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Ionic Liquid
[cmmim][HSO4]
Catalyzed One Pot
Synthesis of
Triaryl Imidazoles
Chapter 5
Department of Chemistry, Sardar Patel University Page | 164
5.1. INTRODUCTION
Imidazole moiety is an important substructure in a number of molecules which exhibit as
array of biological and pharmacological activities. The imidazole ring system is an
important constituent of numerous natural products and medicinally important
compounds. In 1858, a scientist Heinrich Debus [1] for the first time reported a
multicomponent synthesis of imidazole from glyoxal, formaldehyde and ammonia. Later
in 1882, Radiziszewski and Japp independently reported a classical method to obtain 2, 4,
5-triphenyl imidazoles 4 by condensing 1, 2 dicarbonyl compounds 1 with different
aldehydes 2 and ammonia 3 in acidic medium [2,3]. Thr method was modified by
Weidenhagen in 1935[4]. Therefore, this reaction is generally known as the Radziszewski
reaction. Occasionally, it is also called the Radziszewski synthesis, Weidenhagen
Synthesis or Debus-Radziszewski imidazole synthesis.
Among different substituted imidazoles, 2,4,5-trisubstituted imidazoles derivatives
surmount much more attraction of chemist because of excellent biological activities.
Many drug like Omeprazole [5] a proton pump inhibitor, flumazenil [6]. A platelet
coagulation drug in animal and human beings, trifenagrel [7], is a 2,4,5- trisubstituted
aryl-1 H-imidazole derivatives. The effectiveness of the 2,4,5-trisubstituted aryl
imidazoles is substrate dependent; the use of more highly functionalized or sterically
hindered aldehydes severely reduced yields. Afterwards, several new modified
procedures were reported over the past two centuries for the synthesis of these biological
important scaffolds starting from banzil/benzoin, aldehydes and ammonium acetate. The
discovery and development of new catalytical reaction conditions have lead to general
methods for the direct preparation of 2,4,5- triaryl imidazole derivatives in high yield by
development of novel strategies. The detail reports are summarized below.
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Department of Chemistry, Sardar Patel University Page | 165
5.2 RECENT LITERATURE SURVEY
Although there is no general mechanism for Radziszewski synthesis of 2,4,5-triaryl
imidazoles in the cited literature, it is plausible that ammonia (or primary amine) reacts
with a α-dicarbonyl compound to form α-diimine, which then condenses with an
aldehydes to give 2,4,5-tri substituted imidazole derivatives. In the meantime, it is also
possible to form an oxazole as the by-product from this multicomponent condensation.
O
O
NH3O
NH2O
H
O
NHHO
H
-H2O
O
NH
NH3-H2O
NH
NH
HR
O
N
NH
R
OHH
N
NH2
R
NN
R OH
H
-H2O
N
H2N
R
N OH
R
NH
NO
NH2
H
R
-NH3
NO
ROxazole (By product)
Substituted Imidazole
Scheme 5.2 Mechanistic Pathway
HHN
NH
R
O
OH
H
Due to great biological importance, many synthetic strategies have been developed for
the synthesis of substituted imidazoles. Recently, numbers of articles are cited in
literature in which HY-zeolites/Silica gel, ZnCl4, NiCl2, NiCl2·2H2O, Iodine, Sodium
bisulfate, p-TSA, InCl3·3H2O, excess H2SO4, Alum, and PEG supported ionic liquids
have been employed as the catalyst for the synthesis of 2,4,5-triaryl-1H-imidazoles
Chapter 5
Department of Chemistry, Sardar Patel University Page | 166
starting from an aldehydes, a benzil, and ammonium acetate. Some recently reported
methods for the preparation of substituted imidazole derivatives are summarized below.
Sarshar, S. et. al. [8] recently reported the synthesis of highly substituted imidazoles
libraries on solid support using an aldehydes, an amine and a 1,2-dione in presence of
ammonium acetate. The synthesis was accomplished by attaching the aldehyde or amine
component to wang resin via ester or ether linkage. Claiborne, C. F. et. al. [9] carried out
a synthesis of tri and tetra substituted imidazoles under neutral condition by taking N-(2-
oxo)-amides with neat ammonium trifluoroacetate.
