Synthesis of various ferrite (MFe2O4) nanoparticles and their application as efficient and magnetically separable catalyst for biginelli reaction

Article abstract of DOI:10.1166/jnn.2018.14345

Herein, we reports the application of various spinel ferrite nanoparticles, MFe₂O₄ (M = Co, Ni, Cu, Zn), as efficient catalyst for Biginelli reaction. All ferrite nanoparticles were synthesized using a novel aqueous solution based me

Full text of DOI:10.1166/jnn.2018.14345

Article
Journal of
Nanoscience and Nanotechnology
Vol. 18, 2481–2492, 2018
Copyright © 2018 American Scientific Publishers
All rights reserved
Printed in the United States of America
www.aspbs.com/jnn
Synthesis of Various Ferrite (MFe O ) Nanoparticles and
2
4
Their Application as Efficient and Magnetically Separable
Catalyst for Biginelli Reaction
1
1
1
2
Madhurya Chandel , Barun Kumar Ghosh , Debabrata Moitra , Manoj Kumar Patra ,
2
1ꢀ∗
Sampat Raj Vadera , and Narendra Nath Ghosh
1Nano-Materials Laboratory, Department of Chemistry, Birla Institute of Technology and Science,
Pilani K. K. Birla Goa Campus, Zuarinagar, Goa 403726, India
2
Defence Laboratory, Jodhpur 342011, India
Herein, we reports the application of various spinel ferrite nanoparticles, MFe O (M = Co, Ni,
2
4
Cu, Zn), as efficient catalyst for Biginelli reaction. All ferrite nanoparticles were synthesized using
a novel aqueous solution based method. It was observed that, the catalytic activity of the ferrite
nanoparticles followed the decreasing order of CoFe O > CuFe O > NiFe O > ZnFe O . The
2
4
2
4
2
4
2
4
most important feature of these ferrite nanocatalysts is that, these nanoparticles can directly be
used as catalyst and no surface modification or functionalization is required. These ferrite nanopar-
ticles are easily separable from reaction mixture after reaction by using a magnet externally. Easy
IP: 90.140.163.184 On: Mon, 18 Jun 2018 03:06:40
synthesis methodology, high catalytic activity, easy magnetic separation and good reusability make
Copyright: American Scientific Publishers
these ferrite nanoparticles attractive catalysts for Biginelli reaction.
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Keywords: Ferrites Nanoparticles, Biginelli Reaction, Magnetic Separation, Reusability.
1
. INTRODUCTION
anti-inflammatory, antitubercular, antidiabetic, antiepilep-
tic, antileishmanial, antiproliferative activities, etc. A num-
ber of functionalized DHPMs showed their capabilities
to act as antihypertensive agents, potent calcium chan-
nel blockers, mPGES-1 inhibitors, ꢁ1a-adrenergic antago-
nists and A2B receptor antagonists. Very recently usages
of DHPMs in polymers, adhesives, dyes etc. are also
reported. Many researchers have described the importance
of Biginelli reaction and the applications of the products in
Even though the concept of multi-component reaction
(
MCR) is quite old, but till date MCRs are continuing
to fascinate synthetic chemists as powerful and versa-
tile methodology for synthesizing variety of organic com-
pounds. High efficiency, easy operation, cost effectiveness,
large molecular diversity with high product yield are some
of the advantages which MCRs offer over multistep syn-
1
–3
thesis routes.
Biginelli reaction’ is one of the classical but extremely
1
–6
many reviews and detailed references are cited therein.
The growing interest in the synthesis of DHPMs via
Biginelli reaction has necessitated development of new
catalysts because traditional Biginelli methodology often
suffers from harsh reaction conditions, usage of toxic
solvents, low yield, low selectivity, requirement of high
‘
important MCRs where condensation of three component
reactants, i.e., aldehyde, ꢀ-keto ester and urea (or thiourea)
produces 3, 4-dihydropyrimidin-2(1H)-(thi) one (DHPM).
This reaction is continuously attracting the interest of
the researchers, particularly synthetic organic and mate-
rials scientists, because of the therapeutic and pharmaco-
logical properties of Biginelli products, namely DHPMs.
Several DHPMs exhibit wide range of biological activi-
ties such as antitumor, antiviral, antibacterial, antimalarial,
7
–11
temperature, prolonged reaction time etc.
In search
for efficient synthetic methodologies several researchers
have employed varieties of catalysts, such as Brønsted
acids, Lewis acids, Ionic liquids, Biocatalysts, Organocat-
1
0–16
alysts etc.
However, traditional homogeneous catalysts
suffer from the difficulty in recovery of catalysts from
the product and recycling of the catalysts. Owing to the
∗
Author to whom correspondence should be addressed.
