A robust synthesis and characterization of superparamagnetic CoFe2O4 nanoparticles as an efficient and reusable catalyst for green synthesis of some heterocyclic rings

Article abstract of DOI:10.1002/aoc.3536

A robust synthesis for magnetic CoFe₂O₄ nanoparticles via a hydrothermal technique was investigated. The prepared magnetic nanoparticles were characterized using powder X-ray diffraction, scanning, transmission and high-resolution tr

Full text of DOI:10.1002/aoc.3536

Full paper
Received: 7 April 2016
Revised: 29 April 2016
Accepted: 17 May 2016
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.3536
A robust synthesis and characterization of
superparamagnetic CoFe2O4 nanoparticles as
an efficient and reusable catalyst for green
synthesis of some heterocyclic rings
Mahmoud Abd El Aleem Ali El-Remaily*, Ahmed M. Abu-Dief
and Rafat M. El-Khatib
A robust synthesis for magnetic CoFe2O4 nanoparticles via a hydrothermal technique was investigated. The prepared magnetic
nanoparticles were characterized using powder X-ray diffraction, scanning, transmission and high-resolution transmission elec-
tron microscopies, energy-dispersive X-ray and infrared spectroscopies, thermogravimetric analysis and vibrating sample magne-
tometry. Based on the obtained data, the prepared powder was composed of ultrafine particles in nanometer size range with
highly homogeneous spherical shape and elemental composition. Moreover, the prepared magnetic CoFe2O4 nanoparticles were
used as an efficient catalyst for green synthesis of tetrahydropyridines and pyrrole derivatives in excellent yields, with easy work-
up and purification of products by non-chromatographic methods. The catalyst can be recovered for subsequent reactions and
reused without any appreciable loss of activity. Copyright © 2016 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: magnetic CoFe2O4 nanoparticles; hydrothermal synthesis; TEM; tetrahydropyridines; pyrrole; non-chromatographic methods
bromodimethylsulfonium
bromide,[27]
tetrabutylammonium
Introduction
tribromide,[28] L-proline nitrate[29] and thiourea oxide[30] have been
reported for this MCR. Mishra and co-workers have reported L-pro-
line and trifluoroacetic acid as a dual catalytic system for this
MCR.[31] Shaterian and Azizi used imidazolium and guanidinium
acidic ionic liquid for the synthesis of functionalized piperidines.[32]
Pyrroles and their derivatives exhibit various important biological
activities like antibacterial, antioxidant, cytotoxic, insecticidal, anti-
inflammatory, anticoagulant, antiallergic, antiarhythmic, hypoten-
sive and anticonvulsant activities.[33–39] The development of new
MCRs and improving known multicomponent reactions are areas
of considerable current interest. Designing organic reactions in
aqueous media is another attractive area in green chemistry. Water
is an abundant and environmentally benign solvent. This protocol
offers flexibility in tuning molecular complexity and diversity. The
reactions proceed to completion almost instantaneously, and pure
product is obtained, without using any chromatographic tech-
niques, simply by recrystallization from ethanol.
