Inorganic-organic hybrid silica based tin(II) catalyst: Synthesis, characterization and application in one-pot three-component Mannich reaction

Article abstract of DOI:10.1016/j.catcom.2011.12.006

Inorganic-organic hybrid material catalyzed one-pot three-component Mannich reaction of ketones with aromatic aldehydes and different amines at ambient temperatures afforded β-amino carbonyl compounds in excellent yields. This method provides a novel and improved modification of three-component Mannich reaction in terms of mild reaction conditions and clean reaction profiles, using small amount of catalyst, simple workup procedure and ease of recovery and reusability of catalyst.

Full text of DOI:10.1016/j.catcom.2011.12.006

Catalysis Communications 19 (2012) 31–36
Contents lists available at SciVerse ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Inorganic–organic hybrid silica based tin(II) catalyst: Synthesis, characterization and
application in one-pot three-component Mannich reaction
⁎
R.K. Sharma , Deepti Rawat, Garima Gaba
Green Chemistry Network Centre, Department of Chemistry, University of Delhi, Delhi-110007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 July 2011
Received in revised form 25 November 2011
Accepted 1 December 2011
Available online 10 December 2011
Inorganic–organic hybrid material catalyzed one-pot three-component Mannich reaction of ketones with
aromatic aldehydes and different amines at ambient temperatures afforded β-amino carbonyl compounds
in excellent yields. This method provides a novel and improved modification of three-component Mannich
reaction in terms of mild reaction conditions and clean reaction profiles, using small amount of catalyst,
simple workup procedure and ease of recovery and reusability of catalyst.
© 2011 Elsevier B.V. All rights reserved.
Keywords:
Mannich reaction
β-amino ketones
Silica
MCR
Inorganic–organic
1. Introduction
Among various inorganic solids, silica acts as a better support for het-
erogenizing catalysts because of their excellent mechanical, thermal
Recently, multicomponent condensation reactions (MCRs) have
been discovered to be a powerful tool for synthesis of organic com-
pounds as the products are formed in a single step and diversity can
be achieved by simply varying single component [1–3]. The increas-
ing popularity of Mannich reaction for the synthesis of β-amino ke-
tones and aldehydes (Mannich bases) has been fueled by the
ubiquitous nature of nitrogen containing compounds in drugs and
natural products [4]. However, the classic Mannich reaction has limit-
ed applications. Attempts have been made during the past few years
to improve the methodologies based on two-component reactions,
where imine as an electrophile is pre-formed, and then reacted with
various nucleophiles such as enolates, enol ethers and enamines
[5–15]. The most preferable route is one-pot three-component strat-
egy that allowed a wide range of structural variations in the reactants
to give Mannich products in a single step. Recently, direct Mannich
reactions have been realized via Lewis acids [16–21], lanthanides
[22], transition metal salts [23] and organocatalytic approaches
[8,24,25]. However, these methods suffer from several drawbacks
such as low yields, long reaction times, high temperature, tedious
work-up procedures, toxic solvents and use of expensive and air-
sensitive catalyst and non-recoverability and reusability of catalyst.
Heterogenization of homogeneous systems that aims to facilitate
the recovery of the catalyst and to minimize the waste is currently
the subject of a great deal of research in green chemistry [26,27].
and chemical stability [28,29]. In continuation of our ongoing green
chemistry program that utilize heterogeneous inorganic–organic hy-
brid systems [30–34] in various organic transformations, herein we
report a simple, mild and convenient procedure for effecting one-
pot, three-component reaction of aldehyde, amine and ketone for
preparation of β-amino carbonyl compounds using inorganic–organic
hybrid silica based tin catalyst.
2. Experimental
2.1. General remarks
Surface area analysis was carried out at 77 K by Model 2010,
Micromeritics, USA. The content of tin in the heterogenized catalyst
was determined by ICP-MS Agilent 75003 model number G3272A.
The IR spectra were recorded on Perkin Elmer Spectrum 2000 Fourier
transform infrared (FT-IR) spectrometer. 13C CPMAS spectra
were recorded on
a Bruker DSX-300 NMR spectrometer at
75.47 MHz. 1H-NMR spectra were recorded on a Bruker 300 MHz in-
strument using TMS as an internal standard. Qualitative analysis of
catalyst for heavy metals was performed by using energy dispersive
XRF spectrometer (Fischerscope X-ray XAN-FAD BC).
2.2. Catalyst preparation
2.2.1. Preparation of aminopropyl silica gel (SG-NH2)
Silica gel was functionalized according to the reported procedure
[35] using 3-aminopropyltriethoxysilane.
⁎
Corresponding author. Tel./fax: +91 11 27666250.
E-mail address: rksharmagreenchem@hotmail.com (R.K. Sharma).
1566-7367/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2011.12.006

