One-pot synthesis of multisubstituted imidazoles under solvent-free conditions and microwave irradiation using Fe3O4@SiO2-imid-PMAn magnetic porous nanospheres as a recyclable catalyst

Article abstract of DOI:10.1039/c5nj00050e

An efficient, green and ecofriendly procedure has been developed using Fe₃O₄@SiO₂-imid-PMAⁿ as a magnetic catalyst for a rapid and improved synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles under solvent-free conditions and microwave irradiation in excellent yields. The reactions under conventional heating conditions were compared with the microwave-assisted reactions. The operational simplicity, practicability and applicability of this protocol to various substrates make it an interesting alternative to previous procedures. The present approach offers several advantages such as short reaction times, high yields, simplicity of operation, easy work-up, a cleaner reaction and ease of recovery and reusability of the catalyst using a magnetic field. Also, the nanocatalyst can be easily recovered by the application of a magnetic field and reused for the next reactions at least 5 times without distinct deterioration in catalytic activity. SEM, BET, DLS and leaching of the catalyst after each reaction cycle were investigated.

Full text of DOI:10.1039/c5nj00050e

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One-pot synthesis of substituted imidazoles by Fe3O4@SiO2-Imid-PMAn catalyst under solvent-
free conditions

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One-pot synthesis of multisubstituted imidazoles under solvent-free
conditions and microwave irradiation by Fe3O4@SiO2-imid-PMAn
magnetic porous nanosphere as recyclable catalyst
Mohsen Esmaeilpour (1)*, Jaber Javidi (2)* Maryam Zandi (1)
(1) Chemistry Department, College of Science, Shiraz University, Shiraz, Iran
(2) Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences,
Tehran, Iran
(3) Students Research Committee, School of Pharmacy, Shahid Beheshti University of
Medical Sciences, Tehran, Iran
*Corresponding author. Tel.: +98 7116137738, fax: +98 7112286008.
E-mail address: m1250m551085@yahoo.com (M. Esmaeilpour), Jaber Javidi @ gmail.com (J. Javidi)
Abstract
An efficient, green and eco-friendly procedure has been developed using Fe3O4@SiO2-Imid-
PMAn as magnetic catalyst for rapid and an improved synthesis of 2,4,5-trisubstituted and
1,2,4,5-tetrasubstituted imidazoles under solvent-free conditions and microwave irradiation in
excellent yields. The reactions in conventional heating conditions were compared with the
microwave-assisted reactions. The operational simplicity, practicability and applicability of this
protocol to various substrates make it an interesting alternative to previous procedures.
The present approach offers several advantages such as short reaction times, high yields,
simplicity of operation, easy work-up, a cleaner reaction and ease of recovery and reusability of
the catalyst by magnetic field. Also, nanocatalyst can be easily recovered by a magnetic field and
reused for the next reactions for at least 5 times without distinct deterioration in catalytic activity.
SEM, BET, DLS and leaching of catalyst after each reaction cycle were investigated.
Keywords
Fe3O4@SiO2-imid-PMAn magnetic nanocatalyst; Multisubstituted imidazoles; Multicomponent
reaction; Solvent-free reaction; Microwave irradiation
1

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1. Introduction
Imidazole and their derivatives, which usually possess diverse biological activities, play
important roles as versatile building blocks for the synthesis of natural products and as
therapeutic agents. 1,2 In particular, 2, 4, 5-trisubstituted imidazoles are biologically active and
occur in structures of a number of anti-inflammatory, 3 anti-allergic, 4 analgesic 5 and glucagon
receptor antagonism. 6 This core also has been utilized in diverse pharmaceutical applications
such as anti-tumor 7 and anti-thrombotic 8 activities agents.
Appropriately substituted imidazoles are extensively used as glucagon receptors 9 and CB1
cannabinoid receptor antagonists, 10 modulators of P-glycoprotein (P-gp)-mediated multidrug
resistance (MDR), 11 antibacterial 12 and antitumor 13 agents, and also as pesticides. 14 Recent
advances in green chemistry and organometallic catalysis have extended the application of
imidazoles as ionic liquids 15 and N-heterocyclic carbenes. 16 This versatile applicability
highlights the importance of accessing efficient synthetic routes to well-designed highly
substituted imidazole derivatives.
