 74.91; H, 5.41; N, 11.60.
2-(3-Nitrophenyl)-2-(phenylamino)acetonitrile
(Table 2, entry 8). Yield: 95%; pale yellow solid; mp
90–92◦C; 1H NMR (300 MHz, CDCl3/TMS): δ = 4.19
(brs, 1H, NH), 5.6 (s, 1H), 6.8 (d, J = 8.0 Hz, 2H),
6.97 (t, J = 8.0 Hz, 1H), 7.31 (d, J = 10.0 Hz, 2H),
7.7 (t, J = 8.0 Hz, 1H), 8 (d, J = 7.1 Hz, 1H), 8.33
(d, J = 8.0 Hz, 1H), 8.5 (s, 1H); 13C NMR (75 MHz,
CDCl3/TMS): δ = 49.7, 114.7, 121.2, 122.4, 124.5,
REFERENCES
[1] Horva´th, I. T.; Anastas, P. T. Chem Rev 2007, 107,
2169.
[2] Ran, N.; Zhao, L.; Chen, Z.; Tao, J. Green Chem 2008,
10, 361.
[3] Polshettiwar, V.; Varma, R. S. Green Chem 2010, 12,
743.
[4] (a) Melero, J. A.; Grieken, R. V.; Morales, G. Chem
Rev 2006, 106, 3790; (b) Kitano, M.; Nakajima, K.;
Kondo, J. N.; Hayashi, S.; Hara, M. J Am Chem Soc
2010, 132, 6622; (c) Karimi, B.; Khalkhali, M. J Mol
Catal A Chem 2005, 232, 113; (d) Chakraborti, A.
K.; Singh, B.; Chankeshwara, S. V.; Patel, A. R. J
Org Chem 2009, 74, 5967; (e) Kumar, A.; Gupta, G.;
Srivastava, S. J Comb Chem 2010, 12, 458; (f) Pari-
ente, S.; Tanchoux, N.; Fajula, F. Green Chem 2009,
11, 1256.
[5] (a) Yadav, G. D.; Murkute, A. D. Langmuir 2004, 20,
11607; (b) Srilatha, K.; Kumar, C. R.; Devi, B. L. A. P.;
Prasad, R. B. N.; Prasad, P. S. S.; Lingaiah, N. Catal
Sci Technol 2011, 1, 662; (c) Tian, X.; Su, F.; Zhao,
X. S. Green Chem 2008, 10, 951; (d) Getty, E. E.;
Drago, R. S. Inorg Chem 1990, 29, 1186; (e) Luque,
R.; Budarin, V.; Clark, J. H.; Macquarrie, D. J. Green
Chem 2009, 11, 459.
[6] (a) Hicks, J. C.; Mullis, B. A.; Jones, C. W. J Am Chem
Soc 2007, 129, 8426; (b) Quinn, C. R.; Clark, J. H.;
Tavener, S. J.; Wilson, K. Green Chem 2003, 5, 602;
(c) Keana, J. F. W.; Shimizu, M.; Jernstedt, K. K.
J Org Chem 1986, 51, 1641; (d) Karam, A.; Gu, Y.;
Je´roˆme, F.; Douliez, J. P.; Barrault, J. Chem Commun
2007, 2222; (e) Motokura, K.; Itagaki, S.; Iwasawa,
Y.; Miyaji, A.; Baba, T. Green Chem 2009, 11, 1876;
(f) Price, P. M.; Clark, J. H.; Martin, K.; Macquarrie,
D. J.; Bastock, T. W. Org Process Res Dev 1998, 2,
221.
[7] Fan, J.; Chen, S.; Gao, Y. Colloids Surf, B 2003, 28,
199.
[8] (a) Kell, A. J.; Stringle, D. L. B.; Workentin, M. S. Org
Lett 2000, 2, 3381; (b) Wang, J.; Sugawara-Narutaki,
A.; Fukao, M.; Yokoi, T.; Shimojima, A.; Okubo, T.
ACS Appl Mater Interfaces 2011, 3, 1538.
[9] Khalafi-Nezhad, A.; Foroughi, H. O.; Doroodmand,
M. M.; Panahi, F. J Mater Chem 2011, 21, 12842.
[10] (a) Chakraborty, T. K.; Reddy, G. V.; Hussain, K.
A. Tetrahedron Lett 1991, 32, 7597; (b) Leblanc,
J.; Gibson, H. W. Tetrahedron Lett 1992, 33, 6295;
(c) Zhong, Y. L.; Lee, J.; Reamer, R. A.; Askin, D. Org
Lett 2004, 6, 929; (d) Enders, D.; Shilvock, J. P. Chem
Soc Rev 2000, 29, 359; (e) Failla, S.; Finocchiaro, P.;
Consiglio, G. A. Heteroatom Chem 2000, 11, 493.
