Fe3O4@mesoporous SBA-15: A robust and magnetically recoverable catalyst for one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones via the Biginelli reaction

Article abstract of DOI:10.1039/c2dt30106g

A magnetic nanoparticle conjugated mesoporous nanocatalyst (Fe ₃O₄@mesoporous SBA-15) with a high surface area has been synthesized by chemical conjugation of magnetite (Fe₃O₄) nanoparticles with functionalized

Full text of DOI:10.1039/c2dt30106g

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PAPER
Fe O @mesoporous SBA-15: a robust and magnetically recoverable catalyst
3
4
for one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones via the Biginelli
reaction†
a
b
a
John Mondal, Tapas Sen and Asim Bhaumik*
Received 16th January 2012, Accepted 14th March 2012
DOI: 10.1039/c2dt30106g
A magnetic nanoparticle conjugated mesoporous nanocatalyst (Fe O @mesoporous SBA-15) with a high
3
4
surface area has been synthesized by chemical conjugation of magnetite (Fe O ) nanoparticles with
3
4
functionalized mesoporous SBA-15. Functionalized mesoporous SBA-15 containing surface carboxyl and
amino groups was synthesized via the thiol–ene click reaction of cysteine hydrochloride and vinyl
functionalized SBA-15. The catalytic activity of the robust, safe and magnetically recoverable
Fe O @mesoporous SBA-15 nanocatalyst was evaluated in the Biginelli reaction under mild conditions
3
4
for the synthesis of a diverse range of 3,4-dihydropyrimidin-2(1H)-ones. The separation and reuse of the
Fe O @mesoporous SBA-15 nanocatalyst were simple, effective and economical.
3
4
polymers, biopolymers, or insoluble solids by using the mag-
netic separation technique. This environmentally benign and
efficient process for catalyst separation has become an important
tool in recent times from an economic, safety and environmental
Introduction
Superparamagnetic nanoparticles have gained intensive research
interest for their potential applications in magnetic hyperther-
1
2
3
12
mia, drug delivery, magnetic resonance imaging (MRI), fluid
point of view. The separation of magnetic catalysts via mag-
netic separation from the reaction mixture is more effective than
filtration or centrifugation techniques as it prevents the loss of
4
5
transport and catalysis. These superparamagnetic nanoparticles
diameter ∼10 nm) have a great tendency to deform and aggre-
(
13
gate during the course of chemical reactions and as a result the
thermal and chemical stability of these materials changes. The
thermal and chemical stability of these nanoparticles play pivotal
roles in tuning their properties in advanced applications. One
the catalyst and it is a simple and economical tool in the case
14
of industrial processes. The use of Fe O nanoparticle-immobi-
3
4
lized or supported materials has been largely exploited in cataly-
15
sis in this context.
6
way to achieve the target is by surface modification or immobil-
The Biginelli reaction, known for a long time, has attracted
much attention after the discovery of dihydropyridine based
calcium channel modulator drugs such as nifedipine, used in the
ization of these magnetic nanoparticles using appropriate
capping agents such as polymers in order to prevent aggregation.
However these organic capping agents have a great tendency to
decompose at high temperature and consequently metal nanopar-
ticles can deform and aggregate easily. Very recently, organically
functionalized mesoporous materials have gained increasing
16
treatment of cardiovascular diseases. This important class of
heterocyclic compounds has attracted considerable interest over
the past decade due to their wide variety of pharmacological and
therapeutic activities. Functionalized dihydropyrimidinones can
be used as antihypertensive agents, alpha-1a-antagonists, and
7
8
9
importance in their use as adsorbents, catalysts, and sensors,
1
0
17
and in gas storage due to their high surface area and tenability
of the surface functionality. Immobilization of metal nanoparti-
cles at the pore surface of the mesoporous materials is of con-
siderable technological importance for improving the
accessibility, lifetime and reusability of the catalyst in the field of
neuropeptide Y (NPY) antagonists. Some marine natural pro-
ducts such as the alkaloid Batzlladine B are found to be potent
HIV gp-120-CD4 inhibitors which contain the dihydropyrimi-
18
dine-5-carboxylate as a sole unit. Biginelli condensation
involves one-pot multicomponent condensation of an aldehyde,
β-ketoester, and urea–thiourea, which provides the dihydropyri-
midinone derivative. The major drawback of this reaction
involves the low product yields particularly for the aromatic and
aliphatic aldehydes. In order to improve the product yield
various types of homogeneous acid catalysts have been used
11
molecular catalysis. In recent times a tremendous advancement
has been made with magnetic nanoparticles coated with
a
Department of Materials Science, Indian Association for the
Cultivation of Science, Jadavpur 700 032, India. E-mail:
msab@iacs.res.in
1
9
such as polyphosphate esters, HCl–FeCl , SnCl , ZnCl or
3
2
2
b
20
21
Centre for Materials Science, Institute of Nanotechnology and
CuCl2, a bifunctional catalyst with a Brönsted acid, InCl3
and InBr3. The problems traditionally associated with the pro-
Bioengineering, School of Forensic and Investigative Sciences,
University of Central Lancashire, Preston, PR1 2HE, UK
22
cedures include high temperature, prolonged reaction time, and
strong Lewis acidity of the catalyst. Thus heterogeneous acid
†
1
Electronic supplementary information (ESI) available. See DOI:
0.1039/c2dt30106g
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3 4
Scheme 1 Grafting of Fe O nanoparticles to cysteine immobilized SBA-15 using thiol-ene click reaction.