In recent years, being focused on green chemistry using environ-
mentally benign reagents and conditions is one of the most fasci-
nating developments in synthesis of widely used organic
compounds.[1–3] Also, magnetic nanoparticles (MNPs) have re-
ceived a great deal of attention because of their potential biomed-
ical applications in fields such as drug delivery,[4,5] magnetic
resonance imaging,[6] biomolecular sensing,[7] bioseparation[8]
and magneto-thermal therapy.[9] Additionally, recent studies show
that MNPs are excellent catalysts for organic reactions.[10–13] Their
magnetic properties make possible the complete recovery of a cat-
alyst by means of an external magnetic field. These advantages be-
come even more attractive if such reactions can be conducted in
aqueous media. Tetrahydropyridines are widely distributed in natu-
rally occurring alkaloids and synthetic drugs.[14] A variety of struc-
tural features are exhibited by synthetically prepared piperidines,
including many exhibiting significant biological properties. Many
synthetic methods have been extensively studied for
tetrahydropyridines because of their antihistamic,[15] anti-HIV,[16]
Therefore, our work focuses on a new synthesis of stable and
highly monodisperse cobalt ferrite nanoparticles. The magnetic fea-
tures of the resulting modified nanoparticles have also been
anticancer,[17]
antimicrobial,[18]
antimalarial,[19]
anti-
inflammatory[20] and anti-insecticidal[21] activities. A few of them
are also potent inhibitors for many biological systems.[22] Boehm
and Stoker in 1943 reported the first multicomponent reaction
(MCR) between an amine, aldehyde and 1,3-dicarbonyl to synthe-
size functionalized piperidines.[23] Apart from some Lewis and
Bronsted acid catalysts,[24] a few organocatalysts which include
*
Correspondence to: Mahmoud A. A. Ali El-Remaily, Department of Chemistry,
Faculty of Science, Sohag University, Sohag 82524, Egypt. E-mail:
msremaily@yahoo.com
Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524,
Egypt
wet
picric
acid,[25]
p-toluenesulfonic
acid,[26]
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.

M. A. A. El-Remaily et al.
determined and examined for their potential applications. Also, we
report a simple and facile multi-component one-pot synthesis of
tetrahydropyridines and pyrrole derivatives in high yields, using
superparamagnetic CoFe2O4 nanoparticles (8 mol%) as a catalyst.
Most of the above reported synthetic methods for the synthesis
of tetrahydropyridines and pyrrole suffer from one or more draw-
backs, such as hazardous reaction conditions, complex work-up
and purification, strong acidic conditions, high temperature, use
of toxic metal catalysts, poor yields, occurrence of side reactions
and use of expensive reagents. Therefore, the development of a
mild generalized method to overcome these shortcomings still re-
mains an ongoing challenge for the synthesis of
tetrahydropyridines and pyrrole derivatives for organic chemists.
Figure 2. (a) TEM image for the prepared CoFe2O4 nanoparticles. (b)
Calculated size distribution for the prepared CoFe2O4 nanoparticles.
Results and discussion
Structural characterization of prepared CoFe2O4 nanoparticles
Powder X-ray diffraction (PXRD) patterns of the prepared CoFe2O4
MNPs (Fig. 1) show the expected peaks for the cubic inverse
spinel-type structure (Fd-3m space group) of CoFe2O4 (JCPDS PDF
no. 221086). The crystallite size of the sample is about 16 nm, as de-
termined by PXRD line-broadening analysis. A transmission elec-
tron microscopy (TEM) image (Fig. 2(a)) of the prepared
nanoparticles shows uniform distribution of nearly spherical parti-
cles, with an average size of 15 nm (Fig. 2(b)) which is consistent
with the value obtained from PXRD measurements. High-resolution
TEM (HR-TEM) images displayed in Fig. 3 of the prepared nanopar-
ticles show an interplanar spacing of 2.9 Å corresponding to (220)
atomic planes. Selected area electron diffraction (SAED) pattern
(Fig. 4) shows the polycrystalline nature of the samples and all the
rings have been indexed as inverse spinel CoFe2O4 phase. More-
over, SAED and PXRD patterns are found to agree that the (311)
plane shows the most intense reflection. CoFe2O4 nanoparticles
were examined using scanning electron microscopy (SEM)–en-
ergy-dispersive X-ray spectroscopy (EDS), including quantitative
point analysis. This study reveals a homogenous and uniform distri-
bution of the prepared individual particles, and without any appar-
ent preferential concentration in some areas, and the average
molar ratio of Co:Fe elements is 1:2 (Fig. 5).
Figure 3. (a) HR-TEM image for the investigated CoFe2O4 nanoparticles. (b)
HR-TEM micrograph of extracted single CoFe2O4 nanoparticle.
Figure 4. SAED pattern for the investigated CoFe2O4 nanoparticles.
