MCM-41 mesoporous silica: Efficient and reusable catalyst for the synthesis of 2,4,5-trisubstituted imidazoles under solvent-free conditions

Article abstract of DOI:10.1080/15533174.2011.609211

A simple, high-yielding synthesis of 2,4,5-trisubstituted imidazoles from 1,2-diketone/1,2-hydroxyketone and aldehydes in the presence of NH ₄OAc is described. Under solvent-free conditions, aryl and heteroaryl substituted imidazoles are formed in yields ranging from 70 to 90%. Copyright Taylor & Francis Group, LLC.

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Synthesis and Reactivity in Inorganic, Metal-Organic,
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MCM-41 Mesoporous Silica: Efficient and Reusable
Catalyst for the Synthesis of 2,4,5-Trisubstituted
Imidazoles Under Solvent-Free Conditions
a
b
a
Majid M. Heravi , Masoumeh Zakeri & Hoda Haghi
a
Department of Chemistry, School of Sciences, Alzahra University, Vanak, Tehran, I. R.
Iran
b
Young Researchers Club, Islamic Azad University, North Tehran Branch, Tehran, I. R.
Iran
Published online: 02 Dec 2011.
To cite this article: Majid M. Heravi , Masoumeh Zakeri & Hoda Haghi (2011): MCM-41 Mesoporous Silica: Efficient and
Reusable Catalyst for the Synthesis of 2,4,5-Trisubstituted Imidazoles Under Solvent-Free Conditions, Synthesis and
Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 41:10, 1310-1314
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Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry, 41:1310–1314, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1553-3174 print / 1553-3182 online
DOI: 10.1080/15533174.2011.609211
MCM-41 Mesoporous Silica: Efficient and Reusable Catalyst
for the Synthesis of 2,4,5-Trisubstituted Imidazoles Under
Solvent-Free Conditions
1
2
1
Majid M. Heravi, Masoumeh Zakeri, and Hoda Haghi
1
Department of Chemistry, School of Sciences, Alzahra University, Vanak, Tehran, I. R. Iran
Young Researchers Club, Islamic Azad University, North Tehran Branch, Tehran, I. R. Iran
2
NiCl2·6H2O/Al2O3, ZrCl4,[10] ionic liquids,[11] and CAN.[12]
[9]
A simple, high-yielding synthesis of 2,4,5-trisubstituted imida- Although there are several papers reporting the synthesis of
zoles from 1,2-diketone/1,2-hydroxyketone and aldehydes in the
trisubstituted imidazoles using 1,2-diketones, there are few re-
ports in the literature using α-hydroxyketones as statrting ma-
terial. Herein we describe the synthesis of trisubstituted imi-
dazoles by the one-pot condensation of benzil, benzoin with a
substituted benzaldehyde, and ammonium acetate in the pres-
ence of MCM-41 as the catalyst. In the past 10 years a new class
of mesoporous silica materials has become available, materials
constituted of a two-dimensionally ordered array of cylindrical
pores of uniform size disposed parallel to each other and sepa-
rated by thin walls. The pore diameter is adjustable between 2
and 4 nm in the case of MCM-41 silicas. The silica materials are
obtained as a fine powder after removal of the surfactant by cal-
cination. Mesoporous silica materials are promising candidates
for catalytic applications. For these applications it is mandatory
to understand the properties of the inner surfaces as well as
the state of the guest molecules. MCM-41, one member of the
M41S family, possesses a regular hexagonal array of uniform
pore openings with a broad spectrum of pore diameters between
15 and 100 Å.[ The mesoporous structure can be controlled by
a sophisticated choice of templates (surfactants) and changing
reactionparameters(e.g., temperature, compositions). Thepores
of this novel material are nearly as regular as, yet considerably
larger than, those present in crystalline materials such as zeo-
lites, thus offering new opportunities for applications to catal-
ysis. For economic and ecological reasons, organic synthetic
chemists face an increasing obligation to optimize their synthetic
methods in order to produce the desired products in high yields
and selectivities through a safe and environmentally acceptable
[8] process. Thus, the challenge was to replace them by solid MCM-
4
presence of NH OAc is described. Under solvent-free conditions,
aryl and heteroaryl substituted imidazoles are formed in yields
ranging from 70 to 90%.
Keywords benzil, benzoin, click reaction, MCM-41, trisubstituted
imidazoles
INTRODUCTION
The synthesis, reactions, and biological properties of sub-
stituted imidazoles constitute a significant part of modern het-
erocyclic chemistry. Multisubstituted imidazoles, an important
class of pharmaceutical compounds, exhibit a wide spectrum of
[
1]
biological activity. Highly substituted imidazoles like lepidi-
lines[ exhibit micromolar cytotoxicity against several human
2]
[
3]
cancer cell lines. Trifenagrel is a potent 2,4,5-triarylimidazole
that reduces platelet aggregation in several animal species
and humans. Substituted imidazoles are substantially used in
13]
ionic liquids[4] that have been given a new approach to “green
chemistry.” The imidazole compounds are also used in pho-
tography as photosensitive compounds. Recently, multicompo-
nent reactions (MCRs) have attracted considerable attention
since they are performed without the need to isolate any
intermediate and save both energy and raw materials and
also reduce time.[5] 2,4,5-Trisubstituted imidazoles are gen-
erally synthesized by three-component cyclo-condensation of
a 1,2-diketone/1,2-hydroxyketone with an aldehyde and am-
monium acetate, in a process that comprises the use of mi-
crowaves,[ refluxing in acetic acid, silica sulfuric acid,
6]
[7]
4
1, which is easier to separate from the products, and possesses
reusability, high acid strength, and hydrophilic and hydrophobic
properties.
Received 15 September 2010; accepted 26 July 2011.
MMH is thankful to the Iran National Science Foundation for partial
financial support.
In continuation of our ongoing research for the develop-
ment of simple and efficient methods for the synthesis of var-
ious heterocyclic compounds,[ herein we report a simple,
14]
Address correspondence to Majid M. Heravi, Department of Chem-
istry, School of Sciences, Alzahra University, Vanak, Tehran, I. R. Iran. economic, and efficient one-pot method for the synthesis of
E-mail: mmh1331@yahoo.com
2,4,5-triaryl-1H-imidazoles from benzoin or benzil, ammonium
1310

