The one-pot synthesis of 2,4,5-triaryl-imidazoles using heteropolyacids as heterogeneous and recyclable catalysts

Article abstract of DOI:10.1002/jccs.200800178

2,4,5-triaryl imidazoles were obtained in high yields with excellent purity from the condensation of benzaldehydes, NH₄OAc and 1,2-diketone in the presence of a catalytic amount of various heteropolyacids (HPAs).

Full text of DOI:10.1002/jccs.200800178

Journal of the Chinese Chemical Society, 2008, 55, 1199-1203
1199
Communication
The One-pot Synthesis of 2,4,5-Triaryl-imidazoles Using Heteropolyacids
as Heterogeneous and Recyclable Catalysts
Majid M. Heravi,a* Samaheh Sadjadi,a Hossein A. Oskooie,a
Rahim Hekmatshoara and Fatemeh F. Bamoharramb
aDepartment of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
bDepartment of Chemistry, Islamic Azad University Mashhad-Branch, Mashhad, Iran
2,4,5-triaryl imidazoles were obtained in high yields with excellent purity from the condensation of
benzaldehydes, NH4OAc and 1,2-diketone in the presence of a catalytic amount of various heteropoly-
acids (HPAs).
Keywords: Trisubstituted imidazoles; Recyclable catalysts; Heteropolyacids.
The benzimidazole scaffold is a useful structural mo-
tif for displaying chemical functionality in biologically-ac-
tive molecules.1 An optimization of benzimidazole-based
structures has resulted in the marketed medicines such as
Omeprazole 2 and Pimobendan 3 and has led compounds in
a wide range of therapeutic areas (e.g. casein kinase,4 hepa-
titis C virus5). In addition, many of the substituted diaryl
imidazoles are known as the inhibitors of P38 MAP kinase.6
Therefore, the preparation of benzimidazoles has been at-
tracted considerable attention in recent years.
such as Brönsted acidity, a possibility to modify their acid-
base and redox properties by changing their chemical com-
position (substituted HPAs), and the ability to accept and
release electrons, high proton mobility, easy work-up pro-
cedures, easy filtration, and minimization of the cost and
waste generation due to the reuse and recycling of these
catalysts.12-16 Because of their strong acidity, they gener-
ally exhibit a higher catalytic activity than conventional
catalysts such as mineral acids, ion exchange resins, mixed
oxides, zeolites, etc.17
Recently, efficient synthesis of imidazoles from alde-
hydes, 1,2-diketones, and NH4OAc in acetic acid have been
reported.7 The synthesis of 2,4,5-triaryl-imidazoles from
aryl aldehydes and 1,2-diketones or b-hydroxy ketone in
the presence of ionic liquid8(a) and silica sulfuric acid8(b)
have also been described. A variety of solid supports such
as alumina, KSF, silica gel, bentonite, montmorilonite K10
and KSF were tested for the synthesis of 2,4,5-triaryl-imi-
dazoles under microwave irradiation.9
In view of green chemistry, the substitution of harm-
ful liquid acids by solid reusable HPAs as catalyst in or-
ganic synthesis is the most promising application of these
acids.18,19
In connection with our program of using heteropoly
acid in organic reactions.20 We disclose herein our results
for the synthesis of 2,4,5-triaryl-imidazoles using catalytic
amounts of heteropolyacids (Scheme I).
In order to confirm the utility of HPAs, as effective
catalysts, these reactions were repeated in the absence of
the HPAs. In all cases, a mixture of reactants was prepared
according to the abovementioned procedures, refluxed in
the absence of the HPAs.
Heteropoly acids (HPAs) are well-defined molecular
clusters that are remarkable for their molecular and elec-
tronic structural diversities and their significance is quite
diverse in many areas, e.g. catalysis, medicine, and materi-
als science.10-11
The results show that in the absence of the HPAs, the
reaction time is much longer, and the yield of reaction is
lower.
The application of heteropolyacids, HPAs, as cata-
lytic materials has been growing continuously in the cata-
lytic field. These compounds possess unique properties
The structural characteristics of the catalysts are as
* Corresponding author. E-mail: mmh1331@yahoo.com

