Mesoporous silica nanoparticles (MSNs) as an efficient and reusable nanocatalyst for synthesis of β-amino ketones through one-pot three-component Mannich reactions

Article abstract of DOI:10.1039/c6ra02454h

Mesoporous silica nanoparticles (MSNs) proved efficient and reusable in the catalytic synthesis of β-amino ketones, through three-component Mannich reaction of ketones, aromatic aldehydes and aromatic amines under solvent-free conditions. Simple reaction conditions coupled with simple work-ups, makes this methodology a superior option for the synthesis of such β-amino ketones.

Full text of DOI:10.1039/c6ra02454h

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Mesoporous silica nanoparticles (MSNs) as an
efficient and reusable nanocatalyst for synthesis of
b-amino ketones through one-pot three-
component Mannich reactions†
Cite this: RSC Adv., 2016, 6, 32183
Zahra Nasresfahani, Mohammad Zaman Kassaee,* Mohammad Nejati-Shendi,
Esmaiel Eidi and Qazale Taheri
Received 27th January 2016
Accepted 4th March 2016
Mesoporous silica nanoparticles (MSNs) proved efficient and reusable in the catalytic synthesis of b-amino
ketones, through three-component Mannich reaction of ketones, aromatic aldehydes and aromatic amines
under solvent-free conditions. Simple reaction conditions coupled with simple work-ups, makes this
methodology a superior option for the synthesis of such b-amino ketones.
DOI: 10.1039/c6ra02454h
www.rsc.org/advances
drawbacks such as low yields, long reaction times, high
temperature, tedious work-up procedures, toxic solvents and
Introduction
Synthesis of natural molecules, pharmaceuticals and other use of expensive and air sensitive catalysts.
nitrogenous biologically active compounds has long been
Therefore, the search for the new readily available and
1
,2
a signicant branch of organic chemistry. Multicomponent green catalysts is still being actively pursued. In recent
condensation reactions (MCRs) have been discovered to be years, mesoporous materials have attracted much attention
a powerful tool for the synthesis of organic compounds. The because of their many advantageous properties, such as
products are formed in a single step and diversity can be facile synthesis, stable mesostructures, large surface
3
,4
achieved by simply varying a single component. On the areas, well-dened surface properties, versatile inner and
2
7–29
other hand, Mannich reaction is a very useful tool for devel- outer surface chemistry, and good biocompatibility.
5
opment and synthesis of several molecules. This reaction is Also, because of the availability of a large number of free
an important carbon–carbon bond forming reaction in silanol groups on their surface, they could be applied as
3
0
organic synthesis. It is used for preparation of various catalysts. In continuation of our efforts on the development
nitrogen-containing natural products and intermediates of of green and sustainable methods, we are especially inter-
6
–8
signicant pharmaceuticals.
reaction are mainly b-amino carbonyl compounds and their MSNs catalyst.
The products of Mannich ested in preparation and development of efficient and simple
31
In this study, MSNs is employed as
derivatives. The b-amino carbonyl functionality is not only a heterogeneous nanocatalyst in the synthesis of b-amino
a segment of biologically active natural products but also ketones through the Mannich-type reaction of aldehydes,
serves as a key intermediate for synthesis of important anilines and ketones, under solvent-free conditions
nitrogen containing compounds such as b-amino acids, (Scheme 1).
9
–13
b-lactams, and b-amino alcohols.
Therefore, much
consideration has been drawn to the development of new
synthetic methods to prepare these compounds. The
conventional catalysts for classical Mannich reaction of
aldehydes, ketones and amines involve mainly organic or
1
4,15
16
mineral acids like proline,
I , p-dodecyl benzene sul-
2
1
7
18
phonic acid and some Lewis acids. Over the past decades,
1
9–22
23–25
26
ionic liquids,
nanoparticles,
and enzymes have been
investigated. However, these methods suffer from several
Department of Chemistry, Tarbiat Modares University, P. O. Box 14155-4838, Tehran,
Iran. E-mail: kassaeem@modares.ac.ir; drkassaee@yahoo.com; Fax: +98-21-
8
†
1
8006544; Tel: +98-912-1000392
Electronic supplementary information (ESI) available. See DOI:
0.1039/c6ra02454h
Scheme 1 The Mannich-type reaction catalyzed by mesoporous silica
nanoparticles (MSNs).
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Results and discussion
MSNs was prepared (Scheme 2) and characterized by different
techniques, including X-ray diffraction (XRD), scanning elec-
tron microscopy (SEM), transmission electron microscopy
(TEM), Fourier transforms infrared (FT-IR), nitrogen absorption
and desorption analyzes.
X-ray diffraction
X-ray diffraction (XRD) is conducted to determine the structures
of MSNs. The low-angle XRD pattern show three main diffrac-
tion peaks due to (1 0 0), (1 1 0), and (2 0 0) planes, respectively,
which well correspond to the typical diffraction peaks of
hexagonal mesoporous structure (Fig. 1).
