Functionalized superparamagnetic Fe3O4 as an efficient quasi-homogeneous catalyst for multi-component reactions

Article abstract of DOI:10.1039/c4ra06803c

Tetrabutylammonium valinate ionic liquid [NBu₄][Val] supported on 3-chloropropyltriethoxysilane grafted superparamagnetic Fe₃O₄ NPs (VSF) was synthesized and characterized by Fourier transform infrared spectroscopy (FTIR),

Full text of DOI:10.1039/c4ra06803c

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Functionalized superparamagnetic Fe3O4 as an
efficient quasi-homogeneous catalyst for multi-
component reactions†
Cite this: RSC Adv., 2014, 4, 41323
*
U. Chinna Rajesh, Divya and Diwan S. Rawat
Tetrabutylammonium valinate ionic liquid [NBu4][Val] supported on 3-chloropropyltriethoxysilane grafted
superparamagnetic Fe3O4 NPs (VSF) was synthesized and characterized by Fourier transform infrared
spectroscopy (FTIR), X-ray diffraction (XRD), transmission electronic microscopy (TEM), scanning
electronic microscopy (SEM), thermal gravimetric analysis (TGA), and vibrating sample magnetometer
(VSM). The VSF catalyst was used as an efficient “quasi-homogeneous” catalyst for the multi-component
synthesis of 1,4-dihydropyridines and 2-amino-4-(indol-3-yl)-4H-chromenes at room temperature. The
VSF catalyst was recovered using an external magnet and recycled six times without a significant loss in
the catalytic activity. Moreover, VSF as a “quasi-homogeneous” catalyst can bridge the gap between
homogeneous and heterogeneous catalyses.
Received 8th July 2014
Accepted 7th August 2014
DOI: 10.1039/c4ra06803c
www.rsc.org/advances
materials were found to be very limited.17 AAILs were either
solids or liquids of extremely high viscosity, having limitations
Introduction
in efficiencies of heat and mass transfer processes. The physi-
cochemical properties of AAIL may be tuned by changing either
the cations or anions derived from amino or carboxylic acid
functional groups of amino acid to overcome these limita-
tions.18 Recently, tetraalkylammonium-based amino-acid ionic
liquids [NBu4][AA] ILs with lower viscosities were reported as an
efficient medium for the absorption of CO2,19 and also as
ligands or catalysts for few organic conversions.20
The eld of “quasi-homogeneous” catalysis is the frontier
between homogeneous and heterogeneous catalyses. This has
the advantages offered by both heterogeneous catalysis, namely,
the characteristic of the recovery and recyclability of the cata-
lyst, and homogeneous catalysis, namely, the characteristic of
low catalyst loading and the selectivity of the required product.21
In 1996, Bonnemann et al. demonstrated the quasi-homoge-
neous catalytic nature of platinum colloids for the enantiose-
lective hydrogenation of ethylpyruvate to (R)-ethyllactate.22
Schuth et al. reported the efficient use of aluminum-stabilized
copper colloids as a quasi-homogeneous catalyst for methanol
synthesis.23 Recently, Luo et al. reported the ionic liquid sup-
ported MNPs as “quasi-homogeneous” catalyst for the synthesis
of benzoxanthenes.24 In this context, we presumed that the
immobilization or supporting of highly charged low viscous
[NBu4][AA] ILs on solid Fe3O4 NPs can exhibit the properties of
quasi-homogeneous catalysts to bridge the gap between
heterogeneous and homogeneous catalyses.
Superparamagnetic nanoparticles (MNPs) play a pivotal role in
modern science and technologies due to their wide range of
applications in various elds such as biotechnology/biomedi-
cine, data storage, magnetic uids, magnetic resonance
imaging and heterogeneous catalysis.1 The MNPs have been
found as sustainable catalysts or catalyst supports in organic
synthesis due to their unique properties including huge surface
area, non-toxicity, recoverability with an external magnet, and
avoidance of the work up/ltration of the catalyst.2 Function-
alized MNPs have been increasingly exploited in the area of
biomedicine and catalysis.3 Several metal NPs or metal
complexes including palladium,4 gold,5 ruthenium,6 copper,7
osmium,8 platinum and nickel,9 iridium/rhodium,10 vana-
dium,11 and manganese12 have been supported on the MNPs to
explore their catalytic potential for various organic conversions.
Ionic liquid functionalized ferrite materials were used as a
support for the stabilization of various metal NPs.13 However,
limited reports are available on metal free ionic liquid func-
tionalized MNPs as recyclable catalysts for multicomponent
reactions.14
Ionic liquids have been the subject of intense study for the
last few decades due to their applications in various elds
including homogeneous catalysis.15 Amino acid based ionic
liquids (AAIL) have found interesting applications in catalysis,16
but their uses as immobilization or supporting on solid
It is pertinent to study the catalytic potential of such a quasi-
homogeneous catalyst in multi-component reactions for the
construction of biologically relevant scaffolds in a single
step. 1,4-Dihydropyridines (1,4-DHPs) are such privileged
Department of Chemistry, University of Delhi, Delhi-110007, India. E-mail: dsrawat@
chemistry.du.ac.in; Fax: +91-11-27667501; Tel: +91-11-27662683
† Electronic supplementary information (ESI) available: 1H NMR and 13C NMR
spectra of selected compounds. See DOI: 10.1039/c4ra06803c
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pharmacological scaffolds that exhibit signicant biological
activities in the treatment of cardiovascular diseases as calcium
channel blockers.25 Chromenes and indoles are another class of
compounds found in a number of natural products with a wide
range of biological activities.26,27 2-Amino-4-(indol-3-yl)-4H-
chromenes are hybrid molecules, which comprise the incorpo-
ration of two pharmacophores such as chromenes and indoles
with the intention to impart dual biological activities.
