A green and simple method for the synthesis of 2,4,5-trisubstituted-1H-imidazole derivatives using acidic ionic liquid as an effective and recyclable catalyst under ultrasound

Article abstract of DOI:10.1007/s11164-021-04517-4

Abstract: In the current work, an acidic ionic liquid ([{(IMC)-4-OMBH}BIM][HSO₄]₃) has been utilized as an effective and recyclable catalyst for the synthesis of 2,4,5-trisubstituted-1H-imidazole derivatives with high yields under optimal reaction conditions and ultrasound irradiation. Important features of the new catalyst are facile synthesis, cheap reagents and successful reuse for many times. What makes the present method an effective contribution in the field of synthesis of 2,4,5-trisubstituted-1H-imidazole derivatives is the fact that it can be described as environmentally friendly, economical, short reaction time, possible recover of the catalyst, simple workup, safer and mild reaction conditions. Graphic abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-021-04517-4

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-021-04517-4
A green and simple method for the synthesis
of 2,4,5‑trisubstituted‑1H‑imidazole derivatives using
acidic ionic liquid as an eꢀective and recyclable catalyst
under ultrasound
N. SH. Ahmed · H. D. Hanoon1
1
Received: 28 April 2021 / Accepted: 8 June 2021
©
The Author(s), under exclusive licence to Springer Nature B.V. 2021
Abstract
In the current work, an acidic ionic liquid ([{(IMC)-4-OMBH}BIM][HSO ] ) has
4
3
been utilized as an efective and recyclable catalyst ꢀor the synthesis oꢀ 2,4,5-trisub-
stituted-1H-imidazole derivatives with high yields under optimal reaction conditions
and ultrasound irradiation. Important ꢀeatures oꢀ the new catalyst are ꢀacile synthe-
sis, cheap reagents and successꢀul reuse ꢀor many times. What makes the present
method an efective contribution in the ꢁeld oꢀ synthesis oꢀ 2,4,5-trisubstituted-
1
H-imidazole derivatives is the ꢀact that it can be described as environmentally
ꢀ
riendly, economical, short reaction time, possible recover oꢀ the catalyst, simple
workup, saꢀer and mild reaction conditions.
Extended author inꢀormation available on the last page oꢀ the article
Vol.:(012
1
3456789)
3

N. S. Ahmed, H. D. Hanoon
Graphic abstract
Keyword Acidic ionic liquid · Catalyst · Synthesis · 2,4,5-Trisubstituted-1H-
imidazole · Ultrasound irradiation
Introduction
Owing to their important physical and chemical properties, ionic liquids have
aroused great interest in the recent decades. To mention but a ꢀew, they can be
described as being recyclable, non-volatile, thermally stable and non-ꢂammable.
They are, then, known to have broad applications in chemical separations and syn-
thesis [1, 2]. Moreover, ionic liquids can serve as catalysts, and thus, they play a sig-
niꢁcant role in organic synthesis [3–5]. In this respect, they are utilized as catalysts
ꢀ
or many organic reactions such as heterocyclic synthesis [6], alkylation [7], oxida-
tion [8] and dehydration [9].
In the last ꢀew years, ultrasonic irradiation has been widely utilized as an environ-
mentally ꢀriendly technology in the preparation oꢀ organic compounds [10]. Ultra-
sonic irradiation has been proved as an alternative energy source in many organic
reactions. Several organic reactions can be perꢀormed under ultrasound irradiation
with shorter reaction time and excellent yields, as well as saꢀe and mild conditions
[
11–15].
Since its discovery, the imidazole ring has attracted attention due to its their bio-
logical activities. An imidazole ring and its derivatives have pharmaceutical proper-
ties like antibacterial [16], anticancer [17], enzyme inhibitor [18], ꢀungicidal [19],
antiviral [20], anti-inꢂammatory [21], etc., in addition to its industrial activities.
1
3

A green and simple method for the synthesis of…
Imidazole derivatives are extensively used to prepare ionic liquids applied in the
synthesis oꢀ most organic compounds as active catalysts [22, 23].
Due to their wide signiꢁcance, several synthetic protocols ꢀor imidazole deriva-
tives have been developed by using diferent catalysts, such as silica sulꢀuric acid
[
24], ZrCl [25], AMFGO [26], bioglycerol-based carbon [27], oxalic acid [28],
4
K CO [29], HISA [30], SiO -H SO [31], cellulose sulꢀuric acid [32], sodium
2
3
2
2
4
bisulꢁte [33], TBAB [34] and OAc-HPro@Fe O [35]. In the past ꢀew years,
3
4
employment oꢀ ionic liquids as green catalysts has drawn great attention in the prep-
aration oꢀ 2,4,5-trisubstituted-1H-imidazole derivatives [36, 37].
The goal oꢀ the current study is to synthesize the novel ionic liquid via
an inexpensive and easy work-up route (Scheme 1). Then, the ionic liquid
(
1,1’-{3,3’-[(3-(1H-imidazol-3-ium-1-carbonyl)-4-oxocyclohexa-2,5-dien-
1
-ylidene)methylene]bis- (6-hydroxybenzoyl)}bis(1H-imidazol-3-ium) trihydrogen
sulꢀate [{(IMC)-4-OMBH}BIM][HSO ] ) is employed as a new and useꢀul solid
4
3
acid catalyst ꢀor the synthesis oꢀ 2,4,5-trisubstituted-1H-imidazole derivatives under
ultrasonic irradiation (Scheme 2). This strategy ofers several advantages: it is saꢀe,
eco-ꢀriendly, and readily available. Yet, it is characterized by its short reaction times,
simplicity oꢀ operation, excellent yields, and inexpensive catalyst. The procedure
mentioned here is an application oꢀ the ultrasound irradiation technique.
Experimental
Materials and methods
The chemicals utilized in the current work were purchased ꢀrom the commercial
sources. Melting points (m.p.) were determined using an Electro thermal Stuart
SMP 30 capillary melting apparatus. Reactions were monitored using thin layer
chromatography (TLC); spots were detected by placing it in the iodine chamber.
Fourier-transꢀorm inꢀrared (FTIR) spectra were obtained on SHIMADZU FTIR-
8
400S spectrophotometer using potassium bromide disks. Proton nuclear magnetic
1
resonance ( H NMR) spectra were recorded on an INOVA (500 MHz) spectrometer
by utilizing dimethyl sulꢀoxide (DMSO)-d as a solvent and tetramethylsilane (TMS)
6
as an internal standard. Mass (MS) spectra were perꢀormed using an Agilent Tech-
nology (HP) 5973. Field-emission scanning electron microscopy (FESEM) images
and energy-dispersive X-ray (EDX) spectroscopy were measured using FEI Nova
NanoSEM 450. X-ray difraction (XRD) patterns were made using Rigaku Ultima
IV.
1
3