Fourier transform infrared (FT-IR) spectrum of prepared
CoFe2O4 nanoparticles
The FT-IR spectrum of the prepared CoFe2O4 nanoparticles (Fig. S1)
shows a characteristic vibration (around 3450 cmÀ1) and deforma-
tion (at 1634 cmÀ1) bands due to the adsorbed water molecules at
the surface of the prepared nanoparticles. The band at 580 cmÀ1 is
characteristic for metal–oxide vibration band (cobalt ferrite) and
Figure 1. PXRD pattern for the prepared CoFe2O4 nanoparticles.
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CoFe2O4 nanoparticles for green synthesis of heterocyclic rings
Figure 5. (a) SEM image of the prepared nanoparticles. (b) EDS spectrum of
the prepared nanoparticles.
this confirms the spinel structure characteristic of the prepared
cobalt ferrite nanoparticles.
Thermogravimetric analysis (TGA) of prepared CoFe2O4
nanoparticles
The thermal stability of the prepared CoFe2O4 was investigated in
nitrogen. The TGA/DTG curves are shown in Fig. S2. The TG/DTG
curves for CoFe2O4 reveal a total mass loss of ca 6.22% from room
temperature up to 680°C. The mass loss takes place in four stages.
The first stage is with a total mass loss of ca 1.64% in the range
24.91–231.80°C (which reaches a maximum rate at 90°C), attributed
to the vaporization of surface water molecules, while the other
three steps are continuous with a total mass loss of ca 3.58% in
the range 232–680°C (which reach their maximum rate at 310,
420 and 575°C), and may be due to the vaporization of trapped
water molecules and decomposition of organic material.
Figure 6. Magnetic field dependence of magnetization (M–H loops)
measured for the prepared nanoparticles at (a) 5 K and (b) 300 K.
Magnetic characteristics
The magnetic properties of as-prepared CoFe2O4 nanoparticles
were investigated with a quantum vibrating sample magnetometer
at 5 and 300 K (T > TB) with a maximum applied field up to 100 kOe.
The results are shown in Fig. 6 and summarized in Table 1.
The sample is found to be superparamagnetic from the complete
reversibility of the M–H curve recorded at room temperature. The
decrease in the density of magnetization with a decrease in the av-
erage diameter of the nanocrystallites can be attributed to surface
effects and core–shell morphology.[40] The magnetic properties of
the superparamagnetic nanomaterials are very sensitive to the
morphologies and structures CoFe2O4 nanoparticles. The coercivity
behavior indicates that Co atoms in the Fe–O matrix increase mag-
netic anisotropy of the material.[41] It is well known that the surface
spin disorder enhancement caused by the decreasing of particles
size and the coercivity would approach zero under a short thermal
fluctuation (so-called superparamagnetism) if the crystal size is
small enough.[42]
Table 1. Magnetic parameters for the investigated CoFe2O4
nanoparticles
Temperature Coercivity,
Remanent
Saturation
(K)
Hc (kOe) magnetization, Mr (emu magnetization, Ms
gÀ1
)
(emu gÀ1
)
5
10.50
0.70
70.12
24.28
84.42
75.28
300
benzaldehyde and ethyl acetoacetate (Table 2). The obtained
results show that in the presence of CoFe2O4 MNPs the reaction
proceeds to product in high yield; in the absence of catalyst, the re-
action does not progress at all. Also the results in Table 2 indicate
that the optimum amount of the catalyst is 8 mol% of CoFe2O4
MNPs. Notably, increasing this amount does not show any change
in yield and time of reaction.
Subsequently to establish the best reaction conditions, we
focused on the effect of various solvents with varying polarity. It is
observed that water–ethanol (3:1) is the best choice for this reac-
tion over any organic solvents such as CHCl3, CH3CN, DMF, CH3NO2,
PhCH3 and MeOH (Table 3).
CoFe2O4 MNPs were used as an efficient catalyst for the synthesis
of highly functionalized tetrahydropyridines via five-component re-
action of aromatic aldehyde, amine and ethyl acetoacetate in
water–ethanol (3:1) as solvent (Scheme 1 and Table 4). The present
CoFe2O4 nanoparticles as efficient catalyst
In this research,
a general method for the synthesis of
tetrahydropyridines was developed using superparamagnetic
CoFe2O4 nanoparticles as catalyst using a simple and green process.
