One-pot synthesis of multisubstituted imidazoles catalyzed by Dendrimer-PWAn nanoparticles under solvent-free conditions and ultrasonic irradiation

Article abstract of DOI:10.1007/s11164-016-2613-9

An efficient, green and eco-friendly protocol has been developed for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles via one-pot condensation reaction using Dendrimer-PWAⁿ as catalyst under solvent-free conditions or ultrasonic irradiation in excellent yields. The reactions under conventional heating conditions were compared with the ultrasonic-assisted reactions. The operational simplicity, practicability and applicability of this protocol to various substrates make it an interesting alternative to previous procedures. The present methodology offers several advantages such as excellent yields, short reaction times, a cleaner reaction, and the absence of any tedious work-up or purification. The catalyst is easily separated from the products by filtration and also exhibits remarkable reusable activity. SEM, BET and DLS of the catalyst were also investigated after each reaction cycle.

Full text of DOI:10.1007/s11164-016-2613-9

Res Chem Intermed
DOI 10.1007/s11164-016-2613-9
One-pot synthesis of multisubstituted imidazoles
catalyzed by Dendrimer-PWAn nanoparticles
under solvent-free conditions and ultrasonic
irradiation
Mohsen Esmaeilpour1 Jaber Javidi2,3
•
•
Farzaneh Dehghani1 Saeed Zahmatkesh4
•
Received: 25 March 2016 / Accepted: 14 June 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract An efficient, green and eco-friendly protocol has been developed for the
synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles via one-pot
condensation reaction using Dendrimer-PWAn as catalyst under solvent-free con-
ditions or ultrasonic irradiation in excellent yields. The reactions under conventional
heating conditions were compared with the ultrasonic-assisted reactions. The
operational simplicity, practicability and applicability of this protocol to various
substrates make it an interesting alternative to previous procedures. The present
methodology offers several advantages such as excellent yields, short reaction
times, a cleaner reaction, and the absence of any tedious work-up or purification.
The catalyst is easily separated from the products by filtration and also exhibits
remarkable reusable activity. SEM, BET and DLS of the catalyst were also
investigated after each reaction cycle.
Electronic supplementary material The online version of this article (doi:10.1007/s11164-016-2613-9)
contains supplementary material, which is available to authorized users.
&
&
Mohsen Esmaeilpour
m1250m551085@yahoo.com
Saeed Zahmatkesh
zahmatkesh1355@yahoo.com
1
2
Chemistry Department, College of Science, Shiraz University, Shiraz, Islamic Republic of Iran
Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical
Sciences, Tehran, Islamic Republic of Iran
3
4
Students Research Committee, School of Pharmacy, Shahid Beheshti University of Medical
Sciences, Tehran, Islamic Republic of Iran
Department of Science, Payame Noor University (PNU), Tehran, Islamic Republic of Iran
123

