Highly efficient and magnetically recoverable niobium nanocatalyst for the multicomponent biginelli reaction

Article abstract of DOI:10.1002/cctc.201402689

A new magnetically recoverable nanocatalyst was prepared by coating magnetite with niobium oxide (Fe₃O₄@Nb₂O₅) by using a simple wet impregnation method. The Fe₃O₄@Nb₂O₅

Full text of DOI:10.1002/cctc.201402689

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DOI: 10.1002/cctc.201402689
Highly Efficient and Magnetically Recoverable Niobium
Nanocatalyst for the Multicomponent Biginelli Reaction
Carolina G. S. Lima, Sandrina Silva, Ricardo H. GonÅalves, Edson R. Leite, Ricardo S. Schwab,
Arlene G. CorrÞa, and Mꢀrcio W. Paix¼o*[a]
A new magnetically recoverable nanocatalyst was prepared by
coating magnetite with niobium oxide (Fe3O4@Nb2O5) by using
a simple wet impregnation method. The Fe3O4@Nb2O5 nano-
catalyst was fully characterized, and its catalytic activity was
evaluated by using the one-pot, three-component Biginelli re-
action, with the aim to synthesize 1,4-dihydropyrimidinones,
a class of compounds with diverse pharmacological properties.
The developed protocol was applied to a wide range of ali-
phatic and aromatic substrates, and structurally diverse prod-
ucts were obtained in excellent yields. Compared with copper
and nickel nanocatalysts, the Fe3O4@Nb2O5 nanocatalyst dem-
onstrated superior catalytic activity at a remarkably low cata-
lyst loading (0.1 mol%). This niobium nanocatalyst could be
easily separated from the reaction mixture with an external
magnet and was reused several times without any loss of its
catalytic activity. Moreover, although the Biginelli reaction is
a century-old reaction, its mechanism is still a controversial
subject, and our investigation provided an insight into the re-
action mechanism.
Introduction
Catalysis is one of the most important fields in organic synthe-
sis and has been receiving considerable attention from both
academia and industry.[1] In this field, transition-metal com-
pounds are a significant class of catalysts because they are
widely used in some of the most important transformations in
organic synthesis,[2] such as CÀC bond formation, oxidation re-
actions, and reduction reactions.[3] Thus, various homogeneous
catalysts were developed in the last decade and used as tools
in the most diverse types of organic transformations.[4] Howev-
er, despite their numerous advantages, homogeneous catalysts
suffer the drawback of difficult separation from the reaction
medium on completion of the reaction.[5]
For designing and synthesizing different nanocatalysts for
specific applications, many solid supports have been used, for
example, silica,[9] carbon,[10] alumina,[11] and polymers.[12] Among
these supports, magnetic nanoparticles such as magnetite
(Fe3O4) and maghemite (g-Fe2O3) are considered as ideal sup-
ports for the immobilization of catalytic materials because they
are inexpensive, chemically stable, and easy to prepare and
can be recovered by applying an external magnetic field.[13]
Several transition metals, such as palladium,[14] nickel,[15]
cobalt,[16] copper,[17] cerium,[18] molybdenum,[19] ruthenium,[20]
and rhodium,[21] have been immobilized on a magnetic matrix.
Notwithstanding the advances in this field, there are still
a range of opportunities for the design, synthesis, and applica-
tion of improved magnetically recoverable nanocatalysts.
Until recently, niobium compounds have been known for
their advantageous features as a support for catalysts in
a wide range of reactions, mostly in catalytic oxidation reac-
tions.[22] Even though there are a few differences in physico-
chemical properties of niobium and those of its neighbors in
the periodic table (vanadium, molybdenum, and zirconium),
the catalytic behavior and high acidity of niobium compounds
are different from those demonstrated by compounds of the
neighboring elements. Niobium catalysts demonstrate high
acidity on their surface, demonstrating high activity and selec-
tivity, even in the presence of water in the reaction medium.[23]
Because of its exceptional chemical properties, niobium is
an inexpensive metal that is abundant in Earth’s crust.