Fig. 2 The SEM image (a) and the TEM image (b) of MSNs.
SEM and TEM
The SEM image showed that the embedded mesoporous
nanoparticles were present as uniform particles with spherical
morphology (Fig. 2a). TEM image display rather monodispersed
spherical MSNs with a mean diameter of 110 ꢀ 10 nm (Fig. 2b).
FT-IR spectroscopy
Asymmetric and symmetric Si–O–Si stretching vibrations of
ꢁ
1
ꢁ1
1
MSNs appear at 1086 cm and 801 cm respectively. These are Fig. 3 The FT-IR spectrum of MSNs.
ꢁ
along with that of Si–OH at 962 cm and bending Si–O–Si at
61 cm . The broad band around 3450 cm is due to the
ꢁ
1
ꢁ1
4
surface silanols and adsorbed water molecules and the band at
ꢁ1
ꢁ1
MSNs, C–H stretch (2854 cm and 2923 cm ) peaks from
CTAB surfactants disappeared aer the CTAB removal process,
which indicate that no residual CTAB existed in the material
ꢁ1
1635 cm is assigned to the H–O–H bending vibrations of the
free or absorbed water molecules. Also, in the FT-IR spectrum of
(Fig. 3).
Nitrogen absorption and desorption analyzes
The total surface area and average pore diameter of MSNs were
analyzed by the N adsorption and desorption measurements.
2
The Brunauer–Emmett–Teller (BET) isotherm displayed typical
IV isotherm according to the IUPAC classication, showing the
characteristic of mesopores (Fig. 4). The sharp inection over
a narrow relative pressure ranging from 0.18 to 0.29 indicates
that capillary condensation occurs in the mesopores and illus-
trates that MSNs have uniform pores. The surface area, total
pore volume and pore diameter of MSNs determined from the
Scheme 2 Preparation of mesoporous silica nanoparticles (MSNs).
2
ꢁ1
3
ꢁ1
BET equation were 1553 m g , 1.10 cm g and 2.85 nm,
respectively.
Aer characterization of MSNs, its role as a catalyst was
evaluated in synthesis of b-amino ketones. In order to optimize
the reaction conditions, three-component Mannich reaction of
benzaldehyde, aniline and acetophenone was probed using
different amounts of catalyst (5, 10 and 15 mg). The results
showed no substantial improvement in the yield with further
increase of catalyst at room temperature, under solvent-free
conditions. Also, the model reaction was carried out in several
solvents (ethanol, acetone, acetonitrile, toluene, and H O) and
2
found that reaction under solvent-free conditions was most
efficient with respect to reaction time and yield. So, the optimal
conditions of the reaction were selected to use no solvent, at
Fig. 1 XRD pattern of MSNs.
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anilines with either electron-withdrawing or electron-donating
substituents were all suitable to the reactions. However, with
electron-withdrawing substituents in aldehyde and electron-
donating substituents in aniline, increased yield of products
were obtained and the effect was reversed with strong electron-
2
withdrawing substituents such as –NO in aniline.
To further broaden the scope of this protocol, we also
investigated three-component Mannich reaction using cyclo-
hexanone under the same reaction conditions. It was found that
the corresponding b-amino ketones (6) were formed in good to
moderate yields (Table 2). The result showed cyclohexanone was
more reactive than acetophenone and required shorter reaction
times (2–3 h) to give the desired products.
Our suggested probable reaction mechanism for the
synthesis of b-amino ketones mediated by MSNs is outlined in
Scheme 3. We propose that the aldehyde is activated by
hydrogen bonding with free hydroxy groups on surface of MSNs.
Then, amine attacks the carbonyl group of the activated alde-
hyde I, and leads to an iminium ion as the intermediate II. Next,
Fig. 4 Nitrogen adsorption and desorption isotherms of MSNs.
imine III is formed by removing H O from II. The imine III is
2
activated by MSNs to attack of in situ generated enolate IV and
affords the expected b-amino ketone.
To show the merit of MSNs in comparison with other re-
ported catalysts, we summarized several results for Mannich
reaction of aniline and benzaldehyde with acetophenone
room temperature and in the presence of 15 mg catalyst. With
the optimized reaction conditions in hand, different benzalde-
hydes, anilines and acetophenone gave product (4) in moderate
to good yields in 6–15 h (Table 1). Aromatic aldehydes and
(Table 3). In comparison with other catalysts used in literature,
MSNs showed a much higher catalytic activity in terms of very
short reaction time and mild conditions.