There are many synthetic methodologies that have been developed for assembling and decorating
the imidazole ring with diverse functional groups. One of the approaches is using the transition
metal catalyzed direct C–H/N–H functionalization 17 and other approaches include using various
catalytic systems such as I2, 18 SiO2/ NaHSO4, 19 MgSO4, 20 FeCl3.6H2O 21 and etc. They can also
be obtained by use of microwave irradiation, 22 silica sulfuric acid, 23 NiCl2 -6H2O/ Al2O3 24 and
ionic liquids. 25 Many of the reported synthetic protocols for the synthesis of imidazoles suffer
from one of the disadvantages or more such as the harsh reaction condition, the poor yields, the
prolongation of time in the reaction and the use of heavy metal catalysts hazards. Therefore, the
development of a new catalytic system to overcome these shortcomings and fulfill the criteria of
a mild, efficient, and environmentally benign protocol for the synthesis of highly substituted
imidazoles is still desirable and is in demand.
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 and high thermal stability. 26 Although these material are versatile compounds
in their acidic form, their main disadvantages are high solubility in polar solvents and low
surface area. In previous work, 27we introduce a simple, repaid, inexpensive and one step
2

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method, solvothermal, for synthesis of H3PMo12O4 nanoparticles (PMAn) from H3PMo12O4 bulk
particles (PMAb). Acidity of as-prepared nanoparticles was investigated by pyridine adsorption
method. Results showed rising acidity by declining particle size of HPAs.
Nowadays, Fe3O4 nanoparticles, as magnetite nanoparticles, have attracted increasing interest
because of their unique properties including a large surface-to-volume ratio,
superparamagnetism, low toxicity, biocompatibility and their potential applications in various
fields. 28 The Fe3O4 nanoparticles are easily synthesized and functionalized by metal and organo-
catalysts and they can be easily separated from the reaction mixture by external magnetic field
and reused. 29 In our previous study, 30 PMAn were supported on magnetic Fe3O4@SiO2-imid
nanoparticles. Compared to other substrates (silica, acidic ion-exchange resins, active carbon and
nano titania), Fe3O4@SiO2-imid nanoparticles have various advantages such as high loading
capacity, low leaching and simple and efficient recovery procedure. Fig. 1 presents the procedure
for the preparation of Fe3O4@SiO2-imid-PMAn stepwise. In this article, we report a new and
efficient method for one-pot synthesis of substituted imidazoles by Fe3O4@SiO2-Imid-PMAn
catalyst under solvent-free conditions and microwave irradiation (Scheme 1).
Scheme 1 One-pot synthesis of substituted imidazoles by Fe3O4@SiO2-Imid-PMAn catalyst
under solvent-free conditions.
2. Experimental
2.1. Chemicals and instrumentation
3

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Chemical materials were purchased from the Merck Chemical Company in high purity. All the
solvents were distilled, dried and purified by standard procedures. Fourier transform infrared
(FT-IR) spectra were obtained using a Shimadzu FT-IR 8300 spectrophotometer. The 1H NMR
(500 MHz) and 13C NMR (125 MHz) were run on a Bruker Avance DPX-250 using
tetramethylsilane (TMS) as an internal reference. All reactions were carried out using a
laboratory microwave oven (MicroSYNTH, Milestone Company, Italy). Magnetic
characterization was carried out on a vibrating sample magnetometer (Meghnatis Daghigh Kavir
Co., Iran) at room temperature. Scanning electron microscopy (SEM) image was obtained on
Philips XL-30ESEM and dynamic light scatterings (DLS) were recorded on a HORIBA-LB550.
Melting points were measured with an Electrothermal 9100 apparatus. The elemental analyses
(C, H, N) were obtained from a Carlo ERBA Model EA 1108 analyzer carried out on a Perkin–
Elmer 240c analyzer. Therefore, all of the products were characterized by FT-IR, 1H NMR and
13C NMR, and also by comparison with authentic samples.
2.2. Catalyst preparation
2.2.1. Preparation of Fe3O4@SiO2 core–shell
The core–shell Fe3O4@SiO2 nanospheres were prepared by a modified Stober method in our
previous work. 30 In a typical procedure, the mixture of FeCl3.6H2O (1.3 g, 4.8 mmol) in water
(15 mL) was added to the solution of polyvinyl alcohol (PVA 15000), as a surfactant, and
FeCl2.4H2O (0.9 g, 4.5 mmol) in water (15 mL), which was prepared by completely dissolving
PVA in water followed by addition of FeCl2.4H2O. The resultant solution was left to be stirred
for 30 min in 80 oC. Then, hexamethylentetr amine (HMTA) (1.0 mol/L) was added drop by
drop with vigorous stirring to produce a black solid product when the reaction media reaches pH
10. The resultant mixture was heated on water bath for 2 h at 60 oC and the black magnetite solid
product was filtered and washed with ethanol three times and was then dried at 80 oC for 10 h.
