A comparative study of the catalytic activity of Co- and CoFe2O4-NPs in C-N and C-O bond formation: synthesis of benzimidazoles and benzoxazoles from o-haloanilides

Article abstract of DOI:10.1039/c6nj02293f

Nanoparticles of cobalt ferrite (CoFe₂O₄-NPs) and pure cobalt (Co-NPs) were synthesized, and after characterization, their catalytic activities for dehalogenative intramolecular C-O and C-N bond formation reactions were investigated and compared. These inexpensive and efficient catalysts enabled creation of new methods for the synthesis of benzimidazoles and benzoxazoles in green media, with ligand-free and mild reaction conditions. All the reactions resulted in moderate to excellent yields under the optimized reaction conditions; however, the reactions using Co-NPs as the catalyst were completed in relatively shorter reaction times. Furthermore, analysis showed that the reusability of the two catalytic systems is approximately comparable.

Full text of DOI:10.1039/c6nj02293f

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Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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A comparative study between Co- and CoFe2O4-NPs
catalytic activity in C–N and C–O bond formation:
synthesis of benzimidazoles and benzoxazoles from o-
haloanilides
Cite this: DOI: 10.1039/x0xx00000x
Received 00th January 2012,
Accepted 00th January 2012
Abdol R. Hajipoura,b*, Zahra Khorsandia
DOI: 10.1039/x0xx00000x
The nanoparticles of cobalt ferrite (CoFe2O4-NPs) and pure cobalt (Co-NPs) was synthesized,
after characterization, their catalytic activity in dehalogenative intramolecular C-O and C-N
bond formation reaction was investigated and compared. These inexpensive and efficient
catalysts created new methods for syntheses of benzimidazoles and benzoxazoles in green
media, ligand-free and mild reaction conditions. All the reactions resulted in moderate to
excellent yields under optimized reaction conditions; however, reactions using Co-NPs as
catalyst were completed in relatively shorter reaction times. Furthermore, analyses displayed
that the reusability of the two catalytic systems is approximately comparable.
www.rsc.org/
usage of palladium catalysts has their own disadvantages
including contamination to products, high cost, toxicity,
moisture-sensitive nature, hard recovery and consuming
expensive and toxic phosphine ligands.
Development of simple and safe synthetic approaches to
provide new and improved catalysts is one of the most
interesting goals in clean chemistry. Therefore, research for
finding new catalytic systems to formation of C-O and C-N
bonds, having none of the mentioned drawbacks has been
continued and many advances has grown to now.
Introduction
Benzimidazoles and benzoxazoles are important subunits of
many organic, biological and pharmaceutical compounds.1 This
building block structures can be found in some drugs such as
Prilosec, Nexium, Protonix, Famvir, Vermox and Priaxim;2-4
some of other medicinal applications of these compounds
include HIV reverse transcriptase inhibitor L-697, 661,
anticancer agent NSC-693638, estrogen receptor-β agonist
ERB-041, 5- lipoxygenase inhibitor and factor Xa (FXa)
inhibitor.5-8
Recently, among first-row transition metals, cobalt-catalyzed
organic synthesis have attracted much attention; because
cobalt is readily available, non-toxic, low-cost, and stable in
air.41-45 This metal displays very good catalytic activity in
various organic reactions.46-48 Moreover, the use of nano-
crystalline metal oxides as catalysts avoids the recoverability
and synthesis problems, as they usually remain insoluble in
reaction media and can then be easily recycled to be reused.
Furthermore, these nanomaterials, bearing high surface area
and reactive morphologies, are known to catalyze a variety of
cross-coupling reactions for the construction of carbon-carbon
and carbon-heteroatom bonds via dehalogenative paths.49-53
The other class of materials for catalysis is bimetallic
In addition to, in designing catalysts particularly in ortho-
metallated transition metal complexes, these compounds
would be suitable for the use as ligands.9-12
Therefore, considerable efforts to find new efficient and facile
strategies to improve their synthesis would be logical.
Recently, their synthesis has received considerable attention
and numerous synthesis approaches have been reported.13-20
However, development green, facile and efficient methods for
synthesis of these compounds remain complicated.