Balalaie, S. and Arabanian, A. [10] reported four-component condensation of benzil,
aromatic aldehydes, primary amines and ammonium acetate catalyzed by zeolite HY and
silica gel without any solvent under microwave irradiation leading to tetrasubstituted
imidazoles in high yields and purity. Balalaie, S. et. al. [11] reported a Zeolite HY and
silica gel as an efficient catalyst for the three-component condensation of benzil,
benzaldehyde derivatives, and ammonium acetate under solvent-free conditions and
microwave irradiation. Balalaie, S. et. al. [12] again reported one-pot, three-component
condensation of benzil, benzonitrile derivatives and primary amines on the surface of
silica gel under solvent-free conditions and microwave irradiation for the synthesis of
tetrasubstituted imidazoles in high yields.
Usyatinsky, A. Y. et. al. [13] carried out solvent-free microwave assisted synthesis of
2,4,5-substituted and 1,2,4,5-substituted imidazoles by condensation of 1,2-dicarbonyl
compound with aldehydes and amine using acidic alumina impregnated with ammonium
acetate as the solid support.
Frantz, D. E. et. al. [14] reported a one-pot synthesis of substituted imidazoles. The
cornerstone of this methodology involves the thiazolium-catalyzed addition of an
aldehyde to an acyl imine to generate the corresponding α-ketoamide in situ followed by
ring closure to the imidazole in a one-pot sequence. The extension of this methodology
was the one-pot synthesis of substituted oxazoles and thiazoles.
Sparks, R. B. and Combs, A. P. [15] reported a synthesis of 2,4,5-triaryl-imidazoles
directly from the keto-oxime in moderate to good yields via cyclization to the N-
hydroxyimidazole and an unprecedented in situ thermal reduction of the N-O bond upon
microwave irradiation at 200°C for 20 min. Wolkenberg, S. E. et. al. [16] reported a
simple, high-yielding synthesis of 2,4,5-trisubstituted imidazoles from 1,2-diketones and
Chapter 5
Department of Chemistry, Sardar Patel University Page | 167
aldehydes in the presence of NH4OAc. Under microwave irradiation, alkyl-, aryl-, and
heteroaryl-substituted imidazoles were formed in yields ranging from 80 to 99%.
Kidwai, M. et. al. [17] carried out the synthesis of 2,4,5-triaryl-1H-imidazoles under
microwave irradiation. The solvent free microwave assisted method seemed to be
convenient for the synthesis of 2,4,5-triaryl-1H-imidazoles. Kidwai, M. et. al. [18] also
reported elemental iodine as an efficient catalyst for the synthesis of 2,4,5-
triarylimidazoles in excellent yields via condensation of benzoin, ammonium acetate, and
aromatic aldehydes. This was a simple, one-pot, high yielding technique using cheap,
non-toxic iodine in catalytic amounts.
Siddiqui, S. A. et al. [19] reported an improved and rapid one-pot synthesis of 2,4,5-
triaryl imidazoles in a room temperature ionic liquid, which did not need any added
catalyst. The one-pot methodology resulted in excellent isolated yields in short reaction
times was characterized by simple work up procedures and efficient recovery and
recycling of the ionic liquid, which acted as a promoter. Sharma, G. V. M. et al. [20]
carried out the rapid synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted
imidazoles in high yields using ZrCl4 as an efficient catalyst at room temperature. The
reaction required longer reaction time at room temperature depending upon the nature of
different aldehydes taken.
Wang, L. –M. et. al. [21] reported Ytterbium triflate as an efficient catalyst for the
synthesis of 2,4,5-triaryl-1H-imidazoles derivatives via three-component coupling
reactions of benzil, aldehydes and ammonium acetate under mild conditions. The process
presented was operationally simple, environmentally benign and had excellent yield.
Furthermore, the catalyst could be recovered conveniently and reused for at least three
reaction cycles without any loss of activity. Heravi, M. M. et. al. [22] carried out a
synthesis of 2,4,5-triaryl-1H-imidazoles in the presence of catalytic amount of
NiCl2·6H2O supported onto acidic alumina.
Mohammadi, M. M. et. al. [23] carried out the synthesis of trisubstituted imidazoles in
high yields in the presence of potassium aluminum sulfate (alum) as a non-toxic,
reusable, inexpensive and easily available reagent at 70oC. Sangshetti, J. N. et. al. [24]
reported synthesis of 2,4,5-Triaryl-1H-imidazoles from benzoin or benzil, ammonium
acetate, and aromatic or heteroaromatic aldehydes in the presence of sodium bisulfite as
the catalyst. The presented protocol offered significant improvements for the synthesis of
Chapter 5
Department of Chemistry, Sardar Patel University Page | 168
2,4,5-triaryl-1H-imidazoles with regard to yield of products, simplicity in operation, and
cost of catalyst.
