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Nano-Structured Pyrophosphate Na2CaP2O7 as Catalyst for Selective Synthesis of 1,

2-Disubstituted Benzimidazoles in Pure Water

Article  in  Current Organic Chemistry · August 2015

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Current Organic Chemistry, 2015, 19, 000-000 1

Nano-structured Pyrophosphate Na2CaP2O7 as Catalyst for Selective Synthesis of 1,2-

Disubstituted Benzimidazoles in Pure Water

Karim Dänouna,b, Ilham Jiouib, Mohamed Bouhrarac, Mohamed Zahouilya,b, Abderrahim Solhyd,*,
Mustapha Jouiade, Christophe Lenf and Aziz Fihrib,*

Abderrahim Solhy
a
Moroccan Foundation for Advanced Science Innovation and Research (MAScIR),
Rabat Design, Rue Mohamed El Jazouli, Madinat El Irfane 10100-Rabat, Morocco; b
Laboratoire de Matériaux, Catalyse & Valorisation des Ressources Naturelles, URAC
24, Faculté des Sciences et Techniques, Université Hassan II, Mohammedia B.P. 146,
20650, Morocco; c Department of Chemistry, School of Science and Technology, Naz-
arbayev University, 010000 Astana, Republic of Kazakhstan; d Center of Advanced
Materials (CAM), Université Mohammed VI Polytechnique, Lot 660-Hay Moulay Ra-
chid, 43150 Ben Guerir, Morocco; e Institute Center for Energy (iENERGY), Depart-
ment of Mechanical and Materials Engineering, Masdar Institute of Science and
Technology, Abu Dhabi 54224, United Arab Emirates; f Sorbonne Universités, Trans-
formations Intégrées de la Matière Renouvelable, UTC/ESCOM, Centre de Recherche Aziz Fihri
Royallieu, CS60319, F-60203, Compiègne Cedex, France.

Abstract: We report on synthesis of 1,2-disubstituted benzimidazoles in pure water using nanostructured pyrophosphate Na2CaP2O 7. Our
findings showed that this heterogeneous catalyst exhibited high catalytic activity and high selectivity in the synthesis of 1,2-disubstituted
benzimidazoles from direct cyclocondensation of aromatic aldehydes with substituted o-diaminoarene in pure water. The salient benefits
of this method rely on various factors namely: a simple procedure, mildness of the reaction conditions, short reaction times, operational
simplicity, high chemoselectivity, low cost and recyclability of the catalyst.

Keywords: Green chemistry, heterogeneous catalysis, benzimidazoles, diaminoarene, aldehydes, recyclable catalyst.

INTRODUCTION
The synthesis of benzimidazole derivatives has attracted con-
siderable attention over the years due to their application in phar-
maceutical and biological sectors. Indeed, these compounds have
vast medicinal applications as antivirals, anticancers, antihyperten-
sives, antihistamines, antiparasitics, and antiulcers [1-9]. They are
also considered as an important intermediates formany organic and
they can be used as starting materials to synthesize a large variety
of ionic liquidas well as ligands to complex various transition met-
als commonly applied for modeling biological systems [10-13].
Many synthetic methods have been developed for benzimidazoles
synthesis with the most common one being the condensation of
ortho-diaminoarene with carboxylic acids or their derivatives such
as nitriles, imidates, or orthoesters under harsh dehydrating condi-
tions. For instance, concentrated sulfuric acid and polyphosphoric
acid as well as higher temperature [14-16]. Another facile and effi-
cient method reported for the preparation of these compounds is the
reaction of o-diaminoarene with aldehydes by employing an acidic
catalyst under various reaction conditions [17-19]. Recently, several
catalytic systems have been developed to prepare the benzimida-
zoles as Pd(PPh3)4 [20], Montmorillonite K-10 [21], Nanoporous
aluminosilicate [22], Zeolite [23], Tungstate-promoted Zirconia
[24], Copper [25], Zn-proline [26], etc...Although these catalytic
systems are quite satisfactory, many of them still suffer from some
limitations, such as employing large amounts of toxic solvents,
expensive metal catalysts and additives and the formation of several
side reactions. Yet, one of the major issues of these catalytic sys-
tems resides in the fact that they are often non-regioselective and a
mixture of isomers is generally obtained. This turns the characteri-
zation and the separation of the 1,2-disubstituted benzimidazoles
and 2-substituted benzimidazoles to a real concern. Hence, the de-
velopment of an efficient and an environmentally benign chemical
process for the preparation of new biologically relevant molecules,
constitutes a major challenge for chemists in organic synthesis [27,
28]. Besides, conducting reactions in water has many advantages, in
particular it is non-flammable, not expensive, and non-toxic nature
[29]. Moreover, water as solvent will facilitate bimolecular reac-
tions involving ionic intermediates due to its high cohesive energy
density and dielectric constant as well as its high internal pressure.
In this context, this present work was carried out within our
progressive program to develop efficient and environmentally be-
nign protocols for the synthesis of various products [30, 31]. Here,
we report a practical, inexpensive, efficient and green methodology
for direct synthesis of disubstituted benzimidazoles through the
condensation of o-diaminoarene with aldehydes by employing a
bifunctional nano-structured diphosphate as a new catalyst in pure
water under various reaction conditions.

*Address correspondence to these authors at the Laboratoire de Matériaux, Catalyse &
Valorisation des Ressources Naturelles, URAC 24, Faculté des Sciences et Techniques,
Université Hassan II, Mohammedia B.P. 146, 20650, Morocco and Center of Advanced
Materials (CAM), Université Mohammed VI Polytechnique, Lot 660-Hay Moulay
Rachid, 43150 Ben Guerir, Morocco; Tel: (+212) 06-61-98-31-39; Fax: (+212) 05-30-
27-98-27; E-mails: Abderrahim.Solhy@um6p.ma ; a.fihri@mascir.com
RESULTS AND DISCUSSION
The Nano-structured pyrophosphate (Na2CaP2O7) used in this
work was prepared and characterized according to the procedures
described in the previous literature [30, 31]. Indeed our X-Ray Dif-