catalysts, like Al-MCM-41, or FeCl embedded in Al-MCM-41
Synthesis of vinyl functionalized SBA-15. 0.1 g of calcined
SBA-15 in 10 ml of dry toluene was placed in a 25 ml round
bottom flask equipped with a condenser. A solution of vinyltri-
methoxysilane (0.00081 mol, 0.12 g, Aldrich) in 5 ml of dry
toluene was added dropwise to the dispersed SBA-15 solution
under continuous stirring. After the complete addition of the
organosilane precursor the reaction mixture was kept under
refluxing conditions for about 12 h under a nitrogen atmosphere.
After the completion of the reaction, the reaction mixture was
allowed to cool at room temperature. It was filtered through
suction and washed thoroughly with toluene and dichloro-
methane. The colorless white sample was dried at room tempera-
ture and the material was designated as (A).
3
2
3
are used to catalyze this reaction. However, the problem of
leaching of metal from the catalyst surface could be avoided
from these materials. On the other hand owing to the relatively
high saturation magnetization, magnetic recoverability is easily
possible for immobilized Fe O nanoparticles, which can be
3
4
used as a magnetic nanocatalyst via grafting at the surface of a
functionalized mesoporous material having a high surface area.
So a successful strategy for designing an alternative, non-air sen-
sitive, recyclable, easily separable magnetic nanocatalyst having
pore size large enough to allow the diffusion of large molecules,
requiring short reaction times for the Biginelli reaction, is highly
desirable to address these industrial and environmental concerns.
Herein, we first report the synthesis of a robust and magneti-
cally recoverable superparamagnetic Fe O nanoparticle conju-
3
4
Synthesis of cysteine hydrochloride functionalized mesoporous
gated mesoporous SBA-15 (Fe O @mesoporous SBA-15) and
3
4
SBA-15 (B). A mixture of cysteine hydrochloride (142 mg,
its excellent catalytic activity in the Biginelli condensation. (The
outline for the preparation of this magnetic nanocatalyst as
shown in Scheme 1.) Functionalized mesoporous SBA-15 was
prepared by thiol–ene click chemistry of vinyl functionalized
SBA-15 and cysteine hydrochloride in the presence of an 2,2′-
azobis(isobutyronitrile) (AIBN) initiator. The subsequent reac-
tion of the functionalized mesoporous SBA-15 in absolute
ethanol with superparamagnetic Fe O nanoparticles dispersed
−2
0
.00081 mol) in water (20 ml) and AIBN (10 mg, 6.3 × 10
mmol) were added to the as-prepared vinyl functionalized
SBA-15 (A) dispersed in 10 ml methanol solution at room temp-
erature. The mixture was heated at 338 K for 12 h under nitrogen
atmosphere. The reaction mixture was allowed to cool at room
temperature. Then the colorless white material (B) was collected
by filtration after washing several times with water in order to
remove unreacted cysteine hydrochloride.
3
4
in water leads to the formation of a novel Fe O @mesoporous
3
4
SBA-15 nanocatalyst. The nanocatalyst is thoroughly character-
Synthesis of well dispersed superparamagnetic Fe
particles. The synthesis involved dissolving 8.46
FeCl ·4H O and 22.95 g of FeCl ·6H O in 500 ml deionised
water and degassing the solution with nitrogen. The reaction
mixture was then placed in an oil bath previously heated to
3
O
4
nano-
ized by using powder XRD, HR TEM, FE SEM, N sorption
2
g
of
and FT IR spectroscopic tools. The Biginelli condensation reac-
tion proceeds with this catalyst effectively and the recovery of
the Fe O @mesoporous SBA-15 nanocatalyst can be done
2
2
3
2
3
4
easily through magnetic separation. The catalyst was reused
several times without any significant loss in activity.
8
0 °C and 20 ml of aqueous NH (25% w/v) solution was added
3
dropwise to the mixture over 30 min and the reaction allowed to
proceed for a further 1 h at 80 °C. The black reaction product
was washed several times in deionised water until the pH of the
suspension was 7. The solid density in the suspension was
measured to be 32.2 mg ml− by drying 1 ml of suspension at
60 °C overnight.