The difficulty in catalyst separation has led to the develop-
ment of new heterogeneous catalysts for organic transforma-
tions, and supported-heterogeneous catalysts, also called
“semi-heterogeneous” or “quasi-homogeneous” catalysts, have
been used as excellent tools for improving and developing en-
vironmentally benign protocols.[6] Several advantages of sup-
porting catalysts on nanosized materials have been observed,
such as a substantial increase in the surface area of the catalyst
promotes its contact with the reactants, which is consistent
with homogeneous catalysis,[7] along with the additional fea-
ture of the catalyst recovery, which makes the process eco-
friendly and less expensive.[8]
[a] C. G. S. Lima, Dr. S. Silva, R. H. GonÅalves, Prof. Dr. E. R. Leite,
Prof. Dr. R. S. Schwab, Prof. Dr. A. G. CorrÞa, Prof. Dr. M. W. Paix¼o
Department of Chemistry
Considering all these facts and the low application of niobi-
um compounds in organic synthesis,[24] a wide window is now
open for the exploitation of niobium species as catalysts in
acid-demanding chemical processes, such as multicomponent
reactions.
Federal University of S¼o Carlos
S¼o Carlos, S¼o Paulo 13565-905 (Brazil)
E-mail: mwpaixao@ufscar.br
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201402689.
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Scheme 1. Biginelli reaction. R1 =H, alkyl; R2 =OÀalkyl; R3 =H, alkyl, aryl, het-
eroaryl; X=O, S, NR.
In this context, the Biginelli reaction[25] (Scheme 1), a centu-
ry-old reaction, is one of the most well-designed methodolo-
gies used for the synthesis of dihydropyrimidinone (DHPM) or
thione derivatives, an important family of compounds known
for their diverse pharmacological properties, which act as anti-
bacterial, antiviral, and calcium channel modulators as well as
anticancer and antihypertensive agents.[26–32] The reported bio-
logical activities of DHPMs encourage research groups to build
structurally diverse libraries of bioactive compounds that are
active even as racemates.[33,34]
Scheme 2. Synthesis of the niobium nanocatalyst.
TEM (STEM), and temperature-programmed desorption of am-
monia.
The HRTEM images of the nanocatalyst (Figure 1) show that
the particles exhibited an equiaxed morphology and are within
the nanosize range (15–40 nm), with some tendency to cluster-
ing. Moreover, a layer around a small cluster of nanoparticles
can be seen in Figure 1b.
Because DHPM derivatives are widely used, many ap-
proaches for their synthesis can be found in the literature.[35]
Nevertheless, most protocols have severe limitations, for exam-
ple, low yields, high cost and catalyst loadings, and low cata-
lyst recovery and recyclability.
Furthermore, questions about the efficacy of solvent-free
and/or catalyst-free reactions and the effect of heating versus
microwave irradiation still lead to discussions in the scientific
community. To overcome these drawbacks, which have thrown
us toward the search of new, better, and benign conditions for
the Biginelli reaction, we present herein the synthesis, charac-
terization, and application of an efficient, eco-friendly, and
highly recoverable nanocatalyst comprising niobium oxide
supported on magnetite (Fe3O4@Nb2O5).
The catalytic activity of this new magnetically recoverable
niobium nanocatalyst was evaluated for the synthesis of
a wide range of DHPM derivatives with high structural diversity
through the Biginelli reaction. A comparison of the efficiency
of this new nanocatalyst with that of other known transition-
metal nanocatalysts has revealed interesting and promising re-
sults.
Figure 1. a) TEM image, b) HRTEM image, and c) particle size distribution
analysis of the niobium nanocatalyst.
Results and Discussion
Nanocatalyst characterization
To comprehend the formation of this layer around the nano-
particles and to evaluate the incorporation of Nb2O5 into the
Fe3O4 nanoparticle surface, STEM analysis was performed. The
results are depicted in Figure 2, part a of which shows the de-
tails of the bright-field STEM image and the line along which
the energy-dispersive X-ray spectroscopy (EDS) line profiles of
the niobium nanocatalyst (part b) were recorded.
