Zeolites. Efficient and eco-friendly catalysts for the synthesis of benzimidazoles

Article abstract of DOI:10.1007/s00706-005-0407-7

A superior method of synthesis of 2-substituted benzimidazoles by means of the heterogeneous catalysis of synthetic and natural zeolites in the reaction of 1,2-diaminobenzene with acid chlorides is described. Springer-Verlag 2005.

Full text of DOI:10.1007/s00706-005-0407-7

Monatshefte f€ur Chemie 137, 175–179 (2006)
DOI 10.1007/s00706-005-0407-7
Zeolites. Efficient and Eco-friendly Catalysts
for the Synthesis of Benzimidazoles
Majid M. Heravi1;Ã, Mahmood Tajbakhsh2;Ã, Amir N. Ahmadi2,
and Bagher Mohajerani3
1
Department of Chemistry, School of Sciences, Azzahra University, Vanak, Tehran, Iran
2
Department of Chemistry, School of Sciences, Mazandaran University, Babolsar, Iran
3
Chemical and Petrochemical Research Division, Research Institute of Petroleum Industry,
Tehran, Iran
Received August 12, 2005; accepted (revised) September 15, 2005
Published online December 15, 2005 # Springer-Verlag 2005
Summary. A superior method of synthesis of 2-substituted benzimidazoles by means of the hetero-
geneous catalysis of synthetic and natural zeolites in the reaction of 1,2-diaminobenzene with acid
chlorides is described.
Keywords. Benzimidazole; Zeolite; Heulandite; Heterocyclization; 1,2-Diaminobenzene.
Introduction
Benzimidazoles are crucial structures, which are contained in agrochemicals, dye-
stuffs, and high temperature polymer products [1], and have interesting biological
and pharmacological activities [2, 3], including inhibition of phosphodiesterase
IV [4], neuropeptide Y binding [5], and anti-arrythmic and antiviral indications
[6, 7]. 2-Aryl and 2-alkyl-substituted benzimidazoles also exhibit activity against
HIV [8], influenza [9], and HSV-1 viruses [10]. Thus, these compounds have
recently received considerable attention in diverse areas of chemistry [11].
A vast variety of synthesis methods have been developed in recent years to
uncover a number of new reagents for the synthesis of 2-substituted benzimid-
azoles [12–18]. A major drawback of these classical methods is the poor yields,
use of expensive and hazardous reagents and solvents, tedious work-up procedure,
and in some cases failure of the method. In addition, the synthesis of fine chemicals
under environmentally friendly conditions represents a challenging goal in the field
of synthetic organic chemistry [19].
In the last decade there has been a tremendous development mainly due to the
use of solid acids, such as clays and zeolites [20]. Zeolites are strong Bronsted and
Ã
Corresponding authors. E-mail: mmh1331@yahoo.com

176
M. M. Heravi et al.
Lewis acids and have been used as catalyst for various organic reactions. An
extensive application of heterogeneous catalysis in synthetic organic chemistry
can help to render more attractive the processes from both environmental and also
the economic point of view [21]. Despite this interest and advantage, however,
heterogeneous catalysis in heterocyclization has been largely overlooked.
Because of the importance of benzimidazoles [1–18], in continuation of our
interest in the synthesis of heterocyclic compounds containing nitrogen [22], and
ongoing research in heterogeneous catalysis [23], we wish to report our results for
the synthesis of benzimidazoles using synthetic and natural zeolites.
Results and Discussion
The synthesis of 2-substituted benzimidazoles from the reaction of 1,2-diamino-
benzene and an acid chloride using BF3 Á Et2O has been reported [24]. We have
recently introduced a new heulandite type of zeolite (HEU) and used it to catalyze
the Biginelli reaction [25]. During the course of our studies towards the develop-
ment of this zeolite as an efficient heterogeneous catalyst, we employed it for the
one-pot formation of 2-phenylbenzimidazole (3a) from reaction of 1,2-diamino-
benzene with benzoyl chloride via heterocyclization of N-benzoyl-1,2-diaminoben-
zene (2) (Scheme 1).
In a first attempt, 1,2-diaminobenzene (1) was added to benzoyl chloride
(1 equiv) at 0ꢀC in dry dioxane and stirred for 30 min at ambient temperature to
give N-benzoyl-1,2-diaminobenzene. To this crude, natural heulandite type zeolite
(0.25 g) was added and the mixture was heated to 100ꢀC. The progress of reaction
was monitored by TLC using (AcOEt:hexane 1:2) as eluent. Upon completion of
the reaction and usual work-up, the product was identified as 2-phenylbenzimid-
azole (3a). However, the yield of this reaction was 58%. By doubling of the amount
of zeolite and increasing of reaction time, the yield improved only slightly to 60%.
To compare the performance of the catalyst with the synthetic zeolites such as HY
and HZSM-5, we carried out this reaction with the latter two catalysts in various
solvents at different reaction times and temperatures. Our results are summarized
in Tables 1 and 2. These results clearly indicate that HEU and HY zeolites despite
having a greater number of Lewis acid sites (Al) [26], are less effective than the
HZSM-5 zeolite for this heterocyclization.
Inspection of TDP profiles for these zeolites [25], show that the TDP curve for
HZSM-5 zeolite consists of a low temperature (LT) and a high temperature (HT)
peak corresponding to weak and strong acidic sites. In the TDP curves for HY and
Scheme 1

