Preparation of 2-Arylbenzimidazole derivatives using CuO nanoparticles /H2O2 system

Article abstract of DOI:10.1080/24701556.2017.1358182

CuO nanoparticles were prepared in watery lemon juice media and were characterized by XRD, FE-SEM, DLS, TGA and BET analysis. The as-prepared catalyst was efficient and recyclable for a high yielding, and practical method for the synthesis of 2-arylbenzimidazoles via cyclo-condensation reaction of 1,2-benzenediamine and aldehydes using copper oxide (CuO) nanoparticles is reported. Solvents and solvent-free effects on the reaction were investigated. Solvent plays a significant role in the reaction, and best results were achieved in solvent-free condition at 80°C. All reactions were completed in short reaction times (20–120?min) with 76–97% yields.

Full text of DOI:10.1080/24701556.2017.1358182

Inorganic and Nano-Metal Chemistry
ISSN: 2470-1556 (Print) 2470-1564 (Online) Journal homepage: http://www.tandfonline.com/loi/lsrt21
Preparation of 2-Arylbenzimidazole Derivatives
using CuO Nanoparticles /H2O2 system
Abbas Fazlinia & Setareh Sheikh
To cite this article: Abbas Fazlinia & Setareh Sheikh (2017): Preparation of 2-Arylbenzimidazole
Derivatives using CuO Nanoparticles /H2O2 system, Inorganic and Nano-Metal Chemistry, DOI:
10.1080/24701556.2017.1358182
To link to this article: http://dx.doi.org/10.1080/24701556.2017.1358182
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Date: 24 August 2017, At: 01:57

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Preparation of 2-Arylbenzimidazole Derivatives using CuO Nanoparticles /H2O2 system
Abbas Fazlinia*,a, and Setareh Sheikhb
aDepartment of Chemistry, Zarghan Branch, Islamic Azad University, Zarghan, Iran.
bDepartment of Chemistry, Shiraz Branch, Islamic Azad University, Shiraz, Iran
*Correspondence author E-mail: Fazliniaabbas@gmail.com
Abstract
CuO nanoparticles were prepared in watery lemon juice media and were characterized by XRD,
FE-SEM, DLS, TGA and BET analysis. The as-prepared catalyst was efficient and recyclable for
a high yielding, and practical method for the synthesis of 2-arylbenzimidazoles via cyclo-
condensation reaction of 1,2-benzenediamine and aldehydes using copper oxide (CuO)
nanoparticles is reported. Solvents and solvent-free effects on the reaction were investigated.
Solvent plays a significant role in the reaction, and best results were achieved in solvent-free
condition at 80°C. All reactions were completed in short reaction times (20-120 min) with 76-
97% yields.
Graphical Abstract
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Keywords
2-arylbenzimidazole; CuO nanoparticles; lemon water; heterogeneous catalyst; cyclo-
condensation
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Introduction
Among the heterocyclic compounds, which can overcome the viruses and bacteria disease,
benzimidazole derivatives have attracted more attention for many chemistries and pharmacy
professionals, because of their significant activities against several viruses such as HIV, herpes
(HSV-1), antimicrobial, anti-inflammatory, RNA, human cytomegalovirus (HCMV), influenza
and potential antitumour. [1,2] Moreover, these structures have interesting possibilities due to their
potent anti-ulcer, antihypertensive, antiviral, anti-fungal, anti-cancer and anti-histaminic activity.
[1,2]
On the other hands, benzimidazole derivatives are commonly used as intermediates in
[3]
synthetic courses as well as a ligand in asymmetric catalysis.
Due to the widespread use of
benzimidazoles, easy and cost-effective development of new methods based on the synthesis of
these compounds is in demands.
In the past, varieties of oxidative or reductive coupling, bond cleavage, and C-N bond formation
[4-8]
methods for the synthesis of benzimidazoles have been developed.