J. Nanosci. Nanotechnol. 2018, Vol. 18, No. 4
1533-4880/2018/18/2481/012
doi:10.1166/jnn.2018.14345
2481

Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
large surface area nanoparticles exhibited excellent cat-
Chandel et al.
method, followed by forming a coating of SiO on the
2
1
7
alytic activities for organic reactions. Though varieties
of heterogeneous catalysts have been reported for Biginelli
reaction but leaching of catalytically active species from
surface of NiFe O nanoparticles by using sol–gel chem-
2
4
istry of TEOS. Then Preyssler HPA (H NaP W O120ꢃ
1
4
5
30
was immobilized on the surface of core–shell structure
of NiFe O @SiO . Girija et al. reported the preparation
3
ꢂ18
20
the support is one of the major problems.
2
4
2
For the past few years magnetically separable cat-
alysts have gained immense attraction because of
of Fe O nanoparticles supported-nickel(II) complex by
3 4
first synthesizing Fe O nanoparticles by co-precipitation
3
4
1
0
their easy separation after the reaction. Fe O @SiO -
method, followed by a coating of the surface of Fe O
3
4
2
3 4
1
5
imid-H PMo O , Preyssler heteropolyacid supported
silica coated nickel ferrite nanoparticles, functional-
nanoparticles using TEOS. [Ni(bpy) (pytmos)]Cl com-
2 2
3
12 40
1
9
plex was prepared separately by refluxing pyridine-
2-yl-(3-trimethoxysilanyl-propyl)-amine (py-tmop) and
[Ni(bpy) Cl ] in DMF under nitrogen atmosphere for
ized magnetic (Fe O ꢃ nanoparticles supported-nickel(II)
3
4
complex,20 Functionalized Fe O @mesoporous SBA-15,
10
3
4
2
2
1
1
Cu-EDTA-modified APTMS-Fe O @SiO , Cu nanopar-
10 h. [Ni(bpy)2(pytmos)] complex was then immobilized
on the surface of silica coated Fe O . During preparation
3
2
4
2
1
ticle loaded CoFe O @SBA15, Fe O @silica sulfuric
2
4
3
4
3
4
Acid,22 Fe O @Nb O , N -propylcarbamothioyl benza-
18
of Fe O @mesoporous SBA-15 Mondal et al. have
10
3
4
2
5
3 4
2
3
mide Bi(III) on Fe O /SiO , are some the reported
adopted the strategy of synthesizing functionalized meso-
porous SBA-15 first by using thiol-ene click chemistry
of vinyl functionalized SBA-15 and cysteine hydrochlo-
ride in the presence of an 2,2-azobis(isobutyronitrile)
(AIBN) initiator. Then Fe O nanoparticles were pre-
3
4
2
magnetically separable catalysts which are recently used
for Biginelli reaction. In this type of catalyst, magnetic
nanoparticles (such as ferrite nanoparticles) provide nec-
essary magnetic character to the catalysts so that they
3
4
can be attracted by magnet and ultimately can easily be
pared by co-precipitation method in N2 atmosphere.
Finally, Fe O @mesoporous SBA-15 nanocatalysts
recovered.3
ꢂ24ꢂ25
For the synthesis of magnetically sep-
3
4
arable catalysts multi step synthetic routes have gener-
ally employed by scientists. First a core–shell structure
is created by coating the surface of magnetic nanopar-
were prepared by chemical conjugation of Fe O
3 4
nanoparticles onto cysteine hydrochloride functionalized
mesoporous SBA-15. To prepare Cu-EDTA-modified
1
1
ticles with a chemically inert matrix (e.g., SiO ꢃ, fol-
APTMS-Fe O @SiO Sheykhan et al. functionalized
2
3 4 2
lowed by immobilization of catalytically active species on
Fe O @SiO with 3-aminopropyltrimethoxysilane to
3 4 2
IP: 90.140.163.184 On: Mon, 18 Jun 2018 03:06:40
the surface of the core–shell either via impregnation or
obtain an organic inorganic hybrid (Fe O @SiO –(CH ꢃ –
3 4 2 2 3
Copyright: American Scientific Publishers
2
6
functionalization. In another approach the surfaces of the
NH ꢃ. Then EDTA-Cu(II) complex was conjugated with
2
Delivered by Ingenta
2
1
magnetic nanoparticles are first functionalized and then
catalytically active centers (most of the cases metal ions
or nanoparticles) are attached on the surface of magnetic
nanoparticles via functional groups. Some of the synthetic
methodologies which are employed by several researchers
have been discussed below.
