Benzethonium Chloride Catalyzed One Pot Synthesis of 2,4,5-trisubstituted Imidazoles and 1,2,4,5-tetrasubstituted Imidazoles in Aqueous Ethanol as a Green Solvent

Article abstract of DOI:10.13005/ojc/340642

A simple, efficient procedure has been developed using N-cationic surfactant namely Benzethonium chloride (BzthCl, 10 mol%) as novel catalyst for the synthesis of 2,4,5-trisubstituted imidazoles by condensation of aldehyde, ammonium acetate and benzil usi

Full text of DOI:10.13005/ojc/340642

ISSN: 0970-020 X
CODEN: OJCHEG
2018, Vol. 34, No.(6):
Pg. 3004-3015
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Access, Peer Reviewed Research Journal
www.orientjchem.org
Benzethonium Chloride Catalyzed One Pot Synthesis of
2,4,5-trisubstituted Imidazoles and 1,2,4,5-tetrasubstituted
Imidazoles in Aqueous Ethanol as a Green Solvent
D. PARTHIBAN1 and R. JOEL KARUNAKARAN2*
1Department of Chemistry, Arignar Anna Govt Arts College, Cheyyar, India-604407.
2Department of Chemistry, Madras Christian College, Tambaram, Chennai, India-600059.
*Corresponding author E-mail: rjkmcc@yahoo.com
http://dx.doi.org/10.13005/ojc/340642
Received: August 23, 2018; Accepted: November 04, 2018)
ABSTRACT
A simple, efficient procedure has been developed using N-cationic surfactant namely
Benzethonium chloride (BzthCl, 10 mol%) as novel catalyst for the synthesis of 2,4,5-trisubstituted
imidazoles by condensation of aldehyde, ammonium acetate and benzil using EtOH-H2O (1:1) as
0
a green solvent at 70 C. Same reaction condition was applied successfully to demonstrate the
synthesis of various 1,2,4,5-tetrasubstitued imidazoles using aromatic amine as fourth component.
The use of benzethonium chloride as a catalyst with dual functionality as surfactant and ionic liquid
catalyst is the main novelty of described method. The significant feature of this greener protocol
includes high product yields, procedural simplicity and lesser reaction time.
Keywords: 2,4,5-trisubstituted imidazoles, Multicomponent reaction, Benzethonium chloride,
N-cationic surfactant.
INTRODUCTION
they serve as versatile tools for construction of
biologically and pharmaceutically active heterocyclic
motifs.1,2 The imidazole derivatives exhibit a broad
spectrum of biological and pharmacological
activities such as antifungal,3 analgesic and
anti-inflammatory,4 bactericidal,5 antitumor,6
herbicidal,7 anticancer,8 These compounds also
show inhibition against few enzymes such as
heme oxygenase-1, HMG-CoA reductase, fatty
acid amide hydrolase.9 Cimetidine10 -a histamine
H2 receptor antagonist that inhibits stomach acid
production, Omeprazole11-a proton pump inhibitor
used for treatment of gastrophageous reflux disease,
Multi-component reactions (MCRs) play
a significant role in modern organic synthesis
because they are one-pot organic transformations
that assemble three or more substrates into single
desired product. MCRs have been receiving
overwhelming response from scientific research
communities for well over time owing to their
synthetic efficiency of organic transformation,
atom economy, environmentally benign process,
lower energy consumption, minimal by-product
formation and procedural simplicity. Moreover
This is an
Open Access article licensed under a Creative Commons license: Attribution 4.0 International (CC- BY).
