An environmental friendly approach for the synthesis of highly substituted imidazoles using Br?nsted acidic ionic liquid, N-methyl-2-pyrrolidonium hydrogen sulfate, as reusable catalyst

Article abstract of DOI:10.1016/j.molliq.2011.02.012

Br?nsted acidic ionic liquid, N-methyl-2-pyrrolidonium hydrogen sulfate, has been used as an efficient and reusable catalyst for the one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles under thermal solvent-free conditions in excellent yields.

Full text of DOI:10.1016/j.molliq.2011.02.012

Journal of Molecular Liquids 160 (2011) 40–49
Contents lists available at ScienceDirect
Journal of Molecular Liquids
journal homepage: www.elsevier.com/locate/molliq
An environmental friendly approach for the synthesis of highly substituted
imidazoles using Brønsted acidic ionic liquid, N-methyl-2-pyrrolidonium hydrogen
sulfate, as reusable catalyst
⁎
Hamid Reza Shaterian , Mohammad Ranjbar
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan, PO Box 98135-674, Zahedan, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 January 2011
Received in revised form 14 February 2011
Accepted 16 February 2011
Available online 24 February 2011
Brønsted acidic ionic liquid, N-methyl-2-pyrrolidonium hydrogen sulfate, has been used as an efficient and
reusable catalyst for the one-pot synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles
under thermal solvent-free conditions in excellent yields.
© 2011 Elsevier B.V. All rights reserved.
Keywords:
N-methyl-2-pyrrolidonium hydrogen sulfate
2,4,5-trisubstituted imidazoles
1,2,4,5-tetrasubstituted imidazoles
Solvent-free
Ionic liquid
Catalyst
1. Introduction
In continuation of our effort to develop Lewis and Brønsted acid
catalyzed synthetic methodologies [12–15], we report herein, a
Multi-component reactions (MCRs) are powerful tools in
generating products in organic and medicinal chemistry for their
high degree of atom economy and application in the diversity-
oriented convergent synthesis of complex organic molecules from
simple synthesis of 2,4,5-trisubstituted (Scheme 1) and 1,2,4,5-
tetrasubstituted imidazoles (Scheme 2) in high yields using Brønsted
acidic ionic liquid, N-methyl-2-pyrrolidonium hydrogen sulfate, as a
catalyst for the first time.
simple and readily available substrates in
operation [1,2].
a single synthetic
2. Experimental
Imidazoles are an important class of heterocycles being the core
fragment of different natural products and biological systems [3].
Compounds containing imidazole moiety have many pharmacological
properties and play important roles in biochemical processes [4].
Substituted imidazoles that can be used as light-sensitive materials in
photography are known as inhibitors, fungicides and herbicides [5],
plant growth regulators and therapeutic agents [6].
Ionic liquid (IL) technology offers a new and environmentally
benign approach toward modern synthetic chemistry. Ionic liquids
have interesting advantages such as extremely low vapor pressure,
excellent thermal stability, reusability, and talent to dissolve many
organic and inorganic substrates [7]. Ionic liquids have been
successfully employed as solvents and catalyst for a variety of
reactions [8–11], which promise widespread applications in industry
and organic syntheses.
All reagents were purchased from Merck and Aldrich and used
without further purification. All yields refer to isolated products after
purification. Products were characterized by comparison with
authentic samples and by spectroscopy data (IR, 1H NMR and 13C
NMR spectra). The NMR spectra were recorded on a Bruker Avance
DPX 500 MHz instrument. The spectra were measured in DMSO-d6
relative to TMS (0.00 ppm). FT-IR spectra were recorded on a JASCO
FT-IR 460 plus spectrophotometer. Mass spectra were recorded on an
Agilent technologies 5973 network mass selective detector (MSD)
operating at an ionization potential of 70 eV. TLC was performed on
silica-gel Poly Gram SIL G/UV 254 plates.
2.1. Preparation of N-methyl-2-pyrrolidonium hydrogen sulfate as
ionic liquid
N-methyl-2-pyrrolidone (20 mmol) was charged into a 150 mL
three necked flask with a magnetic stirrer. Then equimolar concen-
trated sulfuric acid (98 wt.%) was added dropwise slowly into the
⁎
Corresponding author. Tel.: +98 541 2446565; fax: +98 541 2431067.
E-mail address: hrshaterian@chem.usb.ac.ir (H.R. Shaterian).
0167-7322/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molliq.2011.02.012