N. S. Ahmed, H. D. Hanoon
Scheme 1 Synthesis routes ꢀor the novel catalyst. Regents and conditions: (i) 4H SO , 4NaNO ,CH =O,
2
4
2
2
crushed ice, 0–20 °C; (ii) SOCl , reꢂux/26 h, 75 °C, dichloromethane; (iii) imidazole, Toluene,
2
reꢂux/28 h, 110 °C, ethanol; (iv) H SO , stirr/5 h, NaOH
2
4
Synthesis and characterization of the catalyst
Synthesis of 5,5’‑[(3‑carboxy‑4‑oxocyclohexa‑2,5‑dien‑1‑ylidene)methylene]
bis(2‑hydroxybenzoic acid) (ATA)
A short necked ꢂask containing (10 mL) oꢀ concentrated sulꢀuric acid is immersed
1
3

A green and simple method for the synthesis of…
Scheme 2 Synthesis oꢀ some useꢀul 2,4,5-trisubstituted-1H-imidazole derivatives using [{(IMC)-4-
OMBH}BIM][HSO ] as catalyst
4
3
in a vigorously stirred ice-water bath, while solid sodium nitrite (1.428 g, 0.02 mol)
is being added in small portions. The addition is ꢀollowed by the emission oꢀ oxides
oꢀ nitrogen. Upon completion oꢀ a solution, the salicylic acid (2.857 g, 0.02 mol)
is added in small quantities with stirring with continuous stirring ꢀor 10 min. Aꢀter
that, continue stirring the mixture at 20 °C until the solid compounds have dissolved.
Then, the mixture should be light red to brown, homogeneous and viscous. The mix-
ture is cooled to 0 °C and ꢀormaldehyde [36%] is added slowly under extreme stir-
ring with the temperature remaining below 5 °C. The reaction is complete aꢀter all
the ꢀormaldehyde has been added. Approximately (5 g) oꢀ crushed ice is added, and
(
70 mL) oꢀ ice water is added too. Stirring during the addition should be strong
enough ꢀor the content oꢀ the ꢂask to ꢀorm small pieces oꢀ 5,5’-[(3-carboxy-4-oxo-
cyclohexa-2,5-dien-1-ylidene)methylene]bis(2-hydroxybenzoic acid). The resulting
compound is washed several times by cold water and ꢁltered over a sintered glass,
1
and then dried at 40–50 °C. 92% yield; pale red crystals; m.p: 250–253 °C; H NMR
(
(
(
500 MHz, DMSO-d ) δ ppm: 11.54 (brs, 3H, 3×OH, carboxylic acid groups), 8.17
6
s, 1H, Ar–H), 7.90 (d, J=10.3 Hz, 1H, Ar–H), 7.79–7.06 (m, 6H, Ar–H), 6.94–6.87
m, 1H, Ar–H), 5.59 (brs, 2H, 2×OH, phenol groups).
Synthesis of 5,5’‑{[3‑(chlorocarbonyl)‑4‑oxocyclohexa‑2,5‑dien‑1‑ylidene]
methylene}bis(2‑hydroxybenzoyl chloride) (CATA)
ATA (5 g, 0.013 mol) and thionyl chloride (25 mL, 0.341 mol) were put in a 50 mL
round-bottom ꢂask ꢁtted with a condenser and magnetic stirrer. The mixture was
then reꢂuxed ꢀor 26 h at 75 °C. Aꢀter that, the excess thionyl chloride was removed
using a rotary evaporator ꢀrom the mixture. The resulting solid was washed several
times with dichloromethane, and dried at 60 °C overnight in the oven. 89% yield;
dark red crystals; dissociated in 311 °C.
Synthesis of 1,1’-{3,3’-[(3-(1H-imidazol-3-ium-1-carbonyl)-4-oxocyclohexa-
2
,5-dien-1-ylidene)methylene]bis(6-hydroxybenzoyl)}bis(1H-imidazol-3-ium)
trichloride [{(IMC)-4-OMBH}BIM][Cl] .
3
CATA (3 g, 0.0066 mol) and (2.844 g, 0.0417 mol) oꢀ imidazole were dissolved
in (60 mL) oꢀ toluene. The mixture was reꢂuxed at 110 °C ꢀor 26 h. The mixture was
cooled down aꢀter reaction had been completed, and the crude product was ꢁltered
1
3