The traditional methods have some limitations such as
availability of starting materials and using of either toxic
reagents or harsh reaction conditions in a multistep ways;21-26
hence, to solve these problems, the more appropriate
transition-metal-catalyzed cross-coupling reactions containing
C-N and C-O bonds formation were developed. In almost
nanoparticles,
a category of nanomaterials having new
physical and chemical properties due to synergistic effects
between the two metals;54-56 so, they are highly desirable for
industrial applications, especially as catalyst. The cobalt ferrite
nanoparticles, denoted as CoFe2O4 is of the most important
members of oxide-based spinel ferrites. This ferromagnetic
nanoparticles can be categorized as the most recoverable and
reported methods, the homogeneous palladium27-29 and
28-40
copper
catalysts have been used with ligands and
additives. The later has suffered from some main
disadvantages such as high temperatures, long reaction times
and stoichiometric use of the copper reagent. In addition to,
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reusable catalyst; because of their facile separation from the free conditions. The catalytic activities of these catalysts were
reaction media using an external magnetic field.
comparable; however, cobalt nanoparticles could catalyze the
In continuation of our studies in cross-coupling reactions57-61 reactions in approximately higher yields than cobalt-ferrite
we wish to report the application of two highly active ones.
recyclable catalysts, CoFe2O4 and Co-NPs for benzimidazoles
and benzoxazoles synthesis through intramolecular C–O and C-
N coupling reaction.
Results and discussion
Co-NPs and CoFe2O4 nanoparticles was prepared using
precipitation in aqueous medium via easy and high efficiency
methods. The structures of both catalysts were characterized.
In XRD patterns of Co-NPs, all peaks can be indexed as
hexagonal-close packed (hcp) cobalt and showing the presence
of several cobalt species of CoxOy, especially Co3O4 (JCPDS card
78-1970). Also, FE-SEM and TEM images of both were obtained
along with SEM-EDX spectra and the magnetization curves of
CoFe2O4. The characterization data of catalysts have been
given in supplemental data. The Co loading of both catalysts
was measured by ICP and it was about (43.7 % for CoFe2O4 and
67% for Co3O4).
After optimizing of reaction conditions, these nanoparticles
was employed as catalyst in the intramolecular C–O and C-N
cross coupling reaction to syntheses benzimidazoles and
benzoxazoles. The catalytic activities of these catalysts was
explored in the same conditions and their results was
compared. Initially, in order to find the optimized reaction
conditions, the substrate of N-(2-bromo-phenyl)-benzamide
was selected for model reaction. Several types of bases and
solvents at different temperatures in the presence of various
amount of cobalt nanoparticles as catalyst was employed and
the results was explored to find the best reaction conditions.
The results are given in Table 1.
Firstly, the influence of bases in this reaction was examined, so
different bases with various amounts such as KOH, NaHCO3,
Na2CO3 and K2CO3 was used. The K2CO3 (1.5 eq) was selected
as the best. Next, the effect of several solvents on the reaction
system was studied. It was observed that ethanol was effective
in providing higher conversion, whereas solvents like PEG,
toluene, DMSO and NMP showed lower conversions. We also
examined effect of catalyst in the title reaction employing
different amounts under optimized conditions and 2 mg (1.2
mol%) of catalyst was found to be optimal. A lower catalyst
concentration usually led to slow reactions, however,
increasing the catalyst amount to 4 mg did not have any
further significant effect on yield and reaction times. The
improvement in the conversion (94%) was achieved at 80 ºC.
Higher reaction temperature (130 and 100 ºC) gave no
significant better yield, but in lower reaction temperature (50
ºC), the yield decreased even after long reaction times.
