Highly efficient and convenient Strecker reaction of carbonyl compounds and amines with TMSCN catalyzed by MCM-41 anchored sulfonic acid as a recoverable catalyst

Article abstract of DOI:10.1016/j.tet.2011.10.087

MCM-41 anchored sulfonic acid (MCM-41-SO₃H) was found to be a highly efficient and recoverable heterogeneous catalyst for the three-component Strecker reaction of aldehydes or ketones and diverse amines using trimethylsilyl cyanide (TMSCN) to afford the corresponding α-amino nitriles under mild conditions in high to quantitative yields. The simple experimental procedure along with easy recovery and reusability of the catalyst has led to development of a clean and environmentally friendly approach for the synthesis of α-amino nitriles.

Full text of DOI:10.1016/j.tet.2011.10.087

Tetrahedron 68 (2012) 922e930
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Highly efficient and convenient Strecker reaction of carbonyl compounds
and amines with TMSCN catalyzed by MCM-41 anchored sulfonic acid
as a recoverable catalyst
*
Mohammad G. Dekamin , Zahra Mokhtari
Pharmaceutical and Biologically-Active Compounds Research Laboratory, Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 June 2011
Received in revised form 7 October 2011
Accepted 24 October 2011
Available online 29 October 2011
MCM-41 anchored sulfonic acid (MCM-41eSO3H) was found to be a highly efficient and recoverable
heterogeneous catalyst for the three-component Strecker reaction of aldehydes or ketones and diverse
amines using trimethylsilyl cyanide (TMSCN) to afford the corresponding a-amino nitriles under mild
conditions in high to quantitative yields. The simple experimental procedure along with easy recovery
and reusability of the catalyst has led to development of a clean and environmentally friendly approach
for the synthesis of a-amino nitriles.
Keywords:
Ó 2011 Elsevier Ltd. All rights reserved.
MCM-41eSO3H nanocatalyst
Solid acid
Strecker reaction
a
-Amino nitriles
Carbonyl compounds
TMSCN
1. Introduction
Bu3SnCN,8a Et2AlCN,8b (EtO)2P(O)CN,8c EtOCOCN,8d (CH3)2C(OH)
CN,8e and K2[Fe(CN)6],9 which are often hazardous, toxic, and re-
quire harsh reaction conditions. However, trimethylsilyl cyanide
(TMSCN) is a promising alternative, due to its nature as an effective,
easily-handled, and relatively safe cyanation reagent for the nucle-
ophilic addition to imines10 and carbonyl double bonds.11 It is
noteworthy that TMSCN is able to transfer the cyanide ion only in
the presence of a catalyst. Therefore, the Strecker reaction has been
promoted by a variety of Lewis or Bronsted acid catalysts such as,
Fe(Cp)2PF6,12a InI3,12b RhI3,12c Cu(OTf)2,12d I2,12e BiCl3,12f La(N-
O3)3$6H2O, GdCl3$6H2O,12g NiCl2,12h Ga(OTf)3,12i GaCl3,12j CeCl3,12k
Pr(OTf)3,12l RuCl3,12m FeCl3,12n and p-toluenesulfonic acid.12o These
catalysts all homogeneously catalyze the Strecker reaction. How-
ever, conventional homogeneous catalysts show many limitations
such as the use of expensive or toxic catalytic systems, difficulty in
separation, tedious work-up and waste discarding.12 Hence, the
tendency toward heterogeneous catalysts is of great importance due
to straightforward separation, waste reduction, and simple recovery
and reuse. Heterogeneous conditions have been reported for some
simple catalysts including guanidine HCl,13a LiClO4,13b Fe(ClO4)3,13c
and Zr(HSO4)4.13d However, incorporation of active catalyst species
into an organic or inorganic polymer framework demonstrates
special advantages: additional reactants activation by support, high
surface area, lower contamination of products; and possibility to
apply continuous flow versus batch configuration on large scales.14
The Strecker reaction, which affords a-amino nitriles by con-
densation of an aldehyde, NH3, and KCN, was first reported in 1850.