1385-2728/15 $58.00+.00 © 2015 Bentham Science Publishers

2 Current Organic Chemistry, 2015, Vol. 19, No. ??
.Fig. (1). SEM images of the Na2CaP2O7.
Fig. (2). TEM images of Na2 CaP2O 7.
Scheme 1. Cyclocondensation of benzene-1,2-diamine 1a with benzaldehyde 2a.
fraction experiments carried out showed that the synthesized cata-
lyst was Na2CaP2O7. The specific surface area of the Na2CaP2O7
measured by physical adsorption isotherm at 77K by using Brun-
auer–Emmett–Teller (BET) theory method from the adsorption-
desorption isotherm of nitrogen at its liquid temperature at 77 K
was found to be 4 m2g-1. Helios Nano FEI Scanning Electron Mi-
croscope (SEM) was used to study the morphology of the surface of
the Na2CaP2O7 (Fig. 1). The micrographs revealed a condensed
heterogeneous microsctructure where the particles were dispersed
uniformly with a clear surface roughness. This can be explained by
a heterogeneous growth of the crystallites caused by the adopted
method of the synthesis, consequently affecting the morphology
and also porosity. Once dispersed in water and after sonication, it
was observed that these particles were broken and some rod like
structure starts to be visible in Transmission Electron Microscope
TEM (Fig. 2). More closer analysis of these particles using
HRTEM revealed some crystalline structure with specific periodic-
ity (Fig. 2b). Isolated particle, as shown in Figure 2c, highlights this
feature and exhibits clearly the multilayers structure of this nano-
structured catalyst.
To explore the potential activity of this heterogeneous catalyst,
we initially investigated the reaction of benzene-1,2-diamine 1a
with benzaldehyde 2a as model reaction to establish the feasibility
Dänoun et al.
of our approach and to optimize the reaction conditions (Table 1).
The influence of the various reaction parameters such as reaction
time and solvent effect as well as the amount of catalyst was exam-
ined to determine the best operative experimental conditions for the
selective 1,2-disubstituted benzimidazole (Scheme 1). The reaction
was performed in water at 80°C for different time intervals (Table
1). The yield seems to be sensitive to the reaction time, indeed it
was found that the yield increases with increasing reaction time up
to 3 hours (Table 1, entries 1-3). After this time, further increase of
the reaction time showed no effect on the yield of compound 4
(entries 4-6). Thus, the optimum time for the synthesis of 1,2-
disubstituted benzimidazole 4a was selected to be 3 hours. In addi-
tion, increasing the reaction time allowed controlling the selectivity
during the cyclocondensation of benzene-1,2-diamine 1a with ben-
zaldehyde 2a. After 3 hours of reaction time only the formation of
product 4a was observed (Table 1, entries 4-6) [32].
It is worth noticing here that utilizing eco-friendly solvent such
water in organic synthesis minimizes dramatically the consumption
of expensive and toxic organic solvents and shows both economical
and synthetic advantages. Moreover, conducting reactions in water
can be advantageous, particularly for large-scale industrial applica-
tions, as a result of the ease of purification as well as the environ-
mental friendliness and low-cost of water [33-36]. After exploring
Nano-Structured Pyrophosphate Na2CaP2O7 as Catalyst for Selective Synthesis Current Organic Chemistry, 2015, Vol. 19, No. ?? 3

Table 1. Synthesis of benzimidazoles derivatives 3a and 4a under different reaction times.

Yield (%)a

Entry Time (h) Product 3a Product 4a

1 0.5 17b 60b

2 1 9b 72b

3 2 2b 77b

4 3 None 84c

5 4 None 84c

6 5 None 85 c
a
Conditions: benzene-1,2-diamine 1a (1.0 mmol), benzaldehyde 2a (2.0 mmol), 3 mL of water, 38 mol% of Na2CaP2O7, 80 °C.
b
Calculate by selectivity rapport
c
Isolated yield.

Fig. (3). Effect of solvents on preparation of 1-benzyl-2-phenyl-1H-benzo[d]imidazole 4a.

formation between two products 3 and 4 while we observed high

Fig. (4). Optimization of the amount of Na2 CaP2O 7 for the synthesis of 1-
benzyl-2-phenyl-1H-benzo[d]imidazole 4a.
the scope of various solvents, this nano-catalyst Na2CaP2O7 was
found to be most active in water. Indeed, using water as solvent, the
reaction was completed in 3 hours and we observed the formation
of corresponding product 4a with excellent yield and selectivity
(Fig. 3). Other green solvent like ethanol may be used for this reac-
tion under same conditions as mentioned above, but unfortunately
after 3 hours at 80°C, the reaction was completed with competitive
selectivity for water as solvent. We note, moreover, that inferior
results were also obtained with methanol, propanol and cyclohex-
ane. Based on these results, water was naturally selected as the best
eco-friendly solvent for the rest of our study.
Besides, we observed that catalyst concentration also played an
important role in the synthesis of 1,2-disubstituted benzimidazole.
After testing various amounts of Na2CaP2O7, we were able to de-
termine the optimum yield of product using 38 mol% of catalyst
(Fig. 4). It was notable that further increase of the amount of cata-
lyst showed no effect on the yield of corresponding product.
To investigate the scope of this organic reaction, various substi-
tuted arylaldehydes 2a-h are reacted with o-diaminoarene 1a-b by
the catalytic action of this nanostructured catalyst under same reac-
tive conditions such as temperature (80 °C), ratio of reagents, cata-
lyst weight (100 mg), and reaction time (3 hours). The obtained
resultants are summarized in Table 2. Thereby, we synthesized a
large number of 1,2-disubstituted benzimidazoles derivatives hav-
ing various functional groups in para position in excellent yields
and high selectivity.
Several aromatic aldehydes, with various substituents on the
aromatic ring, were subjected to the condensation reaction. As
shown in Table 2, arylaldehydes with and without electron-donating
substituents gave the desired benzimidazoles with good yields (Ta-
ble 2, entries 2-5). In addition the condensation of the arylaldehydes
4 Current Organic Chemistry, 2015, Vol. 19, No. ?? Dänoun et al.

Table 2. Water mediated synthesis of 1,2-disubstituted benzimidazoles.