H.R. Shaterian, M. Ranjbar / Journal of Molecular Liquids 160 (2011) 40–49
41
O
Ph
Ph
H
Ph
CHO
Ph
Ph
N
N
Catalyst
O
NH4OAC
NH OAC
+
or
O
+
4
+
Solvent-Free
Thermal
X1
X1
Ph
OH
Catalyst = Bronsted acidic ionic liquid, N-methyl-2-pyrrolidonium hydrogen sulfate
Scheme 1. Condensation reaction between benzil or benzoin, benzaldehyde, and ammonium acetate at 100 °C in the presence of N-methyl-2-pyrrolidonium hydrogen sulfate as
Brønsted acidic ionic liquid.
flask at 80 °C for 12 h. The mixture was washed with diethyl ether
three times to remove non-ionic residues and dried in vacuum by a
rotary evaporator to obtain the viscous clear N-methyl-2-pyrrolido-
nium hydrogen sulfate [16].
room temperature. The resulting mixture was heated to 100 °C for the
appropriate time reported in Table 2. After completion of the reaction
which was monitored by TLC, the mixture was washed with water,
and the solid product purified by recrystallization from ethanol. All of
the desired product(s) were characterized by comparison of their
physical data with those of known compounds. Some characterization
data for selected known products are given below.
2.2. General procedure for preparation of 2,4,5-trisubstituted imidazoles
Benzil or benzoin (1 mmol), aldehyde (1 mmol), and ammonium
acetate (4 mmol) were added to N-methyl 2-pyrrolidone hydrogen
sulfate (0.08 g, 0.4 mmol) in an oil bath at room temperature. The
resulting mixture was heated to 100 C for the appropriate time reported in
Table 1. After completion of the reaction which was monitored by TLC, the
mixture washed with water, the solid product purified by recrystallization
from ethanol. All of the desired product(s) were characterized by
comparison of their physical data with those of known compounds.
Some characterization data for selected known products are given below.
2-(4-methoxyphenyl)-4,5-diphenylimidazole (Table 1, Entry 4): 1H
NMR (DMSO-d6, 500 MHz): δ=12.48 (s, 1H), 8.00 (dt, J=8.80 Hz, 2.0 Hz,
2H), 7.51 (d, J=7.2 Hz, 4H), 7.35 (t, J=7.2 Hz, 4H), 7.27 (t, J=7.2 Hz, 2H),
7.04 (dt, J=8.8 Hz, 2.0 Hz, 2H), 3.80 (s, 3H); 13C NMR (DMSO-d6,
125 MHz): δ=55.2, 114.1, 122.9, 126.7, 127.0, 127.7, 128.4, 145.6, 159.4,
ppm; IR (KBr, cm−1): 3400, 3060, 1611, 1490, 1179, 1028, 830, 761.
2-(2,4-Dichlorophenyl)-4,5-diphenylimidazole (Table 1, Entry
18): 1H NMR (DMSO-d6, 500 MHz): δ=12.8 (s, 1H), 7.80 (d,
J=8.4 Hz), 7.81 (s, 1 H), 7.61–7.22 (m, 12H) ppm; 13C NMR
(DMSO-d6, 125 MHz): δ=126.7, 127.2, 127.4, 127.9, 128.2, 128.3,
128.7, 128.8, 129.6, 130.6, 132.4, 132.6, 133.9, 134.8, 137.1,
142.4 ppm; IR (KBr, cm−1): 3427, 3068, 1593, 824, 767.
1,4,5-Triphenyl-2-p-tolyl-1H-imidazole (Table 2, Entry 6): 1H
NMR (DMSO-d6, 500 MHz): δ=2.26 (s, 3 H), 7.08 (d, J=8.0 Hz,
2H), 7.16–7.18 (m, 1H), 7.22–7.25 (m, 6 H), 7.26–7.28 (m, 5H), 7.31–
7.32 (m, 3H), 7.50 (d, J=8.0 Hz, 2H) ppm; 13C NMR (DMSO-d6,
125 MHz): δ=21.5, 127.2, 128.4, 128.9, 129.0, 129.2, 129.50, 129.58,
129.6, 129.9, 131.3, 131.9, 132.0, 135.3, 137.60, 137,63, 138.6,
147.0 ppm; IR (KBr, cm−1): 2935, 1590, 1577, 1492.
1,2-Bis(4-chlorophenyl)-4,5-diphenyl-1 H-imidazole (Table 2,
Entry 10): 1H NMR (DMSO-d6, 500 MHz): δ=7.17–7.19 (m, 1 H),
7.23–7.25 (m, 4H), 7.29–7.32 (m, 5H), 7.38–7.42 (m, 6H), 7.50 (d,
J=7.0 Hz, 2H) ppm; 13C NMR (DMSO-d6, 125 MHz): δ=127.2, 127.4,
129.44, 129.49, 129.9, 130.1, 130.8, 130.9, 131.3, 132.0, 132.3, 134.1,
134.3, 135.0, 136.2, 145.8 ppm; IR (KBr, cm−1): 2987, 1596, 1499,
1411.
For recycling the catalyst, after washing solid products with water
completely, the water containing ionic liquid (IL is soluble in water)
was evaporated under reduced pressure and ionic liquid was
recovered and reused.
3. Results and discussion
For recycling the catalyst, after washing solid products with water
completely, the water containing ionic liquid (IL is soluble in water) was
evaporated under reduced pressure and ionic liquid was recovered and
reused.
Owing to the versatile biological activities of substituted imida-
zoles numerous classical methods for the synthesis of these
compounds have been reported [3–6]. In a typical procedure, benzil
or benzoin, aldehydes, amines, and ammonium acetate are condensed
in the presence of strong protic acid such as H3PO4 [13], H2SO4 [14],
HOAc [15] as well as organo catalyst in HOAc [9] under reflux
conditions. These homogeneous catalysts present limitations due to
the use of corrosive reagents and the necessity of neutralization of the
strong acid media. In addition, the synthesis of these heterocycles in
polar organic solvents such as ethanol, methanol, acetic acid, DMF and
DMSO lead to complex isolation and recovery procedures.
2.3. General procedure for preparation of 1,2,4,5-tetrasubstituted
imidazoles
Benzil or benzoin (1 mmol), aldehyde (1 mmol), amine (1 mmol),
and ammonium acetate (1 mmol) were added to N-methyl-2-
pyrrolidonium hydrogen sulfate (0.08 g, 0.4 mmol) in an oil bath at
O
Ph
Ph
Ph
NH2
CHO
Ph
Ph
N
N
O
Catalyst
X2
NH4OAC
+
or
O
+
X2
+
Solvent-Free
Thermal
X1
X1
Ph
OH
Catalyst = Bronsted acidic ionic liquid, N-methyl-2-pyrrolidonium hydrogen sulfate
Scheme 2. Condensation reaction of benzil or benzoin, benzaldehydes, anilines, and ammonium acetate using N-methyl-2-pyrrolidonium hydrogen sulfate as catalyst at 100 °C.