Published by Oriental Scientific Publishing Company © 2018

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KARUNAKARAN et al., Orient. J. Chem., Vol. 34(6), 3004-3015 (2018)
Trifenagre12 -a potent arachidonate cyclooxygenase
inhibitor, Eprosartan13-an angiotensin II receptor
antagonist,arefewto exemplifythepharmacologically
active synthetic imidazoles. (Fig.1) Imidazole
derivatives are used as task specific ionic liquids
(TSIL), which in turn used as catalyst, green solvents
since TSIL possess low vapour pressure and
temperature stability.14 The photosensitive imidazole
compounds are used in photography.15
by using surfactant system for catalytic organic
transformations. Surfactant system has received
considerable interest as eco-friendly catalysts
and reagents in organic transformations, because
surfactant systems are characterized by their high
capacity for reactants solubilisation, which enables
them as medium and catalyst for organic, inorganic,
polar, and non-polar reactant. They also possess
large liquid-liquid interfacial area which allows
faster diffusion between phases.28 electrostatic and
hydrophobic interactions of surfactants with reactants
has great influence on reactions progress.29
N
NC
H
N
N
HN
S
S
N
H
N
H
N
N
O
O
O
The use of quaternary ammonium salts
such as tributylhexadecylphosphonium bromide,30
tetrabutylammonium bromide31 as a catalyst for
synthesis of tri-, tetra- substituted imidazoles has
been reported recently in the literature. Surfactant
property of various quaternary ammonium salts by
micellar formation has been well documented in the
literature.32, 33, 34, 35. Benzethonium chloride (BzthCl)
is a synthetic quaternary ammonium salt belongs
to the class of bi-tailed N-cationic surfactants, and
it is chemically known as N-benzyl-N,N-dimethyl-2-
(2-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)ethoxy)
ethanaminium chloride. (Fig. 2) This compound has
surfactant and anti-infective properties.36 It is used
in topical antiseptic, mouthwashes, deodorants,
anti-itching ointments, cosmetics.To the best of our
knowledge, benzethonium chloride has not been
used earlier as a catalyst in organic synthesis.
Omeprazole
(a proton pump inhibitor)
Cimetidine
(an anti-ulcerative agent)
HOOC
H
N
COOH
N
N
N
S
O
N
Eprosartan
(a vasodiltor agent)
Trifenagrel
(an arachidonate COX inhibitor)
Fig. 1. Biologically active imidazole compounds
Owing to the wide applicability of imidazole
derivatives in the laboratories, industries and
pharmaceutical ventures, many methods have been
developed for the synthesis of 2,4,5-trisubstituted
imidazoles and 1,2,4,5-tetrasubstituted imidazoles
by employing various catalyst like SiO2:SnO2
nanoparticles,16 Silica chloride (SiO2–Cl),17, SBA-Pr-
SO3H,18 N-acetyl glycine (NAG),19 [bmim]3[GdCl6],20
Fe2O3/ChCl-Urea eutectic mixture,21 10-molybdo-
2-vanadophosphoric acid/ KSF montmorillonite,22
PivOH/NH4OAc23, CuFe2O4 Magnetic nanoparticles,24
H3PW12O40.23H2O/PS@Si,25 [Dsim]HSO4,26
silica-supported SbCl3.27 However, most of the
methods employed for triaryl imidzoles synthesis
have drawbacks such as the use of strongly acidic
conditions, the use of protic acids, prolonged reaction
times, high temperature, high catalyst loading,
low-to-moderate yields, volatile organic solvents and
toxic transition metal catalyst.
From both economical and green
chemistry point of view, design of synthetic
organic transformations should be done using
substances that exhibit little or no toxicity to the
environment and human health. EtOH-H2O(1:1)
has emerging as a promising solvent system for
organic synthesis, because it is inexpensive, stable,
less volatile and non-toxic.37 Moreover, Capello and
co-workers38 reported that ethanol–water mixtures
are ecologically safe compared to pure alcohol for
organic synthesis.
An important drawback of conventional
synthesis of trisubstituted imidazoles is that
expensive polar aprotic solvents are used in order to
solubilise organic substrates together with inorganic
compounds, thereby, high temperatures are used
to make them soluble and to get high yield of the
product; consequently, the salts accumulated in the
mixture slow down the reaction rate by poisoning
the catalyst. But this problem can be overcome
Cl
O
N
O
Fig. 2. Structure of benzethonium chloride
In continuation of our search for simple non-
hazardous methods for organic transformation39,40,41,42
especially for the synthesis of biologically important
heterocyclic organic compounds via multicomponent
,

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KARUNAKARAN et al., Orient. J. Chem., Vol. 34(6), 3004-3015 (2018)
reaction,43 herein we wish to report a facile, efficient,
and environmentally friendly procedure for the
synthesis of 2,4,5-trisubstituted imidazoles via
one-pot multi-component reaction of benzil, aromatic
aldehyde, and ammonium acetate in excellent yields
using benzethonium chloride as a catalyst in EtOH-
H2O(1:1) mixture (Scheme 1).
ether mixture). All the products were thoroughly
1
characterized by FT-IR, H-NMR, 13C-NMR, Mass
spectral analysis.