32
R.K. Sharma et al. / Catalysis Communications 19 (2012) 31–36
13C CP-MAS NMR analysis: 9.3 (\Si\CH2\), 22.3 (\CH2\), 42.9
(\N\CH2\) ppm. IR (KBr): max =3434, 2924, 2851, 1083,
798 cm−1 Surface area analysis: 151.91 m2 g−1
ν
.
2.2.2. Preparation of supported Schiff base ligand (SG-NH2-Sal)
Aminopropylated silica gel (SG-NH2) (5 g) and salicylaldehyde
(5 mmol) were stirred in absolute ethanol and refluxed for 18 h
under nitrogen atmosphere to afford silica supported Schiff base li-
gand. The solid was filtered, dried and then washed with ethanol to
remove the unreacted aldehyde and dried under vacuum at 120 °C
overnight.
IR (KBr): νmax =3434, 2924, 2851, 1655, 1078 cm−1 13C CP MAS
.
NMR analysis: 10.2, 23.8, 41.5, 63.2, 122.9, 135.6, 154.3, 161.4 ppm.
2.2.3. Preparation of silica based tin catalyst (SG-NH2-Sal-Sn)
Silica supported Schiff base ligand (5 g) was added to tin(II)triflate
(2.5 mmol) in dichloromethane. The resulting mixture was stirred at
room temperature for 12 h. The catalyst was filtered and washed
thoroughly with acetone and dried overnight in vacuum at 120 °C
(Scheme 1).
IR (KBr): νmax =3435, 2925, 2851, 1635, 1448, 1070 cm−1. Sur-
face area analysis: 132.35 m2 g1. ICP-MS analysis: Amount of tin
0.76 mmol g−1
.
2.3. Typical experimental procedure for Mannich reaction
Aldehyde (1 mmol), amine (1 mmol), acetophenone (1 mmol)
and catalyst (30 mg) were stirred in dry dichloromethane (5 mL) at
room temperature. The progress of the reaction was monitored by
TLC. After completion of reaction, the catalyst was filtered and the re-
action mixture was diluted with water and stirred for 15 min. The
crude product was finally recrystallized from ethanol to give pure
β-amino ketone.
3. Results and discussion
3.1. Catalyst characterization
The three signals at 9.3, 22.3 and 42.9 ppm observed in the 13C
CPMAS NMR spectrum of SG-NH2 were assigned to \Si\CH2\,
\CH2\ and \N\CH2\ groups, respectively and confirmed the syn-
thesis of modified support (Fig. 1a). The immobilization of salicylal-
dehyde to functionalized silica gel was further confirmed by 13C
CPMAS NMR spectroscopy (Fig. 1b). On complexation, \N\CH2\
peak shifted to 63.29 ppm and the peak at 41.5 ppm is assigned to
the uncomplexed \N\CH2\ group. Six peaks corresponding to phe-
nyl ring are expected to appear in the aromatic region; however, the
resolution of these peaks in solid state NMR was not achieved under
the analysis conditions and therefore, the spectrum showed four
Fig. 1. 13C CPMAS NMR spectra of (a) aminopropylated silica gel (SG-NH2) (b) ligand
grafted silica gel (SG-NH2-Sal).
broad peaks. The Schiff base condensation was confirmed by the pres-
ence of C_N peak at 161.4 ppm. The two peaks at 161 and 154 ppm
were assigned to the phenyl carbon atoms attached to the oxygen
and nitrogen atom of the ligand.
Scheme 1. Schematic representation of the synthetic procedure of silica based tin(II) catalyst.

R.K. Sharma et al. / Catalysis Communications 19 (2012) 31–36
33
Fig. 2. FTIR spectrum of catalyst.
FTIR spectrum of silica gel (SG) showed
a
broad band at
frequency decreased to lower wave number (1635 cm−1) indicative
of formation of metal–ligand bond (Fig. 2).
3467 cm−1 due to \OH stretching vibration of surface silanol.
Bands centered at 1086 cm−1 and 803 cm−1 were assigned to asym-
metric and symmetric Si\O\Si stretching vibrations respectively.
Band at 465 cm−1 and 967 cm−1 were assigned to Si\O\Si bend-
ing and silanol group Si\OH. Peaks at 2924 and 2851 cm−1
were assigned to C\H stretching vibrations of aminopropyl silica
gel (SG-NH2). The significant reduction in the intensity of \OH
stretching and bending vibration bands confirmed proposed silane
grafting mechanism. The spectrum of the immobilized ligand showed
a strong band at 1655 cm−1 due to ν(C_N) stretching vibration
resulting from Schiff condensation between the NH2 group and car-
bonyl group of ligand. On metallation with tin triflate, \C_N
The BET analysis depicted that the surface area decreased after
grafting, in this sequence SG>SG-NH2 >SG-NH2-Sal-Sn. The quanti-
tative estimation of organic functional groups covalently anchored
onto the surface of silica was performed with elemental analysis
and results are shown in Table 1. Chemical analysis of SG-NH2 corre-
sponds to 1.46 mmol g−1 of 3-aminopropyl groups based on nitrogen
percentage whereas for catalyst, the loading of organic moiety onto
silica was 0.77 mmol g−1. The metal loading of catalyst was con-
firmed by ICP-MS and was found to be 0.76 mmol g−1. Further to
support the above observation, catalyst was subjected to energy
Table 2
Investigation of different catalysts in Mannich type reactiona.
Table 1
Entry
Catalyst
Time (h)
Yield (%)b
Physico-chemical parameters of silica gel, aminopropylated silica and catalyst.
1.
2.
3.
4.
No
Silica gel
Tin(II) triflate
SG-NH2-Sal-Sn
24
24
6
Nil
Nil
95
93
Material
Elemental analysis
BET Surface
area (m2/g)
%C
%N
%H
6
SG
–
–
–
235.67
151.91
132.35
a
Benzaldehyde (1 mmol), aniline (1 mmol), acetophenone (1 mmol) and catalyst
(30 mg) were stirred in dry dichloromethane at room temperature.
SG-NH2
SG-NH2-Sal-Sn
5.28
11.83
2.04
1.25
1.26
1.97
b
Yield of isolated products.
Fig. 3. EDXRF spectrum of catalyst (SG-NH2-Sal-Sn).

