Magnetically separable MnFe2O4 nano-material: An efficient and reusable heterogeneous catalyst for the synthesis of 2-substituted benzimidazoles and the extended synthesis of quinoxalines at room temperature under aerobic conditions

Article abstract of DOI:10.1039/c3ra41457d

A simple and efficient protocol has been developed for the synthesis of biologically relevant 2-substituted benzimidazoles and quinoxalines using magnetically separable manganese ferrite (MnFe₂O₄) nanopowder for the first time as a reusable heterogeneous catalyst at room temperature under aerobic conditions. MnFe₂O₄ nanoparticles were prepared by a simple sol-gel method using starch as a bio-polymeric matrix, and characterized by XRD, TEM, EDAX and VSM analyses. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ra41457d

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Magnetically separable MnFe2O4 nano-material: an
efficient and reusable heterogeneous catalyst for the
synthesis of 2-substituted benzimidazoles and the
extended synthesis of quinoxalines at room
temperature under aerobic conditions3
Cite this: DOI: 10.1039/c3ra41457d
Received 25th March 2013,
Accepted 24th June 2013
DOI: 10.1039/c3ra41457d
Goutam Brahmachari,* Sujay Laskar and Puspendu Barik
www.rsc.org/advances
A simple and efficient protocol has been developed for the
synthesis of biologically relevant 2-substituted benzimidazoles
and quinoxalines using magnetically separable manganese ferrite
(MnFe2O4) nanopowder for the first time as a reusable hetero-
geneous catalyst at room temperature under aerobic conditions.
pharmaceuticals12b and various bio-functional molecules.12c
Besides, quinoxalines find useful applications in the field of
organic semiconductor materials13 and organic synthons.14
Such promising pharmacological properties of benzimidazole
and quinoxaline scaffolds have motivated synthetic chemists to
synthesize them, and as a result of which a plenty of synthetic
methods are currently available for both of the N-heterocycles.15–20
However, one-pot synthesis of 2-substituted benzimidazoles
MnFe2O4 nanoparticles were prepared by
a simple sol–gel
method using starch as a bio-polymeric matrix, and characterized
by XRD, TEM, EDAX and VSM analyses.
starting from o-phenylenediamines and aldehydes using
a
condensation-aromatization strategy under oxidative conditions
have recently attained considerable interest; various oxidative and
catalytic reagents, both homo- and heterogeneous, are already
reported for the synthesis of such important moiety.21–62 Although
these methods have certain merits, still most of them are
associated with notable shortcomings such as usage of stoichio-
metric amounts of catalysts, harsh reaction conditions, high
temperature, costly catalysts, operational difficulty, and strong
oxidizing nature of the reagents. In addition, a major concern in
the reaction between o-phenylenediamine and an aldehyde is to
attain 2-substituted benzimidazole selectively; in most of the
cases, a mixture of products including 1,2-disubstituted benzimi-
dazoles is also obtained. Very few methods are concerned with the
Introduction
Benzimidazole and quinoxaline scaffolds are widely distributed
heterocyclic units in pharmaceutical and bioactive natural
products. Benzimidazole-privileged scaffolds exhibit versatile
pharmacological properties and thus find useful clinical applica-
tions.1 Compounds bearing diverse substituents in the benzimi-
dazole motif are associated with a wide range of biological
activities.2 The benzimidazole unit is found to be present in many
marketed drugs (Fig. 1)3–6 being used in different therapeutic
areas, and remarkably effective both with respect to their
corresponding inhibitory activity and favorable selectivity ratio.7,8
Compounds bearing diverse substituents in the benzimidazole
motif are associated with a wide range of biological activities that
include antiulcer, antiviral, antifungal, anticancer, antimalarial,
antihistaminic, anti-helmintic, anti-oxidant and many more.8 In
addition, benzimidazoles have recently been used in the treatment
of diseases such as ischemia-reperfusion injury,9 hypertension,10
and obesity.11 Quinoxaline, another N-heterocyclic scaffold, is well-
known for being a key structural motif in many biocides,12a
Laboratory of Natural Products & Organic Synthesis, Department of Chemistry,
Visva-Bharati University, Santiniketan-731235, West Bengal, India.
