A zeolite promoted expeditious one-pot synthesis of 1-arylmethyl-4,5- dihydro-2-aryl-1H-imidazole

Article abstract of DOI:10.1002/jhet.314

(Chemical Equation Presented) A series of 1-arylmethyl-4,5-dihydro-2-aryl- 1H-imidazoles were synthesized expeditiously in good yields from 1,2-diaminoethane and aromatic aldehydes in the presence of zeolite under microwave irradiation in the absence of s

Full text of DOI:10.1002/jhet.314

350
A Zeolite Promoted Expeditious One-Pot Synthesis of
1-Arylmethyl-4,5-dihydro-2-aryl-1H-imidazole
Vol 47
Ramakanth Pagadala,a Jyotsna S. Meshram,a* Himani N. Chopde,a
and Nagender Reddy Panyalab
aDepartment of Chemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur-440 033,
Maharashtra, India
b
´ˇ ´
Department of Chemistry, Faculty of Science, Masaryk University, Kotlarska 2, 611 37 Brno,
Czech Republic
*E-mail: drjsmeshram@rediffmail.com
Received September 11, 2009
DOI 10.1002/jhet.314
Published online 2 March 2010 in Wiley InterScience (www.interscience.wiley.com).
A series of 1-arylmethyl-4,5-dihydro-2-aryl-1H-imidazoles were synthesized expeditiously in good
yields from 1,2-diaminoethane and aromatic aldehydes in the presence of zeolite under microwave irra-
1
diation in the absence of solvent. The resulting substituted imidazoles are characterized by H and 13C
NMR, elemental analysis, and mass spectral data.
J. Heterocyclic Chem., 47, 350 (2010)
INTRODUCTION
reported in the literature for the synthesis of imidazoles,
such as: (a) synthesis via hetero-Cope rearrangement
[23]; (b) four-component condensation of arylglyoxals,
primary amines, carboxylic acids, and iso-cyanides on
Wang resin [24,25]; (c) reaction of N-(2-oxo)-amides
with ammonium trifluoroacetate [26]. Compounds with
an imidazole ring system have many pharmacological
properties and play important roles in biochemical proc-
esses [27]. Organic chemists have been making extensive
efforts to produce heterocyclic compounds by developing
new and efficient synthetic transformations [28].
Recently, palladium and copper-catalyzed strategies have
been successfully applied to the assembly of various het-
erocyclic compounds via one-pot synthesis [29].
Many of the synthetic protocols for imidazoles
reported so far suffer from one or more disadvantages,
such as harsh reaction conditions, poor yields, prolonged
time period, use of hazardous, and often expensive acid
catalysts. We have employed to achieve simple and
environmentally compatible synthetic methodology for
the synthesis of substituted imidazoles in the presence
of zeolite under MW irradiation.
The use of microwave (MW) irradiation as a non-con-
ventional energy source has become of considerable in-
terest in organic chemistry. This novel method has
proved to be very efficient in various reactions, espe-
cially in organic synthesis [1–5], which has several
advantages over classical thermal conditions in provid-
ing increased reaction rates, simplicity, and improved
yields. The development of one-pot reaction has been of
great interest in organic synthesis because this method-
ology provides easy access to highly complex molecules
from relatively simple reagents under economically
favorable reaction conditions. Thus, the combination of
the one-pot strategy with the use of eco-friendly zeolite
catalysts becomes a powerful means of preparation for
specific target compounds to minimize pollutants and to
reduce production cost [6–9]. MW irradiation has been
used to effect organic reactions, such as cyclization
[10], aromatic substitution [11], oxidation [12], alkyla-
tion [13], decarboxylation [14], radical reactions [15],
condensation [16], peptide synthesis [17], etc.