(Fe O @SiO –(CH ꢃ –NH ꢃ. Ghosh et al. reported the
3 4 2 2 3 2
preparation of Cu nanoparticle loaded CoFe O @SBA15
2
4
by first creating a coating of mesoporous silica (SBA15)
on the surface of CoFe O nanoparticles. Then Cu
2
4
nanoparticles were embedded within the pores of SBA15
by using impregnation technique. To prepare Fe O @silica
3
4
1
5
22
Esmaeilpour et al. employed a multi-step pathway to
prepare Fe O @SiO -imid-H PMo O .
sulfuric acid, Dam et al. in the first step synthesized
Fe O by co-precipitation technique. After that in order
3
4
2
3
12 40
3
4
Step 1: Fe O nanoparticles were prepared by co-
to improve the chemical stability, surface modification
3
4
precipitation method using polyvinyl alcohol (PVA 15000)
as a surfactant and hexamethylenetetramine as precipitat-
ing agent.
was performed by depositing silica on its surface. −SO H
3
groups were attached on the silica surface by reacting
1
8
ClSO H with the −OH groups of silica. Lima et al.
3
Step 2: A coating of SiO was deposited on the surface
have prepared Fe O @Nb O by using an impregnation
3 4 2 5
2
of Fe O nanoparticles by using tetraethyl ortho silicate
method where C H NNbO ·nH O was impregnated over
3
4
4
4
9
2
23
(
TEOS) to obtain Fe O @SiO .
Fe O nanoparticles. Mobinikhaledi et al. have syn-
3 4
3
4
2
n
Step 3: H PMo O nanoparticles (PMA ꢃ were prepared
thesized N -propylcarbamothioyl benzamide Bi(III) on
3
12 40
from its bulk form by hydrothermal method.
Fe O /SiO by using a multi-step methodology, where
3
4
2
Step 4: Fe O @SiO was then functionalized by reflux-
Fe O magnetic nanoparticles were prepared by improved
3
4
2
3 4
ing with 3-chlorotriethoxypropylsilane and imidazole in
p-xylene.
chemical co-precipitation method, followed by synthesis
of Fe O coated with SiO through a modified sol–gel
3
4
2
Step 5: finally Fe O @SiO -imid-H PMo O was syn-
method. Then it was functionalized by (3-aminopropyl)
3
4
2
3
12 40
n
thesized by refluxing Fe O @SiO -imid with PMA in
triethoxysilane (APTES) under N atmosphere to obtain
3
4
2
2
acetonitrile for 24 h under nitrogen atmosphere. Eshghi
et al.19 reported the preparation of Preyssler heteropolyacid
supported silica coated nickel ferrite nanoparticles by first
preparing NiFe O nanoparticles using co-precipitation
aminopropyl-functionalized solid (Fe O /SiO –NH ꢃ,
which was then reacted with benzoyl isothiocyanate
3
4
2
2
in dried toluene in N atmosphere. The resultant solid
2
was then refluxed with Bi(NO ꢃ · 5H O for 24 h to
2
4
3
3
2
2482
J. Nanosci. Nanotechnol. 18, 2481–2492, 2018

Chandel et al.
Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
nanoparticles were obtained by calcining their precursor
synthesize N -propylcarbamothioyl benzamide Bi(III) on
ꢀ
Fe O /SiO .
powders at 550 C for 3 h in air atmosphere.
3
4
2
Though magnetically separable catalysts offer the
advantage of easy recovery but in most of the cases their
methods of preparation are multistep and complicated in
nature as well as require use of costly chemicals. More-
over, leaching of catalytically active species from the
catalyst cannot be avoided after few cycles of catalysis
reaction. These factors limit the large scale and wider
2
.3. Materials Characterization
Room temperature powder X-ray diffraction (XRD) pat-
terns of the synthesized catalysts were recorded using
a powder X-ray diffractometer (Mini Flex II, Rigaku,
Japan) with Cu K radiation at a scanning speed of
3
Coulter, USA) was used to measure the average parti-
cle size of the synthesized catalysts. Room temperature
magnetization was measured using a vibrating Sample
magnetometer (VSM) (EV5, ADE Technology, USA).
Thermogravimetric analysis (TGA) and differential scan-
ning calorimetric (DSC) analysis were carried out using
DTA-60 (Shimaduzu, Japan) and DSC-60 (Shimaduzu,
Japan) repectively. Fourier transform infrared (FT-IR)
spectra of the samples were recorded by infrared spec-
ꢁ
ꢀ
−1
min . Particle size analyzer (Delsa Nano S, Beckman
3
ꢂ24
applications of magnetically separable catalysts.