Therefore, all reactions was carried out at 80 ºC. Finally, this
was chosen as the optimized procedure for the synthesis of 2-
phenyl-benzoxazole from N-(2-bromo-phenyl)-benzamide. As a
whole, the experimental procedure for this reaction using Co-
NPs catalyst is remarkably simple and does not require the use
of toxic or expensive organic solvents or reagents. Additionally,
total consumption of the starting material was observed and
no side products was detected. Considering to excellent
activity of Co-NPs as catalyst in this reaction and recent
widespread applications of magnetic nanoparticles as a solid
supports of heterogonous catalyst which provides a very useful
and efficient separation from reaction medium, use of cobalt
ferrite nanoparticles as a bimetallic catalyst in the same
reaction and comparison study of its activity under similar
In comparison with previous other transition metals catalysts,
these catalytic systems not only are readily prepared in few
steps from available starting materials, but also are low cost
and easy removal from the reaction media. All reactions can
be performed fast and efficiently using small amount of the
catalysts compared to previous reports; because, the nano
structure of these catalysts provides a large surface area for
better interaction with reactants. Recently, two popular
protocols for the construction of the benzoxazole ring using
transition metal catalyst have been developed as: one is
intermolecular condensation/oxidative reaction of o-
aminophenol with an acyl source such as aromatic aldehyde,62-
65 benzylic alcohol,66-67 benzylic amine68 and 1,3- diketones69-71
in the presence of transition metal catalyst and an oxidant
(Figure 1 A). The earliest report of this method was described
by Yang and co-workers which homogenous copper salt and
harsh reaction conditions (at 140 ºC using PhCl as solvent,
KNO3 as oxidant and during 20 h) were used.30 The other is the
transition metal-catalyzed intramolecular cyclization of ortho-
haloanilides, this approach have been improved impressively
by Glorius et al.28 and others (Figure 1 B).73-79 In 2014, Patel
group reported an elegant procedure synthesis to aryl-
substituted benzoxazoles from o-haloanilides in the presence
of CuO nanoparticles and Cs2CO3 at 100 ºC.35 However, this
catalytic system did not give suitable selectivity and to achieve
good yields of aimed products, organic base/ligand such as
TMEDA was found as an essential additive. The synthesis of
benzoxazols in their work were performed during 1-32 h.
A
NH2
OH
N
O
Ar-X
R
R
Ar
metal, intermolecular
X = CHO, CH2OH, CH2NH2, COCH2, COCH2COR or CH3
B
H
N
Ar
N
O
Cyclization
Ar
R
R
O
metal, intramolecular
X
X = Halogen or H
This work
H
N
Ar
N
O
Cobalt catalyst
Ethanol, reflux
Ar
O
X
X = Halogen
Figure 1 Synthetic methods for the construction of benzoxazole
skeleton.
Herein, using our catalytic systems, the syntheses of various
derivatives of benzoxazoles and bezimidazoles was improved
under mild conventional heating in green solvent and ligand-
2 | J. Name., 2012, 00, 1-3
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conditions found to be interesting. Therefore; in continuous, above found optimized conditions.
application of CoFe2O4 as catalyst was also studied under the
Table 1 Optimization studies for the Co-NPs-catalyzed C–O cross-coupling of N-(2-bromo-phenyl)-benzamide as model reaction.a
Entry
Cat (mg (mol %))
Base
Solvent
T (ºC)
Yieldb (%)
Base effect
1
2
3
4
5
5
6
2 (1.2)
2 (1.2)
2 (1.2)
2 (1.2)
2 (1.2)
2 (1.2)
2 (1.2)
KOH (1.5)
NaHCO3(1.5)
Na2CO3(1.5)
K2CO3 (1.5)
K2CO3 (1)
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
80
80
80
80
80
80
80
78
66
43
94
87
94
95
K2CO3 (2)
K2CO3 (3)
Solvent effect
7
8
9
10
2 (1.2)
2 (1.2)
2 (1.2)
2 (1.2)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
DMSO
PEG
NMP
80
80
80
80
94
60
68
50
Toluene
Catalyst effect
11
12
13
14
2 (1.2)
1.5 (0.9)
1 (0.6)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
EtOH
EtOH
EtOH
EtOH
80
80
80
80
94
56
48
96
4 (2.4)
Temperature effect
15
16
17
18
2 (1.2)
2 (1.2)
2 (1.2)
2 (1.2)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
EtOH
EtOH
EtOH
EtOH
120
100
80
96
94
94
77
50
aReaction conditions: N-(2-bromo-phenyl)-benzamide (1.0 mmol), solvent (2 mL) without protection of inert atmosphere, for 8 h.
bIsolated yield.
We explored the generality of Co-NPs and CoFe2O4 catalysts insight into this issue, the catalyst reusability experiments in
application with different substrate to prepare a series of model reactions was carried out. After each cycle, Co-NPs was
benzoxazoles (Table 2) and benzimidazoles (Table 3).
separated from the reaction mixture through centrifugation
Results are reported and compared in these tables. The main followed by washing with diethyl ether and ethanol to remove
advantages of CoFe2O4 and Co-NPs are their good mechanical the organic impurities. After drying, the catalyst was employed
and excellent chemical stabilities at higher temperature. It was in the next run.