Imidazole chemistry currently attracts considerable
attention, where the imidazole derivatives are extensively
applied as N-ligands coordinating transition metals
[18,19]. The application of imidazoles in medicinal
chemistry [20], chemistry of natural products/alkaloids
[21], and 1,3-disubstituted imidazole salts as ionic
liquids [22] are well known. Several methods are
RESULTS AND DISCUSSION
Reactions were carried out simply by mixing 1,2-diami-
noethane with different substituted aromatic aldehydes in
the presence of zeolite under solvent-free condition
C
V
2010 HeteroCorporation

March 2010
A Zeolite Promoted Expeditious One-Pot Synthesis of
1-Arylmethyl-4,5-dihydro-2-aryl-1H-imidazole
351
Scheme 1. MW assisted synthesis of substituted imidazoles.
the yield comparison plot (Fig. 1) of classical and MW
assisted synthesis of the substituted imidazoles that
MW irradiation has been found to be easier, conven-
ient, eco-friendly, and yield of all the products are
more than good as compared with the classical method.
In general, synthesis of substituted imidazole under
thermal conditions may occur in two steps, formation
of Schiff base and its cyclization.
(Scheme 1). All the 1-arylmethyl-4,5-dihydro-2-aryl-1H-
imidazoles derivatives were obtained in excellent yields.
This study describes a successful approach for the
synthesis of substituted imidazoles using a laboratory
MW reactor. This MW technology does not require link-
ing-cleaving chemistry and afford the products immedi-
ately. In a solvent-free cyclization reaction of imidazoles
is developed, which requires MW irradiation of 1,2-dia-
minoethane and aromatic aldehydes in the presence of
zeolite. This support allows for easy separation of the
solid catalyst and product by simple filtration, and in
optimal conditions the supported catalyst can be reused
multiple times. The readily and exclusive formation of
cyclized imidazoles occurs in good yields.
The reaction may tentatively be visualized to occur
via a tandem sequence of reactions depicted in reaction
mechanism (Mechanism 1) involving (i) formation of
N,N0–bis(aryl)ethylenediimine, (ii) protonation of the
N,N0–bis(aryl)ethylenediimine by zeolite and ring clo-
sure leading to a five membered ring in either a sequen-
tial or a concerted manner, (iii) 1,3-hydride transfer, and
(iv) deprotonation. While the aryl groups/nitrogen atom
could stabilize the positively charged intermediates
involved in the intermediate steps, the aromatic stabili-
zation of the resulting imidazoles could provide the im-
petus for the transformation. The reaction under MW
condition goes to completion in 6 min. Physical proper-
ties of the substituted imidazoles are given in Table 2.
Mechanism 1: The possible reaction mechanism.
The same reaction under thermal conditions (Scheme 2)
affords lower yields (Table 1). Hence, it is clear from
EXPERIMENTAL
DMSO solvent and TMS as the internal standard. EI-MS spectra
were determined on a LCQ ion trap mass spectrometer (Thermo
Fisher, San Jose, CA, USA), equipped with an EI source.
General. All the chemicals and solvents were obtained from
Merck (AR grade) and were used without further purification.
Melting points were taken in an open capillary tube. The MW
assisted synthesis of titled compounds were carried out in a
CEM – 908010, bench mate model, 300 watts laboratory MW re-
actor. Elemental analyses were carried out using a Perkin-Elmer,
Synthesis of 1-arylmethyl-4,5-dihydro-2-aryl-1H-imidazoles.
1,2-diaminoethane (0.108 g, 1 mmol), benzaldehyde (0.212 g,
2 mmol), and zeolite (montmorillonite K-10) (0.1 g) was thor-
oughly mixed. The reaction mixture was irradiated for 6 min
with 100 W MWs at 110ꢀC in MW oven in the temperature
control mode. The completion of the reaction was monitored
by TLC. After the irradiation was over, the reaction mixture
was cooled and added into water and extracted with diethyl
1
CHN elemental analyzer model 2400. H NMR and 13C NMR
spectra of the imidazoles were recorded on a Bruker-Avance
(300 MHz), Varian-Gemini (200 MHz) spectrophotometer using
Scheme 2. Synthesis of substituted imidazole under thermal condition.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

352
R. Pagadala, J. S. Meshram, H. N. Chopde, and N. R. Panyala
Vol 47
Table 1
Time and yield comparison between classical and MW irradiation.