Experimental section
Preparation of Fe
The preparation involves the following sub-steps:
174 | Dalton Trans., 2012, 41, 6173–6181
3 4
O @mesoporous SBA-15 nanocatalyst
1
6
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Chemical conjugation of Fe
3
O
4
nanoparticles onto cysteine
9.16 (1H, s), 7.71 (1H, s), 7.35–7.12 (5H, m), 5.14 (1H, d, J = 3
Hz), 4.00 (2H, q, J = 6 Hz), 2.24 (1H, s), 1.18 (3H, t, J = 9 Hz);
hydrochloride functionalized mesoporous SBA-15 (B) to form
Fe O @mesoporous SBA-15 nanocatalyst (C)
13
3
4
C NMR (300 MHz, DMSO-d ) δ 165.3, 152.1, 148.3, 144.8,
6
1
3
2
28.3, 127.3, 126.2, 99.2, 59.1, 53.9, 17.7, 14.0. IR (KBr):
414, 3230, 3109, 2936, 1702, 1649, 1599 cm . Solid, mp
02–203 °C.
0
.1 g of cysteine hydrochloride functionalized SBA-15 material
−1
(
B) was dispersed in 10 ml absolute ethanol solution. Then 1 ml
−1
of the Fe O nanoparticle suspension (32.2 mg ml ) was added
3
4
to the previous solution by a micropipette and the mixture was
allowed to stir at room temperature for 12 h. Then the reaction
mixture was filtered and washed several times with ethanol. The
black colored material was dried at room temperature and it was
designated as (C).
5-Ethoxycarbonyl-4-(4-chlorophenyl)-6-methyl-3,4-dihydro-
pyridin-2(1H)-one (Table 2, entry 2). H NMR (300 MHz,
1
DMSO-d ) δ 9.22 (1H, s), 7.75 (1H, s), 7.39 (2H, d, J = 9 Hz),
6
7.25 (2H, d, J = 9 Hz), 5.13 (1H, d, J = 3 Hz), 4.00 (2H, q, J =
13
6 Hz), 2.23 (3H, s), 1.10 (3H, t, J = 6 Hz); C NMR (300 MHz,
DMSO-d ) δ 166.8, 152.0, 148.7, 143.8, 131.8, 128.2, 127.9,
6
9
1
8.9, 59.3, 53.4, 18.2, 14.1. IR (KBr): 3419, 3246, 3112, 2980,
708, 1646, 1487 cm . Solid, mp 215–216 °C.
General procedure for Fe
dihydropyrimidinones via Biginelli condensation
3
O
4
nanoparticle mediated synthesis of
−1
5
-Ethoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-3,4-dihydro-
To a stirred solution of benzaldehyde (1 mmol, 106 mg), ethyl
acetoacetate (1 mmol, 132 mg) and urea (1.5 mmol, 90 mg) in
1
pyridin-2(1H)-one (Table 2, entry 3). H NMR (300 MHz,
DMSO-d ) δ 9.20 (1H, s), 7.86–7.84 (2H, d, J = 6 Hz), 7.69
(1H, s), 6.86–6.83 (2H, d, J = 9 Hz), 5.09 (1H, d, J = 3 Hz),
6
5
ml of absolute ethanol, the Fe O @mesoporous SBA-15 nano-
3 4
catalyst (50 mg) was added and the mixture was heated in an oil
bath at 363 K and the progress of the reaction was monitored by
TLC. After a period of time the reaction mixture was allowed to
cool and the catalyst was removed by a simple magnet. Then the
reaction mixture (without the nanocatalyst) was evaporated to
dryness under reduced pressure to obtain a solid residue. The
solid residue was stirred in water (3 × 15 ml) and then filtered.
The solid was washed with hexane (3 × 15 ml) and re-crystal-
lized from ethanol to give the pure product. The isolated pure
3
=
.99 (2H, q, J = 6 Hz), 3.79 (3H, s), 2.22 (3H, s), 1.16 (3H, t, J
6 Hz); C NMR (300 MHz, DMSO-d ) δ 165.4, 158.5,
6
13
1
1
1
52.3, 148.0, 137.1, 127.4, 113.7, 99.6, 59.2, 55.0, 53.4, 17.8,
4.1. IR (KBr): 3415, 3241, 3114, 2954, 1708, 1646,
512 cm . Solid, mp 201–202 °C.
−1
5-Ethoxycarbonyl-4-(4-nitrophenyl)-6-methyl-3,4-dihydropyr-
1
idin-2(1H)-one (Table 2, entry 4). H NMR (300 MHz, DMSO-
d
d, J = 9 Hz), 7.91 (1H, s), 5.28 (1H, d, J = 3 Hz), 4.01 (2H, q, J
) δ 9.36 (1H, s), 8.23–8.20 (2H, d, J = 9 Hz), 7.52–7.49 (2H,
6
1
13
product was characterized by H and C NMR, IR data and
melting point respectively and compared with the reported
values.
13
= 6 Hz), 2.26 (3H, s), 1.11 (3H, t, J = 6 Hz); C NMR
(300 MHz, DMSO-d ) δ 164.9, 151.9, 151.6, 149.3, 146.6,
27.5, 123.7, 98.0, 59.3, 53.5, 17.8, 13.8. IR (KBr): 3416, 3237,
6
1
3
085, 2941, 1728, 1694, 1588, 1509 cm− . Solid, mp
1
Characterization techniques
208–209 °C.