SYNTHESIS OF 2,4,5-TRISUBSTITUTED IMIDAZOLES
1311
O
O
Ph
Ph
Ph
CHO
Ph
Ph
N
NH
O
MCM-41
or
NH OAc
4
Solvent-Free
R1
Ph
R1
OH
1
a-m
SCH. 1.
acetate, and aromatic aldehydes using MCM-41 as the catalyst Reusability of MCM-41
under solvent-free conditions (Scheme 1).
Next, we investigated the reusability of MCM-41. At the
end of the reaction, the catalyst could be recovered by a simple
filtration, washed with methanol and subjected to a second run
of the reaction process. In Table 2, the comparison of efficiency
of MCM-41 in synthesis of 1a after four times is reported.
As shown in Table 2, the first reaction using recovered MCM-
EXPERIMENTAL
Materials and Methods
Melting points were measured by using the capillary tube 41afforded a similar yield to that obtained in the first run. In
1
method with an electrothermal 9200 apparatus. H-Nuclear the second, third, and fourth runs, the yields were gradually
magnetic resonance (NMR) spectra were recorded on a Bruker decreased.
AQS AVANCE 300-MHz spectrometer using trimethylsilane
(
TMS) as an internal standard (CDCl3 solution). Infrared (IR)
RESULTS AND DISCUSSION
spectra were recorded using KBr disks on the FT-IR Bruker
Tensor 27. All products were well characterized by comparison
with authentic samples by thin-layer chromatography (TLC)
and spectral and physical data.
In this study, to evaluate and optimize the catalytic sys-
tem, we screened different mesoporous compounds for their
ability to catalyze the synthesis of 2,4,5-trisubstituted imida-
zole compounds (Table 3). MCM-41, immobilized Mn(II) com-
ꢁ
ꢁ
plex with oxygen donor ligand (2,2 bipyridine 1,1 dioxide
bpdo)) within nanoreactors of MCM-41,[ Al-MCM-41,
15]
[16]
(
[
[
General Procedure for the Synthesis of
2
+2
Zn(bpdo)2Cl2]/MCM-41, [Cu(bpdo)2.2H2O] /MCM-41, and
,4,5-Triarylimidazoles 1a–m
A mixture of benzil or benzoin (1.0 mmol), aldehyde
+2
Zn(bpdo)2·2H2O] /Na-montmorillonite-KSF catalysts were
examined in the present study. In the case of supported reagents
the presence of complex in the channels leads to a decrease in
the surface area and the silanol groups. As shown in Table 3,
these catalysts afforded the desired product but only in mod-
erate yields (Table 3, entries 1, 2, 3, 4, and 5). Interestingly, it
was found that MCM-41 could efficiently catalyze this reaction
to affored the desired products in good yields in a relatively
short time. It proved to be an efficient catalyst and gave exclu-
sively 2,4,5-triphenylimidazole 1a in 90% yield in 15 min under
solvent-free conditions (Table 3, entry 6).
(1.0 mmol), ammonium acetate (4 mmol), and MCM-41 (0.05
◦
g) was stirred at 80 C for the appropriate time mentioned in
Table 1. The progress of the reaction was monitored by TLC.
After completion of the reaction, the crude product was dis-
solved in ethanol and the catalyst was separated by filtration.
The filtrate was evaporated under reduced pressure to remove
ethanol,and the resulting product was washed with water, dried
with MgSO4, and evaporated to give the crude product. Further
purification was achieved by recrystallization from ethanol.
The results obtained from MCM-41 catalyzed synthesis of
trisubstituted imidazoles are given in Table 1. These results were
Selected Spectral Data
Compound 1b: 2-(2-Chloro-phenyl)-4,5-diphenyl-1H- obtained by stirring a mixture of aldehyde (1 mmol), benzil (1
−
1
imidazole: IR (KBr): 3425, 1600, 1483, 1438, 694 cm , mmol), ammonium acetate (4 mmol), and MCM-41 (0.05 g) un-
1
H-NMR (300 MHz, CDCl3): δ 7.30–7.48 (m, 9H, ArH), 7.50 der solvent-free conditions for 15 min. After completion of the
(
1
s, 4H, ArH), 8.50–8.52 (dd, 1H, J = 1.67 and J = 8 Hz, ArH), reaction, the mixture was cooled to room temperature. The crude
+
0.31 (br, 1H, NH) ppm. MS: m/z 330 [M ], 315, 294, 267, product from the reaction mixture was dissolved in ethanol and
253, 227, 207, 190, 165, 147, 123,104.
the catalyst was separated by filtration. After evaporating the