Microwave
method
Classical
method
Formula
weight
Reaction
time (min) (%)a
Yield Reaction Yield
(%)a
Compound
time (h)
1
2
3
4
5
6
7
268
326
356
322
272
326
216
6
6
6
6
6
6
6
91
90
85
92
86
82
80
4
4
4
4
4
4
4
65
61
58
61
56
60
59
Figure 1. Graphical representation of yield comparison between classi-
cal and MW Irradiation.
a Isolated yields
114.4, 112.1, 54.9, 50.0, 49.1, 47.9; Mass spectra, m/z ¼ 356
(100%).
1-(4-Dimethylaminobenzyl)-4,5-dihydro-2(4-di methylami-
ether. After filtering the zeolite particles, the ethereal layer
was washed with water, dried with anhydrous sodium sulphate,
and the solvent removed. The crude product was recrystallized
from methanol.
Synthesis of 1-arylmethyl-4,5-dihydro-2-aryl-1H-imida-
zoles by classical method. A mixture of Schiff base (0.7
mmol), catalytic amount of H2SO4 and ethanol (50 mL) were
refluxed for ꢁ4 h. The completion of the reaction was moni-
tored by TLC. After completion of the reaction, the reaction
mixture was set on one side to cool. Solid deposit was col-
lected by the filtration. The crude product was recrystallized
from methanol.
1
nophenyl)-1H-imidazoles (4). H NMR: d 7.56 (d, J ¼ 9 and
2 Hz, 2H, Ar-CH); 7.30 (d, J ¼ 8 and 1 Hz, 2H, Ar-CH); 6.98
(d, J ¼ 9 Hz, 2H, Ar-CH); 6.64 (d, J ¼ 9 Hz, 2H, Ar-CH);
3.88 (s, 2H, CH2); 3.72 (t, J ¼ 7.6 Hz, 2H, CH2); 3.06 (t, J ¼
7.5 Hz, 2H, CH2); 2.98 (s, 12H, CH3); 13C NMR: d 162.7,
152.3, 152.1, 148.1, 129.9, 124.9, 112.0, 78.1, 77.5, 76.9, 62.5,
40.6; Mass spectra, m/z ¼ 322 (100%).
1-(4-Florobenzyl)-4,5-dihydro-2(4-florophenyl)-1H-imidazoles
1
(5). H NMR: d 7.64 (d, J ¼ 8 Hz, 2H, Ar-CH); 7.24 (d, J ¼
8 Hz, 2H, Ar-CH); 7.09 (d, J ¼ 9 Hz, 2H, Ar-CH); 6.98 (d, J
¼ 9 Hz, 2H, Ar-CH); 3.86 (s, 2H, CH2); 3.69 (t, J ¼ 7.6 Hz,
2H, CH2); 3.01 (t, J ¼ 7.6 Hz, 2H, CH2); 13C NMR: d 164.7,
162.7, 160.0, 130.9, 129.8, 128.2, 126.9, 113.8, 113.6, 50.6,
49.1, 48.2; Mass spectra, m/z ¼ 272 (100%).
1-(2-Hydroxybenzyl)-4,5-dihydro-2(2-hydroxyp henyl)-1H-
1
imidazoles (1). H NMR: d 8.36 (s, 2H, AOH); 6.82–7.33 (m,
8H, Ar-CH); 4.0 (s, 2H, CH2); 3.94 (t, J ¼ 7.7 Hz, 2H, CH2);
3.09 (t, J ¼ 7.6 Hz, 2H, CH2); 13C NMR: d 163.0, 160.8,
154.9, 131.2, 129.7, 129.2, 128.1, 122.4, 120.6, 114.3, 111.2,
50.4, 48.1, 40.9; Mass spectra, m/z ¼ 268 (100%).