Powder X-ray diffraction patterns were recorded on a Bruker D-8
Advance SWAX diffractometer operated at 40 kV voltage and
5-Ethoxycarbonyl-4-(4-hydroxyphenyl)-6-methyl-3,4-dihydro-
pyridin-2(1H)-one (Table 2, entry 5). H NMR (300 MHz,
1
4
0 mA current. The instrument has been calibrated with a stan-
DMSO-d ) δ 9.74 (1H, s), 9.12 (1H, s), 7.76 (1H, s), 7.05 (2H,
6
dard silicon sample, using Ni-filtered Cu-K (λ = 0.15406 nm)
d, J = 8.4 Hz), 6.7 (2H, d, J = 8.1 Hz), 5.07(1H, d, J = 3 Hz),
α
13
radiation. Nitrogen adsorption–desorption isotherms were
obtained by using a Bel Japan Inc. Belsorp-HP at 77 K. Prior to
gas adsorption, the samples were degassed for 4 h at 393 K
under high vacuum conditions. A JEOL JEM 6700F field emis-
sion scanning electron microscope was used for the determi-
nation of the morphology of the particles. High resolution
transmittance electron microscope (HR TEM) images were
recorded on a JEOL JEM 2010 transmission electron micro-
scope. FT IR spectra of the samples were recorded using a
Nicolet MAGNA-FT IR 750 Spectrometer Series II. Fe loading
in the sample was estimated by using a Perkin-Elmer Optima
3.98 (2H, q, J = 7 Hz), 2.22 (3H, s), 1.13 (3H, t, J = 6 Hz);
C
NMR (300 MHz, DMSO-d ) δ 166.0, 157.5, 153.1, 148.1,
6
135.8, 127.9, 115.5, 100.4, 59.7, 54.0, 18.2, 14.5. IR (KBr):
3417, 3241, 3120, 2984, 1687, 1649, 1512 cm− . Solid, mp
226–228 °C.
1
5
-Ethoxycarbonyl-4-furfuryl-6-methyl-3,4-dihydropyridin-2
1
(
1H)-one (Table 2, entry 6). H NMR (500 MHz, DMSO-d ) δ
6
9
6
=
.21 (1H, s), 7.72 (1H, s), 7.53 (1H, s), 6.33 (1H, d, J = 2.5 Hz),
.07 (1H, d, J = 3 Hz), 5.18 (1H, d, J = 3.5 Hz), 4.05 (2H, q, J
13
7.5 Hz), 2.21 (3H, s), 1.13 (3H, t, J = 7.2 Hz); C NMR
(
500 MHz, DMSO-d ) δ 164.9, 155.9, 152.3, 149.2, 142.0,
2
100 DV Inductive Coupled Plasma Atomic Emission Spectro-
6
1
13
1
3
10.2, 105.2, 96.7, 59.1, 47.6, 17.6, 14.0. IR (KBr): 3413, 3239,
scope (ICP-AES). H and C NMR experiments were carried
out on a Bruker DPX-300 NMR spectrometer.
119, 2984, 1702, 1644, 1457 cm− . Solid, mp 202–204 °C.
1
5
-Ethoxycarbonyl-4-(3-bromophenyl)-6-methyl-3,4-dihydro-
1
1
13
pyridin-2(1H)-one (Table 2, entry 7). H NMR (300 MHz,
H and C NMR chemical shifts (see ESI†) for different
condensation products reported in Table 2
DMSO-d ) δ 9.25 (1H, s), 7.77 (1H, s), 7.45 (2H, t, J = 9 Hz),
6
7
.32 (2H, m), 5.13 (1H, d, J = 3 Hz), 4.00 (2H, q, J = 6 Hz),
13
5
-Ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyridin-2
2.46 (3H, s), 1.11 (3H, t, J = 9 Hz); C NMR (300 MHz,
1
(
1H)-one (Table 2, entry 1). H NMR (300 MHz, DMSO-d ) δ
DMSO-d ) δ 165.1, 151.9, 148.9, 147.4, 130.7, 130.1, 129.1,
6
6
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Fig. 1 Small angle powder XRD pattern of vinyl functionalized (a),
Fig. 2 Wide angle powder XRD pattern of the Fe
functionalized mesoporous SBA-15. Different planes are indexed.
3
O
4
nanoparticle
3 4
cysteine hydrochloride functionalized (b) and Fe O nanoparticle func-
tionalized mesoporous SBA-15 (c).
