Organic amine grafting on mesoporous silica as a hybrid catalyst for heterogeneous three-component one-pot reaction

Article abstract of DOI:10.1016/j.apcata.2012.08.009

The organic-inorganic hybrid catalyst was prepared by immobilizing 3-methylaminopropyl moiety onto mesoporous silica, MCM-41, and applied for solid base catalyst of three-component one-pot reaction, i.e. Knoevenagel condensation of aldehyde with the active methylene compound to yield an electron deficient alkene which is subjective to be reacted with nitromethane by Michael addition to form tri-substituted primary nitro compound. The catalyst was characterized by powder-XRD, TG-DTA, FT-IR, nitrogen adsorption-desorption measurement and solid-state cross polarization magic angle spinning (CP/MAS) NMR, and exhibited high catalytic activity in three-component one-pot reaction; however, with poor reusability.

Full text of DOI:10.1016/j.apcata.2012.08.009

Applied Catalysis A: General 445–446 (2012) 128–132
Contents lists available at SciVerse ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Organic amine grafting on mesoporous silica as a hybrid catalyst for
heterogeneous three-component one-pot reaction
Kenichi Komura∗, Yuta Mishima, Mamoru Koketsu
Department of Materials Science and Technology, Faculty of Engineering, Gifu University, Gifu City 501-1193, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 June 2012
Received in revised form 2 August 2012
Accepted 11 August 2012
Available online 20 August 2012
The organic–inorganic hybrid catalyst was prepared by immobilizing 3-methylaminopropyl moiety onto
mesoporous silica, MCM-41, and applied for solid base catalyst of three-component one-pot reaction,
i.e. Knoevenagel condensation of aldehyde with the active methylene compound to yield an electron
deficient alkene which is subjective to be reacted with nitromethane by Michael addition to form tri-
substituted primary nitro compound. The catalyst was characterized by powder-XRD, TG–DTA, FT-IR,
nitrogen adsorption–desorption measurement and solid-state cross polarization magic angle spinning
(CP/MAS) NMR, and exhibited high catalytic activity in three-component one-pot reaction; however,
with poor reusability.
Keywords:
Mesoporous silica
MCM-41
Three-component reaction
One-pot reaction
Solid base catalyst
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
system. Thus the development for heterogeneous MCRs should be
a challenging task [23].
The carbon–carbon forming reaction catalyzed by base is a piv-
otal tool in organic synthesis, and vast efforts have been attained
so far. From the viewpoint of catalyst, homogeneous catalysts
such as organic bases have been sufficiently investigated [1]; how-
ever, with increasing the demands for the environmental benign
chemistry, much attention has been paid to the development for
heterogeneous base catalyst that has advantages such as an ease
for removal, recyclability and reusability [2]. Instead of typical solid
base catalysts such as Al2O3 and MgO, the organic–inorganic hybrid
mesoporous silica materials have become a promising candidate
for heterogeneous base catalyst [3,4]. They are successfully applied
in typical reactions such as Knoevenagel condensation [5–12],
Claisen–Schmidt reaction [5], Henry reaction [13–17], Michael
addition [7,18], and so on [19]. Recently, the multicomponent reac-
tions (MCRs) involving base catalyzed C C bond forming reaction
have been designed by utilizing bifunctional mesoporous silica cat-
alyst [20,21]. The MCRs are responsible for higher efficiency, not
only because of intrinsic aspects of the reaction such as superior
atom economy, atom utilization and selectivity, but also because
of extrinsic aspects of the processing reaction such as simpler
procedures and equipment, lower cost, time and energy [22]. How-
ever, the reports on heterogeneous catalyst in MCRs seem to be
poor than those on homogeneous (including asymmetric) catalyst
Our strategy in this study, three-component one-pot reaction,
is based on the combination of typical base catalyzed reactions
such as Knoevenagel condensation and Michael addition illus-
trated in Scheme 1, i.e. Knoevenagel condensation of aldehyde with
active methylene compound bearing electron-withdrawing group
(EWG) offers the formation of unsaturated and electron deficient
product, this can be utilized as Michael acceptor followed by the
addition of nucleophile (Nu−) as Michael donor, resulting in pro-
duction of Michael adduct. It can be expected that the organic amine
immobilized onto mesoporous silica would be responsible for base
catalysis in both reactions, and that the formed product bearing
multi-functional groups should serve as a versatile intermediate
for pharmaceuticals, because they have acceptable substituents for
further chemical transformations in their molecules.
Here, we wish to report the heterogeneous three-component
one-pot reaction over the organic–inorganic hybrid catalyst.
2. Experimental
2.1. Characterizations and materials
Powder X-ray diffraction (XRD) was measured by a Shimadzu
˚
XRD-6000 diffractometer with K␣ radiation (˛ = 1.5418 A). Nitro-
gen adsorption isotherm measurements were carried out on a
Belsorp 28SA apparatus (Bel, Japan). Liquid 1H and 13C NMR mea-
surements in CDCl3 containing tetramethylsilane as an internal
standard and solid-state 13C and 29Si cross polarization (CP) magic
∗
Corresponding author. Tel.: +81 58 293 2600; fax: +81 58 293 2794.
E-mail address: kkomura@gifu-u.ac.jp (K. Komura).
0926-860X/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.apcata.2012.08.009