N. S. Ahmed, H. D. Hanoon
through sintered glass and washed with ethanol ꢀor puriꢁcation and eventually dried
ꢀor 3 days at 50 °C. 93% yield; black crystals; dissociated in 318 °C.
Synthesis of 1,1’‑{3,3’‑[(3‑(1H‑imidazol‑3‑ium‑1‑carbonyl)‑4‑oxocyclohexa‑2,5‑dien‑
‑ylidene)methylene]bis(6‑hydroxybenzoyl)}bis(1H‑imidazol‑3‑ium) trihydrogen
sulfate [{(IMC)‑4‑OMBH}BIM][HSO ] .
1
4
3
Concentrated sulꢀuric acid (50 mL) was careꢀully added to [{(IMC)-4-OMBH}BIM]
[
Cl] (3 g, 0.0066 mol) in a round-bottom ꢂask with vigorous stirring. At room tem-
3
perature, the mixture was stirred mechanically ꢀor 5 h. The mixture was washed with
excess water in a conical ꢂask to remove any non-reacting content. To the above
mixture, (1 g) oꢀ sodium hydroxide was added. To extract the residual salt and acid,
the mixture was ꢁltered and washed with excess water. For 3 h. at 50 °C, the catalyst
1
was dried. 80% yield; dark red crystals; dissociated in 325 °C; H NMR (500 MHz,
+
DMSO-d ) δ ppm: 9.07 (s, 3H, 3×NH , imidazole rings), 7.67 (s, 9H, 3× =CH,
6
imidazole rings), 7.00–6.88 (m, 9H, Ar–H), 5.03 (s, 5H, 2×OH, phenol groups and
−
3
×OH, SO H ).
4
General procedure for the synthesis of 2,4,5‑trisubstituted‑1H‑imidazole
derivatives(4a–j) using H SO as catalyst
2
4
A mixture oꢀ benzil/benzoin (1 mmol), aromatic aldehyde (1 mmol) and ammo-
nium acetate (3 mmol) as the ammonia source in a mixture oꢀ solvents (5 mL) oꢀ
ethanol and water (1:1) was taken, and then H SO as a catalyst (three drops) was
2
4
added at room temperature. The resulting mixture was placed in a water bath oꢀ an
ultrasound device at ultrasonic ꢀrequencies oꢀ 40 kHz, and the ultrasonic power was
kept at 100 W ꢀor the prescribed time at the ambient temperature (Table 4). The
reaction mixture was poured into cold water (20 mL) aꢀter completing the reaction
(
monitored by TLC) and stirred ꢀor 10 min. at room temperature. The solid com-
pound was ꢁltered, washed with water, dried, and recrystallized by ethanol to obtain
2
,4,5-trisubstituted-1H-imidazole derivatives. All other compounds were prepared
utilizing the same procedure.
General procedure for the synthesis of 2,4,5‑trisubstituted‑1H‑imidazole
derivatives(4a–j) using the new catalyst
A mixture oꢀ benzil/benzoin (1 mmol), aromatic aldehyde (1 mmol) and ammonium
acetate (3 mmol) as anammonia source in a mixture oꢀ solvents (5 mL) oꢀ ethanol
and water (1:1) was taken, and then [{(IMC)-4-OMBH}BIM][HSO ] as a cata-
4
3
lyst (0.16 g) was added at room temperature. The resulting mixture was placed in
a water bath oꢀ an ultrasound device at ultrasonic ꢀrequencies oꢀ 40 kHz, and the
ultrasonic power was kept at 100 W ꢀor the prescribed time at the ambient tempera-
ture (Table 4). When the reaction was complete (monitored by TLC), dichlorometh-
ane (25 mL) was added and stirred ꢀor 10 min. The catalyst was removed ꢀrom the
reaction mixture via ꢁltration and washing with dichloromethane ꢀor reuse more
than once (up to ꢁve runs) (Fig. 6). The ꢁltrate is poured into cold water (50 mL)
1
3