1
3
1
25.2, 121.5, 98.6, 59.2, 53.6, 17.8, 14.0. IR (KBr): 3416, 3228,
113, 2976, 2932, 1705, 1654, 1613, 1589 cm . Solid, mp
85–186 °C.
characteristic diffraction peaks in the 2θ region of 0.9 to 2.0 and
these can be attributed to the 100 (strong), 110 (weak) and 200
−1
(
weak) reflections respectively, corresponding to the 2D hexago-
24
nal mesostructure. When the cysteine hydrochloride functiona-
lized SBA-15 (Fig. 1b) is treated with the Fe O nanoparticles
5
-Ethoxycarbonyl-4-(4-methylphenyl)-6-methyl-3,4-dihydro-
1
3
4
pyridin-2(1H)-one (Table 2, entry 8). H NMR (300 MHz,
then a considerable decrease in the intensities of the peaks is
observed (Fig. 1c); however the 2D-hexagonal ordering is
retained. This decrease in the peak intensities is attributed to the
lowering of local order, viz. variations in the wall thickness or
reduction of scattering contrast between the channel wall of the
silicate framework or due to the presence of some adsorbed
Fe O species within the channel structure. The wide angle XRD
DMSO-d ) δ 9.14 (1H, s), 7.67 (1H, s), 7.01 (4H, m), 5.10 (1H,
6
d, J = 3 Hz), 4.00 (2H, q, J = 6 Hz), 2.24 (3H, s), 2.23 (3H, s),
1
3
1
1
5
.11 (3H, t, J = 6 Hz); C NMR (300 MHz, DMSO-d ) δ
6
65.3, 152.2, 148.1, 141.9, 136.3, 128.8, 126.1, 99.4, 59.1,
3.6, 20.6, 17.7, 14.1. IR (KBr): 3165, 1688, 1633 cm . Solid,
−1
mp 215–217 °C.
3
4
5
-Ethoxycarbonyl-4-(2-methoxyphenyl)-6-methyl-3,4-dihydro-
pattern of the magnetic Fe O nanoparticle immobilized
3 4
1
pyridin-2(1H)-one (Table 2, entry 10). H NMR (300 MHz,
DMSO-d ) δ 9.08 (1H, s), 7.24–7.18 (2H, t, J = 9 Hz),
.05–6.95 (2H, dd, J = 9 Hz), 6.95–6.83 (1H, t, J = 9 Hz), 5.48
SBA-15 material is shown in Fig. 2. This XRD pattern has been
indexed and it clearly suggests that the face centered cubic lattice
(fcc) (JCPDS card No. 19-0629) (Fig. 2) type arrangement is
6
7
(
1H, d, J = 3 Hz), 3.93 (2H, q, J = 6 Hz), 3.77 (3H, s), 2.26 (3H,
present in the iron oxide nanocrystallites in Fe O @SBA-15.
3 4
1
3
s), 1.03 (3H, t, J = 6 Hz); C NMR (300 MHz, DMSO-d ) δ
Other characteristic peaks that can be generated due to presence
of impurities like hematite or hydroxide are absent in the wide
angle X-ray powder diffraction pattern. The wide angle XRD
6
1
9
1
65.3, 156.5, 152.1, 148.8, 131.6, 128.6, 127.0, 120.1, 111.1,
7.6, 58.9, 48.8, 17.6. IR (KBr): 3415, 3241, 3114, 2954, 1708,
−1
646, 1512 cm . Solid, mp 254–256 °C.
pattern of the Fe
O @SBA-15 nanocatalyst (Fig. 2) is analogous
3 4
with the XRD patterns of pure Fe O (JCPDS value), which
3
4
5
-Ethoxycarbonyl-6-methyl-4-styryl-3,4-dihydropyrimidin-2
indicates that the crystal structure of Fe O is retained during the
3
4
1
25
(
9
(
1H)-one (Table 2, entry 11). H NMR (500 MHz, DMSO-d ) δ
6
course of the reaction.
The N2 adsorption–desorption
Fe O @SBA-15 nanocatalyst at 77 K is shown in Fig. 3. The
.1 (1H, s), 7.54 (1H, s), 7.48–7.47 (2H, d, J = 5 Hz) 7.36–7.29
3H, m), 6.37 (1H, d, J = 15 Hz), 6.21 (1H, dd, J = 6 Hz, 16
Hz), 4.73 (1H, d, J = 3 Hz), 4.13 (2H, q, J = 6 Hz), 2.2 (3H, s),
.12 (3H, t, J = 5 Hz); C NMR (500 MHz, DMSO-d ) δ
65.1, 152.5, 148.4, 136.2, 129.9, 128.6, 128.0, 127.5, 126.2,
isotherm
of
the
3
4
sample shows a typical type IV isotherm with a very large hys-
1
3
1
1
9
6
teresis loop in the 0.5 to 0.8 P/P range. The isotherm accounts
0
for the relatively ordered mesopore and the hysteresis loop,
26
7.7, 59.1, 51.8, 17.7, 14.2. Solid, mp 225–227 °C.
which is characteristic for the large tubular pores of SBA-15.