General procedure for the synthesis of 1,2,4,5-
tetrasubstituted imidazoles (Scheme 2)
The mixture of aromatic aldehyde
(10 mmol), aromatic primary amine (10 mmol),
benzil (10 mmol), ammonium acetate (10 mmol),
benzethonium chloride (10 mole %) and 10 ml
of EtOH:H2O (1:1) solvent mixture was taken in
100 ml round bottom flask, heated and maintained
at 70°C with stirring for appropriate time and the
progress of the reaction was monitored byTLC.After
completion of the reaction as indicated by TLC, the
reaction mixture was cooled to room temperature.
The reaction volume was reduced and diluted with
10.0 mL of water. The product was extracted with
2x10 mL of ethyl acetate. The organic layer was
dried by MgSO4.The organic layer was concentrated
under vacuum, and the product was purified either
by recrystallizing in hot ethanol or by column
chromatography on silica gel (60-120 Mesh, 20%
EtOAc/Petroleum ether mixture). All the products
EXPERIMENTAL
Various aromatic aldehyde, benzil,
ammonium acetate and other chemicals were
purchased from SD fine, and Avra chemicals.
They were used without further purification. Silica
gel (Column grade) was purchased from SD fine
chemicals. The solvents were purified as per the
standard procedure reported in literature. Melting
points were measured in open capillary tubes on
DeepVision melting point apparatus and are reported
uncorrected.Thin layer chromatography was carried
out on pre-coated sheets of silica gel containing
60 F254 indicator (Merck, Darmstadt, Germany).
Column chromatography was performed with silica
gel (60–120 mesh; SD Fine). 1H-NMR spectra were
recorded on 500MHz Brucker Advance instrument in
DMSO-d6 solvent. 13C-NMR spectra were recorded
on 100 MHz Brucker Advance instrument in DMSO-d6
solvent, chemical shifts (δ) are expressed in ppm
value relative to the internal standard TMS. FT-IR of
all the samples was recorded on Brucker alpha-P
spectrophotometer.Mass spectra were recorded on
Jeol GC Mate II mass spectrometer.
1
were thoroughly characterized by FT-IR, H-NMR,
13C-NMR, Mass spectral analysis.
RESULTS AND DISCUSSION
Initially, we investigated the three-
component condensation reaction of benzil
(10 mmol), benzaldehyde (10 mmol), and ammonium
acetate (20 mmol) in 10 mL of EtOH in the absence
of benzethonium chloride at room temperature for
about 8 hours.Only trace amount of the corresponding
product was obtained (Table 1, entry 1). Then, we
carried out the reaction under similar conditions
in the presence of 10 mol% of benzethonium
chloride. Surprisingly, the product was obtained in
21% yield. This observation clearly indicates that,
if the reaction conditions such solvent, reaction
time, temperature and catalyst load are properly
optimized, benzethonium chloride can be used as an
effective catalyst for this condensation reaction.
General procedure for the synthesis of 2,4,5-
trisubstituted imidazoles (Scheme 1)
The mixture of aromatic aldehyde
(10 mmol), benzil (10 mmol), ammonium acetate
(20 mmol), benzethonium chloride (10 mole %) and
10 ml of EtOH:H2O(1:1) solvent mixture was taken
in 100 ml round bottom flask, heated and maintained
at 70°C with stirring for appropriate time and the
progress of the reaction was monitored byTLC.After
completion of the reaction as indicated by TLC, the
reaction mixture was cooled to room temperature.
The reaction mixture was diluted with 10.0 mL of
water. The product was extracted with 2x10 mL of
ethyl acetate.The organic layer was dried by MgSO4
The organic layer was concentrated under vacuum,
and the product was purified either by recrystallizing
in hot ethanol or by column chromatography on
silica gel (60-120 Mesh, 20% EtOAc/Petroleum
The reaction temperature is considered as
important parameter for determining the feasibility
of chemical reactions, the reaction temperature

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KARUNAKARAN et al., Orient. J. Chem., Vol. 34(6), 3004-3015 (2018)
is particularly important with respect to one pot
MCR reaction because very high temperatures
frequently lead to formation of numerous unwanted
side products. So, in order to study the influence of
temperature on product yield, we have performed
cyclocondensation reaction by varying the
temperature from 400C to 1000C by increment of
100C, highest yield of 83% was obtained at 700C,
and the temperature beyond 700C, there was no
significant change in product yield (Table 1).