Entry R R
Product Yield (%)a

1 1a: R = H 2a: R
= H 4a 84

2 1a: R = H 2b: R
= MeO 4b 82

3 1a: R = H 2c: R
= Me 4c 77

4 1a: R = H 2d: R
= OH 4d 75

5 1a: R = H 2e: R
= Br 4e 86

6 1a: R = H 2f: R
= NO2 4f 89

7 1a: R = H 2g: R
= Cl 4g 85

8 1a: R = H 2h: R
= CN 4h 86

9 1b: R = Br 2a: R
= H 4i 73

10 1b: R = Br 2b: R
= MeO 4j 70

11 1b: R = Br 2f: R
= NO2 4k 77

12 1b: R = Br 2g: R
= Cl 4l 79

13 1b: R = Br 2h: R
= CN 4m 80

14 1b: R = Br 2c: R
= Me 4n 69

15 1b: R = Br 2d: R
= OH 4p 68

16 1b: R = Br 2e: R
= Br 4q 65
a
Conditions: o-diaminoarene (1.0 mmol), arylaldehydes (2.0 mmol), 3 mL of water, amount of Na2CaP2O7 (38 mol%), 3h, 80 °C.

Scheme 2. Unexpected formation of Schiff base salicyldehyde.

having electron-withdrawing substituents such as 4-nitrobenz-
aldehyde 2f, 4-chlorobenzaldehyde 2g and 4-cyanobenzaldehyde 2h
with benzene-1,2-diamine 1a gave the corresponding benzimida-
zoles 4f, 4g and 4h with very good yield (Table 2, entries 6-8).
Additionally, good to excellent yields were obtained in the
condensation of 4-bromobenzene-1,2-diamine 1b with several
substituted aldehydes containing both electron-donating and
withdrawing groups (Table 2, entries 9-16). The position of hy-
droxyl group on in para position of benzaldehyde ring made much
more difference in reactivity and turned this reaction more difficult
and complex because the nucleophilicity of benzaldehyde
cause the nucleophilicity of benzaldehyde decreases. In this con-
text, the reaction of 2-hydroxybenzaldehyde 2i with benzene-1,2-
diamine 1a led to the formation of the Schiff base product 5d under
the same reaction conditions. Surprisingly, the reaction did not
proceed to produce the desired product 5d’ even after heating the
mixture reaction for 6 hours. This unexpected phenomenon was
probably due to the existence of intramolecular hydrogen bonds
which prevented 5d from further cyclization to give 5d’ (Scheme
2). As expected, the condensation of benzene-1,2-diamine 1a with
cinnamaldehyde 2j furnished the desired product 6 with only 49%
Nano-Structured Pyrophosphate Na2CaP2O7 as Catalyst for Selective Synthesis
Scheme 3. Condensation of benzene-1,2-diamine 1a with cinnamaldehyde 2j.
Scheme 4. A proposed pathway for the synthesis of 1-benzyl-2-phenyl-1H-
benzo[d]imidazole 4a.
yield since the coupling reaction of cinnamaldehyde with diamines
was known to be difficult (Scheme 3).
One of the key points to understand the reaction mechanism in
heterogeneous catalysis is the determination of the active surface
sites and the activation processes. The presence of a large popula-
tion of electron pairs on the compounds surface such as P2O74
,
PO43
, Ca2+ and Na+ indicates that the surface of Na2CaP2O7 pre-
sents certainly multicatalytic active sites such as basic sites (BS)
and acidic sites (AS), which is in coherence with the catalysis shape
Fig. (5). Recycling study of Na2CaP2O7 in the synthesis of 1-benzyl-2-phenyl-1H-benzo[d]imidazole 4a.
Current Organic Chemistry, 2015, Vol. 19, No. ?? 5
(presence of various layers) as observed in TEM micrographs (Fig.
2c). The synthesis mechanism of 1,2-disubstituted benzimidazoles
formation was mostly based on direct cyclocondensation process;
the plausible mechanism for this reaction was proposed in Scheme
4. Initially, the acidic sites coordinate with the oxygen atom of the
aldehyde and facilitate the nucleophilic attack the amino group of
benzene-1,2-diamine (i). This first step produces dibenzylidene-o-
phenylenediamine (Shiff base) as intermediate (ii). In the presence
of electrophilic catalyst, the intramolecular 1,3-hydride migration
(iii) was induced to directly give the desired 1,2-disubstituted ben-
zimidazole [37, 38].
The reusability of the catalyst is another important factor from
economical and environmental point of view. In this context, we
continued our study to examine the reusability and recoverability of
the catalyst as an additional important factor in the field of synthetic
phosphate
To achieve this goal, the model reaction of benzene-1,2-
diamine 1a with benzaldehyde 2a was carried out in the presence of
38 mol% of Na2CaP2O7 as heterogeneous catalyst and in water as
solvent. After each cycle, the initial catalystNa2CaP2O7 was re-
moved, dried at 100°C and reused in this condensation process. The
catalyst was found to recycle four times with a partial loss of per-
formance after the third cycle (Fig. 5). This can be explained by the
fact that after each reaction, a small amount of reagents remain
adsorbed on the catalyst even after it was dried, which hinders the
reagents to access to the active sites. This result reveals low per-
formance of the catalysis once reused several times. Nevertheless,
once the recovered catalyst is properly washed and calcined, it re-
trieves its original activity, which means that this treatment after
activity opens the clogged pores allowing the reagents to access
freely to the active sites.
6 Current Organic Chemistry, 2015, Vol. 19, No. ??
CONCLUSION
1,2-disubstituted benzimidazoles were successfully synthesized
via condensation reaction of benzene-1,2-diamine with arylalde-
hydes using Na2CaP2O7 as heterogeneous catalyst. The reactions
were achieved in water as solvent and the catalyst showed great
potential to be reused several times without any loss in activity. The
high product yields, operational simplicity, mild reaction condi-
tions, short reaction times and recyclability as well as the environ-
mental compatibility are the notable advantages of the present pro-
cedure. Moreover, this cheap heterogeneous catalyst, also facile to
synthesize and easily scalable, makes it a potential candidate to
replace the existing homogeneous and expensive heterogeneous
catalysts currently being used in the synthesis of various industri-
ally important and biologically active benzimidazoles.
EXPERIMENTAL SECTION
General Considerations
All commercial reagents were purchased from Aldrich Chemi-
cal Company and were used without further purification. X-ray
diffraction (XRD) patterns of the catalyst were obtained at room
temperature on a Bruker AXS D-8 diffractometer using Cu-K
(
=
0.15418 nm) radiation in Bragg–Brentano geometry (–2). Scan-
ning Electron Microscopy (SEM) observations were carried out on
a Helios Nano FEIafter AuPd metallization. The Transmission
Electron Microscopy (TEM) micrographs were obtained on a
FEI®Tecnaimicroscope operating at 200 kV. Specific surface areas
were determined from the nitrogen physical adsorption/desorption
isotherms (at 77 K) and measured with a Quanta chrome Autosorb-
1 automatic analyzer, using the BET theory at p/p0 = 0.98. NMR
spectra were recorded on a Bruker Avance III 600 MHz NMR spec-
trometer at 298K, with working frequencies of 600.13, 150.902
MHz for proton and carbon, respectively. DMSO-d6 and TMS were
used as solvent and as the internal standard, respectively. Liquid
chromatography-mass spectrometry was used to identify the prod-
ucts; the separation system used was a Waters Acquity UPLC (Wa-
ters, Millford, MA) coupled to Micromass Q-TOF Micro (Waters).
Elution buffers were as follows: (A) water with 0.1% formic acid
and (B) methanol with ratio 60:40, respectively.
General Procedure for the Synthesis of Benzimidazoles Deriva-
tives
To a mixture of o-diaminoarene (1.0 mmol, 1a: 108.1 mg, 1b:
187.0 mg) and arylaldehyde (2.0 mmol, 2a: 212.2 mg, 2b: 272.3
mg, 2c: 240.3 mg, 2d: 244.2 mg, 2e: 370.0 mg, 2f: 302.2 mg, 2g:
281.1 mg, 2h: 262.2 mg, 2i: 244.2 mg, 2j: 264.3 mg) and in water
(3 mL) under open air atmosphere, 38 mol% of Na2CaP2O7 was
added (100 mg). The reaction was stirred at 80°C for three hours.
The progress of the reaction was monitored by thin-layer chroma-
tography using hexane and ethyl acetate (9:1) as eluents. After the
completion of the reaction, the reaction mixture was washed with
ethyl acetate and the catalyst was removed by filtration. The reac-
tion mixture was extracted with dichloromethane and the organic
layers were combined, dried over MgSO4, filtered and evaporated
under reduced pressure. The obtained product was purified by col-
umn chromatography using (hexane: ethyl acetate in the ratio 9:1)
to give 1,2-disubstituted benzimidazoles derivatives 4a-q, 6 and 5d
product. All products were identified by 1H NMR, 13C NMR and
UPLC-MS.
Dänoun et al.
Characterization of 1,2-disubstituted Benzimidazoles
1-benzyl-2-phenyl-1H-benzo[d]imidazole (4a). Using the above
procedure benzene-1,2-diamine (1a, 108.1 mg, 1 mmol) and
benzaldehyde (2a, 212.2 mg, 2 mmol) were converted to 1-benzyl-
2-phenyl-1H-benzo[d]imidazole (4a, 238.5 mg, 84%).White solid,
mp 134-135°C,1H NMR (DMSO-d6, 600 MHz)
7.75-7.23 (m, 3
H), 7.53-7.45 (m, 4 H), 7.29-7.21 (m, 5 H), 7.00 (d, 2 H, J= 7.5
Hz), 5.58 (s, 2 H); 13C aNMR (DMSO-d6, 151 MHz)
154.42 (C2),
143.89 (C7a), 138.10 (C3a), 137.08 (C2

