Sodium bisulfite as an efficient and inexpensive catalyst for the one-pot synthesis of 2,4,5-triaryl-1H-imidazoles from benzil or benzoin and aromatic aldehydes

Article abstract of DOI:10.1007/s00706-007-0766-3

2,4,5-Triaryl-1H-imidazoles were efficiently synthesized from benzoin or benzil, ammonium acetate, and aromatic or heteroaromatic aldehydes in the presence of sodium bisulfite as catalyst. The present protocol offers significant improvements for the synthesis of 2,4,5-triaryl-1H-imidazoles with regard to yield of products, simplicity in operation, and cheap catalyst.

Full text of DOI:10.1007/s00706-007-0766-3

Monatshefte f u¨ r Chemie 139, 125–127 (2008)
DOI 10.1007/s00706-007-0766-3
Printed in The Netherlands
Sodium Bisulfite as an Efficient and Inexpensive Catalyst for the One-pot
Synthesis of 2,4,5-Triaryl-1H-imidazoles from Benzil or Benzoin
and Aromatic Aldehydes
1
1;2
1
Jaiprakash N. Sangshetti , Nagnnath D. Kokare , Sandeep A. Kotharkar ,
1
;Ã
and Devanand B. Shinde
1
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, India
2
New Drug Discovery, Wockhardt Research Centre, Aurangabad, India
Received July 18, 2007; accepted August 2, 2007; published online January 11, 2008
Springer-Verlag 2008
#
Summary. 2,4,5-Triaryl-1H-imidazoles were efficiently syn-
thesized from benzoin or benzil, ammonium acetate, and aro-
matic or heteroaromatic aldehydes in the presence of sodium
bisulfite as catalyst. The present protocol offers significant
improvements for the synthesis of 2,4,5-triaryl-1H-imidazoles
with regard to yield of products, simplicity in operation, and
cheap catalyst.
animal species and humans. In recent years, sub-
stituted imidazoles are substantially used in ionic
liquids [6] that have been given a new approach to
‘
Green Chemistry’. The imidazole compounds are
also used in photography as photosensitive com-
pound [7].
In literature several methods for synthesizing them
are reported, mainly using nitriles and esters [8, 9] as
the starting substrates. Japp and Radziszewski pro-
posed the first synthesis of the imidazole core in
Keywords. Triaryl-1H-imidazoles; Sodium bisulfite; Benzoin;
Benzil; Ammonium acetate.
Introduction
1882, starting from 1,2-dicarbonyl compounds, alde-
Over the century, imidazoles have received signifi-
cant attention due to their reactions and biochemical
properties. Even today, research in imidazole chem-
istry continues. Compounds with an imidazole moi-
ety have biological and pharmaceutical importance
hydes, and ammonia, to obtain 2,4,5-triphenylimida-
zoles [10, 11]. Subsequently, many other syntheses
of this important heterocycle have been published
[12]. For example, 2,4-diaryl-1H-imidazoles are of-
ten obtained from amidines and ꢀ-bromoarylketones
[13]. Moreover, Zhang and Chen described an effi-
cient procedure to obtain unsymmetrical, C5 un-
substituted 2,4-diarylimidazoles. In this approach
acetophenones are oxidized in situ to ꢀ-(tosyloxy)-
acetophenones, which then condense with arylamid-
ines to obtain the desired compounds [14]. Recently,
some methods for synthesis of substituted imid-
azoles have been reported [15, 16]. However, some
of these methods suffer from one or more drawbacks
like high temperature requirement, highly acidic
conditions, and the use of metal cyanides for prepa-
ration of the nitrile compounds that limit their uses
[1]. Several substituted imidazoles are known as
inhibitors of P 38 kinase [2]. Eprosartan is one of
the series of 1-(carboxybenzyl)imdazole-5-acrylic
acids, which is a potent and selective angiotensin
II receptor antagonist [3]. Highly substituted imid-
azoles like lepidilines A and B [4] exhibit micro-
molar cytotoxicity against several human cancer cell
lines. Trifenagrel [5] is a potent 2,4,5-triarylimid-
azole that reduces platelet aggregation in several
Ã
com
Corresponding author. E-mail: dbshinde.2007@rediffmail.