M. Esmaeilpour et al.
Keywords Dendrimer-PWAn nanocatalyst Á Multi-component reactions Á
1,2,4,5-Tetrasubstituted imidazoles Á 2,4,5-Trisubstituted imidazoles Á
Ultrasonic irradiation Á Solvent-free
Introduction
Imidazoles are an important group of five-member nitrogen heterocycles that have
attracted much attention because of the participation in the structure of biologically
active molecules such as Histidine, Histamine, and Biotin [1]. Imidazole moiety is
the core structure of many important drugs such as Losartan, Olmesartan,
Eprosartan, and Trifenagrel [2].
For over a century, multi-substituted imidazoles have been the current mediators
in many compounds of significant biological activity and have absorbed the
attention of synthetic chemists [3–5]. Generally, trisubstituted imidazoles are
synthesized by the condensation of 1,2-diketones, an aldehyde and ammonium
acetate by using various catalysts such as: InCl3Á3H2O [6], Yb(OTf)3 [7], TBAB [8],
Fe3O4@SiO2-Imid-PMAn [9], Nanocrystalline MgAl2O4 [10], Ferric(III) nitrate
supported on kieselguhr [11], SBA-15/2,2,2-trifluoroethanol [12], and HOAc [13].
1,2,4,5-tetrasubstituted imidazoles are synthesized by the condensation of 1,2-
diketones, an aldehyde, ammonium acetate and primary amine in the presence of
various catalysts such as silica gel or silica gel/NaHSO4 [14], K5CoW12O40.3H2O
[15], HY zeolite [16], Fe3O4@SiO2-Imid-PMAn [9], trifluoroethanol [12], HClO4-
SiO2 [17], heteropolyacids [18], FeCl3.6H2O [19], 1-Butyl-3-methylimidazolium
bromide [20], trityl chloride [21], tetrabutyl ammonium bromide [22], alumina [23],
1,4-diazabicyclo[2,2,2]octane (DABCO) [24], nano-TiCl4ÁSiO2 [25], PPA-SiO2
[26], nanocrystalline sulfated zirconia (SZ) [27] and silica-bonded propylpiperazine
N-sulfamic acid (SBPPSA) [28]. However, some of these synthetic methods have
limitations such as harsh reaction conditions, use of hazardous chemicals with often
expensive acid catalysts, complex working and purification procedures, long
reaction times, and moderate yields. Therefore, the development of simple, efficient,
clean, high-yielding and environmentally friendly approaches using new catalysts
for the synthesis of highly substituted imidazoles is an important task for organic
chemists.
In recent years, Keggin-type heteropolyacids (HPAs) have been used as efficient
catalysts for various organic reactions because of their superacidic and redox
properties, low toxicity, ease of handling, low cost, high proton mobility, high
thermal stability and recoverability and reusability [29]. Although these materials
are versatile compounds in their acidic form, their main disadvantages are high
solubility in polar solvents and low surface area (\10 m2/g). Therefore, in a
homogeneous reaction, the isolation of the products and the reuse of the catalyst
after reaction become difficult [30–33]. Therefore, in order to overcome this
problem, these materials are dispersed on supports (such as silica, acidic ion-
exchange resins, active carbon, etc.) which possess a large surface area [29]. Silica
is a very important industrial material and is extensively used for a wide range of
commercial applications such as catalyst supports, resins, molecular sieves, fillers in
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One-pot synthesis of multisubstituted imidazoles catalyzed…
polymers, and in biomedical applications [34]. In particular, silica nanoparticles
with high surface areas have a high interest for many key chemical applications
[35].
Dendrimers are a well-recognized class of precise macromolecules that should
find multiple applications in molecular electronics [36], catalysis [37], sensing [38]
and biomedical applications [39]. Dendrimers are particularly well suited for
hosting metal nanoparticles for the following reasons: (1) the dendrimer templates
themselves are of fairly uniform composition and the nanoparticles are stabilized by
encapsulation within the dendrimer, and therefore they do not agglomerate [40], (2)
the dendrimer branches can be used as selective gates to control the access of small
molecules (substrates) to the encapsulated (catalytic) nanoparticles [41], and (3) the
terminal groups on the dendrimer periphery can be tailored to control the solubility
of the hybrid nanocomposite and can be used as handles for facilitating linking to
surfaces and other polymers [40]. Indeed, dendrimer composites represent an
unusual case of the template and replica working in concert to exhibit functions that
exceed those of the individual components [40].
Recently, organic synthesis has been employing greener methodology, due to the
advantages compared with conventional methods in terms of high selectivity, ease
of handling, cleaner reaction profiles and relatively benign conditions. Greener
synthesis techniques involve mainly solvent-free reactions, ultrasound irradiation
and solid phase synthesis using a catalyst and microwave irradiation. Ultrasound
irradiation-assisted organic synthesis has become an important method for organic
and medicinal chemists in the rapid organic synthesis avoiding byproduct formation
[42].
In continuation of our investigation into developing recyclable nanocatalysts in
the synthesis of useful compounds [43], we have recently successfully developed
nanosilica dendritic polymer-supported H3PW12O40 nanoparticles (Dendrimer-
PWAn) as a recyclable catalyst for the one-pot synthesis of 2H-indazolo [2,1-b]
phthalazine-triones under mild reaction conditions [44].
Encouraged by these efforts and aiming to show the efficiency and generality of
Dendrimer-PWAn as a catalyst, we have utilized this novel catalyst for the synthesis
of tetrasubstituted and trisubstituted imidazoles from simple and easily available
starting materials under much milder reaction conditions (Scheme 1).
Experimental
General
All reagents were obtained from Merck (Germany) and Fluka (Switzerland) and
were used without further purification. Determination of the purity of the substrate
and monitoring of the reaction were accomplished by thin-layer chromatography
1
(TLC) on silica-gel polygram SILG/UV 254 plates. The H NMR and 13C NMR
were run on a Bruker DPX, at 500 and 125 MHz using TMS as the internal
standard. Fourier transform infrared spectroscopy (FT-IR) analysis of the samples
was taken on a Shimadzu FT-IR 8300 spectrophotometer and the sample and KBr
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M. Esmaeilpour et al.
Scheme 1 One-pot synthesis of substituted imidazoles using the Dendrimer-PWAn catalyst under
ultrasonic irradiation or solvent-free conditions
were pressed to form a tablet. A transmission electron microscope (Philips EM208)
with an accelerating voltage of 100 kV was used to examine the morphology and
size of the nanoparticles. Scanning electron microscopy (SEM) images were
obtained on a Philips XL-30ESEM and dynamic light scattering (DLS) were
recorded on a HORIBALB550. Melting points were measured by using the capillary
tube method with an electrothermal 9100 apparatus. The ultrasound apparatus was a
cleaning bath Wiseclear 770 W (Seoul, Korea). The operating frequency was
32 kHz and the output power was 160 W, estimated calorimetrically. The C, H, N
and S elemental analyses were carried out using a Thermofinigan Flash EA-1112
CHNSO rapid elemental analyzer. Therefore, all the products were characterized by
1
FT-IR, H NMR and 13C NMR, and also by comparison with authentic samples.
Synthesis of dendrimer-encapsulated phosphotungstic acid nanoparticles
immobilized on nanosilica
Synthesis of silica nanoparticles
An amount of 0.5 mL TEOS was added into a mixture of 50 mL ethanol, 20 mL
water and 0.5 mL ethylenediamine under ultrasonic irradiation. After 30 min, the
precipitate was isolated by centrifuging and washed several times with ethanol and
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One-pot synthesis of multisubstituted imidazoles catalyzed…
water. The obtained products were dried at 80 °C under vacuum for 2 h and then
calcined at 650 °C for 2 h [44].
Preparation of nSiO2–NH2
Nano-SiO2 (1 g) was added to a solution of 3-chlorotrimethoxypropylsilane
(10 mmol, 2.4 mL) in ethanol (10 mL) and the resultant mixture was under reflux
for 10 h under nitrogen atmosphere. After refluxing, the mixture was cooled to room
temperature and the solid product (nSiO2–Cl) was filtered off, washed with ethanol
and water to remove unreacted species, and dried at 60 °C for 8 h. Then, in a typical
synthetic procedure, 1.2 mL (10 mmol) of bis(3-aminopropyl) amine was added to a
suspension of nSiO2–Cl (1.0 g) in 10 mL acetonitrile, potassium iodide (10 mmol,
1.66 g) and potassium carbonate (10 mmol, 1.38 g). The reaction mixture was
refluxed in an oil bath for 10 h. The solid product was filtered off, washed with a
sufficient amount of distilled water, and dried at 60 °C for 12 h to afford nSiO2–
NH2 nanoparticles [44].
Preparation of nanosilica supported dendritic polymer (P1.5)**
nSiO2–NH2 (1 g) was added to a stirred solution of methyl acrylate (20 mmol,
1.7 mL) in methanol (10 mL). The final mixture was stirred at room temperature for
24 h. Then, the solid material (P0) was separated by filtration, washed with hot
methanol for 6 h in a Soxhlet apparatus to remove the unreacted starting materials,
and finally dried in a vacuum oven at 60 °C. To a slurry of P0 (1 g) in methanol
(10 mL) was added bis(3-aminopropyl) amine (20 mmol, 2.4 mL). The reaction
mixture was refluxed with continuous stirring under inert atmosphere for 4 h. The
final product (P0.5) was filtered, washed with hot methanol for 6 h in a Soxhlet
apparatus to remove the unreacted starting materials and then dried in a vacuum
oven at 60 °C. Then, a well-stirred solution of methyl acrylate (40 mmol, 3.4 mL)
in methanol (15 mL) was added to the stirred solution of P0.5 (1 g). The final
mixture was stirred at room temperature for 24 h. The solid material (P1) was
separated by filtration, washed with hot methanol for 6 h in a Soxhlet apparatus to
remove the unreacted starting materials, and finally dried in a vacuum oven at
60 °C. Then, bis(3-aminopropyl) amine (40 mmol, 4.8 mL) was added to a stirred
solution of P1 (1 g) in 15 mL methanol. The final mixture was refluxed with
continuous stirring under inert atmosphere for 6 h final product (P1.5), filtered,
washed with hot methanol for 6 h in a Soxhlet apparatus to remove the unreacted
starting materials and dried in a vacuum oven at 60 °C [44].
Synthesis of H3PW12O40 nanoparticles (PWAn)
PWAn nanoparticles were prepared as in our previous work [45]. H3PW12O40
nanoparticles (which were labeled as PWAn) were composed by heat treatment of
their bulky forms in an autoclave. HPAs are soluble in polar solvents such as
methanol and water but are insoluble in non-polar solvents such as hexane. In a
typical procedure, 0.3 mmol of bulk H3PW12O40Á14H2O (PWAb) was dispersed in
123

M. Esmaeilpour et al.
50 mL hexane and the obtained mixture was stirred vigorously for 30 min at room
temperature in order to form a homogeneous dispersion, which was transferred into
a Teflon-lined stainless autoclave and filled 80 % of its total volume. The autoclave
was sealed and maintained at 150 °C for 12 h and then cooled to room temperature.
Finally, the produced powder was filtered and dried in a vacuum at 60 °C for 12 h.
Preparation of dendrimer-encapsulated phosphotungstic acid nanoparticles
immobilized on nanosilica (Dendrimer-PWAn)
Figure 1 represents the anchoring of PWAn onto P1.5. Then, 2 g of P1.5 was
dispersed in 40 mL of n-Hexane and ultrasonicated for 30 min. Next, PWAn
(0.5 mmol, 1.48 g) was added into the solution and ultrasonicated for 30 min, and
the mixture was stirred for 24 h at room temperature. Finally, the formed
Dendrimer-PWAn was washed several times with distilled water and then dried in a
desiccator for 6 h. The sample thus prepared was designated as Dendrimer-PWAn
and stored in an airtight bottle for further use [44]. Figure 1 presents the procedure
for the stepwise preparation of Dendrimer-PWAn.
Fig. 1 The structure of Dendrimer-PWAn nanoparticles and characterization by UV–Vis, FT-IR, N2
adsorption–desorption, TEM and DLS techniques
123