), 131.33 (C1
), 130.99
(C4
), 130.21 (C3
, C5
), 129.95 (C4

, C6
), 128.64 (C3

, C7

),
127.25 (C2
, C6
), 123.86 (C5

), 123.39 (C5, C6), 120.46 (C4),
112.27 (C7), 48.63 (C1

);ESI-MS [M+H+]: m/z = 285.0927. Rf:
0.410 (hex/EtOAc 3:1).
1-(4-methoxybenzyl)-2-(4-methoxyphenyl)-1H-benzo[d]imida-
zole (4b). Using the above procedure benzene-1,2-diamine (1a,
108.1 mg, 1 mmol) and 4-methoxybenzaldehyde (2b, 272.3 mg, 2
mmol) were converted to1-(4-methoxybenzyl)-2-(4-methoxy-
phenyl)-1H-benzo[d]imidazole (4b, 264.8 mg, 77 %). White solid,
mp 128-130°C, 1H NMR DMSO-d6, 600 MHz)
7.68 (d, 3 H, J =
8.5 Hz), 7.43 (d,1 H, J = 8.1 Hz), 7.23-7.20 (m, 2 H), 7.09 (d, 2 H,
J = 8.7 Hz), 6.94 (d, 2 H, J = 8.5 Hz), 6.84 (d, 2 H, J = 8.6 Hz),
5.49 (s, 2H), 3.82 (s, 3 H), 3.68 (s,3 H); 13C NMR (DMSO-d6, 151
MHz)
161.66 (C4
), 159.80 (C5

), 154.46 (C2), 143.91 (C7a),
137.06 (C3a), 131.79 (C2
, C6
), 130.04 (C3

, C7

), 128.67 (C2

),
123.65 (C6), 123.59 (C5), 123.34 (C1’), 120.23 (C4), 115.53 (C3
,
5
), 115.44 (C6

, C4

), 112.26 (C7), 56.59 (OCH3), 56.30 (OCH3),
48.20 (C1

); ESI-MS [M+H+]: m/z = 345.1679. Rf: 0.390
(hex/EtOAc 3:1).
1-(4-methylbenzyl)-2-(p-tolyl)-1H-benzo[d]imidazole (4c).
Using the above procedure benzene-1,2-diamine (1a, 108.1 mg, 1
mmol) and 4-methylbenzaldehyde (2c, 240.3 mg, 2 mmol) were
converted to 1-(4-methylbenzyl)-2-(p-tolyl)-1H-benzo[d]imidazole
(4c, 255.1 mg, 82 %). White solid, mp 125-127°C, 1H NMR
(CDCl3, 600 MHz)
8.06 (d, 1 H, J= 7.7 Hz), 7.86(d, 2 H, J = 7.5
Hz), 7.65 (d, 1 H, J = 7.5 Hz), 7.60 (d, 2 H, J = 7.5 Hz), 7.23-7.20
(m, 2 H), 7.15 (d, 2 H, J = 7.5 Hz), 7.01 (d, 2 H, J = 7.5 Hz), 5.43
(s, 2 H), 2.41 (s, 3H), 2.36 (s, 3H); 13C NMR (CDCl3, 151 MHz)