1
26
J. N. Sangshetti et al.
Scheme 1
[17, 18]. Some of the methods have resorted to harsh
conditions (e.g., the formamide synthesis, which re-
Table 1. Optimization of reaction conditions for synthesis of
2,4,5-triphenyl-1H-imidazole using 10 mol% sodium bisulfite
as catalyst
quires excess reagents, H SO as a condensing agent,
2
4
ꢀ
1
[
50–200 C, 4–6 h resulting in yields of 40–90%)
19–21]. Therefore, the development of a mild, effi-
Solvent
Reaction time=min
Yield=%
Acetonitrile
THF
Ethanol
THF=water (1=1)
Acetonitrile=water (1=1)
Ethanol=water (1=1)
45
50
30
50
50
30
93
79
98
78
89
98
cient, and versatile method is still strongly desirable.
In continuation of our ongoing research for the
development of simple and efficient methods for
the synthesis of various heterocyclic compounds
[
22], herein we wish to report a simple, economic,
and efficient one-pot method for the synthesis of
,4,5-triaryl-1H-imidazoles from benzoin or benzil,
2
ammonium acetate, and aromatic aldehydes using
sodium bisulfite as the catalyst.
as solvent, and 10 mol% sodium bisulfite as catalyst.
Using the standardized reaction conditions, a range
of 2-aryl-4,5-diphenylimidazoles were synthesized.
The same methodology was extended for the synthe-
sis of 2-heteroaryl-4,5-diphenylimidazoles using het-
ero-aromatic aldehydes. The results are summarized
in Table 2.
1,2-Diketones (like benzil) are usually prepared
from the ꢀ-hydroxy ketones (like benzoin) catalyzed
by various oxidants. Some of these catalysts are tox-
ic, costly, and also require tedious experimental pro-
cedures [23]. To avoid the preparation of starting
Results and Discussion
Initially, we studied the catalytic efficiency of sodi-
um bisulfite for the synthesis of 2,4,5-triphenyl-1H-
imidazole (4a) using benzil, ammonium acetate, and
benzaldehyde in different solvents and various mol%
of sodium bisulfite (Scheme 1). The title compound
4a was isolated with 98% yield using optimized
reaction conditions (Table 1), ethanol:water (1:1)
Table 2. Synthesis 2,4,5-triaryl-1H-imidazoles using benzil or benzoin, ammonium acetate, aromatic aldehydes, and 10 mol%
sodium bisulfite
ꢀ
Product
Aldehyde
Rection time=min
Yield=%
mp= C
Benzil
Benzoin
Benzil
Benzoin
Found
Reported [Ref.]
4
4
4
a
b
c
benzaldehyde
4-methylbenzaldehyde
4-methoxybenzaldehyde
4-hydroxybenzaldehyde
2-chlorobenzaldehyde
4-(dimethylamino)benzaldehyde
4-chlorobenzaldehyde
4-nitrobenzaldehyde
30
35
30
35
30
30
30
40
30
30
40
50
40
50
30
40
40
60
50
40
98
98
96
95
92
95
98
90
96
95
96
95
93
92
90
90
94
85
92
92
277–279
231–233
229–231
268–270
195–196
255–258
259–262
232–233
220–221
199–201
276–77 [9]
231–232 [9]
227–228 [9]
268–269 [24]
197–198 [24]
257–258 [9]
261–263 [9]
236–238 [9]
216–218 [25]
202–203 [25]
4
d
4
4
e
f
g
4
4
h
4
4
i
j
3,4-dimethoxybenzaldehyde
furan-2-carbaldehyde