1312
M. M. HERAVI ET AL.
TABLE 1
MCM-41 catalyzed synthesis of 2,4,5-trisubstituted imidazoles
◦
(
C)
Mp
(%)
Yield
(Min)
Time
Ref.
(Lit)
Found
Benzoin
Benzil
Benzoin
Benzil
Products
R1
H
Entry
1
17
267–269 269–270
85
90
35
15
1a
1
7
8
190–191 189–190
188–189 190–193
75
80
80
85
35
35
15
15
1b
1c
2-Cl
4-Br
2
3
1
1
7
9
232–233 229–231
302–303 302–303
85
78
88
85
35
35
15
15
1d
1e
4-F
4
5
1
3-Br
1
7
7
199–201 197–198
88
80
90
86
35
35
15
15
1f
4-NO2
3-NO2
6
7
1
300
298–303
1g
1
7
7
232–233 233–235
75
80
85
85
35
35
15
15
1h
1i
4-OH
4-Me
8
9
1
233
230
(Continued on next page)

SYNTHESIS OF 2,4,5-TRISUBSTITUTED IMIDAZOLES
1313
TABLE 1
MCM-41 catalyzed synthesis of 2,4,5-trisubstituted imidazoles (Continued)
◦
(
C)
Mp
(%)
Yield
(Min)
Time
Ref.
(Lit)
Found
Benzoin
Benzil
Benzoin
Benzil
Products
R1
Entry
2
0
202–203 203–204
210–211 210–212
80
75
88
80
35
35
15
15
1j
4-OMe
10
17
1k
2-OMe
11
1
1
0
170
168–170
70
70
75
70
35
35
15
15
1l
2-OH-3-
OMe
12
13
1
185–187 189–191
1m
Furfural
aThe yields refer to isolated products
solvent, pure product was obtained. It should be mentioned that were found to be lower than for benzil (70–85%). The reaction
the desired products could be easily separated in this condition. profile is very clean and no side products are formed. Aldehy-
MCM-41 is not soluble in ethanol at room temperature but the des bearing either electron-withdrawing or electron-donating
products are. While the mixture cooled to room temperature the groups perform equally well in the reaction. Steric effects
products appeared from solution and could be separated by a did not influence the yield significantly; for example, in the
simple filtration. Under the same conditions, this approach can reaction of p-methoxy (Table 1, entry 10) and o-methoxy (Ta-
be repeated for synthesis of these imidazoles when the benzoin ble 1, entry 11) benzaldehyde, the corresponding condensation
was used instead of benzil as a starting material (Scheme 1).
Thus, benzoin effectively participated in the condensation with
aldehyde and ammonium acetate in the presence of MCM-41
to give corresponding trisubstituted imidazoles but the yields
TABLE 3
Synthesis of 2,4,5-triphenylimidazole 1a using in the different
catalysts
a
Entry
Catalyst (0.05 g)
Time (min) Yield (%)
TABLE 2
Reuseability of the MCM-41 for synthesis
1
2
[Mn(bpdo)2Cl2]/MCM-41
[Cu(bpdo)2.2H2O] /MCM-
30
20
70
65
2,4,5-triphenylimidazole 1a.
+2
a
41
Entry
Time (min)
Yield (%)
3
4
[Zn(bpdo)2.Cl2]/MCM-41
25
20
65
30
+2
1
2
3
4
15
30
40
50
80
75
60
55
[Zn(bpdo)2.2H2O] /Na-
montmorillonite-KSF
Al-MCM-41
5
6
20
15
75
90
MCM-41
aIsolated yield
aThe yields refer to isolated products

1314
M. M. HERAVI ET AL.