154.34 (C2), 142.96 (C7a), 140.14 (C3a), 137.49(C4
), 136.03
(C5

), 133.39 (C2

), 129.71 (C1
), 129.47 (C3
, C5
), 129.17 (C4

,
C6

), 127.19 (C3

, C7

), 127.02 (C2’,C6’), 125.91 (C5,C6),
123.32 (C4), 122.92 (C7), 48.41 (C1

), 22.11 (CH3), 21.77 (CH3);
ESI-MS [M+H+]: m/z =313.0685.Rf:0.382 (hex/EtOAc 3:1).
4-(1-(4-hydroxybenzyl)-1H-benzo[d]imidazol-2-yl)phenol (4d).
Using the above procedure benzene-1,2-diamine (1a, 108.1 mg, 1
mmol) and 4-hydroxybenzaldehyde (2d, 244.2 mg, 2 mmol) were
converted to 4-(1-(4-hydroxybenzyl)-1H-benzo[d]imidazol-2-
yl)phenol (4d, 236.4 mg, 75%). Pale yellow solid ,mp 255-257°C,
1
H NMR (DMSO-d6, 600 MHz)
10.82 (s, 1 H), 9.66 (brs, 1 H),
7.86 (d, 1 H, J = 8.0 Hz), 7.80 (d, 1 H, J = 8.0 Hz), 7.77 (d, 2 H, J =
8.5 Hz), 7.60-7.53 (m, 2 H), 7.10 (d, 2 H, J = 8.4 Hz), 6.98 (d, 2 H,
J = 8.3 Hz), 6.71 (d, 2 H, J = 8.4 Hz), 5.63 (s, 2 H); 13C NMR
(DMSO-d6, 151 MHz)
162.94 (C4
), 158.54 (C5

), 151.91(C2),
133.73 (C7a), 133.08 (C3a), 132.28 (C6
, C2
), 129.35 (C7

, C3

),
127.36 (C2

), 126.88 (C1
), 125.81 (C5, C6), 117.56 (C4), 116.66
(C7), 115.57 (C3
, C5), 114.66 (C4

), 113.92 (C6

), 49.45 (C1

);
ESI-MS [M+H+]: m/z = 317.1380. Rf: 0.291 (hex/EtOAc 3:1).
1-(4-bromobenzyl)-2-(4-bromophenyl)-1H-benzo[d]imidazole
(4e). Using the above procedure benzene-1,2-diamine (1a, 108.1
mg, 1 mmol) and 4-bromobenzaldehyde (2e, 370.0 mg, 2 mmol)
were converted to 1-(4-bromobenzyl)-2-(4-bromophenyl)-1H-
benzo[d]imidazole (4e, 379.4 mg, 86%). Pale yellow solid, mp 160-
Nano-Structured Pyrophosphate Na2CaP2O7 as Catalyst for Selective Synthesis
162°C, 1HNMR (DMSO-d6, 600 MHz)
7.74 (d, 3 H, J = 8.3 Hz),
7.66 (d, 2H, J = 8.4 Hz), 7.49 (d, 3 H, J = 8.2 Hz), 7.27-7.25 (m, 2
H), 6.94 (d, 2 H, J = 8.3 Hz), 5.57 (2 H); 13C NMR (DMSO-d6, 151
MHz)
153.84 (C2), 143.87 (C7a), 137.64 (C3a), 137.21 (C2

),
133.56 (C4
), 133.34 (C5

), 132.65 (C3
, C5
), 130.48 (C2
, C6
),
129.95 (C1
), 125.37 (C4

, C6

), 124.90 (C3

), 124.37 (C7

),
122.31 (C5,C6), 120.92 (C7), 112.75 (C4), 48.52 (C1

); ESI-MS
[M+H+]: m/z = 443.9423. Rf: 0.250 (hex/EtOAc 3:1).
1-(4-nitrobenzyl)-2-(4-nitrophenyl)-1H-benzo[d]imidazole (4f).
Using the above procedure benzene-1,2-diamine (1a, 108.1 mg, 1
mmol)and 4-nitrobenzaldehyde (2f, 302.2 mg, 2 mmol) were
converted to 1-(4-nitrobenzyl)-2-(4-nitrophenyl)-1H-benzo[d]
imidazole (4f, 331.6 mg, 89%). White solid, mp 189-192°C, 1H
NMR (DMSO-d6, 600 MHz)
8.33 (d, 2 H, J = 8.6 Hz), 8.15 (d, 2
H, J= 8.4 Hz), 8.00 (d, 2 H, J = 8.5 Hz), 7.80 (d, 1 H,J = 9.0 Hz),
7.54 (d, 1 H, J = 8.1 Hz), 7.34-7.31 (m, 2 H), 7.26 (d, 2 H, J = 8.4
Hz), 5.82 (s, 2 H);13C NMR (DMSO-d6, 151 MHz)
152.26 (C2),
149.22 (C4
), 148.10 (C5