E-mail: brahmg2001@yahoo.co.in; brahmg2001@gmail.com;
Fax: +91-3463-262-526; Tel: +91-3463-262-526
Electronic supplementary information (ESI) available: General methods including
3
preparation, characterization and magnetic evaluation of MnFe2O4 nano-material
are described in detail in the ESI. See DOI: 10.1039/c3ra41457d
Fig. 1 Some of the marketed approved drugs bearing benzimidazole scaffolds.3–6
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Scheme 1 Synthesis of benzimidazoles (3a–p) and quinoxalines (5a–e).
selective formation of 2-substituted benzimidazoles at room
temperature.21f,53,60,61 Looking at the importance of both benzi-
midazole and quinoxaline motifs, there is still an essential need
for the development of mild and recyclable, cost-effective and eco-
friendly heterogeneous catalysts for the facile and efficient
synthesis of such significant biologically relevant N-heterocycles
at room temperature.
Very recently, development of recyclable heterogeneous cata-
lysts based on magnetic nanoparticles has invoked tremendous
interest among synthetic chemists due to their emerging
applications in organic synthesis coupled with their effective
catalytic performance under mild reaction conditions and easy re-
cyclization.63–67 Manganese ferrite (MnFe2O4) is one of the most
important spinel ferrite magnetic oxides where oxygen has fcc
close packing and Mn2+ and Fe3+ ions can occupy either
tetrahedral (A) or octahedral (B) interstitial sites.68 Due to its good
magnetic characteristics coupled with simple preparative meth-
ods,69–75 it finds immense applications in various technological
fields;75–79 hence, synthesis of this spinel ferrite from readily
available non-toxic starting materials using bio-polymeric matrix
as a green template is of interest in material industry as well. To
the best of our knowledge, still there is no report on the direct
application of manganese ferrite (MnFe2O4) as catalyst in organic
synthesis. In continuation of our efforts to develop green synthetic
methodologies for organic transformations,80 we herein wish to
report for the first time on the development of a facile and
efficient synthesis of 2-substituted benzimidazoles and quinox-
alines at room temperature under aerobic conditions using
Scheme 3 Proposed mechanism for the catalytic synthesis of benzimidazoles.
Results and discussion
We prepared a magnetically separable catalyst of manganese
ferrite (MnFe2O4) nano-materials by a simple sol–gel method from
Table 1 Optimization of reaction conditions for the synthesis of 2-substituted
benzimidazolea
Entry
Catalyst
Solvent
Time (h)
%Yieldb
manganese ferrite as
a
magnetically reusable catalyst
(Scheme 1). MnFe2O4 has been prepared with a very low-cost
green method using starch as a bio-polymeric matrix. The present
method is not only selective to 2-substituted benzimidazoles, but
also is experimentally safe and simple, clean and efficient,
environmentally benign, and robust as a whole. The results are
summarized in Schemes 1–3 and Tables 1–3.
1
2
3
4
5
6
7
8
TBATB
CuCl2
Cu dust
CuBr
SiO2–HClO4
ZnO NP
ZnO NP
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
CH3CN
EtOH
CH3CN
EtOH
EtOH
CH3CN
Toluene
THF
DCM
DMF
H2O
MeOH
MeOH
MeOH
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
4
51
50
52
54
trace
59
63
49
70
59
83
91
52
53
48
50
trace
31
NiCl2
9
Fe3O4 NP
CuFe2O4 NP
MnFe2O4 NP
MnFe2O4 NP
MnFe2O4 NP
MnFe2O4 NP
MnFe2O4 NP
MnFe2O4 NP
MnFe2O4 NP
No catalyst
MnFe2O4 NP
MnFe2O4 NP
10
11
12
14
15
16
17
18
19
20
21c
92
trace
24
a
Catalyst (10 mol%), o-phenylenediamine (1 mmol), benzaldehyde (1
b
mmol), solvent (3–5 mL), rt, in the presence of air. Isolated yield.
Scheme 2 MnFe2O4 NP-catalyzed selective synthesis of 2-substituted benzimida-
zole (3) at room temperature under open air.
c
Under nitrogen atmosphere.
