Novel Approach to Benzimidazoles Using Fe3O4 Nanoparticles as a Magnetically Recoverable Catalyst

Article abstract of DOI:10.1016/S1872-2067(11)60329-X

Magnetically recoverable Fe₃O₄ nanoparticles have been synthesized as a catalyst for the cyclocondensation of 1,2-phenylenediamines with orthoesters under solvent-free conditions. Catalyst loadings can be as low as 1 mol% to give high yields of the corresponding benzimidazole derivative at 80 °C. This green method offers significant advantages in terms of its simplicity, low catalyst loadings, high product yields, and non-toxic nature. The Fe₃O₄ nanoparticles were characterized by X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy.

Full text of DOI:10.1016/S1872-2067(11)60329-X

CHINESE JOURNAL OF CATALYSIS
Volume 33, Issue 2, 2012
Online English edition of the Chinese language journal
Cite this article as: Chin. J. Catal., 2012, 33: 298–301.
ARTICLE
Novel Approach to Benzimidazoles Using Fe3O4
Nanoparticles as a Magnetically Recoverable Catalyst
Bahador KARAMI1,*, Shaghayegh NIKOSERESHT2, Saeed KHODABAKHSHI1
1Department of Chemistry, Yasouj University, Yasouj, Iran
2Department of Chemistry, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran
Abstract: Magnetically recoverable Fe3O4 nanoparticles have been synthesized as a catalyst for the cyclocondensation of
1,2-phenylenediamines with orthoesters under solvent-free conditions. Catalyst loadings can be as low as 1 mol% to give high yields of the
corresponding benzimidazole derivative at 80 °C. This green method offers significant advantages in terms of its simplicity, low catalyst
loadings, high product yields, and non-toxic nature. The Fe3O4 nanoparticles were characterized by X-ray diffraction, transmission electron
microscopy, and Fourier transform infrared spectroscopy.
Key words: ferroferric oxide nanoparticle; 1,2-phenylenediamine; orthoester; benzimidazole
The challenge in chemistry is to develop practical methods
with convenient conditions and reagents, and the concept of
“green chemistry” is becoming ever important in the scientific
community. Green chemistry is emerging as a high-priority
guiding principle for organic synthesis. Recently, the prepara-
tion and application of nanoparticles (NPs) in organic synthesis
has been the subject of intense interest [1–4]. Using NPs offers
advantages for “clean” chemistry, since, in addition to being
readily recovered, they are non-toxic and widely accessible.
The NP surface can also be functionalized to append catalyti-
cally active groups [5,6].
In this work, we describe a new and green strategy for the
preparation of novel and known benzimidazoles using Fe3O4
nanoparticles. These have proved as powerful, safe, and recy-
clable catalysts under solvent-free conditions. In a previous
study, Goosen and co-workers [7] reported the catalytic de-
carboxylative cross-ketonisation of aryl- and alkylcarboxylic
acids using Fe3O4 nanoparticles.
[16], and raf kinase [17]. The most prominent benzimidazole
compound in nature is N-ribosyldimethylbenzimidazole, which
serves as an axial ligand for cobalt in vitamin B12 [18].
Until now, several methods for the synthesis of benzimida-
zoles and derivatives thereof have been reported. The most
common method is the condensation of an arylenediamine with
a carbonyl equivalent [19,20]. Esters, lactones, and anhydrides
can also produce benzimidazoles through the cyclization of
amide [21]. However, some of these reported methods suffer
from drawbacks, such as the requirement for toxic and expen-
sive catalysts and solvents, long reaction times, low yields, and
difficult work-up procedures.
1 Experimental
1.1 Preparation of Fe3O4 nanoparticles
FeCl3 (5.2 g) and FeCl2 (2.0 g) were successively dissolved
in 25 ml distilled water with 0.85 ml 12.1 mol/L HCl. The
resulting solution was added dropwise to a 250 ml 1.5 mol/L
NaOH solution with vigorous stirring. The last step generates
an instant black precipitate. The precipitate was isolated in a
magnetic field, and the supernatant was removed from the
precipitate through decantation [22].
In recent years, the development of improved synthetic
routes to heterocyclic compounds has attracted special atten-
tion [8–10]. Among the wide variety of nitrogen heterocycles
that have been explored as pharmaceutically important com-
pounds, benzimidazoles exhibit relatively high biological ac-
tivities. They have exhibited activity against cancer [11], HIV
[12,13], herpes (HSV-1) [14], influenza [15], certain fungi
Received 24 August 2011. Accepted 7 November 2011.
*Corresponding author. Tel: +98-741-2223048; Fax: +98-741-2242167; E-mail: karami@mail.yu.ac.ir
Copyright © 2012, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(11)60329-X