), 145.52 (C2

), 143.84 (C7a), 137.26
(C3a), 137.14 (C1
), 131.56 (C3

, C7

), 128.63 (C2
, C6
), 125.15
(C3
), 125.13 (C5
), 124.92 (C4

), 124.15 (C6

), 121.02 (C5, C6),
112.45 (C4, C7), 48.39 (C1

); ESI-MS [M+H+]: m/z = 375.0297.
Rf: 0.236 (hex/EtOAc 3:1).
1-(4-chlorobenzyl)-2-(4-chlorophenyl)-1H-benzo[d]imidazole
(4g). Using the above procedure benzene-1,2-diamine (1a, 108.1
mg, 1 mmol)and 4-chlorobenzaldehyde (2g, 281.1 mg, 2 mmol)
were converted to 1-(4-chlorobenzyl)-2-(4-chlorophenyl)-1H-
benzo[d]imidazole (4g, 298.8 mg, 85%). White solid, mp 137-
139°C, 1H NMR (DMSO-d6, 600 MHz)
7.74 (d, 3 H, J = 8.4 Hz),
7.61 (d, 2 H, J =8.5 Hz), 7.50 (d, 1 H, J = 9.0 Hz), 7.35 (d, 2 H, J =
2 H), 7.28-7.26 (m, 2 H), 7.00 (d, 2 H, J = 8.4 Hz), 5.59 (s, 2 H);
13
C NMR (DMSO-d6, 151 MHz)
153.66 (C2), 143.88 (C7a),
136.44 (C3a), 134.91 (C2

), 133.70 (C4
), 132.34 (C5

), 130.53
(C3
, C5
), 130.32 (C2
, C6
), 130.13 (C4

, C6

), 129.54 (C1
),
124.72 (C3

, C7

), 124.18 (C5,C6), 120.85 (C7), 112.64 (C4),
48.36 (C1

); ESI-MS [M+H+]: m/z = 353.1679 Rf: 0.245
(hex/EtOAc 3:1).
4-(1-(4-cyanobenzyl)-1H-benzo[d]imidazol-2-yl)benzonitrile
(4h). Using the above procedure benzene-1,2-diamine (1a, 108.1
mg, 1 mmol) and 4-cyanobenzaldehyde (2h, 262.2 mg, 2 mmol)
were converted to 4-(1-(4-cyanobenzyl)-1H-benzo[d]imidazol-2-
yl)benzonitrile (4h, 286.6 mg, 86%). Pale yellow solid, mp 192-
194°C, 1H-NMR (DMSO-d6, 600 MHz)
5.56 (2H, s), 7.12 (1H,
dd),7.31-7.42 (4H, m), 7.79-7.90 (3H, m), 8.21- 8.29 (4H, m), 13C
NMR (DMSO-d6, 151 MHz)
151.45 (C2), 143.23 (C7a), 141.13
(C3a), 135.86 (C2

), 133.10 (C1
), 131.94 (C3
, C5
), 129.16 (C4

,
C6

), 128.76 (C3

, C7

), 125.96 (C2
, C6
), 124.49 (C5, C6),
122.40 (C4), 121.63 (C7), 118.60 (CN), 113.78 (CN), 112.36 (C4
),
110.40 (C5

), 48.20 (C1

); ESI-MS [M+H+]: m/z = 335.1659. Rf:
0.223 (hex/EtOAc 3:1).
1-benzyl-6-bromo-2-phenyl-1H-benzo[d]imidazole (4i). Using
the above procedure 4-bromobenzene-1,2-diamine (1b, 187.0 mg, 1
mmol) and benzaldehyde (2a, 212.2 mg, 2 mmol) were converted to
1-benzyl-6-bromo-2-phenyl-1H-benzo[d]imidazole (4i, 263.8 mg,
73%). White solid, mp 144-147°C, 1H NMR (DMSO-d6, 600 MHz)
8.10 (d, J = 8 Hz, 1H), 7.96-7.95 (m, 4 H), 7.63-7.61 (d, 2 H, J =
7.5 Hz ), 7.52-7.49 (m, 4 H), 7.00 (d, 2 H), 5.60 (s, 2 H); 13C NMR
(DMSO-d6, 151 MHz)
167.77 (C2), 133.34 (C7a), 131.21 (C3a),
129.72 (C2

), 129.55 (C1
), 129.51 (C5), 127.07 (C3
, C5
), 126.55
(C4

, C6

and C4’), 126.53 (C3’’,C7’’), 123.86 (C2’,C6’), 123.39
(C5’’), 120.46 (C4, C6), 112.27 (C7), 48.63 (C1

); ESI-MS
[M+H+]: m/z = 364.9754. Rf: 0.255 (hex/EtOAc 3:1).
Current Organic Chemistry, 2015, Vol. 19, No. ?? 7
6-bromo-1-(4-methoxybenzyl)-2-(4-methoxyphenyl)-1H-benzo
[d]imidazole (4j). Using the above procedure 4-bromobenzene-1,2-
diamine (1b, 187.0 mg, 1 mmol) and 4-methoxybenzaldehyde (2b,
272.3 mg, 2 mmol) were converted to 6-bromo-1-(4-methoxy-
benzyl)-2-(4-methoxyphenyl)-1H-benzo[d]imidazole (4j, 295.6 mg,
70%). White solid, mp 186-188°C, 1H NMR (DMSO-d6, 600 MHz)

8.30 (d, 1H, J = 8.0 Hz), 7.55 (d, 2 H, J = 8.5 Hz), 7.27-7.23 (m, 2
H), 7.09 (d, 2 H, J = 8.7 Hz), 6.94 (d, 2 H, J = 8.5 Hz), 6.84 (d, 2 H,
J = 8.6 Hz), 5.49 (s, 2 H), 3.82 (s, 3 H), 3.68 (s,3 H); 13C NMR
(DMSO-d6, 151 MHz)
161.66 (C4’), 159.80 (C5’’), 154.46 (C2),
143.91 (C7a), 137.06 (C3a), 131.79 (C2’,C6’), 130.04 (3’’,C7’’),
128.67 (C2’’), 123.65 (C5), 123.59 (C7), 123.34 (C4), 120.23
(C1’), 115.53 (C6), 115.44 (C4’’,C6’’), 112.26(C3’,C5’) , 56.59
(OCH3), 56.30 (OCH3), 48.20 (C1