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appeared to be mandatory for carrying out the transformation. A
detailed mechanistic study on oxygen-catalyzed coupling for this
reaction was reported earlier by Smith and Ho.81
Table 2 The influence of oxygen on the condensation reaction of o-phenyle-
nediamine and benzaldehyde catalyzed by MnFe2O4 nanopowdera
Then we checked the activity of the catalyst in the presence of
oxygen atmosphere. For this purpose, 1 mmol of o-phenylenedia-
mine was reacted with 1 mmol of benzaldehyde in the presence of
10 mol% of MnFe2O4 at room temperature under oxygen
atmosphere using both methanol and acetonitrile as solvents.
The result showed that reaction under oxygen atmosphere
(balloon) underwent at a faster rate and was completed within
1.33–1.75 h and 4–4.5 h, respectively, affording almost similar
yield of the product 3a (entry 1; Table 2). To generalize the
observation, we carried out few more reactions with varying
benzaldehydes; in all the cases the reaction proceeded at faster
rate under oxygen atmosphere giving similar kind of yields. The
results were summarized in Table 2. Hence, it appeared clearly
that the present catalyst MnFe2O4 nano-materials can efficiently
use up aerial oxygen for effecting the transformation.
Entry
Aldehyde
Solvent
Time (h)
Yield (%)b
1
Benzaldehyde
MeOH
CH3CN
MeOH
CH3CN
MeOH
CH3CN
MeOH
CH3CN
MeOH
CH3CN
1.33
4.0
1.75
4.0
1.33
4.0
1.5
4.0
4.5
4.5
91
89
93
87
92
90
85
83
41
36
2
4-Methylbenzaldehyde
4-Fluorobenzaldehyde
4-Chlorobenzaldehyde
4-Fluorobenzaldehyde
3
4
5c
a
MnFe2O4 nano-catalyst (10 mol%), o-phenylenediamine (1 mmol),
aldehyde (1 mmol), MeOH/CH3CN (3–5 mL), rt, in the presence of
O2 atmosphere. Isolated yield. Without catalyst.
b
c
It is worthy to mention that the present method showed
excellent selectivity in furnishing 2-substituted benzimidazole (3)
even when the reaction was carried out with 1 equiv. of
o-phenylenediamine (1) and 2 equiv. of 4-methylbenzaldehyde
(2) using MnFe2O4 (10 mol%) in methanol under open air in 90%
yield at 6 h along with a trace amount of 39 (Scheme 2). Such
selectivity is seldom observed in literature;21f in most of the cases
1,2-disubstituted benzimidazole (39) was found to be the major
product under Lewis acidic conditions.
Encouraged by the above results, we examined the applications
and scope of our method with varying diamines and aldehydes. By
using methanol as solvent at room temperature, 2-substituted
benzimidazoles with various functional groups were obtained in
excellent yields (Table 3, entries 1–16) under MnFe2O4 NP-catalysis
in open air. The aromatic aldehydes containing both electron-
donating and electron-withdrawing groups such as F, Cl, Br, CN,
OH, OMe, tri-OMe, Me underwent the reaction smoothly affording
the corresponding 2-substituted benzimidazoles (3a–n) in 59–94%
yields within reasonable time frames (4–20 h) at room tempera-
ture. It is also noteworthy that the bulky anthracene-9-carbox-
ylaldehyde substrate underwent smooth reaction to afford the
corresponding 2-substituted benzimidazole derivative (3m) in
good yield (63%) following this protocol (Table 3, entry 13). The
aliphatic aldehyde, butyraldehyde was also found to take part in
the reaction (Table 3, entry 15, 16). To our delight, the present
methodology is further extended for the synthesis of quinoxaline
derivatives (5a–e) in ethanolic medium with good yields (Table 3,
entries 17–21). The results are summarized in Table 3.
the reaction between FeCl3?6H2O and Mn(CH3COO)2?4H2O in a
stoichiometric ratio of 2 : 1 using starch as a cost-effective and
green biopolymeric matrix; the modified methodology is discussed
in detail in the experimental and ESI. Characterization and
3
magnetic measurement of the catalyst prepared by this method
was evaluated by XRD, TEM, EDAX and VSM (Fig. 2 and 3; ESI ).
