Fe3O4@chitosan nanoparticles: A valuable heterogeneous nanocatalyst for the synthesis of 2,4,5-trisubstituted imidazoles

Article abstract of DOI:10.1039/c4ra03176h

Chitosan-coated Fe₃O₄ nanoparticles (Fe ₃O₄@CS) were prepared simply through in situ co-precipitation of Fe²⁺ and Fe³⁺ ions via NH ₄OH in an aqueous solution of chitosan and their catalytic activity was investigated in the synthesis of 2,4,5-trisubstituted imidazoles by a one-pot condensation of benzil derivatives, aryl aldehydes and ammonium acetate in EtOH. This novel method offers several advantages compared to those reported in the previous literature, including avoiding the use of harmful catalysts, easy and quick isolation of the products, excellent yields, mild and clean conditions, and simplicity of the methodology. High catalytic activity and ease of recovery using an external magnetic field are additional eco-friendly attributes of this catalytic system. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra03176h

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Fe3O4@chitosan nanoparticles: a valuable
heterogeneous nanocatalyst for the synthesis of
2,4,5-trisubstituted imidazoles
Cite this: RSC Adv., 2014, 4, 20932
*
Zohre Zarnegar and Javad Safari
Chitosan-coated Fe3O4 nanoparticles (Fe3O4@CS) were prepared simply through in situ co-precipitation of
Fe2+ and Fe3+ ions via NH4OH in an aqueous solution of chitosan and their catalytic activity was investigated
in the synthesis of 2,4,5-trisubstituted imidazoles by a one-pot condensation of benzil derivatives, aryl
aldehydes and ammonium acetate in EtOH. This novel method offers several advantages compared to
those reported in the previous literature, including avoiding the use of harmful catalysts, easy and quick
isolation of the products, excellent yields, mild and clean conditions, and simplicity of the methodology.
High catalytic activity and ease of recovery using an external magnetic field are additional eco-friendly
attributes of this catalytic system.
Received 8th April 2014
Accepted 25th April 2014
DOI: 10.1039/c4ra03176h
www.rsc.org/advances
low toxicity and price.19 Other important features of these
magnetic catalysts are high catalytic activity, simple magnetic
1. Introduction
separation of them using an external magnet, high degree of
chemical stability in various organic and inorganic solvents,
reusability and benign character in the context of green chem-
istry. As a result, magnetically recyclable nanocatalyst systems
have enabled researchers to apply nanocatalysts as greener and
sustainable options for organic transformations.20
Imidazole derivatives are a class of heterocyclic compounds that
contain nitrogen and are currently under intensive focus due to
their wide range of applications, because they have many phar-
macological properties and play important roles in biochemical
processes.1,2 The imidazole compounds are known to possess
NO synthase inhibition and antifungal, antibiotic, antimycotic,
antiulcerative, antitumor, antibacterial, and CB1 receptor
antagonistic activities.3,4 Various substituted imidazoles act as
inhibitors of p38 MAP kinase5 and B-Raf kinase,6 plant growth
regulators,7 glucagon receptors,8 pesticides,9 and therapeutic
agents.10 Thus, synthesis of these important heterocyclic nucleus
have rekindled our interest in obtaining trisubstituted imid-
azole. Accordingly, a number of synthetic methods have been
reported for the synthesis of 2,4,5-trisubstituted imidazoles.
These methods involve condensation of aldehyde, benzil and
ammonium acetate by using various catalytic systems.11–18 Owing
to the wide range of pharmacological and biological activities,
the development of economical, effective, clean, high-yielding
and mild environmental benign protocols is still desirable and is
in demand. Moreover, the design of efficient, valuable, and
recoverable catalysts is important for both economical and
environmental points of view.
On the other hand, recently biopolymers such as cellulose,21
starch,22 chitosan (CS)20,23 or wool24 have been used as hetero-
geneous catalytic systems. In this context, chitosan can play a
major role as a natural, biocompatible, and biodegradable
polymer. Literature survey shows that a wide range of applica-
tions have been reported for chitosan in different elds such as
drug delivery, cosmetics, water treatment, food packaging, fuel
cells, membranes, hydrogels, surface conditioners, and cata-
lyst.25 Chitosan as a polyaminosaccharide, can be explored as a
mild bifunctional heterogeneous catalyst in organic reactions.
