Superoxide ion promoted synthesis of 2-Arylbenzimidazoles from schiff bases

Article abstract of DOI:10.2174/1570178612666151028210206

Background: Benzimidazoles exhibit a wide range of biological activities, including antiparasitic, antiulcer, antihypertensive, antihistaminic, anticancer, antiemetic and antiinflammatory agents. Methods: Tetraethylammonium superoxide has been generated in situ by the phase transfer reaction of potassium superoxide and tetraethylammonium bromide in dry dimethylformamide at room temperature and subsequently allowed to react with a number of Schiff's bases. Results: The Synthesis of 2-Arylbenzimidazoles from Schiff bases using in situ generated tetraethylammonium superoxide in dry DMF, at room temperature. Conclusion: The role of in situ generated Et4NO2 as an efficient agent to promote the synthesis of 2-Arylbenzimidazole from Schiff base has been demonstrated under mild conditions.

Full text of DOI:10.2174/1570178612666151028210206

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Letters in Organic Chemistry, 2016, 13, 67-70
67
Superoxide Ion Promoted Synthesis of 2-Arylbenzimidazoles from Schiff
Bases
*
Raghvendra S. Raghuvanshi , Virendra P. Yadav and Vinod K. Singh
Department of Chemistry, Faculty of Science, Udai Pratap (Autonomous) College, Varanasi 221002,
India
Received October 27, 2014: Revised October 06, 2015: Accepted October 26, 2015
Abstract:
Background: Benzimidazoles exhibit a wide range of biological activities, including antiparasitic,
antiulcer, antihypertensive, antihistaminic, anticancer, antiemetic and antiinflammatory agents.
Methods: Tetraethylammonium superoxide has been generated in situ by the phase transfer reaction of
potassium superoxide and tetraethylammonium bromide in dry dimethylformamide at room tempera-
ture and subsequently allowed to react with a number of Schiff's bases.
Results: The Synthesis of 2-arylbenzimidazoles from Schiff bases using in situ generated tetraethylammonium superoxide
in dry DMF, at room temperature.
4 2
Conclusion: The role of in situ generated Et NO as an efficient agent to promote the synthesis of 2-arylbenzimidazole
from Schiff base has been demonstrated under mild conditions.
Keywords: Benzimidazole, oxidative cyclization, superoxide.
INTRODUCTION
N
CH
R
N
KO / Et NBr
2
4
R
Benzimidazoles exhibit a wide range of biological activi-
ties, including antiparasitic, antiulcer, antihypertensive,
antihistaminic, anticancer, antiemetic and antiinflammatory
agents [1-5]. There exist two general methods for synthesiz-
ing 2-substituted benzimidazoles. One is the coupling of o-
phenylenediamines and carboxylic acids or their derivatives,
which often required strong acidic conditions at high tem-
perature or under microwave irradiation [6-11]. The other
method involves oxidative cyclization of Schiff bases, de-
rived from the condensation of o-phenylenediamines and
aldehydes, using various oxidants such as lead tetraacetate
DMF, RT
N
H
NH
2
1
a - h
Scheme 1.
RESULTS AND DISCUSSION
2a - h
Tetraethylammonium superoxide has been generated in
situ by the phase transfer reaction of potassium superoxide
and tetraethylammonium bromide in dry dimethylformamide
at room temperature and subsequently allowed to react with
a number of Schiff's bases viz., N-benzylidene-o-phenyl-
enediamine 1a, N-p'-chlorobenzylidene-o-phenylenediamine
[
12, 13], nickel peroxide [14], active manganese dioxide [15]
and barium manganate [16]. However, second method usu-
ally involves use of transition metals that require tedious
chromatography purification of the desired product. Re-
cently, some other methods for the preparation of benzimi-
dazole derivatives have been reported [17].
1
b, N-m'-nitrobenzylidene-o-phenylenediamine 1c, N-p'-nitro-
benzylidene-o-phenylenediamine 1d, N-p'-hydroxybenzyl-
idene-o-phenylenediamine 1e, N-p'-methylbenzylidene-o-
phenylenediamine 1f, N-p'-methoxybenzylidene-o-phenyl-
enediamine 1g, N-2-furylmethylene-o-phenylenediamine 1h
to bring out an oxidative cyclization to give the correspond-
ing benzimidazoles 2a-h in reasonably good to excellent
yields (Table 1).
In light of the above and as a part of the ongoing research
on superoxide chemistry [18], herein a mild and efficient
protocol is reported for the synthesis of 2-
arylbenzimidazoles from Schiff bases using in situ generated
tetraethylammonium superoxide in dry DMF, at room tem-
perature (Scheme 1).
The reaction was accomplished by using a 3.0 fold molar
excess of KO
spect to substrate 1. Generally, the substrate was allowed to
react with Et NO for 3-6 hrs at room temperature. The reac-
2 4
and 1.5 fold molar excess of Et NBr with re-
4
2
*
Address correspondence to this author at the Department of Chemistry,
tion was then quenched with cold brine solution followed by
work-up to afford the products. The total disappearance of
the starting material was checked by thin layer chromatogra
Faculty of Science, Udai Pratap (Autonomous) College, Varanasi 221002,
India; Tel: +91-9415812182; E-mails: rsr_itbhu@rediffmail.com, and
rsrupc@gmail.com
1
875-6255/16 $58.00+.00
© 2016 Bentham Science Publishers