Bahador KARAMI et al. / Chinese Journal of Catalysis, 2012, 33: 298–301
R2
H
N
Fe3O4 nanoparticles
(1 mol%)
G
R2
NH2
NH2
O
G
R1
+ 3 R2OH
+
Solvent-free, 80 oC
O
N
R1
R2
O
G: H, Me, NO2, Benzoyl
R1 and R2: H, Me, Et
3
1
2
Scheme 1. Synthesis of benzimidazole derivatives using Fe3O4 nanoparticles.
1.2 Characterization of Fe3O4 nanoparticles
and ꢂ is the Bragg’s angle. For the (311) reflection, the average
size of the Fe3O4 nanoparticles was estimated to be around 13
nm.
Figure 2 shows the TEM image of the Fe3O4 nanoparticles.
The TEM image reveals spherical Fe3O4 nanoparticles with an
average size of 10 nm.
Transmission electron microscopy (TEM) studies were car-
ried out with a JEOL JEM 3010 instrument, operating at an
accelerating voltage of 300 kV. X-ray diffraction (XRD, D8,
Advance, Bruker, axs) patterns were obtained for the charac-
terization of the heterogeneous catalysts. Fourier transform
infrared (FT-IR) spectra were recorded on a Shimadzu-470
spectrometer using KBr pellets.
The FT-IR spectrum for the Fe3O4 nanoparticles is shown in
Fig. 3. The absorbance bands at 584.3 cm–1 are ascribed to
Fe2+ꢀO2–, and are consistent with those reported for spinel
Fe3O4 [29,30].
1.3 Synthesis of benzimidazole derivatives
In the past few years, we have been involved in a program
directed towards developing simple, novel, and facile methods
for the preparation of organic compounds using a range of
catalysts and readily available starting materials [23–27]. In
this study, we present a simple route towards novel and known
benzimidazoles 3 through the reaction of 1,2-phenylenedia-
mines 1 with orthoesters 2 using Fe3O4 nanoparticles as a
A mixture of 1,2-phenylenediamine 1 (1 mmol), orthoester 2
(1 mmol), and Fe3O4 nanoparticles (2.32 mg, 1 mol%) was
stirred and heated at 80 °C for the appropriate time. Upon
completion (as adjudged by TLC, silica-gel 60 F254
,
n-hexane:ethyl acetate), hot EtOH/H2O (50/50, 10 ml) was
added to the reaction mixture and the catalyst was separated
through magnetic absorption using a magnet. After separating
the catalyst, the solution was heated and filtered to afford the
pure product 3 in the crystal form. At the end of the reaction,
the separated catalyst was washed with diethyl ether, dried at
130 °C for 1 h, and reused in another cycle. The general pro-
cedure is shown in Scheme 1.
120
100
80
60
40
20
0
All synthesized compounds (3a–3i) were characterized via
analytical and spectroscopic methods. Melting points were
1
determined on a KRUSS model instrument. H NMR spectra
were recorded on a Bruker Avance II 400 NMR spectrometer at
400 MHz, in which CDCl3 was used as solvent and TMS as the
internal standard. All products (except for novel compounds)
were characterized through comparison with the reported in the
literatures [23–27].
20
30
40
50
60
70
2θ/(o )
Fig. 1. XRD pattern for the Fe3O4 nanoparticles.
2 Results and discussion
Figure 1 shows the XRD pattern for the Fe3O4 nanoparticles.
A number of prominent Bragg reflections, as assigned from
their indices ((220), (311), (400), (422), (511), and (440)),
reveal that the resultant nanoparticles are Fe3O4 with a spinel
structure [28]. The size of the Fe3O4 nanoparticles was also
determined from X-ray line broadening, using the De-
bye-Scherrer formula, which is given as D = 0.9ꢀ/ꢁcosꢂ, where
D is the average crystalline size, ꢀ is the applied X-ray wave-
length, ꢁ is the angular line width at half maximum intensity,
Fig. 2. TEM image for the Fe3O4 nanoparticles.