Shitole, N. V. et. al. [25] used L-Proline as an efficient organocatalyst for one-pot
synthesis of 2,4,5-triaryl substituted imidazole by the reaction of an aldehyde, a benzil
and an ammonium acetate. The short reaction time and excellent yields made this
protocol practical and economically attractive. Wang, R. et. al. [26] used Yttrium(III)
trifluoroacetate as an efficient catalyst for reaction of benzil, aldehydes, and ammonium
acetate under mild and solvent-free conditions to afford the corresponding 2,4,5-
triarylimidazoles in high yields and short reaction time. The catalyst Yttrium(III)
trifluoroacetate could be recovered conveniently and reused several times in the reaction
without significant loss of catalytic activity.
Fong, D. et. al. [27] reported a novel recyclable temperature-dependant phase-separation
catalytic system comprised of PEG1000-based functional dicationic acidic ionic liquid
and propylene glycol monomethyl ether in the synthesis of 2,4,5-trisubstituted imidazoles
via one-pot three-component condensation with various aldehydes, benzil and ammonium
acetate in reasonable to good yield of 81–95%. The reaction was accomplished
homogeneously at 70oC and the product was separated from the catalyst system by
liquid/liquid phasic-separation at room-temperature.
Nagargoje, D. et. al. [28] carried out a one pot, three-component condensation of
benzoin/benzil, an aldehyde, and ammonium acetate using diethyl bromophosphate as a
mild oxidant for the synthesis of trisubstituted imidazole compounds. Under ultrasound
irradiation, a smooth condensation occurred to get the 2,4,5-triaryl-1H-imidazole
compounds in good to excellent yields.
Chapter 5
Department of Chemistry, Sardar Patel University Page | 169
5.3 OBJECTIVES
The objectives of the present work
1. To carry out ionic liquid mediated synthesis of 2,4,5-triaryl-1H-imidazoles in
order to search for a novel mild and efficient procedure.
2. To carry out study on effect of ionic liquid and solvent on reaction under different
energy sources.
3. To carry out spectroscopic characterization of synthesized 2,4,5-triaryl-1H-
imidazoles.
The work carried out to meet the said objective is described in the following sections.
The synthesis of 2,4,5-triaryl-1H-imidazoles using conventional energy sources and
microwave irradiation are correspondingly covered in section 5a and 5b. The
spectroscopic characterization is dealt with in section 5c with spectral data of all
synthesized 2,4,5-triaryl-1H-imidazoles, some selected spectra are also put on view in the
same section.
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Department of Chemistry, Sardar Patel University Page | 170
5.4 RESULT AND DISCUSSION
The synthesis of 2,4,5-triaryl-1H-imidazoles 4 (Scheme 5.4a.1) was carried out by one-
pot reaction of benzil 1, various aldehydes 2 and ammonium acetate 3 in presence of
carboxy functionalized ionic liquid [cmmim][HSO4] under conventional thermal heating
and under microwave irradiation in absence of any added catalyst. The most optimum
reaction condition and the role of ionic liquid to accelerate the reaction are discussed in
this section.
5.4.1 Reaction optimization under conventional method
Table 5.1 Optimization for the synthesis of 2,4,5-triaryl-1H-imidazole in
[cmmim][HSO4] for the model reaction of 4a
Entry CatalystAmmount of
Catalyst (mg)Solvent Temp.(
oC)
Time
(h)
Yield
(%)
1 [cmmim][HSO4] 400 - 70oC 4 34
2 [cmmim][HSO4] 100 EtOH Reflux 3 58
3 [cmmim][HSO4] 200 EtOH Reflux 3 78
4 [cmmim][HSO4] 300 EtOH Reflux 1.5 92
5 [cmmim][HSO4] 400 EtOH Reflux 1.5 89
6 No catalyst 0 EtOH Reflux 6 -
aAll the reactions were monitored to completion using TLC
bYield after crystallization of 4a.
Chapter 5
Department of Chemistry, Sardar Patel University Page | 171
Table 5.2 Effect of solvent on the synthesis of 2,4,5-triaryl-1H-imidazoles using 300
mg [cmmim][HSO4] as a catalyst for preparation of 4a.
