Catalytic role of sodium dodecyl sulfate: Selective synthesis of 1, 2-disubstituted benzimidazoles in water

Article abstract of DOI:10.1016/j.catcom.2011.01.005

A simple and efficient procedure for the synthesis of 1, 2-disubstituted benzimidazoles has been developed by a one-pot reaction of o-phenylenediamine with both aromatic and aliphatic aldehydes in the presence of sodium dodecyl sulfate in aqueous medium at room temperature in open air without any organic solvent. The surfactant is recycled. A plausible mechanistic approach has also been suggested.

Full text of DOI:10.1016/j.catcom.2011.01.005

Catalysis Communications 12 (2011) 744–747
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Catalytic role of sodium dodecyl sulfate: Selective synthesis of 1, 2-disubstituted
benzimidazoles in water
⁎
Pranab Ghosh , Amitava Mandal
Department of Chemistry, University of North Bengal, Darjeeling, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient procedure for the synthesis of 1, 2-disubstituted benzimidazoles has been developed by
a one-pot reaction of o-phenylenediamine with both aromatic and aliphatic aldehydes in the presence of
sodium dodecyl sulfate in aqueous medium at room temperature in open air without any organic solvent. The
surfactant is recycled. A plausible mechanistic approach has also been suggested.
© 2011 Elsevier B.V. All rights reserved.
Received 11 November 2010
Received in revised form 23 December 2010
Accepted 6 January 2011
Available online 14 January 2011
Keywords:
Benzimidazole
Sodium dodecyldulfate
Water
One pot
1. Introduction
developed to prepare functionalized benzimidazoles. However,
directly employing the condensation–aromatisation reaction of o-
Functionalized benzimidazoles represent an important class of
N-containing heterocyclic compounds and have received considerable
attention in recent times because of their applications as antiulcers,
antihypertensives, antivirals, antifungals, anticancers and antihista-
mines among others [1–5]. They are important intermediates in many
organic reactions [6,7] and act as ligands to transition metals for
modelling biological systems [8,9]. In addition, the treatment potency of
benzimidazoles in diseases such as ischemia–reperfusion injury [10],
hypertension [11], obesity [12] etc. have been recently reported. Owing
to the potential biological and other technical interest of the
benzimidazole family of compounds, a number of synthetic strategies
have been developed for the preparation of substituted benzimidazoles.
There are currently a number of synthetic methodologies available
for the synthesis of benzimidazoles. Generally, the condensation of o-
phenylenediamines and carboxylic acids (or their derivatives such as
nitriles, imidates, and orthoesters) had been widely used for the
benzimidazole synthesis, but harsh dehydrating conditions
(170–180 °C) are usually required [13–15]. Alternative approaches
such as palladium catalyzed tandem carbonylation–cyclization reac-
tion of o-phenylenediamine [16], palladium catalyzed tandem
dehydration coupling reaction of 2-bromoaniline [17], rhodium
catalyzed hydroformylation reaction of N-alkenyl phenylenediamines
[18], reductive cyclization reaction of o-nitroaniline with aldehydes
[19], solid-phase supported synthesis [20] etc. have also been
phenylenediamines and aldehydes under oxidative condition turned
out to be the most facile and effective method to synthesize 2-
substituted benzimidazole 4 [21–27] and 1, 2-disubstituted benz-
imidazole 3 from readily available cheap starting materials [28–32].
Among the reactions of o-phenylenediamine with aldehyde, the
selectivity in forming 1, 2-disubstituted benzimidazole 3 and 2-
substituted benzimidazole 4 is an issue of high interest. As a large body
of protocols have been established for synthesizing benzimidazoles of
type 4 [21–27], relatively rare methods have been reported to directly
prepare 1, 2-disubstituted benzimidazole 3 with ideal selectivity [28–32].
Recently, several elegant catalyst systems have been developed to prepare
3 in excellent chemoselectivity by employing some organic solvents and
water as the medium in the presence of costly organometallic catalysts
[27,29,31,32]. The use of large volumes of volatile hazardous organic
solvents and toxic rare earth metal catalysts in industrial processes posed
a serious threat to the environment. Thus, procedures involving
alternative benign solvents in reaction, isolation and purification are of
high priority in industry. Given the desire for developing more economical
and facile methods of less environmental impact in organic synthesis, we
wish to report herein the sodium dodecyl sulfate (SDS) catalyzed selective
synthesis of 1, 2-substituted bezimidazole derivatives in water at room
temperature.
2. Results and discussion
We initially employed o-phenylenediamine and benzaldehyde
(1:1 mmol) for the reaction in water, but could not get the expected 1,
2-disubstituted benzimidazole, along with a mixture of the three
⁎
Corresponding author. Tel.: +91 353 2776381; fax: +91 353 2699001.
E-mail address: pizy12@yahoo.com (P. Ghosh).
1566-7367/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2011.01.005