42
H.R. Shaterian, M. Ranjbar / Journal of Molecular Liquids 160 (2011) 40–49
Table 1
Synthesis of 2,4,5-trisubstituted imidazoles via a one-pot pseudo four-component reaction in the presence of N-methyl-2-pyrrolidonium hydrogen sulfate as Brønsted acidic ionic
liquid (0.08 g, 0.4 mmol) under thermal solvent-free condition at 100 °C.
Entry
1
Aldehydes
Reaction time (h)
Yield %
Benzil
87
M.P/°C
Found
270
Benzil
1.5
Benzoin
2
Benzoin
86
Reported[Ref.]
269[19]
2
2
2.5
89
85
233–236
232–235[20]
3
4
2.5
2.5
3
87
83
90
78
203–206
231–233
205–207[21]
230–232[21]
2.5
5
6
2
1
3
85
78
80
89
210
210–210.5[21]
216–218[22]
1.5
217–220
7
1.5
2.5
95
97
233
233[19]
8
9
1
1
2
96
95
92
90
204–207
270–273
205[23]
272[17]
1.5
10
1.5
1.5
93
89
261–263
260.5–262[24]
11
12
1.5
2
1.5
2.5
96
92
98
97
287–289
176–178
285–287[18,25]
176.5–177[26]
13
2
2.5
95
93
196–198
195–197[27]