It has received great interest as the oldest and most viable multi-
component reaction (MCR) in organic synthesis due to the CeC
bond formation and rich chemistry of the nitrile functional group.1
For example, subsequent hydrolysis of
straightforward route for the synthesis of
and technical scale even after 160 years of the initial introduction of
the Strecker reaction. -Amino acids are themselves key precursors
a
-amino nitriles is the most
a-amino acids on both lab
a
for the synthesis of proteins and have several applications as chiral
building blocks in the pharmaceutical industry.2 For instance,
saframycin A shows potential anti-tumor activity.3 Furthermore,
a-
amino nitriles are versatile intermediates for the preparation of 1,2-
diamines, and nitrogen or sulfur-containing heterocycles such as
imidazoles and thiadiazoles.4,5
a
-Amino nitriles are generally prepared by the nucleophilic ad-
dition of the cyanide anion to an imine formed in situ (classical
Strecker reaction)6 or preformed (modified Strecker reaction).7
A
number of alternative cyanide sources have been introduced to
overcome problems associated with KCN. Examples include
* Corresponding author. Tel.: þ98 (0)21 7724 0284; fax: þ98 (0)21 7322 7703;
e-mail address: mdekamin@iust.ac.ir (M.G. Dekamin).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.10.087

M.G. Dekamin, Z. Mokhtari / Tetrahedron 68 (2012) 922e930
923
In recent years, some heterogeneous Lewis or Bronsted acid
catalytic systems consisting of poly(4-vinylpyridine)eSO2 com-
plex,15a silica-bonded S-sulfonic acid,15b silica sulfuric acid,15c
montmorillonite,15d organic polymer-supported scandium trifla-
te,15e Co(II) complex interphase catalyst,15f cellulose sulfuric acid,15g
silica-supported heteropoly acid,15h and mesoporous inorga-
niceorganic scandium triflate15i have also been developed. There-
fore, it is still desirable to develop an efficient and convenient
heterogeneous protocol for the Strecker reaction. In this context,
development of mesoporous materials (MCMs), which show a one-
dimensional hexagonal array, high surface area (>1000 m2 gꢀ1),
large pore volume (up to 0.99 cm3 gꢀ1), tunable pore size, ease of
modification of the surface properties and excellent thermal,
hydrothermal, chemical, and mechanical stability has attracted
extensive interest by many research groups as potential heteroge-
neous catalysts to replace homogeneous catalytic systems.16 How-
ever, one of the limitations of MCMs as acid catalysts is due to low
acid strength of mesoporous silicas.16,17 In order to overcome this
drawback, different methods of enhancing their acidity including
replacement of Si atoms in the lattice by metal ions such as Al,6a B,
Fe,18a and Zr18b or anchoring acidic organic groups such as 3-
sulfonic propyl19 and inorganic sulfonic acid (eSO3H)20 have been
described. Fortunately, the presence of a high concentration of
silanol groups in MCM-41 provides convenient anchoring of in-
organic sulfonic acid (eSO3H) to the surface of silica to carry out
various organic transformations with increased selectivities.19,20 To
the best of our knowledge, these easily accessible nano-ordered
solid Bronsted acids have not been sufficiently explored as re-
coverable catalysts. Recently, we have introduced nano-ordered
BeMCM-41 for the efficient and selective three-component
Strecker reaction.18a In continuation of our interest in the Strecker
reaction catalyzed by modified MCM-41 materials and other or-
ganic transformations using silylating reagents,11,18a,21 we wish
herein to disclose the promising catalytic activity of highly ordered
mesoporous silica functionalized with a grafted sulfonic acid group
(MCM-41eSO3H) 1 in the one-pot three-component Strecker re-
action of carbonyl compounds, and amines with TMSCN at ambient
temperature. The catalytic activity of MCM-41eSO3H 1 is notable
especially for less reactive ketones (Scheme 1).
improve the yield and the reaction time. Screening of the solvents
was also carried out under similar reaction conditions. CH2Cl2 and
CH3CN were also examined for the above model reaction (entries
7 and 8, Table 1). Therefore, EtOH emerged as the superior me-
dium to afford the desired product 4a faster and in higher yield.
On the other hand, the model reaction was not completed in
a reasonable time under solvent-free conditions (entry 9, Table 1).
Furthermore, 3-aminopropyltriethoxysilan-modified MCM-41 (3-
APeMCM-41eSO3H) required a longer reaction time compared to
MCM-41eSO3H in the same conditions (entry 10, Table 1).
In previous investigations performed by us and other research
groups, the catalytic activity of modified MCM-41 materials by
boron (BeMCM-41), ferric (FeeMCM-41)18a zirconium (ZreMCM-
41)18b and other mesoporous such as TUD-1 by gallium (GaeTUD-
1)22 have been studied. It is obvious that this alteration improved
the efficiency of the method and the desired product was obtained
in very low catalyst loading and short reaction time (entries 11e13,
Table 1). Encouraged by these results, aromatic, heteroaromatic,
and aliphatic aldehydes or ketones with aromatic and aliphatic
amines were subjected to the Strecker reaction under the opti-
mized reaction conditions (MCM-41eSO3H; 5 mg per mmol of
carbonyl compound, 1.2 equiv of TMSCN, room temperature, EtOH).