P. Ghosh, A. Mandal / Catalysis Communications 12 (2011) 744–747
745
R
2
NH
N
N
2
N
N
N
R
2
CHO
R
1
R
2
R
1
R
1
R
2
R
1
N
H
NH
2
R
2
R
2
4a
1a
3a
2a
5a
Scheme 1. Plausible transformations.
Table 1
Optimisation of benzimidazole synthesis using benzaldehyde and o-phenylenediamine with varying surfactants.
Entry
Ratio of aldehyde
and diamine
Surfactant
Amount of
surfactant (mg)
Temp (°C)
Time (h)
% Yielda of 3
% Yielda of 4
% Yield of 5a
1
2
3
4
5
6
7
8
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
SDS
SDS
SDS
SDS
SDS
SDS
SDS
SDS
TBAB
TBAB
TBAB
CTAB
CTAB
CPC
100
50
20
15
10
7
5
5
100
100
200
100
200
100
200
100
200
100
200
RT
RT
RT
RT
RT
RT
RT
50
RT
50
100
RT
100
RT
100
RT
100
RT
0.5
0.5
0.5
0.5
0.5
0.5
0.5
8
10
10
10
10
10
10
10
10
10
10
10
96
94
96
94
95
80
64
68
78
76
80
66
68
78
80
76
78
68
74
4
6
4
6
5
Nil
Nil
Nil
Nil
Nil
5
6
7
7
9
15
30
25
15
15
16
15
17
18
20
16
18
28
22
9
10
11
12
13
14
15
16
17
18
19
4
19
15
4
2
8
4
4
4
CPC
TBAH
TBAH
TBAI
TBAI
100
a
% Yield refers to the isolated yield of all the compounds.
other products at room temperature under open atmosphere
(Scheme 1). An increase in the reaction time, reaction temperature
and by changing the molar proportion of the reactants does not make
any influence on the ratio of the product distribution. As it is reported
that surfactants can also catalyse many reactions [33,34] we
attempted the above study using 1 mmol of anhydrous SDS in the
above reaction mixture of o-phenylenediamine and benzaldehyde
(1:2 mmol) using the same reaction condition at room temperature.
This revised protocol gave only a single product by a very simple
workup procedure which was identified as 1, 2-disubstituted
benzimidazole (3a).
This excellent chemoselectivity induced by sodium dodecyl sulfate
(SDS) inspired us to investigate this transformation in details. In order to
establish an optimised reaction protocol, varied reaction conditions
were applied (Table 1) on the above model study using 1 equiv mmol of
o-phenylenediamine and 2 equiv mmol of benzaldehyde including the
use of different types of surfactants viz. SDS, Tetra-n-butylammonium
bromide (TBAB), Cetyl trimethyl ammonium bromide (CTAB), Cetyl
pyridinium chloride (CPC) and Tetra-n-butylammonium iodide (TBAI)
in different proportions (Table 1). It is interesting to note that, although
all the surfactants used gave 3, as the major product but SDS showed
excellent selectivity in forming the desired product 3. Based on the
above study as depicted in Table 1, we finally optimised the reaction
condition as follows: 10 mg SDS in water is to be used for a 1:2 mmol
ratio of \o-phenylenediamines and aldehydes at room temperature.
After getting established the optimised reaction condition, we
attempted to generalize the designed protocol using a wide variety of 1,
2 diamines and aldehydes. Except few aliphatic aldehydes the developed
process found to be excellent both in terms of yield, selectivity and time
(Table 2). The synthesis of such kind of benzimidazole derivatives from
aliphatic aldehydes were not addressed by many of the existing methods.
The aldehydes with electron donating (Entries 6, 7 and 12 Table 2) as well
as with electron withdrawing groups (Entries 2–5, 8, 11, 20 and 21
Table 2) participated in the reaction uniformly. Apparently, the nature and
position of substitution on the aryl ring did not make any much different in
reactivity. Sensitive molecules like furan-2-aldehyde, 5-bromo thiophene-
2-aldehyde, pyridine-4-carboxaldehyde (Entry 13, 14, & 23 Table 2)
produced the corresponding benzimidazoles without any difficulty. In
significance, when the reaction of naphthalene-1-carboxaldehyde and o-
phenylenediamine was carried out following our method, gave excellent
yield of the corresponding benzimidazole (Entry 16, Table 2). The study
also indicated that unsubstituted aromatic aldehydes gave better yields
of the product compared to the substituted systems and that the
response of aliphatic aldehydes towards the conversion is not
encouraging. As shown in Table 2 (Entry 15, Table 2), cinnamaldehyde
furnished corresponding product 3o in modest yield whereas
valeraldehyde gave only traces amount of target product. The scope
of this reaction has been explored by subjecting the protocol on
different diamines and aldehydes following Scheme 2.
This fascinating applicability of the method towards diversified 1,
2-diamines and aldehydes prompted us to design some large benz-
imidazole derivatives that can serve as lead compound in pharmaceu-
tical research and to our delight we have able to synthesize a large
benzimidazole derivative (A) from a reaction between 3,3/-diamino
benzidine (B) and benzaldehyde (C) in excellent yield (Scheme 3).
A plausible mechanism (Scheme 4) of the reaction has been
proposed on the basis of formation of a Schiff base as intermediate
which has been isolated and characterized by NMR spectroscopy.
Further, it is also observed that the prepared Schiff base (5) when
subjected to undergo the same reaction under identical condition i.e.
NH
2
N
N
Sodium dodecylsulfate
Water, Rt
R
2
CHO
R
1
R
2
R
1
NH
2
2
1
3
R
2
Scheme 2. Preperation of 1, 2-disubstituted benzimidazole.