The synthesis of
benzimidazoles is reported by Palladium-catalyzed oxidative C--H amination of N,N′-
bis(aryl)amidines.[9] Majumdar, et-al. reported the synthesis of benzimidazoles via condensation
of 1,2-diamino benzene and β-ketoester/amide followed by C-C bond cleavage using a catalytic
amount of SiO2--FeCl3.[10] Recently, an efficient method for the preparation of multi-substituted
benzimidazoles was developed by Ugi 4CC/aza-Wittig sequence.[11]
The condensation of 1,2-benzenediamine with aldehydes or carboxylic acids derivatives is the
reaction which, has been more attention due to its simplicity. This method is achieved in the
presence of various catalysts under thermal and microwave conditions. Some of catalysts used
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[12]
[13]
[14]
are Ytterbium perfluorooctane sulfonates,
H2O2/HCl,
H2O2/Fe(NO3)3,
Ceric
ammonium nitrate (CAN), [15] oxone®, [16] PEG-400, [17] SiO2-FeCl3, [18] and BF3.OEt2. [19]
However, there are several reports of the use of copper salts such as Cu(OAc)2, CuBr, and CuI as
catalysts for the synthesis of benzimidazoles,[20-24] the use of green prepared CuO nanoparticles
for the synthesis of 2-arylbenzimidazoles by the reaction of 1,2-benzenediamine and aldehydes is
hereto-unknown.
In continue of our works on the synthesis of heterocyclic compounds,[25-29] herein, we report the
synthesis of benzimidazoles from the cyclo-condensation reaction of 1,2-benzenediamine and
aldehydes using CuO nanoparticles as an efficient catalyst and H2O2 as an oxidant (Scheme 1).
Result and Discussions
The crystal phase of the CuO nanoparticles was examined by powder X-ray diffraction (XRD)
analysis (Figure 1). The representative XRD peaks appear in 32.5, 35.4, 35.5, 38.7, 38.9, 48.7,
58.3, 61.5, 65.8, 66.2 and 68.1 [2Theta degree] could be indexed to the monoclinic crystal
system of CuO [Reference Code: 00-005-0661, Space group: C2/c]. The average crystal size of
the CuO nanoparticles was estimated using Scherrer’s formula as 50 nm.
Figure 2 shows the FE-SEM image of CuO nanoparticles prepared in a solution of lemon water.
High-resolution FE-SEM micrograph reveals the nano-diameter and uniform shape of CuO
particles. The particle size was confirmed to be less than 100 nm.
DLS measurement technique investigated the particle size distribution analysis of CuO
nanoparticles. A Zetasizer Nano ZS (Malvern) was used for measuring the size distribution of
nanoparticles in ethanol as solvent. The sample was dispersed in ethanol (1gL1) and sonicated in
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for 2h. The results of DLS analysis is shown in Figure 3. According to DLS-measurement, the
size distribution of the nanoparticles is almost in less than 100 nm with an average of 53 nm.
Figure 4 shows the thermogravimetric analysis (TGA) of CuO nanoparticles after and before
calcination at 500°C. In both samples, the endothermic peaks are related to the removal of water
and organic contaminants. The calcined CuO nanoparticles show a maximum of 6% weight
losses which can be attributed to the elimination of surface adsorbed water of CuO nanoparticles
(Figure 4a). The weight losses of the crude sample, however, is about 66% which can be
considered as belonging to the removal of adsorbed water and organic contaminants present in
lemon water (Figure 4b). These organic contaminants may be adsorbed on the surface of CuO or
bonded to the Cu ions.
The nitrogen adsorption-desorption isotherm shows the inner porous nature of CuO nanoparticles
(Figure 5). As shown in Figure 4, the IV type isotherm of nanoparticles indicates the mesoporous
characteristic of the sample. Barrett--Joyner--Halenda (BJH) method was used for the pore size
distribution of CuO nanoparticles, and the isotherm is shown in Figure 6. Figure 6 illustrated that
the samples have mesopore structure with the pore radius between 4 and 8 nm. The specific
surface area of CuO nanoparticles was measured by BET (Brunauer--Emmett-- Teller) method
and was found to be 96 m2g−1.