A green and simple method for the synthesis of…
and stirred at room temperature ꢀor 10 min. Aꢀter adding water to the organic layer,
a crude product is obtained. Two phases were extracted; the solvent is evaporated
aꢀterwards. The resulting solid was dried and recrystallized ꢀrom ethanol to get
2
,4,5-trisubstituted-1H-imidazole derivatives. All other compounds were prepared
utilizing the same procedure.
Spectral data for the products
2
-(4-chlorophenyl)-4,5-diphenyl-1H-imidazole (4a) Yellow solid; M.p. 247–249 °C
1
(
lit. 248–250 °C) [38]; H NMR (500 MHz, DMSO-d ) δ (ppm): 7.61 (t, J=7.7 Hz,
6
6
H, Ar–H), 7.77 (t, J=7.4 Hz, 4H, Ar–H), 7.84 (d, J=8.3 Hz, 2H, Ar–H), 7.92
−
1
(
(
d, J=7.4 Hz, 2H, Ar–H), 10.26 (s, NH); IR (KBr) ῡ (cm ): 1670(C=N), 3066
−1
+
Ar–H), 3317 (NH) cm ; MS (ESI): m/z=330 [M ].
N,N-dimethyl-4-(4,5-diphenyl-1H-imidazol-2-yl)benzenamine (4b) Light brown
1
solid; M.p. 256–258 °C (lit. 255–257 °C) [39]; H NMR (500 MHz, DMSO-d ) δ
6
(
ppm): 3.02 (s, 6H, 2×CH ), 6.77 (d, J=8.8 Hz, 2H, Ar–H), 7.62 (t, J=7.9 Hz,
3
4
H, Ar–H), 7.68 (d, J=9.9 Hz, 4H, Ar–H), 7.79 (t, J=8.0 Hz, 2H, Ar–H), 7.93 (d,
−
1
J=8.4 Hz, 2H, Ar–H), 9.67 (s, NH); IR (KBr) ῡ (cm ): 1674(C=N), 2862 (C–H),
−1
+
3
064 (Ar–H), 3317 (NH) cm ; MS (ESI): m/z=339 [M ].
2
-(4-nitrophenyl)-4,5-diphenyl-1H-imidazole (4c) Orange solid; M.p. 199–201 °C
1
(
lit. 200–202 °C) [40]; H NMR (500 MHz, DMSO-d ) δ (ppm): 7.62 (t, J=7.6 Hz,
6
2
H, Ar–H), 7.79 (t, J=7.7 Hz, 4H, Ar–H), 7.92 (d, J=7.3 Hz, 4H, Ar–H), 8.16 (d,
J=8.8 Hz, 2H, Ar–H), 8.41 (d, J=8.6 Hz, 2H, Ar–H), 10.16 (s, NH); IR (KBr) ῡ
−1
−1
(
(
cm ): 1334 and 1529 (NO ); 1666(C=N), 3066 (Ar–H), 3312 (NH) cm ; MS
2
+
ESI): m/z=341 [M ].
2
-(2-methoxyphenyl)-4,5-diphenyl-1H-imidazole (4d) Brown solid; M.p.
1
2
07–209 °C (lit. 205–208 °C) [41]; H NMR (500 MHz, DMSO-d ) δ (ppm): 3.90
6
(
(
s, 3H, OCH ), 7.06 (t, J=7.4 Hz, 1H, Ar–H), 7.21 (d, J=8.4 Hz, 1H, Ar–H), 7.62
3
t, J=7.7 Hz, 3H, Ar–H), 7.78 (t, J=7.4 Hz, 4H, Ar–H), 7.92 (d, J=8.3 Hz, 5H,
−1
Ar–H), 10.36 (s, NH); IR (KBr) ῡ (cm ): 1668(C=N), 2866 (C–H), 3064 (Ar–H),
−1
+
3
317 (NH) cm ; MS (ESI): m/z=326 [M ].
2
-methoxy-4-(4,5-diphenyl-1H-imidazol-2-yl)phenol (4e) Pale yellow solid; M.p.
1
1
65–167 °C (lit. 166 °C) [42]. H NMR (500 MHz, DMSO-d ) δ (ppm): 3.84 (s,
6
3
H, OCH ), 6.96 (d, J=9.2 Hz, 1H, Ar–H), 7.41 (t, J=8.9 Hz, 2H, Ar–H), 7.63
3
(
t, J=7.7 Hz, 4H, Ar–H), 7.79 (t, J=8.0 Hz, 2H, Ar–H), 7.92 (d, J=8.2 Hz, 4H,
−
1
Ar–H), 9.77 (s, OH), 10.24 (s, NH); IR (KBr) ῡ (cm ): 1668(C=N), 2856 (C–H),
−
1
+
3
068 (Ar–H), 3176 (NH and OH) cm ; MS (ESI): m/z=342 [M ].
3
-(4,5-diphenyl-1H-imidazol-2-yl)phenol (4f) Brown solid; M.p. 256–258 °C (lit.
1
2
1
1
57–258 °C) [43]. H NMR (500 MHz, DMSO-d ) δ (ppm): 7.10 (d, J=9.4 Hz,
6
H, Ar–H), 7.24 (s, 1H, Ar–H), 7.35 (d, J=7.5 Hz, 1H, Ar–H), 7.41 (t, J=7.7 Hz,
H, Ar–H), 7.62 (t, J=7.8 Hz, 2H, Ar–H), 7.79 (t, J=7.4 Hz, 4H, Ar–H), 7.92 (d,
−
1
J=7.7 Hz, 4H, Ar–H), 9.91 (s, OH), 9.93 (s, NH); IR (KBr) ῡ (cm ): 1672 (C=N),
−1
+
3
066 (Ar–H), 3217 (NH), 3313 (OH) cm ; MS (ESI): m/z=312 [M ].
4
-(4,5-diphenyl-1H-imidazol-2-yl)phenol (4 g) Dark yellow solid; M.p.
1
2
31–232 °C (lit. 232–233 °C) [44]. H NMR (500 MHz, DMSO-d ) δ (ppm): 6.93
6
1
3

