Rapid one-pot preparation of 2-substituted benzimidazoles from esters using microwave conditions

Article abstract of DOI:10.1080/00397910600764204

A high-yielding one-pot procedure for the generation of 2-substituted benzimidazoles first from esters using a microwave procedure is described. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600764204

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Rapid One‐Pot Preparation of 2‐Substituted
Benzimidazoles from Esters using Microwave
Conditions
Xiaobi Jing a , Qihua Zhu a , Feng Xu a , Xinfeng Ren b , Dong Li a & Chaoguo
Yan a
a College of Chemistry and Chemical Engineering, Yangzhou University,
Yangzhou, China
b College of Chemistry and Chemical Engineering, Shanghai University of
Engineering Science, Shanghai, China
Version of record first published: 16 Feb 2007
To cite this article: Xiaobi Jing, Qihua Zhu, Feng Xu, Xinfeng Ren, Dong Li & Chaoguo Yan (2006): Rapid
One‐Pot Preparation of 2‐Substituted Benzimidazoles from Esters using Microwave Conditions, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:18,
2597-2601
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Synthetic Communicationsw, 36: 2597–2601, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600764204
Rapid One-Pot Preparation of 2-Substituted
Benzimidazoles from Esters using
Microwave Conditions
Xiaobi Jing, Qihua Zhu, and Feng Xu
College of Chemistry and Chemical Engineering, Yangzhou University,
Yangzhou, China
Xinfeng Ren
College of Chemistry and Chemical Engineering, Shanghai University of
Engineering Science, Shanghai, China
Dong Li and Chaoguo Yan
College of Chemistry and Chemical Engineering, Yangzhou University,
Yangzhou, China
Abstract: A high-yielding one-pot procedure for the generation of 2-substituted
benzimidazoles first from esters using a microwave procedure is described.
Keywords: Benzimidazole formations, microwave, preparation
INTRODUCTION
Microwave-assisted organic synthesis (MAOS) is an acknowledged quick
alternative and green technology in synthetic organic chemistry.[1] Many
organic reactions proceed much faster and with higher yields under
microwave irradiation than with conventional heating. Moreover, this
technology provides easier workup procedures.
Received in Japan December 19, 2005
Address correspondence to Xiaobi Jing, College of Chemistry and Chemical
Engineering, Yangzhou University, Yangzhou 225002, China. E-mail: jingxiaobi@
yahoo.com.cn
2597

2598
X. Jing et al.
Scheme 1.
Compounds with imidazole ring systems have many pharmaceutical
activities and play important roles in biochemical processes.[2] Benzimida-
zoles and substituted imidazoles have been widely used in the medical
field.[3] At the same time, some of them belong to highly stable fluorescent
derivatives.[4,5] A number of methods are available for synthesis of these
compounds. A traditional method for synthesis of benzimidazoles is the
reaction between phenylenediamine and carboxylic acid under harsh dehydra-
ting reaction conditions,[6] for example, in the presence of HCl, PPA (poly-
phosphoric acid), H3BO3, or p-toluenesulfonic acid. Some new methods
reported under microwave irradiation require PPA as catalyst[5,7] or Montmor-
illonite KSF or SiO2 as solid support.[8] Many methods for synthesizing sub-
stituted imidazoles have been reported. Traditional synthesis in refluxing
HOAc or DMF require a long reaction time of about 3 h.[9] Two research
groups have recently reported microwave-assisted synthesis of benzimidazoles
on solid support,[10] but all these methods involve fussy treatment and a rela-
tively long reaction time. Until now, microwave-assisted synthesis of benzi-
midazoles from esters has not been reported. Herein we report a simple and
rapid synthesis of benzimidazoles from esters with microwave assistance.
RESULTS AND DISCUSSION
At first, we wanted to synthesize N,N0-diacetyl-1,2-phenylenediamine based
on the reaction of 1,2-phenylenediamine with ethyl acetate in ethyldiol
Table 1. Microwave-assisted synthesis of substituted benzimidazoles
T
(min)
Yield
(%)
Entry
R1
ClCH2
R2
Mp (8C)
a
b
c
d
e
f
ClCH2
CH3
1.5
1.5
1.5
1.5
1.5
1.5
1.5
95
.99
97
165–166
174–176
177–179
173–174
171–172
162–163
.300
CH3
HOCH2
Et
HOCH2
Et
.99
94
H
H
n-C5H10
2-Benzimidazoleyl
n-C5H10
CH2CO2Et
94
92
g