746
P. Ghosh, A. Mandal / Catalysis Communications 12 (2011) 744–747
Table 2
Preperation of diversified benzimidazole derivatives in aqueous SDS.
Entry
R1
R2
Time
Temperature
Product
% Yield
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
0.5 h
2 h
1.5 h
1.5 h
8 h
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
90 °C
Rt
R t
Rt
Rt
Rt
Rt
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
96
88
87
85
79
85
83
82
85
82
79
82
85
75
78
69
82
76
74
72
75
84
82
68
Trace
84
4-CH3OC6H4
4-FC6H4
4-ClC6H4
4-NO2C6H4
4-NMe2C6H4
4-Isopopyl C6H4
3-NO2C6H4
3-OHC6H4
2 h
1.5 h
24 h
5 h
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
3-OPhC6H4
2-ClC6H4
2-OHC6H4
3 h
1.5 h
15 h
4 h
6 h
5 h
6 h
2 h
7 h
8 h
Furan-2-yl
5-Bromo-thiophene-2-yl
PhCH=CH2
1-Napthyl
4-Isopopyl C6H4
3-OPhC6H4
5-Bromo-thiophene-2-yl
2-ClC6H4
4-ClC6H4
Ph
Pyridine 4-carboxaldehyde
H
Valeraldehyde
Cyclohexayl
3-CH3
3-CH3
3-CH3
3-CH3
3-benzoyl
3-benzoyl
H
H
H
H
Rt
Rt
Rt
Rt
90 °C
Rt
Rt
3s
3t
5 h
12 h
14 h
14 h
8 h
12 h
4 h
3u
3v
3w
3x
3y
3z
Rt
% Yield refers to the isolated yield of all the compounds after chromatographic separation.
CHO
H N
NH
2
N
Water, SDS
N
+
2
2
1h, r.t
N
N
H N
NH
2
B
C
A
Scheme 3. Preperation of a bis benzimidazole.
at room temperature in presence of SDS in water also yielded the
same product in excellent yield. It is then followed by the nucleophilic
attack of the catalyst on one of the eletrophilic imino carbon.
Subsequent cyclisation and 1, 3-hydride shift leads to the formation
of benzimidazoles (3).
extract of the reaction mixture for a fresh run is a great advantage of
the developed process. Gratifyingly, it was tested that the recovered
water layer can be reused for six consecutive runs (Table 3).
3. Conclusion
As was mentioned earlier, a easy work up procedure of the
reaction and reuse of the catalyst, SDS directly from the aqueous
Based on the above discussions, we can conclude that commercially
available sodium dodecyl sulfate can be used as a cheap source to
synthesize 1, 2-disubstituted benzimidazole derivatives in an expeditious
and selective way in water at ambient temperature. Several functional
groups such as –Cl, –Br, –NO2, –OMe and sensitive molecules like 5-bromo
thiophene-2-carboxaldehyde, furan-2-carboxaldehyde are compatible
with the reaction conditions. The reaction procedures are operationally
straightforward, mild, and environmentally protecting, and moreover the
amount of water and SDS used, is reusable. Since benzimidazole
derivatives are often used in the synthetic, medicinal and biological
chemistry, the reaction procedure, being endowed with so many
attractive features, could find applications as alternative green reaction
methodology. Explorations of further applications of surfactants like
sodium dodecyl sulfate are underway in our laboratory.
Cat
Nu
+
+
OHC
OHC
NH
NH
2
N
N
Water, SDS
Step-I
2
5
Nucleaphilic attack on the electrophilic
centre by the catalyst
Step-II
Cat
4. Experimental
Nu
N
N
N
N
Hydride ion transfer
H
4.1. General procedure for 1, 2-disubstituted benzimidazole
+
Cat
Nu
Step-III
In a typical experimental procedure, o-phenylelenediamine and
benzaldehyde in 1:2 molar ratios was taken in a 100 ml round bottom
flask. To this water and 10 mg sodium dodecyl sulfate was admixed.
3
Scheme 4. Plausible mechanism of benzimidazole formation in water-SDS.

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No. of cycles
% Yield
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2
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4
5
6
0
1
2
3
4
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92
87
82
78
72
68
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The reaction mixture was then allowed to stir at room temperature
with magnetic spinning bar. A foamy mass appeared immediately and
get settled like a precipitate. After the completion of the reaction, the
solid reaction mixture was washed with dichloromethane (5×4`) and
the washings were collected and evaporated under vacuum. The
crude product was then crystallized from ethanol. The desired
purified product was characterized by spectral (IR, 1H and 13C NMR)
data and compared to those reported in literature.
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