The Fe3O4 nanoparticles used as a solid support for the catalyst
were prepared through coprecipitation by using urea as the
pH-controlling agent. The Fe3O4@Nb2O5 nanocatalyst was syn-
thesized by using a simple wet impregnation method with am-
monium niobate oxalate hydrate (C4H4NNbO9·3H2O) as the
niobium source (Scheme 2). The hydrolysis of the niobium pre-
cursor in alkaline medium leads to the aggregation of niobium
hydroxides over the surface of Fe3O4 nanoparticles, which un-
dergo condensation to eliminate water and form the Nb2O5
layer.
The EDS line profile (Figure 2b) shows the niobium and iron
compositions along the line shown in Figure 2a. Notably, the
niobium composition is constant along the entire line. The iron
composition is higher in the center of the nanoparticle cluster
and lower at the edges: at the left edge of the sample (from 0
to 15 nm), the iron composition is constant and almost zero,
whereas in the center (from 16 to 125 nm), the iron composi-
Both the support and the final nanocatalyst were fully char-
acterized by using XRD, inductively coupled plasma optical
emission spectroscopy, high-resolution TEM (HRTEM), scanning
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The temperature-programmed desorption of ammonia was
performed to study the effect of the Nb2O5·nH2O shell, also
known as niobic acid, on the acidity of the nanocatalyst. The
results reveal that the acidity of the nanocatalyst is at least
13 times higher than that observed with Fe3O4 nanoparticles
(see details in the Supporting Information).
To evaluate the effect of the Nb2O5 shell on the magnetic
properties of this material, measurements were performed on
a superconducting quantum interference device. The magneti-
zation curves of both the Fe3O4 sample and the niobium nano-
catalyst is shown in Figure 4. The saturation magnetization of
the Fe3O4 sample was 82 emugÀ1 and of the niobium nanoca-
talyst 70 emugÀ1, which indicates that the functionalization of
Fe3O4 with niobium species did not affect its magnetic behav-
ior considerably.
Figure 2. a) Bright-field STEM image showing the amorphous Nb2O5 on the
Fe3O4 surface, and b) EDS line profile. Scale bar=20 nm.
tion is considerably higher; at the right edge of the sample
(from 126 to 140 nm), the iron composition is again zero.
These results suggest that Nb2O5 completely coats the nano-
particle cluster and forms a 15 nm thick layer around it. The
EDS results are fairly interesting because the formation of
a layer around the Fe3O4 support eliminates any possibility of
iron oxides participating in catalytic reactions. The EDS ele-
mental maps were also acquired at low magnification to con-
firm the homogeneity of Nb2O5 on the Fe3O4 surface (Figure 3).
Figure 4. Magnetization curves of Fe3O4 and the niobium nanocatalyst. Inset:
Catalyst separated from reaction medium by a magnet.
Evaluation of the catalytic activity of the niobium nanocata-
lyst in the DHPM synthesis
The catalytic activity of the niobium nanocatalyst was evaluat-
ed in the synthesis of DHPMs through the Biginelli reaction.
Thus, the multicomponent reaction between benzaldehyde,
ethyl acetoacetate, and urea was chosen as the model reaction
to search for optimal conditions. Bearing this in mind, different
benign solvents and catalysts as well as catalyst loadings were
studied (Table 1).
Figure 3. EDS elemental maps of Fe3O4@Nb2O5: a) bright-field STEM image,
b) dark-field STEM image, c) Fe map, d) Nb map, and e) Fe+Nb map. Scale
bars=500 nm.
These maps also revealed that the surface of the nanocatalyst
is rich in niobium, and the combined results of electron mi-
croscopy suggested that the nanocatalyst forms a well-defined
layer around Fe3O4, which forms a core–shell structure.