[11] (a) Dyker, G. Angew Chem, Int Ed Engl 1997, 36,
1700; (b) Bergner, I.; Wiebe, C.; Meyer, N.; Opatz,
Heteroatom Chemistry DOI 10.1002/hc

8
Khalafi-Nezhad, Ollah Foroughi, and Panahi
T. J Org Chem 2009, 74, 8243; (c) Duthaler, R. O.
Tetrahedron 1994, 50, 1539; (d) Matier, W. L.; Owens,
D. A.; Comer, W. T.; Deitchman, D.; Ferguson, H. C.;
Seidehamel, R. J.; Young, J. R. J Med Chem 1973, 16,
897.
12, 1343; (c) Zhang, G. W; Zheng, D. H; Nie,
J.; Wang, T.; Ma, J. A. Org Biomol Chem 2010,
8, 1399; (d) Heydari, A.; Arefi, A.; Khaksar, S.;
Shiroodi, R. K.
J Mol Catal A: Chem. 2007,
271, 142; (e) Shaabani, A.; Maleki, A.; Soudi, M.
R.; Mofakham, H. Catal Commun 2009, 10, 945;
(f) Yadav, J. S.; Reddy, B. V. S.; Eshwaraiah, B.; Srini-
vas, M.; Vishnumurthy, P. New J Chem 2003, 27, 462;
(g) Jarusiewicz, J.; Choe, Y.; Yoo, K. S.; Park, C. P.;
Jung, K. W. J Org Chem 2009, 74, 2873.
[12] (a) Strecker, A. Ann Chem Pharm 1850, 75, 27; (b)
Kaur, P.; Wever, W.; Pindi, S.; Milles, R.; Gu, P.; Shi,
M.; Li, G. Green Chem 2011, 3, 1288–1292.
[13] (a) Hatano, M.; Hattori, Y.; Furuya, Y.; Ishihara,
K. Org Lett 2009, 11, 2321; (b) Goodman, M. J
Am. Chem. Soc. 2009, 131, 4070; (c) Surendra, K.;
Srilakshmi Krishnaveni, N.; Mahesh, A.; Rao, K. R. J
Org Chem 2006, 71 2532.
[17] (a) Narasimhulu, M.; Reddy, T. S.; Mahesh, K. C.;
Reddy, S. M.; Reddy, A. V.; Venkateswarlu, Y. J Mol
Catal A: Chem 2007, 264, 288; (b) Karimi, B.; Zareyee,
D. J Mater Chem 2009, 19, 8665; (c) Acosta, F. C.;
Expo´sito, A. S.; Armas, P. D.; Tellado, F. G. Chem
Commun 2009, 6839; (d) Niknam, K.; Saberi, D.;
Sefat, M. N. Tetrahedron Lett 2010, 51, 2959.
[18] (a) Heydari, A.; Khaksar, S.; Pourayoubi, M.;
Mahjoub, A. R. Tetrahedron Lett 2007, 48, 4059;
(b) Shaabani, A.; Maleki, A. Appl Catal A: Gen 2007,
331, 149; (c) Chen, W. Y.; Lu, J. Synlett 2005, 2293;
(d) Kumar, M. A.; Babu, M. F. S.; Srinivasulu, K.;
Kiran, Y. B.; Reddy, C. S. J Mol Catal: A Chem 2007,
265, 268; (e) Surendra, K.; Krishnaveni, N. S.; Ma-
hesh, A.; Rao, K. R. J Org Chem 2006, 71, 2532.
[14] (a) Groger, H. Chem Rev 2003, 103, 2795; (b) Karimi,
B.; Maleki, A. Chem Commun 2009, 5180; (c) Yet, L.
Angew Chem, Int Ed 2001, 40, 871.
[15] (a) Ranu, B. C.; Dey, S. S.; Hajra, S. Tetrahedron
2002, 58, 2529; (b) De, S. K.; Gibbs, R. A. Tetrahedron
Lett 2004, 45, 7407; (c) Yadav, J. S.; Reddy, B. V. S.;
Eswaraiah, B.; Srinivas, M. Tetrahedron 2004, 60,
1767; (d) Reddy, B. M.; Thirupathi, B.; Patil, M. K. J
Mol Catal A: Chem 2009, 307, 154; (e) Khan, N. H.;
Agrawal, S.; Kureshy, R. I.; Abdi, S. H. R.; Singh, S.;
Suresh, E.; Jasra, R. V. Tetrahedron Lett 2008, 49,
640; (f) Shen, Z. L.; Ji, S. J.; Loh, T. P. Tetrahedron
2008, 64, 8159.
[19] Zolfigol,
9509.
M.
A.
Tetrahedron
2001,
57,
[16] (a) Mojtahedi, M. M.; Abaee, S.; Alishiri, T.
Tetrahedron Lett 2009, 50, 2322; (b) Rajabi, F.;
Ghiassian, S.; Saidi, M. R. Green Chem 2010,
[20] Busto, E.; Gotor-Fernandez, V.; Gotor, V. Org Process
Res Dev 2011, 15, 236.
Heteroatom Chemistry DOI 10.1002/hc