1-(2-Nitrobenzyl)-4,5-dihydro-2(2-nitrophenyl)-1H-imidazoles
1
(6). H NMR: d 7.41–8.51 (m, 8H, Ar-CH); 3.97 (s, 2H, CH2);
1-(3-Nitrobenzyl)-4,5-dihydro-2(3-nitrophenyl)-1H-imidazoles
3.74 (t, J ¼ 7.7 Hz, 2H, CH2); 2.99 (t, J ¼ 7.6 Hz, 2H, CH2);
13C NMR: d 162.9, 147.7, 147.4, 134.2, 131.3, 128.9, 127.8,
127.0, 120.2, 50.7, 47.9, 40.1; Mass spectra, m/z ¼ 326
(100%).
1
(2). H NMR: d 7.52-8.53 (m, 8H, Ar-CH); 4.04 (s, 2H, CH2);
3.81 (t, J ¼ 7.6 Hz, 2H, CH2); 3.05 (t, J ¼ 7.6 Hz, 2H, CH2);
13C NMR: d 162.8, 147.7, 147.2, 136.2, 133.1, 132.4, 132.1,
127.9, 122.8, 122.5, 117.8, 52.3, 49.9, 49.7; Mass spectra, m/z
¼ 326 (100%).
1
1-(Furyl)-4,5-dihydro-2(furyl)-1H-imidazoles (7). H NMR:
d 7.84 (d, J ¼ 2 Hz, 1H,); 7.43 (d, J ¼ 2 Hz, 1H); 6.41–6.67
(m, 3H); 6.21 (d, J ¼ 3 Hz, 1H); 4.59 (s, 2H, CH2); 3.45 (t, J
¼ 7.5 Hz, 2H, CH2); 2.91 (t, J ¼ 7.6 Hz, 2H, CH2); 13C
NMR: d 163.1, 147.3, 142.8, 142.1, 141.0, 109.8, 109.6,
109.2, 105.2, 45.6, 44.2, 37.8; Mass spectra, m/z ¼ 216
(100%).
1-(3,4-Dimethoxybenzyl)-4,5-dihydro-2(3,4-dimethoxyphenyl)-
1
1H-imidazoles (3). H NMR: d 6.39–7.02 (m, 6H, Ar-CH);
3.90 (s, 2H, CH2); 3.69 (s, 12H, CH3); 3.59 (t, J ¼ 7.6 Hz,
2H, CH2); 2.88 (t, J ¼ 7.7 Hz, 2H, CH2); 13C NMR: d 162.4,
150.9, 148.8, 148.5, 147.3, 129.1, 125.2, 122.0, 120.4, 114.7,
Table 2
Physical and analytical data of substituted imidazoles.
% Calcd (Found)
H
Compound
Ar
Formula
mp (ꢀC)
C
N
1
2
3
4
5
6
7
o-OHC6H4
m-NO2C6H4
m, p-(OCH3)2C6H4
p-(CH3)2NC6H4
p-FC6H4
C16H16N2O2
C16H14N4O4
C20H24N2O4
C20H26N4
90
119
115
127
97
71.62 (71.60)
58.89 (59.03)
67.40 (67.62)
74.50 (74.31)
70.58 (70.49)
58.89 (58.94)
66.65 (66.31)
6.01 (6.04)
4.32 (4.26)
6.79 (6.83)
8.13 (8.09)
5.18 (5.11)
4.32 (4.26)
5.59 (5.70)
10.44 (10.42)
17.17 (17.24)
07.86 (07.81)
17.38 (17.30)
13.95 (13.91)
17.17 (17.20)
12.96 (12.91)
C16H14N2F2
C16H14N4O4
C12H12N2O2
o-NO2C6H4
2-furyl
104
121
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2010
A Zeolite Promoted Expeditious One-Pot Synthesis of
1-Arylmethyl-4,5-dihydro-2-aryl-1H-imidazole
353
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amounts and reaction times. The one-pot nature of the
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet