VO(acac)2 catalyzed condensation of o-phenylenediamine with aromatic carboxylic acids/aldehydes under microwave radiation affording benzimidazoles

Article abstract of DOI:10.1016/j.cclet.2010.10.031

Vanadyl acetylacetonate, VO(acac)₂, has been found to be very effective catalyst for synthesis of a variety of benzimidazoles under solvent-free condition. The methodology involves the exposure of a mixture of o-phenylenediamine and a selected aromatic carboxylic acid/aldehyde to microwave radiation without the use of any solvent or supporting agents. The benzimidazoles were obtained in quick time with high yields.

Full text of DOI:10.1016/j.cclet.2010.10.031

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 296–299
www.elsevier.com/locate/cclet
VO(acac)2 catalyzed condensation of o-phenylenediamine with
aromatic carboxylic acids/aldehydes under microwave radiation
affording benzimidazoles
*
Madhudeepa Dey, Krishnajyoti Deb, Siddhartha Sankar Dhar
Department of Chemistry, National Institute of Technology, Silchar, Silchar 788010, Assam, India
Received 28 June 2010
Available online 23 December 2010
Abstract
Vanadyl acetylacetonate, VO(acac)2, has been found to be very effective catalyst for synthesis of a variety of benzimidazoles
under solvent-free condition. The methodology involves the exposure of a mixture of o-phenylenediamine and a selected aromatic
carboxylic acid/aldehyde to microwave radiation without the use of any solvent or supporting agents. The benzimidazoles were
obtained in quick time with high yields.
# 2010 Siddhartha Sankar Dhar. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Vanadyl acetylacetonate; o-Phenylenediamine; Microwave irradiation; Solvent-free
Benzimidazoles have been known to be a very important class of heterocyclic organic compounds [1]. In recent
years, this class of organic compounds has garnered a lot of attention, especially due to their applications in various
biological studies [2]. Some noteworthy biological activities of benzimidazoles are against several viruses including
antimicrobial agents [3], anti-inflammatory [4], potential anti-tumor agents [5] and anti-parasitic agents [4]. They also
have wide spread applications in fluorescence, chemo-sensing, crystal engineering and corrosion science [1]. They can
also act as ligand to transition metals for modeling biological systems [6].
Thus looking into the spectrum of pharmacological activities along with their potential role as a ligand for
biologically modeled transition metal complexes, a number of new methods for the synthesis of benzimidazoles have
been discovered and reported [7]. Traditionally, benzimidazoles have most commonly been prepared from the reaction
of o-phenylenediamine with carboxylic acids under harsh dehydrating reactions, utilizing strong acids [8]. However,
though the use of milder reagents, particularly Lewis acids [9], inorganic clay [10] or mineral acids [11] has improved
both the yield and purity of this reaction, many of these processes suffer limitations such as drastic reaction condition,
low yields, tedious work up procedures and co-occurrence of several side reactions. There is also a report of a very
tedious and difficult experimental procedure [12] that uses water as the solvent at its critical temperature under high
pressure. One of the recent reports [1] indicates that VO(acac)2 can be used as a catalyst for benzimidazoles synthesis
particularly if used in combination with other reagents such as CeCl3 or Ti(OBu)4. However, some of the features of
* Corresponding author.
E-mail address: ssd_iitg@hotmail.com (S.S. Dhar).
1001-8417/$ – see front matter # 2010 Siddhartha Sankar Dhar. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.10.031

[()TD$FIG]
M. Dey et al. / Chinese Chemical Letters 22 (2011) 296–299
297
NH2
N
VO(acac)2
Ar
+
Ar-COOH/Ar-CHO
N
H
Microwave irradiation
NH2
1
2a-l
3a-l
Scheme 1.
this method such as use of environmentally unfavourable chlorinated solvent CH2Cl2, long reaction time are not very
encouraging. As a consequence, the introduction of newer improved methods to overcome such limitations is still an
experimental challenge.
In our continuous effort to design and develop environmentally benign methodologies for catalyst preparation
including metal acetylacetonates [13] and organic transformation reactions [14,15], we wish to report here an
alternative protocol for rapid synthesis of pharmacologically important benzimidazoles using catalytic amount of
VO(acac)2 under microwave irradiation and solvent-free conditions (Scheme 1).
1. Experimental
Melting points were determined in open capillaries and are uncorrected. The completion of reactions was
1
monitored by TLC. IR spectra were recorded on KBr matrix with Perkin Elmer BX-FTIR spectrometer. H NMR
spectra were recorded in DMSO-d6 using TMS as internal standard on a 400 MHz Varian spectrometer. Microwave
oven equipped with a turntable was used (Godrej 30E BLGX having maximum output of 1000 watt).
In a typical procedure, o-phenylenediamine (1 mmol), aromatic acids/ aromatic aldehydes (1.1 mmol) and the
catalyst VO(acac)2 (0.05 mmol) were ground together in a pestle mortar. The resulting mixture was irradiated with
microwave at a power of 180 watt for short period of time (Table 1). The conversion of the reactants into
corresponding benzimidazoles was monitored by TLC. The resulting solid was taken in methanol and the solution
was filtered through a short column to remove the little undissolved catalyst. The solution was then dried by
evaporation of the solvent through rotary evaporator. The product thus obtained was recrystallized from methanol.
All the products were characterized by comparing the melting points and spectral data with authentic samples [16–
22].
Spectral and physical data of selected compounds: 3a: Mp 289–291 8C; IR (KBr): 3046, 1444, 1410, 1275, 970,
745 cmꢀ1; 1H NMR (400 MHz, DMSO-d6): d 12.7 (s, 1H, NH), 7.95 (m, 2H, C20-H, C60-H), 7.25–7.35 (m, 5H, C4-H,
C7-H, C30-H,C40-H,C50-H), 7.05 (m, 2H, C5-H, C6-H); 3b: Mp 182 8C; IR (KBr): 3442, 3320, 2960, 1675,
1478 cmꢀ1; 1H NMR (400 MHz, DMSO-d6): d 9.8 (s, 1H, NH), 6.7–7.7 (8H, m), 5.0 (s, 1H, OH) 3c: Mp 291 8C; IR
1
(KBr): 3041, 1450, 1402, 1280, 965, 750 cmꢀ1; H NMR (400 MHz, DMSO-d6,): d 12.5 (s, 1H, NH), 8.20 (d, 2H,
J = 8.7 Hz, C20-H, C60-H), 7.6 (d, 2H, J = 8.4 Hz, C30-H, C50-H), 7.30 (d, 2H, C4-H, C7-H), 7.10 (m, 2H, C5-H, C6-
H); 3 g: Mp 219 8C; IR (KBr): 3450, 3050, 1590, 1439, 1310, 1277, 740 cmꢀ1; 1H NMR: 7.18–7.21 (m, 2H), 7.50 (t,
1H, J = 6.50 Hz), 7.60–7.61 (m, 2H), 7.98 (t, 1H, J = 7.70 Hz), 8.31 (d, 1H, J = 7.70 Hz), 8.71 (d, 1H, J = 4.5 Hz),
13.04 (br. 1H); 3 h: Mp 245–248 8C; IR (KBr): 3068, 1449, 1402, 1280, 746 cmꢀ1; 1H NMR: 13.05 (s, 1H, NH), 9.35
(d, 1H, J = 8.2 Hz, C20-H), 8.75 (d, 1H, J = 1.8 Hz, C60-H), 8.60 (m, 1H, C40-H), 7.70 (m, 3H, C4-H, C7H, C50-H),7.40
(m, 2H, C5-H, C6-H); 3i: Mp 309–310 8C; IR (KBr): 3063, 1523, 1444, 1357, 973, 746 cmꢀ1; 1H NMR: 12.9 (s, 1H,
NH), 8.90 (s, 1H, C60-H), 8.50 (d, 1H, J = 6.9 Hz, 640-H), 8.10 (d, 1H, J = 7.2 Hz, 20 H), 7.70 (t, 1H, J = 7.2, 6.9 Hz,
C30-H), 7.50 (m, 2H, C4-H) 7.2 (m, 2H, C5-H, C6-H).
2. Results and discussion
As shown in Table 1 aromatic carboxylic acids and aromatic aldehydes react with o-phenylenediamine in rather
similar fashion to give the corresponding benzimidazoles in very good yields. Best results in respect of the catalyst
were obtained when VO(acac)2 was taken in 5 mol%. Lower loading of the catalyst resulted in lower yields in longer
reaction time, while higher amount of catalyst except for 2f and 2i did not increase the product yields significantly in
comparable reaction time. The absence of either the catalyst or the MW radiation also produced benzimidazoles for
some of the reactants. But such reactions required longer reaction times and the yields of the products obtained were
also very low.