Then Fe3O4 nanoparticle (0.50 g, 2.1 mmol) was dispersed in the mixture of ethanol (50 mL),
deionized water (5 mL) and tetraethoxysilane (TEOS) (0.20 mL), followed by the addition of 5.0
mL of NaOH (10 wt%). This solution was stirred mechanically for 30 min at room temperature.
4

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Then the product, Fe3O4@SiO2, was separated by an external magnet, and was washed with
deionized water and ethanol three times and dried at 80 oC for 10 h.
2.2.2. Preparation of Fe3O4@SiO2-imid
Fe3O4@SiO2 (1 g) was added to the solution of 3-chlorotriethoxypropylsilane (1 mmol, 0.241 g)
and imidazole (1 mmol, 0.0680 g) in p-xylene (20 mL) and the resultant mixture was under
reflux for 24 h under nitrogen atmosphere. After refluxing for about 24 h, the mixture was cooled
to room temperature, filtered by an external magnet and the product was washed with xylene to
remove any reacted species and dried at 70 oC for 6 h. 30
2.2.3. Preparation of H3PMo12O40 nanoparticles (PMAn)
PMAn nanoparticles were prepared in our previous work, 27 which is a simple and single step
method. In a typical procedure, 5 mmol of bulk H3PMo12O40 (PMAb) was dispersed in 50 mL n-
Octane and the resulting dispersion was stirred vigorously for 30 min at room temperature to
form a homogeneous dispersion. This dispersion was transferred into a Teflon-lined stainless
autoclave filling 80% of the total volume. The autoclave was sealed and maintained at 150 oC for
12 h. The autoclave was then cooled to room temperature. Finally, the resulted powder was
filtered and washed for several times by octane, and dried in a vacuum at 80 oC for 12 h.
2.2.4. Preparation of Fe3O4@SiO2-imid-PMAn
Fig. 1 represents the anchoring of PMAn onto Fe3O4@SiO2- imid. Fe3O4@SiO2-imid (1.0 g) was
added to an acetonitrile solution of PMAn (1.0 mmol) in 20 mL was taken in a round-bottom
flask. The mixture was refluxed for 24 h under nitrogen atmosphere. After 24 h, the mixture was
filtered by an external magnet, washed with acetonitrile and dichloromethane, and dried at 70oC
for 6 h. FT-IR spectrum of the catalyst showed the expected bands, including distinctive bands
due to anchoring of PMAn onto Fe3O4@SiO2-imid. 30
2.3. General procedure for the synthesis of 1,2,4,5- tetrasubstituted imidazoles
A mixture of benzil (1 mmol), ammonium acetate (1 mmol), aldehyde (1 mmol), primary
aliphatic and aromatic amine (1 mmol) and Fe3O4@SiO2-imid-PMAn catalyst (0.03 g) was
5

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stirred with a glass bar at 110 oC or irradiated in a microwave oven at 100 W for the appropriate
time. The progress of reaction was followed by TLC. After the reaction was completed, the
catalyst was separated by an external magnet and reused as such for the next experiment. The
reaction mixture was dissolved in acetone and filtered. The filtrate was concentrated on a rotary
evaporator under reduced pressure and the solid product obtained was washed with water and
recrystallized from acetone–water 8:1 (v/v). Pure products were obtained in excellent yields, as
summarized in Table 2.
2.4. General procedure for the preparation of 2,4,5-trisubstituted imidazoles
In a 50 mL round bottom flask a mixture of 1,2-diketone (1 mmol), ammonium acetate (3
mmol), aldehyde (1 mmol), and Fe3O4@SiO2-imid-PMAn catalyst (0.03 g) was stirred at 110 oC
or irradiated in a microwave oven at 100 W for the appropriate time. After completion of the
reaction which was monitored by TLC using eluent (1:4 mL, petroleum ether: ethyl acetate), the
mixture was washed with water completely and the solid product dissolved in hot ethyl acetate.
Then, the mixture was filtered by an external magnet for removing the unsolvable catalyst and
the filtrate was cooled to afford the pure product.
3. Results and discussion
First of all, the Fe3O4@SiO2 nanosphere core-shell is synthesized. Then, H3PMo12O40
nanoparticles were synthesized by the treatment of H3PMo12O40 with n-Octane as solvent by a
solvothermal method and this nano heteropolyacid immobilized onto imidazole functionalized
Fe3O4@SiO2 nanoparticles (Fig. 1). 30 The Fe3O4, Fe3O4@SiO2 and Fe3O4@SiO2-imid-PMAn
nano catalysts were characterized by various methods such as transmission electron microscopy
(TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform
infrared (FT-IR), Vibrating sample magnetometer (VSM) and etc. As shown in Fig. 1
Fe3O4@SiO2-imid-PMAn nanoparticles have spherical shapes with approximately 50 nm
diameters. The size distribution of these is centered at a value of 55 nm. Themagnetic properties
of Fe3O4, Fe3O4@SiO2, Fe3O4@SiO2-imid-PMAn nanoparticles were measured by VSM at room
temperature. All the samples show a typical superparamagnetic behavior. Hysteresis
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phenomenon was not found and the magnetization curves were coincident. The saturation
magnetizati magnetization of samples is 63.4, 39.7, 33.2 emu g-1, respectively.