Catalytic preparation of 2-arylbenzimidazole derivatives
When benzene-1,2-diamine reacted with benzaldehyde, an equilibrium will be created between
starting materials and (E)-2-(benzylideneamino)aniline (A) as an intermediate (Scheme 2). The
formed Schiff base (intermediate A) subsequently equilibrated with 2-phenyl-2,3-dihydro-1H-
benzo[d]imidazole (intermediate B), as reported by Kumar et-al.. [30]
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As the aim of this procedure is to prepare a variety of 2-aryl benzimidazoles, thus the presence of
an oxidant is needed. Given chemical durability and environmentally friendly, H2O2 is a good
candidate to be an oxidant in the above reaction. Due to the high activation barrier of hydrogen
peroxide, it should be activated by a catalyst [31-32]. CuO nanoparticles could be a suitable
activator for H2O2 oxidant. The mechanism involves the formation of an intermediate complex of
H2O2 and CuO [31] which finally decomposed by the formation of H2O via oxidative
dehydrogenation of adduct B affords the desired 2-arylbenzimidazoles (Scheme 2).
Initially, the cyclo-condensation of benzaldehyde (1.0 mmol), and benzene-1,2-diamine (1
mmol) was performed in different solvents and catalyst dosages (Table 1). In a solvent with a
boiling point less than 70°C e.g. Et2O, cyclohexane, CH2Cl2, and hexane no product was formed.
In other solvents including CH3CN, THF, DMF, MeOH, EtOH, and EtOAc a complex mixture
was formed due to the reaction of solvents with starting materials and oxidant. Thus solvent-free
was chosen as the suitable media for this transformation. Further, to optimize the catalyst
dosages, various amount of catalyst including 0.5, 0.25, 0.1 and 0.05 mmol were investigated.
The results show that under the solvent-free condition the 0.25 mmol of CuO nanoparticles
provides the desired products in higher yield.
Next, by applying the optimal reaction conditions, the effect of substitution of electron-
withdrawing and electron-donating groups on the aromatic ring of aldehydes, on the reaction rate
and efficiency of the reaction was investigated. In general, electron-withdrawing groups have
experienced higher reaction rate than those of electron-donating groups. The substitution in the
ortho position will be reduced the rate of productivity of the reaction. Despite the reaction times,
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the yields of all the reactions are excellent (Table 2). 2-Pyridinecarbadehyde also contributed to
the reaction and gave the product in 76% yield.
The recyclability of the catalyst was checked using the following condition: benzaldehyde (1.0
mmol), and benzene-1,2-diamine (1 mmol) and CuO nanoparticles (0.25 mmol). During the
purification of the products, the catalyst was separated by simple filtration, dried and reused for
the similar reaction. The results of catalyst recovery are shown in Figure 7. As shown, the
recovered CuO nanoparticles could reuse without significant loss in its catalytic activity.
In summary, we have utilized a novel, inexpensive and environmentally friendly method for the
synthesis of copper oxide nanoparticles in a watery lemon juice media. The as-prepared copper
oxide nanoparticles were used in the synthesis of 2-arylbenzimidazoles via cyclo-condensation
reaction of 1,2-benzenediamine and aldehydes which were shown a high efficiency on the
productivity in a short reaction time. This method is feasible, is environmentally friendly from
the view of organic material removal in the preparation copper oxide nanoparticles and is
advantageous for the high-efficiency production of 2-arylbenzimidazoles.
Experimental
The chemicals used were purchased from Merck and Aldrich companies. For the measurement of
powder X-Ray diffraction patterns a D8-Advance Bruker axs, diffractometer (CuKα radiation, λ
= 1.54178 Å) was used. A HITACHI Microscope (Model S-4160) was applied for creation of
Field Emission Scanning Electron Microscopy (FE-SEM) images. N2 adsorption, specific surface
area, and total pore volume measurements were carried out using Quantachrome instrument
(Model Nova 2000, USA). A Malvern Zetasizer Nano ZS (ZEN 3600) device was used for the
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13
Dynamic light scattering (DLS) measurement. The H-and C-NMR spectra were measured in
DMSO-d6 by a Bruker Avance DPX 400 MHz instrument. Melting points were determined in
open capillaries with a BUCHI 510 melting point apparatus.