In this regard, chitosan contains both amino groups and
primary and secondary hydroxyl groups in higher concentra-
tions. Therefore, chitosan can activate the electrophilic and
nucleophilic components of the reactions by hydrogen bonding
and lone pairs, respectively.23a
Herein we wish to report a new efficient and practical route
for the one-pot three-component synthesis of trisubstituted
imidazoles by the condensation of benzil derivatives, aryl
aldehydes and ammonium acetate catalyzed by Fe3O4@CS
nanoparticles. This new approach has several superiorities
versus previous reports for the synthesis of highly substituted
imidazole derivatives and opens an important eld to the use of
magnetically recoverable and environmentally benign hetero-
geneous nanocatalyst in the synthesis of pharmaceutically
important heterocyclic compounds (Scheme 1).
In recent decade, magnetic nanoparticles (MNPs) have
appeared as an excellent type of catalyst support because of
their good stability, easy synthesis and functionalization, high
surface area and facile separation by magnetic forces, as well as
Laboratory of Organic Compound Research, Department of Organic Chemistry, College
of Chemistry, University of Kashan, P.O. Box: 87317-51167, Kashan, I.R. Iran. E-mail:
Safari@kashanu.ac.ir; safari_jav@yahoo.com; Fax: +98 361 5912397; Tel: +98 361
591 2320
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Scheme 1 One-pot synthesis of 2,4,5-trisubstituted imidazoles catalyzed by Fe3O4@CS.
Scheme 2 Preparation steps for fabricating heterogeneous Fe3O4@CS nanoparticles.20b,26
which corresponds to the stretching vibration of Fe–O groups;
indicating that the magnetic Fe3O4 MNPs are coated by chitosan
(Fig. 1(c)).20
2. Results and discussion
Fe3O4 nanoparticles are prepared by chemical co-precipitation
of Fe2+ and Fe3+ ions with molar ratio 1 : 2, in presence of chi-
tosan, followed by the hydrothermal treatment (Scheme 2).
The magnetically heterogeneous catalyst, Fe3O4@CS nano-
particles, is characterized by FT-IR (Fig. 1), XRD (Fig. 2), TGA
(Fig. 3), SEM (Fig. 4), and VSM (Fig. 5). The FT-IR spectra of
chitosan, Fe3O4, and Fe3O4@CS, consistent with their respective
structures (Fig. 1). The FT-IR spectrum of chitosan (Fig. 1(a))
shows a broad band at 3433 cmꢀ1 which corresponds to the
stretching vibrations of O–H and N–H groups. Peaks appearing
at 2923 and 2855 cmꢀ1 are characteristic of C–H stretching
vibrations. The band at 1634 cmꢀ1 is assigned to N–H bending
vibration and that of 1423 cmꢀ1 to C–O stretching of primary
alcoholic groups in chitosan. The band at 1084 cmꢀ1 display the
stretching vibrations of the C–O bond. The Fe–O stretching
vibration near 576 cmꢀ1, O–H stretching vibration near 3429
cmꢀ1, O–H deformed vibration near 1620 cmꢀ1 were observed
for Fe3O4 MNPs in Fig. 1(b). For Fe3O4@CS nanoparticles, chi-
tosan absorptions appear in addition to a peak at 580 cmꢀ1
To conrm the presence of crystalline Fe3O4 and Fe3O4@
chitosan nanoparticles, the structure of the magnetic nano-
particles was characterized by XRD and the diffractogram is
shown in Fig. 2. There are eight diffraction peaks: (2 2 0), (3 1 1),
(4 0 0), (3 3 1), (4 2 2), (3 3 3), (4 4 0) and (5 3 1) in the Fe3O4 and
Fe3O4@chitosan, which is the standard pattern for crystalline
magnetite with spinel structure (JCPDS card no. 01-1111).27 It is
clearly seen there is little inuence of the dispersant on the
structure of magnetic particles, except that the amorphous
phase of chitosan appears as a scattered maximum on the
background as seen from Fig. 2(b). As shown in Fig. 2(b), the
XRD patterns conrm that the coating process did not induce
any phase change of Fe3O4 MNPs.
In order to obtain information on the thermal stability, TGA
experiments are carried out by heating Fe3O4 and Fe3O4@CS up
to 600 ꢁC (Fig. 3). The weightloss of Fe3O4@CS nanoparticles is
about 40% at 250–350 ꢁC, corresponding to the thermal
decomposition of chitosan chains over Fe3O4 nanoparticles.26
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Fig. 1 IR spectra of (a) chitosan, (b) Fe3O4, (c) Fe3O4@CS and (d) recovered Fe3O4@chitosan.