In view of developing an efficient green approach for the
synthesis of 1,4-dihydropyridines, very few MNPs such as nano-
g-Fe2O3, g-Fe2O3–SO3H, Fe3O4–CeO2 and ZrO2–Al2O3–Fe3O4
have been reported as recyclable catalysts.28–31 To the best of our
knowledge, there is no report on the one-pot synthesis of 2-
amino-4-(indol-3-yl)-4H-chromenes via Knoevenagel/Pinner/
Friedel–Cras reaction using MNPs as recyclable catalysts. As a
part of our ongoing work towards the development of efficient
recyclable catalysts for the synthesis of biologically important
molecules,32 we report, herein, the VSF as a quasi-homogeneous
catalyst for the synthesis of 1,4-dihydropyridines and 2-amino-
4-(indol-3-yl)-4H-chromenes.
Fig. 1 X-ray diffraction patterns of (a) Fe3O4 NPs; (b) Si@Fe3O4; (c) VSF.
Results and discussions
Synthesis and characterization of VSF catalyst
VSF nanomaterial was synthesized by the graing of the tet-
rabutylammonium valinate [NBu4][Val] ionic liquid (VIL) on
3-chloropropyltriethoxysilane coated Fe3O4 NPs using
a
simple conventional heating protocol (Scheme 1) and char-
acterized by Fourier transform infrared spectroscopy (FT-IR),
X-ray diffraction (XRD), transmission electronic microscopy
(TEM), scanning electronic microscopy (SEM), thermal
gravimetric analysis (TGA), and vibrating sample magnetom-
eter (VSM).
The XRD pattern of Fe3O4 clearly conforms to the formation
of a cubic spinel structure with the diffraction peaks (2q) at
30.16ꢀ, 35.53ꢀ, 43.33ꢀ, 53.64ꢀ, 57.39ꢀ and 62.76ꢀ, which corre-
spond to the (2 2 0), (3 1 1), (4 0 0), (4 2 2), (5 1 1), and (4 4 0)
phases, respectively (Fig. 1). The XRD pattern is in well agree-
ment with the reported data (JCPDS no. 65-3107).33 The mean
crystallite size and the mean particle size were determined
using the Scherrer formula and found to be 11.6 nm.
The calculated mean crystallite size is consistent with that
measured from the TEM images. There were no considerable
changes observed in the X-ray diffraction pattern and crystallite
size of silica coated ferrite and VSF (Fig. 1b and c). However, the
intensity of the related peaks of silica-coated and VSF are
slightly reduced (Fig. 1).
Fig. 2 FT-IR of (a) Fe3O4 NPs; (b) Si@Fe3O4; (c) VIL; (d) VSF.
The functional groups of the as-synthesized VSF material
and its precursors were characterized from the FT-IR technique,
as shown in Fig. 2. Three characteristic bands corresponding to
Fe–O vibration and surface hydroxyl groups of Fe3O4 appeared
at 581, 1622 and 3426 cmꢁ1, respectively (Fig. 2a). The charac-
teristic bands of chloropropyl silane coated ferrite appeared at
1039, 1129 cmꢁ1 and 2940, 1415 cmꢁ1, which correspond to the
Fig. 3 Low to high magnified SEM images of (a), (b) Fe3O4 NPs and (c),
Scheme 1 Synthesis of [NBu4][Val]@Si@Fe3O4 (VSF) catalyst.
41324 | RSC Adv., 2014, 4, 41323–41330
(d) VSF.
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Si–O–Si stretching and C–H stretching bands, respectively
(Fig. 2b). The characteristic bands at 1666 cmꢁ1 correspond to
the carbonyl functional group of [NBu4][Val] (Fig. 2c). Moreover,
the presence of functional groups in VSF such as Fe–O, Si–O–Si,
C–H, and carbonyl conformed to the bands at 581, 1129 and
1039, 1415, 1657 cmꢁ1, respectively (Fig. 2d).
The surface morphology of Fe3O4 NPs and VSF was charac-
terized from the scanning electronic microscopy (SEM) tech-
nique, as shown in Fig. 3. The results clearly showed that there
was a change in the morphology of VSF (Fig. 3c and 3d) as
compared with Fe3O4 NPs (Fig. 3a and 3b). Furthermore, the
internal morphology and size of VSF NPs were characterized
from transmission electronic microscopy (TEM), as shown in
Fig. 4.
The particle size of VSF NPs was calculated from TEM and
found to be varying from 7.35 nm to 12.5 nm, which is consis-
tent with the result calculated from the PXRD data using the
Scherrer formula.
Fig. 5 TGA curves of (a) Fe3O4 NPs; (b) Si@Fe3O4; (c) VSF.
of chloropropyl triethoxysilane and [NBu4][Val] on Fe3O4 NPs,
respectively. Moreover, the results indicate that these materials
showed a typical superparamagnetic behavior with negligible
remanence, Mr (emu gꢁ1), and coercivity, Hc (Oe), as shown in
the inset (Fig. 6). The superparamagnetic behavior and high
saturation magnetization of these materials are very benecial
in heterogeneous catalysis as it is easily recoverable by external
magnetic elds.
The thermal stability and percentage of organic functional
groups chemisorbed/graed on Fe3O4 NPs were determined by
TGA analyses (Fig. 5). The weight loss at a temperature of 150 ꢀC
can be attributed to the water desorption from the surface of
MNPs (Fig. 5). The curve in (Fig. 5b) shows a weight loss of 4.4%
ꢀ
in the temperature range of 150–550 C corresponding to the
decomposition of 3-chloropropyltriethoxysilane on Fe3O4. The
curve in (Fig. 5c) shows a weight loss of 6.1% corresponding to
the decomposition of [NBu4][Val]. Moreover, the weight loss
above 600 ꢀC corresponds to the decomposition of Fe3O4 to
3FeO. The TGA calculations reveal that 6.1% of the ionic liquid
was graed on Fe3O4 NPs.