The search for optimal conditions for the Biginelli reaction
using the newly developed niobium nanocatalyst started by
studying the catalyst loading. To understand how this parame-
ter affected the reaction, three reactions were performed with
ethanol as the solvent at 808C (Table 1, entries 1–3). The yields
of these three reactions indicated that the catalyst loading has
a significant effect on the reaction result, and with use of
a high catalyst loading (10 mol%; entry 1), no product forma-
tion was observed, whereas small loadings (1 and 0.1 mol%;
entries 2 and 3) afforded products in excellent yields. No prod-
uct was formed with the high catalyst loading perhaps be-
cause of the high acidity of niobium, which may have interact-
ed with urea, preventing it from reacting as required. This hy-
The powder XRD measurements confirmed the Fe3O4 crystal-
lographic phase and the average size of the crystallites, esti-
mated by the Debye–Scherrer equation, was 17 nm (Figure S1).
The powder XRD patterns of Fe3O4@Nb2O5 showed only the
characteristic diffraction peaks of Fe3O4 (as expected) because
of the amorphous character of Nb2O5·nH2O.[36] The exact
amount of niobium in the nanocatalyst was determined from
inductively coupled plasma optical emission spectroscopy anal-
ysis, and it was found to be 6.5 wt%.
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with bulk Nb2O5 (entry 8) gave a lower yield. These results
confirm that the catalytic activity derives from the highly acidic
niobium species present on the nanocatalyst surface as well as
that it is increased significantly by the increase in the surface
area of the catalyst, which is a result of supporting the active
phase in a nanosized material. After obtaining the optimal re-
action conditions, we focused on comprehending how other
analogous magnetically recoverable transition-metal catalysts
affect the reaction. To accomplish this, the efficiency of the
niobium nanocatalyst was compared with that of the already
known copper and nickel nanocatalysts under optimal reaction
conditions. Our results (Figure 5) indicate that both the nature
Table 1. Optimization of the reaction conditions for the synthesis of
DHPMs through the Biginelli reaction.
Entry[a] Catalyst
Catalyst loading [mol%] Solvent
ethanol
Yield[b] [%]
1
2
3
4
5
6
7
8
Fe3O4@Nb2O5 10
0
99
99
20
Fe3O4@Nb2O5
Fe3O4@Nb2O5
Fe3O4@Nb2O5
Fe3O4@Nb2O5
Fe3O4@Nb2O5
Fe3O4@Nb2O5
Nb2O5
1
ethanol
ethanol
water
0.1
0.1
0.1
0.1
0.1
0.1
0.6[d]
–
glycerol 52
PEG 400 39
–
98[c]
24
60
54
ethanol
ethanol
ethanol
9
Fe3O4
10
–
[a] Unless otherwise specified, all the reactions were performed with
benzaldehyde (1.0 mmol), ethyl acetoacetate (1.0 mmol), urea (1.5 mmol),
and catalyst (0.1 mol%) in the presence of ethanol (500 mL) in a closed
vial at 808C for 12 h; [b] Isolated yields; [c] Solvent-free reaction per-
formed with a benzaldehyde/ethyl acetoacetate/urea molar ratio of 1:2:2
at 808C for 2 h; [d] 1.6 mg Fe3O4 (equal to the amount used as support
for 0.1 mol% loadings of niobium nanocatalyst).
Figure 5. Evaluation of the catalyst effect on the Biginelli reaction.
pothesis was not thoroughly studied; however, the isolation of
the Knoevenagel intermediate as the single product of the re-
actions performed with high catalyst loadings strongly sug-
gests that niobium withdraws the urea component from the
reaction. Moving forward to the investigation of the effect of
the solvent on this catalytic system, five reactions were per-
formed with 0.1 mol% of the niobium nanocatalyst loading in
the presence of eco-friendly solvents, such as water, glycerol,
polyethylene glycol 400 (PEG 400), and ethanol (entries 3–6),
or in the absence of a solvent (entry 7). The best solvent for
this reaction protocol proved to be ethanol (entry 3), in which
the desired product was isolated in 99% yield. The reaction
performed in water afforded a low yield (entry 4), which could
be due to the low solubility of chemicals in this polar solvent,
whereas similar complications were observed for glycerol
(entry 5). With PEG 400 as the solvent, the separation of the
desired DHPMs from the reaction medium was compromised,
which caused the yield to decrease to 39% (entry 6).
and the loading of the nanocatalyst have a significant effect
on the yields of the Biginelli product. As shown in Figure 5, if
the three nanocatalysts were evaluated at a 10 mol% loading,
the niobium nanocatalyst afforded no product because the
Knoevenagel intermediate was the only isolated product (93%
yield) whereas copper and nickel nanocatalysts produced
DHPMs in high yields (99% for both).