In order to study the catalytic effects of CoFe2O4 MNPs, catalytic
behaviors of various types of catalysts such as CoCl2, CoO powder,
CoO MNPs, FeCl3, Fe3O4 powder, Fe3O4 MNPs, CoFe2O4 powder
and CoFe2O4 MNPs were compared in the reaction of aniline,
Appl. Organometal. Chem. (2016)
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M. A. A. El-Remaily et al.
Table 2. Optimization of model reaction using various catalystsa
to afford the intermediate 5 with elimination of water. Next,
tautomerization of 5 generates intermediate 6, which immediately
undergoes intramolecular Mannich-type reaction to give intermedi-
ate 7. Eventually, the intermediate 7 tautomerizes to generate the
desired tetrahydropyridine 4a due to conjugation with the ester
group (Scheme 2).
Hence, we investigated the effects of various reaction param-
eters on the catalytic activity in order to optimize the protocol
for formation of 1H-pyrrole derivatives (Scheme 3). We chose
the reaction of aniline (2 mmol) with ethyl pyruvate (2 mmol)
as a model reaction under microwave irradiation; the results
are summarized in Table 5. It is noted that in the absence of
CoFe2O4 MNP catalyst, there is no detectable amount of the de-
sired product formed (Table 5, entry 1). The results show clearly
that the catalyst is effective for this transformation. Various cata-
lyst concentrations were also tested and use of a higher amount
of catalyst does not improve the yield (Table 5, entries 14 and 15)
while 8 mol% gives the best result (Table 5, entry13). When com-
paring with other catalysts, the CoFe2O4 MNPs give the best re-
sult (Table 5, entries 2–8).
Entry
Catalyst (mol%)
Time (min)
Yield (%)b
1
Without catalyst
CoCl2Á6H2O (10)
240
180
180
180
180
180
180
180
60
0
23
30
32
52
57
74
68
70
78
86
90
94
94
93
2
3
FeCl3Á6H2O (10)
4
CoO powder (10)
CoO MNPs (10)
5
6
Fe3O4 powder (10)
Fe3O4 MNPs (10)
CoFe2O4 powder (10)
CoFe2O4 MNPs (2)
CoFe2O4 MNPs (4)
CoFe2O4 MNPs (6)
CoFe2O4 MNPs (7)
CoFe2O4 MNPs (8)
CoFe2O4 MNPs (9)
CoFe2O4 MNPs (10)
7
8
9
10
11
12
13
14
15
60
60
60
60
60
60
aReaction conditions: 1 (2 mmol), 2a (2 mmol), 3 (1 mmol) and catalyst
(0.08 mmol) in a mixture of water and ethanol (3:1 ratio) refluxed at
120°C.
bIsolated yield based on 4a.
Then, the reactions were conducted in the presence of various
solvents such as CHCl3, CH3CN, DMF, CH3NO2, PhCH3 and MeOH
(Table 6). A good yield of 96% is obtained in water–ethanol (1:3)
(Table 6, entry 7).
To explain the role of microwaves, reactions were compared
under reflux conditions (method A) and with microwave irradia-
tion (method B) in H2O–EtOH (1:3) in the presence of 8 mol% of
CoFe2O4 MNPs (Table 7). When the reaction is carried out under
reflux conditions the reaction proceeds with long times and
yields of products are comparatively low, while the same reac-
tion carried under microwave irradiation gives excellent yields
of products in short reaction times. Moreover the structures of
compounds 5a and 5c were confirmed via X-ray crystallographic
analysis[41,42] (Figures 7 and 8) and their close packing structures
are shown in Figs 9 and 10.