3
All the diffraction peaks of the XRD pattern can readily be indexed
to face-centred cubic phase [space group Fd3m(227)] of spinel
MnFe2O4 [JCPDS 00-073-1964] as shown in Fig. 2. The particle size
as obtained from XRD is y50 nm. The TEM image (Fig. 3a)
indicates the average size of the nanocrystals in the range of 50–
100 nm. The matrix of the EDAX shows strong Mn, Fe and O
peaks. No trace of other element is evident. The molar ratios of
Mn : Fe : O is 1 : 1.75 : 3.27. This is almost in accordance with
the theory formula of MnFe2O4. The coercive fields (Hc) and
saturation magnetizations (Ms) were calculated from the curves
(ESI ). The MnFe O nanoparticles possess saturation magnetiza-
3
2
4
tion of 30.03 emu g21 and coercivity of 168 (2193) G.
To optimize the reaction conditions, we initially attempted the
synthesis of 2-phenylbenzimidazole (3a) from the reaction of
o-phenylenediamine (1; 1 mmol) and benzaldehyde (2; 1 mmol) in
the presence of various catalysts and solvents as summarized in
Table 1. It was revealed that solvent plays a crucial role in this
reaction. From the experimental results (Table 1), use of 10 mol%
MnFe2O4 appeared to be the most facile and efficient catalyst in
the series for the synthesis of 2-phenylbenzimidazole (3a) under
open air at room temperature in methanol. Reactions with
supermagnetic Fe3O4@NP and CuFe2O4@NP were observed to
furnish just moderate yields of 3a of 70% and 59%, respectively
(entries 9 and 10; Table 1). The catalyst-free reaction provided only
28% yield of 3a in methanol under open air (entry 19; Table 1).
Control experiment using 10 mol% MnFe2O4 under nitrogen
atmosphere (in the absence of open air) was found not to proceed
much, giving a very low yield of 2-phenylbenzimidazole at 24 h
under the optimized conditions. Thus the presence of oxygen
We herein propose a plausible mechanism (Scheme 3) for the
facile formation of 2-substituted benzimidazoles (3) under the
reaction conditions where MnFe2O4 acts as a bifunctional-like
Lewis acid as well as an oxidative agent. It is supposed that the
reaction proceeds via activation of aldehyde (2) by MnFe2O4
followed by condensation with diamine (1) leading to the
formation of imine derivative (8) stabilized by MnFe2O4. The
resulting imine eventually undergoes ring closure by the
intramolecular attack of second amino group on CLN double
bond (8) to give hydrobenzimidazole (9) that subsequently
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Table 3 MnFe2O4 nano-catalyzed synthesis of 2-substituted benzimidazoles (3a–p)a and quinoxalines (5a–e)b at room temperaturec
Entry
1
Diamine
Carbonyl Compound
Time (h)
4
Product
Yield (%)
92
2
3
4
5
6
7
8
9
6
94
94
87
88
59
82
67
76
4
5
7
20
5
20
15
10
11
12
15
4
75
87
91
5
13
14
18
6
63
85
15
16
20
15
62
65
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Table 3 (Continued)
Entry
17
Diamine
Carbonyl Compound
Time (h)
2.5
Product
Yield (%)
91
18
19
2.5
2.5
83
81
20
21
2.5
2.5
80
70
a
b
aldehyde (1 mmol), diamine (1 mmol), MnFe2O4 NP (10 mol%), MeOH (3–5 mL), air, rt. diketone (1 mmol), diamine (1 mmol), MnFe2O4
c
NP (10 mol%), EtOH (3 mL), air, rt for 2.5 h. Isolated yield.
undergoes aromatization by aerial oxidation under the reaction
conditions to afford the desired 2-substituted benzimidazole (3).
The proposed mechanism is supported by the control experiment
under nitrogen atmosphere which leads to a trace of final product.
Another major advantage of the protocol is simple recovery and
easy reusability of the heterogeneous catalyst. Upon completion of
the reactions, the catalyst was recovered from the reaction mixture
simply by applying a strong external permanent magnet (as shown
in Fig. 5) followed by washing with ethanol/acetone and dried at
100 uC for 2 h. The recovered MnFe2O4 was reused successfully in
subsequent reactions without significant loss of catalytic perfor-
Fig. 2 X-ray diffraction patterns of the MnFe2O4 nanoparticles.
mance as illustrated in Fig. 4. We also examined the feasibility of
the present method for a somewhat scaled-up (on the gram scale)
experiment with 1,2-phenylenediamine (1.08 g; 10 mmol) and
Fig. 3 (a) Bright field Transmission Electron Micrographs and (b) EDAX obtained by HRTEM of MnFe2O4 nanoparticles.