Fig.1 Process for preparation of immobilization of H3PMo12O40 nanoparticles (PMAn) on
imidazole functionalized Fe3O4@SiO2 nanoparticle. 30
Then to optimize the reaction conditions in terms of solvent, temperature and amount of catalyst,
a model reaction was performed by the condensation of benzil (1 mmol), benzaldehyde (1
mmol), aniline (1 mmol) and ammonium acetate (1 mmol) under solvent free conditions at
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different temperatures with variant amounts of catalyst Fe3O4@SiO2-Imid-PMAn and the
observations are as follows: in the absence of catalyst at 110 °C formation of product was not
observed even after 12 h (Table 1, entry 1). To improve the yield of the product the above
reaction was tested with 0.01, 0.02, 0.03 and 0.04 g catalyst at 110 °C (Table 1, entry 2-5) and
observed the maximum yield (92%) in shorter reaction time (1.5 h) with 0.03 g catalyst. Further
increasing of catalyst loading does not affect the yield (Table 1, entry 5). The effect of
temperature was studied by carrying out the model reaction at different temperatures under
solvent free (room temperature, 60 oCand 100 oC) (Table 2, entries 6-8) and the best result was
obtained at 110 oC (Table 2, entry5). Increasing the temperature to 120 °C has no effect in the
yield of product (Table 1, entry 9). As it was shown in Table 1, solvent free condition at 110 ºC
with 0.03 g catalyst is obviously the best choice for these reactions (Table 1, entry 4).
The use of other solvents such as MeOH, EtOH, CH3CN, CH2Cl2, PhCH3 and H2O afforded the
desired product in lower yields (Table 1, entries 10-16).
During the past two decades many investigations have established the critical role of microwave
irradiation in the rate acceleration of diverse chemical reactions. 31 Considering this fact, we
decided to examine our methodology under microwave irradiation. Therefore, the reaction was
repeated under solvent free conditions in microwave irradiation with different amounts of
catalyst (Table 1, entries 17-19) and observed the maximum yield (94%) in shorter reaction time
(10 min) with 0.03g catalyst (Table 1, entries 18).
Table 1 Condensation of benzil, benzaldehyde, aniline and ammonium acetate under different
conditions.a
Entry
Solvent/catalyst amount (g)
Solvent-free/None
Solvent-free/0.01
Solvent-free/0.02
Solvent-free/0.03
Solvent-free/0.04
Solvent-free/0.03
Solvent-free/0.03
Solvent-free/0.03
Solvent-free/0.03
MeOH/0.03
Conditions
110oC
110oC
110oC
110oC
110oC
rt
Time (h)
Yieldb (%)
12
-
1
2
3
4
5
6
7
8
2
2
1.5
1.5
4
4
2
1.5
4
4
24
82
92
91
17
53
85
92
57
65
51
60oC
100oC
120oC
Reflux
Reflux
Reflux
9
10
11
12
EtOH/0.03
CH3CN/0.03
4
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Reflux
Reflux
Reflux
4
4
4
23
29
15
48
88
94
94
13
14
15
16
17
18
19
CH2Cl2/0.03
CHCl3/0.03
PhCH3/0.03
Reflux
4
H2O/0.03
MW(100W)
MW(100W)
MW(100W)
15 min
10 min
10 min
Solvent-free/0.02
Solvent-free/0.03
Solvent-free/0.04
aConditions: benzil (1mmol), benzaldehyde (1mmol), aniline (1mmol) and ammonium acetate (1 mmol).
bYields refer to isolated pure product.
Then, 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) was successfully condensed with benzil and ammonium acetate under
solvent free conditions at 110 °C or under microwave conditions (Scheme 2) and the results are
displayed in Table 2. As be seen the yields were good to excellent without preparation of any
side products and the reaction times are very low. Aromatic aldehydes bearing such functional
groups as nitro, chloro, bromo, methyl, or methoxy were able to affect the imidazole synthesis.