N. S. Ahmed, H. D. Hanoon
(
d, J=8.4 Hz, 4H, Ar–H), 7.62 (t, J=7.7 Hz, 2H, Ar–H), 7.75–7.80 (m, 4H, Ar–H),
−
1
8
.92 (d, J=8.4 Hz, 4H, Ar–H), 9.78 (s, OH), 10.59 (s, NH); IR (KBr) ῡ (cm ):
−
1
1
670 (C=N), 3066 (Ar–H), 3171 (NH), 3311 (OH) cm ; MS (ESI): m/z=312
+
[
M ].
2
-(3,4-dimethoxyphenyl)-4,5-diphenyl-1H-imidazole (4 h) Dark yellow solid;
1
M.p. 214–216 °C (lit. 215–217 °C) [43]. H NMR (500 MHz, DMSO-d ) δ (ppm):
6
3
.82 (s, 3H, OCH ), 3.86 (s, 3H, OCH ), 7.16 (d, J=8.2 Hz, 1H, Ar–H), 7.38 (s, 1H,
3 3
Ar–H), 7.55 (dd, J =8.2, J =1.8 Hz, 1H, Ar–H), 7.62 (t, J=7.8 Hz, 2H, Ar–H),
1
2
7
.78 (t, J=7.8 Hz, 4H, Ar–H), 7.92 (d, J=8.3 Hz, 4H, Ar–H), 9.84 (s, NH); IR
−1
(
KBr) ῡ (cm ): 1666 (C=N), 2820 and 2906 (C–H); 3063 (Ar–H), 3309 (NH)
−1
+
cm ; MS (ESI): m/z=356 [M ].
2
,4,5-triphenyl-1H-imidazole (4i) Pale yellow solid; M.p. 268–270 °C (lit.
1
2
69 °C) [45]. H NMR (500 MHz, DMSO-d ) δ (ppm): 7.62 (t, J=7.6 Hz, 3H,
6
Ar–H), 7.79 (t, J=7.3 Hz, 6H, Ar–H), 7.92 (d, J=7.7 Hz, 6H, Ar–H), 10.22 (s,
−1
−1
NH); IR (KBr) ῡ (cm ): 1668 (C=N), 3066 (Ar–H), 3317 (NH) cm ; MS (ESI):
+
m/z=256 [M ].
2
-(4-bromophenyl)-4,5-diphenyl-1H-imidazole (4j) Brown solid; M.p.
1
1
88–190 °C (lit. 189–191 °C) [46]. H NMR (500 MHz, DMSO-d ) δ (ppm): 7.61
6
(
t, J=7.8 Hz, 6H, Ar–H), 7.77 (t, J=7.9 Hz, 4H, Ar–H), 7.92 (d, J=8.3 Hz, 4H,
−1
Ar–H), 9.99 (s, NH); IR (KBr) ῡ (cm ): 1668(C=N), 3066 (Ar–H), 3319 (NH)
−1
+
cm ; MS (ESI): m/z=374 [M ].
Results and discussion
Synthesis of catalyst
Initially, a new catalyst ([{(IMC)-4-OMBH}BIM][HSO ] ) was synthesized
4
3
according to the steps shown in Scheme 1, and the structure was deduced ꢀrom diꢀ-
1
ꢀ
erent techniques (FTIR, H NMR, SEM, EDS and XRD).
1
FTIR and H NMR analysis
An analysis was made ꢀor FTIR spectra oꢀ [{(IMC)-4-OMBH}BIM][HSO ] and
4
3
the other three products (Fig. 1). FTIR spectrum oꢀ ATA (Fig. 1a) showed a broad
−
1
absorption band in the range (2400–3400 cm ) assigned to O–H bond stretch-
−
1
ing as well as two absorption peaks at 1674 and 1608 cm due to C = O bonds
stretching. FTIR spectrum oꢀ CATA (Fig. 1b) observed the absorption band at
−
1
1
749 cm attributed to C = O bond stretching in the acyl chloride group. In addi-
−
1
tion, a new absorption peak at 582 cm corresponding to C–Cl bond stretching
appeared. FTIR spectrum oꢀ [{(IMC)-4-OMBH}BIM][Cl] (Fig. 1c) exhibited
3
−
1
the disappearance oꢀ the band at 582 cm due to the C–Cl bond. Besides, the
−
1
three absorption peaks appear at 3142, 1626 and 1383 cm attributed to N–H,
C = N and C-N bonds stretching in imidazole ring, respectively. FTIR spectrum oꢀ
−
1
[
{(IMC)-4-OMBH}BIM][HSO ] (Fig. 1e) displayed at 1033 cm due to S = O
4 3
1
3

A green and simple method for the synthesis of…
Fig. 1 FTIR spectra oꢀ a ATA, b CATA, c [{(IMC)-4-OMBH}BIM][Cl] , d [{(IMC)-4-OMBH}BIM]
3
[
HSO ] (The catalyst)
4 3
−
1
−
bond, and another absorption band at 617 cm assigned to S–O bond in SO H
4
1
group. H NMR spectra ꢀor ATA and [{(IMC)-4-OMBH}BIM][HSO ] were also
4
3
1
measured (Fig. 2). H NMR spectrum oꢀ ATA (Fig. 2a) showed a broad peak at
1
1
1.54 ppm ꢀor three protons (3 × OH) in carboxylic groups. H NMR spectrum
oꢀ [{(IMC)-4-OMBH}BIM][HSO ] (Fig. 2b) exhibited a signiꢁcant peak at
4
3
+
9
.07 ppm due to protons (3 × NH ) as well as another peak at 7.67 ppm assigned
to protons (3 × = CH) in imidazole rings. Moreover, the peak at 11.54 ppm disap-
peared; this was attributed to protons in carboxylic acids [47–49].
1
3

N. S. Ahmed, H. D. Hanoon
Fig. 2 1H NMR spectra oꢀ a ATA and b [{(IMC)-4-OMBH}BIM][HSO4]3
1
3

A green and simple method for the synthesis of…
SEM and EDX analysis
Surꢀace morphology oꢀ each oꢀ ATA, CATA, [{(IMC)-4-OMBH}BIM][Cl] and
3
[
{(IMC)-4-OMBH}BIM][HSO ] was examined using SEM (Fig. 3). SEM image
4
3
oꢀ ATA (Fig. 3a) shows a ꢂat surꢀace and small particles, which is consistent
with previous study [37]. Aꢀter chlorination, SEM image oꢀ CATA (Fig. 3b) dis-
played slightly diferent with SEM image oꢀ ATA. SEM images oꢀ [{(IMC)-4-
OMBH}BIM][Cl] and [{(IMC)-4-OMBH}BIM][HSO ] (Fig. 3c,d) exhibited
3
4 3
aggregation, which indicated the eꢃciency oꢀ the modiꢁcation procedure and ion
exchange with sulꢀuric acid. This aggregation occurs because oꢀ the approaching
positive and negative sides in ionic liquid compounds. EDX analysis (Fig. 4) was
also carried out to analyze the structure oꢀ the catalyst and the other three com-
pounds. As expected, nitrogen and sulꢀur elements appear in the EDX spectrum
ꢀ
or the catalyst (Fig. 4d), and the presence oꢀ a sulꢀur atom on the surꢀace oꢀ the
catalyst conꢁrms the success oꢀ the ion-exchange reaction [37, 50].
Fig. 3 SEM images oꢀ a ATA, b CATA, c [{(IMC)-4-OMBH}BIM][Cl] and d [{(IMC)-4-OMBH}
3
BIM][HSO ]
4
3
1
3

N. S. Ahmed, H. D. Hanoon
Fig. 4 EDX spectra oꢀ a ATA, b CATA, c [{(IMC)-4-OMBH}BIM][Cl] and d [{(IMC)-4-OMBH}
3
BIM][HSO ] . Arrows (in green, red and blue) indicate characteristic chlorine, nitrogen and sulꢀur peaks,
4
3
respectively
XRD analysis
XRD is a useꢀul technique to analyze the structure oꢀ a catalyst (Fig. 5). The XRD
pattern oꢀ ATA (Fig. 1a) exhibits a broad band in the 2θ range (12°–33°) because
oꢀ the presence oꢀ the amorphous carbon the presence in aromatic rings, while the
XRD pattern oꢀ [{(IMC)-4-OMBH}BIM][HSO ] (Fig. 4b) displays peaks at 2θ
4
3
values oꢀ 16.9°, 25.2° and 28.6°. The peaks appearing in the pattern oꢀ the new
catalyst indicate its transꢀormation into a crystalline compound [37, 51].
Optimization of reaction conditions
In order to determine the optimum reaction conditions, the reaction between
4
-chlorobenzaldehyde, ammonium acetate and benzil was selected as a model
reaction (4a) (Scheme 2). Various solvents and mole ratios were studied ꢀor the
model reaction (Tables 1 and 2). Ethanol and water (1:1), as a solvent (Table 1,
Entry 2), obtained the best yield. Highest percentage yield was ꢀound by using
1
:1:3 as the molar ratio, (Table 2, Entry 3). When we used 0.16 g oꢀ catalyst in
the model reaction, the reaction gave a maximum yield (Table 3, Entry 5).
With optimal reaction conditions, we studied a wide range oꢀ aldehydes and
benzil/benzoin under ultrasonic irradiation (Table 4). It has been observed that
these reactions gave high yields with simple workup. We also investigated the
activity oꢀ the new catalyst via comparing it with the sulꢀuric acid (Table 4). The
results showed that the new catalyst was better than the sulꢀuric acid. This is due
1
to the highly acidic nature oꢀ the new catalyst. Through FTIR, H NMR and mass
1
3

A green and simple method for the synthesis of…
Fig. 5 XRD patterns oꢀ a ATA and b [{(IMC)-4-OMBH}BIM][HSO4]3
Table 1 Efect oꢀ solvent on the
Yield (%)b
Entry
Solvent
synthesis oꢀ 2,4,5-trisubstituted-
a
1
H-imidazole derivatives
1
2
3
4
5
6
7
8
9
Pure H O
ethanol
94
68
95
84
67
86
94
75
89
90
75
2
H O/ethanol (1:1)
2
H O/ethanol (4:1)
2
Acetonitrile
Tetrahydroꢀuran
H O/acetonitrile (1:1)
2
H O/acetonitrile (4:1)
2
H O/THF (1:1)
2
1
0
H O/THF (4:1)
2
1
1
Free solvent
a
Reaction conditions: benzil/4-chlorobenzaldehyde/ammonium ace-
tate, ultrasound irradiation at ambient temperature
Isolated yield
b
Blod value represents the best percentage
spectroscopy, the structures oꢀ all products (4a–j) were determined. Additionally,
the melting points were established by comparison with their known in the litera-
ture [38–46].
1
3