products were obtained in 88% and 80% yields, respectively.
Additionally, heterocyclic aldehyde (Table 1, entry 13) delivers
the corresponding imidazoles in high yield. All the synthesized
imidazoles have been characterized on the basis of elemental
and spectral studies.
The substitution of traditional homogeneous catalysts for het-
erogeneous ones could form a more environmentally friendly
substitute in catalyzed organic reactions. Such catalysts offer
many advantages compared to their homogeneous counter parts:
no need for solvents or the use of less toxic ones (e.g., hydro-
carbons), milder reaction conditions, easier separation of the
catalyst from the reaction mixture by filtration, and its possible
regeneration and reuse, reducing the creation of waste and thus
harm to the environment.
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nium acetate in chemoselectivity. J. Org. Chem. 2003, 68, 5415–5418.
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catalyst for the synthesis of trisubstituted imidazoles. J. Mol. Catal. A Chem.
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CONCLUSION
In summary, this article describes a convenient and efficient
process for the synthesis of trisubstituted imidazoles through
the three-components coupling of benzil or benzoin, aldehy-
des, and ammonium acetate using MCM-41 as a solid sup-
1
2,4,5-triaryl-1H-imidazoles. J. Chem. Sci. 2008, 5, 463–467.
port. This methodology offers very attractive features such as 13. Beck, J.S.; Vartuli, J.C.; Roth, W.J.; Leonowicz, M.E.; Kresge, C.T.;
Schmitt, K.D.; Chu, C.T.; Olson, D.H.; Sheppard, E.V.; McCullen, S.B.;
Higgins, J.B.; Schlenker, J.L. A new family of mesoporous molecular
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reduced reaction times, higher yields, and economic viability
of the catalyst, when compared with the conventional method
as well as with other catalysts, and will have wide scope in
1
14, 10834–10843.
organic synthesis. The simple procedure combined with easy
of recovery and reuse of this catalyst makes this method eco-
nomic, benign, and a waste-free chemical process for the syn-
thesis of trisubstituted imidazoles. The catalyst can be prepared
easily with readily available inexpensive reagents, and is het-
erogeneous and nonhazardous. We believe that this procedure is
1
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ꢁ
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APPENDIX
Ph
Ph
1
HNMR (500 MHz, CDCl3): δ = 7.30–7.48 (m, 9H, Ar), 7.50(s, 4H, Ar),
.50–8.52(d.d, 1H, J = 1.67, J = 8 Hz, Ar), 10.31 (s, br, 1H, NH) ppm.
2
N
NH
8
−1
+
FTIR (KBr, cm , υ): 3425, 1600, 1483, 1438.694. MS: m/z 330 [M ],
15, 294,267, 253, 227, 207, 190, 165, 147, 123,104, 89.
Cl
3