We have also observed that the electronic effect on the aldehydes had influence on the yield and
time of reaction conditions: that is, aryl aldehydes with electron-withdrawing groups reacted
rapidly (Table 2, entries 4, 5, 12-15, 22, 27), while substitution of electron-rich groups on the
benzene ring decrease the reactivity (Table 2, 3, 7-10, 16, 17, 23-26). Also, the substrate scope of
the reaction was evaluated using another primary amine i.e. benzyl amine. Both aromatic and
aliphatic primary amines have been successfully subjected to this method (Table 2). Beside this,
our methodology has been used successfully for heteroaromatic aldehydes, and corresponding
imidazoles were obtained in excellent yields and without any byproduct (Table 2, entries 11, 18,
19). Also, microwave irradiation has shown better yields and especially reaction times.
All the products obtained were fully characterized by 1H NMR and 13C NMR spectroscopy and
by comparison of their physical and spectral data with those of authentic samples.
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Scheme 2 Synthesis of 1,2,4,5-tetrasubstituted imidazoles via a one-pot four component
condensation reaction in the presence of Fe3O4@SiO2-Imid-PMAn catalyst.
Table 2 Synthesis of 1,2,4,5-tetrasubstituted imidazoles via a one-pot four component
condensation reaction in the presence of Fe3O4@SiO2-Imid-PMAn catalyst.
Entry
R1
R2
Product
Time (min) (MW)/(110
oC)
Yield (%)b (MW)/(110 oC)
Mp. (◦C) (Lit.)c Ref
.
10/90
95/92
91/89
89/86
97/94
96/92
95/90
92/88
90/86
89/83
90/87
94/93
95/90
97/91
95/94
93/89
90/85
89/84
93/87
88/85
87/84
86/85
88/83
86/81
90/84
88/81
90/85
94/90
217-219
190-191
(218)32
(189)32
5aa
5ab
5ac
5ad
5ae
5af
5ag
5ah
5ai
1
2
3
4
5
6
7
8
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
15/120
20/150
8/75
10/75
8/75
4-CH3-C6H4
4-OH-C6H4
4-Cl-C6H4
4-Br-C6H4
C6H5
4-CH3-C6H4
3-CH3O-C6H4 C6H5CH2
4-CH3O-C6H4 C6H5CH2
281-282 (280-281)33
162-164 (160-163)34
210-212 (207-211)34
159-161 (158-160)32
164-166 (165-166)32
129-131
C6H5CH2
C6H5CH2
15/90
20/150
20/150
17/150
7/75
10/60
5/50
10/75
5/60
12/90
15/90
156-158 (157-160)35
136-138 (134-135)36
9
5aj
5ak
5al
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
4-HO-C6H4
2-furyl
C6H5CH2
C6H5CH2
C6H5CH2
4-CH3-C6H4
4-CH3-C6H4
4-CH3-C6H4
4-CH3-C6H4
4-CH3-C6H4
4-CH3-C6H4
4-CH3-C6H4
CH3
157
(156-157)36
147-149 (146-148)36
221
4-Cl-C6H4
4-NO2-C6H4
3-NO2-C6H4
4-CN-C6H4
4-CH3-C6H4
3-HO-C6H4
2-thienyl
5am
5an
5ao
5ap
5aq
5ar
5as
5at
5au
5av
5aw
5ax
5ay
5az
5ba
150-152 (149-151)37
202-203 (198-201)38
190-192
233-235 (235-237)38
201-203 (199-202)38
219-221 (218-220)38
145-147 (144-145)32
209-211
8/75
18/180
12/120
15/150
12/150
20/180
15/150
15/120
12/120
10/90
3-indolyl
C6H5
4-CH3-C6H4
4-Br-C6H4
4-CH3-C6H4
4-CH3-C6H4
4-CH3O-C6H4 n-Pr-NH2
4-CH3-C6H4
4-Cl-C6H4
CH3
CH3
202-204
161-163
153-154 (151-153)36
79-81
82-84
88
(164)36
cyclohexyl
iso-C4H9
(76-80)39
(78-83)39
(85-87)39
n-Pr-NH2
n-Pr-NH2
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aReaction conditions: benzil (1 mmol), aldehyde (1 mmol), primary amine (1 mmol) and ammonium acetate (1 mmol) in the
presence of Fe3O4@SiO2-Imid-PMAn catalyst at 110°C and/or under Microwave Irradiation.
bIsolated yield.
cMelting points reported in the parenthesis refer to the literature melting points.
In order to explore the applicability of this method, the same reaction conditions were used for
synthesis of 2,4,5-trisubstituted imidazoles via a one-pot, cyclo-condensation of benzil (1 mmol),
aldehyde (1 mmol) and ammonium acetate (3 mmol) under solvent-free classical heating
conditions and using microwave irradiation are given in Table 2.