Entry Solvent Temp. (oC) Time (h)a Yield (%)b
1 EtOH Reflux 1.5 91
2 MeOH Reflux 1.5 88
3 H2O Reflux 3 76
4 CH2Cl2 Reflux 3 60
5 CH3CN Reflux 3 65
aAll the reactions were monitored to completion using TLC
bYield after crystallization of 4a.
By taking carboxy functionalized ionic liquid, [cmmim][HSO4] as the catalyst, the one-
pot condensation of benzil (10 mmol), benzaldehyde (10 mmol) and ammonium acetate
(25 mmol) in ethanol was carried out. When reaction was carried out alone in carboxy
functionalized ionic liquid [cmmim][HSO4] (400 mg), the reaction proceeded with
comparatively low yield (Entry 1, Table 5.1). This may be due to low solvation capacity
of ionic liquid and hence reaction becomes non-homogeneous. The use of ethanol along
with ionic liquid increased the yield of the reaction. As the amount of ionic liquid
increased, the yield was increased up to 91% using 300 mg of [cmmim][HSO4] (Entry 4,
Table 5.1). It was noticed that there was no any significant change observed in reaction
time and yield by increasing the amount of ionic liquid [cmmim][HSO4] beyond 300 mg.
Same reaction was carried out by taking 400 mg ionic liquid in presence of ethanol as co-
solvent but no significant change in yield was observed (Entry 5, Table 5.1). No
significant formation of the product was observed, when reaction was carried out by
taking ethanol as the only solvent without ionic liquid (Entry 6, Table 5.1). Optimization
of the reaction condition was continued by employing 300 mg [cmmim][HSO4] in a
variety of solvent (Table 5.2). Ionic liquid [cmmim][HSO4] (300 mg) in ethanol was
found to be best optimization reaction condition for the formation of 2,4,5-triaryl-1H-
imidazoles.
Chapter 5
Department of Chemistry, Sardar Patel University Page | 172
5.4.1.1 Reaction characterization data for the synthesis of 2,4,5-triaryl-1H-
imidazoles
Based on above optimization, a number of 2,4,5-triaryl-1H-imidazoles were successfully
synthesized using 300 mg IL in ethanol at refluxing temperature from a variety of
aldehydes. It was noticed that aldehydes having electron donating/withdrawing
substituents reacted in short reaction time to afford the 2,4,5-triaryl-1H-imimdazoles in
very good to excellent yields. The various aldehydes employed and the characteristic data
for them are shown in Table 5.4a.3.
Table 5.3 Characteristic data for all synthesized 2,4,5-triaryl-1H-imidazoles
derivatives varying aldehydes
Compound RReaction time
a
(h) Yield (%)b
4a C6H5 1.5 91
4b 4-NO2C6H4 2.5 89
4c 4-Cl C6H4 2 91
4d 4-OCH3 C6H4 1.5 90
4e 4-OH C6H4 1.5 93
4f 4-OH-3-OCH3 C6H3 2 89
4g 4-F C6H4 2 90
4h 2-Cl C6H4 2 90
4i 3-NO2 C6H4 2.5 88
4j 2-NO2 C6H4 2.5 88aAll the reaction were run till the completion as indicated by TLC
b isolated yield after crystallization
All the reactions were monitored by TLC and proceeded till the completion of the
reaction as indicated by TLC. All the synthesized 2,4,5-triaryl-1H-imidazoles were
homogeneous on TLC and pure enough for further practical use. However, all the
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Department of Chemistry, Sardar Patel University Page | 173
synthesized compounds were crystallized from hot ethanol and the % yield was
calculated after crystallization step. All the compounds were characterized by melting
point,1H NMR,
13C NMR spectral techniques. Additional conformation for the structures
is also obtained by IR, 13C NMR (APT) and mass spectroscopic studies for the
representative samples from the series. All the data were in agreement with the
compounds cited in the literature.
5.4.1.2 Mechanism
The IL, [cmmim][HSO4] promotes the reaction due to its inherent Bronsted acidity. The –
COOH proton of [cmmim][HSO4] is capable of bonding with carbonyl oxygen of benzil
as well as an aldehyde. The capacity of IL to form the bond with substrate may push the
reaction in forward direction. Based on this, the plausible mechanism for the reaction is
given as under (Scheme 5.4).
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Department of Chemistry, Sardar Patel University Page | 174
5.4.1.3 Experimental
All the aromatic aldehydes, benzil, ammonium acetate and solvents were of loboratory
grade and used as obtained without further purification. The reactions were performed in
50 ml round bottom flask equipped with a refluxing condenser and magnetic stirrer in a
preheated oil bath.