Preparation of CuO nanoparticles:
20 mmol of copper acetate was dissolved in 50 mL of distillate water and subsequently mixed
with 100 mL of lemon water. The solution was refluxed for 30 min with vigorous stirring.
Afterward, the pH value was increased to basic area by the addition of sodium hydroxide solid
into the above boiling solution. The mixture was cooled, centrifuged and the precipitate was
washed with distilled water dried and calcinated in 500°C for 2h.
Typical Procedure:
1,2-benzenediamine (1 mmol), aryl aldehydes (1 mmol) and H2O2 (aq. 30%; 0.5 mL) were
charged into a test tube and combined with CuO nanoparticles (0.25 mmol). The mixture was
heated up to 80°C until completion of the reaction (Table 2). After completion (TLC
monitoring), the contents was cooled to 25°C, dissolved in CH2Cl2 and filtrate to remove the
catalyst. Finally, the crude product was purified by recrystallization from ethanol after removal
of CH2Cl2.
Acknowledgments
The authors are grateful to the Islamic Azad University-Zarghan Branch research council for
partial support of this investigation.
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Table 1: Optimization of the reaction conditions (Scheme 1)
Entry
1
Catalyst amount
(mmol)
Solvent (5
mL)
Hexane
Temperature
(°C)
Time (h)/
Yield (%)a
2/0
0.25
Reflux
2
3
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.5
Cyclohexane
Reflux
Reflux
Reflux
80
2/0
2/0
Et2O
CH2Cl2
THF
DMF
EtOAc
EtOH
CH3CN
MeOH
-
4
2/0
5
2/36
6
80
2/48
7
Reflux
Reflux
Reflux
Reflux
80
2/56*
8
2/75*
9
2/71*
10
11
12
13
14
2/69*
30min/93
30min/89
30min/68
30min/31
-
80
0.1
-
80
0.05
-
80
aIsolated yield
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* complex mixture
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Table 2: Synthesis of 2-arylbenzimidazole derivatives using CuO nanoparticles (0.25 mmol) as
catalyst
Entry
Aldehyde
Time
(min)
Yield
(%)a
m.p. [lit. m.p.°C]ref
1
Benzaldehyde
30
93
85
79
77
94
90
89
97
97
86
96
90
287-289 [288-290]15
287-289 [288-290]15
233-235 [232-234]16
241-243 [240-242]9
225-227 [225-226]9
269-271 [268-270]9
293-295 [292-293]15
314-316 [312-314]9
308-310 [310-311]15
210-212 [209-210]9
233-235 [232-234]11
251-253 [250-252]16
2
3,4,5-Trimethoxybenzaldehyde
3,4-Dimethoxybenzaldehyde
2-Hydroxybenzaldehyde
4-Methoxybenzaldehyde
4-Methylbenzaldehyde
4-Chlorobenzaldehyde
4-Nitrobenzaldehyde
3-Nitrobenzaldehyde
2-Nitrobenzaldehyde
2-Chlorobenzaldehyde
4-Flourobenzaldehyde
120
90
80
56
50
30
20
20
55
45
40
3
4
5
6
7
8
9
10
11
12
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13
2-Pyridinecarbadehyde
60
76
215-217 [217-219]8
aIsolated yields.
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Figure 1: X-ray diffraction (XRD) spectra of CuO particles
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Figure 2: FE-SEM image of CuO nanoparticles
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Figure 3: particle size distribution analysis of CuO nanoparticles
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Figure 4: Thermo gravimetric analyses of CuO nanoparticles after calcinations at 500 °C (a) and
before calcinations (b)
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Figure 5: The nitrogen adsorption-desorption isotherm of CuO nanoparticles.
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Figure 6: the pore size distribution of CuO nanoparticles
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Figure 7: Reusability of CuO nanoparticles
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Scheme 1: Preparation of 2-aryl benzimidazoles
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Scheme 2: Proposed mechanism for the preparation of 2-arylbenzimidazoles
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