K. Komura et al. / Applied Catalysis A: General 445–446 (2012) 128–132
129
EWG
H2C
Nu
Nu-
EWG
EWG
EWG
EWG
R
R
CHO
R
Michael
addition
Knoevenagel
condensation
EWG
Scheme 1.
angle spinning (MAS) NMR spectra were recorded at ambient tem-
perature by using 4 mm diameter zirconia rotor with a spinning rate
of 6 kHz (ECA-500 NMR spectrometer, JEOL Ltd.). FT-IR measure-
ment was performed by PerkinElmer 2000. Thermal gravitational
analysis (TGA) and differential thermal analysis (DTA) were car-
ried out by using a Shimadzu DTG-50 analyzer at a ramping rate of
10 K/min under an air stream. All of reagents were commercially
available and used without purification.
NMR spectrum, thus all structural descriptions are ignored in this
text.
3. Results and discussion
3.1. Characterization of MAP-M41 catalyst
Fig. 1 shows powder XRD charts of MCM-41 (a) and MAP-
M41 (b), respectively. The peaks corresponding to MCM-41 were
observed in the low-angle region indexed on a hexagonal unit cell
with p6mn space group (a); however, the slight decrease in peak
intensity associated with (1 1 0) and (2 0 0) reflections was observed
after immobilization (b). It is clear that MAP-M41 has mesoporous
allay structure without collapse during modification.
The nitrogen adsorption–desorption isotherms of MCM-41 (a)
and MAP-M41 (b) are given in Fig. 2. They show typical type-IV
isothermal curves, and the significant decreasing of the adsorbed
N2 was observed in MAP-M41, resulting in the decreased sur-
face area from 1048 to 784 m2 g−1 and pore volume from 1.00 to
0.48 cm3 g−1, respectively.
2.2. Synthesis of MCM-41
Mesoporous silica MCM-41 was synthesized by according to the
reported procedure [24,25]. A 25.1 g of hexadecyltrimethylammo-
nium bromide (HDTMABr) was completely resolved in 77.0 g of
distilled water at 50 ◦C (solution A). In a 300 mL beaker, a 28.1 g of
sodium silicate (SiO2: 29.3%, Na2O: 9.3% in water) was added into
an aqueous H2SO4 solution (0.31 mmolg−1), then was added into
the solution A. After stirring for 1 h at ambient temperature, the pH
of the solution was adjusted to 9.98 by adding H2SO4 solution. The
resulting white suspension was transferred into a 500 mL of bottle
(polypropylene), and stood at 100 ◦C for 9 days. The obtained white
powder was washed with distilled water and EtOH thoroughly and
dried at 50 ◦C for overnight. The calcination of as-synthesized MCM-
41 was taken place at 550 ◦C for 6 h.
Fig. 3 shows the FT-IR spectra of MCM-41 (a) and MAP-M41 (b)
in the range of 1300–2000 cm−1. The characteristic band assignable
to the stretching vibration of C N bond was observed at 1465 cm−1
in MAP-M41, indicating that N-methylaminopropyl moiety is effec-
tively immobilized on mesoporous silica.
TG–DTA analysis of MAP-M41 revealed the clear weight loss
at around 250 ◦C accompanying with exothermic reaction (see
Supporting Information), and the amount of the supported amine
based on the weight loss in TG is estimated as 1.21 mmol g−1 [25].
2.3. Immobilization of organic amine on MCM-41 (MAP-M41)
The heterogeneous dry toluene solution containing the
calcined MCM-41 and the prescribed silylating agent, 3-
aminopropyltrimethoxysilane, was refluxed for 6 h. After filtration,
the resulting pale yellow solid was washed with toluene and EtOH
thoroughly. Then the solid was dried at 50 ◦C for overnight.
2.4. Trimethylsilyl end capped MCM-41 (MAP-M41 (TMS))
The suspension of the well-dried MAP-M41 (0.80 g) in
dry toluene (55 mL) was added 1,1,1,3,3,3-hexamethyldisilazane
(1.5 mL) at room temperature. The resulting mixture was stirred
for 4 h, and then, the obtained solid was washed with toluene
and EtOH, respectively. This procedure was repeated three times
to sufficiently substitute the trimethylsilyl moiety to the exposing
silanol.
2.5. One-pot reaction
Into the mixture of benzaldehyde (0.50 mmol) and ethyl
cyanoacetate (0.60 mmol) in toluene (1.0 mL) was added the cata-
lyst (10 mol%; the supported amine base) and stirred for 1 h at 60 ◦C.
The mixture was subjected to the addition of CH3NO2 (1.0 mmol) at
the same temperature and stirred for extended 4 h. The catalyst was
removed by filtration, and the organic filtrate was concentrated in
vacuo. The resulting crude product was purified by column chro-
matography using n-hexane/EtOAc (4/1) as an eluent to determine
the isolated yield. The structural assignment was done by 1H and
13C NMR spectra comparing with the reported spectral data. The
diastereomer ratios of all products are estimated at 50:50 by 1H
Fig. 1. Powder XRD charts of MCM-41 (a) and MAP-M41 (b).