2-Substituted Benzimidazoles from Esters
2599
Scheme 2.
Table 2. Analytical data for the compounds a–g
Compound
1H NMR
MS(FAB)
IR
Mp (8C)
a
7.56 (t, 2H, J ¼ 3.2 Hz,
J ¼ 5.7 Hz), 7.21 (t, 2H,
J ¼ 3.1 Hz, J ¼ 5.9 Hz),
4.89 (s, 2H)
166:(Mþ) 3059, 3004, 2941, 165–166
2850, 1623,
1488, 1441,
741, 700
b
c
12.17 (s, 1H), 7.43 (s, 2H), 132:(Mþ) 3061, 2992, 2918, 174–176
7.09 (t, 2H, J ¼ 3.0 Hz,
1624, 1555,
1449, 1418,
1386, 736
J ¼ 5.7 Hz), 2.47 (s, 3H)
12.06 (s, 1H), 7.27 (d, 2H, 162:(Mþ) 3176, 3142, 3054, 177–179
J ¼ 60.6 Hz), 6.90
(s, 2H), 5.59 (s, 1H),
4.72 (s, 1H), 1.29 (d, 3H,
J ¼ 3.1 Hz)
2823, 2706,
1623, 1591,
1535, 1486,
1455, 1434, 747
d
e
f
9.80 (s, 1H), 7.58 (s,2H),
7.25 (s, 2H), 3.03 (d, 2H,
J ¼ 7.1 Hz), 1.47
(m, 3H)
146:(Mþ) 3053, 2974, 2915, 173–174
2762, 1545,
1410, 1382, 745
12.46 (s, 1H), 8.21 (s, 1H), 118:(Mþ) 3115, 3063, 2941, 171–172
7.59 (t, 2H, J ¼ 23.9 Hz,
J ¼ 26.9 Hz), 7.12
(m, 2H)
7.55 (m, 2H), 7.22 (t, 2H, 188:(Mþ) 3051, 2952, 2928, 162–163
2860, 2795,
1587, 1458,
1409, 748
J ¼ 2.9 Hz, J ¼ 5.5 Hz),
2.95 (t, 2H, J ¼ 7.6 Hz),
1.86 (td, 1H, J ¼ 7.5 Hz,
J ¼ 14.9 Hz), 1.31
2865, 2734,
1624, 1538,
1420, 748
(m, 1H), 0.82 (m, 3H)
g
12.42 (m, 2H), 7.50(s, 4H), 256:(Mþ) 3062, 2846, 2739, .300
7.14(s, 4H)
1624, 1591,
1545, 1486,
1433, 743

2600
X. Jing et al.
using microwave irradiation. However, we got 2-ethyl-benzimidazole quanti-
tatively instead (Scheme 1).
Based on this reaction, we synthesized several substituted benzimida-
zoles, and the results are given in Table 1 and Scheme 2. Our investigation
suggested that the substituted benzimidazoles are very easily obtained in
yields of more than 90% when irradiating 1,2-phenylenediamine with esters
in the microwave oven with 165 W for only about 90 s. When lowering the
power, the reaction time would be prolonged. However, the yields would be
lower. When the power is greater than 500 W, the mixture would carbonize.
In a word, we have developed a simple and efficient synthesis of substituted
benzimidazole compounds from esters.
EXPERIMENTAL
Melting points were determined with a Kolfer micromelting-pointing
apparatus and were uncorrected. IR spectra were recorded on a FTS-40
spectrophotometer in KBr. 1H NMR were measured on a Bruker DPX-
600M spectrometer. Chemical shifts are referred to TMS on the d scale. MS
were performed on ZAB-HS spectrometer.
Typical Procedure for Preparation of Substituted Benzimidazoles
1,2-Phenylenediamine dihydrochloride (1 mmol) was added to the ester
(1 mmol) solution of 10 ml of HOCH2CH2OH, and the solution was irradiated
in the microwave oven at 165 W for 1.5 min. After cooling, the reaction
mixture was diluted with 100 ml of water and neutralized with aq Na2CO3
(PH ¼ 7.0–8.0). The solid was filtered and crystallized from 90% EtOH to
give the titled compound.
All the analytical data for the compounds a–g are given in Table 2.
ACKNOWLEDGMENT
This research was supported by the National Natural Science Foundation of
China (20572091; 20576111) and Cultivation and Construction Fund for the
State Key Subject of Physical Chemistry.
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