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the prepared catalyst was evaluated by XRD, TEM, EDAX and VSM
analyses (ESI ).
3
Representative experimental procedure for the synthesis of
2-substituted benzimidazoles and quinoxalines
Synthesis of 2-(4-fluorophenyl)-1H-benzimidazole (3c). In a
typical reaction, 4-fluorobenzaldehyde (124 mg; 1 mmol) and
o-phenylenediamine (108 mg; 1 mmol) were dissolved in 3–5 mL
of MeOH in a 10 mL reaction tube. To this solution, MnFe2O4 (23
mg; 10 mol%) was added and stirred vigorously for 24 h at room
temperature under open atmosphere with the aid of an external
bar magnet. The progress of the reaction was monitored by TLC.
After the completion of reaction, the solvent was evaporated and
the reaction mixture was extracted with dichloromethane/ethyl
acetate (3 6 10 mL) for 7–10 h and allowed the mixture to settle
the catalyst which was then separated by the simple application of
a strong external magnet. The organic extract was dried in sodium
sulphate and the product was finally obtained after chromato-
graphic purification. The product was characterized by elemental
Fig. 4 Recyclability chart.
1
analyses and spectral studies including FT-IR, H-NMR, and 13C-
NMR data. These data for the known entries are in good
agreement with those reported in literature.21f,g,53,60 The residual
catalyst was further washed with ethanol followed by acetone,
dried under vacuum at 100 uC and reused.
Fig. 5 Magnetic separation of MnFe2O4 nano-materials by an external magnet.
4-methylbenzaldehyde (1.2 g; 10 mmol) using 10 mol% of
MnFe2O4 nano-catalyst at room temperature in methanol; the
reaction was found to proceed smoothly affording the desired
product, 2-(p-tolyl)-1H-benzo[d]imidazole (3b) 90% yield within 6
h, almost similarly in all respects with 1 mmol scale entry (Table 3,
entry 2). This experiment demonstrated the efficiency of the
catalyst for large scale production as well.
Characterization data for new entries
4-(1H-Benzo[d]imidazol-2-yl)benzonitrile (3h). Creamy white
solid, m.p.: 235–236 uC; IR (KBr): nmax = 3045, 2228, 1608, 1517,
1493, 1441, 1277, 966, 840, 746, 573 cm21; H-NMR (400 MHz,
1
DMSO-d6): d = 13.19 (1H, s, NH), 8.34 (2H, d, J = 8.4 Hz, Ar–H), 8.0
(2H, d, J = 8 Hz, Ar–H), 7.71–7.59 (2H, m, Ar–H), 7.26 (2H, br s, Ar–
H); 13C-NMR (100 MHz, DMSO-d6): d = 149.83, 134.72, 133.39,
127.43, 123.80, 122.68, 119.82, 119.07, 112.33, 112.15. Anal. Calcd.
for C14H9N3: C, 76.70; H, 4.14; N, 19.17; Found: C, 76.72; H, 4.13;
N, 19.15.
Experimental
General methods and instrumentations are described in the ESI.
3
6-Chloro-2-phenyl-1H-benzo[d]imidazole (3i). Off-white solid,
m.p.: 184 uC; IR (KBr): nmax = 3068, 3042, 1616, 1568, 1510, 1441,
1223, 964, 839, 700, 571 cm21; 1H-NMR (400 MHz, DMSO-d6): d =
13.12 (very weak, br s, NH), 8.18 (2H, dd, J = 7.6 Hz & 1.2 Hz, Ar–
H), 7.66 (1H, br s, Ar–H), 7.62–7.49 (4H, m, Ar–H), 7.23 (1H, dd, J =
8.4 Hz, 2.4 Hz, 2 Hz, Ar–H); 13C-NMR (100 MHz, DMSO-d6): d =
153.10, 130.16, 130.15, 129.46, 127.05, 126.89, 122.83. Anal. Calcd.
for C13H9ClN2: C, 68.28; H, 3.97; N, 12.25; Found: C, 68.26; H, 3.98;
N, 12.28.