H.R. Shaterian, M. Ranjbar / Journal of Molecular Liquids 160 (2011) 40–49
43
Table 1 (continued)
Entry
Aldehydes
Reaction time (h)
Yield %
Benzil
97
M.P/°C
Found
263
Benzil
1.5
Benzoin
2
Benzoin
95
Reported[Ref.]
14
15
262–264[21]
1
2
98
92
242–243
241–242[18]
16
17
1
1.5
2.5
96
89
98
87
N265
N260[18]
2.5
269–271
270[17]
18
1.5
2.5
95
97
176–178
176.5–177[26]
201–202[28]
19
20
1.5
2
1.5
2.5
92
90
95
92
200–202
261–263
261.5–263.5[21]
189–190[27]
257–258[27]
21
22
1.5
1.5
2.5
1.5
92
92
90
98
189–191
256–258
23
24
1.5
2
2.5
2.5
95
87
95
80
202–204
242–243
202–203[28]
243[17]
25
26
2
2
3
90
90
98
92
290–292
242–243
291.5–292[21]
241–242[29]
2.5
(continued on next page)

44
H.R. Shaterian, M. Ranjbar / Journal of Molecular Liquids 160 (2011) 40–49
Table 1 (continued)
Entry
Aldehydes
Reaction time (h)
Yield %
Benzil
93
M.P/°C
Found
Benzil
1.5
Benzoin
2.5
Benzoin
95
Reported[Ref.]
27
243–244
242–244[30]
28
29
S
2.5
3
2.5
3.5
92
90
97
92
260–262
200–201
260–261[27]
200–201[27]
CHO
30
2
2.5
93
97
199
197[31]
31
3
3.5
78
82
261–262
261[17]
Yields refer to isolated pure products. The known products were characterized and compared for their physical properties (M.p, 1H NMR, 13C NMR and FT-IR) with authentic samples.
Table 2
Synthesis of 1,2,4,5-tetrasubstituted imidazoles via a one-pot four component condensation reaction in the presence of N-methyl-2-pyrrolidonium hydrogen sulfate as Brønsted
acidic ionic liquid (0.08 g, 0.4 mmol) under thermal solvent-free condition at 100 °C.
Entry
1
Aldehydes
Amines
Reaction time/min
Yield %
Benzil
90
M.P/°C
Found
Benzil
20
Benzoin
Benzoin
95
Reported[Ref.]
218[32]
25
220–221
2
30
35
95
93
159–160
158–160[32]
3
4
5
35
40
45
40
50
60
75
76
70
73
78
78
211–213
125–127
152–154
208–211[33]
124–126[33]
151–153[33]
6
7
30
30
35
35
80
82
87
78
200–203
164–165
189[32]
165–166[32]