A plausible reaction mechanism (Scheme 4) is suggested in
which the catalyst may activate ethyl pyruvate to react with an-
iline and give the ethyl 2-anilinoacrylate 3a and imine 3b. The
reaction between the ethyl 2-anilinoacrylate 3a and imine 3b
is an intermolecular Mannich reaction in the presence of
CoFe2O4 MNPs to produce intermediate 4. The final product 5
is afforded from intermediate 4 with elimination of EtOH
(Scheme 4).
Table 3. Optimization of model reaction using various solvents
Entry
Solvent
Time (min)
Yield (%)a
1
2
3
4
5
6
7
CHCl3
CH3CN
180
180
180
180
180
120
60
64
71
82
80
69
88
94
DMF
CH3NO2
PhCH3
MeOH
H2O–EtOH (3:1)
aIsolated yield.
Recycling of the catalyst is an important process from various as-
pects such as environmental concerns, costs of the catalyst and its
toxicity. Therefore, we studied the recycling of the CoFe2O4 MNP
catalyst for synthesis of tetrahydropyridines and pyrrole derivatives
under optimized conditions (Fig. 11). The catalyst was recovered
using a magnetic field and was washed with ethanol, dried at
50°C under vacuum to remove residual solvents and reused for sub-
sequent reactions at least five times without observation of appre-
ciable loss in its catalytic activity.
Scheme 1. Synthesis of tetrahydropyridine derivatives 4a–p.
approach offers several advantages such as high yields, environ-
mental benignity, simple work-up, excellent yield of products, short
reaction times as well as recoverability and reusability of the
catalyst.
Experimental
We turned our attention to a study of the mechanistic aspect of
this one-pot, five-component reaction. A plausible reaction mecha-
nism (Scheme 2) is suggested. The catalyst may activate the ethyl
acetoacetate and benzaldehyde to react with aniline and give the
β-enaminone 1 and imine 2. The reaction between β-enaminone
1 and imine 2 is an intermolecular Mannich reaction in the pres-
ence of CoFe2O4 MNPs to produce intermediate 3. Subsequently,
the reaction of activated aldehyde with intermediate 3 proceeds
Materials
All reagents were of analytical grade and used without further pu-
rification. Co(NO3)2Á6H2O and Fe(NO3)3Á9H2O (Sigma-Aldrich) were
used as cobalt and iron precursors while NaOH (pellets, 98%, Alfa
Aesar) acted as precipitant. All solutions were prepared with doubly
distilled water.
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CoFe2O4 nanoparticles for green synthesis of heterocyclic rings
Table 4. Synthesis of tetrahydropyridine derivatives 4a–p
Product
R
R1
Time (min)
Yield (%)
Product
R
R1
Time (min)
Yield (%)
4a
4b
4c
4d
4e
4f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
60
60
70
60
90
80
80
70
94
93
90
94
91
92
93
92
4i
4j
4-MePh
Ph
Ph
100
60
89
92
89
85
90
90
92
88
4-MeOPh
2-MeOPh
4-ClPh
4-ClPh
4-ClPh
4-ClPh
4-ClPh
4-ClPh
4-ClPh
4-ClPh
4k
4l
4-MeOPh
2-MeOPh
4-ClPh
90
90
2-ClPh
4m
4n
4o
4p
100
90
4-BrPh
4-FPh
4g
4h
4-FPh
4-NO2Ph
4-MePh
100
120
4-NO2Ph
Table 5. Optimization of model reaction using various catalystsa
Entry
Catalyst (mol%)
Time (min)
Yield (%)b
1
Without catalyst
CoCl2Á6H2O (10)
45
30
30
30
30
30
30
30
10
10
10
10
10
10
10
Trace
30
37
34
51
63
82
66
72
81
89
92
96
96
96
2
3
FeCl3Á6H2O (10)
4
CoO powder (10)
CoO MNPs (10)
5
6
Fe3O4 powder (10)
Fe3O4 MNPs (10)
CoFe2O4 powder (10)
CoFe2O4 MNPs (2)
CoFe2O4 MNPs (4)
CoFe2O4 MNPs (6)
CoFe2O4 MNPs (7)
CoFe2O4 MNPs (8)
CoFe2O4 MNPs (9)
CoFe2O4 MNPs (10)
7
8
9
10
11
12
13
14
15
aReaction conditions: 1a (2 mmol), 2 (2 mmol) and catalyst (0.08 mmol)
in a mixture of water and ethanol (1:3 ratio).
bIsolated yield based on 5a.