A wide range of aldehydes containing electron-withdrawing and electron-donating groups were
investigated. Aldehydes containing electron-withdrawing groups such as, chloro, bromo and
nitro underwent condensation in short reaction times with excellent isolated yields with both of
conditions (Scheme 2 and Table 3, entries 2-8). Aldehydes containing electron-donating groups
such as methyl, methoxy and hydroxyl required longer reaction time. (Table 2, 9-14). Using
microwave irradiation gave comparable yields of products but with shorter reaction time,
compared to conventional heating.
A mechanism for the catalytic activity of Fe3O4@SiO2 -Imid-PMAn in the synthesis of imidazole
derivatives is shown in Scheme 4. 44 After the protonation of the carbonyl group of the aryl
aldehyde and the nucleophilic attack of the nitrogen atoms of ammonia, obtained from NH4OAc,
and aniline to it, intermediate (Ι) is formed. In the presence of Fe3O4@SiO2 -Imid-PMAn,
intermediate (Ι) condenses with benzil to form intermediate (Π) which in turn forms
tetrasubstituted imidazoles by dehydration.
Scheme 2 Synthesis of 2,4,5-trisubstituted imidazole derivatives catalyzed by Fe3O4@SiO2-
Imid-PMAn catalyst.
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Table 3 Synthesis of 2,4,5-trisubstituted imidazole derivatives catalyzed by Fe3O4@SiO2-Imid-PMAn catalyst.
Entry
1
2
3
4
5
6
7
R
Product Time (min) (MW)/(110 oC) Yield (%)b (MW)/(110 oC) Mp. (◦C) (Lit.)c Ref.
C6H5
10/75
94/88
96/89
91/87
93/86
97/94
95/91
89/85
90/83
88/87
87/81
89/86
84/79
82/76
80/73
273-274 (272-273)18
261-262 (262-263)18
198-200 (199-201)40
264-266 (265-267)18
237-239 (239-242)41
174-175 (172-173)41
262-264 (261-263)4]
203-204 (201-202) 41
227-228 (226-227)18
256-258 (255-256)42
226-228 (227-228)42
254-256 (256-257)18
257-258 (255-256)42
207-209 (209-211)43
6a
6b
6c
6d
6e
6f
4-Cl-C6H4
2-Cl-C6H4
3-NO2-C6H4
4-NO2-C6H4
2,4-Cl2C6H3
4-Br-C6H4
5/60
8/75
8/75
5/60
5/75
10/80
8/75
6g
6h
6i
6j
6k
6l
2-Br-C6H4
8
9
4-CH3-C6H4
4-Me2N-C6H4
4-CH3O-C6H4
4-HO-C6H4
3,5-(MeO)2C6H3
2-HO-C6H4
15/90
18/120
15/120
18/150
20/180
20/180
10
11
12
13
14
6m
6n
aReaction conditions: benzil (1 mmol), aldehyde (1 mmol) and ammonium acetate (3 mmol) in the presence of
Fe3O4@SiO2 -Imid-PMAn catalyst (0.03 g) at 110 °C and/or under Microwave Irradiation.
bIsolated yield.
cMelting points reported in the parenthesis refer to the literature melting points.
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Scheme 4 Probable mechanism for the formation of tetrasubstituted imidazoles using Fe3O4@SiO2-Imid-
PMAn as catalyst.
Fe3O4@SiO2-Imid-PMAn magnetic catalyst dispersed in solvent can be easily separated by
external magnetic field within several minutes without the need for a filtration step, and then can
be readily re-dispersed with slight shake, indicating directly that the nanoparticles possess
magnetic properties. Such magnetic separation performance makes the nanoparticles more
effective and convenient in application. The reusability and recovery of the catalyst are important
issues, especially when the reactions use solid catalysts. For the recycling study, the reusability
of Fe3O4@SiO2-Imid-PMAn catalysts were investigated in the synthesis of 1,2,4,5-
tetrasubstituted imidazoles and in the synthesis of 2,4,5-trisubstituted imidazoles under solvent-
free at 110 oC and using microwave irradiation (Fig. 2A). In order to confirm the reusability and
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stability of this magnetic nanocatalyst it was recovered by a magnetic field and the remaining
solid was washed with ethyl acetate (3×10 mL), dried and the catalyst reused for subsequent
reactions for at least 6 times without any activation process (Fig. 2A, a, b, c, d).