observed that substrates with electron releasing group were In reaction which used CoFe2O4, ferromagnetic nanoparticles
converted to corresponding products in more excellent yields of the catalyst was separated easily by creation of an external
compared with substrates contain electron-withdrawing magnetic bar. These isolated nanoparticles after washing with
group. As shown in tables, benzimidazoles compared to ethanol and drying on air was employed in the next run. Both
benzoxazoles gave better conversions in shorter reaction of our catalysts was successfully recovered with difference
times. After successfully synthesizing benzoxazoles and methods and reused for several times without any significant
benzimidazoles from various substrates, we then sought to losing of its activity. The table of reusability investigation
increase the substrate scope of this methodology, and o- results was given in supplementary data.
chlorobenzanilides was chosen. Chloric substrates are The yield of the reaction using Co-NPs in the 6th run reduced
generally ignored due to their inertness toward cross-coupling from 94 to 74%. In the case of CoFe2O4-NPs, the first decrease
reactions. Some o-chloroanilides reacted well under this cobalt was observed at 6th run resulting in 67% yield of the isolated
nanoparticle-catalyzed conditions to give the respective product. Compared to its first run 73%; it fund that the
benzoxazoles in moderate yields, as shown in Table 2 and CoFe2O4-NPs, in spite of lower catalytic activity gave more
Table 3, though the reactions took longer times. This slow reusability than Co-NPs.
reaction rate is perhaps due to the high bond energy of C–Cl Moreover, to explore the leaching of these catalysts, two
bonds compared to C–Br bonds.
similar control experiments was performed in each case. To
As a result, the reactions gave good results in the formation of this end, the reaction of N-(2-bromo-phenyl)-benzamide was
the desired products by applying both catalysts. However, carried out simultaneously in two different vessels under the
using Co-NPs catalyst reactions required approximately shorter exactly same conditions. In each case, the reaction progress
times to be completed. This founding indicate the better was monitored using TLC after 4 hours the catalyst was
activity of the cobalt nanoparticles compared to cobalt ferrite separated from one of these vessels using centrifuge or
ones.
external magnetic bar, while the other was remained
The separation and reusability of noble metal catalysts are the unchanged. Thereafter, both of the reactions were continued
trends of the catalysis industry and green chemistry, not only under the same conditions. After another 4 hours, both the
for lowering costs, but also for avoiding pollution. To gain reactions were stopped and their completion was again
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examined. The results showed that the reaction in the absence completion of the reaction in the other vessel was improved.
of the catalyst were not proceeded any more, while
Table 2. Synthesis of substituted benzoxazolesa
Entry
Substrate
Product
Cat. CoFe2O4
Yieldb [%]
73
Cat. Co-NPs
Yieldb [%]
94
Time [h]
10
TOF (h−1)c
6.1
Time [h]
8
TOF (h−1)c
9.8
N
O
1
H
N
O
Br
NO2
N
O
2
3
10
10
64
56
5.3
4.7
8
8
87
80
9.1
8.3
NO2
H
N
O
Br
NO2
NO2
N
O
H
N
O
Br
Me
Cl
N
4
5
10
10
82
71
6.8
5.9
8
8
94
89
9.9
9.8
Me
Cl
H
N
O
O
Br
N
H
N
O
O
Br
OMe
Br
N
6
7
10
10
79
62
6.6
5.2
8
8
96
87
10
H
OMe
Br
N
O
O
Br
N
9.1
H
N
O
O
Br
N
O
8
9
16
16
32
23
1.7
1.2
16
16
75
79
3.9
4.1
H
N
O
Cl
NO2
N
NO2
OMe
H
N
O
O
O
Cl
OMe
N
O
10
16
27
1.4
16
82
4.3
H
N
Cl
aReaction conditions: substrate (1.0 mmol), catalyst (2 mg), K2CO3 (4 equiv.) and refluxing in EtOH (2 mL) under air.
bIsolated yield
c(mol product/mol cobalt) (h−1).
This investigation was occurred for both catalysts and their for Co-NPs showed a value of 66.7%; it was found that no
heterogeneously properties was same. In addition, the significantly leaching was occurred during the reaction for both
leaching of cobalt from the catalysts was measured by ICP- catalysts. However, our observation clearly demonstrated that
OES, the cobalt content for recycled CoFe2O4 was 43.1 % and these catalysts were heterogeneous in nature.