5.4.1.3.1. General procedure for the synthesis of 2,4,5-triaryl-1H-imidazoles
A mixture containing benzil (10 mmol), substituted aldehydes (10 mmol), ammonium
acetate (25 mmol) and [cmmim][HSO4] (30 mg) in ethanol was refluxed in a 50 ml
capacity round bottom flask. After completion of the reaction (as indicated by TLC) the
reaction mixture was diluted with water (10 ml). The solid separated was filtered through
a sintered funnel under suction, washed with water (5x3 ml) and then crystallized from
hot ethanol to afford 2,4,5-triaryl-1H-imidazoles. The aqueous filtrate was heated at 80oC
under reduced pressure (10 mm Hg) for 5 h to leave behind the IL in neat complete
recovery, pure enough to use in next run without further purification. The recovered ionic
liquid was found to be equally effective for at least four runs in the synthesis of 4a.
5.4.1.3.2 Recovery of Ionic liquid
The activity of recycled ionic liquid was studied in the model reaction of benzil,
benzaldehyde, and ammonium acetate to afford 4a. After filtration of solid product,
aqueous layer was subjected to vacuo at 80°C under reduced pressure (10 mm of Hg) for
5 h to leave behind the ionic Liquid. This recovered IL was reused in the next run without
any further purification by charging with the same substrate. As shown in Figure 5.1 the
recovered ionic liqud can be reused at least four times without significant decrease in the
yields.
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Department of Chemistry, Sardar Patel University Page | 175
1 2 3 4
0
20
40
60
80
898990909091 9191
%Yield
Reaction cycle
Conventional
Microwave irradiation
91
Figure 5.1 Recyclability of [cmmim][HSO4] in model reaction of benzaldehyde, benzil
and ammonium acetate to afford 4a.
Chapter 5
Department of Chemistry, Sardar Patel University Page | 176
5.4.2 Reaction optimization under microwave irradiation
The literature survey reveals that many catalysts have been employed for the synthesis of
2,4,5-triaryl imidazoles but the potentiality of microwave/ionic liquid (MW/ILs)
synergetic couple uniquely for the synthesis of substituted imidazoles has not been
explored much. Keeping in mind the literature reports, we tried the combined use of ionic
liquid and organic solvent for the synthesis of 2,4,5-triaryl-1H-imidazoles under
microwave irradiation.
Initially, the reaction of benzil (10 mmol), benzaldehyde (10 mmol), and
ammonium acetate (25 mmol) was carried out by using 300 mg [cmmim][HSO4] in
ethanol as reaction promoter with respect to different power levels of MW set-up. The
optimization data with respect to power level of microwave are given in Table 5.4.
Table 5.4 Data representing the optimization of reaction condition for synthesis of
2,4,5-triaryl-1H-imidazoles under microwave set up
Entry
Power
levels in
Watt
Reaction
time
(min)a
%
YieldPurity of product
1 140 8.0 0 Reaction not proceeded
2 210 7.0 25
Contained some impurity along with
starting materials
3 240 7.0 25
4 280 7.0 37
5 350 6.0 70
6 420 5.0 93Fine purity
7 450 5.0 92
8 490 4.0 73Impure with degraded product, more loss
of yield9 560 4.0 69
10 700 4.0 58
aAll the reactions were run till the end as indicated by TLC.
From the series of experiments for the optimization of power level in microwave,
it was found that an increase in the power level of microwave above 450 watt the product
was found to be impure with degraded products. Thus, it was found that the reaction at
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Department of Chemistry, Sardar Patel University Page | 177
power level 6 (420 Watt) provided 2,4,5-triaryl-1H-imidazoles in good yield with high
purity. This power level was chosen for further studies to synthesize imidazoles to be
covered under the present study.
5.4.2.1 Characteristic data showing the synthesis of synthesized 2,4,5-triaryl-1H-
imidazoles under microwave irradiations
All the aldehydes have proceeded in short reaction times under MW irradiation to afford
2,4.5-triaryl-1H-imidazoles in excellent yields. MW/ILs induced protocol showed the
ability to tolerate various aldehydes containing both electron donating and electron
withdrawing substituents. Characteristic data for all the synthesized 2,4,5-triaryl-1H-
imidazoles are given in Table 5.5.