The magnetic properties of VSF, Si@Fe3O4, and Fe3O4 NPs
were measured by vibrating a sample magnetometer (Fig. 6).
The saturation magnetization of bare Fe3O4 was found to be
44.8 emu gꢁ1. There was a slight decrease in the magnetization
of Si@Fe3O4 and VSF, namely, 36.1 and 37.3 emu gꢁ1, respec-
tively. This slight decrease was due to the successful supporting
VSF as a quasi-homogeneous catalyst for multi-component
reactions
Initially, the catalytic potential of VSF NPs was investigated for
the synthesis of 1,4-dihydropyridines via the Hantzsch reaction,
as shown in Scheme 2. The optimization of the reaction
conditions was studied for the model reaction between 1,3-
cyclohexanedione, benzaldehyde, ethyl acetoacetate and
ammonium acetate for the synthesis of 1,4-dihydropyridine 5a.
The reaction was performed in the presence of different VSF
catalyst loading amounts under benign solvents such as water,
EtOH and without solvent at room temperature (Table 1, entries
1–6). The results showed that 2 mol% of the catalyst and ethanol
Fig. 4 (a)–(d) Low to high magnified TEM images of VSF.
Fig. 6 Magnetization curves of Fe3O4 NPs; Si@Fe3O4; and VSF.
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Table 2 VSF catalyzed one-pot synthesis of 1,4-dihydropyridinesa
Entry
R
R1
Product 5 Time (min) Yieldb (%)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
Me
H
H
H
4-NO2
4-Cl
5a
5b
5c
5d
5e
5f
5g
5h
5i
25
40
40
35
45
30
20
20
20
25
40
40
94
87
95
91
93
89
93
92
93
94
91
85
4-Br
4-CN
4-Me
4-OMe
3,4-OMe
3-OMe
H
Scheme 2 VSF catalyzed one-pot synthesis of 1,4-dihydropyridines.
9
Table 1 Optimization study for VSF catalyzed one-pot synthesis of
1,4-dihydropyridine 5aa
10
11
12
5j
5k
5l
4-OBn
13
EAA
H
5m
35
85
a
1,3-Cyclohexanedione (1 mmol), aldehyde (1 mmol), ethylacetoacetate
(1 mmol), NH4OAc (1.5 mmol), VSF catalyst (2 mol%) and EtOH (4 mL)
b
at room temperature. Isolated yield.
Entry
Catal. (mol%)
Solvent
Time (min)
Yieldb (%)
aldehydes bearing electron donating groups such as OMe and
Me at the para and meta positions gave excellent yields within
short reaction times (Table 2, entries 6–9).
1
2
3
4
5
6
7
8
9
10
VSF (10)
VSF (10)
VSF (10)
VSF (5)
VSF (2)
VSF (1)
Fe3O4 (2)
Si@Fe3O4 (2)
[NBu4][Val] (2)
No catalyst
Water
EtOH
No solvent
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
60
40
80
30
30
70
84
65
84
90
80
50
40
A comparative study on the catalytic performance of VSF with
other MNP catalysts for the synthesis of 1,4-dihydropyridines
5a, 5m and 5j are shown in Table 3. To our delight, VSF is the
best quasi-homogeneous catalyst to afford products 5a and 5m
in high yields at room temperature with turn over number
values of 39.66 and 35.86, respectively. In contrast, other MNPs
such as nano-g-Fe2O3, g-Fe2O3–SO3H, Fe3O4–CeO2 and ZrO2–
Al2O3–Fe3O4 are either required under the high temperature
condition (80–90 ꢀC) to yield the products or low TON values are
obtained (Table 3).
30
120
120
30
60
Trace
240
a
1,3-Cyclohexanedione (1 mmol), aldehyde (1 mmol), ethylacetoacetate
(1 mmol), NH4OAc (1.5 mmol), catalyst (mol%) and solvent (4 mL) at
b
room temperature. Isolated yield.
We further extended the scope of VSF catalyst for the
synthesis of 2-amino-4-(indol-3-yl)-4H-chromenes via Knoeve-
nagel/Pinner/Friedel–Cras reaction, as shown in Scheme 3.
In order to nd the optimum reaction condition, a model
reaction between salicylaldehyde, indole and malononitrile
using 2 mol% VSF catalyst in the presence of various polar and
non-polar solvents was studied. Interestingly, when water was
used as the solvent, the reaction proceeded smoothly to afford
product 9a in an excellent yield of 93% (Table 4, entry 6).
However, organic solvents such as EtOH, DMSO, CH3CN, THF
and CH2Cl2 gave product 9a in poor to moderate yields of 40–
60% (entries 1–5). The reason for the high catalytic activity of
the VSF catalyst in water as the solvent can be the tendency of
water to enhance the rate of organic reactions due to interac-
tions such as hydrogen bonding and the “Breslow effect,”
wherein the hydrophobic aggregation of organic molecules
decreases the area of a non-polar surface, which, in turn,
reduces the activation energies.34
as a solvent was the best combination to afford product 5a in
excellent yield within a short reaction time (Table 1, entry 5).
When the reactions were performed in the presence of Fe3O4
and Si@Fe3O4 NPs under optimized conditions, product 5a was
formed in moderate yields (entries 7 and 8). In the presence of
[NBu4][Val] as a catalyst, product 5a was formed in 60% yield
(entry 9). Next, we studied the model reaction in the absence of
a catalyst under optimized conditions; a trace amount of
product formation was observed even aer a prolonged reaction
time (Table 1, entry 10). However, the catalytic activity of either
Fe3O4 (heterogeneous) or [NBu4][Val] (homogeneous) alone was
found to be sluggish with moderate yields of 5a. The combined
properties of VSF, a quasi-homogeneous catalyst, gave the
best result to afford DHP 5a in 90% yield at room temperature
(Table 1, entry 5).