As illustrated in Fig. 4, the particle size was studied by easily and quickly separated from the reaction mixture with the
scanning electron microscopy (SEM) and the identication of help of an external magnet, which proves that magnetic prop-
Fe3O4@chitosan was based on the analysis of SEM images. The erty of the Fe3O4@chitosan as nanocatalyst is strong enough for
obtained SEM images of nanoparticles clearly showed that easy recovery and reuse from the reaction mixture.
Fe3O4 nanoparticles were properly supported on chitosan.
To show the efficiency of the Fe3O4@chitosan as magnetic
Magnetic measurements of Fe3O4 and Fe3O4@chitosan catalyst, initially, we sought a mild and convenient method for
nanoparticles were investigated with VSM. The hysteresis loops the synthesis of 2,4,5-trisubstituted imidazole derivatives at
of Fe3O4 and Fe3O4@chitosan nanoparticles are shown in Fig. 5. heating condition. Our investigation began with the evaluation
It can be seen that both materials show ferromagnetic behavior. of Fe3O4@chitosan as heterogeneous catalyst in the reaction of
The magnetic saturation values of Fe3O4 MNPs and Fe3O4@ benzaldehyde (1 mmol), benzil (1 mmol) and ammonium
chitosan nanoparticles are 66.58 and 20.17 emu gꢀ1, respec- acetate (5 mmol) as model reaction. The use of 0.05 g of
tively. The decrease in magnetic saturation for Fe3O4@chitosan Fe3O4@chitosan as nanocatalyst in EtOH afforded a 95% yield
is attributed to the cover of chitosan polymeric matrix on the (Table 1, entry 4) of the desired product 4a. Among the tested
surface of magnetic Fe3O4 MNPs.28 However, such a magnetic solvents such as chloroform, dichloromethane, methanol,
property is strong enough for the as-prepared Fe3O4@chitosan ethanol, and acetonitrile, the formation of product 4a was more
to be easily separated from EtOH under a magnetic eld. The facile and proceeded to give highest yield, in EtOH as solvent.
magnetic effect of Fe3O4@chitosan under an external magnetic The results indicated that the yield gradually decreased as we
eld is shown in Fig. 6. Clearly, the Fe3O4@chitosan can be moved from highly polar to less polar solvents. To evaluate and
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Fig. 4 SEM morphology of (a) unmodified Fe3O4 magnetic nano-
particles, (b) Fe3O4@chitosan nanocomposite and (c) Fe3O4@chitosan
after being used 6 times.
Fig. 2 XRD patterns of the (a) Fe3O4 MNPs, (b) Fe3O4@CS nano-
composite and (c) chitosan.
Fig. 5 Magnetization curves for the Fe3O4 MNPs and Fe3O4@chitosan
nanocomposite at room temperature.
Fig. 3 TGA curves for (a) uncoated MNPs and (b) Fe3O4@chitosan
nanocomposite.
We next examined a wide variety of aldehydes and 1,2-dike-
optimize the catalytic system, one-pot condensation to give 4a tones to establish the scope of this catalytic transformation
was examined with Fe3O4, chitosan Fe3O4@chitosan as catalyst (Table 2). Various aromatic aldehydes bearing electron
(Table 1). Interestingly, it was found that Fe3O4@chitosan was donating and electron withdrawing substituents underwent this
proved to be an efficient catalyst and gave exclusively 1-(phenyl)- cyclocondensation to furnish trisubstituted imidazoles in high
2,4,5-triphenylimidazole 4a in 95% yield in 2 h under reux yields. Also, benzil derivatives afforded the corresponding
conditions (Table 1). As Table 1 shows, initial screening studies imidazoles in high yields. In general, this synthetic protocol was
identied that all the above-mentioned catalysts shows a good clean and no side products were detected. In all cases, the
catalytic activity for the model reaction but Fe3O4@chitosan reactions proceeded efficiently under mild conditions. The
exhibited highest catalytic activity as compared with Fe3O4 and results reveal that the unique heterogeneous Fe3O4@chitosan
chitosan. We believe that this composite has two active nanoparticles appears as an effective catalyst which produces
components for catalytic activity containing chitosan and high yields through a simple procedure.
magnetite. With notice to these results, Fe3O4@chitosan were
chosen as the best catalyst for further work.