With the decrease in the catalyst loading to 1 mol%, all
three nanocatalysts afforded good yields: 99% for both copper
and niobium nanocatalysts and 95% for nickel. At a nanocata-
lyst loading of 0.1 mol%, full conversion was achieved only
with the niobium nanocatalyst, whereas the nickel and copper
nanocatalysts demonstrated a diminished performance and af-
forded the product in only 70 and 72% yields, respectively. To
study the effect of microwave irradiation on this catalytic
system, four experiments were performed at 80 and 1208C
either with ethanol as a solvent or without any solvent. The re-
sults of these experiments (Scheme 3) indicated that micro-
wave irradiation does not have a pronounced effect on the re-
action performance in the presence of a solvent, which is in ac-
cordance with previous studies by Kappe and co-workers.[38]
As depicted in Scheme 3, the reaction performed in the
presence of ethanol at 808C afforded an 80% yield after 2 h
and the Knoevenagel adduct was isolated as a byproduct.
Even after longer reaction times (4 h) under the same condi-
tions, the reaction could not be completed, and the isolated
yield of DHPM 4 was slightly higher (86%). If the temperature
was increased to 1208C, the Knoevenagel adduct 5 was com-
pletely consumed after 30 min; however, a byproduct, 1,4-di-
hydropyridine (DHP; 5, also known as the Hantzsch ester), was
observed; the DHP product is formed through the condensa-
tion of benzaldehyde, 2 equiv. of the b-ketoester, and ammo-
In the absence of a solvent (entry 7), the reaction afforded
the Biginelli product in 98% yield after 2 h. However, if the sol-
vent-free approach was applied to the multicomponent reac-
tion using other substituted benzaldehydes, the reaction did
not proceed well, probably owing to the physical state and
low solubility of the aldehydes in other components of the re-
action. The limitations of the solvent-free Biginelli reaction
have already been revealed by other research groups.[37]
To examine the significance of supporting the catalyst on
Fe3O4 nanoparticles, we performed the reaction with bulk
Nb2O5 as a catalyst (entry 8), with bare Fe3O4 nanoparticles
(entry 9), and without any nanocatalyst (entry 10). Under opti-
mal reaction conditions, the reactions performed without any
catalyst (entry 10) and with bare Fe3O4 nanoparticles (entry 5)
gave similar moderate yields whereas the reaction performed
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ed in Figure 6, in the first run the
components were converted to
the desired product (>99% iso-
lated yield). In the subsequent
runs, the conversion to the
DHPM products was complete,
and the isolated yields began de-
creasing only after the seventh
run.
In addition to pointing out the
advantage of the use of low-
loading catalysts, the recyclability
studies of Fe3O4@Nb2O5 showed
that this catalyst could be reused
several times without any loss of
its catalytic activity.
The mechanism of the Biginelli
reaction is still a controversial
subject; however, it is already
known that the reaction that
leads to the formation of the
DHPM product can occur
Scheme 3. Evaluation of the Biginelli reaction under microwave irradiation.
nia, which is produced in situ by the decomposition of the
urea component, a common side reaction that occurs in the
presence of water at temperatures above 908C. Under these
reaction conditions, the DHP product was formed in 35% yield
whereas the DHPM product was formed in 55% yield. If the re-
action was performed in the absence of any solvent, the yield
at 808C was 10% more than the yield at 1208C, and in both
cases the Hantzsch ester was isolated as a byproduct.