With these interesting results, we investigated the generality
of VSF catalyst for several substituted aryl aldehydes, 1,3-
cyclohexanedione/dimedone and ammonium acetate under
optimized conditions, as shown in Table 2. The aryl aldehydes
having electron withdrawing groups such as NO2, Cl, Br and CN
at the para position showed less reactivity as compared with
simple benzaldehyde (Table 2, entries 2–5). Moreover, the
Next, we examined the generality of the VSF catalyst for the
synthesis of substituted 2-amino-4-(indol-3-yl)-4H-chromenes
9a–9g from various substrates such as indoles (6a–6c), 2-
hydroxy aromatic aldehydes (7a, 7b) and active methylene
compounds (8a, 8b), as shown in Table 5. Interestingly, almost
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Table 3 Comparative study of MNP catalysts for the synthesis of 1,4-dihydropyridines 5a, 5j and 5m
5
Catalyst
Time (min)
Temp. (ꢀC)
Yield (%)
TON
Ref.
5m
5m
5j
5m
5a
g-Fe2O3
25
60
33
90
25
35
90
90
RT
80
RT
RT
95
98
93
94
94
85
6.53
9.44
3.75
43.34
39.66
35.86
28
29
30
31
—
—
g-Fe2O3–SO3H
Fe3O4–CeO2
ZrO2–Al2O3–Fe3O4
VSF
5m
VSF
Probably, the high catalytic activity of the VSF catalyst is due to
the presence of active sites such as low-coordinated sites and
surface vacancies of nano Fe3O4, and carboxylate anion and
ammonium ions from ionic liquids can act as the conjugate
base and acid, respectively. Moreover, the combination of both
these properties makes VSF as an efficient quasi-homogeneous
catalyst. The basic sites of VSF can promote the Knoevenagel
condensation between salicylaldehyde 7a and malononitrile 8a
to afford olenic product 10, followed by a Pinner reaction to
yield iminochromene intermediate B. Furthermore, the Friedel–
Cras alkylation of indole 6a with iminochromene B results in
the formation of 2-amino-4-(indol-3-yl)-4H-chromene 9a.
Scheme 3 VSF catalyzed one-pot synthesis of 2-amino-4-(indol-3-
yl)-4H-chromenes.
The recyclability of VSF catalyst was investigated for the
Table 4 Effect of solvent on VSF catalyzed one-pot synthesis of 2- reaction between 1,3-cyclohexanedione, benzaldehyde, ethyl
amino-4-(indol-3-yl)-4H-chromene 9aa
Entry
Solvent
Time (min)
Yieldb (%)
1
2
3
4
5
6
EtOH
90
90
90
90
90
30
60
55
50
43
40
93
DMSO
CH3CN
THF
CH2Cl2
Water
a
Reaction conditions: indole (1 mmol), salicylaldehyde (1 mmol),
malononitrile (1 mmol), VSF catalyst (2 mol%), and solvent (1.5 mL)
b
were stirred at room temperature. Isolated yield.
all the substrates afforded the desired products selectively in
good to excellent yields of 80–94% within short reaction times
(Table 5, entries 1–7).
The plausible mechanism of VSF catalyzed one-pot synthesis
Fig. 7 Plausible mechanism of VSF catalyzed one-pot synthesis of 2-
of 2-amino-4-(indol-3-yl)-4H-chromene 9a is depicted in Fig. 7. amino-4-(indol-3-yl)-4H-chromene 9a.
Table 5 VSF catalyzed one-pot synthesis of 2-amino-4-(indol-3-yl)-4H-chromenesa
Aldehyde
7
Entry
Indole 6
Comp. 8
Product 9
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
6a
6a
6b
6b
6c
6c
6a
7a
7a
7a
7a
7a
7a
7b
8a
8b
8a
8b
8a
8b
8a
9a
9b
9c
9d
9e
9f
15, 60c
30
20
35
15
94, 55c
85
87
82
90
30
35
83
87
9g
a
Reaction conditions: indoles (1 mmol), 2-hydroxyaromatic aldehydes (1 mmol), malononitrile (1 mmol), VSF catalyst (2 mol%), and water (1.5 mL)
were stirred at room temperature. Isolated yield. c Fe3O4 used as a catalyst.
b
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measurement was performed on a JEOL 2100F transmission
electron microscope. The samples were supported on carbon-
coated copper grids for the TEM experiment. The melting points
were measured using a Buchi B-540 melting-point apparatus
and are uncorrected. The 1H and 13C NMR spectra were
measured on a Brucker AC-200 instrument.
Procedure for the preparation of Fe3O4 MNPs
The Fe3O4 nanoparticles were prepared according to Massart's
method. An aqueous solution of 2 eq. FeCl3$6H2O (5.8 g in 50
mL water) was mixed with an aqueous solution of 1 eq. FeCl2-
$4H2O (2.2 g in 50 mL water). The mixture was stirred vigorously
at 85 ꢀC for 30 min, and then 10 mL of ammonia (28% aqueous
solution) was added quickly. The reaction was further stirred for
another 30 min at 85 ꢀC to afford Fe3O4 nanoparticles as a black
precipitate. The obtained Fe3O4 NPs were collected using an
external magnet, washed with water followed by ethanol, and
Fig. 8 Recycling study of VSF catalyst for the synthesis of 1,4-dihy-
dropyridine 5a.
acetoacetate and ammonium acetate in the synthesis of 1,4-
dihydropyridine 5a, as shown in Fig. 8.