Table 5.5 Characteristic data for the synthesized 2,4,5-triaryl-1H-imidazoles under
MW irradiation
Compound RReaction timea
(min) Yield (%)b
4a C6H5 5.0 93
4b 4-NO2C6H4 6.5 90
4c 4-Cl C6H4 6.0 92
4d 4-OCH3 C6H4 5.5 93
4e 4-OH C6H4 5.0 94
4f 4-OH-3-OCH3 C6H3 6.0 91
4g 4-F C6H4 5.5 92
4h 2-Cl C6H4 5.5 92
4i 3-NO2 C6H4 6.5 90
4j 2-NO2 C6H4 6.5 88aAll the reaction were run till the completion as indicated by TLC
bIsolated yield after crystallization
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Department of Chemistry, Sardar Patel University Page | 178
5.4.2.2 Mechanism
The mechanistic pathway for the reaction is expected to be same as given in section
5.4.1.2 of this chapter.
5.4.2.3 Experimental
All the chemicals were of laboratory grade and used as obtained without any further
purification. The reactions were performed in scientific microwave system (Catalyst
system ‘CATA-R’ 700 W).
5.4.2.3.1 General procedure for the synthesis of 2,4,5-triaryl-1H-imidazoles
derivatives
A mixture containing benzil (10 mmol), aldehyde (10 mmol), ammonium acetate (25
mmol), and [cmmim][HSO4] (30 mg) in ethanol was charged in a 50 ml round bottom
flask. The mixture was stirred with magnetic stirrer for few seconds to ensure reaction to
become homogeneous. Then, reaction mixture was subjected to microwave irradiation at
60% power level (CATA-R, 700 W) for appropriate time. After completion of the
reaction (as indicated by TLC) the reaction mixture was diluted with water (10 ml). The
solid separated was filtered through a sintered funnel under suction, washed with water
(5x3 ml) and then crystallized from hot ethanol to afford 2,4,5-triaryl-1H-imidazoles. The
aqueous layer was subjected to vacuo at 80oC under reduced pressure (10 mm of Hg) for
5 h to leave behind the Ionic Liquid, pure enough to use in next run without further
purification. The recovered ionic liquid was found to be equally effective for at least four
cycles in the synthesis of 4a.
5.4.2.3.2 Recyclability of ionic liquid
In this study, the recyclability of carboxy functionalized [cmmim][HSO4] ionic liquid has
been investigated by using model reaction of benzil, benzaldehyde, and ammonium
acetate to afford 4a. Since the product is insoluble in water, it was easily filtered after
reaction mixture was diluted with water. After filtration, the aqueous layer was subjected
to vacuo at 80oC under reduced pressure (10 mm of Hg) for 5 h to leave behind the Ionic
Liquid. Recovered ionic liquid was subjected to next run of the reaction by charging with
Chapter 5
Department of Chemistry, Sardar Patel University Page | 179
the model reactants. As shown in Figure 5.1, the reaction can be repeated for at least four
times without any further purification of recovered ionic liquid to yield the targeted
compound with almost comparable efficiency.
5.5 CONCLUSION
In conclusion, the conventional method is an easy and general method for the synthesis of
2,4,5-triaryl-1H-imidazoles via one-pot condensation reaction between benzil, aldehyde
and ammonium acetate in presence of catalytic amount of ionic liquid. This method
worked under mild reaction condition, produced compounds in good yields and with
nearly complete recovery of ionic liquid. The activity of ionic liquid persisted for next
four runs with same efficiency with the model reaction. The synergic effect of
microwave-ionic liquid couple provides an easy and green route to synthesize 2,4,5-
triaryl-1H-imidazoles. The milder reaction conditions, absence of additional catalyst,
high reaction rates, excellent yields, easy work up procedures and MW-IL strategy make
this procedure more advantageous over the conventional acid/base catalyzed thermal
processes and its environment friendly with minimal or no waste.
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Department of Chemistry, Sardar Patel University Page | 180
5.6 CHARACTERIZATION
All the compounds were characterized by 1H NMR and 13C NMR (APT) techniques.