After exploring all major aspects of the Biginelli reaction by
using the newly developed niobium nanocatalyst, we investi-
gated the scope of the reaction for the synthesis of DHPMs
(Scheme 4). Under optimal reaction conditions, the reaction
was performed at 808C with ethanol as an eco-friendly solvent
and a low nanocatalyst loading (0.1 mol%). The formation of
DHPM products was not affected by steric and electronic ef-
fects in the aryl moiety of the aldehydes, because both sub-
strates having one or more electron-donating or -withdrawing
groups led to the formation of products 4 and 6–17, with
yields in the range of 84–95%. With aliphatic aldehydes, prod-
ucts 18 and 19 were obtained, with yields decreasing from ex-
cellent to good (78 and 76%, respectively). Similarly, the
choice of urea or thiourea did not have a significant effect on
the yields, which were achieved in the range of 83–92% (prod-
ucts 20–25).
Figure 6. Evaluation of the recyclability of the niobium nanocatalyst.
through three different pathways[39] in which the process starts
by the formation of three possible intermediates: Knoevenagel,
iminium, or enamine (Scheme 5). To gain insight into the reac-
tion mechanism in the presence of the niobium nanocatalyst,
we performed an experiment under optimal reaction condi-
tions, in which the composition of the reaction medium was
monitored over time by injecting aliquots withdrawn from the
reaction medium at regular time intervals in GC–MS analysis
(Figure 7). As shown in Figure 7, the concentration of the initial
GC–MS injection (at t=30 min) was approximately 70% for the
Knoevenagel adduct and 30% for the Biginelli product. As the
reaction proceeded, the intermediate concentration decreased
quickly whereas the Biginelli product concentration increased.
This finding suggests that the reaction evaluated under opti-
mal reaction conditions occurs via the Knoevenagel intermedi-
ate mechanism.
After evaluating the scope of the Biginelli reaction by using
the new niobium catalytic system, we focused on the recycla-
bility of the nanocatalyst and scaling up of the reaction
(Figure 6).
On the basis of the experimental observations and the as-
sumption that the reaction occurs via the Knoevenagel inter-
mediate mechanism, we proposed a catalytic cycle (Scheme 6).
In the proposed reaction mechanism, the reaction starts with
the Knoevenagel condensation between the b-ketoester A and
the aldehyde B, forming the adduct C, which, after water elimi-
To accomplish that, the reactions were performed on
a 10 mmol scale under optimal reaction conditions. After the
completion of the reaction, the nanocatalyst was separated
from the reaction medium with a magnet, washed with etha-
nol, dried under vacuum, and reused several times. As depict-
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nation, gives a,b-conjugated
enone D. This intermediate is at-
tacked by an amino group of
a urea or thiourea molecule E,
which gives F.
An intramolecular attack of
the remaining amino group of
the urea moiety on the neigh-
boring carbonyl group forms the
six-membered
structure
G,
which regenerates the nanocata-
lyst. Finally, the elimination of
water gives the Biginelli product.
Conclusions
Herein, we have developed and
characterized a highly efficient
magnetically recoverable niobi-
um nanocatalyst from inexpen-
sive precursors magnetite and
ammonium niobate(V) oxalate
hydrate. This new niobium nano-
catalyst has great advantages
compared with nickel and
copper nanocatalysts, especially
in terms of the amount of the
catalyst required in the reaction.
If the niobium nanocatalyst is
used in the acid-demanding
multicomponent Biginelli reac-
tion, it proves to be quite effec-
tive and affords dihydropyrimidi-
none/thione products in good to
excellent yields with a low cata-
lyst loading (0.1 mol%) under
optimal reaction conditions.
Moreover, owing to its magnetic
behavior, the nanocatalyst can
be recovered easily and reused
Scheme 4. Scope of the reaction for the synthesis of DHPMs by Biginelli condensation.
several times without any loss of its catalytic activity. Robust-
ness, magnetically recoverable nature, and high efficiency are
the notable features of this nanocatalyst. Further investigation
of this nanocatalytic system in other acid-demanding organic
transformations is ongoing in our laboratory.
Experimental Section
General
1
The H and 13C NMR spectra were recorded on a Bruker ARX-400
spectrometer (400 and 100 MHz, respectively). All NMR spectra
were obtained with DMSO-d6. Column chromatography was per-
formed using Merck Silica Gel (230–400 mesh). Thin-layer chroma-
tography (TLC) was performed using Merck Silica Gel GF254, 0.25
mm thickness. For visualization, TLC plates were either placed
under UV light or stained with KMnO4 solution.