H
O
H
N
X
O
O
Benzethonium chloride
EtOH:H2O(1:1), 70 0
+
+
NH4+OAc-
C
N
X
X = H, 4-Br, 4-Cl, 2-OH, 4-OH, 4-CH3, 4-OCH3
Scheme 1. Benzethonium chloride catalyzed synthesis of 2,4,5-trisubstituted imidazoles
Table 1: Effect of temperature on synthesis of
trisubstituted imidazole
of benzethonium chloride was superior to other
quaternary ammonium salt.Thus, the best result was
obtained for benzethonium chloride. (Table 3, entry 4).
This observation is due to the fact that benzethonium
chloride contains two strong hydrophobic tails
(R’=1-(2-ethoxyethoxy)-4-(2,4,4-trimethylpentan-2-
yl)phenyl, R”= benzyl), (Fig. 1), the hydrophobicity
inside the miceller core of benzethonium chloride
is higher when compared to other quaternary
ammonium salt such as benzyltriethylammonium
chloride (TEBAC), benzyltripropylammonium
chloride (TPBAC), benzyltributylammonium chloride
(TBAC) etc., and consequently it gives higher
product yield.( entry 4 of Table 3).
Entry
Temp (0C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
r.t
40
50
60
70
80
90
100
8
8
8
21
32
38
51
83
83
82
81
6
1.5
1.5
1.5
1.5
To study the effect of solvent, the reaction
Table 2: Effect of solvent on synthesis of
trisubstituted imidazoles#
was carried out at 700C using benzethonium chloride
as catalyst in different solvent such as acetone
ethanol, methanol and acetonitrile etc. we found
that, in non-polar solvents such as dichloromethane,
acetone, and acetonitrile, the products were obtained
in poor yield (Table 2, entry 2, 5, 6). However, in
polar solvents like ethanol, methanol the product was
obtained in moderate yield in comparison with non-
polar solvents (Table 2, entry 3, 4). When the reaction
was performed in water, 39% product was formed.
Then, we found that ethanol-water (1:1) mixture
seemed to be most appropriate reaction medium,
and gives 95% of product yield. (Table 2; entry 7).
Entry
Solvent
Temp (0C)
Yield (%)
1
2
3
4
5
6
7
8
9
Water
Acetone
Methanol
70
70
70
70
70
70
70
70
70
70
70
39
33
53
82
29
27
95
71
82
94
93
Ethanol
Dichloromethane
Acetonitrile
Ethanol-water(1:1)a
Ethanol-water(1:3)
Ethanol-water(3:1)
To demonstrate the effect of surfactant/
quaternary ammonium salt as catalyst, various
commercially available cationic, anionic and
non-ionic surfactants were employed for the
cyclocondensation reaction of benzaldehyde, benzil,
and ammonium acetate in ethanol-water (1:1, v/v)
system and the obtained results are summarized in
Table 3. It is observed that for all other quaternary
ammonium salt/surfactant used as catalysts, very
low conversion of 2,4,5-trisubstituted imidazoles
was achieved. It was found that the catalytic ability
10 Ethanol-water(1:1)b
11 Ethanol-water(1:1)c
#The reaction was conducted with benzil (10 mmol),
benzaldehyde (10 mmol) and ammonium acetate
(20 mmol) using 10 mol% of benzethonium chloride
catalyst at 700C.
a catalytst (10 mol %)
b catalytst (15 mol %)
c catalytst (20 mol %)

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KARUNAKARAN et al., Orient. J. Chem., Vol. 34(6), 3004-3015 (2018)
Table 3: Effect of catalyst on synthesis of trisubstituted imidazoles##
Entry Surfactant/Quaternary ammonium salt
Temp (0C) Yield (%)
1
2
3
4
5
6
7
Benzyltriethylammonium chloride(TEBAC)
Benzyltripropylammonium chloride(TPBAC)
Benzyltributylammonium chloride (TBAC)
Benzethonium chloride (BzthCl)
sodiumdodecyl sulfate (SDS)
70
70
70
70
70
70
70
13
21
45
95
29
31
37
Cetyltrimethylammonium bromide(TMCAB)
Triton X-100
## The reaction was conducted with benzil (10 mmol), benzaldehyde (10 mmol) and
ammonium acetate (20 mmol) using different catalyst at 700C
Table 4: Benzethonium chloride catalyzed synthesis of 2,4,5-trisubstituted imidazoles
Entry
Aldehyde
Product
Time(min.)
