Ionic liquid [EMIM]OAc under ultrasonic irradiation towards the first synthesis of trisubstituted imidazoles

Article abstract of DOI:10.1016/j.ultsonch.2010.01.015

The ionic liquid 1-ethyl-3-methylimidazole acetate ([EMIM]OAc) was found to be a mild and effective catalyst for the efficient, one-pot, three-component synthesis of 2-aryl-4,5-diphenyl imidazoles at room temperature under ultrasonic irradiation. This procedure has many obvious advantages compared to those reported in the previous literatures, including avoiding the use of harmful catalysts, reacting at room temperature, high yields, simplicity of the methodology.

Full text of DOI:10.1016/j.ultsonch.2010.01.015

Ultrasonics Sonochemistry 17 (2010) 749–751
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Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Short Communication
Ionic liquid [EMIM]OAc under ultrasonic irradiation towards the first synthesis
of trisubstituted imidazoles
*
*
Hongjun Zang , Qiuhong Su, Yingming Mo, Bo-Wen Cheng , Song Jun
Department of Material Science and Chemistry Engineering, Tianjin Polytechnic University, Tianjin Municipal Key Laboratory of Fiber Modification and Functional Fiber,
Tianjin 300160, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 January 2010
Received in revised form 26 January 2010
Accepted 31 January 2010
Available online 4 February 2010
The ionic liquid 1-ethyl-3-methylimidazole acetate ([EMIM]OAc) was found to be a mild and effective
catalyst for the efficient, one-pot, three-component synthesis of 2-aryl-4,5-diphenyl imidazoles at room
temperature under ultrasonic irradiation. This procedure has many obvious advantages compared to
those reported in the previous literatures, including avoiding the use of harmful catalysts, reacting at
room temperature, high yields, simplicity of the methodology.
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
Multicomponent
1-Ethyl-3-methylimidazole acetate
Ionic liquid
2-Aryl-4,5-diphenyl imidazoles
Ultrasound
1. Introduction
this reaction by some common Lewis acid catalysts [16–18], but
in many cases the yield was dissatisfactory and they also acted
Imidazole derivatives are a very interesting class of heterocyclic
compounds because they have many pharmacological properties
and play important roles in biochemical processes [1,2]. Many of
the substituted imidazoles are known as inhibitors of P38 map ki-
nase, fungicides and herbicides and therapeutic agents [3–5]. Re-
cent advances in green chemistry and organometallic catalysis
has extended the application of imidazoles as ionic liquids and
N-heterocyclic carbenes [6,7]. Owing to the wide range of pharma-
cological and biological activities, the synthesis of imidazoles has
become an important target in current years.
A number of methods have been developed for the synthesis
of 2-aryl-4,5-diphenyl imidazoles. In these procedures, 1,2-dike-
tone, an aldehyde and ammonium acetate are condensed in the
presence of a strong protic acid (such as H3PO4 [8], H2SO4 [9]
and HOAc [10]) or other catalysts in HOAc [11] under reflux con-
ditions. Isolation of the product is then achieved by neutralization
of the reaction mixture. Later, one-pot condensations of an alde-
hyde and ammonium acetate with 1,2-diketone have been
achieved by using solid supports under microwave irradiation
[12–15]. Despite their potential utility, most of these methods
are not environmentally friendly. They require a high tempera-
ture (180–200 °C), created by microwave irradiation, and the
use of a solid support. Recently, much work has done to catalyze
against the concept of ‘‘green chemistry”. Ionic liquids have also
been reported to catalyze this reaction [19–21]. However, these
methods often require heating the reaction mixture to high tem-
perature. 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 2-aryl-4,5-diphenyl imidazoles is highly desirable.
In recent years, ionic liquids have attracted increasing interest
in the context of green synthesis [22]. Although ionic liquids were
initially introduced as alternative green reaction media because of
their unique chemical and physical properties of nonvolatility,
nonflammability, thermal stability, and controlled miscibility
[23–25], nowadays they have evolved beyond this, showing their
significant role in controlling reactions as catalysts [26,27]. We
have also recently shown that they can promote and catalyze
important organic transformations at room temperature under
ultrasound irradiation [28,29].
Ultrasound irradiation has been considered as a clean and use-
ful protocol in organic synthesis during the last three decades,
compared with traditional methods, the procedure is more conve-
nient. Moreover, a large number of organic reactions can be carried
out in higher yield, shorter reaction time or milder conditions un-
der ultrasonic irradiation [30]. As a part of our program aiming at
developing environmental friendly methodologies for the prepara-
tion of fine chemicals and in continuation of our interest in ionic
liquids catalyzed organic reactions [28,29], we wish to report an
* Corresponding authors. Tel.: +86 22 2401 9762; fax: +86 22 2452 8055.
E-mail address: chemhong@126.com (H. Zang).
1350-4177/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2010.01.015