H.R. Shaterian, M. Ranjbar / Journal of Molecular Liquids 160 (2011) 40–49
45
Table 2 (continued)
Entry
Aldehydes
Amines
Reaction time/min
Yield %
Benzil
80
M.P/°C
Found
Benzil
40
Benzoin
Benzoin
82
Reported[Ref.]
8
55
25
20
25
201–203
201–202[32]
170–172[34]
187–189[33]
149–151[33]
9
20
15
20
97
96
97
90
98
95
172–175
188–200
146–149
10
11
12
13
14
15
20
15
20
25
20
93
91
97
98
95
98
221–223
160–162
197–199
219–220[33]
156–158[33]
196–197[33]
15
16
20
45
25
45
92
89
95
87
167–168
190–193
163–165[34]
188–191[33]
17
18
19
35
20
55
45
25
60
85
98
85
93
95
80
130–133
149–152
164–167
128–130[34]
146–148[34]
164[34]
20
30
35
90
92
155–157
156–157[34]
(continued on next page)

46
H.R. Shaterian, M. Ranjbar / Journal of Molecular Liquids 160 (2011) 40–49
Table 2 (continued)
Entry
Aldehydes
Amines
Reaction time/min
Yield %
Benzil
92
M.P/°C
Found
Benzil
20
Benzoin
Benzoin
95
Reported[Ref.]
21
25
135–137
134–135[34]
22
40
45
87
75
158–161
157–160[35]
23
24
20
25
30
35
95
86
95
90
281–284
229–231
280–281[36]
226–228[37]
25
26
27
28
29
35
25
20
20
45
45
30
25
35
45
92
95
90
87
90
89
90
95
92
95
200–203
299–291
200–201
233–234
216–218
199–202[38]
289–290[38]
198–201[38]
230–232[37]
215–217[38]
30
40
45
85
89
219–221
218–220[38]
31
35
45
87
83
188–190
185–187[37]

H.R. Shaterian, M. Ranjbar / Journal of Molecular Liquids 160 (2011) 40–49
47
Table 2 (continued)
Entry
Aldehydes
Amines
Reaction time/min
Yield %
Benzil
89
M.P/°C
Found
185
Benzil
45
Benzoin
Benzoin
83
Reported[Ref.]
32
55
184–186[34]
33
20
25
97
95
250–253
248–251[37]
34
35
60
25
65
25
80
89
78
92
106–108
161–163
104–105[34]
165–167[33]
36
37
20
25
30
35
90
92
96
95
141–142
154–155
140–142[34]
150–152[34]
38
20
25
95
97
186–187
183–185[37]
39
40
25
45
30
55
85
85
90
82
145–146
113–116
144–146 [37]
112–115[33]
Yields refer to isolated pure products. The known products were characterized and compared for their physical properties (M.p, 1H NMR, 13C NMR and IR) with authentic samples.
First report, the condensation reaction of benzil or benzoin
(1 mmol), aldehyde (1 mmol), and ammonium acetate (4 mmol) in
the presence of ionic liquid, N-methyl-2-pyrrolidonium hydrogen
sulfate (0.08 g, 0.4 mmol), as catalyst produces 2,4,5-trisubstituted
imidazoles under solvent-free conditions at 100 °C (Scheme 1).
The stoichiometric amount of ammonium acetate in the prepara-
tion of 2,4,5-trisubstituted imidazoles is 2. We can prepare 2,4,5-
trisubstituted imidazoles using two equivalents of ammonium acetate
but we observed in our experiment and other published papers, if we
use inexpensive and available ammonium acetate having more than
two equivalents, the reaction will show better results. Thus, a slight
excess of the ammonium acetate was found to be advantageous and
hence the molar ratio of benzil or benzoin to ammonium acetate was
kept at 1:4. The efficiency and versatility of the ionic liquid as catalyst
for the preparation 2,4,5-trisubstituted imidazoles were demonstrat-
ed by the wide range of substituted and structurally diverse aldehydes
to synthesize the corresponding products in high to excellent yields
(Table 1). The presence of electron donating groups on the aromatic
aldehyde resulted in the corresponding products in low yields and the
reaction was sluggish, however the presence of electron-withdrawing
groups afforded the corresponding 2,4,5-trisubstituted imidazoles in
shorter reaction time with higher yields. Also, benzil in comparison
with benzoin gives corresponding products in shorter reaction time
rather than benzoin but there was no effect in the yield of
corresponding 2,4,5-trisubstituted imidazoles.
Next, as part of our program aimed at developing useful new synthesis
methods based on the use of mentioned ionic liquid as a catalyst, we have
studied the four-component one-pot synthesis of 1,2,4,5-tetrasubstituted
imidazoles by condensing benzil or benzoin (1 mmol), aldehyde
(1 mmol), amine (1 mmol), and ammonium acetate (1 mmol) using a
catalytic amount of N-methyl-2-pyrrolidonium hydrogen sulfate (0.08 g,
0.4 mmol) under solvent-free conditions at 100 °C.
The substrate scope of the reaction was then evaluated using a
variety of structurally diverse aldehydes and amines. Both aliphatic and