Yield(%)
Melting point (0C)
Found Lit
O
H
N
a
b
45
60
95
273-275
270–27217
H
N
H
O
89
300-302
302–30422
H
N
H
O
N
NO2
NO2
Br
H
N
c
d
e
45
45
60
85
94
81
248-250
263-265
200-201
250–25222
260–26517
200–20217
Br
N
H
O
H
N
Cl
Cl
N
H
O
H
H
N
N
HO
HO
H
N
O
OH
f
60
60
87
89
238-240
229–231
235–23717
232–23422
OH
N
H
O
H
N
g
CH3
CH3
N
H
O
H
N
220-22325
230–23217
OCH3
h
i
60
45
90
91
219-221
231-233
OCH3
N
H
CH3
CH3
O
H
H
N
CH3
CH3
N
230–23222
202–20422
255–25722
H
j
k
l
90
75
60
79
83
86
233–234
200–202
257-259
N
N
N
H
O
O
N
H
N
O
S
N
O
S
H
O
H
N
N
H

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KARUNAKARAN et al., Orient. J. Chem., Vol. 34(6), 3004-3015 (2018)
In order to study the practical applicability
of this condensation reaction, a series of 2,4,5-
trisubstituted imidazoles were synthesized from
benzil, ammonium acetate with various aldehydes,
in the presence of 10 mol % benzethonium
chloride in EtOH-water(1:1) mixture at reflux
temperature (Table 4).An array of aromatic aldehyde
was found to be suitable reactant to form the
corresponding trisubstituted imidazoles in high
yields.Aromatic aldehydes having electron-donating
and withdrawing groups were well tolerated
(Table 4, entries a-e). Interestingly, heterocyclic
aldehyde such as furaldehyde, thiophene
carboxaldehyde were also very good candidates
for the reaction, providing highly substituted
imidazoles in excellent yields (Table 4, entry j,k,l.)
Alkyl aldehyde, such as isobutyraldehyde was also
underwent reaction smoothly with 91% product yield.
(Table 4, entry i).
Encouraged by the success of a three
component reaction, the attention was turned to
evaluate feasibility of our protocol for the synthesis
of tetrasubstituted imidazole derivatives by utilizing
four component reactions under identical reaction
conditions with the addition of a stoichiometric ratio
of various aromatic amines as the fourth component
(Scheme 2).
Y
H
O
NH2
O
O
N
N
X
Benzethonium chloride
EtOH:H2O(1:1), 70 0
NH4+OAc-
+
+
+
C
Y
X
X= H, 4-OH, 4-CH3, 3-NO2
Y= H, 2-Cl, 4-CH3, 4-OCH3, 4-OH
Scheme 2. Benzethonium chloride catalyzed Synthesis of 1,2,4,5-trisubstituted imidazoles
To our surprise, the reaction underwent
smoothly irrespective of nature, electronic effect of
the substituent on the aromatic rings, and obtained
the desired tetrasubstituted imidazole compounds
in excellent yields. (Table 5, entry a-h). From these
results, it is clear that aniline with electron donating
alkyl and alkoxy group such as toluene, anisidine
(Table 5, entry e, g, h) reacted smoothly and resulted
in high yield.When aniline with electron withdrawing
group such as chloroaniline, nitroaniline were used
they reaction rate is decreased slightly.
Spectral data for selected compounds
2,4,5-Triphenyl-1H-imidazole (Table 4, Entry a)
White solid; Yield: 95%; m.p: 273–2750C;
IR (neat, cm-1) : 3216 (N-H), 3058(C-H, Ar), 1628
(C=N),1588 (C=C); 1H NMR (400 MHz, DMSO-d6):
δ 12.70 (1H ,s, N-H), 8.10 (2H,d, Ar-H), 7.57–7.23
(m, 13H, Ar-H); 13C NMR (100 MHz, DMSO-d6): δ
145.96, 137.56, 135.63, 131.54, 130.80, 129.16,
128.76, 127.53, 126.99, 125.65; Mass (m/z): Calcd
for C21H16N2: 296.13; Found: 294.05.