The structure of trisubstituted imidazoles 4a–l was deduced
from their high-eld 1H NMR, IR, Rf, and UV spectral data. Also,
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to methoxy group. In this gure, the signals of aromatic protons
can be seen at d ¼ 7.4–8.1 ppm. The signal around d ¼ 12.5 ppm
is related to the NH proton. Presence of this signal conrmed
the formation of desired products in this reaction. To prove NH
group, we have investigated hydrogen–deuterium exchange
protocol for compound 4b (Fig. 6(b)). In this method, a drop of
D2O is placed in the NMR tube containing the acetone solution
of the compound 4b. Aer shaking a sample and sitting for a
few minutes, the NH hydrogen is replaced deuterium, causing it
to disappear from the spectrum at d ¼ 12.5 ppm.
A plausible mechanism for this reaction catalyzed by
Fe3O4@chitosan is shown in Scheme 3. In the case of trisub-
stituted imidazole the reaction proceeds through diamine
intermediate A. The aldehydic carbonyl oxygen are activated by
Fe3O4 (Fe+3 and Fe+2) and chitosan supported magnetic nano-
particles and subsequent condensation with two molecules of
ammonia to form diamine intermediate A. The free hydroxyl
and amino groups distributed on the surface of chitosan sup-
ported Fe3O4 in high concentrations activate the carbonyl group
of the aldehyde.23a Condenses with the carbonyl carbons of the
1,2-diketone followed by dehydration to afford the imino
intermediate B, which rearranges to the required trisubstituted
imidazoles.1
One of the advantages of this active, non-toxic, and envi-
ronmentally benign heterogeneous bio-polymer catalyst is its
ability to perform as a recyclable reaction medium. In a
typical procedure, aer completion of the reaction, the
magnetic nanocatalyst is easily and efficiently separated from
the product by attaching an external magnet to the reaction
vessel, followed by simple decantation of the reaction solu-
tion (Fig. 7). The recycled catalyst could be reused six times
without great loss of catalytic activity (Fig. 8). The recovered
nanocatalyst was characterized with FT-IR spectroscopy
(Fig. 1(d)). In IR spectrum, the band from 580 cmꢀ1 is
assigned to the stretching vibrations of (Fe–O) bond in Fe3O4,
and the band at about 1027 cmꢀ1 is belong to the stretching
of the (C–O) bond. The coated cross-linked chitosan
ensured the stability of the Fe3O4 core during the catalytic
process, so as to obtain a high recyclability. Aer 6 times of
reuse, chitosan may be destroyed and Fe3O4 having lost the
protection of chitosan was easy to aggregate (as shown in
SEM image Fig. 4(c)) or oxidize. There for, the catalyst would
be lost in the solution and recovery efficiency decreased
gradually.23b
Fig. 6 1H NMR spectra of 2-(4-methoxyphenyl)-4,5-diphenyl-1H-
imidazole (4b) in (a) acetone + DMSO-d6 and (b) acetone + D2O.
Table 1 Effect of the amount of Fe3O4@chitosan nanoparticles and
solvents on the synthesis of compound 4a under reflux condition
Entry Catalyst (g)
Solvent
EtOH
Time (h) Yield (%)
1
—
5
3
2
2
2
2
2
3
3
5
5
15
60
72
95
94
70
80
90
70
55
40
2
3
4
5
Fe3O4@chitosan (0.03) EtOH
Fe3O4@chitosan (0.04) EtOH
Fe3O4@chitosan (0.05) EtOH
Fe3O4@chitosan (0.06) EtOH
3. Conclusions
6
Fe3O4 (0.05)
EtOH
EtOH
7
Chitosan (0.05)
In summary, a new, simple, efficient and environmentally
benign method for the synthesis of 2,4,5-trisubstituted
imidazoles by the use of renewable and heterogeneous
Fe3O4@chitosan as magnetic biocatalyst has been described.
Clean reaction proles, excellent yields, the use of a one-pot
and multicomponent procedure for the synthesis of imidaz-
8
Fe3O4@chitosan (0.05) MeOH
9
10
11
Fe3O4@chitosan (0.05) Acetonitrile
Fe3O4@chitosan (0.05) Chloroform
Fe3O4@chitosan (0.05) Dichloromethane
1
their melting points were compared with literature reports. H oles, reusability of the catalyst, practicability, and opera-
NMR spectra for compound 4b is given in Fig. 6. In the 1H NMR tional simplicity are the important features of this
spectra Fig. 6(a), the signal around d ¼ 3.85 ppm corresponding methodology.