Preparation of MnFe2O4 catalyst
MnFe2O4 nanoparticles were prepared by a simple sol–gel method.
FeCl3?6H2O (6 mmol) and Mn(CH3COO)2?4H2O (3 mmol) were
used in a stoichiometric ratio of 2 : 1. A homogeneous aqueous
solution of starch was prepared by stirring for 30 min at 90 uC.
Mn(CH3COO)2?4H2O was then added to the starch solution under
N2 atmosphere on vigorous stirring. Subsequently, FeCl3?6H2O
was added to the solution; the reaction temperature was kept
between 90–100 uC in an oil bath for 2 h. After then aqueous
ammonium hydroxide was added into the reaction mixture to
maintain the pH of 13–14, and the resulting solution was
magnetically stirred for another 2 h. On completion of the
reaction, the flask was allowed to cool down to room temperature.
The black precipitate obtained was washed with deionised water
and then dried at 100 uC for 12 h. The dried black-powder was
then placed into clean alumina crucibles and annealed in the
presence of air at a temperature of 900 uC for 4 h to get rid of the
excess carbon and the unreacted organic residues and also to
obtain a pure MnFe2O4 phase (yield 90% based on the calculation
of FeCl3?6H2O). Characterization and magnetic measurement of
6-Chloro-2-(4-fluorophenyl)-1H-benzo[d]imidazole (3j). Off-
white solid, m.p.: 204–206 uC; IR (KBr): nmax = 3082, 3040, 1609,
1534, 1491, 1234, 962, 839, 808, 571, 504 cm21 1H-NMR (400
;
MHz, DMSO-d6): d = 13.12 (bs, s, NH), 8.22(2H, dd, J = 8.4 Hz & 5.6
Hz, Ar–H), 7.76–7.66 (2H, m, Ar–H), 7.40 (2H, t, J = 8.4 Hz & 7.6 Hz,
Ar–H), 7.22 (1H, d, J = 7.2 Hz, Ar–H); 13C-NMR (100 MHz, DMSO-
d6): d = 164.90, 162.43, 152.32, 145.10, 134.25, 129.36, 126.75,
122.98, 120.43, 118.64, 116.57, 113.01, 111.44; Anal. Calcd. for
C13H8ClFN2: C, 63.30; H, 3.27; N, 11.36; Found: C, 63.29; H, 3.29;
N, 11.39.
2-(2-Chlorophenyl)-1H-benzo[d]imidazole (3n). Off-white
solid, m.p.: 179–182 uC; IR (KBr): nmax = 3051, 3005, 1625, 1568,
1433, 1272, 973, 854, 565 cm21;1H-NMR (400 MHz, DMSO-d6): d =
12.76 (br, s, NH), 7.92 (1H, dd, J = 7 Hz, 2.4 Hz & 2 Hz, Ar–H), 7.71–
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7.60 (3H, m, Ar–H), 7.57–7.5 (2H, m, Ar–H), 7.26–7.24 (2H, m, Ar–
H); 13C-NMR (100 MHz, DMSO-d6): d = 149.52, 132.50, 132.06,
131.61, 130.76, 130.39, 127.85, 127.58, 122.70, 120.03; Anal. Calcd.
for C13H9ClN2: C, 68.28; H, 3.97; N, 12.25; Found: C, 68.26; H, 3.95;
N, 12.29.
6-Chloro-2-propyl-1H-benzo[d]imidazole (3p). White amor-
phous powder; IR (KBr): nmax = 3003, 2922, 1612, 1544, 1528, 1450,
1035, 746, 513 cm21; 1H-NMR (400 MHz, DMSO-d6): d = 12.39 (br,
s, NH), 7.52–7.47 (2H, m, Ar–H), 7.12 (1H, d, J = 8 Hz, Ar–H), 2.78
(2H, t, J = 7.6, 7.2 Hz, –CH2–), 1.82–1.79 (2H, q, J = 7.2, 5.2 Hz,
–CH2–), 1.17 (3H, t, J = 7.2 Hz, –CH3); 13C-NMR (100 MHz, DMSO-
d6): d = 170.72, 157.03, 125.85, 121.62, 117.83, 112.39, 30.85, 21.24,
14.44. Anal. Calcd. for C10H11ClN2: C, 61.70; H, 5.70; N, 14.39;
Found: C, 61.73; H, 5.71; N, 14.36.