2-(3-nitrophenyl)-4,5-diphenyl-1H-imidazole(Table
4, Entry b)
All the synthesized compounds were
characterized by FT-IR, 1H NMR, 13C NMR, and Mass
spectral analysis.IR spectra of the compounds show
characteristic absorption band at 3207-3261 cm-1 for
N-H stretch, 3010-3072 cm-1 for aromatic C-H group,
1628-1678 cm-1 for C=N group, around 1580 for C=C
Yellow solid; Yield: 89%; M.P: 300-3020C;
IR (neat, cm-1) : 3261 (N-H), 3061(C-H, Ar), 1678
(C=N),1580 (C=C); 1H NMR (400 MHz, DMSO-d6):
δ 12.64 (1H ,s, NH), 8.97 (1H,s, Ar-H/nitrophenyl),
8.57 (1H,d, Ar-H/nitrophenyl), 8.22 (1H,d, Ar-H/
nitrophenyl), 7.80 (1H,t, Ar-H/nitrophenyl) 7.56–7.31
(m, 10H, Ar-H); 13C NMR (100 MHz, DMSO-d6): δ
148.75, 143.89, 132.33, 131.77, 130.81, 128.90
128.28, 127.83, 122.95, 119.97; Mass (m/z): Calcd
for C21H15N3O2:341.36, Found 340.76.
1
groups. The H NMR spectrum of all compounds
shows characteristic peaks at 7.10-8.97 ppm for
aromatic protons of all the 2,4,5-trisubstituted
imidazoles and 1,2,4,5-tetrasubstituted imidazoles.
The N-H proton appeared as a singl et al., 12.50
ppm in all the spectra. The other signals and peaks
1
of the IR and H NMR are in complete agreement
with the assigned structures. 13C NMR exhibited
peaks characteristic for the compounds. The mass
spectra of the compounds displayed a molecular ion
peak at m/z values, which corresponds well with the
theoretical value.
2-isopropyl-4,5-diphenyl-1H-imidazole (Table 4, Entry i)
Pale yellow solid; Yield: 91%; m.p: 231-
2330C; IR (neat, cm-1) : 3221 (N-H), 3031 (C-H, Ar),
1686(C=N),1594(C=C);1HNMR(400MHz, DMSO-d6): δ
11.93 (1H ,s, NH), 7.65-7.39 (10H,m, Ar-H), 3.04 (1H,

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KARUNAKARAN et al., Orient. J. Chem., Vol. 34(6), 3004-3015 (2018)
m,-CH), 1.32(6H, d, two CH3); 13C NMR (100 MHz, DMSO-
d6): δ 153.56, 136.24, 135.42, 132.72, 132.12, 130.07,
129.68,129.00,128.52,127.48,126.53,28.23,22.16;Mass
(m/z): Calcd for C18H18N2:262.35, Found: 261.85
Table 5: Benzethonium chloride catalyzed synthesis of 1,2,4,5-tetrasubstituted
imidazoles
Entry
a
X
H
Y
H
Product
Time(min)
70
Yield (%)
94
N
N
Cl
N
b
c
d
H
2-Cl
2-Cl
90
60
75
91
95
90
N
Cl
N
N
4-OH
4-OH
OH
CH3
N
4-CH3
OH
N
OCH3
N
N
OH
e
f
4-OH
4-OCH3
H
80
90
89
87
3-NO2
N
N
NO2
Cl
N
N
g
h
3-NO2
4-CH3
2-Cl
90
75
85
88
NO2
OH
4-OH
N
CH3
N
4-(1-(2-chlorophenyl)-4,5-diphenyl-1H-imidazol-
2-yl)phenol (Table 5,Entry c)
134.79, 132.29, 131.16, 130.08, 129.03, 128.47,
127.31, 126.69, 121.59, 115.55; Mass (m/z): Calcd
for C27H19N2OCl: 422.12, Found: 422.16.