Additional confirmation was obtained by IR and mass spectrometry of some
representative compounds. 1H NMR and 13C NMR (APT) were recorded on BRUKER
AVANCE 400 MHz instrument using CDCl3 as a solvent. GC-MS data were recorded on
Perkin Elmer, Autosystem XL GC+. FT IR spectra were recorded on Shimadzu FT-IR-
S8401 spectrophotometer using KBr. The representative spectra are included at the end
of the section for perusal.1H NMR spectra for compound 4d and 4e are given in Figures
5.2 and 5.7 respectively. 13C NMR spectra for same compounds are described in Figures
5.3 and 5.8 respectively.13C NMR (APT) spectra for same compounds are described in
Figures 5.4 and 5.9 respectively. The mass spectra of same compounds are shown in
Figures 5.5 and 5.10 respectively. The infrared spectra for 4d and 4e are given in Figures
5.6 and 5.11 respectively. The other parameters like solubility and melting points were
checked by the standard methods and compared with the reported one if available from
the literature.
The1H NMR data is interpreted in terms of number of protons, splitting pattern and their
relative δ values. The 13C NMR APT experiments are also conducted for the additional
conformation of the structures. Addition conformation for the structures is also obtained
by mass spectrometric and by infrared spectroscopic studies for the representative
samples from the series. The molecular structures and characterization data for all
synthesized 2,4,5-triaryl-1H-imidazoles are given below in tabular form.
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Spectral Data: 4a
2,4,5-triphenyl-1H-imidazole (4a)
Molecular Formula C21H16N2
Molecular Weight (gm/mol) 296.37
Melting Point (oC) 274-276
1H NMR (400 MHz, DMSO-d6) : δ = 7.46–8.18 (m, 15H), 12.61 (s, 1H) 13C NMR (400 MHz, DMSO-d6) : δ = 122.1, 127.2, 128.5, 129.1, 136.5
Spectral Data: 4b
2-(4-nitrophenyl)-4,5-diphenyl-1H-imidazole (4b)
Molecular Formula C21H15N3O2
Molecular Weight (gm/mol) 341.36
Melting Point (oC) 231-233
1H NMR (400 MHz, DMSO-d6) : δ = 7.25–7.57 (m, 10H), 7.78 (d, J=9 Hz, 2H), 8.50 (d,
J=9 Hz, 2H), 12.59 (s, 1H)
13C NMR : δ = 122.7, 124.2 127.3, 127.6, 132.8, 146.7, 160.8
Spectral Data: 4c
2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazole
(4c)
Molecular Formula C21H15ClN2
Molecular Weight (gm/mol) 330.81
Melting Point (oC) 262
1H NMR (400 MHz, DMSO-d6) : δ = 7.47-7.55 (m, 10H), 7.62-7.64 (d, J=8 Hz, 2H),
8.04-8.06 (d, J=8.1 Hz, 2H), 12.47 (s, 1H)
13C NMR (400 MHz, DMSO-d6) : δ = 126.90, 127.89, 128.43, 131.71, 134.23, 135.81,
161.52
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Spectral Data: 4d
2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazole
(4d)
Molecular Formula C22H18N2O
Molecular Weight (gm/mol) 326.39
Melting Point (oC) 234-236
1H NMR (400 MHz, DMSO-d6) : δ = 3.85 (s, 3H), 7.03-7.06 (d, J= 8 Hz, 2H), 7.23-7.52
(m, 10H), 8.01-8.04 (d, J= 8 Hz, 2H), 12.52 (s, 1H)
13C NMR (400 MHz, DMSO-d6) : δ = 55.16, 114.05, 123.09, 126.39, 126.66, 127.02,
127.37, 131.24, 135.26, 136.73, 145.59, 159.38
13C NMR (APT) : Up Peaks: 123.09, 145.59, 135.26, 136.73 159.38
Down Peaks: 55.16, 114.05, 126.39, 126.66, 127.02, 127.37, 131.24
IR (KBr): 1216, 1636, 2465, 2893, 3428
MS Data: m/z = 326 [M+]
Spectral Data: 4e
2-(4-hydroxyphenyl)-4,5-diphenyl-1H-imidazole
(4e)
Molecular Formula C21H16N2O