One-pot synthesis of multisubstituted imidazoles catalyzed…
General procedure for the synthesis of 1,2,4,5-tetrasubstituted imidazoles
A mixture of benzil (1 mmol), aldehyde (1 mmol), ammonium acetate (1.2 mmol),
primary aliphatic and aromatic amines (1 mmol) and Dendrimer-PWAn catalyst
(0.035 or 0.04 g) was stirred in an oil bath at 90 °C or sonicated (160 W) in EtOH
(3 mL) at room temperature for an appropriate period of time. The progress of the
reaction was followed by TLC. After completion of the reaction as indicated by
TLC, the crude product from the reaction mixture was dissolved in hot ethanol and
the catalyst was separated by filtration. The filtrate was concentrated on a rotary
evaporator under reduced pressure and the solid crude product obtained was washed
with water and recrystallized from ethanol for more purification.
General procedure for the preparation of 2,4,5-trisubstituted imidazoles
A mixture of 1,2-diketone (1 mmol), aldehyde (1 mmol), ammonium acetate
(3 mmol) and Dendrimer-PWAn catalyst (0.035 or 0.04 g) was stirred in an oil bath
at 90 °C or sonicated (160 W) in EtOH (3 mL) at room temperature for an
appropriate time. After completion of the reaction, which was monitored by TLC
using an eluent (1:4 mL, petroleum ether: ethyl acetate), the mixture was washed
with water completely and the solid product dissolved in hot ethanol. Then, the
mixture was filtered for removing the unsolvable catalyst and the filtrate was cooled
to afford the pure product.
Results and discussion
In our previous work [44], first of all, we adopted a facile method to prepare a type
of porous silica nanoparticles (n-SiO2) from tetrasthyl orthosilicate as the source of
silica. Then, dendritic polymer supported on nanosilica with surface amino groups
was fabricated. Finally, H3PW12O40 nanoparticles (PWAn) were synthesized by the
treatment of H3PW12O40 powder with n-hexane as solvent by a solvothermal
method and then immobilized onto the dendrimer polymer-functionalized
nanosilica.
The synthesized nanostructures were characterized by FT-IR, X-ray diffraction,
thermogravimetric analysis, DLS, N2 adsorption–desorption isotherm analysis, UV–
vis and elemental analysis [44]. The morphology of the catalyst was characterized
using transmission electron microscopy (TEM). The acidity of the catalyst was
determined by FT-IR pyridine adsorption spectroscopy [44].
The FT-IR spectra of nSiO2, PWAn and Dendrimer-PWAn nanoparticles are
shown in Fig. 1. As shown in Fig. 1, surface functionalization of nanosilicate with
dendritic polymer-supported nano-H3PW12O40 caused nanoparticles to aggregate
while their size increased to about 40 nm. In TEM images of these particles, the
PWAn nanoparticles were clearly seen. The size distribution of these is centered at a
value of 40 nm. The presence of PWAn species anchored on the support was
confirmed by UV–vis spectroscopy [44].
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M. Esmaeilpour et al.
For nSiO2, the adsorption peaks at 794 and 1103 cm-1 correspond to the
symmetric and antisymmetric stretching vibration of the Si–O–Si bond in the
oxygen–silica tetrahedron, respectively. The FT-IR spectrum for PWAn shows four
bands in the range 500–1200 cm-1 and these bands are assigned at 764, 872, 972
and 1080 cm-1, which correspond to mas(W–Oe–W), mas(W–Oc–W), mas(W–Ot)
and mas(P–O*), respectively. It also shows a weak band in the region of 586 cm-1
which corresponds to the d(P–O) vibration. In the case of the Dendrimer-PWAn
nanoparticles, the peak at 1080 cm-1 overlaps with the Si–O–Si stretching
vibration. However, new peaks and non-overlapped bands at 977, 881 and
769 cm-1 are observed on the FT-IR spectra of Dendrimer-PWAn, indicating that
PWAn was successfully anchored to the dendritic polymer [44]. Also, the textural
properties of Dendrimer-PWAn were evaluated from the nitrogen adsorption–
desorption isotherms, and the respective specific surface area (BET method), pore
volume (BJH method) and average pore radius were calculated [44]. According to
the ICP-AES analysis, the amounts of PWAn immobilized on the nanosilica-
supported dendritic polymer was found to be 39.7 wt% (0.14 mmol/g) [44].
The size and surface area of the prepared SiO2, PWAn, fresh Dendrimer-PWAn
and the Dendrimer PWAn after the sixth cycle are shown in Table 1.
Due to the ability of Dendrimer-PWAn as a mild and efficient acid catalyst, we
decided to apply this catalyst for the synthesis of tetrasubstituted and trisubstituted
imidazoles.
In the first stage, to obtain the best reaction conditions, the reaction of benzil,
benzaldehyde, aniline and ammonium acetate was chosen as a model reaction. The
model reaction was checked under solvent-free conditions at 90 °C and various
amounts of catalyst. As ishown in Table 2, the best result was obtained when we
carried out the model reaction in the presence of 0.035 g of catalyst (Table 2, entry
5). This condensation was carried out with low amounts of Dendrimer-PWAn of
0.01, 0.02, 0.025 and 0.03 and the corresponding products were obtained in longer
reaction times and lower yields (Table 2, entries 1–4). On the other hand, higher
amounts of catalyst did not improve the yield or reaction time (Table 2, entry 6).
The model reaction was also examined in the absence of a catalyst under solvent-
free conditions at 130 °C and the reaction did not proceed even after 720 min
(Table 2, entry 7). Then, we decided to reflux the model reaction in the presence of
0.035 g of Dendrimer-PWAn and a variety of solvents such as H2O, EtOH, MeOH,
CHCl3, CH2Cl2, PhCH3, CH3CN and ClCH2CH2Cl. The data in Table 2 show that
this four-component condensation was accomplished in protic solvents such as H2O,
Table 1 Size and surface area of prepared nanoparticles
Substance
Size (nm)
TEM
Surface area (m2/g)
DLS
Nano-SiO2
PWAn
Dendrimer-PWAn fresh
Dendrimer-PWAn after the sixth cycle
20
25
35
57
25
30
40
65
531
242
479
459
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One-pot synthesis of multisubstituted imidazoles catalyzed…
Table 2 Condensation of benzil, benzaldehyde, aniline and ammonium acetate under different
conditions
Entry Catalyst amount (g) Solvent
Conditions
Time (min) Yielda (%)
1
0.01
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
EtOH
90 °C
90 °C
90 °C
90 °C
90 °C
90 °C
130 °C
Reflux
120
120
60
36
76
87
91
96
94
–
2
0.02
3
0.025
0.03
4
30
5
0.035
0.04
30
6
30
7
None
0.035
0.035
0.035
0.035
0.035
0.035
0.035
0.035
0.035
0.035
0.035
0.035
None
0.01
720
120
120
120
120
120
120
120
120
240
120
45
8
81
72
65
31
26
54
23
32
27
61
91
96
–
9
MeOH
Reflux
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
H2O
Reflux
CH2Cl2
Reflux
CHCl3
Reflux
CH3CN
Reflux
PhCH3
Reflux
ClCH2CH2Cl
Solvent-free
Solvent-free
Solvent-free
Solvent-free
EtOH
Reflux
rt
60 °C
80 °C
100 °C
30
Ultrasound (160 W)/rt
Ultrasound (160 W)/rt
Ultrasound (160 W)/rt
Ultrasound (160 W)/rt
Ultrasound (160 W)/rt
Ultrasound (160 W)/rt
Ultrasound (160 W)/rt
Ultrasound (160 W)/rt
60
EtOH
45
52
77
80
89
94
93
71
78
86
53
48
85
90
93
0.02
EtOH
45
0.03
EtOH
30
0.035
0.04
EtOH
15
EtOH
15
0.045
0.04
EtOH
15
H2O
30
0.04
EtOH/H2O (1:1) Ultrasound (160 W)/rt
EtOH/H2O (2:1) Ultrasound (160 W)/rt
30
0.04
30
0.04
CH2Cl2
CH3CN
EtOH
Ultrasound (160 W)/rt
Ultrasound (160 W)/rt
Ultrasound (80 W)/rt
Ultrasound (120 W)/rt
Ultrasound (200 W)/rt
45
0.04
45
0.04
30
0.04
EtOH
20
0.04
EtOH
15
Conditions: benzil (1 mmol), benzaldehyde (1 mmol), aniline (1 mmol) and ammonium acetate
(1.2 mmol)
a
Yields refer to isolated pure product
EtOH and MeOH under reflux, and the corresponding products were obtained in 65,
81 and 72 % yields after 2 h, respectively (Table 2, entries 8–10). Aprotic solvents
such as CHCl3, CH2Cl2, PhCH3, CH3CN and ClCH2CH2Cl afforded the desired
123