In search for a magnetically separable catalyst which
will not suffer the aforesaid limitations, we thought of
exploring pure single phase ferrite nanoparticles as cat-
alyst for Biginelli reaction. Here, we are reporting the
synthesis of CoFe O , NiFe O , CuFe O and ZnFe O
2
4
2
4
2
4
2
4
nanoparticles and their catalytic activity towards Biginelli
reaction. These ferrite nanoparticles were synthesized by
using a single step preparation method in an aqueous
medium and the as synthesized ferrite nanoparticles were
used as catalyst without further surface modification. Syn-
thesized ferrite nanoparticles were characterized by using
X-ray Diffraction (XRD), Thermogravimetric Analysis
1
trophotometer (IRAffinity-1, Shimadzu, Japan). H NMR
(
Nuclear Magnetic Resonance) spectra were recorded on a
BRUKER 400 ULTRA SHIELD PLUS (400 MHz) instru-
ment using deuteriated solvent. field emission scanning
electron microscopy (FESEM) Quanta 250 FEG (FEI) was
used to record the images of ferrites nanoparticles.
(
TGA), Differential Scanning Calorimetric (DSC), parti-
cle size analyzer and Field Emission Scanning Electron
Microscopy (FESEM).
2.4. Catalysis Reaction
First CoFe O , NiFe O , CuFe O and ZnFe O
4
2
4
2
4
2
4
2
IP: 90.140.163.184 On: Mon, 18 Jun 2018 03:06:40
. EXPERIMENTAL DETAILS
2
2
nanoparticle catalyzed Biginelli reactions were performed
Copyright: American Scientific Publishers
.1. Materials Used
in solventless condition using two model reactions. In a
typical reaction benzaldehyde, urea and ethyl acetoacetate
(or acetylacetone) were used in 1:1.5:1 molar ratio in
mmol concentration. These reactants were mixed thor-
oughly along with calculated amount synthesized ferrite
nanoparticles in a round bottomed flask and then heated at
Delivered by Ingenta
Cobalt nitrate hexahydrate (Co(NO ꢃ · 6H O), Iron
3
2
2
nitrate nonahydrate (Fe(NO ꢃ · 9H O), copper nitrate
3
3
2
trihydrate (Cu(NO ꢃ · 3H O), nickel nitrate hexahydrate
3
2
2
(
6
Ni(NO ꢃ · 6H O), zinc nitrate hexahydrate (Zn(NO ꢃ ·
3
2
2
3 2
H O), ethylenediaminetetraacetate (EDTA), urea and
2
ꢀ
thiourea were purchased from Merck, India. Benzalde-
hyde, 2-cholorobenzaldehyde, 4-cholorobenzaldehyde,
80 C for certain time. After cooling the reaction mixture
was poured into ice cooled water and catalyst was sepa-
rated by applying an external magnet. The product was
then recrystallized. The purity of the products obtained by
Biginelli reaction was verified using H NMR, FT-IR and
melting point determination by DSC.
4
-methoxybenzaldehyde, ethyl acetoacetate and acety-
lacetone were purchased from Sigma-Aldrich. All the
chemicals were used without further purification. Deion-
ized water was used throughout the experiment.
1
2
.2. Synthesis of Ferrite Nanoparticles
3
. RESULTS AND DISCUSSION
CoFe O , NiFe O , CuFe O and ZnFe O nanoparticles
were synthesized by using a novel EDTA precursor based
method in aqueous medium.
2
4
2
4
2
4
2
4
DSC scan of precursor powders showed the appearance
of a strong exothermic peak in the temperature of 250–
2
7ꢂ28
ꢀ ꢀ
50 C with a peak at 400 C. TGA thermogram of the
In this method corre-
5
sponding metal nitrates (e.g., Co(NO ꢃ ·6H O, Ni(NO ꢃ ·
3
2
2
3
2
precursors also indicated a major weight loss (∼75%) in
ꢀ ꢀ
6
9
H O, Cu(NO ꢃ ·3H O, Zn(NO ꢃ ·6H O and Fe(NO ꢃ ·
2
3
2
2
3
2
2
3
2
the temperature of 250–550 C. Beyond 550 C neither
any significant weight loss in TGA nor appearance of any
peak in DSC was observed (Fig. 1). These results indi-
cate that oxidative thermal decomposition of carbonaceous
H O) and EDTA were used as starting materials. Initially,
2
stoichiometric amount of metal nitrates were dissolved
in water. Then calculated amount of aqueous solution of
EDTA were added to the metal nitrate mixture solution
with constant stirring keeping molar ratio of total metal
ion: EDTA 1:1. The resulting mixtures were then dried
on a hotplate. Thus floppy carbon rich precursor powders
were obtained. CoFe O , NiFe O , CuFe O and ZnFe O
ꢀ
component of the precursors occurs up to 550 C. Hence,
the precursor powders were calcined at 550 C to obtain
ferrite nanoparticles.