4 | J. Name., 2012, 00, 1-3
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Table 3. Synthesis of substituted benzimidazoles
Entry
Substrate
Product
Cat. CoFe2O4
Cat. Co-NPs
Time (h)
8
Yield (%)
51
TOF (h−1)c
5.3
Time (h)
6
Yield (%)
69
TOF (h−1)c
9.6
N
N
1
H
N
Me
Me
N
Br
OH
Cl
OH
N
2
3
4
8
8
8
62
58
69
6.5
6.0
7.2
6
6
6
84
76
83
11.7
10.5
11.5
Cl
H
N
N
N
Br
OH
Me
OH
N
Me
H
N
N
N
Br
OH
NO2
OH
N
NO2
H
N
N
N
Br
OH
OH
OH
N
N
5
6
8
8
75
79
7.8
8.2
6
6
91
89
12.6
12.4
H
N
OH
N
Br
OH
OH
NH2
N
N
NH2
H
N
N
Br
OH
OH
OH
OH
NH2
N
N
7
8
11
11
34
22
2.6
1.7
10
10
59
53
4.9
4.4
NH2
H
N
N
Cl
OH
NO2
N
N
NO2
H
N
N
Cl
OH
aReaction conditions: substrate (1.0 mmol), catalyst (2 mg), K2CO3 (4 equiv.) and refluxing in EtOH (2 mL) under air.
bIsolated yield
c(mol product/mol cobalt) (h−1)
In previous studies, it were demonstrated that the metal in cross-coupling reactions for the construction of C–N and C–
impurities presented in the iron can catalyze such coupling O bonds to synthesis of derivatives of benzimidazoles and
reaction;80-81 but, herein we found that pure cobalt benzoxazoles using ethanol as a green solvent in mild reaction
nanoparticles is more efficient in these coupling reactions conditions. The combination of advantages displayed by the
which can be caused to the more surface area and more heterogonous catalysts, such as reasonable catalytic activity,
concentration of effective metal compared to cobalt ferrite.
stability and reusability, mean that these catalysts may be
Generally, the inexpensive our catalysts were compatible with considered as a viable alternative in cross-coupling reactions
a wide range of functional groups and exhibited good activity on efficiency, environmental and economic grounds.
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The previous reports confirmed that nano cobalt are more
active than catalytic system containing cobalt salts and ligands
in Heck cross coupling reaction, because the reduction of
cobalt in the first step of coupling reaction in the medium of
reaction is too hard for cobalt salts;82 so, herein two control
experiments was done using 5 mol% of CoSO4 and phosphine
ligands as catalyst in model reaction under the optimized
reaction conditions. The reactions were stopped after 8 hours
and the progress of reaction were determined exactly. The
results displayed that CoSO4/PPh3 is unable to catalyze the
reaction effectively.
1. Experimental
1.1 Materials
All general chemicals were supplied by Merck Chemicals
(Germany). All of the reagents were used without any further
purification. The products were purified via crystallization
process to obtain the corresponding products in to 83-96 %
yields. Melting points were determined using Stuart Scientific
1
SMP2 apparatus. H and 13C NMR were performed on Bruker-
avance 400 MHz spectrometer in CDCl3 using TMS as internal
standard. The Fourier transform infrared (FT-IR) spectra were
recorded on a Jasco-680 (Japan) spectrophotometer in KBr
pellets and reported in cm−1. A scanning electron microscope
(SEM) (Philips XL 20) was used to observe the size and
morphology of the catalyst. XRD patterns were recorded by an
Xpert MPD, X-ray diffractometer using CuKα radiation.
A
plausible mechanism for the formation of 2-phenyl-
benzoxazole from N-(2-bromo-phenyl)-benzamide is proposed
in Scheme 1. The base plays a crucial catalytic role in first step
of reaction cycle; the interactions between the
morphologically active cobalt and cobalt ferrite nanoparticles
and anilide may lead to the formation of a Co-cluster, which on
oxidative addition to the C–X bond may give intermediate 1.
Complex 1 then undergoes an intermolecular dehalogenation
which continues the catalytic cycle. Complex 2 may undergo to
reductive elimination of Co nanoparticles heterocyclic
compounds as shown in Scheme 1.