); ESI-MS [M+H+]: m/z =
424.1328 Rf: 0.290 (hex/EtOAc 3:1).
6-bromo-1-(4-nitrobenzyl)-2-(4-nitrophenyl)-1H-benzo[d]imi-
dazole (4k). Using the above procedure 4-bromobenzene-1,2-
diamine (1b, 187.0 mg, 1 mmol) and 4-nitrobenzaldehyde (2f,
302.2 mg, 2 mmol) were converted to 6-bromo-1-(4-nitrobenzyl)-2-
(4-nitrophenyl)-1H-benzo[d]imidazole (4k, 347.6 mg, 77%). Yel-
low solid, mp 220-222°C, 1H NMR (DMSO-d6, 600 MHz)
8.78
(d,1 H, J = 7.1 Hz), 8.43 (d, 2 H, J = 8.4 Hz), 8.35 (d, 2 H, J = 8.5
Hz), 7.59 (d, 1 H, J = 9.0 Hz), 7.56 (d, 1 H, J = 8.1 Hz), 7.34-7.31
(m, 2 H), 7.26 (d, 2 H, J = 8.4 Hz), 5.82 (s, 2 H); 13C NMR
(DMSO-d6, 151 MHz)
151.83 (C2), 144.22 (C4
), 143.84 (C5

),
137.26 (C2

), 137.14 (C7a), 131.56 (C3a), 128.63 (C1
), 125.13
(C3

, C7

), 125.15 (C2
, C6
), 124.92 (C3], C5
), 124.15 (C4

,
C6

), 121.02 (C5), 114.44 (C4, C6), 112.45 (C7), 48.39 (C1

);
ESI-MS [M+H+]: m/z = 454.2456 Rf: 0.215 (hex/EtOAc 3:1).
6-bromo-1-(4-chlorobenzyl)-2-(4-chlorophenyl)-1H-benzo[d]
imidazole (4l). Using the above procedure 4-bromobenzene-1,2-
diamine (1b, 187.0 mg, 1 mmol) and 4-chlorobenzaldehyde (2g,
281.1 mg, 2 mmol) were converted to 6-bromo-1-(4-chlorobenzyl)-
2-(4-chlorophenyl)-1H-benzo[d]imidazole (4l, 339.6 mg, 79%).
Light yellow solid, mp 158-159°C,1H NMR (DMSO-d6, 600 MHz)

8.18 (d, 1H, J =8.0 Hz), 7.95 (d, 2 H, J =8.5 Hz), 7.84 (d, 2 H,J =
8.4 Hz), 7.61 (d, 2 H, J =8.5 Hz), 7.35 (d, 2 H, J = 2 H), 7.00 (d, 2
H, J = 8.4 Hz), 5.60 (s, 2 H); 13C NMR (DMSO-d6, 151 MHz)

151.11 (C2), 150.64 (C7a), 148,61 (C3a), 140.54 (C2

), 135.77
(C1
, C4
), 131.18 (C5

), 131.12 (C3
, C5
), 128.19 (C2
, C6
),
126.48 (C4

, C6

and C5), 124.85 (C3

, C7

), 124.22 (C7), 116.64
(C4, C6), 48.36 (C1

); ESI-MS [M+H+]: m/z = 432.0987. Rf: 0.227
(hex/EtOAc 3:1).
4-(6-bromo-1-(4-cyanobenzyl)-1H-benzo[d]imidazol-2-yl)ben-
zonitrile (4m). Using the above procedure 4-bromobenzene-1,2-
diamine (1b, 187.0 mg, 1 mmol) and 4-cyanobenzaldehyde (2h,
262.2 mg, 2 mmol) were converted to 4-(6-bromo-1-(4-
cyanobenzyl)-1H-benzo[d]imidazol-2-yl)benzonitrile (4m, 328.9
mg, 80%). Pale yellow solid, mp 210-212°C, 1H NMR (DMSO-d6)

8.76 (s,1H), 8.11 (d,2H), 8.06-8.00 (m,4H), 7.77-7.74 (m,4H),
5.56 (2H, s), 13C NMR (DMSO-d6, 151 MHz)
151.72 (C2),
143.17 (C7a), 141.07 (C3a), 135.93 (C2

), 134.09 (C1
), 132.71
(C3
, C5
), 129.69 (C4

, C6

), 129.28 (C3

, C7

), 126.59 (C2
,
C6
), 124.37 (C5), 123.71 (C4, C6), 120.76 (C7), 118.07 (CN),
113.89 (CN), 112.42 (C4
), 110.24 (C5

), 48.16 (C1

); ESI-MS
[M+H+]: m/z = 414.9459. Rf: 0.196 (hex/EtOAc 3:1).
6-bromo-1-(4-methylbenzyl)-2-(p-tolyl)-1H-benzo[d]imidazole
(4n). Using the above procedure 4-bromobenzene-1,2-diamine (1b,
187.0 mg, 1 mmol)and 4-methylbenzaldehyde (2c, 240.3 mg, 2
mmol) were converted to 6-bromo-1-(4-methylbenzyl)-2-(p-tolyl)-
1H-benzo[d]imidazole (4n, 268.6 mg, 69%). White solid ,mp 145-
8 Current Organic Chemistry, 2015, Vol. 19, No. ??
147°C, 1H NMR (DMSO-d6,600 MHz)
8.06 (d, 1 H, J = 7.7 Hz),
7.84 (d, 2 H, J = 7.3 Hz), 7.38 (d, 2 H, J = 7.5 Hz), 7.23-7.15 (m, 4
H), 7.06 (d, 2 H, J = 7.5 Hz), 5.43 (s, 2 H), 2.41 (s, 3H), 2.36 (s,
3H); 13C NMR (DMSO-d6, 151 MHz)
167,76 (C2), 142.96 (C7a),
140.14 (C3a), 130.06 (C4
), 129.88 (C5

), 129.79 (C2

), 129.40
(C1
), 128.48 (C3
, C5
), 127.02 (C2
, C6
), 126.43 (C3

, C4

, C6


and C7

), 126.21 (C5) 122.92 (C4, C6), 120.76 (C7), 48.41 (C1

),
22.11 (CH3), 21.59 (CH3); ESI-MS [M+H+]: m/z = 392.3037. Rf:
0.365 (hex/EtOAc 3:1).
4-(6-bromo-1-(4-hydroxybenzyl)-1H-benzo[d]imidazol-2-
yl)phenol (4p). Using the above procedure 4-bromobenzene-1,2-
diamine (1b, 187.0 mg, 1 mmol) and 4-hydroxybenzaldehyde (2d,
244.2 mg, 2 mmol) were converted to 4-(6-Bromo-1-(4-
hydroxybenzyl)-1H-benzo[d]imidazol-2-yl)phenol (4p, 267.3 mg,
68%). Yellow solid, mp
270°C,1H NMR (DMSO-d6, 600 MHz)