M. Esmaeilpour et al.
product in very low yields after 2 h (Table 2, entries 11–15). As shown in Table 2, a
solvent-free condition with 0.035 g of the catalyst is obviously the best choice for
these reactions (Table 2, entry 5). The effect of temperature was also studied by
carrying out the model reaction in the presence of 0.035 g of the catalyst at room
temperature, 60, 80 and 100 °C under solvent-free conditions. It was observed that
the corresponding products were obtained in 27, 61, 91 and 96 % yields,
respectively (Table 2, entries 16–19), and the best results were obtained at 90 °C
(Table 2, entry 5).
Considering the ability of ultrasonic irradiation for the acceleration of organic
reactions, we examined the model reaction under ultrasonic irradiation (160 W) in
EtOH as a solvent at room temperature in the presence of various amounts of
catalyst. As is clear from Table 2, the best results were obtained in the presence of
0.04 g of the catalyst and the corresponding product was obtained in 94 % yield
after 15 min (Table 2, entry 25). The model reaction was also examined in the
absence of a catalyst under ultrasonic irradiation in EtOH at room temperature and
the reaction did not proceed even after 1 h (Table 2, entry 20).
We also checked the model reaction under ultrasonic irradiation in the presence
of 0.04 g of catalyst and a variety of solvents such as H2O, EtOH/H2O (1:1), EtOH/
H2O (2:1), CH2Cl2 and CH3CN, and the desired products were obtained in very low
yields at longer reaction times (Table 2, entries 27–31).
However, the synthesis of organic compounds under ultrasound irradiation has
been limited by the need for a specialized apparatus that may not be available in
many laboratories. Because of this limitation, we report here on ultrasonic
irradiations in the presence of 0.04 g of the catalyst at room temperature in EtOH
and in solvent-free conditions in the presence of 0.035 g of the catalyst at 90 °C
(Table 2, entries 5 and 25) for the synthesis of imidazoles.
In order to study the effect of intensity power of the ultrasonics on the reaction,
the reaction was also performed at 80, 120, 160 and 200 W of power of the
ultrasonic bath (Table 2, entries 32–34). An increase of ultrasonic power led to a
relatively higher yield and shorter reaction times before the ultrasound power
intensity reached 160 W, and then the yield decreased slightly with increasing
ultrasound power intensity.
The scope and efficiency of the process was explored under the optimized
conditions. For this purpose, a broad range of structurally diverse aromatic
aldehydes as well as amines (aliphatic or aromatic) were condensed with benzil and
ammonium acetate under solvent-free or ultrasonic irradiation (Scheme 2). The
results are summarized in Table 3.
The yields obtained were good to excellent without the formation of any side
products.
Aromatic aldehydes having electron-withdrawing groups (Table 3, entries 2, 3,
6–8, 18, 23 and 26) reacted at a faster rate compared with aromatic aldehydes
substituted with electron-releasing groups (Table 3, entries 4, 5, 9, 10, 14–17, 24,
25, 27–29 and 30). Moreover, the neutral conditions of our methodology make it
possible to use acid-sensitive aldehydes without side reactions and/or byproducts. In
addition, both of our methodologies have been successfully used for heteroaromatic
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One-pot synthesis of multisubstituted imidazoles catalyzed…
O
R2
N
N
R1
H
O
Dendrimer-PWAn catalyst
(2)
O
R1
NH4OAc
(4)
Solvent-free/90oC
or
R2NH2
Ultrasonic/EtOH/rt
(3)
(5a-5ad)
(1)
Scheme 2 Synthesis of tetrasubstituted imidazoles in the presence of Dendrimer-PWAn
aldehydes, and corresponding imidazoles were obtained in excellent yields and
without any byproducts (Table 3, entries 11, 12, 19 and 21).
Moreover, in all of the above cases, it is clear that using ultrasonic irradiation
gave comparable yields of products but with shorter reaction times, compared to
conventional heating in solvent-free conditions.
In order to probe the applicability of this method, the same reaction conditions
were applied for the synthesis of 2,4,5-trisubstituted imidazoles via a one-pot, cyclo-
condensation of benzil, a series of aldehydes and ammonium acetate under solvent-
free conditions and using ultrasonic irradiation (Scheme 3). The results are
summarized in Table 4.
A wide range of aldehydes containing electron-withdrawing and electron-
donating groups were investigated. Aldehydes containing electron-donating groups
required longer reaction times (Table 4, entries 2–8). Aldehydes containing
electron-withdrawing groups underwent condensation in shorter reaction times
with excellent isolated yields (Table 4, entries 9–15). Using ultrasonic irradiation
gave comparable yields of products but with shorter reaction times, compared to
conventional heating in solvent-free conditions.
A plausible mechanism for the formation of 1,2,4,5-tetrasubstituted imidazoles
catalyzed by Dendrimer-PWAn is shown in Scheme 4.
Initially, the catalyst can activate the carbonyl groups of aldehyde and benzil to
decrease the energy of transition state. Then nucleophilic attack of the nitrogen of
ammonia, obtained from NH4OAc, and amine on the protonated carbonyl group,
resulted in the formation of diamine intermediate (7). In the presence of Dendrimer-
PWAn, intermediate (7) condenses with benzil (8) to form intermediate (9) which in
turn forms tetrasubstituted imidazoles by dehydration.
To compare the reactivity of the Dendrimer-PWAn with previously reported
catalysts, a comparative chart is presented in Table 5. Although all the catalysts
listed in Table 5 were able to produce good yields of corresponding products, some
of these reactions were carried out under harsh reaction conditions such as high
temperature and some required long reaction times. Also, some of the catalysts
listed in Table 5 are not reusable and thus our reusable catalyst and green
methodologies have been established as a better alternative compared to the
reported methods for the fabrication of corresponding products.
123