Molecular Weight (gm/mol) 312.36
Melting Point (oC) 198
1H NMR (400 MHz, DMSO-d6) : δ = 4.12 (s, 1H), 6.84-6.87 (d, J= 8 Hz, 2H), 7.18-7.55
(m, 10H), 7.89-7.92 (d, J= 8 Hz, 2H), 12.42 (s, 1H)
13C NMR (400 MHz, DMSO-d6) : δ = 115.37, 121.59, 127.00, 127.48,131.26, 136.55,
144.7, 159.2
13C NMR (APT): Up Peaks: 121.59, 131.26, 136.55, 144.70, 159.20
Down Peaks: 115.37, 127.00, 127.48, 128.57
IR (KBr): 1216, 1638, 2465, 2998, 3432, 3596
MS Data: m/z = 312 [M+]
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Spectral Data: 4f
2-(4-hydroxy-3- methoxyphenyl)-4,5-diphenyl-
1H-imidazole (4f)
Molecular Formula C22H18N2O2
Molecular Weight (gm/mol) 342.39
Melting Point (oC) 191
1H NMR (400 MHz, DMSO-d6) : δ = 3.85 (s, 3H), 6.90–6.96 (d, J= 8.2 Hz, 1H), 7.21–
7.29 (m, 5H), 7.32–7.37 (d, J= 8.1 Hz, 1H), 7.48–7.50 (m, 5H), 7.65–7.72 (d, J=8 Hz,
1H), 12.52 (s, 1H)
13C NMR (400 MHz, DMSO-d6) : δ = 55.1, 108.5, 114.6, 118.1, 121.1, 126.2, 127.3,
127.5, 132.3, 146.3, 146.8
Spectral Data: 4g
2-(4-fluorophenyl)-4,5-diphenyl-1H-imidazole (4g)
Molecular Formula C21H15FN2
Molecular Weight (gm/mol) 314.36
Melting Point (oC) 313-315
1H NMR (400 MHz, DMSO-d6): δ = 7.43-7.52 (m, 10H), 7.59-7.64 (d, J=8 Hz, 2H),
7.98-8.00 (d, J=8.1 Hz, 2H), 12.49 (s, 1H)
13C NMR (400 MHz, DMSO-d6) : δ = 114.32, 127.45, 128.43, 131.21, 135.74, 147.87,
159.20
Spectral Data: 4h
2-(2-chlorophenyl)-4,5-diphenyl-1H-imidazole (4h)
Molecular Formula C21H15ClN2
Molecular Weight (gm/mol) 330.81
Melting Point (oC) 270-271
1H NMR (400 MHz, DMSO-d6): δ = 7.37–7.47 (m, 10H), 7.55–7.59 (dd, J=9 Hz, 1H),
7.67–7.69 (d, J=8 Hz, 2H), 8.12–8.15 (dd, J=8.79 Hz, 1H), 12.5 (s, 1H)
13C NMR (400 MHz, DMSO-d6) : δ = 125.4, 125.6, 126.5, 126.9, 127.2, 128.4, 128.6,
128.8, 129.6, 130.1, 130.5, 142.2
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Spectral Data: 4i
2-(3-nitrophenyl)-4,5-diphenyl-1H-imidazole (4i)
Molecular Formula C21H15N3O2
Molecular Weight (gm/mol) 341.36
Melting Point (oC)
1H NMR (400 MHz, DMSO-d6): δ = 7.62-7.68 (m, 10H), 7.79-7.82(dd, J=7.9 Hz, 1H),
8.34-8.37 (dd, J=7.9 Hz), 8.62-8.69 (d, 2H), 12.58 (s,1H)
13C NMR (400 MHz, DMSO-d6) : δ = 123.54, 127.54, 129.43, 131.67, 133.98, 136.34,
146.65, 160.03
Spectral Data: 4j
2-(2-nitrophenyl)-4,5-diphenyl-1H-imidazole (4j)
Molecular Formula C21H15N3O2
Molecular Weight (gm/mol) 341.36
Melting Point (oC)
1H NMR (400 MHz, DMSO-d6): δ = 7.60-7.67 (m, 10H), 7.74-7.76 (t, J=7.9 Hz, 1H),
7.95-8.08 (d, 3H), 12.61 (s, 1H)
13C NMR (400 MHz, DMSO-d6) : δ = 123.21, 126.51, 127.52, 129.32, 133.25, 135.23,
138.20, 147.14, 150.55
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Figure 5.21H NMR spectrum of compound 4d
Figure 5.313C NMR spectrum of compound 4d
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Figure 5.413C NMR (APT) spectrum of compound 4d
Figure 5.5 Mass spectrum of compound 4d
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Figure 5.6 Infrared spectrum of compound 4d
Figure 5.71H NMR spectrum of compound 4e
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Figure 5.813C NMR spectrum of compound 4e
Figure 5.913C NMR (APT) spectrum of compound 4e
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Figure 5.10 Mass spectrum of compound 4e
Figure 5.11 IR spectrum of compound 4e
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