N. S. Ahmed, H. D. Hanoon
Table 2 Efect oꢀ mole ratio on the synthesis oꢀ 2,4,5-trisubstituted-1H-imidazole derivativesa
Entry
Mole ratio (A:B:C)
Yield (%)b
1
2
3
4
5
1:1:1
1:1:2
1:1:3
1:1:4
1:1:5
75
67
95
93
71
a
Reaction conditions: benzil/4-chlorobenzaldehyde/ammonium acetate, ultrasound irradiation at ambient
temperature
Isolated yield
b
Blod value represents the best percentage
Table 3 Efect oꢀ the catalyst
Yield (%)b
Entry
Catalyst (g)
amount on the synthesis
oꢀ 2,4,5-trisubstituted-1H-
imidazole derivativesa
1
2
3
4
5
6
0.01
0.02
0.04
0.08
0.16
0.20
76
85
87
92
98
96
a
Reaction conditions: benzil/4-chlorobenzaldehyde/ammonium ace-
tate (1:1:3 mol ratio), (EtOH:water, 1:1) (5 mL), t=40 min. in the
presence oꢀ the catalyst under ultrasound irradiation
b
Isolated yield
Blod value represents the best percentage
Reusability of the catalyst
At the end oꢀ the reaction, the new catalyst ([{(IMC)-4-OMBH}BIM][HSO ] ) was
4
3
ꢁ
ltrated and washed with dichloromethane, and then utilized in another reaction
without any new addition. The catalyst could be reused ꢁve times (Fig. 6). This is
1
3

A green and simple method for the synthesis of…
1
3

N. S. Ahmed, H. D. Hanoon
Fig. 6 Reusability oꢀ the catalyst
very important in green chemistry and industrial applications. Generally, the new
catalyst exhibited high catalytic activity as well as the possibility simply isolated
ꢀ
rom the reaction mixture.
Conclusions
In conclusion, a highly eꢃcient route has been developed to synthesize oꢀ a series
oꢀ 2,4,5-trisubstituted-1H-imidazole derivatives with high yields in the presence oꢀ
[
{(IMC)-4-OMBH}BIM][HSO ] as an eco-ꢀriendly and efective catalyst under
4 3
ultrasound irradiation. The new catalyst has been successꢀully reused several times,
which is considered the highlights oꢀ this method, as well as the reactions are per-
ꢀormed smoothly and under mild conditions.
Supplementary Information The online version contains supplementary material available at https://doi.
org/10.1007/s11164-021-04517-4.
Acknowledgements We are thankꢀul to the Department oꢀ Chemistry, College oꢀ Science, University oꢀ
Kerbala, ꢀor their support.
References
1
.
R. Sheldon, Chem. Commun. 23, 2399 (2001)
2
.
Q. Ji, X. Yu, A.E.A. Yagoub, M. Li, O.A. Fakayode, D. Yan, C. Zhou, L. Chen, Catal. Lett. 150, 1373
(
2020)
3
.
Y. Liu, L. Li, C.X. Xie, Res. Chem. Intermed. 42, 559 (2016)
4
.
M.A. Shaikh, M. Farooqui, S. Abed, Res. Chem. Intermed. 44, 5483 (2018)
5
. A. Zhu, Q. Li, W. Feng, D. Fan, L. Li, Catal. Lett. 151, 720 (2021)
6
.
M.A.P. Martins, C.P. Frizzo, D.N. Moreira, N. Zanatta, H.G. Bonacorso, Chem. Rev. 108, 2015 (2008)
7
. A. Taheri, B. Lai, C. Cheng, Y. Gu, Green Chem. 17, 812 (2015)
8
.
M. Vaꢀaeezadeh, M.M. Hashemi, RSC Adv. 5, 31298 (2015)
9
.
L. Shen, H. Yin, A. Wang, X. Lu, C. Zhang, F. Chen, Y. Wang, H. Chen, J. Ind. Eng. Chem. 20, 759
(2014)
1
1
1
1
0. K. Valadi, S. Gharibi, R. Taheri-Ledari, A. Maleki, Solid State Sci. 101, 106141 (2020)
1. A. Dandia, D.S. Bhati, A.K. Jain, G.N. Sharma, Ultrason. Sonochem. 18, 1143 (2011)
2. M. Rouhani, A. Ramazani, S.W. Joo, Ultrason. Sonochem. 22, 391 (2015)
3. A. Ramazani, M. Rouhani, S.W. Joo, Ultrason. Sonochem. 28, 393 (2016)
1
3