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Table 2 One-pot synthesis of 2,4,5-trisubstituted imidazoles catalyzed by Fe3O4@chitosan under reflux condition
Entry
R1, R2
R3
Product
Time (h)
Yield (%)
mprep./mplit. (ꢁC)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
OMe
OMe
OMe
F
H
p-OMe
m-OMe, p-OMe
p-Cl
m-OMe
2-Naphthyl
m-OMe, m-OMe
H
4a
4b
4c
4d
4e
4f
4g
4h
4i
2
3
2
95
90
92
96
98
98
98
95
90
95
98
98
(271–273)/(270–272) [ref. 29]
(230–231)/(228–231) [ref. 29]
(214–216)/213–216 [ref. 30]
(260–262)/(260–261) [ref. 30]
(258–260)/(259–262) [ref. 29]
(274–275)/(273–276) [ref. 30]
(255–257)/(254–256) [ref. 30]
(202–204)/(201–203) [ref. 29]
(184–186)/(183–185) [ref. 29]
(228–230)/(228–230) [ref. 31]
(206–208)/(207–208) [ref. 30]
(273–275)/(273–275) [ref. 31]
2.5
2.5
2.5
3.5
3
3.5
3
1
9
p-OMe
10
11
12
2-Naphthyl
m-OMe, p-OMe
2-Naphthyl
4j
4k
4l
F
1
Scheme 3 Plausible mechanism of the reaction.
with a Bruker DRX-400 spectrometer at 400 and 100 MHz
respectively. NMR spectra were obtained in DMSO-d6 and
acetone solutions and are reported as parts per million (ppm)
downeld from tetramethylsilane as internal standard. Fourier
transform infrared spectroscopy (FT-IR) spectra were obtained
with potassium bromide pellets in the range 400–4000 cmꢀ1
with a Perkin-Elmer 550 spectrometer. The UV-vis measure-
ments were obtained with a GBC cintra 6 UV-vis spectropho-
tometer. Nanostructures were characterized using a Holland
Fig. 7 Separation of the nanocatalyst from the reaction mixture by an
external magnet.
4. Experimental
4.1. Chemicals and apparatus
All reagents were purchased from Merck and Aldrich and used
without further purication. Melting points were determined in
open capillaries using an Electrothermal Mk3 apparatus and
are uncorrected. H NMR and 13C NMR spectra were recorded
1
Fig. 8 Reusability of Fe3O4@chitosan for the synthesis of 4a and 4b.
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Philips Xpert X-ray powder diffraction (XRD) diffractometer 1H, N–H), 8.12 (d, 2H, 3J ¼ 8.8 Hz, Ar-H), 7.58–7.59 (m, 4H, Ar-
(CuK, radiation, l ¼ 0.154056 nm), at a scanning speed of 2ꢁ H), 7.30–7.36 (m, 6H, Ar-H), 7.04 (d, 2H, 3J ¼ 8.4 Hz, Ar-H), 3.85
minꢀ1 from 10ꢁ to 100ꢁ (2q). Scanning electron microscope (s, 3H, OCH3).
(SEM) was performed on a FEI Quanta 200 SEM operated at a
4.4.3. 2-(3,4-Dimethoxyphenyl)-4,5-diphenyl-1H-imidazole
20 kV accelerating voltage. The samples for SEM were prepared (4c, C23H20N2O2). White powder; Rf (in petroleum
by spreading a small drop containing nanoparticles onto a ether : ethylacetate; 7 : 3(v/v)): 0.23; UV (CHCl3) lmax(nm): 350;
silicon wafer and being dried almost completely in air at room IR (KBr) ꢀn (cmꢀ1): 3430 (N–H), 1600 (C]C), 1500 (C]N), 1257
temperature for 2 h, and then were transferred onto SEM (C–O); 1H NMR (CDCl3, 400 MHz) d (ppm): 9.8 (s, 1H, N–H),
conductive tapes. The transferred sample was coated with a thin 8.53–8.58 (m, 3H, Ar-H), 7.27–7.33 (m, 9H, Ar-H), 6.90 (d, 1H, 3J
layer of gold before measurement. The magnetic properties ¼ 7.6 Hz, Ar-H), 3.92 (s, 3H, OCH3), 3.89 (s, 3H, OCH3).
were characterized by a vibrating sample magnetometer (VSM,
Lakeshore7407) at room temperature.