Tables 2 and 3 show the scope of the reaction using a number of
representative carbonyl compounds and amines wherein high to
quantitative yields of the corresponding a-amino nitriles 4 were
isolated within a short reaction time in all the cases studied.
Upon completion of the reaction, the catalyst was removed
from the reaction mixture simply by filtration during crystalliza-
tion of the products or their usual work-up. In general, substrates
containing electron-withdrawing groups required shorter reaction
times compared to those with electron-donating groups,
depending on the amine. Furthermore, MCM-41eSO3H worked
well with acid sensitive electron-rich heterocyclic aldehydes such
as furfural, thiophene-2-carbaldehyde, and cinnamaldehyde to
provide the corresponding products in high yields without for-
mation of any polymerization products (entries 10e12).12g On the
other hand, ketones showed lower reactivity under optimal re-
action conditions in comparison to aldehydes due to more steric
hindrance around their carbonyl group.12h,i To the best of our
knowledge, only a few studies on the Strecker reaction with ke-
tones have been reported in the literature.6a,12gei,18,23e26
We observed considerable effects on the rate of reaction, ob-
tained yield, and simplicity of the procedure using EtOH compared
to other solvents such as CH2Cl2, CH3CN, DMF, THF in the Strecker
reaction.12,15,18,23 This may be attributed mainly to the low solu-
bility of the products in EtOH. On the other hand, EtOH can activate
a carbonyl group for amine nucleophilic attack via hydrogen
bonding. Furthermore, TMSCN itself can be activated by EtOH as
a Lewis base (Scheme 2). The latter property may be anticipated for
solvents such as DMF and THF in lower intensities. Indeed, products
having melting points higher than 60 ꢁC precipitated out of the
reaction mixture and therefore afforded higher yields. The solu-
bility of the products also influences nucleophilicity of the amine
used. For instance, aniline 3a provided generally higher yields than
4-methylaniline 3b and even benzyl amine 3c. To investigate the
reaction mechanism, progress of the reaction was monitored by TLC
using authentic samples of corresponding cyanohydrin trime-
thylsilyl ethers 511 and imines (intermediate III)10 in the reaction of
carbonyl compounds 2a, 2d, 2e, 2h, and 2k with amine 3a. It was
found that cyanohydrin trimethylsilyl ether products (5aey) were
not observed in the presence of primary amines and the reaction
proceeds through the formation of the imine intermediate. How-
ever, some (E)- and (Z)-isomers of the corresponding imine were
observed, which were completely converted to the desired prod-
ucts 4aey after the times indicated in Table 2. In an additional
experiment, the corresponding imine of the model reaction was
O
MCM-41-SO3H
EtOH, r.t.
NHR"
CN
+
R"NH2
+
TMSCN
R'
R
R
R'
Scheme 1. Strecker reaction of carbonyl compounds and amines with TMSCN cata-
lyzed by MCM-41eSO3H.
2. Results and discussion
In order to obtain the best reaction conditions, the reaction of
4-chlorobenzaldehyde 2a, aniline 3a, and TMSCN (mole ratio
1:1:1.2) as model reactants in EtOH was chosen and the effect of
MCM-41eSO3H loading was examined. The results have been
summarized in Table 1. It is noteworthy that only a trace amount
of the desired a-amino nitrile 4a was formed in the absence of
catalyst 1 even after 24 h (entry 1, Table 1). Using 75 mg of MCM-
41 per mmol of 2a, a moderate yield of 50% was obtained after the
same time (entry 2, Table 1). Interestingly, it was found that the
reaction smoothly proceeded in the presence of only catalytic
amounts of 1 to afford the corresponding a-amino nitrile 4a in
very short reaction times (entries 3e5, Table 1). Furthermore,
both 96% and absolute EtOH required a similar reaction time to
afford the desired product in quantitative yield (entries 5 and 6,
Table 1). According to these data, the optimum amount of catalyst
was 5 mg per 1 mmol of model substrates. Both the lesser
(2.5 mg) and the higher (7.5 mg) amount of catalyst did not

924
M.G. Dekamin, Z. Mokhtari / Tetrahedron 68 (2012) 922e930
Table 1
Three-component Strecker reaction of 4-chlorobenzaldehyde 2a and aniline 3a with TMSCN by various catalystsa
O
NH2
OSiMe3
CN
CN
MCM-41-SO3H
H
N
+
+
+
TMSCN
H
Cl
Cl
Cl
4a
5a
2a
3a
Entry
Catalyst
Amount of catalyst (mg)
Solvent
Time (min)
Yieldb 4a (%)
Yieldb 5a (%)
1
2
3
4
5
6
7
8
d
d
75
7.5
5
2.5
5
5
5
5
5
EtOH
EtOH
EtOH
EtOH
EtOH
EtOHc
CH2Cl2
CH3CN
d
24 (h)
24 (h)
25
30
45
30
60
70
24 (h)
90
5
50
91
98
90
98
97
88
15
86
98
95
91
0
0
0
0
0
0
0
0
0
0
0
0
d
MCM-41
MCM-41eSO3H
MCM-41eSO3H
MCM-41eSO3H
MCM-41eSO3H
MCM-41eSO3H
MCM-41eSO3H
MCM-41eSO3H
MCM-41eAPeSO3H
BeMCM-41
9
10
11
12
13
EtOH
EtOH
CH2Cl2
d
50
50
20
1.5 (h)
6 (h)
30
FeeMCM-41
GaeTUD-122
a
Reaction conditions: 4-chlorobenzaldehyde 2a (1 mmol), aniline 3a (1 mmol), TMSCN (1.2 mmol), catalyst, solvent (1.5 mL), room temperature.