750
H. Zang et al. / Ultrasonics Sonochemistry 17 (2010) 749–751
CHO
C2H5
Ph
Ph
N
N
Ph
Ph
(10%)
R
O
O
N
CH3COO
H3C
NH4OAc
+
+
))), r.t.
EtOH,
N
H
R
1
2a-j
3a-j
Scheme 1. Synthesis of 2,4,5-trisubstituted imidazoles.
Table 1
Condensation of benzil, 4-chlorobenzaldehyde and ammonium acetate under different conditions.a
Entry
Catalyst
Amount of catalyst (mol%)
Solvent
Method
Temp. (°C)
Time (h)
Yield (%)b
Ref.
1
2
3
4
5
6
7
8
[EMIM]OAc
[EMIM]OAc
[EMIM]OAc
No catalyst
[EMIM]OAc
[EMIM]OAc
[EMIM]OAc
[EMIM]OAc
[EMIM]OAc
InCl3ꢁ3H2O
20
10
5
EtOH
EtOH
EtOH
EtOH
EtOH/H2O (9.5:5)
EtOH/H2O (8:2)
CH2Cl2
CH3CN
EtOH
Ultrasound
Ultrasound
Ultrasound
Ultrasound
Ultrasound
Ultrasound
Ultrasound
Ultrasound
25–30
25–30
25–30
25–30
25–30
25–30
25–30
25–30
25–30
25–30
Reflux
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
9.4
0.7
94
96
74
15
89
48
20
51
18
71
90
–
–
–
–
–
–
–
–
0
10
10
10
10
10
10
10
9
10
11
High speed stirring
High speed stirring
High speed stirring
–
[16]
[17]
MeOH
EtOH
NiCl2ꢁ6H2O/Al2O3
a
Benzil:4-chlorobenzaldehyde:NH4OAc (1 mmol:1 mmol:10 mmol).
Isolated yield.
b
efficient and simple procedure for preparation of 2-aryl-4,5-diphe-
nyl imidazoles at room temperature under ultrasonication using
ionic liquid [EMIM]OAc as catalyst (see Scheme 1).
3g White powder, 1H NMR (DMSO-d6, 300 MHz) d 7.30–7.37
(m, 10H), 7.45–7.49 (dd, J = 9.1 Hz, 1H), 7.57–7.59 (d, J = 8.2 Hz,
2H), 8.02–8.05 (dd, J = 8.79 Hz, 1H), 10.5 (brs, 1H). Anal. Calc. for
C21H25N2Br: C, 67.21; H, 4.03; N, 7.47; Found: C, 67.25; H, 4.01;
N, 7.46.
2. Experimental
2.1. Chemicals and apparatus
3. Results and discussion
All reagents were purchased from commercial sources and li-
quid aldehydes were purified by distillation prior to use. [EMI-
M]OAc was synthesized based on the literature [31]. Melting
points were recorded on an electrothermal apparatus and were
uncorrected. The 1H NMR was measured on a Bruker AVANCE
300 spectrometer using TMS as internal standard. Elemental anal-
yses were obtained using a Perkin–Elmer auto-analyzer. Sonication
was performed in Kunshan KQ-250B ultrasonic reactor with a fre-
quency of 40 kHz and a nominal power of 250 W. The reaction
flasks were located in the maximum energy area in the water bath,
where the surface of reactants (reaction vessel) is slightly lower
than the level of the water, and the addition or removal of water
controlled the temperature of the water bath. The temperature of
the water bath was controlled at 25–30 °C,
Initially, we sought a mild and convenient method for the syn-
thesis of 2-aryl-4,5-diphenyl imidazoles at room temperature.
Our investigation began with the evaluation of [EMIM]OAc as a
catalyst in the reaction of benzil (1 equiv), 4-chlorobenzaldehyde
(1 equiv) and ammonium acetate (10 equiv) at ambient temper-
ature under ultrasonic irradiation. The use of 20 mol% of [EMI-
M]OAc in ethanol afforded a 94% yield (Table 1, entry 1) of the
desired product. Optimization of the reaction conditions was
undertaken to increase the yield employing catalyst loadings in
a wide variety of solvents. The results were summarized in Table