6
8
Letters in Organic Chemistry, 2016, Vol. 13, No. 1
Raghuvanshi et al.
Table 1. Reaction of in situ generated Et NO
4
2
with various Schiff bases (1a-h).
Substrate (1)
Entry
Substituent (R)
Product (2)
Yield (%)
A
B
C
D
E
Ph
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2f
83
72
68
80
81
77
74
69
p-ClC
m-NO
p-NO
p-OHC
p-CH
p-CH OC
2-Furyl
6
H
4
2
C
6
H
4
2
6 4
C H
6 4
H
F
3
C
6
H
4
G
H
3
6
H
4
1g
1h
2g
2h
N
CH
R
N
CH
R
.
2
.
+
O
+ HO
2
NH
2
NH
_
N
H
N
H
R
.
2
.
O
+
HO
HO
+
O
2
2
2
_
N
.
H
N
H
.
+
O
2
+
O
2
N
H
R
N
H
R
.
N
H
N
.
+
HO
R
+
H O
2 2
2
N
H
R
N
H
Scheme 2.
phy (TLC). The identity of all known compounds was con-
firmed by IR, H NMR and comparison with literature spec-
tral and m.p. values [12,13,16,19-21].
(4Å) prior to use. Schiff bases were prepared according to a
literature procedure [13]. Melting points were measured in
open capillaries and are uncorrected. IR spectra were re-
corded on a Jasco FT/IR-5300 spectrophotometer. NMR
spectra were run on a Jeol AL300 FT-NMR and chemical
shift is expressed as ꢀ(ppm), using TMS as internal refer-
ence.
1
Based on product isolation and existing chemistry [22-
·
2
4] of
O
¯
2
, a plausible mechanism is outlined for the oxida-
tive cyclization observed (Scheme 2).
General Procedure for the Reaction of in situ Generated
Tetraethylammonium Superoxide with Schiff Bases 1a-h
CONCLUSION
4 2
In conclusion, the role of in situ generated Et NO as an
Potassium superoxide (0.43 g; 6 mmol) and tetraethy-
lammonium bromide (0.63 g; 3 mmol) were weighted under
nitrogen atmosphere using an atmosbag and were transferred
into a two-necked round bottom flask, equipped with mag-
netic stirrer, nitrogen inlet and a Liebig condenser protected
by calcium chloride drying tube. Dry dimethylformamide
efficient agent to promote the synthesis of 2-
arylbenzimidazole from Schiff base has been demonstrated
under mild conditions.
EXPERIMENTAL
(
25 mL) was added to it and the mixture was agitated mag-
Potassium superoxide and tetraethylammonium bromide
were procured from E. Merck, and were used as received.
Dry DMF from Aldrich, was stored over molecular sieves
netically for 15 min to facilitate the formation of tetraethy-
lammonium superoxide. Finally, the Schiff base 1a-h (2

Superoxide Ion Promoted Synthesis
Letters in Organic Chemistry, 2016, Vol. 13, No. 1
69
mmol) was admitted to it and the stirring was continued at
room temperature for 3-6 hrs in the presence of nitrogen to
avoid atmospheric moisture until the complete loss of the
starting material was indicated by TLC. After the reaction
was over, the mixture was treated with brine solution (20
mL) to decompose the unreacted potassium superoxide. The
ACKNOWLEDGEMENTS
The authors are thankful to the Council of Scientific and
Industrial Research (CSIR), New Delhi for financial support.
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ꢀ
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