Aer the completion of reaction, the catalyst was separated
from the reaction mixture magnetically using an external
magnet. The catalyst was washed with ethanol 3–4 times in
ꢀ
dried at 80 C in an oven.
ꢀ
order to remove the residual product, dried at 70 C and used
for the next cycle. The procedure was repeated six times: there
was no signicant loss in the catalytic activity of the VSF catalyst
(Fig. 8).
General procedure for the synthesis of [NBu4][Val] ionic liquid
[NBu4][Val] ionic liquid was prepared by a modied literature
method.35 Tetrabutylammonium hydroxide solution (40%, 10
mmol) was added to an aqueous suspension of valine (10
mmol). The resultant reaction mixture was stirred at room
temperature for 12 h. The water was removed in vacuo at 80 ꢀC,
and the resultant residue was dissolved in CH3CN (40 mL) and
ltered to remove the unreacted valine. The ltrate was dried
over Na2SO4, ltered and excess of the solvent was removed in
vacuo to afford the desired tetrabutylammonium valinate ionic
liquid as low viscous colourless oil.
Conclusions
We have developed VSF as a superparamagnetic quasi-homo-
geneous catalyst to bridge the gap between homogeneous and
heterogeneous catalyses for the multi-component synthesis of
1,4-dihydropyridines and 2-amino-4-(indol-3-yl)-4H-chromenes.
The present protocol can provide a superior alternative to the
existing methods with advantages such as the catalyst being
non-toxic, superparamagnetic and easily recoverable with an
external magnet and the avoidance of the work up/ltration and
high activity/selectivity with excellent yields. The high catalytic
activity of the VSF catalyst is due to the presence of active sites
such as low-coordinated sites, surface vacancies of nano Fe3O4,
and carboxylate anion and ammonium ions from [NBu4][Val]
ionic liquid.
Procedure for the preparation of Fe3O4@Si(CH2)3-NVIL (VSF)
The supporting of the [NBu4][Val] ionic liquid on silica graed
ferrite is illustrated in Scheme 1. In a typical procedure, 3 g of
Fe3O4 and 3-chloropropyltriethoxysilane (6 mmol) in 40 mL of
dry toluene was reuxed under nitrogen for 12 h. The obtained
graed Fe3O4@Si(CH2)3–Cl was ltered out, washed twice with
dry toluene and once with anhydrous diethyl ether, and dried at
75 ꢀC for 6 h in vacuum. Then, [NBu4][Val] ionic liquid (10
mmol) was added to the round bottom ask containing Fe3-
O4@Si(CH2)3–Cl (1 mmol) and K2CO3 (5 mmol) in 50 mL of dry
toluene and the mixture was reuxed for 24 h. The resulting
solid was ltered out, washed and dried in a similar manner to
give Fe3O4@Si(CH2)3-NVIL (VSF). Aer ꢀthe usual workup and
washings, the material was dried at 75 C for 5 h in a vacuum
oven.
Experimental
Powder X-ray diffraction (PXRD) patterns were recorded using a
Siemens D500 instrument that used Cu-Ka radiation (l ꢂ
˚
1.54050 A) and equipped with the AT Diffract soware. The
crystalline phases were identied by comparison with JCPDS
®les.10. TGA analysis (Perkin Elmer, Pyris Diamond) with a
heating rate of 10 ꢀC minꢁ1 in nitrogen atmosphere was used to
study the thermal decomposition behavior of the samples with
respect to a-Al2O3 as the reference. Fourier transform infrared
(FT-IR) spectra were recorded on a Perkin Elmer device, and the
General procedure for the synthesis of 1,4-dihydropyridines
(5a–5m)
samples were prepared by mixing the samples with KBr. Scan- A mixture of 1,3-cyclohexanedione 1 (1 mmol), aldehyde 2 (1
ning electron microscopy (SEM) measurement was performed mmol), ethyl-acetoacetate 3 (1 mmol), ammonium acetate 4 (1.5
on a JEOL JSM-6610LV electron microscope. The super- mmol), and VSF nanoparticles (2 mol%) in ethanol (4 mL) were
paramagnetic properties of the samples were studied using a stirred at room temperature. Aer the completion of the reac-
superconducting quantum interference device (SQUID) tion (monitored by TLC), the superparamagnetic VSF catalyst
magnetometer. The transmission electron microscopy (TEM) was separated from the reaction mixture using an external
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magnet. The obtained crude products (5a–5m) were puried by MHz, CDCl3) d (ppm) 7.93 (br s, 1H), 7.74 (s, 1H), 7.21–7.13
recrystallization from hot ethanol. The puried compounds (m, 4H), 7.04–6.96 (m, 2H), 6.28 (s, 1H), 5.24 (s, 1H), 4.12–4.04
were characterized by IR, 1H NMR, 13C NMR, HRMS, and (m, 2H), 1.16 (t, J ¼ 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) d
elemental analysis.
(ppm) 169.43, 160.24, 148.98, 134.76, 127.69, 126.37, 124.71,
Ethyl-4-(4-(benzyloxy)phenyl)-2-methyl-5-oxo-1,4,5,6,7,8-hex- 124.18, 123.30, 122.96, 122.72, 121.83, 115.60, 112.60, 112.18,
ahydroquinoline-3-carboxylate (5k). Off white solid; mp 250– 59.44, 31.02, 14.30; HRMS (ES): calcd 412.0423, found
253 ꢀC; IR (KBr) 3294, 3215, 3081, 2938, 1697, 1607, 1490, 1384, 412.0421; anal. calcd for C20H17BrN2O3: C, 58.13; H, 4.15; N,
1
1224, 1176, 1080 cmꢁ1; H NMR (400 MHz; DMSO; Me4Si) d ¼ 6.78; found: C, 58.12; H, 4.13; N, 6.79.