M. Esmaeilpour et al.
123

One-pot synthesis of multisubstituted imidazoles catalyzed…
123

M. Esmaeilpour et al.
H
N
O
O
O
Dendrimer-PWAn catalyst
R
+
2NH4OAc
+
R
H
Solvent-free/ 90oC
or
N
Ultrasonic/EtOH/rt
(6a-6o)
Scheme 3 Synthesis of 2,4,5-trisubstituted imidazole derivatives
Table 4 Synthesis of 2,4,5-trisubstituted imidazole derivatives catalyzed by Dendrimer-PWAn
Entry
R
Product Solvent-free/ Ultrasound
90 °C
M.P. (°C)
Time Yield Time Yield Found
(min) (%)a (min) (%)a
Reported
(references)
1
2
3
4
5
6
7
C6H5
6a
6b
6c
6d
6e
6f
20
45
60
70
90
100
70
93
90
84
83
78
85
87
15
20
20
25
25
30
25
94
88
87
85
83
82
86
274–275 (272–273) [48]
225–226 (227–228) [49]
257–258 (256–257) [48]
256–257 (255–256) [49]
210–212 (209–211) [7]
253–254 (255–256) [49]
201–202 (198–200) [50]
4-CH3O-C6H4
4-HO-C6H4
4-Me2N-C6H4
2-HO-C6H4
3,5-(MeO)2C6H3
4-HO-3-MeO-
C6H3
6g
8
4-CH3-C6H4
2-Br-C6H4
4-Br-C6H4
2-Cl-C6H4
6h
6i
45
20
25
18
15
15
15
10
87
86
90
88
94
96
87
96
25
10
15
10
8
90
92
88
91
95
93
90
95
228–229 (226–227) [48]
200–201 (201–202) [51]
258–259 (261–263) [51]
187–188 (199–201) [52]
260–261 (262–263) [48]
9
10
11
12
13
14
15
6j
6k
6l
4-Cl-C6H4
2,4-Cl2C6H3
3-NO2-C6H4
4-NO2-C6H4
6m
6n
6o
5
173
(172–173) [51]
10
5
266–268 (265–267) [48]
240–241 (239–242) [51]
Reaction conditions: benzil (1 mmol), aldehyde (1 mmol) and ammonium acetate (3 mmol), solvent-free/
90 °C, Dendrimer-PWAn (0.035 g) or EtOH (3 mL), r.t, Dendrimer-PWAn (0.04 g), ultrasonic irradiation
a
Isolated yield
The reusability of the catalyst was also examined in the synthesis of 1,2,4,5-
tetrasubstituted imidazoles and in the synthesis of 2,4,5-trisubstituted imidazoles
under solvent-free conditions and ultrasonic irradiation (Fig. 2a). The catalyst was
recovered after each run, washed three times with ethyl acetate (5 mL), dried in an
oven at 80 °C, and tested for its activity in subsequent runs. It was found that the
catalyst could be reused at least 6 times without distinct deterioration in catalytic
activity (Fig. 2A, a–d). Also, to confirm if any aggregation of the PWAn
123

One-pot synthesis of multisubstituted imidazoles catalyzed…
NH4OAc
NH3 + HOAc
H
O
O
H2N
Ph
NHR
H
H2N
Ph
OH
H+
H
H2N
Ph
OH2
H
Dendrimer-PWAn
RNH2
-H2O
NH3
Ph
H
Ph
H
(7)
H
H
+H2O
Ph
H2N
H
HO
Ph
Ph
O
O
Ph
OH
N
Ph
Ph
N
2H+
2H+
RHN
Ph
Ph
Ph
N
Ph
+H2O
N
Ph
OH
HO
R
R
(9)
(8)
-2H2O
N
Ph
Ph
Ph
N
H
Ph
-H+
Ph
N
N
R
Ph
R
Scheme 4 Probable mechanism for the formation of tetrasubstituted imidazoles using Dendrimer-PWAn
as the catalyst
Table 5 Comparing the efficiency of various catalysts with Dendrimer-PWAn in the synthesis of 2,4,5-
triphenyl imidazole (6a)
Entry
Catalyst
Solvent
Condition
Time
(min)
Yield
(%)a
References
1
Zeolite
EtOH
EtOH
MeOH
EtOH
EtOH
EtOH
–
Reflux
60
45
80
87
90
70
96
93
93
73
92
95
90
94
87
90
98
93
93
94
[27]
2
Nano-sulfated zirconia
L-proline
Reflux
[27]
3
60 °C
Reflux
540
90
[53]
4
K10
[27]
5
Polymer-ZnCl2
KH2PO4
Reflux
240
40
[54]
6
Reflux
[55]
7
[Hbim]BF4
InCl3Á3H2O
Yb(OTf)3
100 °C
r.t
25
[56]
8
MeOH
HOAc
Isopropanol
EtOH
EtOH
EtOH
EtOH
EtOH
–
720
120
20
[6]
9
70 °C
82 °C
Reflux
[7]
10
11
12
13
14
15
16
17
18
a
TBAB
[8]
Zr(acac)4
150
25
[57]
Zr(acac)4
Ultrasound/r.t
Ultrasound/r.t
Reflux
[57]
[EMIM]OAc
SA-MNPs
45
[51]
120
25
[58]
SA-MNPs
Ultrasound/40 °C
120 °C
90 °C
Ultrasound/r.t
[58]
MgAl2O4
Dendrimer-PWAn
Dendrimer-PWAn
30
[10]
–
20
This work
This work
EtOH
15
Isolated yield
123

M. Esmaeilpour et al.
Fig. 2 A Recyclability of Dendrimer-PWAn in the synthesis of 1,2,4,5-tetrasubstituted imidazoles (a,
b) and in the synthesis of 2,4,5-trisubstituted imidazoles (c, d); B–D TEM, SEM and DLS images of
Dendrimer-PWAn nanoparticles after six reaction cycles. a Reaction conditions: benzil (1 mmol),
benzaldehyde (1 mmol), aniline (1 mmol), ammonium acetate (1.2 mmol), Dendrimer-PWAn (0.035 g)
under solvent-free at 90 °C. b Reaction conditions: benzil (1 mmol), benzaldehyde (1 mmol), aniline
(1 mmol), ammonium acetate (1.2 mmol), EtOH (3 mL), Dendrimer-PWAn (0.04 g) under ultrasound
irradiation. c Reaction conditions: benzil (1 mmol), benzaldehyde (1 mmol), ammonium acetate
(3 mmol), Dendrimer-PWAn (0.035 g) under solvent-free at 90 °C. c Reaction conditions: benzil
(1 mmol), benzaldehyde (1 mmol), ammonium acetate (3 mmol), EtOH (3 mL), Dendrimer-PWAn
(0.04 g) under ultrasound irradiation
nanoparticles occurs, TEM analysis of the reused catalyst was performed (Fig. 2B).
After six repeated reaction cycles, we did not observe any significant change in the
morphology of the catalyst, but some PWAn particles might have aggregated onto
the surfaces of the matrices. This may take place through the leaching/redeposition
processes during the catalytic reactions.
To investigate further the Dendrimer-PWAn, SEM and DLS images of the
catalyst after the sixth recycling in the synthesis of 1,2,4,5-tetraphenylimidazole
(5a) under solvent-free conditions at 90 °C have been represented in Fig. 2C, D. As
shown in Fig. 2C, the image shows that the prepared nanoparticles had approx-
imately spherical shapes. Drying the solution of Dendrimer-PWAn nanoparticles on
a microscopic slide led to the formation of distinct agglomerates.
123