.
1200 J. Chin.Chem.Soc.,Vol.55,No.6,2008
Heravi et al.
.
Scheme I
follow:
Table 1. Synthesis of 2,4,5-triaryl-imidazoles using
H14[NaP5W30O110] under refluxing condition
Preyssler’s anion, [NaP5W30O110]
14-, has an approxi-
mate D5h symmetry and consists of a cyclic assembly of
five PW6O22 units. A sodium ion is located within the poly-
anion on the fivefold axis and 1.25 above the pseudo mirror
plane that contains the five phosphorus atoms.21 Preyssler
polyanion, as a large anion, provides many “sites” on the
oval-shaped molecule that are likely to render the catalyst
effective.
Mp/ref. (°C)
Entry
R1
R2
Yield%a
Found
Reported23
1
2
3
4
5
H
H
H
CH3
NO2
H
95
92
275
233
240
313
261
275
233
H
80
240
NO2
H
78
313-315
261-3
Cl
85.5
a Yields of isolated products.
The Keggin anions have an assembly of 12 corner-
shared octahedral MoO6 from trimetallic groups [Mo3O13]
around a heteroatom tetrahedron PO4. The introduction of
the vanadium (V) into the Keggin framework of [PMo12O40]3-
is beneficial for catalysis reactions. Usually, positional iso-
mers are possible and coexisted when two or more vana-
dium atoms are incorporated into the Keggin structure.
Studies on these isomers in catalytic reactions indicate that
different isomers cause to show different reactivities.
With this respect to the catalytic performances for
these catalysts and the overall effects of all isomers, for
synthesizing of them, the reaction conditions to synthesis
of positional vanadium-substituted isomers separately can
not be controlled, and the relationship between the struc-
tures of H3+xPMo12-xVxO40 (x = 1, 2) is revealed, hence, the
study of their catalytic activity is difficult. However, be-
cause the metal substitution may modify the energy and the
composition of the LUMO and redox properties for the
mentioned heteropolyacids with different charges, the en-
ergy and the composition of the LUMOs have significant
effects on the catalytic activity. Substitution of vanadium
ions into the molybdenum framework stabilize the LUMOs
because these orbitals derive, in part from vanadium d-
orbitals which have been assumed to be more stable than
those of molybdenum and tungsten.22 The abundance of
different isomers may also play an important role in cata-
lytic performance. In addition, different positional Mo
atom(s) substituted by the V atom(s) in [PMo12O40]3- may
create different vanadium chemical environments, thus
causing these catalysts to exhibit varying catalytic perfor-
Table 2. Synthesis of 2,4,5-triaryl-imidazoles using various
heteropolyacids under refluxing condition
Entry
R1
R2
Catalyst
Yield%a
1
H
H
H
H
H14[NaP5W30O110
H6[P2W18O62]
]
95
92
2
3
H
H
H5[PMo10V2O40]
H4[PMo11VO40]
90
4
H
H
88
5
H
CH3
CH3
CH3
CH3
NO2
NO2
NO2
NO2
H
H14[NaP5W30O110
H6[P2W18O62]
]
]
]
]
92
6
H
90
7
H
H5[PMo10V2O40]
H4[PMo11VO40]
H14[NaP5W30O110
H6[P2W18O62]
86.5
85
8
H
9
H
80
10
11
12
13
14
15
16
17
18
19
20
H
77.2
75
H
H5[PMo10V2O40]
H4[PMo11VO40]
H14[NaP5W30O110
H6[P2W18O62]
H
73.5
78
NO2
NO2
NO2
NO2
H
H
74
H
H5[PMo10V2O40]
H4[PMo11VO40]
H14[NaP5W30O110
H6[P2W18O62]
72
H
70.3
85.5
82
Cl
H
Cl
H
Cl
H5[PMo10V2O40]
H4[PMo11VO40]
80
H
Cl
78.4
a Yields of isolated products.
mances. The results for H14[NaP5W30O110] are summarized
in Table 1.
The effects of various heteropolyacids on synthesis of
2,4,5-triaryl-imidazoles are shown in Table 2.
The effect of temperature was studied by carrying out
the reactions at different temperatures [room temperature,