The BET surface area for the pure SBA-15 and Fe O @SBA-15
3
4
2
−1
2
−1
nanocomposite are 610 m g and 291 m g respectively. A
considerable decrease in the BET surface area upon grafting of
Results and discussion
The small angle X-ray powder diffraction patterns for the meso-
porous vinyl functionalized (A), cysteine hydrochloride functio-
nalized (B) and Fe O nanoparticle conjugated SBA-15 (C) are
shown in Fig. 1. The vinyl functionalized (Fig. 1a) and cysteine
hydrochloride functionalized SBA-15 (Fig. 1b) show three
Fe
SBA-15 material (B) clearly suggests that the Fe
cles have been anchored on the inner surface of the mesopores
and some pore mouths have been partially blocked by the Fe
crystallites. The pore size distribution of the Fe @SBA-15
3
O
4
nanocrystallites at the surface of the functionalized
O
3 4
nanoparti-
3
4
O
3 4
O
3 4
6176 | Dalton Trans., 2012, 41, 6173–6181
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Fig. 3
2 3 4
N adsorption–desorption isotherm of the Fe O nanoparticle
functionalized mesoporous SBA-15 material. The pore size distribution
estimated through the NLDFT method is shown in the inset.
nanocomposite sample calculated by employing the non-local
density functional theory (NLDFT) method shown in the inset of
Fig. 3 suggests a uniform distribution of large mesopores
throughout the sample with pore dimensions of ca. 6.2 nm. The
3
−1
calculated pore volume (0.374 cm g ) and pore size of ca.
.2 nm for the Fe O @SBA-15 nanocomposite is sufficient to
6
3
4
carry out liquid phase catalytic reactions.
Electron microscope images of the Fe O @SBA-15 nanocom-
3
4
posite are shown in Fig. 4. An FE SEM image of the Fe O @
3
4
mesoporous SBA-15 catalyst is shown in Fig. 4a. As seen from
the figure, the nanocatalyst is composed of tiny spherical nano-
particles of dimension ca. 40 nm and the particles are uniformly
distributed throughout the specimen. On the other hand the HR
TEM image shown in Fig. 4b suggests the uniform ordered
arrangement of pores having dimension ca. 6–7 nm throughout
the sample and these are arranged in a honey-comb like hexago-
nal array as confirmed by the FFT pattern shown in the inset of
Fig. 4b. Further, in this TEM image, black spots are uniformly
distributed throughout the sample and this can be attributed to
the presence of superparamagnetic Fe O nanoparticles on the
Fig. 4 FE SEM image of the Fe
porous SBA-15 (a). HR TEM images of Fe O nanoparticle functiona-
3 4
lized mesoporous SBA-15 material (b) (FFT pattern is shown in the
inset) and respective selected area electron diffraction pattern (c).
3
O
4
nanoparticle functionalized meso-
3
4
mesopores. The crystal planes corresponding to crystalline
Fe O have been calculated from the SAED (Selected Area Elec-
3
4
tron Diffraction) pattern of the material and are depicted in
Fig. 4c. The grafting of Fe O nanoparticles at the surface of
3
4
SBA-15 and its large surface area could be utilized in liquid
phase reactions as active functional groups at the surface of func-
tionalized mesoporous materials have previously shown good
2
7
catalytic activity for different condensation reactions.
Fe O @SBA-15 nanocomposite formation via the thiol–ene
3
4
click reaction between cysteine hydrochloride functionalized
SBA-15 and Fe O was established from the FT IR spectroscopy
3
4
results (Fig. 5). The absorption bands for vinyl functionalized
SBA-15 (Fig. 5a) at 1643 cm−1 and 3069 cm could be
assigned to the CvC stretching vibration and antisymmetric
vCH2 vibration mode of the vinyl group. For the cysteine
hydrochloride functionalized SBA-15 (Fig. 5b) no band was
−1
Fig. 5 FT IR spectra of the of vinyl functionalized (a), cysteine hydro-
3 4
chloride functionalized (b) and Fe O nanoparticle functionalized meso-
−1
observed at 2080 cm , which is the stretching frequency of the
porous SBA-15 (c).
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magnetic nanocatalyst can be recycled seven times and magnetic
separation was easily achieved by using a simple bar magnet.
The difference in the catalytic activity between the simple and
supported catalytic materials might be explained on the basis of
the highly dispersed Fe O on porous materials, and also the
3
4
acidity on the surface of the materials plays a key role in the acti-
vation of urea and ethyl acetoacetate for the synthesis of 3,4-
dihydropyridin-2(1H)-one derivatives.
3 4
Scheme 2 Biginelli reaction catalyzed by Fe O @functionalized
mesoporous SBA-15.
The catalytic activity of Fe O @SBA-15 was investigated in a
3
4
one pot Biginelli condensation for the synthesis of 3,4-dihydro-
pyrimidin-2(1H)-ones for various aromatic aldehydes containing
electron donating and withdrawing groups. The aldehydes with
electron donating (Table 2, entries 3 and 8) and electron with-
drawing (Table 2, entries 2, 4, 5, 7) groups participated in the
condensation reaction uniformly. The nature and the position of
substitution in the aromatic ring did not have much effect on the
reaction. The meta-substituted aromatic aldehyde undergoes the
condensation reaction (Table 2, entry 7) without any difficulty.