Isolated yield.
Absolute EtOH was used instead of 96% EtOH.
b
c
Table 2
Three-component Strecker reaction of various aldehydes and amines with TMSCN catalyzed by MCM-41eSO3H under optimal conditions
O
NHR'
CN
MCM-41-SO3H
EtOH, r.t.
+
R'NH2
+
TMSCN
H
R
R
H
2
3
4
Entry
1
Aldehyde
Amine
Producta
Time (min)
Yieldb (%)
Mp (ꢁC)
Lit. mp (ꢁC)
O
CN
NH2
H
N
H
30
98
114e116
110e11212a
Cl
Cl
3a
2a
4a
Cl
O
NH2
Cl
CN
H
N
2
3
4
5
6
50
45
15
15
30
94
92
98
98
98
61e63
87e88
Oil
63e6613d
H
3a
3a
4b
2b
2c
O
CN
NH2
H
H
N
H
15a
Br
Br
4c
O
O
CN
NH2
N
H
Oil9
O2N
O2N
O2N
O2N
3a
3a
3a
2d
2e
4d
NH2
CN
H
N
H
86e88
108e110
89e9215b
4e
O
CN
NH2
H
N
H
112e11412k
NC
NC
2f
4f

M.G. Dekamin, Z. Mokhtari / Tetrahedron 68 (2012) 922e930
925
Table 2 (continued )
Entry Aldehyde
Amine
Producta
Time (min)
Yieldb (%)
Mp (ꢁC)
Lit. mp (ꢁC)
O
NH2
NH2
NH2
CN
H
O
N
H
7
70
97
76e78
76e7812a
3a
3a
2g
4g
CN
H
H
N
H
8
90
90
95
95
98
93
93
87
85
96
97
95
90
69e71
93e94
123e125
67e69
98e100
Oil
72e7413d
Me
Me
2h
2i
4h
O
CN
N
H
9
95e9612a
MeO
MeO
3a
3a
3a
4i
O
NH2
CN
N
H
H
10
11
12
13
14
15
16
17
18
120
160
160
190
250
65
120e12212a
68e6912a
98e10012a
Oil28
2j
4j
H
NH2
N
H
O
O
CN
O
O
4k
2k
2l
H
N
NH2
H
S
S
CN
3a
4l
O
NH2
CN
H
N
H
3a
3a
2m
4m
NH2
O
CN
N
H
Oil
Oil4
H
2n
2a
4n
CH3
O
NH2
CN
H
N
H
85e8715b
89e9029
75e7630
102e10415b
H3C
H3C
H3C
H3C
83e85
85e87
Oil
Cl
Cl
3a
3b
3b
3b
4o
CH3
O
NH2
NH2
NH2
CN
H
N
H
60
O2N
O2N
O2N
2d
2e
4p
CH3
O
CN
O2N
H
N
H
60
4q
CH3
O
CN
H
N
H
140
104e106
(continued on next page)
2g
4r

926
M.G. Dekamin, Z. Mokhtari / Tetrahedron 68 (2012) 922e930
Table 2 (continued )
Entry
Aldehyde
Amine
Producta
Time (min)
145
Yieldb (%)
Mp (ꢁC)
Lit. mp (ꢁC)
CH3
O
NH2
CN
H
N
H
H3C
19
90
101e103
103e10431
MeO
MeO
3b
3c
2i
4s
CN
O
NH2
H
N
H
20
21
22
23
24
60
50
89
89
89
87
89
Oil
Oil
Oil
Oil
Oil
Oil9
Oil9
Oil9
Oil9
Oil9
Cl
Cl
2a
4t
CN
O
NH2
H
N
H
O2N
O2N
O2N
3c
3c
2d
2e
4u
CN
O
NH2
NH2
NH2
NH2
O2N
N
H
H
90
4v
O
CN
N
H
H
O
90
3c
3c
3c
4w
2g
CN
N
H
H
H
110
Me
Me
HO
2h
2o
4x
O
CN
N
H
HO
25
120
98
208e211
Present work
4y
a
All compounds, except product 4y (entry 25), are known and their structures were established from their spectral data and melting points as compared with literature values.