34
R.K. Sharma et al. / Catalysis Communications 19 (2012) 31–36
Table 3 (continued)
Table 3
Synthesis of β-amino ketones using three component procedure catalyzed by silica
Entry
R
R′
Product
time
(h)
yieldb(%)
89
based tin(II) catalysta.
R'
NH2
CHO
COCH3
Br
N
i.
\H
3-Br
6.0
(TfO)Sn
NH
O
O
+
+
R'
R
NH
O
R
Entry
a.
R
R′
Product
time
(h)
yieldb(%)
Cl
88
4-Cl
4-Cl
7.5
\H
\H
6.0
93,93,92,90,89,88
j.
NH
O
NH
O
Cl
b.
4-Br
\H
6.5
89
k.
l.
\H
\H
2-
OCH3
2-NO2
–
–
NH
O
Br
a
Reaction conditions: acetophenone (1 mmol), aldehyde (1 mmol), aniline
c.
4-Cl
\H
6.0
8.0
91
87
(1 mmol) and catalyst (30 mg) were stirred in dry dichloromethane at room tempera-
ture.
b
Isolated yields.
NH
O
dispersive X-rays. XRF spectrum of tin confirms its immobilization
onto the modified silica gel (Fig. 3).
Cl
d.
4-OCH3 \H
3.2. Catalytic activity
NH
O
We have performed a set of preliminary experiments on acetophe-
none, aniline and benzaldehyde as a model reaction. In the initial inves-
tigation, different catalysts and solvents were screened in the model
reaction. The reaction did not progress even after 24 h in the absence
of catalyst or when silica was used (Table 2 entries 1 and 2). However,
tin immobilized on functionalized silica proved to be an efficient cata-
lyst with high product yields. Tin(II) triflate gave good results but lack
of recyclability and its corrosive nature limits its application.
Among the screened solvent systems, dichloromethane was the
solvent of choice, since the reaction proceeded smoothly and afforded
the desired adducts in high yields. The high temperature could im-
prove the reaction rate and shorten the reaction time, but favor side
reactions and the oxygenolysis of aldehyde and amine. It was found
that the room temperature was an appropriate condition for Mannich
reaction.
H3CO
4-CH3
\H
6.0
92
e.
NH
O
H3C
f.
4-NO2
\H
6.5
80
NH
O
Encouraged by the remarkable results obtained for above condi-
tions, and in order to show the generality and scope of this protocol,
we used various aldehydes and amines. Thus, a variety of aromatic al-
dehydes and amines, including electron-withdrawing and electron-
donating groups, was tested using this method. The desired products
were obtained in good yields using catalytic amount of catalyst and
the results are shown in Table 3. When ortho-substituted amines
were used as substrate, the reaction did not proceed to completion
and reason could be attributed to steric hindrance.
O2N
O2
N
\H
4-NO2
7.0
84
g.
NH
O
Presumably due to the Lewis acidity of tin triflate, the role of cat-
alyst is the activation of precursors through coordination leading the
desired product. The reaction of aldehyde and amine leads to an imi-
nium ion as the intermediate followed by the attack of in-situ gener-
ated enolate (Scheme 2).
The separation of heterogeneous catalyst by filtration was easy
and possible within a short time. After the completion of reaction,
the heterogeneous catalyst was separated from the reaction mixture
h.
\H
3-NO2
7.0
86
NO2
NH
O

R.K. Sharma et al. / Catalysis Communications 19 (2012) 31–36
35
Scheme 2. Proposed reaction mechanism.
and the amount of the tin in filtrate was determined by ICP-MS. The
Acknowledgment
catalyst was used at least 5 times under the same conditions as for
the initial run of the catalyst. Negligible leaching was observed. The
recyclability data demonstrates high stability of the catalyst under
the reaction conditions.
The authors would like to thank Indian Institute of Science (IISc),
Bangalore for performing the 13C NMR measurements.
In order to verify whether the observed catalysis is truly heteroge-
neous or not, the catalytic reactions were carried out using catalyst
under the conditions indicated in Table 3 and the solid catalyst was
removed by filtration at about half the specified reaction time period.
Then, the filtrate was allowed to react under the same conditions. No
increase in the yield was observed suggesting that the observed catal-
ysis is truly heterogeneous.
Appendix A. Supplementary data
Supplementary data to this article can be found online at doi:10.
1016/j.catcom.2011.12.006.
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