Potassium aluminum sulfate (alum): An efficient catalyst for the one-pot synthesis of trisubstituted imidazoles

Article abstract of DOI:10.1007/s00706-008-0875-7

Trisubstituted imidazoles were synthesized in high yields in the presence of potassium aluminum sulfate (alum) as a non-toxic, reusable, inexpensive, and easily available reagent at 70°C.

Full text of DOI:10.1007/s00706-008-0875-7

Monatsh Chem 139, 935–937 (2008)
DOI 10.1007/s00706-008-0875-7
Printed in The Netherlands
Potassium aluminum sulfate (alum): an efficient catalyst
for the one-pot synthesis of trisubstituted imidazoles
1
2
2
Ali A. Mohammadi , Mersede Mivechi , Hassan Kefayati
1
Department of Chemistry, Faculty of Science, Islamic Azad University-branch Sabzevar,
Sabzevar, Iran
2
Department of Chemistry, Faculty of Science, Islamic Azad University-branch Rasht, Rasht, Iran
Received 11 December 2007; Accepted 17 December 2007; Published online 5 July 2008
Springer-Verlag 2008
#
Abstract Trisubstituted imidazoles were synthesized
in high yields in the presence of potassium aluminum
sulfate (alum) as a non-toxic, reusable, inexpensive,
of strong protic acid, such as H PO [17], H SO
3 4 2 4
[18], AcOH [19] as well as an organo catalyst in
AcOH [19] under reflux conditions; isolation of prod-
uct requires neutralization of the reaction mixture.
Since solid acids are environmentally friendly with
respect to corrosiveness, safety, less waste, and ease
of separation and recovery, replacement of these liq-
uid acids is desirable in the chemical industry.
Recently, a few research groups have reported one-
pot condensation of ꢀ-hydroxy ketone, ꢀ-ketoxime,
ꢀ
and easily available reagent at 70 C.
Keywords Imidazole; Multicomponent condensations; Ben-
zil; Benzoin; KAl(SO ) ꢁ 12H O (alum).
4
2
2
Introduction
Multi-component condensations (MCCs) constitute
an especially attractive synthesis strategy for rapid
and efficient generation of molecules due to the fact
that the products are formed in a single step and also
the diversity could be achieved simply by varying
the reacting components.
Multi-substituted imidazoles are an important
class of compounds in the field of pharmaceuticals
and exhibit a wide spectrum of biological activities
or 1,2-diketone, aldehyde, and NH OAc on solid
4
supports under microwave irradiation [20–23].
However, in spite of their potential utility, most of
these methods not only need high temperatures
ꢀ
(180–200 C) but also the reactions were conducted
in AcOH.
Results and discussion
[1–3]. Owing to the versatile biological activities of
During the course of our studies toward development
of new routes for the synthesis of highly substituted
heterocycles [24–26] using potassium aluminum sul-
fate (alum) catalysts [27, 28], we wish to introduce
an efficient procedure for the synthesis of trisubsti-
tuted imidazoles 4a–4p via one-pot condensation
of 1,2-diketone 1a or ꢀ-hydroxy ketone 1b with
these compounds, numerous classical methods for
their synthesis have been reported [4–16]. In a ty-
pical procedure, a 1,2-diketone, an aldehyde, and
ammonium acetate are condensed in the presence
Correspondence: Ali A. Mohammadi, Department of
Chemistry, Faculty of Science, Islamic Azad University-
branch Sabzevar, P.O. Box 9618814711, Sabzevar, Iran.
E-mail: aliamohammadi@iaus.ac.ir
aldehyde 2a–2p and NH OAc in the presence of
4
KAl(SO ) ꢁ 12H O (alum) as a non-toxic, reusable,
4
2
2