A green and simple method for the synthesis of…
1
4. M. Mirza-Aghayan, M. Mohammadi, Z. Ahmadi, R. Boukherroub, Catal. Lett. 150, 2959 (2020)
5. N.G. Shabalala, N. Kerru, S. Maddila, W.E. van Zyl, S.B. Jonnalagadda, Chem. Data. Collect. 28,
1
100467 (2020)
16. M. Antolini, A. Bozzoli, C. Ghiron, G. Kennedy, T. Rossi, A. Ursini, Bioorg. Med. Chem. Lett. 9, 1023
(1999)
1
7. Y. Özkay, İ Işıkdağ, Z. İncesu, G. Akalın, Eur. J. Med. Chem. 45, 3320 (2010)
8. L. Salerno, M.N. Modica, G. Romeo, V. Pittalà, M.A. Siracusa, M.E. Amato, R. Acquaviva, C.D. Giac-
omo, V. Sorrenti, Eur. J. Med. Chem. 49, 118 (2012)
1
1
9. S. Lauꢀer, P. Koch, Org. Biomol. Chem. 6, 437 (2008)
2
0. D. Sharma, B. Narasimhan, P. Kumar, V. Judge, R. Narang, E. Clercq, J. Balzarini, Eur. J. Med. Chem.
44, 2347 (2009)
2
1. V.G. Silva, R.O. Silva, S.R.B. Damasceno, N.S. Carvalho, R.S. Prudencio, K.S. Aragao, M.A. Guima-
raes, S.A. Campos, L.M.C. Veras, M. Godejohann, J.R.S.A. Leite, A.L.R. Barbosa, J.V.R. Medeiros, J.
Nat. Prod. 76, 1071 (2013)
2
2. Z. Zhou, Y. Yuan, Y. Xie, M. Li, Catal. Lett. 148, 2696 (2018)
2
3. H.D. Hanoon, E. Kowsari, M. Abdouss, H. Zandi, M.H. Ghasemi, Res. Chem. Intermed. 43, 1751
(2017)
2
2
2
4. A. Shaabani, A. Rahmati, J. Mol. Catal. A Chem. 249, 246 (2006)
5. M. Kidwai, P. Mothsra, V. Bansal, R. Goyal, Monatsh Chem. 137, 1189 (2006)
6. H.D. Hanoon, E. Kowsari, M. Abdouss, M.H. Ghasemi, H. Zandi, Res. Chem. Intermed. 43, 4023
(2017)
27. K. Ramesh, S.N. Murthy, K. Karnakar, Y.V.D. Nageswar, K. Vijayalakhshmi, B.L.A.P. Devi, R.B.N.
Prasad, Tetrahedron Lett. 53, 1126 (2012)
2
2
3
3
3
8. N.D. Kokare, J.N. Sangshetti, D.B. Shinde, Synthesis 18, 2829 (2007)
9. M.M. Ramaiah, P.B. Shubha, H. Prasad, N.S. Shivananju, Tetrahedron Lett. 61, 151705 (2020)
0. H.D. Hanoon, S.M. Radhi, S.K. Abbas, A.I.P. Conꢀ, Proc. 2144, 020005 (2019)
1. Z. Golestaneh, M. Ghashang, Tetrahedron Lett. 60, 151194 (2019)
2. K.F. Shelke, S.B. Sapkal, G.K. Kakade, B.B. Shingate, M.S. Shingare, Green Chem. Lett. Rev. 3, 27
(2010)
3
3. J.N. Sangshetti, N.D. Kokare, S.A. Kothakar, D.B. Shinde, Monatsh Chem. 139, 125 (2008)
3
4. M.V. Chary, N.C. Keerthysri, S.V.N. Vupallapati, N. Lingaiah, S. Kantevari, Catal. Commun. 9, 2013
(2008)
3
5. H. Aghahosseini, A. Ramazani, K. Ślepokura, T. Lis, J. Colloid Interꢀace Sci. 511, 222 (2018)
6. B. Sonyanaik, K. Ashok, S. Rambabu, D. Ravi, A. Kurumanna, P. Madhu, B. Sakram, Russ. J. Gen.
Chem. 88, 537 (2018)
3
3
3
3
4
4
4
7. D.A. Hilal, H.D. Hanoon, Res. Chem. Intermed. 46, 1521 (2020)
8. K.R. Babu, S. Maripi, S.B. Madasu, N.R. Appna, Chem. Sci. Trans. 6, 428 (2017)
9. J. Saꢀari, S.D. Khalili, S.H. Banitaba, J. Chem. Sci. 122, 437 (2010)
0. R.S. Joshi, P.G. Mandhane, M.U. Shaikh, R.P. Kale, C.H. Gill, Chinese Chem. Lett. 21, 429 (2010)
1. T. Shamsi, A. Amoozadeh, E. Tabrizian, S.M. Sajjadi, React. Kinet. Mech. Catal. 121, 505 (2017)
2. S.V. Nalage, M.B. Kalyankar, V.S. Patil, S.V. Bhosale, S.U. Deshmukh, R.P. Pawar, Open Catal. J. 3, 58
(2010)
4
4
4
3. M. Alikarami, M. Amozad, Bull Chem. Soc. Ethiop. 31, 177 (2017)
4. S. Samai, G.C. Nandi, P. Singh, M.S. Singh, Tetrahedron 65, 10155 (2009)
5. S.A. Siddiqui, U.C. Narkhede, S.S. Palimkar, T. Daniel, R.J. Lahoti, K.V. Srinivasan, Tetrahedron 61,
3539 (2005)
4
4
4
4
6. M. Heidari, M. Rezaei, R. Badri, Heterocycl Commun. 21, 73 (2015)
7. M.N. Seꢀat, D. Saberi, K. Niknam, Catal. Lett. 141, 1713 (2011)
8. M. Goswami, M.M. Dutta, P. Phukan, Res. Chem. Intermed. 44, 1597 (2018)
9. R. de Mello, L.H. Santos, M.M. Pupo, K.I. Eguiluz, G.R. Salazar-Banda, A.J. Motheo, J. Solid State
Electrochem. 22, 1571 (2018)
5
0. F. Shirini, O.G. Jolodar, M. Seddighi, H.T. Borujeni, RSC Adv. 5, 19790 (2015)
1. M. Nurhadi, J. Eꢀendi, S.L. Lee, T.M.I. Mahlia, S. Chandren, C.S. Ho, H. Nur, J. Taiwan Inst. Chem.
Eng. 46, 183 (2015)
5
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N. S. Ahmed, H. D. Hanoon
Authors and Aꢀliations
N. SH. Ahmed · H. D. Hanoon1
1
*
H. D. Hanoon
haitham.alshebly@uokerbala.edu.iq
1
Department oꢀ Chemistry, College oꢀ Science, University oꢀ Kerbala, Kerbala, Iraq
1
3