4.4.4. 2-(4-Chlorophenyl)-4,5-diphenyl-1H-imidazole (4d,
21H15N2Cl). White powder; Rf (in petroleum
C
ether : ethylacetate; 7 : 3(v/v)): 0.86; UV (CHCl3) lmax(nm): 348;
IR (KBr) ꢀn (cmꢀ1): 3433 (N–H), 1602 (C]C), 1485 (C]N), 1H
NMR (CDCl3, 400 MHz) d (ppm): 9.6 (s, 1H, N–H), 7.83–7.85 (d,
2H, 3J ¼ 8.4 Hz, Ar-H), 7.56 (m, 4H, Ar-H), 7.41–7.43 (d, 2H, 3J ¼
8.4 Hz, Ar-H), 7.27–7.37 (m, 6H, Ar-H).
4.2. Preparation of the Fe3O4@CS
Fe3O4@CS nanoparticles were prepared using chemical copre-
cipitation described in the literature.26 In short, 1.5 g of chito-
san (molecular weight: 100 000–300 000) is dissolved in 100 mL
of 0.05 M acetic acid solution; to which FeCl2$4H2O (1.29 g,
0.0065 mol) and FeCl3$6H2O (3.51 g, 0.013 mol) are added. The
resulting solution is mechanically stirred for 6 h at 80 ꢁC under
Ar atmosphere. Subsequently, 6 mL of 25% NH4OH is injected
dropwise into the reaction mixture with constant stirring. Aer
30 min, the mixture is cooled to room temperature and chitosan
coated over magnetic nanoparticles were separated by magnetic
decantation and washed three times with distilled water, then
ethanol, and nally dried under vacuum at room temperature
(Scheme 3).
4.4.5. 2-(3-Methoxyphenyl)-4,5-diphenyl-1H-imidazole (4e,
C
22H18N2O).
White
powder;
Rf
(in
petroleum
ether : ethylacetate; 7 : 3(v/v)): 0.37; UV (CHCl3) lmax(nm): 346;
IR (KBr) ꢀn (cmꢀ1): 3435 (N–H), 1591 (C]C), 1482 (C]N), 1241
(C–O); 1H NMR (CDCl3, 400 MHz) d (ppm): 9.5 (s, 1H, N–H), 7.54
(m, 1H, Ar-H), 7.43–7.27 (m, 1H, Ar-H), 6.95 (d, 1H, 3J ¼ 8 Hz, Ar-
H), 3.89 (s, 3H, OCH3).
4.4.6. 2-(2-Naphthyl)-4,5-diphenyl-1H-imidazole
(4f,
C
28H18N2). White powder; Rf (in petroleum ether : ethylacetate;
7 : 3(v/v)): 0.79; UV (CHCl3) lmax(nm): 344, IR (KBr) ꢀn (cmꢀ1):
3434 (N–H),1631 (C]C), 1501 (C]N), 1H NMR (CDCl3, 400
MHz) d (ppm): 9.6 (s, 1H, N–H), 8.37 (s, 1H, Ar-H), 8.1 (d, 1H, 3J
¼ 8 Hz, Ar-H), 7.76–7.95 (m, 3H, Ar-H), 7.61 (m, 3H, Ar-H), 7.52–
4.3. General procedure for the synthesis of 2,4,5-
trisubstituted imidazoles
3
7.53 (t, 3H, J ¼ 7.6 Hz, Ar-H), 7.34–7.38 (m, 6H, Ar-H).
A mixture of benzil (1 mmol), aldehyde (1 mmol), ammonium
acetate (0.4 g, 5 mmol) and Fe3O4@CS (0.05 g) in 10 mL ethanol
was taken in a 50 mL ask and the reaction mixture was stirred
under reux condition for the stipulated period of time. The
progress of the reaction was monitored by TLC. Aer the reac-
tion was completed, the catalyst was separated by an external
magnet. The reaction mixture was concentrated on a rotary
evaporator under reduced pressure and the solid product
obtained was washed with water and recrystallized from
acetone–water 9 : 1 (v/v) to produce the desired 2,4,5-trisubsti-
tuted imidazoles.