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K. Komura et al. / Applied Catalysis A: General 445–446 (2012) 128–132
Fig. 4. Solid state 13C (A) and 29Si (B) CP/MAS NMR spectra of MAP-M41.
Fig. 2. N2 adsorption–desorption isotherms of MCM-41 (a) and MAP-M41 (b).
Solid-state 13C and 29Si CP/MAS NMR spectra of MAP-M41
are given in Fig. 4 (A and B). In 13C CP/MAS spectrum (Fig. 4A),
the clear four peaks assignable as one methyl carbon (CH3) and
three methylene carbons (CH2) of N-methylaminopropyl moiety
are observed at 9.9 ppm, 25 ppm, 44 ppm and 66 ppm, regardless of
their peak intensities. While, two broad peaks at around −105 ppm
(Q3 and Q4) and −65 ppm (T2 and T3) are observed in 29Si spec-
trum (Fig. 4B). These are distinguishable and assignable as −60 ppm
(T2) and −67 ppm (T3), −101 ppm (Q3) and −109 ppm (Q4), where
Scheme 2.
3.2. Three-component one-pot reaction
In order to find out the optimized conditions and catalyst, we
have examined the model reaction utilizing benzaldehyde (1),
ethyl cyanoacetate (2) and nitromethane (3) in toluene (Scheme 2).
Upon the optimized conditions (see Supporting Information), then
we have surveyed the catalyst, and the results are given in Table 1.
Absence of catalyst and MCM-41 are inert for this reaction (entries
1 and 2). The organic base catalyst, triethylamine, moderately pro-
duced the product 4 in 47% yield (entry 3), and the organic amine
supported mesoporous catalyst bearing primary aminopropyl
moiety (AP-M41) showed good performance in 65% yield (entry
4). The MAP-M41 catalyst exhibited the highest in 82% yield (entry
5); however, albeit the advantage of heterogeneous catalyst, the
significant deactivation occurred in the reaction by the reused
T
m = RSi(OSi)m(OH)3−m and Qn = Si(OSi)n(OH)4−n [7,26].
Table 1
Survey of catalyst.a
Entry
Catalyst
Yieldb of 4 (%)
1
2
3
4
5
6
7
8
None
MCM-41
Triethylamine
AP-M41
0
0
47
65
82
37
2
MAP-M41c
MAP-M41d
MAP-M41e
MAP-M41 (TMS)f
66
a
Reaction was carried out by using benzaldehyde (0.5 mmol), ethyl cyanoacetate
(0.6 mmol) and CH3NO2 (1.0 mmol) in dry toluene (1.0 mL) in the presence of catalyst
(10 mol%; based on amine).
b
Isolated yield.
Fresh catalyst.
Reused catalyst of entry 5.
Reused catalyst of entry 6.
c
d
e
f
End capped by TMS catalyst.
Fig. 3. FT-IR spectra of MCM-41 (a) and MAP-41 (b).