Isolated yield.
b
treated with 1 under the optimal reaction conditions. It was found
covalently anchored sulfonic acid onto the surface of MCM-41
catalyst under heterogeneous catalysis conditions. Moreover, high
yield of the products, easy work-up, the ecologically clean pro-
cedure, and reusability of catalyst for at least five reaction cycles
without significant lose of its activity will make the present method
a valuable methodology for the Strecker reaction.
that the desired product 4a was obtained quantitatively (98%) after
5 min. These findings along with substituent effects all demon-
strate that formation of imine intermediate is the key step in the
one-pot three-component Strecker reaction catalyzed by MCM-
41eSO3H (Scheme 2).
To prove whether the catalytic performance of MCM-41eSO3H in
the Strecker reaction is heterogeneous or not, the following experi-
ment was also performed. A mixture of the model reaction was fil-
tered off after 15 min, and the filtrate was stirred further at room
temperature. It was found thatonly 40% of the desired product 4awas
obtained after 24 h. On the other hand, the separated MCM-41eSO3H
catalyst in the model reaction was subjected to a further run after
simple recovery process including washing by EtOAc and subsequent
drying at 50 ꢁC. Quantitative conversion of substrates was observed
and the average 95% isolated yield obtained over five consecutive
studied runs (Fig. 1). These findings demonstrate that nano-ordered
MCM-41eSO3H is stable enough to serve as a solid acid and hetero-
geneous catalyst under the optimal reaction conditions.
4. Experimental section
4.1. General
All chemicals and reagents were purchased from Merck and
Aldrich and used without further purification except for benzal-
dehyde, for which a fresh distilled sample was used. MCM-41 was
synthesized according to the literature.27 Tetraethylorthosilicate
(TEOS) and cetyltrimethylammonium bromide (CTAB) were used as
source of silicon and structure directing agent, respectively. Ana-
lytical TLC was carried out using Merck 0.2 mm silica gel 60 F-254
Al-plates. All yields refer to the isolated products after purification.
MCM-41eSO3H was synthesized according to the reported pro-
cedure and was characterized by FTIR spectroscopy and scanning
electron microscopy (SEM).20 Products were characterized by
spectroscopy data (IR, 1H NMR, and 13C NMR spectra) and melting
points. FTIR spectra were recorded as KBr pellets on a Shimadzu FT
3. Conclusion
In conclusion, we have developed a mild, straightforward, and
green procedure for the synthesis of a-amino nitriles using reusable

M.G. Dekamin, Z. Mokhtari / Tetrahedron 68 (2012) 922e930
927
Table 3
Three-component Strecker reaction of various ketones and amines with TMSCN catalyzed by MCM-41eSO3H under optimal conditions
O
NHPh
CN
MCM-41-SO3H
EtOH, r.t.
+
PhNH2
+
TMSCN
R'
R
R
R'
3a
4
2
Entry
1
Ketone
Producta
Time (min)
170
Yieldb (%)
Mp (ꢁC)
Lit. mp (ꢁC)
O
CN
CH3
N
H
Me
97
161e164
164e16612a
O2N
O2N
2a'
4a'
O
CN
N
H
CH3
2
3
4
180
180
180
89
92
91
140e142
83e85
140e14212a
CH3
4b'
2b'
H3C
H
N
CH3
O
O
83e8523
O
CN
2c'
4c'
H
O
NC
N
69e72
70e7128
2d'
4d'
O
CN
N
5
200
87
81e83
25
H
2e'
4e'
F
O
CN
F
N
H
6
210
75
Oil
Present work
2f'
4f'
a
All compounds, except product 4f0 (entry 6), are known and their structures were established from their spectral data and melting points as compared with literature values.