9.08 (brs, 1H), 7.40–7.29 (m, 5H), 7.02 (d, J ¼ 7.9 Hz, 2H), 6.80 (d,
2-Amino-4-(2-methyl-1H-indol-3-yl)-4H-chromene-3-carbon-
J ¼ 8.5 Hz, 2H), 4.99 (s, 2H), 4.81 (s, 1H), 3.96 (q, J ¼ 7.3 Hz, 2H), itrile (9e). Yellow solid; mp 202–204 ꢀC; IR (KBr) 3331, 2961,
2.46–2.45 (m, 2H), 2.25 (s, 3H), 2.19–2.16 (m, 2H), 1.90–1.68 (m, 2933, 2185, 1646, 1604, 1576, 1486, 1457, 1394, 1224, 1040, 744,
4H), 1.11 (t, J ¼ 7.3 Hz, 3H) ppm. 13C NMR (100 MHz; DMSO; 593, 562 cmꢁ1; H NMR (400 MHz, CDCl3) d (ppm) 7.86 (br s,
1
Me4Si) d ¼ 194.62, 167.04, 156.30, 151.11, 144.56, 140.35, 1H), 7.23 (d, J ¼ 8.5 Hz, 1H), 7.16–7.14 (m, 1H), 7.08–7.00 (m,
137.28, 128.36, 127.47, 114.00, 111.24, 103.64, 69.00, 58.98, 3H), 6.96–6.95 (m, 2H), 6.92–6.88 (t, J ¼ 7.3 Hz), 5.10 (s, 1H),
36.70, 34.64, 26.07, 20.76, 18.19, 14.14 ppm. HRMS (ES): calcd 4.52 (s, 2H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3) d (ppm)
417.1940, found 417.1937; anal. calcd for C26H27NO4: C, 74.80; 158.84, 148.70, 135.43, 131.97, 129.49, 127.90, 126.93, 124.94,
H, 6.52; N, 3.35; found: C, 74.79; H, 6.51; N, 3.36.
122.67, 121.06, 120.16, 119.34, 118.15, 115.94, 113.87, 60.56,
Ethyl-2-methyl-5-oxo-4-(3-(prop-2-yn-1-yloxy)phenyl)-1,4,5,6,7,8- 31.23, 11.57; HRMS (ES): calcd 367.0320, found 367.0322; anal.
hexahydroquinoline-3-carboxylate (5l). White solid; mp 260– calcd for C19H15N3O: C, 75.73; H, 5.02; N, 13.94; found: C, 75.72;
ꢀ
263 C; IR (KBr) 3279, 3243, 3077, 2941, 1701, 1607, 1488, 1381, H, 5.04; N, 14.01.
1221, 1037 cmꢁ1; 1H NMR (400 MHz; DMSO; Me4Si) d ¼ 9.14 (brs,
1H), 7.09 (t, J ¼ 7.3 Hz, 1H), 6.75 (d, J ¼ 7.3 Hz, 1H), 6.72–6.69 (m,
Acknowledgements
2H), 4.87 (s, 1H), 4.67 (s, 2H), 3.98 (q, J ¼ 7.3 Hz, 2H), 3.53 (s, 1H),
2.26 (s, 3H), 2.18 (s, 3H), 1.87–1.74 (m, 3H), 1.12 (t, J ¼ 7.3 Hz, 3H)
ppm. 13C NMR (100 MHz; DMSO; Me4Si) d ¼ 194.52, 166.71,
156.93, 151.51, 149.29, 145.00, 128.64, 120.41, 114.25, 111.37,
110.87, 103.31, 79.31, 77.93, 59.06, 55.07, 36.67, 35.34, 26.11,
20.74, 18.21, 14.14 ppm. HRMS (ES): calcd 365.1627, found
365.1630; anal. calcd for C22H23NO4: C, 72.31; H, 6.34; N, 3.83;
found: C, 72.30; H, 6.36; N, 3.82.
DSR acknowledges the Council of Scientic and Industrial
Research (02(0049)/12/EMR-II), New Delhi, India and University
of Delhi, Delhi, India for their nancial support. UCR is
thankful to UGC for the award of a senior research fellowship
(SRF). We thank USIC-CIF, University of Delhi, for assisting to
aquire analytical data.
Notes and references
General procedure for the synthesis of 2-amino-4-(indol-3-yl)-
4H-chromene derivatives (9a–9f)
1 H. Lu, E. L. Salabas and F. Schuth, Angew. Chem., Int. Ed.,
2007, 46, 1222; N. Koukabi, E. Kolvari, A. Khazaei,
M. A. Zolgol, B. S. Shaghasemic and H. R. Khavasid,
Chem. Commun., 2011, 47, 9230; V. Polshettiwar, R. Luque,
A. Fihri, H. Zhu, M. Bouhrara and J. M. Basset, Chem. Rev.,
2011, 111, 3036.
2 R. B. N. Baig and R. S. Varma, Chem. Commun., 2013, 49, 752;
Q. M. Kainz and O. Reiser, Acc. Chem. Res., 2014, 47, 667.
3 C. Berry and A. S. G. Curtis, J. Phys. D: Appl. Phys., 2003, 36,
198; C. C. Berry, J. Phys. D: Appl. Phys., 2009, 42, 224003;
A. Akbarzadeh, M. Samiei and S. Davaran, Nanoscale Res.
Lett., 2012, 7, 144.
4 S. Shylesh, L. Wang and W. R. Thiela, Adv. Synth. Catal.,
2010, 352, 425; J. Liu, X. Peng, W. Sun, Y. Zhao and C. Xia,
Org. Lett., 2008, 10, 3933; S. Ko and J. Jang, Angew. Chem.,
2006, 118, 7726.