Fig. 2 (A) Recyclability of Fe3O4@SiO2-Imid-PMAn in the synthesis of 1,2,4,5-tetrasubstituted
imidazoles (b,d) and in the synthesis of 2,4,5-trisubstituted imidazoles (a,c). (B) SEM and DLS
images of Fe3O4@SiO2-imid-PMAn nanoparticles after six reaction cycles.
aReaction conditions: benzil (1 mmol), benzaldehyde (1 mmol), ammonium acetate (3 mmol), Fe3O4@SiO2- Imid-
PMAn (0.04 g) under solvent-free at 110oC.
bReaction conditions: benzil (1 mmol), benzaldehyde (1 mmol), aniline (1 mmol), ammonium acetate (1 mmol),
Fe3O4@SiO2- Imid-PMAn (0.04 g) under solvent-free at 110 oC.
cReaction conditions: benzil (1 mmol), benzaldehyde (1 mmol), ammonium acetate (3 mmol), Fe3O4@SiO2- Imid-
PMAn (0.03 g) under Microwave Irradiation.
dReaction conditions: benzil (1 mmol), benzaldehyde (1 mmol), aniline (1 mmol), ammonium acetate (1 mmol),
Fe3O4@SiO2- Imid-PMAn (0.03 g) under Microwave Irradiation.
SEM and DLS images of the catalyst after the six recycle in the synthesis of 1,2,4,5-
tetraphenylimidazole (5aa) under solvent-free conditions at 110 oC have been represented in Fig.
2B. As shown in Fig. 2B, Fe3O4@SiO2-imid-PMAn nanoparticles had an average diameter of 75
nm, were of uniform size, and showed good dispersity. Additionally, the hydrodynamic diameter
of catalyst was investigated by DLS technique (Fig. 2B). This size distribution is centered at a
value of 70 nm. Generally, the size of catalysts will be increased after each cycle and leaching of
H3PMo12O40 and increasing of catalyst size lead to decreases the yield.
To determine the exact species responsible for the observed reactions and to measure the extent
of PMAn leaching after the reactions, we have used the hot filtration test. 45 For this aim, we have
studied the condensation of benzil, benzaldehyde, aniline and ammonium acetate in the presence
of Fe3O4@SiO2- Imid-PMAn catalyst under solvent free conditions at 110 oC. Then we carried
out a ‘hot filtration’ test; when the reaction was half done, Fe3O4@SiO2- Imid-PMAn
nanoparticles were removed in situ at the reaction temperature, and the reactants were allowed to
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undergo further reaction in the solution. We confirmed that there was too small conversion of
the reactants in the absence of the nanoparticles. These results indicate that there was little active
PMAn species in the solution phase.
The amounts of the nano heteropolyacid leaching into solution for the reaction benzil,
benzaldehyde, aniline and ammonium acetate under solvent free conditions at 110oC was
detected by checking the molybdenum (Mo) loading amount before and after each reaction cycle
through ICP. The amount of Mo leaching after the first run was determined by ICP analysis to be
only 0.47%, and after 6 repeated recycling was 3.92%. Therefore, the analysis of the reaction
mixture by the ICP technique showed the leaching of H3PMo12O40 was negligible.
Additionally, the size and surface area of catalysts after each reaction cycle for the synthesis of
1,2,4,5-tetraphenylimidazole (5aa), was investigated by DLS and nitrogen physisorption method
(BET) respectively and results are provided in Table 4. As shown, the size of catalysts will be
increased after each cycle. Generally, leaching of PMA, increase of catalyst size and decrease of
surface area led to a decrease in the yield of reaction.
Mean article size a (nm)
MW method Thermal method MW method Thermal method
Surface area b (m2 g-1)
Run
56
60
62
62
63
68
58
61
65
65
68
70
422
415
399
390
381
376
420
400
391
389
370
357
1
2
3
4
5
6
a By DLS.
b By BET.
Conclusion
In conclusion, an extremely efficient method has been developed for the synthesis of biologically
active three and tetrasubstituted imidazoles via condensation of benzil with various aromatic
aldehydes, a primary amine and ammonium acetate using Fe3O4@SiO2-Imid-PMAn as a
recyclable nanocatalyst under solvent-free conditions and microwave irradiation. This method is
bestowed with several unique merits, such as cleaner reaction profiles, high reaction rates and
excellent yields, simple experimental and work-up procedures, no side reactions and use of
recyclable and environmentally benign nature of catalyst, and thus significantly contributes to
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the practice of green chemistry. In addition, the excellent catalytic performance and the easy
preparation, thermal stability and separation of the catalyst by external magnetic field make it a
good heterogeneous system and a useful alternative to other heterogeneous catalysts.
Selected data
(Table 2, 5aa) 1,2,4,5-Tetraphenylimidazole
1H NMR (500 MHz, DMSO-d6) δ: 7.20-7.45 (m, 20H); 13C NMR (125 MHz, DMSO-d6) δ: 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, 87.12; H, 5.37; N, 7.57%.