Zeolites. Efficient and Eco-friendly Catalysts
177
Table 1. Comparison of efficiency of zeolites in preparation of 2-phenylbenzimidazole
Entry
Catalyst
Catalyst weight=ga
Time=h
Yield=%
1
2
HZSM-5
HZSM-5
HZSM-5
HZSM-5
HY
0.25
0.25
0.25
0.5
3
7
61
63
64
81
60
63
61
58
50
60
3
12
3
4
5
0.25
0.25
0.5
3
6
HY
7
7
HY
3
8
HEU
0.25
0.25
0.5
3
9
HEU
7
10
HEU
3
a
Catalyst weight per 0.01 mol o-phenylenediamine
Table 2. The effect of solvent, temperature, and catalyst amount (HZSM-5) on 2-phenylbenzimi-
dazole synthesis
Entry
Catalyst weight=g
Solvent
Dioxane
Time=h
Temp=ꢀC
Yield%
1
2
3
4
5
0.25, 0.5, 1
3
100–102
140–150
70–72
61, 81, 82
0.5
0.5
0.5
0.5
Xylene
1.5
3
82
Tetrahydrofuran
Tetrahyrofuran
Acetonitrile
69
7
70–72
71
3
80–82
82.5
HEU no HT peak is observed. Since by using HZSM-5 in comparison with HEU
and HY zeolites, this heterocyclization gives a higher yield, it seems that the
presence of strong acidic sites rather than the greater number of Lewis acidic sites
favor this reaction.
As shown in Table 2, the heterocyclization reaction is facilitated by increasing
the reaction temperature. The reaction proceeded in xylene at 140–150ꢀC to give a
high yield at a shorter reaction time, whereas the yield was low in THF at 70–72ꢀC.
Also we observed a high yield using acetonitrile due to increased solvent polarity
under the same reaction conditions. On the other hand, the amount of catalyst was
optimized at 0.5 g per 0.01 mol of o-phenylenediamine, and a larger amount of
catalyst is not effective (Entry 1, Table 2).
The results disclosed in Table 3 show the scope and generality of the method
with the HZSM-5 catalyst. One of the salient features of this method is that elec-
tron poor or rich benzoyl chlorides as well as alkanoyl chlorides give excellent
yields and purities. The catalyst can be used up to 5 times without any activity loss
or appreciable changes in product yields.
In conclusion, we have compared the performance of synthetic and natural
zeolites as commercial available, inexpensive, and reusable catalysts in the synthe-
sis of 2-substituted benzimidazoles. The reasonable reaction times, high yields,
simple work-up procedure, and a one-pot reaction without the necessity to isolate
the N-acylphenylenediamines are main merits of this method.

178
M. M. Heravi et al.
Table 3. HZSM-5 catalyzed synthesis of benzimidazole derivatives
R
Time=h
Yield=%a
mp=ꢀCb
Found
Ref.
3a
3b
3c
3d
3e
3f
C6H5
3
5
3
3
3
3
5
5
3
3
3
3
3
81
71
83
82
80
81
70
69
79
80
72
73
71
292–294
262–265
263–234
235–239
178–181
201–204
204–207
324–327
241–244
261–263
168–169
179–180
160–164
290–293 [27]
264–265 [27]
234 [28]
2-NO2C6H4
2-ClC6H4
3-ClC6H4
2-OMeC6H4
3-OMeC6H4
3-NO2C6H4
4-NO2C6H4
2-BrC6H4
4-MeC6H4
CH3
238 [28]
179–180 [29]
205 [29]
3g
3h
3i
204–206 [14]
322–323 [27]
246 [28]
3j
264–265 [27]
168–170 [30]
177–179 [30]
160–162 [24]
3k
3l
C2H5
3m
C3H7
a
Yields refer to isolated products; b all compounds are known and their physical and spectroscopic
data were in good agreement with those of authentic samples
Experimental
General Procedure for the Synthesis of 2-Substituted Benzimidazoles
To a stirred solution of 10mmol o-phenylenediamine in 30 cm3 dry dioxane were added dropwise
10mmol appropriate acid chloride in 40cm3 dry dioxane at 0ꢀC for 20 min. After about 30min of
stirring at room temperature, 0.5 g zeolite were added. The mixture was heated at 100–102ꢀC for 3 h.
Then it was cooled to room temp and the resulting solid was collected by filtration and dissolved in
60cm3 CHCl3. The catalyst was removed by filtration and the solution was washed with NaOH (5%
w=w). After evaporation of the solvent, the resulting solid product was recrystallized from ethanol to
give the pure product. All products are known compounds and were characterized by mp, IR, 1H NMR,
and MS.
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