Isolated yield.
b
IR-8400S spectrometer. SEM micrographs were obtained, using
liquor and washed with deionized water. The sample was dried at
45 ꢁC for 12 h. The synthesized MCM-41 was calcined at 550 ꢁC for
5 h to remove all the surfactant.
a JEOL microscope model JEM 6300 (Japan). 1H NMR (500 MHz) and
13C NMR (125 or 75 MHz) spectra were obtained using Bruker DRX-
500 Avance and Bruker DRX-300 Avance spectrometers at ambient
temperature, respectively. Microanalysis of the products was car-
ried out by a CHNS/O analyzer (PerkineElmer Series II, 2400).
Melting points were determined using an Electrothermal 9100
apparatus and are uncorrected.
4.3. General procedure for preparation of MCM-41eSO3H
MCM-41wasmodifiedusinga100 mLsuction flask equipped with
a constant pressure dropping funnel containing chlorosulfonic acid
(ClSO3H)and a gasinlettubeforconductingHClgas overanadsorbing
solution. MCM-41 (1 g) suspended in CH2Cl2 (5 mL) was charged to
the flask and ClSO3H (2 mL) was then added drop-wise over a period
of30 minatroomtemperature.HClgaswasevolvedfromthereaction
vessel immediately. After complete addition of ClSO3H, the mixture
was stirred for 30 min and the solvent was evaporated under reduced
pressure to obtain MCMeSO3H as a light gray solid.20
4.2. General procedure for preparation of MCM-41
A typical MCM-41 preparation was as follows: diethylamine
(2.7 g) was added to deionized water (42 mL) in a 200 mL beaker
while the mixture was stirred at room temperature. After 10 min,
CTAB (1.47 g) was added to the above solution under stirring step
by step for 30 min until a clear solution was obtained. Then, TEOS
(2.1 g) was added drop-wise to the solution. The pH of the reaction
mixture was adjusted to 8.5 by slow addition of hydrochloric acid
solution (1 M). At this stage, the precipitate was formed. After 2 h,
under slow stirring, the solid product was filtered from the mother
4.4. Typical procedure for the synthesis of a-amino nitriles
To a mixture of carbonyl compound (2aeo or 2a0ef0, 1 mmol),
amine (3aec, 1 mmol), and TMSCN (1.2 mmol, 0.15 mL) was added

928
M.G. Dekamin, Z. Mokhtari / Tetrahedron 68 (2012) 922e930
O
O
O
O
O
SO2
OH
NHR"
CN
Si
O
Si
O
H
R
R'
O
R
R'
(2)
(4)
(1)
O
O
O
O+
O
O
Me
Me
Si
CN
Si
O
Si
Si
O
H
O
O
H
Me
Me
O3SO
Si Me
O+
O3SO
(I)
+
H
Si
Me
H
X = O
R"NH2
H(Et)
H
R
O
H
CN
X
(3)
(V)
(V')
R"
X = N
R'
R'
R
O
O
O
Si
Si
O
O
TMSCN
O
O
H
O3SO
Si
Si
O
O3SO
O
H
H
H
O
R"
H
N
N
R
EtOH
+
(III)
R'
R'
R
R"
EtOH
(II)
O
O
O
Si
Si
O
H
O
O3SO
H
Et
O
H2O
H
+
N
R
R'
R"
(IV)
Scheme 2. Plausible mechanism for the Strecker reaction of carbonyl compounds (2) and amines (3) with TMSCN catalyzed by MCM-41eSO3H 1.
MCM-41eSO3H (1, 5 mg) in 96% EtOH (1.5 mL) at room temperature.
The mixture was stirred for an appropriate time indicated in Table 2
or Table 3. After completion of the reaction, as indicated by TLC, 96%
EtOH (5 mL) was added to the reaction mixture. The obtained
mixture was directly crystallized or filtered to remove the catalyst 1
from solid and viscous products, respectively. In the case of viscous
products, the organic solvent of the filtrate was evaporated under
reduced pressure to obtain essentially pure products in most cases.
Further purification of the viscous products could be performed by
silica gel column chromatography (EtOAcehexane, 1:10).
above general procedure for synthesis of a-amino nitriles. After the
first run, which gave the corresponding 2-(N-anilino)-2-(4-
chlorophenyl) acetonitrile in 98% isolated yield (100% conver-
sion), the catalyst washed with fresh aliquot of EtOAc (3ꢂ5 mL),
dried in an oven at 50 ꢁC, and then was subjected to a second
Strecker reaction from which it also gave the Strecker products in
100% conversion (96% isolated yield); the average chemical yield for
five repeated runs was 94% (Fig. 1).