Bahador KARAMI et al. / Chinese Journal of Catalysis, 2012, 33: 298–301
100
50
0
Table 3 Synthesis of new benzimidazole derivatives using 1 mol%
Fe3O4 nanoparticles at 80 °C under solvent-free conditions
O
O
NH2
NH2
N
R
N
H
R = H, Me, Et
ꢀ
3j 3k
Time
(min)
17
14
10
Yielda
(%)
85
82
88
Melting
point (°C)
136–138
136–138
168–170
140–142
Product
Orthoester
R
3j
3j
3k
3l
HC(OEt)3
HC(OMe)3
MeC(OMe)3
EtC(OEt)3
H
H
Me
Et
3000
2500
2000
Wavenumber (cm−1)
Fig. 3. FT-IR spectrum for the Fe3O4 nanoparticles.
1500
1000
500
12
90
aIsolated yields.
magnetically recoverable catalyst (Scheme 1).
To identify the suitable reaction conditions for the synthesis
of benzimidazole derivatives 3 using these Fe3O4 nanoparti-
cles, triethyl orthoformate and o-phenylene diamine were
selected as the model reaction. As can be seen in Table 1, we
found that in the absence of the catalyst, the reaction did not
proceed, even at a high temperature. Through screening, we
found that this reaction proceeded smoothly with 1 mol%
catalyst at 80 °C under solvent-free conditions in only 12 min.
Higher loadings of catalyst did not affect a marked influence on
the product yield. This may be due to the coordination of ex-
cessive catalyst to the diamine.
Encouraged by the above results, we then focused our at-
tention on 4-benzoyl-1,2-phenylenediamine, to prepare new
benzimidazoles 3j, 3k, and 3l. The results obtained are sum-
marized in Table 3.
The 1H NMR spectrum for 3l gave a triplet for the protons of
the methyl group (δ = 1.47), a quartet for the protons of the
methylene group (δ = 3.00) and a set of multiplet signals (δ =
7.82–7.45, 7.23–7.27) that correspond to the aromatic protons.
The resonance for the NH proton appeared as a broad signal at
δ = 10.80–10.40. The carbonyl groups in the 13C NMR spec-
trum of 3l appeared at δ = 197.62.
To prove the general applicability of this method, after op-
timizing the reaction conditions, different orthoesters and
o-phenylenediamines were examined. The results are summa-
rized in Table 2.
To compare the catalytic activity of Fe3O4 powder with that
of the Fe3O4 nanoparticles, two parallel reactions were per-
formed. As shown in Table 4, the product yields were moderate
(55%–75%) after 50–70 min with the Fe3O4 powder, whilst the
Table 1 Synthesis of benzimidazole (3a) catalyzed with various load-
ings of Fe3O4 nanoparticles at 80 °C under solvent-free conditions
Table 4 Comparing the catalytic activities of Fe3O4 powder and Fe3O4
nanoparticles in the synthesis of benzimidazoles.
Catalyst amount (mol%)
Time (min)
Yielda (%)
Fe3O4 powder
Yielda (%) Time (min)
Fe3O4 NPS
Yielda (%) Time (min)
50b
91
90
90
Product
—
1
3
5
540
12
12
3a
3g
3i
75
60
55
50
56
70
91
91
82
12
7
8
15
aIsolated yields. bNot completed.
aIsolated yields.
Table 2 Synthesis of benzimidazole derivatives using 1 mol% Fe3O4
nanoparticles at 80 °C under solvent-free conditions
100
80
60
40
20
0
Time
(min)
12
15
17
36
22
25
7
Yieldb
(%)
91
88
93
77
84
80
91
Melting point (°C)
Found Ref. [31]
Producta
G
R1 R2
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
H
H
H
Et
172–174 170–172
176–178 172–174
166–168 163–165
108–110 112–114
198–200 198–200
165–167 160–163
208–210 206–208
225–227 225–227
178–180 177–179
Me Me
Et
H
Et
Et
Me
Me Me Me
Me Et
NO2
NO2 Me Me
NO2 Et Et
Et
Et
1
2
3
4
5
H
Cycle
10
8
82
82
Fig. 4. Recyclability of the Fe3O4 nanoparticle catalyst in the synthesis of
3a at 80 °C under solvent-free conditions (reaction time = 12–15 min).
aIdentified by comparison with authentic samples. bIsolated yields.

Bahador KARAMI et al. / Chinese Journal of Catalysis, 2012, 33: 298–301
8
9
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Fe3O4 nanoparticles provided excellent yields (82%–91%)
after 8–12 min under solvent-free conditions.
The design and synthesis of recoverable catalysts is a highly
challenging interdisciplinary field, which combines chemistry,
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A green methodology for the preparation of novel and
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