A fast procedure for the preparation of benzimidazole derivatives using polymer-supported with trifluoromethanesulfonic acid as novel and reusable catalyst

Article abstract of DOI:10.4067/S0717-97072013000300026

A highly selective synthesis of benzimidazoles from the reaction of o-phenylenediamines and aromatic aldehydes in the presence of PVP- trifluoromethanesulfonic acid is reported, and morphological investigation was reported by FT-IR. The remarkable advanta

Full text of DOI:10.4067/S0717-97072013000300026

J. Chil. Chem. Soc., 58, Nº 3 (2013)
A FAST PROCEDURE FOR THE PREPARATION OF BENZIMIDAZOLE DERIVATIVES USING POLYMER-
SUPPORTED WITH TRIFLUOROMETHANESULFONIC ACID AS NOVEL AND REUSABLE CATALYST
CHANGIZ KARAMI1*, KEIVAN GHODRATI1*, MINA IZADI2, AZITA FARROKH1, SEDIGHEH JAFARI 2,
MARYAM MAHMOUDIYANI2, AND NAHID HAGHNAZARI1
1 Department of Chemistry, Kermanshah Branch, Islamic Azad University, Kermanshah. Iran
2Department of Chemistry, Razi University, Kermanshah. Iran
(Received: October 8, 2012 - Accepted: April 20, 2013)
ABSTRACT
A highly selective synthesis of benzimidazoles from the reaction of o-phenylenediamines and aromatic aldehydes in the presence of PVP- trifluoromethanesul-
fonic acid is reported, and morphological investigation was reported by FT-IR. The remarkable advantages of this method are the simple experimental procedures,
shorter reaction times, high yields of product, and non-toxic catalyst. However, the reactions were performed in solvent-free and the catalyst could be reused for
several runs.
Keywords: Green chemistry; polymer-supported reagents; Benzimidazoles; reusable catalyst
INTRODUCTION
EXPERIMENTAL
In the last ten years, supported reagents on polymers have become increas-
ingly applied in organic synthesis 1, because the reactions are carried out with
simple work-up, easy product isolation, and mild reaction conditions 2. Benz-
imidazole is a kind of substances which have found practical applications in
Materials and Techniques
All reagents and solvents were purchased from Sigma-Aldrich and Merck,
chemical companies. Yields refer to isolated pure products. The benzimid-
azoles derivatives were characterized by comparison of their spectral (IR,
1HNMR), TLC and physical data with authentic samples, and the IR spectra of
the samples (as KBr pellets) were recorded using a Rayleigh WQF-510 spec-
trophotometer in the range of 400– 4000 cm −1. Melting points were determined
using Electrothermal 9300 Melting Point. 1H NMR and 13CNMR spectra were
recorded on Bruker 200 MHz and 50 MHz spectrometer.
3
organic synthesis , and the benzimidazole nucleus are found in a variety of
pharmaceuticals as cardiotonic agents,4 potential antitumor 4 poli(ADP-ribose)
phosphorilase inhibitors, 5 Histamine H4 receptor binders, 6 antiparasitic, 7 car-
8
4
9
9
diovascular, anticancers, antimicrobials, and antihypertensives, . Due to
the high importance of 2-aryl-1H-benzimidazoles for the preparation of bio-
logically active molecules, their synthesis has been received considerable at-
tention. The condensation of 1,2-phenylendiamines with carboxylic acids or
Preparation of PVP-Tf2O
A Trifluoromethanesulfonic acid (TfOH) (2.0 ml) was added to poly (4-vi-
nylpyridine)(2 g), and it was stirred magnetically for 2h at room temperature.
The suspension was filtered and washed with CH2Cl (2 × 5 ml) and the poly
(4-vinylpyridine)-supported with tifluoromethansulf2onic acid (PVP -TfOH)
was obtained. The activity of this polymer was determined by potentiometric
titration with a 0.1 N solution of NaOH. The activity of polymer was calculated
(0. 1 g of catalysis equal to 0.08 mmol).