48
H.R. Shaterian, M. Ranjbar / Journal of Molecular Liquids 160 (2011) 40–49
Table 3
Comparison of the efficiency of various catalysts with N-methyl-2-pyrrolidonium hydrogen sulfate in the synthesis of 2,4,5-trisubstituted imidazoles.
Entry
Catalyst
Conditions
Time (min)
Yield (%)
Ref.
1
2
3
4
5
6
8
9
InCl3·3H2O
KH2PO4
Yb(OPf)3
Zr(acac)4
L-proline
[H bim]BF4
MeOH/R.T
492
60
360
120
540
60
76
89
80
95
87
94
89
98
[39]
[40]
[41]
[42]
[23]
[19]
[43]
Present work
Reflux in EtOH
C10F18/80 °C
Reflux in EtOH
Methanol/60 °C
100 °C
NiCl2·6H2O/Al2O3
N-methyl-2-pyrrolidonium hydrogen sulfate
Reflux in EtOH
100 °C
90
60
Based on the preparation of 2-(4-nitrophenyl)-4,5-diphenyl-1H-imidazole (Table 1, Entry 15).
Table 4
Comparison of the efficiency of various catalysts with N-methyl-2-pyrrolidonium hydrogen sulfate in the synthesis of 1,2,4,5-tetrasubstituted imidazoles.
Entry
Catalyst
Conditions
Time (min)
Yield (%)
Ref.
1
2
3
4
5
6
7
8
9
BF3/SiO2
SiO2
NaHSO4/SiO2
InCl3·3H2O
L-proline
AlCl3
MgCl2
SnCl4
140 °C
CH2Cl2/R.T
140 °C
120
120
120
440
540
120
120
120
120
30
92
90
92
79
88
53
50
60
95
98
[41]
[44]
[33]
[39]
[23]
[41]
[41]
[32]
140 °C
Methanol/R.T
Methanol/60 °C
140 °C
140 °C
140 °C
K5CoW12O40.3H2O
N-methyl-2-pyrrolidonium hydrogen sulfate
[37]
Present work
10
100 °C
Based on the preparation of 1-benzyl-4,5-diphenyl-2-P- tolyl-1H-imidazole (Table 2, Entry 7).
aromatic aldehydes and primary amines could be subjected success-
fully to this protocol. Aromatic aldehydes and amines produced high
yields of 1,2,4,5-tetrasubstituted imidazoles, whereas aliphatic alde-
hydes and amines produced moderate to lower yields of the
corresponding imidazoles (Table 2, Entries 3–5, 8, 19, 34). The presence
of electron donating groups on the aromatic aldehydes and aromatic
anilines resulted in the corresponding products in low yields and the
reaction was sluggish, however the presence of electron-withdrawing
O
O S O
N
O
O
NH4OAC
H
H3C
H
H
+
NH3
O
O
R
O S O
O
N
O
H
OH
H3C H
Ph
Ph
R
HN
NH
CH
+H+
Ph
Ph
O
Ph
Ph
O
O
-H2O
H
NH3
(II)
R
NH
NH
(I)
NH4OAC
(III)
H CH3
N
O
O
H
O S O
O
Ph
Ph
N
-H+
Ph
Ph
OH
H
R
N
Ph
Ph
-H2O
R
N
NH
CH
N
H
H
R
N
H
(IV)
Scheme 3. Mechanism of condensation reaction between benzil, benzaldehyde, and ammonium acetate in the presence of N-methyl-2-pyrrolidonium hydrogen sulfate as Brønsted
acidic ionic liquid.