Room temperature wide angle powder XRD patterns of
the powders, which were obtained after calcinations of
ꢀ
2
4
2
4
2
4
2
4
J. Nanosci. Nanotechnol. 18, 2481–2492, 2018
2483

Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
Chandel et al.
technique using a particle size analyzer (Fig. 3) and it
was observed that, the average particle size of the calcined
ferrite powders lies in the range of 12–15 nm with poly-
dispersity index of ± 0.2 to 0.4. FESEM was utilized to
examine the surface morphology of the calcined powders
and are shown in Figure 4. It was observed that calci-
nation of precursor powders produce loosely agglomerate
nanosized powders (with average particle size in the range
of 15–20 nm). FESEM micrographs also confirmed that
ꢀ
though the calcination was conducted at 550 C, but calci-
nation does not result in any large grain growth or sintering
of the particles.
XRD, TGA-DSC and FESEM analysis of the synthe-
sized precursors and calcined powders clearly confirmed
that single-phase ferrite nanopowders are formed due to
oxidative decomposition of precursor. Precursor powders
are formed after evaporation of a homogeneous aqueous
mixture solution of metal nitrate and EDTA. Here EDTA
plays a duel role. As it is a strong multidentate chelating
agent, it prevents the segregation or intermittent precipita-
tion of metal ions from solution during evaporation. It also
helps to form of a fluffy, voluminous, porous, carbon-
rich precursor. Nascent metal oxides, which are basically
small atomic clusters with proper chemical homogeneity,
are formed and finally ferrite nanoparticles are produced
as a result of decomposition of precursor. Gases (such as
Figure 1. TGA-DSC thermograms of the precursor powder in air.
precursor powders, are shown in Figure 2. In the XRD
spectra diffraction patterns peaks were observed at 2ꢄ =
ꢀ
1
8ꢅ16ꢂ29ꢅ90ꢂ35ꢅ32ꢂ36ꢅ81ꢂ42ꢅ86ꢂ53ꢅ22ꢂ56ꢅ68 and 62.24 ,
which are corresponding to (111), (220), (311), (222),
400), (422), (511) and (440) planes and characteristic
peaks of CoFe O (JCPDS 22–1086), NiFe O (JCPDS
(
2
4
2
4
1
0–0325), CuFe O (JCPDS 34–0425) and ZnFe O
2 4 2 4
(
JCPDS 79–1150). From XRD analysis it was concluded
that, calcinations of precursor powders resulted in forma-
tion of pure single-phase CoFe O , NiFe O , CuFe O and
2
4
2
4
2
4
ZnFe O nanopowders. No impurity phase was detected
2
4
IP: 90.140.163.184 On: Mon C, O1 8
, J Nu On 2ꢃ 0 1a r8e 0e 3v :o0 l 6v e: 4d 0during oxidative decomposition
2
x
in XRD patterns of the synthesized samples. Crystal-
lite sizes of the nanopowders were calculated by using
Copyright: American S co ife nc ta i rf ibc o Pn ur bi cl ihs h pe r resc ursor. This helps not only to dissi-
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pate the heat of combustion but also prevent the sintering
of fine particles during the formation of nanosized ferrite
Scherrer’s formula and it was observed that the crystal-
lite size of CoFe O , NiFe O , CuFe O and ZnFe O
2
4
2
4
2
4
2
4
2
9
powders.
Room temperature magnetic property of the synthesized
CoFe O , NiFe O , CuFe O and ZnFe O nanopowders
nanopowders were 29.62, 11.92, 21.19 and 21.93 nm
respectively.
Average particle size of the synthesized nanopow-
ders were also determined by Dynamic Light Scattering
2
4
2
4
2
4
2
4
were determined by using a VSM and the obtained mag-
netic hysteresis loops (M vs. H) of these nanoparticles
are shown in Figure 5. The values of saturation magneti-
zation (M ꢃ and coercivity (H ꢃ of the synthesized ferrite
s
c
nanoparticles are listed in Table I. It has been observed
that, M values of the synthesized ferrites are decreas-
s
ing in the order of CoFe O > NiFe O > CuFe O >
2
4
2
4
2
4
ZnFe O because the number of electrons in the d orbital
2
4
2
+
2+
2+
are increasing in the order of Co < Ni < Cu and
Zn . The ferromagnetic nature of CoFe O , NiFe O ,
2
+
2
4
2
4
CuFe O and ZnFe O nanopowders has been exploited
2
4
2
4
for their magnetic separation from reaction mixture after
catalysis reactions.