The sterically hindered ortho-substituted aromatic aldehyde
(Table 2, entry 10) underwent the condensation reaction without
any difficulty. Several sensitive functional groups such as –Cl,
Table 1 Screening of iron catalysts for the formation aof 5-
ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihydropyridin-2(1H)-one
b
Entry
Catalyst
Time (h)
Yield (%)
1
2
3
4
5
6
FeCl
FeCl
Fe powder
Nano-Fe
SBA-15
Cys-SBA-15
3
·6H
·4H
2
O
O
5
5
6
6
15
10
37.5
30.0
35.0
50.0
0.0
2
2
3
O
4
0.0
a
b
Benzaldehyde–ethyl acetoacetate–urea = 1 : 1 : 1.5. Yields refer to
–
Br, –NO attached to the aromatic ring are compatible with this
2
isolated product.
reaction procedure. The unsaturated aldehyde (Table 2, entry 11)
also takes part in the reaction very smoothly. The yields of the
products are shown in Table 2. The catalytic activity of
Fe O @SBA-15 was studied both at high temperature (363 K)
S–H bond for cysteine hydrochloride. Thus this result suggests
that the thiol–ene click reaction occurs between the S–H group
of cysteine hydrochloride and the vinyl functionalized SBA-15.
3
4
28
as well as at room temperature (298 K, Table 2, entry 9). As seen
from the table, Fe O @SBA-15 is highly efficient in catalyzing
3
4
Further, bands due to CvC and vCH of the vinyl group have
2
this three-component coupling reaction at elevated temperature
and for different aldehydes it takes only 5–7 h for the completion
of reactions. The turn over frequencies (TOFs) for all the alde-
disappeared in the cysteine hydrochloride functionalized
SBA-15 (B). This result indicates that the vinyl group has been
converted into a –CH –S– group by the thiol–ene click reaction
−1
2
hydes are very high (ca. 136–200 h ). When the reaction was
with cysteine hydrochloride. On the other hand, an additional
carried out in the absence of the catalyst no conversion was
observed. Thus, the one pot three-component condensation reac-
tion was consistent irrespective of the nature of the substituents
−
1
band observed at 578 cm in the Fe O @SBA-15 nanocompo-
3
4
29
site (Fig. 5c) could be attributed to the Fe–O spinel structure.
(electron withdrawing and electron donating) present in the aro-
matic ring when this reaction was catalyzed by the Fe O @
SBA-15 mesoporous nanocatalyst.
3
4
Catalysis
The Biginelli condensation reaction over the Fe O @mesopor-
3
4
ous SBA-15 nanocatalyst (C) is shown in Scheme 2. We have
screened a wide range of iron catalysts known in the literature
Reusability of the catalyst
(Table 1) and found that the yields of 5-ethoxycarbonyl-4-
phenyl-6-methyl-3,4-dihydropyridin-2(1H)-one ranged from ca.
Magnetic separation is a more attractive and simple technique
than the filtration or centrifugation techniques as it prevents the
loss of the catalyst and increases the reusability of the catalyst.
Separation of the Fe O @SBA-15 nanocatalyst from the reaction
3
0
3
0%–50%. When FeCl ·6H O was used as a catalyst the Bigi-
3 2
nelli condensation products were obtained in low yields. Also in
some cases the products could not be isolated and the catalyst
could not be reused for further cycles. When we used
FeCl ·4H O as a catalyst (Table 1) the yield becomes still lower
3
4
mixture becomes very easy owing to the superparamagnetic
nature of Fe O nanoparticles at room temperature. In the mag-
2
2
3 4
with no reusability of the catalyst. When pure SBA-15 and cys-
SBA-15 (Table 1) were used as catalysts no reaction was
observed. However, when the reaction was conducted in the
presence of nano-Fe O catalyst the yield of the condensation
netic separation technique the catalyst became adsorbed onto the
31
magnetic stirring bar when the stirring was stopped. Then the
catalyst was washed with ethyl acetate, oven dried (temperature
and time) and then directly used for the next cycle reaction
without further purification. A recyclability test was performed
by taking the condensation reaction of benzaldehyde, ethyl
acetoacetate and urea as a representative case. We have plotted
the recycling efficiency of the catalyst for seven consecutive cat-
alytic cycles for the condensation reaction of benzaldehyde,
ethyl acetoacetate and urea (ESI, Fig. S1†). This result suggested
that our novel Fe O @SBA-15 nanocatalyst can be recycled
3
4
product was increased from 30% to 50%. However due to the
colloidal nature of the Fe O nanocatalyst it was reused for only
3
4
two cycles and separation becomes a very tedious job. It was
noted that when Fe O nanoparticles were impregnated into our
3
4
functionalized SBA-15 (having high surface area) the catalytic
activity of the nanocatalyst becomes much higher than that of
the corresponding nano-Fe O catalyst. Also in this case the
3
4
3 4
6178 | Dalton Trans., 2012, 41, 6173–6181
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Table 2 Biginelli condensation reaction catalyzed by Fe
3
O
4
@SBA-15
TOF (h−1)
a
Entry
1
Aldehyde
Product
Yield (%)
85
Time (h)
6
168.8
2
80
7
136.2
3
4
5
6
7
82
84
82
78
80
7
5
5
5
5
139.6
200.2
195.4
185.9
190.7
8
82
10
6
162.8
b
9
12
9.9
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Table 2 (Contd.)