10
their derivatives in the presence of strong acids such as mineral acids or
polyphosphoric acid 11 and the thermal or acid-promoted cyclization of N-(N-
arylbenzimidoyl)-1,4-benzoquinoneimines 12 was include the methods of benz-
imidazole synthesis 13. Direct condensation of o-aryldiamines and aldehydes
is not a good synthetic reaction, as it is well known to yield a complex mix-
ture. In this case, the addition of transition metal, namely copper (II) acetate 14
,
catalyzed by Fe(ClO4)3 15, mercury oxide 16 or lead tetracetate 17 allow a partial
selective synthesis of benzimidazoles. In recent years, solvent-free synthesis of
benzimidazoles under microwave irradiation using Yb(OTf)3 18, Lithium bro-
mide catalyzed 19, KSF clay20, PPA21, metal halide supported alumina22 and
solid support23 have been reported. Unfortunately, many of these processes
suffer some limitations, such as drastic reaction conditions, low yields, boring
work up procedures and co-occurrence of several side reactions. Therefore, the
development of a cost effective, safe and environment friendly reagent system
is desirable. In addition to, organic synthesis in the absence of a solvent is a
powerful tool for the generation of structurally diverse molecules. Solvent-free
reactions often, have special selectivity, are easy to set-up and work-up, and
are faster, which have aroused great interest 24. These aspects, coupled with
the lower overall costs of running a reaction without solvent and no specially
needed equipment, could become a decisive factor in industry. Herein, we wish
to disclose a novel protocol for the rapid synthesis of a variety of benzimid-
azoles using a catalytic amount of PVP-TfOH under solvent-free conditions,
and the reaction of this supported reagent is simple work-up, easy product iso-
lation, and mild reaction conditions. However, the reaction was carried out in
neat at 70 °C for 6 minutes, using o-phenylenediamine (1 mmol), aldehyde
(1.1 mmol), and H O2 (30%, 3 mmol, 0.3 mL) in the presence of PVP- trifluo-
romethanesulfonic2acid (0.2mg) (Scheme 1).
Typical Procedure for the Preparation of Benzimidazoles
A mixture of o-phenylenediamine (1 mmol), 4-chlorobenzaldehyde (1.1
mmol), and H O2 (30%, 3 mmol), and PVP- TfOH (0. 2 g) was stirred mag-
netically for 62min at 70 °C, and the progress of the reaction was monitored
by TLC. After completion of the reaction, the reaction mixture filtered and
washed with CH Cl2 (15 ml) there time. If further purification was needed, by
recrystallization 2it was dissolved in EtOH (10 mL) and then poured into ice
water (30 mL). The pure solid product was filtered, washed with ice water, and
subsequently dried.
2-(4-Chlorophenyl)-1H-benzimidazole (Table 3, entry 1): mp 290-293°C;
1H-NMR (200 MHz, DMSO-d6,): δ =7.10 (m, 2H), 7.30 (m, 2H), 7.6 (d, 2H,
J=8.4 Hz), 8.20 (d, 2H), 12.5 (s, 1H, NH): 13 C-NMR (50 MHz, DMSO-d6):
δ= 115.4, 123.2, 128.6, 128.9, 129.4, 134.3, 138.9, 152.9.
RESULTS AND DISCUSSION
In this study, we became interested to explore a new reagent (PVP-TfOH)
for the synthesis of various benzimidazole derivatives, and the PVP-TfOH ca-
talysis was prepared via a reaction of rifluoromethanesulfonic acid with poly
(4-vinylpyridine) (Scheme 2).
Scheme 1. Synthesis of Benzimidazole Derivatives in the presence of
PVP–TfOH.