10.82 (s, 1 H), 9.66 (s, 1 H), 8.66 (d,1H), 7.90 (d, 1 H, J = 8.0 Hz),
7.82 (d, 1 H, J = 8.0 Hz), 7.78 (d, 2 H, J= 8.5 Hz), 7.64-7.55 (m, 2
H), 7.08 (d, 2 H, J = 8.4 Hz), 7.00 (d, 2 H, J = 8.3Hz), 5.53 (s, 2 H);
13
C NMR (DMSO-d6, 151 MHz)
162.94 (C4
), 158.54 (C5

),
151.91 (C2), 133.73 (C7a), 133.08 (C3a), 132.28 (C6
, C2
), 129.35
(C7

, C3

), 127.36 (C2

), 126.88 (C1
), 125.81 (C5), 117.56 (C6),
116.66 (C4), 115.57 (C7), 114.66 (C3
, C5
), 113.92 (C4

, C6

),
49.45 (C1

); ESI-MS [M+H+]: m/z = 396.1258. Rf: 0.256
(hex/EtOAc 3:1).
6-bromo-1-(4-bromo-benzyl)-2-(4-bromo-phenyl)-1H-benzoi-
midazole (4q). Using the above procedure 4-bromobenzene-1,2-
diamine (1b, 187.0 mg, 1 mmol) and 4-bromobenzaldehyde (2e,
370.0 mg, 2 mmol) were converted to 6-bromo-1-(4-bromo-
benzyl)-2-(4-bromo-phenyl)-1H-benzoimidazole (4q, 337.5 mg,
65%). White solid, mp 196-198°C, 1HNMR (DMSO-d6, 600 MHz)

8.76 (s, 1H), 7.74 (d, 3 H, J = 8.3 Hz), 7.66 (d, 2H, J= 8.4 Hz),
7.58 (d, 3 H, J = 8.2 Hz), 7.25-7.20 (m, 2 H), 5.60 (2 H); 13C NMR
(DMSO-d6, 151 MHz)
153.84 (C2), 143.87(C7a), 137.64 (C3a),
137.21 (C2

), 133.56 (C4
), 133.34 (C5

), 132.65 (C3
, C5
),
130.48 (C2
), 129.95 (C6
), 125.37 (C4

, C6

), 124.90 (C3

),
124.37 (C7

), 122.31 (C6), 120.92 (C5), 112.75 (C4), 48.52 (C1

);
ESI-MS [M+H+]: m/z = 522.1245. Rf: 0.221 (hex/EtOAc 3:1).
2,2'-(1,2-phenylenebis(azan-1-yl-1-ylidene))bis(methan-1-yl-1-
ylidene)diphenol (5d). Using the above procedure benzene-1,2-
diamine (1b, 108.1 mg, 1 mmol) and 2-hydroxybenzaldehyde (2i,
244.2 mg, 2 mmol) were converted to 2,2'-(1,2-phenylenebis(azan-
1-yl-1-ylidene))bis(methan-1-yl-1-ylidene)diphenol (5d, 261.3 mg,
83%). Yellow solid, mp 160-162°C, 1H NMR (DMSO-d6, 600
MHz)
12.94 (s, 2 H), 8.94 (s, 2H), 7.68-7.65 (m, 2 H), 7.48-7.39
(m, 6 H), 7.00-6.95 (m, 4 H); 13C NMR (DMSO-d6, 151 MHz)

165.25 (C2, 2C), 161.57 (C4, 2C), 143.46 (C1
, 2C), 134.64 (C6,
2C), 133.65 (C8, 2C), 129.01 (C3’, 2C), 120.95 (C2’, 2C), 120.68
(C7, 2C), 120.28 (C3, 2C), 117.86 (C5, 2C); ESI-MS [M+H+]: m/z
= 317.1157. Rf: 0.304 (hex/EtOAc 3:1).
1-cinnamyl-2-(E)-styryl-1H-benzo[d]imidazole (6). Using the
above procedure benzene-1,2-diamine (1a, 108.1 mg, 1 mmol) and
cinnamaldehyde (2j, 264.3 mg, 2 mmol) were converted to 1-
cinnamyl-2-(E)-styryl-1H-benzo[d]imidazole (6, 163.7 mg, 49%).
Pallow yellow oil, mp 129-131°C, 1H NMR (DMSO-d6, 600 MHz)

7.91 (d, 1 H, J = 16.0 Hz), 7.80 (d, 2 H, J = 7.5 Hz), 7.67-7.59 (m,
2 H), 7.57 (d, 1 H, J = 16.0 Hz), 7.42 (t, 2 H, J= 7.5 Hz), 7.36 (t, 3
H, J = 7.0 Hz), 7.28-7.21 (m, 5 H), 6.57 (d, 1 H, J = 16.0 Hz), 6.49-
6.43 (m, 1 H), 5.28 (d, 2 H, J = 5.5 Hz); 13C NMR (DMSO-d6, 151
MHz)
151.82 (C2), 144.12 (C3a), 137.36 (C7a), 137.14 (C3’),
137.04 (C4’’), 136.53 (C2
), 132.70 (C3

), 130.14 (C8

), 130.00
(C6

), 129.82 (C5
), 129.03 (C7
), 128.72 (C5

, C9

), 127.57 (C8
,
Dänoun et al.
C4
), 126.38 (C7

), 123.45 (C6
), 123.39 (C1
), 119.84 (C2

),
115.48 (C5, C6), 111.70 (C4, C7), 45.72 (C1

); ESI-MS [M+H+]:
m/z= 337.1819. Rf: 0.440 (hex/EtOAc 3:1).
CONFLICT OF INTEREST
The authors confirm that this article content has no conflict of
interest.
ACKNOWLEDGEMENTS
The financial assistance of the Office Chérifien des Phosphates
in the Moroccan Kingdom (OCP Group) towards this research is
hereby acknowledged. This work was supported also by grant from
the OCP Foundation.
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Accepted: August 06, 2015