1.2. General procedure for preparation of cobalt (ΙΙ)
nanoparticles
In a typical procedure, a solution of 0.5 M (10 mL) of cobalt
sulfate was prepared using dematerialized water. Then,
required amount of hydrazine (2 M, 10 mL) and NaOH solution
(10 mL, 60%) was injected slowly into cobalt solution drop by
drop under sonication at 30–40 ͦC. After the injection, the
H
N
Ph
mixture was sonicated continuously for 20 min. The black
precipitate was collected and washed with de-ionized water
for several times and then washed thoroughly with dilute HCl
to remove traces of alkali and with ethanol. Finally, the
mixture was separated by centrifugation. The powder was
dried under vacuum oven at 50 ºC for overnight.
N
Ph
:B
_
N
X K+
X
Ph
Br
Br
Co-NPs
X
H
oxidative
addition
reductive
elimination
N
Ph
Ph
_
N
X K+
_
1.3.
nanoparticles (CoFe2O4-NPs)
General for preparation of cobalt ferrite
X
1
Br
2
The solutions of iron nitrate (Fe(NO3)3(9H2O) (0.2 M, 10 mL )
and cobalt nitrate (Co(NO3)2(6H2O) (0.1 M, 10 mL) were
prepared separately and mixed together. A solution of NaOH
(3 M) was added slowly to the flask, until pH to reach 12.
Finally, oleic acid (3 drops) was added to the solution as
surfactant. Then, the suspension was vigorously stirred using a
K+
KBr
Scheme 1. Possible mechanism
Conclusions
mechanical stirring at 90 ºC for
2 h. After complete
In summary, efficient methods for the synthesis of substituted
benzimidazoles and benzoxazoles using green and inexpensive
cobalt catalysts in ligand-free conditions have been developed.
Two different catalysts of magnetic and pure cobalt was
synthesized and their activities in the intramolecular C–O and
C-N bond formation reaction was compared. These
nanoparticles are easily made, air-stable, low cost and
efficient. Both of catalysts can be recovered and reused
without remarkable loss of activity. Comparison of these two
catalytic system shows that their activity is very close to each
other; however, cobalt nanoparticles could catalyzed the
reactions in approximately shorter reaction times compared to
cobalt ferrite ones. These methods found as clean processes
and produce a wide range of benzimidazoles and benzoxazoles
as an important heterocyclic compounds in high yields. These
procedure have the some advantages of high efficiency,
simplified work-up and isolation procedures, and catalyst
recyclability. The reactions are simple, general and efficient.
precipitation, the residue was washed with double distilled
water (3 × 25 mL) Finally, the mixture was separated by
magnetic bar and dried under vacuum oven at 50 ºC for
overnight.
1.4. General procedure for synthesis of benzimidazoles
and benzoxazoles,
Benzoxazole: In a round-bottomed flask equipped with a
condenser and a magnetic stirrer, 2-bromoaniline (172 mg, 1
mmol) and 4-hydroxy-benzoyl chloride (166 μL, 1.5 mmol),
reacted together in aqueous sodium hydroxide (10 mL, 30 %)
to obtain bromoamids. N-(2-bromo-phenyl)-4-hydroxy-
benzamide (204 mg, 0.7 mmol), K2CO3 (207 mg, 1.5 mmol) and
cobalt catalyst (2 mg) was stirred in ethanol (2 mL) under air
atmosphere for the appropriate time (Table 2). The progress of
the reaction was monitored by TLC (eluent: n-hexane /ethyl
acetate, 4:1). After completion of the reaction CH2Cl2 (15 mL)
was added and the catalyst was separated by centrifuge. The
catalyst was washed and dried. The residue was purified by
6 | J. Name., 2012, 00, 1-3
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ARTICLE
DOI: 10.1039/C6NJ02293F
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Benzimidazole: In a round-bottomed flask equipped with a
condenser and a magnetic stirrer, 2-bromoaniline (0.172 g, 1
mmol) and 4-hydroxy-benzoyl chloride (166 μL, 1.5 mmol)
reacted together to obtain bromoamids. Next, N-2-
bromophenylbenzamide and 1 equivalent of phosphorus
pentachloride reacted together at 100 ºC after 24 h, 4-amino-
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phenyl)-N'-(4-hydroxy-phenyl)-benzamidine (183 mg, 0.5
mmol), K2CO3 (207 mg, 1.5 mmol) and cobalt catalyst (2 mg)
was added to reaction mixture and refluxed in ethanol (2 mL)
under air atmosphere. The progress of the reaction was
monitored by TLC (eluent: n-hexane /ethyl acetate, 4:1). After
completion of the reaction (Table 3), the resulting mixture was
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/ethyl acetate, 9:1) to yield final compounds (83-91%).
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Or