Spectral data for the selected compounds:
2-(N-Anilino)-2-(4-chlorophenyl)acetonitrile (Table 2, entry 1)
4.5. Reusability of MCM-41eSO3H
White solid, mp 114e116 ꢁC; IR (KBr):
n
3405, 2928, 2232, 1609,
1522, 1458, 1260, 1080, 782 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d
4.14
The reusability of the catalyst 1 was investigated in the con-
secutive Strecker reaction of 4-chlorobenzaldehyde 2a and aniline
3a with TMSCN. The reactions were carried out according to the
(br s, 1H), 5.46 (s, 1H), 6.81 (d, J¼8.1 Hz, 2H), 6.97 (t, J¼7.3 Hz, 1H),
7.32 (t, J¼7.7 Hz, 2H), 7.47 (d, J¼8.3 Hz, 2H), 7.58 (d, J¼8.3 Hz, 2H)
ppm; 13C NMR (CDCl3):
d 49.7, 114.2, 117.7, 120.8, 129.4, 129.6, 132.3,
135.5, 144.4 ppm.12a,b,13d,15i,23
2-(N-Anilino)-2-(4-methoxyphenyl)acetonitrile (Table 2, entry 9)
98
96
100
90
80
70
60
50
40
30
20
10
0
93
93
91
White solid, mp 93e94 ꢁC; IR (KBr):
n
3328, 2925, 2349, 1602,
1504, 1440, 1248, 1172, 754 cmꢀ1; 1H NMR (500 MHz, CDCl3):
d
3.87
(s, 3H), 4.51 (br s, 1H), 5.39 (s, 1H), 6.81 (d, J¼7.8 Hz, 2H), 6.92 (t,
J¼7.4 Hz, 1H), 7.00 (d, J¼7.8 Hz, 2H), 7.30 (t, J¼8.7 Hz, 2H), 7.53 (d,
J¼8.7 Hz, 2H) ppm; 13C NMR (CDCl3):
d 49.4, 55.3, 114.0,114.4,118.4,
119.9, 125.8, 128.5, 129.4, 144.7, 160.2 ppm.9,12a,b,13d,15i,23
2-(N-Anilino)-2-furfuryl acetonitrile (Table 2, entry 11)
Dark brown solid, mp 67e69 ꢁC; IR (KBr):
n
3362, 3045, 2351,
1602, 1556, 1490, 1311, 1161, 746 cmꢀ1; 1H NMR (500 MHz, CDCl3):
4.12 (br s, 1H), 5.52 (s, 1H), 6.44 (d, J¼4.7 Hz, 1H), 6.61 (t, J¼4.7 Hz,
d
1
2
3
4
5
Run
1H), 6.81 (d, J¼7.8 Hz, 2H), 6.96 (t, J¼7.8 Hz, 1H), 7.28 (t, J¼7.8 Hz,
2H), 7.51 (d, J¼4.7 Hz,1H) ppm; 13C NMR (CDCl3):
d 48.2, 111.1, 111.9,
116.3, 122.4, 1130.0, 134.4, 137.2, 146.2 ppm.12aec,13d,15i,23
Fig. 1. Recyclability of MCM-41eSO3H catalyst 1 for the Strecker reaction.

M.G. Dekamin, Z. Mokhtari / Tetrahedron 68 (2012) 922e930
929
€
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2-(4-Tolylamino)-2-(4-chlorophenyl)acetonitrile (Table 2, entry 15)
White solid, mp 83e85 ꢁC; IR (KBr):
3336, 2921, 2356, 1620,
1515, 1490, 1093, 813 cmꢀ1 1H NMR (500 MHz, CDCl3):
2.31 (s,
n
;
d
3. (a) Myers, A. G. J. Am. Chem. Soc. 1999, 121, 10828; (b) Myers, A. G.; Kung, D. W.