3
.1. Catalysis Test
To evaluate the catalytic activity of the synthesized
CoFe O , NiFe O , CuFe O and ZnFe O nanoparticles
2
4
2
4
2
4
2
4
two Biginelli reactions were performed in solventless
condition using PhCHO as aldehyde, Ethylacetoacetate
(
or Acetylacetone) as 1,3 diketone and Urea. The reac-
Figure 2. Powder XRD patterns of (a) CoFe O (b) NiFe O
4
2
4
2
(
c) CuFe O and (d) ZnFe O .
tions are presented as reaction 1 and 2. All the ferrite
2
4
2
4
2484
J. Nanosci. Nanotechnol. 18, 2481–2492, 2018

Chandel et al.
Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
Figure 3. Particle size distribution of synthesized ferrite nanoparticles.
nanoparticles exhibited their very good catalytic efficiency
As it has been observed that, all synthesized ferrite
nanoparticles have the capability to act as efficient cata-
lysts for the above mentioned two model Biginelli reac-
IP: 90.140.163.184 On: Mon, 18 Jun 2018 03:06:40
for these reactions (Table II).
Copyright: American Scientific Publishers
Delivered by Ingenta
tions. More Biginelli reactions were performed using
different aldehydes, 1,3 diketones and urea (or thiourea).
In these cases owing to the highest M value CoFe O
s
2
4
was used as catalyst. As our main objective is to develop
efficient but magnetically separable catalyst for Biginelli
reaction, we have chosen CoFe O as catalyst because
2
4
its high M value will help to recover the catalyst more
s
efficiently when magnetic separation procedure will be
applied. Table III shows CoFe O can efficiently catalyze
2
4
Biginelli reactions involving verities of aldehyde and 1,3
diketones in solventless condition. The purity of the prod-
ucts obtained from these ferrite nanoparticle catalyzed Big-
inelli reactions were verified by using FT-IR (Fig. 6),
1
(
(
1)
2)
H NMR (Fig. 7) and DSC (Fig. 8) and corresponding data
are given below.
3
.2. Spectra Data of the Products, Which were
Obtained From Ferrite Nanoparticle Catalyzed
Biginelli Reactions
3
.2.1. Entry-1: 5-Acetyl-6-Methyl-4-Phenyl-3, 4-
Dihydropyrimidin-2(1H)-one
−1
FTIR (KBr): 3247, 3112, 2926, 1727, 1706, 1644 cm .
1
H NMR (CDCl3 400 MHz) ꢆ = 2ꢅ11(s, 3H), 2.30
(
(
2
s, 3H), 5.27 (s, 1H), 7.25–7.33 (m, 5H), 7.83
ꢀ
15
s, 1H), 9.18 (s, 1H). Solid mp 234–235 C (reported
35–236 C).
ꢀ
J. Nanosci. Nanotechnol. 18, 2481–2492, 2018
2485

Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
Chandel et al.
Table I. Magnetic properties of the synthesized ferrite nanoparticles.
Catalyst
M (emu/g)
H (kOe)
s
c
CoFe O
49.92
31.10
13.83
4.68
1.18
1.61
0.22
0.12
2
4
4
NiFe O
2
4
CuFe O
2
ZnFe O
2
4
3
.2.4. Entry-4: 4-(4-Chlorophenyl)-6-Methyl-2-Oxo-
,2,3,4-Tetrahydropyrimidine-5-Carboxylate
FTIR (KBr): 3243, 3119, 2975, 1896, 1730, 1636, 1571,
1
1
1
493 H NMR (CDCl 400 MHz) ꢆ = 1ꢅ08 (t, 3H), 2.26
3
(
s, 3H), 3.96–4.01 (m, 2H), 5.27 (s, 1H), 5.78 (s, 1H),
7
2
.90 (s, 1H), 8.21–8.23 (d, 3H), 9.36 (s, 1H). Solid mp
11–213 C (reported 214–215 C).
ꢀ
15
ꢀ
Figure 4. FESEM micrograph of synthesized ferrite nanoparticles.
3
.2.5. Entry-5: 6-Methyl-2-Oxo-4-(Thiophen-2-Yl)-
1
,2,3,4-Tetrahydropyrimidine-5-Carboxylate
FTIR (KBr3336, 3235, 3120, 2973, 1701, 1651, 1463,
3
.2.2. Entry-2: Ethyl-6-Methyl-2-Oxo-4-Phenyl-
,2,3,4-Tetrahydropyrimidine-5-Carboxylate
FTIR.(KBr): 3340, 3257, 3123, 2926, 1706, 1675, 1613,
1
1
2
2
218, 1096 H NMR (CDCl 400 MHz) ꢆ = 1ꢅ18 (t, 3H),
3
1
.23 (s, 3H), 4.06–4.08 (m, 2H), 5.42 (s, 1H), 6.89 (d,
H), 7.35 (s, 1H), 7.90 (s, 1H), 9.30 (s, 1H). Solid mp
−1 1
1
2
7
2
586 cm . H NMR (CDCl 400 MHz) ꢆ = 1ꢅ18 (t, 3H),
ꢀ
15
ꢀ
3
209–210 C (reported 209–210 C).