Entry Aldehyde
TOF (h−1)
a
Product
Yield (%)
81
Time (h)
5
1
0
193.0
11
80
6
158.9
a
b
TOF = Turn over frequency = moles of substrate converted per mole of Fe per h. Reaction was carried out at 298 K.
seven times without significant loss of catalytic activity. Further,
after the seventh catalytic cycle the magnetic Fe O @SBA-15
3
4
nanocatalyst was characterized by powder XRD and IR studies.
The small angle powder XRD pattern of the reused catalyst
(ESI, Fig. S2†) suggested that the mesophase of the catalyst was
retained, whereas the characteristic peaks of Fe O4 were
3
observed in the wide angle powder XRD pattern (ESI, Fig. S3†).
−1
Moreover, the peak at 580 cm in the FT IR spectrum (ESI,
Fig. S4†) clearly suggested that the Fe–O spinel structure was
retained in the reused magnetic nanocatalyst. This result indi-
cates the very high chemical stability of our Fe O @SBA-15
3
4
nanocatalyst and thus it is suitable for many catalytic cycles.
Hot filtration test
A hot filtration test was performed in order to confirm that the
catalytic activity was generated from the conjugated Fe O nano-
3
4
particles on the mesoporous SBA-15 matrix and not from
leached Fe O in the reaction mixture. In this technique the con-
3
4
densation reaction of benzaldehyde, ethylacetoacetate and urea
was carried out at 363 K for 3 h in the presence of the
Fe O @SBA-15 magnetic nanocatalyst. At this stage the yield
3
4
of the product was 67%. The catalyst was then filtered off under
hot conditions and with the filtrate, which was obtained after
separation of the catalyst after 3 h, the reaction was continued for
another 3 h at the same reaction temperature. But no correspond-
ing increase of product yield beyond 67% was observed. Further,
the Fe content in the Fe O @SBA-15 material before the cataly-
3
4
−
1
tic run was 0.839 mg l . After the seventh reaction cycle the Fe
content was marginally decreased to 0.807 mg l−1 (this decrease
is within the experimental error of chemical analysis). This result
confirms the heterogeneous nature of the magnetic nanocatalyst
Fig. 6 Catalytic cycle for the Biginelli condensation reaction.
outlined in Fig. 6. The electrophilicity of the carbonyl carbon
atom of both aldehyde and active methylene compound (here
ethyl acetoacetate) increases due to coordination with the highly
porous Fe O nanoparticles grafted at the surface of the functio-
in this Biginelli condensation reaction and no leaching of Fe O4
3
occurs during the course of the reaction.
3
4
nalized SBA-15. Then the aromatic aldehyde and ethyl acetoace-
tate undergo aldol type condensation to offer the corresponding
aldol-type product. Further, electron deficient sites present at the
Proposed catalytic mechanism
The possible reaction pathway for the Biginelli three-component
condensation mediated by Fe O @mesoporous SBA-15 is
surface of the Fe
O nanoparticle grafted functionalized SBA-15
3 4
3
4
6180 | Dalton Trans., 2012, 41, 6173–6181
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could coordinate with the N-donor sites of urea molecules and
thus stabilize/activate it for the 1,4-addition reaction of urea.
This leads to the aldol type intermediate (X) to generate ureides
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(
Y) that ultimately cyclize to Biginelli products (Z) with the
3
2
elimination of a water molecule. Here the role of the magnetic
1
nanoparticles is firstly easy magnetic recovery and separation.
Further, the surface Fe-sites in the Fe O grafted nanocatalyst
3
4
could stabilize the urea molecules by adsorbing at its surface,
which facilitates the reaction, and the high surface area of the
supporting mesoporous host is necessary for the high turn-over
frequency of the reaction.
1
1
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2
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recoverable heterogeneous catalyst for the one-pot Biginelli con-
densation for the synthesis of different value added 3,4-dihydro-
pyrimidin-2(1H)-ones. The magnetic nature of this
heterogeneous nanocatalyst allows for its easy separation from
the reaction mixture by using a simple bar magnet. Good cataly-
tic activity and recycling efficiency in this condensation reaction
advocate the potential application of this Fe O nanoparticle
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1
1
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3
4
010, 3943–3953.
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synthesis of organic target molecules involving pyrimidine
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6
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JM thanks CSIR, New Delhi for his respective senior research
fellowship. AB wishes to thank DST, New Delhi for an extra-
mural project grant.
2
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