Scheme 2
e-mail: Changiz.Karami@gmail.com
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J. Chil. Chem. Soc., 58, Nº 3 (2013)
The FT-IR spectrum of PVP and the PVP-TfOH catalyst was shown in
(Fig 1). The catalyst is solid and solid state IR spectrum was recorded using
the KBr disk technique. The Fig 1a is showed the FT-IR spectrum of PVP, and
also the FT-IR spectrums (Fig 1b) is showed the new signals appeared to the
signals observed for PVP. These new peaks are assigned to the C-F stretching
from 1000 to 1400 cm-1 and sulfonates S=O stretching near 1175-1300cm-1
,
S-O stretching near 1000-750 cm-1, and broad OH stretching absorption around
3500 and 2800 cm-1
Fig 1. A) FTIR spectrum of poly (4-vinylpyridine) in KBr, and (B)
PVP+TfOH
Initially, a reaction was carried out in neat at 70 °C, using o-phenylenedi-
amine (1 mmol), 4-chlorobenzaldehyde (1.1 mmol), and H2O2 (30%, 3 mmol)
in the presence of PVP-TfOH. With this optimistic result in hand, we further
probed the best reaction condition by using different amounts of PVP- TfOH.
An increase amount of catalyst from 0.1g to 0.2g not only decreased the reac-
tion time from 9 min to 6 min but also increased the product yield from 90 to
95%. This showed that the catalyst concentration plays a major role in optimi-
zation of the product yield. Although the use of 0.3g of this catalyst permitted
the reaction time to be decreased to 5 min, the yield is become persistent. These
results indicate that the amount of catalyst is required (Fig.2a).
In the (Scheme 3) the suggested mechanism for the preparation of benz-
imidazoles was shown that the actual oxidant is H2O2. wherein the absence of
H2O2 resulted in an extremely slow reaction in sufficient for complete product
formation even after 15 h. whoever, imine derivative was obtained as only
product. Also, different amounts of H2O2 in conditions as (Tables 3), and the
results are depicted in (Fig.2b).
Fig.2. a) Effect of catalyst weight and b) Effect of Amounts of H2O2 (con-
ditions as Tables 3).
Table 1. Effect of temperature for the preparation of 2-(4-chlorophenyl)-
1H-benzo[d]imidazole under solvent-free using PVP-TfOH catalysts as cata-
lyst (0.2 g).
Entry
Temperature(°C)
Time(min)
Yield (%)
1
2
3
4
5
rt
2h
15
6
60
95
95
95
96
50
70
100
110
4
4
Certainly, solvent plays a critical role in the reactions; therefore, we de-
cided to investigate the effect of various solvents and select an appropriate
condition for the preparation of benzimidazole. Therefore, we screened dif-
ferent solvents such as acetonitrile, ethanol, THF, acetonitrile, water, toluene,
and solvent free for the preparation of benzimidazole, as a typical example, the
4-chlorobenzaldehyde and 1,2-phenylendiamine as substrates in the presence
of (0. 2 g) catalyst and H2O (3 mmol)in different solvents at 70°C (Table 2).
Solvent -free was found to 2be the most efficient for this transformation. The
reactions in other solvents required longer reaction time and low yield
Table 2. Reaction of chlorobenzaldehyde, 1,2-phenylendiamine under 6
min conditions.
Entry
Solvent a
Ethyl acetate
Acetonitrile
Ethanol
Yield (%)
1
2
3
4
5
6
7
62
20
62
10
25
95
30
Scheme 3. The proposed mechanism for the preparation of benzimidazoles
To evaluate the effect of reaction temperature, the effect of temperature
on the rate of reaction was studied at different temperatures for the prepara-
tion of benzimidazoles in the presence of PVP-TfOH system (Table 1). It was
observed that the reaction was found to be very slow at room temperature. At
50 °C, the reaction proceeded smoothly and almost the complete conversion of
the product was observed. Further increase in temperature to 70, 90 and 110 °C
increased the rate of reaction. Therefore, we kept the reaction temperature at 70
°C (giving short reaction time and high yield).
n-hexane
H2O
Solvent- Free
THF
a Refluxed
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J. Chil. Chem. Soc., 58, Nº 3 (2013)
Table 3. Reaction conditions: o-phenylenediamine (1 mmol); aldehyde (1.1 mmol); H2O2 (30%, 3 mmol) in the presence of PVP-TfOH (0. 2g).