9
36
A. A. Mohammadi et al.
inexpensive, and easily available catalyst in ethanol
under classical heating conditions (Scheme 1).
We found that this condensation might be conduct-
ed in various solvents as is evident from Table 1.
Most excitingly, the condensation could also be car-
ried out in ethanol with an excellent yield.
When a mixture of benzil (1a), benzaldehyde (2a),
ꢀ
and NH OAc (3) was stirred in ethanol at 70 C in the
4
presence of a catalytic amount of alum, the reaction
was completed within 2.5 h. Workup of the reaction
mixture showed that imidazole 4a was prepared in
Scheme 1
9
3% yield.
Table 1 KAl(SO ) ꢁ 12H O (alum)-catalyzed condensation
4
2
2
Encouraged by this achievement, we extended the
reaction of benzil (1a) or benzoin (1b) and NH OAc
of benzil (1), benzaldehyde (2a), and NH OAc (3), under
4
a
4
different reaction conditions
with a range of other aldehydes 2b–2p under similar
conditions, furnishing the respective imidazoles 4b–
b
Entry
Solvent
Yield of 3a=%
4p in good yields. The optimized results are summa-
rized in Table 2.
1
2
4
5
H O
2
70
93
60
40
CH CH OH
3
2
CH CN
3
None
In conclusion, we were able to introduce an effi-
cient and environmentally friendly approach for the
synthesis of biologically active trisubstituted imid-
azoles via condensation of 1,2-diketone or ꢀ-hy-
droxy ketone with various aromatic aldehydes and
a
The reaction were carried out in the presence of 1 mmol
benzil, 1 mmol benzaldehyde, 4 mmol NH OAc, and 0.3 g
4
ꢀ
KAl(SO ) ꢁ 12H O at 70 C for 150 min
4
2
2
b
Isolated yield
ꢀ
a
Table 2 One-pot synthesis of trisubstituted imidazoles in the presence of alum under classical heating conditions at 70 C
1
b
ꢀ
Entry
R
Products 4
Yield=%
Time=h
mp= C
Found
Reported
1
2
3
4
5
6
7
8
9
C H
6
a
b
c
d
e
f
g
h
i
93
94
87
85
93
89
90
95
92
90
82
85
92
82
86
89
88
89
83
91
88
2.5
2.5
3.5
4
3
3
3
2.5
3
4
3.5
3
3
3.5
4
4
3
272–273
226–228
228–231
212–214
259–261
252–254
282–286
198–202
230–232
285–286
242–244
246–248
242–244
>280
208–209
249–251
272–273
226–228
228–231
259–261
282–286
269 [1]
232–235 [2]
230–232 [29]
210–210.5 [29]
262–264 [29]
261.5–263.5 [29]
285–287 [29]
205–207 [29]
233 [1]
291.5–292 [29]
–
–
241–242 [30]
>260 [30]
202–203 [31]
– [18]
5
4-CH C H
6 4
3
4-CH OC H
6
3
4
4
2-CH OC H
3
6
4-ClC H
6
4
4-BrC H
6
4
3-ClC H
6
4
2-MeC H
6
4
4-OHC H
6
4
10
11
12
13
14
15
16
17
18
19
20
21
1-naphthyl
4-CH SC H
6 4
4-CH O CC H
6 4
j
k
l
3
3
2
4-NO C H
2
3-NO C H
2
2-furyl
m
n
o
p
a
b
c
e
g
6
4
4
6
2-thienyl
C H
4-CH C H
c
c
c
c
c
269 [1]
6
5
3
232–235 [2]
230–232 [29]
262–264 [29]
285–287 [29]
3
6
4
4-CH OC H
3
3.5
3.5
3.4
6
4
4-ClC H
6
4
4
3-ClC H
6
a,c
Reaction conditions: benzil or benzoin (for entry 17–21) (1 mmol), aldehyde (1 mmol), NH OAc (4 mmol), and KAl(SO ) ꢁ
4
4 2
ꢀ
1
2H O (0.3 g), 70 C
2
b
Isolated yield

Trisubstituted
937
ammonium acetate using potassium aluminum sul-
fate (alum) as a non-toxic, reusable, inexpensive,
and easily available reagent at 70 C. Corrosiveness
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1
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þ
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(
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4
Methyl 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoate
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(
2
3 18 2 2
ꢀ
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1
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3
045 (C–H), 1694 (C¼O), 1607 (C¼C) cm
(
(
(
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3
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3
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6
5
1
8
2.5, 125.3, 127.3, 128.1, 128.3, 129.2, 129.8, 132.7, 134.2,
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þ
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Acknowledgements
(
2006) J Fluor Chem 127:1570
We greatefully acknowledge the financial support from the
Research Council of Islamic Azad University-branch Sabzevar
and of Islamic Azad University-branch Rasht.
3
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Commun 35:1369