K. Komura et al. / Applied Catalysis A: General 445–446 (2012) 128–132
131
Table 2
Table 3
Results of reactions over MAP-M41 catalyst.a
Results of reactions over MAP-M41 catalyst.a
Entry
Aldehyde
Product
Yieldb (%)
Entry
Substrate
Product
Yieldb (%)
1
2
3
4
5
6
R = H
82
R = CH3
R = OCH3
R = Cl
R = CF3
R = NO2
79
65
87
90
20
1
R1 = CN
R1 = CN
R1 = CO2Me
R1 = COCH3
R1 = COCH3
R2 = CN
63
82
12
10
10
2
3
4
5
R2 = CO2Et
R2 = CO2Me
R2 = CO2Me
R2 = COCH3
a
Reaction was performed by using benzaldehyde (0.5 mmol), active methylene
compound (0.6 mmol) and CH3NO2 (1.0 mmol) in dry toluene (1.0 mL) in the pres-
ence of catalyst (10 mol%; based on amine).
b
Isolated yield.
7
8
83
67
59
by the Michael addition with nitromethane 3 in the presence of
MAP-M41 catalyst. The functional groups at para position slightly
influenced the reaction, the electron-donating group, OCH3, low-
ering the acceptance of a nucleophile agent, declined the yield
in 65% (entry 3). Other hands, bearing the electron-withdrawing
groups is found to be favorable, resulting in the increase of
yields (entries 4 and 5); however, due to poor solubility of p-
nitrobenzaldehyde, low yield in 20% was observed (entry 6). The
reactions using aliphatic branched and linear aldehydes offered the
corresponding products in moderate to good yields (entries 7–9).
The effect of acidity at the methylene moiety was elucidated by
the reaction of benzaldehyde 1 and five compounds followed by
the addition of nitromethane 3 over MAP-M41 catalyst (Table 3).
Among the used compounds, the use of ethyl cyanoacetate 2
showed highest yield in 82% (entry 2). The highest acidity at the
methylene proton of malononitrile, unfortunately, the complex
mixture was observed due to over reaction of nitromethane to
the product (entry 1) [27,28]. Others are almost inert in this reac-
tion (entries 3–5), suggesting that appropriate acidity sufficiently
proceeds the reaction to afford the product in high yield.
CH3(CH2)6CHO
9
a
Reaction was performed by using aldehyde (0.5 mmol), ethyl cyanoacetate
(0.6 mmol) and CH3NO2 (1.0 mmol) in dry toluene (1.0 mL) in the presence of catalyst
(10 mol%; based on amine).
b
Isolated yield.
catalyst in 37% yield (entry 6), further, almost no activity was
observed in 2% yield (entry 7). TG–DTA measurement revealed that
this is due to the unknown heavy organics accumulated onto the
catalyst surface. The exposing silanol on the pore wall of MCM-41
affects its catalytic activity, i.e. MAP-M41(TMS) catalyst, of which
surface silanol was capped by trimethylsiloxy bond, moderately
provided the product 4 in 66% yield (entry 8). It is known that
surface silanol of mesoporous silica catalyst sometimes plays
critical role in catalysis, harmonizing a weak acidic site and organic
amine moiety triggers the excellent catalytic performance as
acid-base cooperative catalyst [14].
A
plausible reaction mechanism of the three-component
one-pot reaction of benzaldehyde 1, ethyl cyanoacetate 2 and
nitromethane 3 over MAP-M41 catalyst is illustrated in Scheme 3. In
general the reaction starts from withdrawing a proton of the active
methylene compound of 2 (Scheme 3, left circle). The resulting
Table 2 presents the results of the reaction using various alde-
hydes, aromatics and aliphatics, with ethyl cyanoacetate 2 followed
Scheme 3.

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K. Komura et al. / Applied Catalysis A: General 445–446 (2012) 128–132
zwitterionic intermediate readily reacts with iminium ion which is
formed by aldehyde 1 and catalyst accompanying the dehydration,
and then 1,2-elimination allowed to afford the Knoevenagel con-
densation product 5 accompanying the regeneration of the catalyst.
After finishing the reaction, reflecting the sufficient consumption
of the active methylene compound 2, the catalyst reactivates the
added nitromethane 3 by the abstraction of a proton, resulting in
the formation of a nucleophile (Scheme 3, right circle). The con-
jugative addition of the activated nitromethane with 5 smoothly
produces the ␣-cyano-␤-nitromethyl ketene acetal intermediate
which is a tautomer to form the product 4, and in this step the cat-
alyst is also regenerated again, accomplishing the enclosure of the
catalytic circle.
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Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/
j.apcata.2012.08.009.
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