4.4.7. 2-(3,5-Dimethoxyphenyl)-4,5-diphenyl-1H-imidazole
(4g, C23H20N2O2). White powder; Rf (in petroleum
ether : ethylacetate; 7 : 3(v/v)): 0.37; UV (CHCl3) lmax(nm): 344,
IR (KBr) ꢀn (cmꢀ1): 3434 (N–H), 1601 (C]C), 1470 (C]N), 1155
(C–O); 1H NMR (acetone + DMSO-d6, 400 MHz) d (ppm): 12.9 (s,
1H, N–H), 8.01–8.07 (m, 4H, Ar-H), 7.83–7.88 (m, 5H, Ar-H), 7.78
3
4
(d, 2H, J ¼ 7.8 Hz, Ar-H), 7.64 (t, 1H, J ¼ 2 Hz, Ar-H), 3.31 (s,
6H, OCH3).
4.4.8. 2-(Phenyl)-4,5-bis(4-methoxyphenyl)-1H-imidazole
(4h, C23H20N2O2). White powder; Rf (in petroleum
ether : ethylacetate; 7 : 3(v/v)): 0.62; UV (CHCl3) lmax(nm): 344;
IR (KBr) ꢀn (cmꢀ1): 3430 (N–H), 1613 (C]C), 1504 (C]N), 1248
(C–O); 1H NMR (acetone + DMSO-d6, 400 MHz) d (ppm): 12.7 (s,
1H, N–H), 8.62 (d, 2H, 3J ¼ 7.2 Hz, Ar-H), 7.87–7,97 (m, 7H, Ar-
4.4. Product characterization data of 2,4,5-trisubstituted
imidazoles
4.4.1. 2,4,5-Triphenyl-1H-imidazol (4a, C21H16N2). White H); 7.80 (d, 1H, 3J ¼ 7.2 Hz, Ar-H), 7.38–7.42 (m, 3H, Ar-H), 4.27
powder; Rf (in petroleum ether : ethylacetate; 7 : 3(v/v)): 0.74; UV (s, 6H, OCH3).
(CHCl3) lmax(nm): 334; IR (KBr) ꢀn (cmꢀ1): 3434 (N–H),1597 (C]
4.4.9. 2-(4-Methoxyphenyl)-4,5-bis(4-methoxyphenyl)-1H-
C), 1490 (C]N), 1H NMR (acetone + DMSO-d6, 400 MHz) d imidazole (4i, C24H22N2O3). White powder; Rf (in petroleum
3
(ppm): 12.9 (s, 1H, N–H), 8.63 (d, 2H, J ¼ 7.9 Hz, Ar-H), 8.08– ether : ethylacetate; 7 : 3(v/v)): 0.28; UV (CHCl3) lmax(nm): 348,
7.14 (m, 4H, Ar-H), 7.92 (m, 4H, Ar-H), 7.83 (t, 3J ¼ 8 Hz, 2H, Ar- IR (KBr) ꢀn (cmꢀ1): 3426 (N–H), 1612 (C]C), 1507 (C]N), 1261
3
3
H), 7.73 (t, J ¼ 7 Hz, 2H, Ar-H), 7.67 (t, J ¼ 8 Hz, 1H, Ar-H).
(C–O); 1H NMR (acetone + DMSO-d6, 400 MHz) d (ppm): 12.7 (s,
4.4.2. 2-(4-Methoxyphenyl)-4,5-diphenyl-1H-imidazole (4b, 1H, N–H), 8.53 (d, 2H, 3J ¼ 8.8 Hz, Ar-H), 7.92–7.97 (m, 4H, Ar-
C
22H18N2O).
White
powder;
Rf
(in
petroleum H), 7.47 (m, 4H, Ar-H), 7.33 (d, 2H, 3J ¼ 8 Hz, Ar-H), 4.29 (s, 9H,
ether : ethylacetate; 7 : 3(v/v)): 0.64; UV (CHCl3) lmax(nm): 338; 3OCH3).