298
M. Dey et al. / Chinese Chemical Letters 22 (2011) 296–299
Table 1
Reactions of o-phenylenediamine with (Ar)–COOH/(Ar)–CHO in presence of VO(acac)2 under MW irradiation.
Entry
1
Aromatic acid/aldehyde
Time (min)
3.5
Product
Yield (%)a
91
References
[16]
[
[TD$INLE]
N
COOH
2a
2b
N
H
3a
2
3
E
2
4
]
88
88
[17]
[16]
N
COOH
N
H
OH
HO
3b
N
Cl
COOH 2c
Cl
NH2
Br
N
H
3c
3d
3e
4
5
6
E
4
N
85
[18]
[19]
[20]
N
H2N
COOH 2d
N
H
4.5
89
N
Br
COOH
2e
N
H
5
E
87b
N
COOH
N
H
O N
2
2f
NO2
3f
7
[
3
[
92
[21]
N
COOH
N
2g
2h
N
H
N
3g
8
9
N
3
]
90
[22]
[20]
N
COOH
N
H
N
N
3h
4.5
E
85b
CHO
N
N
H
NO2
3i
NO2
2i
10
11
E
4
]
83
80
[16]
[22]
N
CHO
Cl
N
H
3j
Cl
2j
3.5
CHO
N
N
N
H
N
2k
3k

M. Dey et al. / Chinese Chemical Letters 22 (2011) 296–299
299
Table 1 (Continued )
Entry
12
Aromatic acid/aldehyde
Time (min)
2.5
Product
Yield (%)a
88
References
[16]
[
[TD$INLE]
CHO
N
N
H
2l
3l
a
Isolated yield.
b
VO(acac)2 required was 10 mol%. The yields of the benzimidazoles were very poor when the reactions were carried out without the catalyst or
the MW radiation for the same amount of reaction times.
The reaction times of the present protocol indicate that the duration of the exposure of the reactants to microwave is
very short which reflects the cost-effectiveness of the protocol. The yields mentioned in the table are isolated yields
after re-crystallization from methanol. The reaction time indicated in the table is the complete conversion time of the
substrate to product. The mechanistic pathways of these catalytic reactions are not quite comprehensible. However, it
is evident that the catalyst used did not undergo oxidation to vanadium(V) as the test for vanadium(V) was not obtained
from the recovered catalyst.
3. Conclusion
In conclusion, we have developed an improved and alternative method for condensation of o-phenylenediamine
with aromatic aldehydes and carboxylic acids to obtain corresponding benzimidazoles efficiently catalyzed by
vanadyl acetylacetonate under microwave irradiation. The attractive features of this methodology are high conversion,
shorter reaction time, clean and quick work-up procedure and solvent-free conditions.
Acknowledgment
We are grateful to the Department of Science and Technology (DST), New Delhi, Government of India for
providing financial support (SR/FTP/CS-100/2007).
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