5 R. L. Oliveira, P. K. Kiyohara and L. M. Rossi, Green Chem.,
2010, 12, 144; J. Ge, T. Huynh, Y. Hu and Y. Yin, Nano
Lett., 2008, 8, 931.
A mixture of indoles 6 (1 mmol), 2-hydroxy aromatic aldehydes 7
(1 mmol), active methylene compounds 8 (1 mmol), and (2
mol%) VSF nanoparticles in 1.5 mL of water were stirred at
room temperature. Aer the completion of the reaction
(monitored by TLC), the superparamagnetic VSF catalyst was
separated from the reaction mixture using an external magnet.
The obtained crude products were recrystallized from ethanol to
get pure compounds (9a–9f).
2-Amino-4-(5-bromo-1H-indol-3-yl)chroman-3-carbonitrile (9c).
Yellow solid; mp 180–182 ꢀC; IR (KBr) 3449, 3382, 3320, 3241,
3206, 3083, 2852, 2346, 2372, 2195, 1661, 1612, 1583, 1491, 1449,
1456, 1422, 1405, 1332, 1273, 1259, 1227, 1076, 1098, 1042, 845,
882, 794, 752, 580, 521 cmꢁ1; 1H NMR (400 MHz, CDCl3) d (ppm)
8.20 (br s, 1H), 7.39 (br s, 1H), 7.22–7.16 (m, 4H), 7.05–6.95 (m,
3H), 5.02 (s, 1H), 4.63 (s, 2H); 13C NMR (100 MHz, CDCl3) d (ppm)
159.59, 148.75, 135.86, 129.66, 128.55, 127.54, 125.43, 124.13,
122.60, 121.81, 120.42, 118.84, 116.58, 113.12, 60.49, 32.70; HRMS
(ES): calcd 367.0320, found 367.0322; anal. calcd for C18H14BrN3O:
C, 58.71; H, 3.83; N, 11.41; found: C, 58.72; H, 3.82; N, 11.41.
'Ethyl-2-amino-4-(5-bromo-1H-indol-3-yl)-4H-chromene-3-
carboxylate (9d). Yellow solid; mp 145–147 ꢀC; IR (KBr) 3412,
3318, 2958, 2926, 1731, 1666, 1607, 1518, 1483, 1455, 1399,
6 R. B. N. Baig and R. S. Varma, ACS Sustainable Chem. Eng.,
2013, 1, 805; S. Wang, Z. Zhang, B. Liu and J. Li, Ind. Eng.
Chem. Res., 2014, 53, 5820.
7 R. B. N. Baiga and R. S. Varma, RSC Adv., 2014, 4, 6568;
T. Zeng, L. Yang, R. Hudson, G. Song, A. R. Moores and
1297, 1227, 1185, 1043, 883, 750, 654 cmꢁ1 1H NMR (400
;
This journal is © The Royal Society of Chemistry 2014
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View Article Online
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Paper
C. J. Li, Org. Lett., 2011, 13, 442; R. B. N. Baig and R. S. Varma, 25 D. Kumar, V. B. Reddy, S. Sharad, U. Dube and S. Kapur, Eur.
Green Chem., 2012, 14, 625.
J. Med. Chem., 2009, 44, 3805; W. Kemnitzer, J. Drewe,
S. Jiang, H. Zhang, C. C. Grundy, D. Labreque,
M. Bubenick, G. Attardo, R. Denis, S. Lamothe,
H. Gourdeau, B. Tseng, S. Kasibhatla and S. X. Cai, J. Med.
Chem., 2008, 51, 417.
8 K. Fujita, S. Umeki, M. Yamazaki, T. Ainoya, T. Tsuchimoto
and H. Yasuda, Tetrahedron Lett., 2011, 52, 3137.
9 M. J. Jacinto, R. Landers and L. M. Rossi, Catal. Commun.,
2009, 10, 1971; R. Liu, Q. Zhao, Y. Li, G. Zhang, F. Zhang
and X. Fan, J. Nanomater., 2013, 2013, DOI: 10.1155/2013/ 26 A. M. El-Nagger, A. M. Abdel-El-Salam, F. S. M. Latif and
602602.
M. S. A. Ahmed, Pol. J. Chem., 1981, 55, 793;
K. A. Ohemeng, C. F. Schwender, K. P. Fu and J. F. Barrett,
Bioorg. Med. Chem. Lett., 1993, 3, 225; G. P. Ellis and
I. M. Lockhart, in The Chemistry of Heterocyclic Compounds:
Chromenes, Chromanones, and Chromones, ed. G. P. Ellis,
Wiley-VCH, New York, 2007, vol. 31, pp. 1–1196.
10 R. A. Reziq, H. Alper, D. Wang and M. L. Post, J. Am. Chem.
Soc., 2006, 128, 5279; G. Liu, H. Gu, Y. Sun, J. Long, Y. Xu
and H. Lia, Adv. Synth. Catal., 2011, 353, 1317.
11 M. Bagherzadeh, M. M. Haghdoost and A. Shahbazirad, J.
Coord. Chem., 2012, 65, 591.
12 P. Riente, C. Mendoza and M. A. Pericas, J. Mater. Chem., 27 A. Casapullo, G. Bifulco and I. R. Bruno, J. Nat. Prod., 2000,
2011, 21, 7350; H. R. Shaterian and M. Aghakhanizadeh,
Catal. Sci. Technol., 2013, 3, 425; Y. Kong, R. Tan, L. Zhao
and D. Yin, Green Chem., 2013, 15, 2422.
63, 447; F. D. Horgen, D. B. D. Santos, G. Goetz,
B. Sakamoto, Y. Kan, H. Nagai and P. J. Scheuer, J. Nat.
Prod., 2000, 63, 152.