1. The yield increased to 96% using 10 mol% of [EMIM]OAc (Table
1, entry 2). However, a reduction in yield was observed by
decreasing the catalyst loading to 5 mol% (Table 1, entry 3). In
the absence of the catalyst, the reaction proceeded sluggishly
2.2. General procedure for synthesis of 2-aryl-4,5-diphenyl imidazoles
Table 2
Synthesis of 2-aryl-4,5-diphenyl imidazoles catalyzed by [EMIM]OAc under ultra-
sonication at room temperature.
[EMIM]OAc
(0.0170 g,
0.1 mmol),
aromatic
aldehyde
(1.0 mmol) and ammonium acetate (0.7708 g, 10 mmol) was
added to a solution of benzil (0.2102 g, 1.0 mmol) and 10 mL eth-
anol in a 100 mL flask. The reaction mixture was irradiated at room
temperature for required time. The progress of the reaction was
monitored by TLC. After completion of the reaction, the mixture
was concentrated under reduced pressure to remove the solvent.
The resulting solution was extracted by ethyl acetate
(3 ꢀ 10 mL). The organic layer was dried over Na2SO4 and concen-
trated. The product was purified by chromatography through a col-
umn of silica-gel using ethyl acetate/petroleum ether as an eluent.
The authenticity of the known products was established by
comparing their melting points with the counterparts in the
literatures.
Entry
R
Time (min)
Yield (%)a
MP (°C)
Found
Report
a
b
c
d
e
f
g
h
i
C6H5
4-ClC6H4
2-ClC6H4
4-NO2C6H4
3-NO2C6H4
2,4-Cl2C6H3
2-BrC6H4
4-CH3OC6H4
2-CH3OC6H4
4-OHC6H4
45
90
80
70
90
90
85
90
80
90
87
96
91
70
87
92
71
74
76
89
274–275
262–264
197–199
239–242
317–319
172–173
201–202
222–225
207–208
266
275–276 [13]
258–260 [13]
199–201 [33]
235–238 [13]
313–315 [13]
174–175 [21]
–
226–228 [13]
208–210 [33]
265–267 [33]
j
a
Isolated yield.

H. Zang et al. / Ultrasonics Sonochemistry 17 (2010) 749–751
751
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that reaction solvents played a significant role in the model reac-
tion. Different solvents for the reaction were examined. The
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on the yield of this reaction, The use of EtOH/H2O (9.5:5) and EtOH/
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tant in these solvents. Other solvents such as CH3CN and CH2Cl2
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at room temperature. The yields of 3b was very low (18%). It was
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mation under milder conditions. The reason may be the phenome-
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An efficient and environmentally friendly method has been
developed for the preparation of 2-aryl-4,5-diphenyl imidazoles
catalyzed by 10 mol% of [EMIM]OAc under ultrasonic irradiation.
The use of sonication combining ionic liquid in the three-compo-
nent condensation brings up the merits like milder conditions,
low pollution, good yields and simple work-up.
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Acknowledgement
The project was supported by the Tianjin National Natural Sci-
ence Foundation (Nos. 07JCYBJC02200 and 09JCZDJC22700).
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