Table 1 MSNs catalyzed one-pot three component Mannich reaction
of aromatic aldehydes, aromatic amines, and acetophenone
a,b
Table 2 MSNs catalyzed one-pot three component Mannich reaction
a,b
of aromatic aldehydes, aromatic amines, and cyclohexanone
a
a
Reaction conditions: aromatic aldehydes (1 mmol), aromatic amines
Reaction conditions: aromatic aldehydes (1 mmol), aromatic amines
(
1 mmol), and acetophenone (1 mmol), all of the reactions were (1 mmol), and cyclohexanone (1 mmol), all of the reactions were
b
b
carried out with 15 mg of MSNs at room temperature. Isolated yields. carried out with 15 mg of MSNs at room temperature. Isolated yields.
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Fig. 6 FT-IR spectra of fresh and recovered catalysts.
reaction conditions and hence can be easily separated by
centrifugation followed by washing. The catalyst was washed
ꢂ
with ethanol and dried at 80 C and used for another Mannich
reaction, the recycled catalyst could be reused ve times without
signicant loss of its activity (Fig. 5). As shown by comparison of
the FT-IR spectra to that of fresh catalyst and recovered catalyst
aer ve runs had no obvious change in structure (Fig. 6), the
recyclability data demonstrates high stability of the catalyst
under the reaction conditions.
Scheme 3 Plausible reaction mechanism for one-pot three compo-
nent Mannich reaction of benzaldehyde, aniline, and acetophenone in
the presence of MSNs.
Table 3 Comparison of MSNs with other catalysts reported in the
literature for Mannich reaction of aniline and benzaldehyde with
acetophenone
Experimental
Entry Catalyst, condition
Time (h) Yield (%) Ref.
Chemical reagents in high purity were purchased from Merck
and Aldrich and were used without further purication. Fourier
transform infrared (FT-IR) spectra were recorded using KBr
1
2
3
4
5
6
7
CeCl
Yb(PFO)
3
$7H
2
O, rt, EtOH
10
8
9
12
9
8
95
94
98
95
92
93
95
32
33
34
35
36
23
3
ꢂ
, rt, EtOH
CAN, 45 C, PEG
HClO –SiO , rt, EtOH
Saccharose, rt, H O/EtOH
Cu-NP, MeOH, rt, N
MSNs, rt, solvent-free
ꢁ1
pellets in the range 400–4000 cm on a Nicolet IR-100 infrared
4
2
spectrometer. The NMR spectra were recorded on a Bruker DRX
2
1
2
500-Avance spectrometer operating at 500 MHz for H NMR in
6
This work
DMSO-d and CDCl with TMS as an internal standard. X-ray
6
3
diffraction (XRD) was performed on Philips XPert 1710 diffrac-
ꢀ
tometer. The latter appeared with Co Ka (a ¼ 1.79285 A) voltage:
The recovery and reuse of catalysts are highly valued in
4
0 kV. The particle morphology was examined by SEM (KYKY
a green process. Subsequently, reusability performance of MSNs
nanocatalyst was investigated using the Mannich reaction
EM3200 – 25 kV) and TEM (Zeiss EM10C 80 kV).
(benzaldehyde, aniline, and cyclohexanone) under the optimal
Preparation of mesoporous silica nanoparticle
conditions. The catalyst remains insoluble under the present
37
MSNs was prepared using the sol–gel method. Briey, 0.5 g of
CTAB and 0.14 g of NaOH were mixed in 240 mL deionized
ꢂ
water. The solution was stirred vigorously at 80 C for 2 h, then
2.5 mL of TEOS is added, and the reaction was continued for
another 2 h. The as-prepared product (MSNs-CTAB) was washed
3
times with ethanol and redispersed in 200 mL of ethanol
ꢂ
containing 2 g of NH
4
NO
3
, at 80 C. The remaining mixture was
reuxed for 6 h. In this process the CTAB template was
removed. The resulting precipitate was collected by centrifu-
gation and washed with ethanol repeatedly. Finally, it was dried
under vacuum to give MSNs product as a white powder.
General procedure for the synthesis of b-amino carbonyl
compounds
Fig. 5 Reusability of MSNs in the reaction of benzaldehyde (1 mmol),
aniline (1 mmol), cyclohexanone (1 mmol) and catalyst (15 mg) under
solvent-free conditions.
In a typical experiment, to mixture of ketones (1 mmol),
aromatic aldehydes (1 mmol) and anilines (1 mmol), MSNs
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(
15 mg) was added, the mixture was stirred at room temper-
Acknowledgements
ature for appropriate time, the reaction was monitored by
TLC. Aer completion of the reaction, acetone was added and We acknowledge Tarbiat Modares University for partial support
catalyst was removed by centrifugation, product was recrys- of this work.
tallized from EtOH. The catalyst was used in the next run
under the same conditions as for the initial run of the
catalyst. The purity of these products was ascertained by their
Notes and references
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ꢂ
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7
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ꢂ
ꢁ1
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