Scheme 2. Possible mechanism for the synthesis of tetrahydropyridine
derivatives.
Table 6. Optimization of model reaction using various solvents
Entry
Solvent
Time (min)
Yield (%)a
1
2
3
4
5
6
7
CHCl3
CH3CN
30
30
30
30
30
30
10
70
78
87
82
78
83
96
DMF
CH3NO2
PhCH3
MeOH
H2O–EtOH (1:3)
aIsolated yield.
Scheme 3. Synthesis of 1H-pyrrole derivatives 5a–j.
to serve as a surfactant that covers MNPs and prevents agglomera-
tion. The obtained solution was stirred for an additional 1 h to en-
sure mixing of PEG with the reactants. After that, the pH of the
solution was adjusted to 12. This can be achieved by adding 2 M
NaOH drop-by-drop with stirring. After continuous stirring at
500 rpm for 2 h, a homogeneous solution containing hydroxide
precipitates of the reactants was obtained. The obtained solutions
up to total volume of 80 ml were put in to autoclaves. Finally, the
Synthesis of CoFe2O4 nanoparticles
To prepare CoFe2O4 MNPs, in an appropriate ratio, stoichiometric
molar amounts of Co(NO3)2Á6H2O and Fe(NO3)3Á9H2O were each
dissolved in 15 ml of distilled water to form a clear solution and
mixed together. The mixture was stirred with a magnetic stirrer un-
til the reactants were dissolved completely. During the stirring pro-
cess, 10 ml of PEG-400 was added dropwise to the solution mixture
Appl. Organometal. Chem. (2016)
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M. A. A. El-Remaily et al.
Table 7. Synthesis of 1H-pyrrole derivatives 5a–j
Product
R
Method A
Method B
Time (h) Yield (%)a Time (min) Yield (%)a
5a
5b
5c
5d
5e
5f
H
4-Br
4
2
3
3
5
2
4
5
5
6
89
87
86
87
72
83
85
75
80
77
10
10
10
15
15
10
15
15
15
15
96
95
94
89
88
93
94
87
90
86
4-Cl
4-NO2
4-OH
4-OMe
4-CH3
naphthyl
2-CH3
3-CH3
5g
5h
5i
5j
aIsolated yield.
Figure 9. Close packing structure of compound 5a.
Figure 10. Close packing structure of compound 5c.
Figure 7. X-ray crystal structure of compound 5a.
Scheme 4. Possible mechanism for the synthesis 1H-pyrrole derivatives.
Figure 11. Recyclability of CoFe2O4 MNPs in the model reaction for (a)
synthesis of tetrahydropyridine 4a and (b) synthesis of 1H-pyrrole
derivative 5a.
Figure 8. X-ray crystal structure of compound 5c.
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CoFe2O4 nanoparticles for green synthesis of heterocyclic rings
autoclaves were left in an oven at 180°C for 24 h and then were
allowed to cool to room temperature gradually. The products were
centrifuged and washed several times with deionized water, ace-
tone and absolute ethanol. Then the samples were put again in
an oven at 90°C to dry for 3 h. The solid-phase samples obtained
were ground in a mortar to powder them. Obtained powders were
used further for all of the measurements.
calibrating line position and line shape in powder diffractometers.
The morphology of samples was studied using field-emission
SEM, performed with a JSM-6100 microscope (JEOL, Japan) at an
acceleration voltage of 30 kV. The chemical composition of the
synthesized nanostructures was also analyzed using an energy-
dispersive X-ray analysis unit attached to the SEM instrument.