13 R. A. Reziq, D. Wang, M. Post and H. Alpera, Adv. Synth. 28 N. Koukabi, E. Kolvari, A. Khazaei, M. A. Zolgol,
Catal., 2007, 349, 2145.
14 P. Riente, C. Mendoza and M. A. Pericas, J. Mater. Chem.,
B. S. Shaghasemic and H. R. Khavasid, Chem. Commun.,
2011, 47, 9230.
2011, 21, 7350; Z. quikun, H. Xiaotong and T. Boa, RSC 29 N. Koukabi, E. Kolvari, M. A. Zolgol, A. Khazaei,
Adv., 2013, 3, 9924; Y. Kong, R. Tan, L. Zhao and D. Yin,
Green Chem., 2013, 15, 2422.
B. S. Shaghasemi and B. Fasahati, Adv. Synth. Catal., 2012,
354, 2001.
´
15 R. Giernoth, Angew. Chem., Int. Ed., 2010, 49, 2834; H. Ohno 30 M. B. Gawande, V. D. B. Bonifacio, R. S. Varma,
and K. Fukumoto, Acc. Chem. Res., 2007, 40, 1122; W. Miao
and T. H. Chan, Org. Lett., 2003, 5, 5003; C. Roosen,
I. D. Nogueira, N. Bundaleski, C. A. A. Ghumman,
O. M. N. D. Teodorod and P. S. Branco, Green Chem., 2013,
¨
P. Muller and L. Greiner, Appl. Microbiol. Biotechnol., 2008,
15, 1226.
81, 607.
31 A. Wang, X. Liu, Z. Su and H. Jing, Catal. Sci. Technol., 2014,
4, 71.
16 J. C. Plaquevent, J. Levillain, F. Guillen, C. Malhiac and
A. C. Gaumont, Chem. Rev., 2008, 108, 5035; G. Tao, L. He, 32 S. Manohar, U. C. Rajesh, S. I. Khan, B. L. Tekwani and
W. Liu, L. Xu, W. Xiong, T. Wang and Y. Kou, Green Chem.,
2006, 8, 639.
17 W. Chen, Y. Zhang, L. Zhu, J. Lan, R. Xie and J. You, J. Am.
Chem. Soc., 2007, 129, 13879.
18 J. Kagimoto, K. Fukumoto and H. Ohno, Chem. Commun.,
2006, 2254; G. Tao, L. He, N. Sun and Y. Kou, Chem.
Commun., 2005, 3562.
19 H. Yu, Y. T. Wu, Y. Y. Jiang, Z. Zhou and Z. B. Zhang, New J.
Chem., 2009, 33, 2385; Z. Feng, F. C. Gang, W. Y. Ting,
W. Y. Tao, L. A. Min and Z. Z. Bing, Chem. Eng. J., 2010,
160, 691.
D. S. Rawat, ACS Med. Chem. Lett., 2012, 3, 555; N. Kumar,
S. I. Khan, Beena, G. Rajalakshmi, P. Kumaradhas and
D. S. Rawat, Bioorg. Med. Chem., 2009, 17, 5632; N. Kumar,
S. I. Khan, M. Sharma, H. Atheaya and D. S. Rawat, Bioorg.
Med. Chem. Lett., 2009, 19, 1675; S. Manohar, S. I. Khan
and D. S. Rawat, Bioorg. Med. Chem. Lett., 2010, 20, 322;
A. J. Krzysiak, D. S. Rawat, S. A. Scott, J. E. Pais,
M. Handley, M. L. Harrison, C. A. Fierke and R. A. Gibbs,
ACS Chem. Biol., 2007, 2, 385; R. Mamgain, R. Singh and
D. S. Rawat, J. Heterocycl. Chem., 2009, 46, 69; K. Arya,
U. C. Rajesh and D. S. Rawat, Green Chem., 2012, 14, 3344;
A. Thakur, M. Tripathi, U. C. Rajesh and D. S. Rawat, RSC
Adv., 2013, 3, 18142; U. C. Rajesh, S. Manohar and
D. S. Rawat, Adv. Synth. Catal., 2013, 355, 3170.
20 N. Itagaki, M. Kimura, T. Sugahara and Y. Iwabuchi, Org.
Lett., 2005, 7, 4185; J. E. Hein, J. Bures, Y. Lam,
M. Hughes, K. N. Houk, A. Armstrong and
D. G. Blackmond, Org. Lett., 2011, 13, 5644; J. Yan and 33 P. Wang, A. Kong, W. Wang, H. Y. Zhu and Y. K. Shan, Catal.
L. Wang, Synthesis, 2010, 3, 447. Lett., 2010, 135, 159.
21 J. Zhang, W. Zhang, Y. Wang and M. Zhanga, Adv. Synth. 34 K. Pirkanniemi and M. Sillanpaa, Chemosphere, 2002, 48,
Catal., 2008, 350, 2065; A. Biffis, S. Cunial, P. Spontoni and
L. Prati, J. Catal., 2007, 251, 1.
22 H. Bonnemann and G. A. Braun, Angew. Chem., 1996, 35,
1992.
1047; A. Chanda and V. V. Fokin, Chem. Rev., 2009, 109,
725; M. O. Simon and C. J. Li, Chem. Soc. Rev., 2012, 41,
1415; R. Breslow, Acc. Chem. Res., 1991, 24, 159.
35 C. R. Allen, P. L. Richard, A. J. Ward, L. G. A. V. Water,
A. F. Masters and T. Maschmeyer, Tetrahedron Lett., 2006,
47, 7367.
´
23 S. Vukojevic, O. Trapp, J. D. Grunwaldt, C. Kiener and
F. Schuth, Angew. Chem., 2005, 44, 7978.
24 Q. Zhang, H. Su, J. Luo and Y. Wei, Green Chem., 2012, 14, 201.
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