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3H), 3.96 (br s, 1H), 5.41 (s, 1H), 6.71 (d, J¼7.9 Hz, 2H), 7.10 (d,
J¼8.0 Hz, 2H), 7.46 (d, J¼8.4 Hz, 2H), 7.57 (d, J¼8.3 Hz, 2H) ppm; 13C
NMR (CDCl3):
d 20.5, 50.0, 114.6, 118.0, 128.5, 129.4, 129.9, 130.0,
132.5, 135.4, 142 ppm.12i
ꢀ
2-(N-Benzylamino)-2-(4-chlorophenyl)acetonitrile (Table 2, entry
20)
ꢀ
Light yellow oil; IR (KBr):
725 cmꢀ1; 1H NMR (500 MHz, CDCl3):
(br s,1H), 7.28e7.42 (m, 5H), 7.53 (d, J¼7.0 Hz, 2H), 7.52 (d, J¼7.0 Hz,
n
3323, 3029, 2362, 1664, 1473, 1099,
d
2.0 (s, 1H), 3.75 (s, 2H), 4.75
2H) ppm; 13C NMR (CDCl3):
d 51.47, 53.0, 118.52, 127.9, 128.6, 128.8,
129.3, 133.3, 135.2, 138.0 ppm.12c,23
2-(N-Benzylamino)-2-(4-hydroxyphenyl)acetonitrile (Table 2, en-
try 25)
Cream solid, mp 208e211 ꢁC;
n
3443, 3313, 3196, 3063, 3030,
2916, 2362, 2328, 1668, 1600, 1514, 1452, 1283 cmꢀ1 1H NMR
(500 MHz, CDCl3): 2.14 (br s, 1H), 3.82 (s, 2H), 4.90 (s, 1H), 5.01 (br
9. Zheng, L.; Yuanhong, M.; Jun, X.; Jinghong, Sh.; Hongfang, C. Tetrahedron Lett.
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;
d
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S. K.; Gibbs, R. A. Synth. Commun. 2005, 35, 961; (m) De, S. K. Synth. Commun.
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s, 1H), 6.52 (d, J¼7.2 Hz, 2H), 6.76 (d, J¼7.2 Hz, 2H), 7.16 (d, J¼8.0 Hz,
2H), 7.23 (t, J¼8.0 Hz, 1H), 7.31 (d, J¼8.0 Hz, 2H) ppm; 13C NMR
(75 MHz, CDCl3)
d 44.9, 55.0, 112.8, 115.9, 126.7, 127.6, 127.9, 128.1,
130.0, 137.5, 161.9 ppm. Anal. Calcd for C15H14N2O: C, 75.61; H, 5.92;
N, 11.76; Found: C, 75.56; H, 5.99; N, 12.02.
2-(N-Anilino)-2-(4-nitrophenyl)propanenitrile (Table 3, entry 1)
Yellow crystalline solid, mp 161e164 ꢁC; IR (KBr):
n
3382, 3068,
2942, 2246, 1923, 1691, 1604, 1515, 1346, 1264, 1177, 1099, 852, 743,
692 cmꢀ1; 1H NMR (500 MHz, CDCl3):
2.0 (s, 3H), 4.48 (br s, 1H),
d
6.50 (d, J¼8.5 Hz, 2H), 6.81 (t, J¼7.4 Hz, 1H), 7.11 (t, J¼7.5 Hz, 2H),
7.81 (d, J¼8.8 Hz, 2H), 8.25 (d, J¼8.8 Hz, 2H) ppm.12a,23
2-(N-Anilino)-2-(4-flourophenyl)benzonitrile (Table 3, entry 6)
Light yellow oil; IR:
1227,1151, 851, 735, 698 cmꢀ1; 1H NMR (500 MHz, CDCl3):
s, 1H), 6.43 (d, J¼7.8 Hz, 2H), 6.60 (t, J¼7.4 Hz, 3H), 6.86 (t, J¼8.5 Hz,
2H), 7.04e7.20 (m, 9H) ppm; 13C NMR (75 MHz, CDCl3)
60.05,
n
3064, 2361, 2324, 1647, 1597, 1502, 1282,
d
4.14 (br
d
113.0, 115.1, 116.0, 116.9, 126.4, 127.5, 128.9, 129.2, 130.1, 137.9, 140.4,
141.5, 163.3 ppm. Anal. Calcd for C20H15FN2: C, 79.45; H, 5.00; N,
9.27; Found: C, 79.32; H, 5.12; N, 9.14.
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Acknowledgements
We are grateful for the financial support from The Research
Council of Iran University of Science and Technology (IUST), Iran
(Grant No. 160/354). We would also like to acknowledge the sup-
port of Iran Nanotechnology Initiative Council (INIC). We also thank
Dr. Ali Bumajdad from Kuwait University, Kuwait for helpful dis-
cussions and technical staff of the analytical units of SAF (Kuwait
University) for their assistance to obtain SEM micrographs.
Supplementary data
IR spectrum and SEM images of MCM-41eSO3H 1 along with IR,
1H and 13C NMR spectra of compounds 4a, 4i, 4k, 4o, 4t, 4y, 4a0, and
4f0. Supplementary data associated with this article can be found in
online version, at doi:10.1016/j.tet.2011.10.087.
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