One-pot synthesis of multisubstituted imidazoles catalyzed…
Table 6 BET result of n-SiO2 and Dendrimer-PWAn
Entry
Sample/cycle reusability
Specific surface
area (m2/g)
Pore volume
(cm3/g)
Average pore
radius (nm)
1
2
3
4
5
Silica
531
479
475
470
459
1.3
0.6
0.5
0.3
0.1
10.2
6.1
5.2
4.0
2.8
Dendrimer-PWAn
Dendrimer-PWAn/(1)a
Dendrimer-PWAn/(3)a
Dendrimer-PWAn/(6)a
Calculated by the BJH method
a
BET surface areas for the catalyst after recycling
Additionally, the hydrodynamic diameter of catalyst was investigated using the
DLS technique (Fig. 2D). This size distribution is centered at a value of 65 nm.
Generally, the size of catalysts will be increased after each cycle and leaching of
H3PW12O40 and the increase of the catalyst size leads to decreases in the yield.
N2 adsorption–desorption isotherm analysis provided information on the specific
surface area and porosity of the prepared samples. The specific surface area values,
the average pore diameter (according to the BJH method) and total pore volume are
listed in Table 6. According to the BET isotherm, the active surface area of n-SiO2,
Dendrimer-PWAn and the catalyst after six recyclings was estimated as 531, 479
and 459 m2/g, respectively.
To determine the exact PWAn species responsible for the observed reactions and
to measure the extent of tungsten (W) leaching after the reactions, we used the hot
filtration test [59]. For this aim, we have studied the model reaction between
reaction benzil, benzaldehyde, aniline and ammonium acetate under ultrasonic
irradiation in ethanol. The reaction mixture was filtered after 62 % conversion (GC)
to remove the catalyst. Continuation of the reaction upon the resulting filtrate under
the same conditions showed 67 % conversion (GC) after 25 min. This result showed
that the amount of leaching of the catalyst into the reaction mixture should be low
and confirmed that the catalyst acts heterogeneously in the reaction.
The amounts of the nano-heteropolyacid leaching into solution for the reaction
benzil, benzaldehyde, aniline and ammonium acetate under ultrasonic irradiation in
ethanol at room temperature were detected by checking the tungsten (W) loading
amount before and after each reaction cycle through ICP. The amount of W leaching
after the first run was determined by ICP analysis to be only 0.18 %, and after 6
repeated recyclings was 1.86 %. Therefore, the analysis of the reaction mixture by
the ICP technique showed that the leaching of H3PW12O40 was negligible.
Conclusion
In conclusion, we have been able to introduce an efficient and environmentally
friendly approach for the synthesis of biologically active three tetrasubstituted
imidazoles via condensation of benzil with various aldehydes, a primary amine and
123

M. Esmaeilpour et al.
ammonium acetate using Dendrimer-PWAn as a recyclable catalyst under solvent-
free conditions and ultrasonic irradiation. The promising points for the presented
methodology are efficiency, generality, simple work-up procedure, short reaction
time, high yield, easy recovery and reuse of the catalyst, environmentally benign
and user-friendly process and simplicity which makes it a useful and attractive
process for the synthesis of highly substituted imidazoles.
Selected spectral data
(Table 2, 5a) 1,2,4,5-tetraphenylimidazole 1H NMR (500 MHz, DMSO-d6) d:
7.20–7.45 (m, 20H); 13C NMR (125 MHz, DMSO-d6) d: 124.1, 124.5, 125.1, 126.9,
128.3, 129.1, 130.3, 130.6, 132.9, 134.3, 136.8, 139.0, 139.2, 139.5, 139.8, 140.1,
144.6; FT-IR (KBr, cm-1) = 1446, 1477, 1493, 1604; Anal. Calcd. for C27H20N2:
C, 87.07; H, 5.41; N, 7.52 %. Found: C, 86.97; H, 5.44; N, 7.46 %.
(Table 2, 5b) 2-(4-bromophenyl)-1,4,5-triphenyl-1H-imidazole 1H NMR, 500 MHz
(DMSO-d6) d: 7.16–7.33 (m, 15H), 7.48 (d, J = 7.08 Hz, 4H); 13C NMR (125 MHz,
CDCl3/DMSO-d6) d: 122.7, 127.2, 127.4, 129.0, 129.3, 129.5, 129.7, 130.4, 131.0,
131.9, 132.0, 132.4, 135.1, 137.2, 137.9, 145.8.
(Table 2, 5c) 2-(4-chlorophenyl)-1,4,5-triphenyl-1H-imidazole 1H NMR (500 MHz,
CDCl3) d: 7.08 (d, J = 6.9 Hz, 2H), 7.15 (d, J = 6.9 Hz, 2H), 7.26–7.33 (m, 11H),
7.42 (d, J = 7.8 Hz, 2H), 7.63 (d, J = 8.7 Hz, 2H); 13C NMR (125 MHz, CDCl3/
DMSO-d6) d: 127.4, 127.9, 128.6, 128.7, 128.8, 129.1, 129.7, 130.4, 130.7, 131.5,
136.9, 145.9; FT-IR (KBr, cm-1) = 693, 764, 835, 1081, 1407, 1493, 1595, 2913,
3108; Anal. Calcd. for C27H19N2Cl: C, 79.70; H, 4.71; N, 6.88 %. Found: C, 79.64; H,
4.78; N, 6.81 %.
(Table 2, 5d) 1,4,5-triphenyl-2-p-tolyl-1H-imidazole 1H NMR (500 MHz, DMSO-
d6) d: 2.26 (s, 3H), 7.08 (d, J = 8.0 Hz, 2H), 7.16–7.18 (m, 1H), 7.22–7.25 (m, 6H),
7.26–7.28 (m, 5H), 7.31–7.32 (m, 3H), 7.50 (d, J = 8.0 Hz, 2H); 13C NMR
(125 MHz, DMSO-d6) d: 21.5, 127.2, 128.4, 128.9, 129.0, 129.2, 129.50, 129.58,
129.6, 129.9, 131.3, 131.9, 132.0, 135.3, 137.60, 137.63, 138.6, 147.0; FT-IR (KBr,
cm-1) = 691, 765, 827, 1347, 1492, 1601, 2931, 3024, 3052; Anal. Calcd. for
C28H22N2: C, 87.01; H, 5.74; N, 7.25 %. Found: C, 87.11; H, 5.66; N, 7.27 %.
(Table 2, 5e) 4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenol 1H NMR (500 MHz,
DMSO-d6) d: 6.64 (d, J = 9.0 Hz, 2H), 7.18–7.24 (m, 9H), 7.27–7.28 (m, 3H),
7.30–7.32 (m, 3H), 7.47–7.49 (d, J = 7.0 Hz, 2H), 9.60 (s, 1H); 13C NMR
(125 MHz, DMSO-d6) d: 115.8, 122.1, 127.1, 127.2, 128.9, 129.1, 129.3, 129.6,
129.9, 130.6, 131.4, 131.5, 132.0, 135.5, 137.3, 137.7, 147.3, 158.4; Anal. Calcd. for
C27H20N2O: C, 83.48; H, 5.19; N, 7.21 %. Found: C, 83.55; H, 5.16; N, 7.27 %.
(Table 2, 5f) 4-(4,5-diphenyl-1-p-tolyl-1H-imidazol-2-yl)benzonitrile 1H NMR
(500 MHz, DMSO-d6) d: 2.24 (s, 3H), 7.08–7.49 (m, 14H), 6.68 (d, J = 7.5 Hz,
2H), 7.95 (d, J = 7.5 Hz, 2H); 13C NMR (125 MHz, DMSO-d6) d: 21.4, 111.3, 115.2,
123