2-substituted benzimidazoles. The catalytic system could also be
extended successfully for the synthesis of quinoxaline derivatives.
The significant features of this newly developed eco-friendly green
procedure are easy separation of the heterogeneous catalyst from
reaction mixture, just by the application of an external magnet,
and its reusability, operational simplicity, room temperature
condition, energy-efficiency, clean reaction profiles, high selectivity
and good yields.
Acknowledgements
The authors are thankful to the Chemistry Department, Visva-
Bharati, CDRI, Lucknow, IIT, Kharagpur, and IIT, Guwahati,
India for the spectral and other measurements. S. L. is grateful
to the CSIR, New Delhi for awarding him a Senior Research
Fellowship. G. B. is also thankful to the CSIR for the financial
support [No. 02(0110)/12/EMR-II dated 01.11.2012].
Synthesis of 2,3-diphenylquinoxaline (5a). In a typical
procedure, benzil (1 mmol), 1,2-phenylenediamines (1 mmol),
and the catalyst MnFe2O4 (10 mol%) were placed in a 10 mL glass
tube previously charged with a external bar magnet containing 3
mL aqueous ethanol. The reaction mixture was stirred for 2.5 h
vigorously. The progress of the reaction was monitored by TLC.
The mixture was allowed to settle the catalyst which was then
removed by the application of a simple magnetic environment; the
resulting reaction mixture was extracted with dichloromethane/
ethyl acetate (3 6 10 mL). The extract was dried in sodium
sulphate and the product was finally obtained after chromato-
graphic purification. The product was characterized by elemental
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´
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data. These data for the known entries are in good agreement with
those reported in literature.20
Characterization data for new entries
2,3-Di(furan-2-yl)quinoxaline (5b). IR (KBr): Pale yellow solid,
m.p. 135 uC; nmax = 3109, 1622, 1570, 1485, 1329, 1225, 1150, 1067,
1007, 760, 663 cm21; 1H-NMR (300 MHz, CDCl3): d = 9.36 (2H, d, J
= 7.5 Hz, Ar–H), 8.52 (2H, d, J = 7.5 Hz, Ar–H), 8.30 (2H, dd, J = 6
Hz & 3 Hz, Ar–H), 7.84 (2H, dd, J = 6 Hz & 3.9 Hz, 3.6 Hz, Ar–H),
7.79–7.69 (2H, m, Ar–H); 13C-NMR (75 MHz, CDCl3): d = 142.41,
142.15, 132.02, 130.28, 129.75, 129.44, 127.92, 126.24, 122.90. Anal.
Calcd. for C16H10N2O2: C, 73.27; H, 3.84; N, 10.68; Found: C, 73.29;
H, 3.81; N, 10.67.
6-Chloro-2,3-di(furan-2-yl)quinoxaline (5c). Dark brownish
solid, m.p. 120–125 uC; IR (KBr): nmax = 3119, 2959, 1628, 1599,
1507, 1072, 750, 594 cm21; 1H-NMR (300 MHz, CDCl3): d 8.24–7.67
(6H, m, Ar–H), 6.71 (3H, br s, Ar–H); 13C-NMR (75 MHz, CDCl3): d
= 151.31, 150.46, 150.38, 145.69, 145.51, 143.12, 142.55, 140.58,
138.90, 135.45, 131.62, 130.79, 127.68, 113.98, 113.68, 112.64. Anal.
Calcd. for C16H9ClN2O2: C, 64.77; H, 3.06; N, 9.44; Found: C, 64.72;
H, 3.09; N, 9.43.
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Conclusions
In conclusion, we have developed an energy-efficient green
procedure for the facile synthesis of selectively 2-substituted
benzimidazoles at room temperature from the reaction between
ortho-phenylenediamines and aldehydes on the surface of a
magnetically separable and reusable heterogeneous MnFe2O4
nano-catalyst under aerobic conditions in methanol. The present
protocol offers an easy access for a wide spectrum of diverse
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