The One-pot Synthesis of 2,4,5-Triaryl-imidazoles
J. Chin. Chem. Soc., Vol. 55, No. 6, 2008 1201
sion of H14[NaP5W30O110] with catalytic conditions re-
ported in previous works was performed. The results are
summarized in Table 4. H14[NaP5W30O110] is green, reus-
able catalyst.
Table 3. Effect of different reaction time and temperature on
synthesis of 2,4,5-triaryl-imidazoles using
H14[NaP5W30O110
]
Yield%a
Time
(min)
Entry
R1
R2
25 °C
50 °C
82 °C
EXPERIMENTAL
1
H
H
H
H
10
15
20
30
10
15
20
30
10
15
20
30
10
15
20
30
10
15
20
30
79
80
85
88
70
78
79
84
60
62
70
73
58
64
68
70
66
74
75
78
80
85
89
92
76
81
82
88
65
68
74
77
63
68
71
74
71
78
79
82
83
88
90
95
79
84
87
92
68
73
77
80
66
72
75
78
74
80
82
85.5
2
Chemicals and apparatus
3
H
H
All the chemicals were obtained from Merck Com-
pany and used as received. H14[NaP5W30O110] was pre-
pared according to the earlier works.26,27 H4[PMo11VO40]
and H5[PMo10V2O40] were prepared according to the previ-
ous literatures.28,30 The Wells-Dawson H6[P2W18O62] was
prepared as described elsewhere31 from an aqueous solu-
tion of a/b K6P2W18O62·10H2O salt, which was treated
with ether and concentrated (37%) HCl solution. All of the
reported 2,4,5-triaryl imidazoles are the known products.
4
H
H
5
H
CH3
CH3
CH3
CH3
NO2
NO2
NO2
NO2
H
6
H
7
H
8
H
9
H
10
11
12
13
14
15
16
17
18
19
20
H
H
H
NO2
NO2
NO2
NO2
H
H
1
All of products were characterized by IR and H NMR
H
H
techniques. The compression of melting points of obtained
products with authentic samples was performed to estab-
lish the structure of products as well. The results are sum-
marized in Table 1 and cited in references 23.
Cl
H
Cl
H
Cl
H
Cl
a Yields of isolated products.
Instruments
GC-Mass analysis was performed on a GC-Mass
model: 5973 network mass selective detector, GC 6890
egilent. IR spectra were obtained with a buck 500 scientific
25 °C, 50 °C and under refluxing temperature (82 °C)]. As
it is shown in Table 3, the yields of reactions increased as
the reaction temperature raised. From these results, it was
concluded that refluxing temperature would be the best
temperature for all reactions.
1
spectrometer. H NMR spectra were recorded on a FT-
NMR Bruker 90 MHz.
General procedure
Benzaldehydes (2 mmol), NH4OAc (2 mmol) and
1,2-diketone (2 mmol), were solved in acetonitrile (10
mL). Catalyst (0.01 mmol) was subsequently added to the
reaction mixture. The reaction mixture was refluxed at re-
flux temperature of 0.5 h.
For the investigation of the reaction time, the yield of
reactions was studied at different time (10, 15, 20, 30 min,
respectively). The results indicate that in each reaction, the
yield is a function of the reaction time and the best time for
all reactions was optimized to be 30 min.
The progress of the reaction was monitored by TLC.
After the completion of the reaction, the catalyst was fil-
tered off and the solvent was evaporated. The pure products
were obtained by the column chromatography. All products
To show the merit of H14[NaP5W30O110] in synthesis
of 2,4,5-triaryl-imidazoles, synthesis of 2,4,5-triphenyl-
imidazole was selected as model reaction and the compres-
Table 4. Comparison of the catalyst effects in the synthesis of 2,4,5-triphenyl-imidazole
Entry Condition Catalyst Yield%
Reflux in acetonitrile for 0.5 h H14[NaP5W30O110 95
1
]
2
3
4
5
Solvent free condition at 130 °C
Microwave irradiation
Silica sulfuric acid
Silica sulfuric acid
NiCl2.6H2O/Al2O3
[Hbim]BF4
8324
8524
9423
9525
Refluxed in ethanol for 25 min
Stirring for 60 min

1202
J. Chin. Chem. Soc., Vol. 55, No. 6, 2008
Heravi et al.
Table 5. The comparison of efficiency of H14[NaP5W30O110] in synthesis of 2,4,5-triaryl-
imidazoles after five times
Yield%a (after different times of recycling)
Entry
R1
R2
First
Second
Third
Forth
Fifth
1
2
3
4
5
H
H
H
CH3
NO2
H
95
92
92.5
90
90
87
76
74
81
88
85.5
73
87
82
70
69
76
H
80
78
NO2
H
78
76.2
83
71
Cl
85.5
79
a Yields of isolated products.
Received June 26, 2008.
were identified by the comparison of their physical and
spectroscopic data with those reported for authentic sam-
ples.
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