Figure 7. Evaluation of reaction medium composition monitored over time
by GC-MS.
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Scheme 5. Possible mechanisms for the Biginelli reaction.
Preparation of Fe3O4 nanoparticles
FeCl3·6H2O (5.4 g, 33 mmol) and urea (3.6 g, 60 mmol) were dis-
solved in water. The mixture was stirred at 908C for 2 h. After cool-
ing to RT, FeCl2·4H2O (2.0 g, 15 mmol) was added to the solution
and the pH was adjusted to 10 with NaOH solution (0.1 molLÀ1).
The obtained hydroxides were treated in an ultrasonic bath for
30 min. After aging for 12 h, the fine black powder (Fe3O4) was
washed several times with distilled water and separated with
a magnet. The washing process was repeated until the pH of the
suspension became neutral. The obtained solid was washed once
with ethanol and dried under vacuum.
Preparation of the nanocatalysts
General procedure: The nanocatalysts were prepared by using the
wet impregnation method, in which Fe3O4 (2 g) was dispersed in
water followed by the addition of the metal oxide precursor salt
(C4H4NNbO9·nH2O, CuCl2·2H2O, and Ni(NO3)2·2H2O for niobium,
copper, and nickel nanocatalyst, respectively, to obtain 10 wt%).
After stirring the mixture for 1 h at RT, the pH was adjusted to 12
with NaOH solution (1 molLÀ1). After stirring the mixture for 20 h
at RT, the nanocatalysts obtained were washed with distilled water
and separated with a magnet. The washing process was repeated
until the pH of the suspension became neutral. The obtained solid
was washed once with ethanol and dried under vacuum.
Scheme 6. Catalytic cycle proposed for the Biginelli reaction via the Knoeve-
nagel intermediate mechanism.
Niobium nanocatalyst-mediated synthesis of DHPMs by Bigi-
nelli condensation
General procedure: A mixture of aldehyde (1 mmol), acetoacetate
(1 mmol), urea or thiourea (1.5 mmol), ethanol (500 mL), and niobi-
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silica gel with hexane/acetate as an eluent.
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Acknowledgements
We gratefully acknowledge the S¼o Paulo Research Founda-
tion—FAPESP (2009/07281-0 and 2013/06558-3) and Conselho
Nacional de Desenvolvimento Cientꢀfico e Tecnolꢁgico (CNPq)
[INCT-Catꢂlise and Instituto Nacional de Biotecnologia Estrutural
e Quꢀmica Medicinal em DoenÅas Infecciosas (INBEQMeDI)] for fi-
nancial support and CBMM for the donation of niobium salts.
C.G.S.L. thanks Coordenażo de AperfeiÅoamento de Pessoal de
Nꢀvel Superior (CAPES) and S.S. cordially acknowledge FAPESP
(12/04986-5) for their fellowships.
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Keywords: iron
· magnetic properties · multicomponent
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Received: August 27, 2014
Published online on && &&, 0000
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These are not the final page numbers!

FULL PAPERS
C. G. S. Lima, S. Silva, R. H. GonÅalves,
E. R. Leite, R. S. Schwab, A. G. CorrÞa,
M. W. Paix¼o*
&& – &&
Highly Efficient and Magnetically
Recoverable Niobium Nanocatalyst for
the Multicomponent Biginelli Reaction
Magnetic personality: A new magneti-
cally recoverable nanocatalyst,
synthesize 1,4-dihydropyrimidinones.
The new nanocatalyst proves to be
highly efficient in synthesizing a wide
range of Biginelli products and has the
advantage of a remarkably low catalyst
loading (0.1 mol%) and high reusability.
Fe3O4@Nb2O5, is prepared and fully char-
acterized. Its catalytic activity is evaluat-
ed by using the one-pot, three-compo-
nent Biginelli reaction, with the aim to
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 10
&10
&
ÞÞ
These are not the final page numbers!