H.R. Shaterian, M. Ranjbar / Journal of Molecular Liquids 160 (2011) 40–49
49
ammonium acetate in a pseudo four-component reaction and affords
the corresponding 2,4,5-trisubstituted imidazoles in high yields. Also
this recyclable catalyst has been used for preparation of 1,2,4,5-
tetrasubstituted imidazoles by one-pot four-component condensation
of benzil or benzoin, aldehydes, amines and ammonium acetate in
excellent yields under solvent-free and conventional heating condi-
tions. The recovered ionic liquid was reused for seven cycles without
loss of its activities.
Acknowledgments
We are thankful to the University of Sistan and Baluchestan
Research Council for the partial support of this research.
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in shorter reaction times with higher yield. Also, benzil reacts in shorter
reaction time rather than benzoin but without any effect on the yields.
To show the merit of the present work in comparison with
reported results in the literature, we compared results of N-methyl-2-
pyrrolidonium hydrogen sulfate with reported catalysts in the
synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imida-
zoles. As shown in Tables 3 and 4, the ionic liquid can act as a suitable
catalyst with respect to reaction times and yields of the products.
The proposed mechanism for the reaction using ionic liquid as
catalyst is also described for the preparation of 2,4,5-trisubstituted
imidazoles from the reaction of benzil, aldehyde and ammonium
acetate in Scheme 3. According to literature report [17,18], hydrogen
bonding can occur between the solute (benzil) and the cationic
(N+\H) or ionic component (SO−4 \H) of ionic liquid. Brønsted acidic
ionic liquid, N-methyl-2-pyrrolidonium hydrogen sulfate can activate
the carbonyl groups of benzil and aldehydes to decrease the energy of
transition state. Then nucleophilic attack of the nitrogen of ammonia
obtained from NH4OAc on the activated carbonyl group, resulted in
the formation of aryl aldimine (I) and α-imino ketone (II), and it
followed by the nucleophilic attack of the in-situ generated imine to
carbonyl of aryl aldimine giving the intermediate (III). Their
subsequent intramolecular interaction leads to cyclization and
eventually to the formation of intermediate (IV) which dehydrates
to the 2,4,5-trisubstituted imidazoles.
We also investigated the recycling of the catalyst under solvent-
free conditions using a model reaction of 4-methylbenzaldehyde
(1 mmol), benzylamine (1 mmol), benzil (1 mmol), and ammonium
acetate (1 mmol) (Table 2, Entry 7). After completion of the reaction,
water was added and the precipitated mixture was filtered off for
separation of crude products. After washing the solid products with
water completely, the water containing ionic liquid (IL is soluble in
water) was evaporated under reduced pressure and ionic liquid was
recovered and reused (Fig. 1). We also calculate turnover frequency
(TOF) to discuss the activity of the catalyst. The substrate conversion
percentage to the product was 100% and TOF obtained 5 h−1. The
recovered catalyst was reused seven runs without any loss of its
activities and the activity (TOF) did not decrease.
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4. Conclusions
N-methyl-2-pyrrolidonium hydrogen sulfate efficiently catalyzes
the condensation reaction of benzil or benzoin, aldehydes and