White solid; Yield: 95%; IR (neat, cm-1):
3430 (O-H, phenolic), 3062 (C–H aromatic), 1661
(C=N), 1533 (C=C, aromatic); 1H NMR (400 MHz,
DMSO-d6): δ 9.73 (1H, s, O-H), 7.94 (1H, d, Ar–H),
7.68 (2H, d, Ar–H), 7.54-7.43 (3H, m, Ar–H ), 7.41-
7.34 (2H, m, Ar–H ), 7.31-7.15 (8H, m, Ar–H ), 6.6
(2H, d, Ar–H); 13C NMR (100 MHz, DMSO-d6): δ
195.31, 158.30, 146.97, 137.04, 136.04, 135.01,
4-(4,5-diphenyl-1-(p-tolyl)-4,5-dihydro-1H-
imidazol-2-yl)phenol (Table 5, Entry d)
Brown solid; Yield: 90%; IR (neat, cm-1):
3447 (O-H, phenolic) 3062 (C–H, aromatic), 2587
(C-H, aliphatic), 1676 (C=N), 1577 (C=C, aromatic);
1H NMR (400 MHz, DMSO-d6): δ 10.08 (1H, s,

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KARUNAKARAN et al., Orient. J. Chem., Vol. 34(6), 3004-3015 (2018)
phenolic O-H), 8.45 (1H, d, Ar–H ), 7.94, (3H, d,
Ar–H), 7.82-7.75 (4H, m, Ar–H), 7.65-7.62 (3H ,t,
Ar–H ), 7.24-7.07 (5H, m, Ar–H ), 6.89 (2H, d, Ar–H),
2.30 (3H, s, methyl); 13C NMR (100 MHz, DMSO-d6):
δ 195.1, 160.95, 159.59, 149.80, 136.05, 135.04,
132.69, 130.24, 128.94, 128.56, 128.08, 126.76,
121.26, 116.08, 115.55, 21.02; Mass (m/z): Calcd
for C28H22N2O: 402.49, Found: 402.16.
3017 (C–H, aromatic), 2594 (C-H, aliphatic), 1654
(C=N), 1586 (C=C, aromatic), 1249( C-O, alkyl aryl
ether); 1H NMR (400 MHz, DMSO-d6): δ 9.69 (1H,
s, phenolic O-H), 7.48 (2H, d, Ar–H), 7.29, (3H, d,
Ar–H), 7.24-7.21 (6H, m, Ar–H), 7.16-7.14 (3H ,m,
Ar–H ), 6.86 (2H, d, Ar–H ), 6.68 (2H, d, Ar–H), 3.37
(3H, s, methoxy); 13C NMR (100 MHz, DMSO-d6): δ
159.22, 157.99, 147.10, 136.70, 135.15, 131.29,
130.20, 128.90, 126.76, 121.87, 115.41, 114.48,
55.70; Mass (m/z): Calcd for C28H22N2O2: 418.17,
Found: 419.16.
4-(1-(4-methoxyphenyl)-4,5-diphenyl-4,5-dihydro-
1H-imidazol-2-yl)phenol (Table 5, Entry e)
Brown solid; Yield: 89%; IR (neat, cm-1):
Fig. 3. 1H spectra of 2,4,5-Triphenyl-1H-imidazole (Table 4, Entry a)
Fig. 5. IR spectra of 2,4,5-Triphenyl-1H-imidazole (Table 4, Entry a)
Benzethonium chloride can form two type
of micelle depends on nature of the solvent. In a
non-polar solvent, benzethonium chloride forms
a reverse micelle in which the hydrophilic end of
surfactant are aligned at the centre of the micelle
and the hydrophobic groups spreads away from
Fig. 4. 13C spectra of 2,4,5-Triphenyl-1H-imidazole (Table 4, Entry a)

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KARUNAKARAN et al., Orient. J. Chem., Vol. 34(6), 3004-3015 (2018)
the centre, while in polar solvent like ethanol and
water, benzethonium chloride forms regular micellar
aggregation in which the hydrophobic groups of
surfactant are aligned and concentrated at centre
of the micelle and the hydrophilic groups spreads
away from the core.29 The enhanced reaction rate is
due to the fact that non-polar organic reactants are
trapped easily inside the hydrophobic micelle core.