TEM, HR-TEM and SAED studies were performed with a JEOL JEM-
2100F transmission electron microscope operated at an accelerat-
ing voltage of 200 kV, equipped with a field emission gun and an
ultrahigh-resolution pole-piece that provided a point-resolution
better than 0.19 nm. The samples for TEM were dispersed in etha-
nol, sonicated and sprayed on a carbon-coated copper grid and
then allowed to air-dry. Finally, a Gatan SOLARUS 950 was used be-
fore observation.
All melting points were recorded with a Melt-Temp II melting
point apparatus. IR spectra were measured as KBr pellets with a
Shimadzu DR-8001 spectrometer. [1]H NMR spectra were recorded
with a Bruker DRX 400 MHz using tetramethylsilane as an internal
reference and DMSO-d6 and CDCl3 as solvents. All compounds were
checked for their purity on TLC plates.
General procedure for piperidine derivatives (4a–p)
To a 50 ml round-bottom flask were added aromatic aldehyde
(2 mmol), aromatic amine (2 mmol) and ethyl acetoacetate (1 mmol)
in the presence of 8 mol% of CoFe2O4 nanoparticles in water and
ethanol (3:1 ratio) as a solvent. Then the reaction mixture was
refluxed at 120°C for the stipulated period of time (60–120 min).
The progress of the reaction was monitored by TLC. After comple-
tion of the reaction, the catalyst was separated magnetically. The re-
action mixture was allowed to stand overnight. The solid material
was filtered off, washed with water, dried and recrystallized from
ethanol to furnish pure piperidine derivatives. All products have
been reported previously.[24–32,40]
General procedure for 1H-pyrrole derivatives (5a–j)
Conclusions
Method A
A robust synthesis of CoFe2O4 highly stable magnetic nanocatalyst
has been presented using a combined hydrothermal and co-
precipitation process. It is used as an efficient and environmentally
friendly nanocatalyst with average particle size of 15 nm for organic
reactions. Additionally, the magnetic properties make possible the
complete recovery of the catalyst by means of an external magnetic
field, and it could be reused up to five times without any significant
loss of the initial catalytic activity. These advantages become even
more attractive if such reactions can be conducted in aqueous
media.
To a 50 ml round-bottom flask were added aromatic amine
(2 mmol) and ethyl pyruvate (2 mmol) in the presence of 8 mol%
of CoFe2O4 nanoparticles in water and ethanol (1:3 ratio) as a sol-
vent. Then the reaction mixture was refluxed at 120°C for the stipu-
lated period of time (2–6 h). The progress of the reaction was
monitored by TLC. After completion of the reaction, the catalyst
was separated magnetically. The reaction mixture was allowed to
stand overnight. The solid material was filtered off, washed with wa-
ter, dried and recrystallized from ethanol to furnish pure 1H-pyrrole
derivatives. Some products have been reported previously.[44–46]
Acknowledgments
Method B
The authors are deeply grateful to Sohag University in Egypt for
supporting and facilitating this study. Mahmoud A. A. El Remaily ac-
knowledges Prof. Dr. F. Santoyo-Gonzalez, Granada University,
Spain, Prof. Dr. Santigo Gracia Granda, Oviedo University, Spain,
and Prof. Dr. Ahmed M. M. Soliman for facilitating this study.
To a 50 ml round-bottom flask were added aromatic amine
(2 mmol) and ethyl pyruvate (2 mmol) in the presence of 8 mol%
of CoFe2O4 nanoparticles in water and ethanol (1:3 ratio) as a sol-
vent. Then the reaction mixture was subjected to microwave irradi-
ation for the stipulated period of time (10–15 min). The progress of
the reaction was monitored by TLC. After completion of the reaction,
the catalyst was separated magnetically. The solid material was ob-
tained quickly and filtered off, washed with water, dried and recrys-
tallized from ethanol to furnish pure 1H-pyrrole derivatives. Some
products have been reported previously.[43,44,46]
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Supporting information
Additional supporting information may be found in the online ver-
sion of this article at the publisher’s web site.
Figure S1: FT-IR spectra for the prepared CoFe2O4 nanoparticles.
Figure S2: TG/DTG curves for the prepared CoFe2O4 nanoparticles.
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