One-pot synthesis of multisubstituted imidazoles catalyzed…
121.0, 127.12, 127.18, 128.7, 129.1, 129.36, 129.39, 130.1, 130.3, 131.1, 131.4, 132.0,
137.2, 138.7, 143.9, 147.5, 153.33, 153.66.
(Table 2, 5g) 2-(3-nitrophenyl)-4,5-diphenyl-1-p-tolyl-1H-imidazole 1H NMR
(500 MHz, DMSO-d6) d: 2.26 (s, 3H), 7.32–7.39 (m, 6H), 7.54–7.56 (m, 8H),
7.77 (t, J = 7.7 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 8.52 (d, J = 7.5 Hz, 1H), 8.95
(s, 1H).
(Table 2, 5h) 2-(4-nitrophenyl)-4,5-diphenyl-1-p-tolyl-1H-imidazole 1H NMR
(500 MHz, DMSO-d6) d: 2.28 (s, 3H), 7.15–7.20 (m, 5H), 7.24–7.27 (m, 4H),
7.31–7.32 (m, 3H), 7.50 (d, J = 7.5 Hz, 2H), 7.63 (d, J = 8.5 Hz, 2H), 8.14 (d,
J = 9.0 Hz, 2H); 13C NMR (125 MHz, DMSO-d6) d: 21.5, 124.3, 127.2, 127.6,
129.0, 129.1, 129.3, 129.5, 129.6, 130.7, 130.8, 131.9, 133.7, 134.5, 134.8, 137.3,
138.7, 139.5, 144.7, 147.5.
(Table 2, 5i) 3-(4,5-diphenyl-1-p-tolyl-1H-imidazol-2-yl)phenol 1H NMR
(500 MHz, DMSO-d6) d: 2.26 (s, 3H), 6.68–6.70 (m, 2H), 6.97–7.31 (m, 14H),
7.47 (d, J = 7.5 Hz, 2H), 9.48 (s, 1H).
(Table 2, 5j) 4,5-diphenyl-1,2-dip-tolyl-1H-imidazole 1H NMR (500 MHz,
DMSO-d6) d: 2.25 (s, 3H), 2.26 (s, 3H), 7.08–7.10 (m, 6H), 7.15–7.17 (m, 1H),
7.21–7.24 (m, 5H), 7.47–7.49 (m, 2H); 13C NMR (125 MHz, DMSO-d6) d: 21.4,
21.5, 127.2, 128.6, 128.9, 129.0, 129.1, 129.2, 129.3, 129.5, 130.4, 131.4, 132.0,
135.0, 135.4, 137.5, 138.5, 138.8, 147.0.
(Table 2, 5k) 4,5-diphenyl-2-(thiophen-2-yl)-1-p-tolyl-1H-imidazole 1H NMR
(500 MHz, DMSO-d6) d: 2.31 (s, 3H), 6.51 (d, J = 3.5 Hz, 1H), 6.62 (t,
J = 4.5 Hz, 1H), 7.18–7.29 (m, 12H), 7.47–7.50 (m, 3H); 13C NMR (125 MHz,
DMSO-d6) d: 21.6, 126.1, 127.1, 127.3, 127.9, 128.3, 129.0, 129.3, 129.6, 130.8,
130.9, 131.9, 132.1, 133.8, 134.4, 134.9, 137.6, 139.9, 142.3.
(Table 2, 5l) 3-(4,5-diphenyl-1-p-tolyl-1H-imidazol-2-yl)-1H-indole 1H NMR
(500 MHz, DMSO-d6) d: 2.32 (s, 3H), 6.24 (s, 1H), 7.17–7.39 (m, 15H), 7.58 (d,
J = 7.5 Hz, 2H), 8.59 (d, J = 8.0 Hz, 1H); 13C NMR (125 MHz, DMSO-d6) d:
21.6, 106.6, 112.3, 120.7, 122.7, 122.9, 124.2, 126.9, 127.0, 129.0, 129.3, 129.7,
130.3, 130.8, 131.7, 132.0, 135.4, 135.8, 136.3, 137.0, 139.3, 144.4.
(Table 2,
5m)
1-benzyl-2-(phenyl)-4,5-diphenyl-1H-imidazole 1H
NMR
(500 MHz, DMSO-d6) d: 5.12 (s, 2H), 6.76–6.82 (d, J = 7.8 Hz, 2H), 7.18–7.41
(m, 14H), 7.55–7.65 (m, 4H); 13C NMR (125 MHz, DMSO-d6) d: 48.2, 126.0,
126.4, 126.9, 127.3, 128.2, 128.5, 128.6, 128.7, 128.9, 129.1, 130.5, 130.8, 131.0,
132.7, 134.1, 137.3, 137.9,148.1; FTIR (KBr, cm-1) = 695, 763, 1352, 1494, 1523,
1603, 3028, 3067; Anal. Calcd. for C28H22N2: C, 87.01; H, 5.74; N, 7.25 %. Found:
C, 87.13; H, 5.79; N, 7.16 %.
(Table 2, 5n) 1-benzyl-2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole 1H
NMR (500 MHz, DMSO-d6) d: 3.77 (s, 3H), 5.13 (s, 2H), 6.76 (d, J = 7.0 Hz,
2H), 6.90 (d, J = 9.0 Hz, 2H), 7.13–7.21 (m, 6H), 7.26–7.28 (m, 2H), 7.38–7.39
(m, 3H), 7.46 (d, J = 7.0 Hz, 2H), 7.58 (d, J = 9.0 Hz, 2H); 13C NMR (125 MHz,
123