(Table 2, 5ab) 1,4,5-Triphenyl-2-p-tolyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ:
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, 86.96; H, 5.68; N, 7.29%.
(Table 2, 5ac) 4-(1,4,5-Triphenyl-1H-imidazol-2-yl)phenol
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 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, 83.41; H, 5.25; N, 7.18%.
(Table 2, 5ad) 2-(4-Chlorophenyl)-1,4,5-triphenyl-1H-imidazole
1H NMR (500 MHz, CDCl3) δ: 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) δ: 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, 79.61; H, 4.67; N, 6.93%.
(Table 2, 5ae) 2-(4-bromophenyl)-1,4,5-triphenyl-1H-imidazole
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1H NMR, 500 MHz (DMSO-d6) δ: 7.16–7.33 (m, 15H), 7.48 (d, J= 7.08 Hz, 4H); 13C NMR (125 MHz,
CDCl3/DMSO-d6) δ: 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, 5af) 1-Benzyl-2-(phenyl)-4,5-diphenyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 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,
87.09; H, 5.66; N, 7.19%.
(Table 2, 5ag) 1-Benzyl-2-(4-methylphenyl)-4,5-diphenyl-1H-imidazole
1HNMR (500 MHz, DMSO-d6) δ: 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, 5ah) 1-Benzyl-2-(3-methoxyphenyl)-4,5-diphenyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 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, 5ai) 1-Benzyl-2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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, DMSO-d6) δ: 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, 83.65; H, 5.87; N, 6.70%.
(Table 2, 5aj)1-Benzyl-2-(4-hydroxyphenyl)-4,5-diphenyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 47.6, 115.3, 121.5, 125.6, 126.0, 127.1, 128.1, 128.5, 128.8,
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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, 83.49; H, 5.47; N, 6.89%.
(Table 2, 5al) 1-Benzyl-2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazole.
1H NMR (500 MHz, DMSO-d6) δ: 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)
δ: 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, 79.84; H, 5.03; N, 6.66%. Found: C, 79.87; H, 5.11; N, 6.60%.
(Table 2, 5am) 2-(4-Nitrophenyl)-4,5-diphenyl-1-p-tolyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 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, 5an) 2-(3-Nitrophenyl)-4,5-diphenyl-1-p-tolyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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, 5ao) 4-(4,5-Diphenyl-1-p-tolyl-1H-imidazol-2-yl)benzonitrile
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 21.4, 111.3, 115.2, 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, 5ap) 4,5-Diphenyl-1,2-dip-tolyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 2.25 (s, 3H), 2.26 (s, 3H), 7.08-7.10 (m, 6H), 7.15-7.17 (m, 1H), 7.21-
7.23 (m, 4H), 7.24-7.30 (m, 5H), 7.47-7.49 (m, 2H); 13C NMR (125 MHz, DMSO-d6) δ: 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, 5aq) 3-(4,5-Diphenyl-1-p-tolyl-1H-imidazol-2-yl)phenol
1H NMR (500 MHz, DMSO-d6) δ: 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).
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(Table 2, 5ar) 4,5-Diphenyl-2-(thiophen-2-yl)-1-p-tolyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 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, 5as) 3-(4,5-Diphenyl-1-p-tolyl-1H-imidazol-2-yl)-1H-indole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 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, 5at) 1-Methyl-2,4,5-triphenyl- 1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 3.58 (s, 3H), 7.38-7.40 (m, 3H), 7.43-7.45 (m, 2H), 7.58-7.60 (m, 5H),
7.72-7.73 (m, 3H), 7.94-7.96 (m, 2H); 13C NMR (125 MHz, DMSO-d6) δ: 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, 5au) 1-Methyl-4,5-diphenyl-2-p-tolyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 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, 5av) 2-(4-Bromophenyl)-1-methyl-4,5-diphenyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 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, 5az) 2-(4-methylphenyl)-4,5-diphenyl-1-propyl-1H- imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 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,
85.24; H, 6.95; N, 7.89%.
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(Table 2, 5ba) 2-(4-Chlorophenyl)-4,5-diphenyl-1-propyl-1H-imidazole
1H NMR (500 MHz, DMSO-d6) δ: 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) δ: 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, 77.27; H, 5.65; N, 7.56%.
(Table 3, 6k) 2-(4-Methoxyphenyl)-4,5-diphenyl-1H-imidazole
1H NMR (500 MHz, CDCl3) δ: 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) δ: 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, 80.81; H, 5.71; N,
8.69%.
Acknowledgements
Authors are grateful to the council of Iran National Science Foundation and University of
Shiraz for their unending effort to provide financial support to undertake this work.
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