Time (min)/Yield (%)
Product
Substrates
Substrate
NH2
Entry
N
Cl
C
Cl
6(95)
1
CHO
CHO
N
H
NH2
N
NH2
NH2
O2N
C
5(96)
5(95)
O2N
2
3
N
H
CHO
N
NH2
NH2
C
N
H
O2N
NO2
N
NH2
NH2
CHO
Cl
C
6(94)
5(96)
4
5
N
H
Cl
N
NH2
NH2
F
MeO
Me
HO
N
C
CHO
F
N
H
N
NH2
NH2
C
15(90)
12(95)
8(96)
6
7
8
9
MeO
Me
CHO
N
H
N
NH2
NH2
C
CHO
CHO
N
H
N
NH2
NH2
C
HO
N
H
N
NH2
NH2
C
N
20(80)
N
CHO
N
H
NH2
NH2
CHO
OH
C
C
12(93)
11(95)
15(90)
10
11
12
N
H
OH
N
NH2
NH2
CHO
N
H
H
N
NH2
NH2
H2
C
H2 H2
C
OHC
C
C
H2
N
a The products were characterized by comparison of their spectroscopic and physical data with authentic samples synthesized by reported procedures.
b Yields refer to pure isolated products.
The generality of this reaction was examined using several types of aldehydes with o-phenylenediamine under the optimized reaction conditions. In all cases,
the reactions gave the corresponding products. In order to study the generality of this procedure, a series of benzimidazoles compounds were synthesized using
several types of aldehydes. A ratio of 1,2-phenylendiamine(1mol), aryl aldehyde (1.1mol), H2O2 (3mmol), PVP-TfOH (0.2g) was found to be optimum for the cou-
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J. Chil. Chem. Soc., 58, Nº 3 (2013)
pling of aryl aldehydes and 1,2-phenylendiamines and the results are presented
in (Table 3). As shown, variety of substituted aromatic aldehydes such as either
electron-donating (Table 3, entry 7-11) or electron-withdrawing, substituents
(Table 3, entry 2-6) were successfully employed to prepare the correspond-
ing benzimidazole derivatives in excellent yields. In addition, aryl and alkyl
aldehydes could also be used for efficient preparation of various heterocyclic-
benzimidazoles (Table 3, entry 11 and 12).
The re-use of PVP/ TfOH was investigated in the reaction between 4-chlo-
robenzaldehyde, o-phenylenediamine (1 mmol), 4-chlorobenzaldehyde (1.1
mmol), and H2O2 (30%, 3 mmol, 0.3 mL). After completion of the reaction,
the reaction mixture was filtered, and the catalyst was recovered after each run,
washed three times with acetone, dried in a room temperature prior to use and
tested for its activity in the subsequent run and no fresh catalyst was added.
The catalyst was tested three times. It was seen that the catalyst displayed very
good reusability (Fig. 3).
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Fig. 3, Reusability of the catalyst (conditions as in Tables 3)
CONCLUSIONS
In summary, we have developed a new polymer-supported by Trifluoro-
methanesulfonic for the synthesis of benzimidazoles. Our method has several
advantages including short reaction times, mild conditions, excellent yields,
inexpensive and non-toxic catalyst, simple operation and work-up. Addition-
ally, the protocol does not require volatile and hazardous organic solvents and
an additional ultrasound or microwave oven. The elimination of the solvent has
obvious environmental benefits with regard to the depletion of solvent waste.
Also the catalyst could be successfully recovered at least for three runs without
significant loss in activity.
ACKNOWLEDGMENT
We are thankful to the Islamic Azad university branch of Kermanshah for
the partial support for this work
SUPPLEMENTARY MATERIAL:
Complete experimental procedures and relevant spectra (1H NMR and 13
C
NMR spectra) for some compounds. This material is available in Supporting
Information
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