M. Esmaeilpour et al.
DMSO-d6) d: 48.5, 56.0, 114.9, 124.0, 126.4, 126.9, 127.0, 128.0, 128.9, 129.3,
129.6, 129.7, 130.6, 130.8, 131.6, 131.7, 135.5, 137.5, 138.3, 147.9, 160.5; Anal.
Calcd. for C29H24N2O: C, 83.63; H, 5.81; N, 6.73 %. Found: C, 83.55; H, 5.72; N,
6.67 %.
(Table 2, 5o) 1-benzyl-2-(3-methoxyphenyl)-4,5-diphenyl-1H-imidazole 1H
NMR (500 MHz, DMSO-d6) d: 3.68 (s, 3H), 5.16 (s, 2H), 6.79 (d, J = 7.5 Hz,
2H), 7.15–7.19 (m, 4H), 7.20–7.21 (m, 5H), 7.30–7.31 (m, 3H), 7.40–7.41 (m, 3H),
7.46–7.47 (m, 2H); 13CNMR (125 MHz, DMSO-d6) d: 48.6, 55.9, 114.6, 115.6,
121.7, 126.4, 127.0, 127.1, 128.0, 128.9, 129.4, 129.74, 129.78, 130.5, 131.1, 131.4,
131.7, 132.8, 135.4, 137.7, 138.2, 147.7, 160.0; FT-IR (KBr, cm-1) = 691, 1214,
1479, 1574, 1606, 2897, 3021.
(Table 2, 5p) 1-benzyl-2-(4-methylphenyl)-4,5-diphenyl-1H-imidazole 1HNMR
(500 MHz, DMSO-d6) d: 2.33 (s, 3H), 5.14 (s, 2H), 7.13–7.16 (m, 2H),
7.18–7.21 (m, 2H), 7.24–7.29 (m 4H), 7.32–7.35 (m, 3H), 7.39–7.44 (m, 6H),
7.54 (d, J = 8.0 Hz, 2H).
(Table 2, 5q) 1-benzyl-2-(4-hydroxyphenyl)-4,5-diphenyl-1H-imidazole 1H NMR
(500 MHz, DMSO-d6) d: 5.12 (s, 2H), 6.71–7.35 (m, 17H), 7.45–7.52 (d,
J = 7.5 Hz, 2H), 9.65 (s, 1H); 13C NMR (125 MHz, DMSO-d6) d: 47.6, 115.3,
121.5, 125.6, 126.0, 127.1, 128.1, 128.5, 128.8, 128.9, 129.6, 130.0, 130.8, 134.7,
136.5, 137.5, 147.5, 158.0; FT-IR (KBr, cm-1) = 1487, 1557, 1607, 2930; Anal.
Calcd. for C28H22N2O: C, 83.56; H, 5.51; N, 6.96 %. Found: C, 83.47; H, 5.58; N,
6.90 %.
(Table 2, 5r) 1-benzyl-2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazole 1H NMR
(500 MHz, DMSO-d6) d: 5.16 (s, 2H), 6.75 (d, J = 7.0 Hz, 2H), 7.13–7.20 (m, 6H),
7.29–7.30 (m, 2H), 7.40–7.41 (m, 3H), 7.45–7.50 (m, 4H), 7.68 (d, J = 8.0 Hz,
2H); 13C NMR (125 MHz, DMSO-d6) d: 48.6, 126.5, 127.0, 127.2, 128.1, 128.9,
129.4, 129.5, 129.8, 130.5, 131.0, 131.3, 131.4, 131.6, 134.4, 135.2, 137.9, 146.7;
FT-IR (KBr, cm-1) = 693, 754, 1031, 1447, 1496, 1602, 2904, 3106; Anal. Calcd.
for C28H21ClN2: C, 79.75; H, 5.18; N, 6.49 %. Found: C, 79.87; H, 5.11; N, 6.60 %.
(Table 2, 5t) 1,2-bis(4-chlorophenyl)-4,5-diphenyl-1H-imidazole 1H NMR
(500 MHz, DMSO-d6) d: 7.17–7.19 (m, 1H), 7.23–7.25 (m, 4H), 7.29–7.32 (m,
5H), 7.38–7.42 (m, 6H), 7.50 (d, J = 7.0 Hz, 2H); 13C NMR (125 MHz, DMSO-d6)
d: 127.2, 127.4, 129.0, 129.2, 129.44, 129.49, 129.9, 130.1, 130.8, 130.9, 131.3,
132.0, 132.3, 134.1, 134.3, 135.0, 136.2, 145.8.
(Table 2, 5u) 4-(4,5-diphenyl-2-(thiophen-2-yl)-1H-imidazol-1-yl)phenol 1H
NMR (500 MHz, DMSO-d6) d: 6.58 (s, 1H), 6.77 (d, J = 8.0 Hz, 2H), 6.95 (m,
1H), 7.18–7.50 (m, 13H), 9.88 (s, 1H); 13C NMR (125 MHz, DMSO-d6) d: 116.7,
126.1, 127.1, 127.3, 127.8, 127.9, 128.3, 129.0, 129.23, 129.29, 131.0, 131.1, 131.9,
132.3, 133.9, 135.0, 137.4, 142.6, 158.9.
(Table 2, 5v) 1-methyl-2,4,5-triphenyl-1H-imidazole 1H NMR (500 MHz,
DMSO-d6) d: 3.58 (s, 3H), 7.38–7.40 (m, 3H), 7.43–7.45 (m, 2H), 7.58–7.60 (m,
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One-pot synthesis of multisubstituted imidazoles catalyzed…
5H), 7.72–7.73 (m, 3H), 7.94–7.96 (m, 2H); 13C NMR (125 MHz, DMSO-d6) d:
34.8, 124.5, 127.6, 128.4, 128.6, 129.4, 129.6, 129.7, 129.8, 130.0, 130.2, 130.8,
131.1, 131.8, 132.6, 145.5.
(Table 2, 5w) 2-(4-bromophenyl)-1-methyl-4,5-diphenyl-1H-imidazole 1H NMR
(500 MHz, DMSO-d6) d: 3.47 (s, 3H), 7.15 (t, J = 7.2 Hz, 1H), 7.21 (t, J = 7.2 Hz,
2H), 7.43–7.45 (m, 4H), 7.50–7.53 (m, 3H), 7.72–7.77 (m, 4H); 13C NMR
(125 MHz, DMSO-d6) d: 33.9, 122.9, 127.1, 128.9, 129.6, 129.9, 130.7, 131.44,
131.49, 131.5, 131.7, 132.4, 135.5, 137.5, 146.6.
(Table 2, 5x) 1-methyl-4,5-diphenyl-2-p-tolyl-1H-imidazole 1H NMR (500 MHz,
DMSO-d6) d: 2.45 (s, 3H), 3.56 (s, 3H), 7.23–7.38 (m, 5H), 7.44–7.47 (m, 3H),
7.50–7.55 (m, 4H), 7.58–7.60 (m, 2H); 13C NMR (125 MHz, DMSO-d6) d: 21.9,
34.7, 128.5, 129.6, 129.7, 130.2, 130.5, 130.7, 131.0, 131.72, 131.77, 145.6.
(Table 2, 5z) 2-(4-chlorophenyl)-4,5-diphenyl-1-propyl-1H-imidazole 1H NMR
(500 MHz, DMSO-d6) d: 0.51 (t, J = 7.6 Hz, 3H), 1.34 (m, J = 7.6 Hz, 2H), 3.81
(t, J = 8.4 Hz, 2H), 7.15–7.30 (m, 12H), 7.34 (d, J = 8.4 Hz, 2H); 13C NMR
(125 MHz, DMSO-d6) d: 11.0, 23.5, 46.3, 126.5, 126.6, 128.5, 129.2, 129.4, 129.6,
130.5, 130.6, 130.8, 131.2, 133.3, 134.9, 136.1, 146.9; FTIR (KBr, cm-1) = 1009,
1487, 1644, 3021; Anal. Calcd for C24H22ClN2: C, 77.30; H, 5.68; N, 7.51 %.
Found: C, 77.41; H, 5.62; N, 7.42 %.
(Table 2, 5aa) 2-(4-methylphenyl)-4,5-diphenyl-1-propyl-1H-imidazole 1H NMR
(500 MHz, DMSO-d6) d: 0.52 (t, J = 7.4 Hz, 3H), 1.30 (m, J = 7.4 Hz, 2H), 2.50
(s, 3H), 3.80 (t, J = 7.6 Hz, 2H), 7.12–7.35 (m, 12H), 7.50 (d, J = 8 Hz, 2H); 13C
NMR (125 MHz, DMSO-d6) d: 11.3, 22, 24.2, 53.4, 121.1, 122.9, 124, 125.3. 126.2,
127, 127.9, 128.8, 130.2, 130.9, 133, 142.4, 156.2; FTIR (KBr, cm-1) = 1492,
1622, 3026; Anal. Calcd. for C25H24N2: C, 85.19; H, 6.86; N, 7.95 %; Found: C,
85.09; H, 6.78; N, 7.91 %.
(Table 3, 6b) 2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole 1H
NMR
(500 MHz, CDCl3) d: 3.83 (s, 3H), 6.98 (d, J = 7.6 Hz, 2H), 7.18–7.68 (m,
10H), 7.82 (d, J = 7.6 Hz, 2H), 9.14 (s, 1H); 13C NMR (125 MHz, CDCl3) d:
160.1, 146.0, 128.5, 127.7, 126.6, 122.7, 114.2, 110.0, 55.3; Anal. Calcd. For
C22H18N2O: C, 80.96; H, 5.56; N, 8.58 %; Found: C, 80.86; H, 5.41; N, 8.65 %.
Acknowledgments Authors are grateful to the council of Iran National Science Foundation and
University of Shiraz for their unending efforts to provide financial support to undertake this work.
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