Sodium Bisulfite as an Efficient and Inexpensive Catalyst
material 1,2-diketones like benzil, the synthesis of
127
JR, Landvatter SW, Strickler JE, McLauhlin MM,
Siemens IR, Fisher SM, Livi JP, White JR, Adams
JL, Young PR (1994) Nature 372: 739
4
a was studied using benzoin. Surprisingly, using
similar reaction conditions, 4a was isolated in 96%
yield. Encouraged by this result, we extended the
methodology for the synthesis of various 2,4,5-
triaryl-1H-imidazoles using benzoin and various ar-
omatic aldehydes. The yields obtained were in the
range of 85–96%.
In conclusion, using 10 mol% sodium bisulfite as
catalyst, 2,4,5-triaryl-1H-imidazoles were efficiently
synthesized with better yields from benzil and even
as well as benzoin. For all the presented reactions,
the ethanol–water solvent was used, which is rela-
tively environmentally benign.
[
3] Pierce ME, Carini DJ, Huhn G, Wells GJ, Arnett JF
(1993) J Org Chem 58: 4642
[4] Cui B, Zheng BL, He K, Zheng QY (2003) J Nat Prod
66: 1101
[
[
5] Abrahams SL, Hazen RJ, Batson AG, Phillips AP (1989)
J Pharmacol Exp Ther 249: 359
6] a) Wasserscheid P, Keim W (2000) Angew Chem Int Ed
Eng 39: 37872; b) Bourissou D, Guerret O, Ggabbai FT,
Bertrand G (2000) Chem Rev 100
[7] Satoru I (1989) Japn Kokkai Tokyo Koho 117: 867
[
8] Grimmett MR (1996) In: Katritzky AR, Rees CW,
Scriven EFV (eds) Comprehensive Heterocyclic Chem-
istry II, vol. 3. Pergamon, NewYork, p 77
[9] Balalaie S, Arabanian A, Hashtroudi MS (2000) Mon-
atsh Chem 131: 945
[
[
[
10] Radziszewski B (1882) Chem Ber 15: 1493
11] Japp FR, Robinson HH (1882) Chem Ber 15: 1268
12] For example, see: Grimmett MR (1996) In: Katritzky
AR, Rees C, Scriven EFV (eds) Comprehensive Hetero-
cycle Chemistry II, vol. 3. Pergamon Press, Elmsford,
NY, p 457
Experimental
1
H NMR spectra were recorded on a 400 MHz Varian-Gemini
spectrometer and are reported as ppm downfield from internal
standard TMS. Mass spectra were taken with Micromass-
QUATTRO-II of WATERS mass spectrometer. Melting points
were determined in capillary tubes.
[
13] Li B, Chiu CKF, Hank RF, Murry J, Roth J, Tobiassen H
(2006) Org Proc Res Dev 6: 682
[
[
14] Zhang PF, Chen ZC (2000) Synthesis 14: 2075
15] a) Nagarapu L, Apuri S, Kantevari S (2007) J Mol Catal
A-Chem 266: 104; b) Kidwai M, Mothsra P, Bansal V,
Goyal R (2006) Monatsh Chem 137: 1189
General Method for the Synthesis of 2,4,5-Triaryl-1H-
imidazoles
A mixture of 0.104 g sodium bisulfite (10 mol%), 2.8g ammo-
nium acetate (40 mmol), and 10 mmol benzil or benzoin was
3
dissolved in 20cm ethanol=water (1=1, v=v) and to this mix-
[16] Kidwai M, Mothsra P (2006) Tetrahedron Lett 47:
029
[17] Davidson D, Weiss M, Jelling M (1937) J Org Chem 2:
19
[18] Zhang EJ, Moran EJ, Woiwode TF, Short KM, Mjalli
AM (1996) Teterahedron Lett 37: 351
5
ture, 12 mmol aromatic aldehyde were added. Then, the reac-
ꢀ
tion mixture was heated at 80 C till completion of reaction
(TLC). The reaction mixture was cooled to room temperature
3
3
and poured on 50 cm ice-water to get the solid precipitated. It
was collected by filtration, washed with water, and dried to
give the corresponding 2,4,5-triaryl-1H-imidazoles.
[19] Usyatinsky AY, Khmelnitsky YL (2000) Tetrahedron
Lett 41: 5031
[20] Wasserman HH, Long YO, Zhang R, Parr J (2002)
Tetrahedron Lett 43: 3351
All synthesized compounds were characterized with
H NMR and mass. Also the melting points recorded were
1
compared with the corresponding literature melting points and
found to be matching.
[
21] Deprez P, Guillaume J, Becker R, Corbier A,
Didierlaurent S, Fortin M, Frechet D, Hamon G,
Heckmann B, Heitsch H, Kleemann HW, Vevert JP,
Vincent JC, Wagner A, Zhang J (1995) J Med Chem
Acknowledgements
3
8: 2357
22] a) Kokare ND, Nagawade RR, Rane VP, Shinde DB
2007) Synthesis 4: 766; b) Kotharkar SA, Jadhav MR,
The authors are grateful to the Head Dr. D.B. Shinde,
Department of Chemical Technology, Dr. Babasaheb
Ambedkar Marathwada University, Aurangabad – 431004
[
(
Nagawade RR, Bahekar SS, Shinde DB (2005) Lett Org
Chem 2: 398; c) Bahekar SS, Shinde DB (2004) Tetra-
hedron Lett 45: 7999; d) Bahekar SS, Kotharkar SA,
Shinde DB (2000) Mendeleev Commun: 2
(MS), India for providing the laboratory facility.
References
[
23] a) Weiss M, Abbel M (1948) J Am Chem Soc 70:
3666; b) McKillop A, Swann B, Ford ME, Taylor EC
(1973) J Am Chem Soc 95: 3641; c) Zhang GS, Shi QZ,
Chen MF, Cai K (1997) Synth Commun 27: 953
[
1] a) Claiborne CF, Liverton NJ, Nguyen KT (1998) Tet-
rahedron Lett 39: 8939; b) Zhang C, Sarshar S, Morgan
EJ, Krane S, Rodarte JC, Benbatoul KD, Dixon R, Mjalli
AMM (2000) Bioorg Med Chem 10: 2603
[24] White DM, Sonnenberg J (1964) J Org Chem 29: 1926
[25] Zhou JF, Song YZ, Tu SJ (2005) Synth Commun 35:
1369
[2] Lee JC, Laydon JT, McDonnell PC, Gallagher TF,
Kumar S, Green D, McNully D, Blumenthal M, Heys