.37 (s, 3H), 4.07 (q, 2H), 5.42 (s, 1H), 5.61 (s, 1H),
.28 (s, 1H), 7.30–7.35 (m, 5H), 7.76 (s, 1H). Solid mp
ꢀ
15
ꢀ
04–205 C (reported 205–206 C).
Table II. % of yields of the products of ferrite nanoparticle catalyzed
Biginelli reaction.
IP: 90.140.163.184 On: Mon, 18 Jun 2018 03:06:40
3
.2.3. Entry-3: 4-(2-Chlorophenyl)-6 C- Mo pe tyh r yi gl -h2 t-: OAx mo -e rican Scientific Publishers
Ethyl-6-methyl-2-oxo-4-
phenyl-1,2,3,4-
tetrahydropyrimidine-
5-carboxylate (Yield %)
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1
,2,3,4-Tetrahydropyrimidine-5-Carboxylate
5
-acetyl-6-methyl-
1
FTIR (KBr): 3235, 3101, 2956, 2936, 1701, 1639 H NMR
4-phenyl-3,4-dihydropyrimidin-
2(1H)-one (Yield %)
Catalyst
(
(
(
2
CDCl 400 MHz) ꢆ = 1ꢅ08 (t, 3H), 2.46 (s, 3H), 4.04
3
q, 2H), 5.73 (s, 1H), 5.90 (s, 1H), 7.23–7.28 (m, 4H), 7.40
CoFe O
89.0
56.1
65.0
38.8
92.6
53.1
75.6
35.6
2
4
ꢀ
15
m, 1H), 8.31 (s, 1H). Solid mp 216–217 C (reported
16–218 C).
NiFe O
2
4
ꢀ
CuFe
O
2
4
ZnFe O
2
4
Table III. CoFe O nanoparticle catalyzed synthesis of 3,4-dihydro-
2
4
pyrimidin-2(1H)-ones/thiones.
b
Entry
R1
R2
X
Time (h)
Yield (%)
1
2
3
4
5
6
7
C H
CH3
OEt
OEt
OEt
OEt
OEt
OEt
O
O
O
O
O
S
1
1
1.25
1.25
1.5
1
89.0
92.6
84.9
89.2
79.1
78.6
85.4
6
5
5
C H
6
2-Cl–C H
4-Cl–C H
6
4
4
6
2-Thiophene
C H
6
5
4-OCH –C H
4
O
1.5
3
6
Notes: Reaction condition: Aldehyde (1 mmol), 1,3-Diketone (1 mmol)
Figure 5. Room temperature magnetic hysteresis loop of the synthe-
sized ferrite nanoparticles.
Urea/Thiourea (1.5 mmol) CoFe O (10 mg), Solvent free, Reaction temperature
80 C. Isolated yield.
2
4
ꢀ
b
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Chandel et al.
Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
IP: 90.140.163.184 On: Mon, 18 Jun 2018 03:06:40
Copyright: American Scientific Publishers
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Figure 6. FT-IR spectra of biginelli products.
3
.2.6. Entry-6: 6-Methyl-4-Phenyl-2-Thioxo-
3.2.7. Entry-7: 4-(4-Methoxyphenyl)-6-Methyl-2-Oxo-
1
,2,3,4-Tetrahydropyrimidine-5-Carboxylate
1,2,3,4-Tetrahydropyrimidine-5-Carboxylate
FTIR (KBr): 3250, 3113, 2954, 2832, 1730, 1644, 1521
1
FTIR (KBr): 3336, 3177, 3106, 1658, 1571 H NMR
1
(
4
(
2
CDCl3 400 MHz) ꢆ = 1ꢅ18 (t, 3H), 2.37 (s, 3H),
H NMR (CDCl 400 MHz) ꢆ = 1ꢅ12 (t, 3H), 2.24 (s,
3
.10 (q, 2H), 5.42 (s, 1H), 7.28 (s, 1H), 7.36
3H), 3.34 (s, 2H), 3.97–4.00 (q, 2H), 5.09 (s, 1H), 6.88
(d, 2H), 7.13–7.15 (m, 2H), 7.67 (s, 1H), 9.16 (s, 1H).
ꢀ
15
m, 5H), 7.85 (s, 1H) Solid mp 208–209 C (reported
08–210 C).
ꢀ
ꢀ
15
ꢀ
Solid mp 204–205 C (reported 201–203 C).
J. Nanosci. Nanotechnol. 18, 2481–2492, 2018
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Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
Chandel et al.