The micelles formation of Benzethonium chloride
in aqueous ethanol solutions increase solubility of
non polar organic molecules viz benzil, aldehyde by
micro-compartmentalize them, which ensures the
close proximity and increased local concentrations
of reactants inside the micelles, and thereby the
reaction rates improves significantly (Fig.11).Hence
benzethonium chloride surfactant micellar systems
act as highly efficient heterogeneous media for
catalytic reactions of cyclocondensation of benzil,
aldehyde and ammonium acetate.
Fig. 6. Mass spectra of 2,4,5-Triphenyl-1H-imidazole (Table 4, Entry a)
Fig. 7. 1H NMR spectra of 4-(4,5-diphenyl-1-(p-tolyl)-4,5-dihydro-1H-imidazol-2-yl)phenol (Table 5, Entry d)
Moreover, the synthesis of trisubstituted
imidazole involves formation of water molecules that
should be removed from reaction vessel in order to
shift the equilibrium dynamics towards product side.
In conventional cyclocondensation reaction, water is
not removed from the reaction environment which
retards the reaction rate.To overcome this problem,
mild to strong dehydrating agent such s sulphuric
acid, phosphoric acid are usually used. But, in
benzethonium chloride surfactant medium, water is
effectively used for micelle formation thereby alters
the equilibrium towards products, which increases
the reaction speed, and this phenomenon is the key
advantage of this method.

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KARUNAKARAN et al., Orient. J. Chem., Vol. 34(6), 3004-3015 (2018)
Fig. 8. 13C NMR spectra of 4-(4,5-diphenyl-1-(p-tolyl)-4,5-dihydro-1H-imidazol-2-yl)phenol (Table 5, Entry d)
Fig. 9. 1H-NMR spectra of 4-(1-(4-methoxyphenyl)-4,5-diphenyl-
4,5-dihydro-1H-imidazol-2-yl)phenol (Table 5, Entry e)
Fig. 10. 13C-NMR spectra of 4-(1-(4-methoxyphenyl)-4,5-
diphenyl-4,5-dihydro-1H-imidazol-2-yl)phenol (Table 5, Entry e)
H
O
X
cyclocondensation
hydrophobic core
O
O
dehydration
HO
OH
+
HN NH
HN
N
H
NH3
H2O
+
NH4 CH3COO-
Fig. 11. Miceller promoted multicomponent synthesis of trisubstituted imidazoles
Itissuggestedthatthecatalystbenzethonium
chloride increases the electrophilicity at carbon
atom of carbonyl group of the aldehyde thereby it
facilitates nucleophilic addition of ammonia cross
polarized C=O, which leads to formation of diamine
intermediate (4) by dehydration. Cyclocondenstion
of intermediate (4) with benzil followed by elimination
of water leads to formation of intermediate (7),
which in turn undergoes1,5 proton shift to form 2,4,5
triarylimidzole.(8) (Scheme 3).

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KARUNAKARAN et al., Orient. J. Chem., Vol. 34(6), 3004-3015 (2018)
Cl
three-component cyclocondensation of benzil,
aromatic aldehydes and ammonium acetate in
ethanol:water (1:1) solvent system. Benzethonium
chloride acts both as surfactant and phase
transfer catalyst. All synthesized compounds were
characterized by FT-IR, 1H NMR, 13C NMR, and Mass
spectral analysis.The developed method has several
advantages compared to the conventional synthesis
of tri-, tetra-aryl imidazoles that higher conversion of
product was achieved in significantly lower reaction
temperature and the reaction does not result in
formation of undesired side product. The process
also does not require the removal of water during the
synthesis using vacuum distillation methods.
N
R'
R''
H
2
H
4
H
NH
H
O
HO
NH2
H2
N
NH2
-H2
O
NH3
NH3
3
Cl
1
N
O
O
R'
R''
Cl
R'
N
R''
5
HO
HN
OH
HN
N
NH
H
-2H2
O
N
N
H
H+ shift
8
6
7
where
O
R' =
R'' =
O
ACKNOwLEDGEMENT
Scheme 3. Mechanism of synthesis of trisubstituted imidazoles
CONCLUSION
We are thankful to Faculty of Department of
Chemistry, Arignar Anna Government Arts College,
Cheyyar, India-604407 and Faculty of Department
of Chemistry, Madras Christian College, Chennai,
India-600059.
In conclusion, we have demonstrated for
the first time the effective utilization of benzethonium
chloride as a sole catalyst for the one-pot
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