IR (KBr) ꢀn (cmꢀ1): 3432 (N–H), 1611 (C]C), 1494 (C]N), 1250
4.4.10. 2-(2-Naphthyl)-4,5-bis(4-methoxyphenyl)-1H-imid-
(C–O); 1H NMR (acetone + DMSO-d6, 400 MHz) d (ppm): 12.5 (s, azole (4j, C27H22N2O2). Cream powder; Rf (in petroleum
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ether : ethylacetate; 7 : 3(v/v)): 0.48; UV (CHCl3) lmax(nm): 360;
IR (KBr) ꢀn (cmꢀ1): 3425 (N–H), 1613 (C]C), 1511 (C]N),
9 T. Maier, R. Schmierer, K. Bauer, H. Bieringer, H. Buerstell
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1247(C–O); H NMR (DMSO-d6, 400 MHz) d (ppm): 12.7 (s, 1H,
N–H), 8.56 (s, 1H, Ar-H), 8.22 (d, 1H, 3J ¼ 8 Hz, Ar-H), 7.96–7.98 10 J. Heeres, L. J. J. Backx, J. H. Mostmans and J. Van Custem,
(m, 4H, Ar-H), 7.46–7.51 (m, 8H, Ar-H), 6.97 (m, 3H, Ar-H), 3.76
(s, 3H, OCH3), 3.69 (s, 3H, OCH3).
J. Med. Chem., 1979, 22, 1003–1005.
11 A. Shaabani and A. Rahmati, J. Mol. Catal. A: Chem., 2006,
249, 246–248.
4.4.11. 2-(3,4-Dimethoxyphenyl)-4,5-bis(4-uorophenyl)-1H-
imidazole (4k, C23H18F2N2O2). Cream powder; Rf (in petroleum 12 K. Sivakumar, A. Kathirvel and A. Lalitha, Tetrahedron Lett.,
ether : ethylacetate; 7 : 3(v/v)): 0.24; UV (CHCl3) lmax(nm): 340; IR 2010, 51, 3018–3021.
(KBr) ꢀn (cmꢀ1): 3440 (N–H), 1604(C]C), 1504 (C]N), 1228(C–O); 13 K. F. Shelke, S. B. Sapkal, S. S. Sonar, B. R. Madje,
1H NMR (DMSO-d6, 400 MHz) d (ppm): 12.9 (s, 1H, N–H), 8.19 (d,
2H, 3J ¼ 8 Hz, Ar-H); 8.05 (m, 4H, Ar-H), 7.78 (t, 2H, 3J ¼ 8 Hz, Ar-
H), 7.58 (m, 3H, Ar-H), 4.34 (s, 3H, OCH3), 4.30 (s, 3H, OCH3).
4.4.12. 2-(2-Naphthyl)-4,5-bis(4-uorophenyl)-1H-imidazole
B. B. Shingate and M. S. Shingare, Bull. Korean Chem. Soc.,
2009, 30, 1057–1060.
14 S. D. Jadhave, N. D. Kokare and S. D. Jadhave, J. Heterocycl.
Chem., 2009, 45, 1461–1464.
(4l, C25H16N2F2). White powder; Rf (in petroleum 15 H. Weinmann, M. Harre, K. Koeing, E. Merten and
ether : ethylacetate; 7 : 3(v/v)): 0.73; UV (CHCl3) lmax(nm): 352,
U. Tilestam, Tetrahedron Lett., 2002, 43, 593–595.
IR (KBr) ꢀn (cmꢀ1): 3433 (N–H), 1669 (C]C), 1559 (C]N), 16 J. Liu, J. Chen, J. Zhao, Y. Zhao, L. Li and H. Zhang, Synthesis,
1
1247(C–O); H NMR (DMSO-d6, 400 MHz) d (ppm): 12.9 (s, 1H,
2003, 2661–2666.
N–H), 8.58 (s, 1H, Ar-H), 8.23 (d, 1H, 3J ¼ 7.2 Hz, Ar-H), 7.94–8.21 17 N. D. Kokare, J. N. Sangshetti and D. B. Shinde, Synthesis,
(m, 4H, Ar-H)),7.47–7.56 (m, 5H, Ar-H), 7.33 (t, 2H, 3J ¼ 8.4 Hz,
Ar-H), 7.16 (t, 2H, 3J ¼ 8.4 Hz, Ar-H).
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18 M. M. Khodaei, K. Bahrami and I. Kavianinia, J. Chin. Chem.
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19 X. Zheng, S. Luo, L. Zhang and J. P. Cheng, Green Chem.,
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Acknowledgements
We gratefully acknowledge the nancial support from the
Research Council of the University of Kashan for supporting
this work by Grant (no. 256722/29).
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