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Figure 7. Continued.
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Chandel et al.
Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
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Copyright: American Scientific Publishers
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Figure 7. Continued.
J. Nanosci. Nanotechnol. 18, 2481–2492, 2018
2489

Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
Chandel et al.
Figure 7. 1H NMR spectra of biginelli products.
Though several scientists attempted to establish the
mechanism of Biginelli reaction by performing experi-
ments as well as theoretical studies, but even today this is
are very popular for this reaction, which is presented as
Scheme 1. The proposed reaction mechanisms are
(i) Iminium route: here the reaction proceeds via for-
mation of iminium intermediate through condensation
2
a topic of debate. However, three proposed mechanisms
IP: 90.140.163.184 On: Mon, 18 Jun 2018 03:06:40
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Figure 8. DSC thermogram of Biginelli products.
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Chandel et al.
Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
Scheme 2. The plausible mechanism involved in Biginelli reaction cat-
alyzed by ferrite nanoparticles in the synthesis of DHPM.
3
.3. Reusability
The stability of catalytic activity of the catalysts was
verified by recovering them from reaction mixture after
completion of catalysis reaction. Recovery of the ferrite
Scheme 1. Three proposed mechanisms for Biginelli reaction.
IP: 90.140.163.184 On: Mon, 18 Jun 2018 03:06:40
nanoparticles were performed by using a simple magnet
Copyright: American Scientific Publishers
between aldehyde and urea, which undergoes a nucle-
Delivered b ye xI nt e gr ne an l tl ay . As a representative, the magnetic separation of
ophilic addition with a ꢀ-keto ester leading to DHPM.
CoFe O nanocatalyst is presented in Figure 9(a). After
2
4
(
ꢀ
ii) Enamine route: here condensation between urea and
-keto ester produces enamine intermediate, which pro-
duces DHPM by reacting with aldehyde
iii) Knoevenagel type reaction mechanism: here the
recovery, the catalysts were washed with distilled water
and acetone for 2–3 times and dried. Then the recov-
ered catalyst was used for the next catalysis reaction.
It was observed that there was no significant change in
catalytic activity upto 5 cycles (Fig. 9(b)). After 5th cycle,
there was a small (∼2–5%) change observed. XRD and
FESEM analyses of the recycled catalysts were performed,
which confirmed that there was no significant change in
(
reaction between aldehyde and ꢀ-keto ester leads to
form an intermediate, which reacting with urea forms
DHPM.
In the present case, the plausible reaction mechanism
of ferrite nanoparticle catalyzed Biginelli reaction might
be as follows: Initially the coordination of aldehyde and
ethyl acetoacetate with ferrite nanoparticles enhances the
electrophilicity of their carbonyl carbon. Then aldol type
condensation between aromatic aldehyde and ethyl ace-
toacetate forms the corresponding aldol-type product as an
intermediate (Intermediate-I). In the next step, the elec-
tron deficient sites present at the surface of the ferrite
nanoparticle coordinate with the N-donor sites of urea
molecules and thus stabilize/ activate it for 1,4-addition
reaction. This leads to the generation of Intermediate-II.
Ultimately cyclization of intermediate-II via elimination
of a water molecule results in formation of DHPM.
The plausible reaction mechanism can be presented as
Scheme 2. Similar mechanism has been proposed by
Mondal et al. for Fe O @mesoporous SBA-15 catalyzed
Biginelli reaction.
3
4
Figure 9. (a) Magnetic separation and (b) Recycling results for Big-
1
0
inelli reaction of CoFe O nanocatalyst.
2
4
J. Nanosci. Nanotechnol. 18, 2481–2492, 2018
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Synthesis of Various Ferrite Nanocatalysts for Biginelli Reaction
Chandel et al.
Acknowledgment: Dr. N. N. Ghosh gratefully acknowl-
edges financial support from CSIR, India (CSIR Sanction
letter No. 02(147)/13/EMR-II).
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(
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. CONCLUSION
In this paper, we are reporting the use of pure ferrite
nanoparticles (CoFe O , NiFe O , CuFe O and ZnFe O ꢃ
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4
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(
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2
4
2
4
2
4
2
4
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separation from the reaction mixture after completion
of reaction. One of the major advantages these fer-
rite nanocatalysts offer is unlike other reported magneti-
cally separable catalysts, here no surface modification is
required. Easy method of preparation, no requirement of
surface modification, excellent catalytic efficiency for Big-
inelli reaction under solventless condition, easy magnetic
recovery and good reusability of the recovered catalysts
make these ferrite nanoparticles attractive candidates as
catalysts for Biginelli reactions.
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2
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Received: 24 January 2017. Accepted: 7 February 2017.
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