Highly efficient one pot synthesis of benzimidazoles from 2-nitroaniline and PhSiH3 as reducing agent catalyzed by Pd/C as a heterogeneous catalyst

Article abstract of DOI:10.1016/j.tetlet.2021.152940

This work reports an efficient route for the synthesis of benzimidazole from o-nitroaniline in the presence of carbon dioxide atmosphere, PhSiH₃ as a reducing agent catalyzed by Pd/C as a catalyst. Benzimidazoles have become the focus of organic chemists, as benzimidazole is an important intermediate in medicinal chemistry. We have developed more efficient route for the synthesis benzimidazole and various substituted benzimidazoles have been synthesized in good to excellent yield. The TBD (1,5,7-Triazabicyclo [4.4.0] dec-5-ene) is selected as a base as it promotes the CO₂ insertion. Benzimidazoles were synthesized through reduction of nitro group followed by cyclization of amine using CO₂ as a carbon source. Moreover, the Pd/C catalyst can be recycled up to five recycle run without significant changes in the yield of the product.

Full text of DOI:10.1016/j.tetlet.2021.152940

Tetrahedron Letters 68 (2021) 152940
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Tetrahedron Letters
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Highly efficient one pot synthesis of benzimidazoles from 2-nitroaniline
and PhSiH3 as reducing agent catalyzed by Pd/C as a heterogeneous
catalyst
⇑
Vishal V. Phatake, Bhalchandra M. Bhanage
Department of Chemistry, Institute of Chemical Technology (ICT), Mumbai 400019, India
a r t i c l e i n f o
a b s t r a c t
Article history:
This work reports an efficient route for the synthesis of benzimidazole from o-nitroaniline in the presence
of carbon dioxide atmosphere, PhSiH3 as a reducing agent catalyzed by Pd/C as a catalyst. Benzimidazoles
have become the focus of organic chemists, as benzimidazole is an important intermediate in medicinal
chemistry. We have developed more efficient route for the synthesis benzimidazole and various substi-
tuted benzimidazoles have been synthesized in good to excellent yield. The TBD (1,5,7-Triazabicyclo
[4.4.0] dec-5-ene) is selected as a base as it promotes the CO2 insertion. Benzimidazoles were synthesized
through reduction of nitro group followed by cyclization of amine using CO2 as a carbon source.
Moreover, the Pd/C catalyst can be recycled up to five recycle run without significant changes in the yield
of the product.
Received 30 December 2020
Revised 9 February 2021
Accepted 12 February 2021
Available online 23 February 2021
Keywords:
Nitroaniline
Carbon dioxide
PhSiH3
Heterogeneous catalyst
Benzimidazole
Pd/C
Ó 2021 Elsevier Ltd. All rights reserved.
TBD
Introduction
Literature shows that there are only a few reports available on
the direct conversion of o-nitroaniline to benzimidazole in the pres-
The capture and utilization of CO2 is an efficient method to mit-
igate the rising concern of global warming related to CO2 emission.
The utilization of carbon dioxide (CO2) has been increasing interest
as the requirement of sustainable development and environmental
concerns [1–4]. The CO2 is generally used as a renewable, green
and economical C1 source and the chemical transformation of
CO2 has been extensively studied. A variety of value-added chem-
icals such as formamides [5,6], formic acids [7], carbonates [8,9],
carbamates [2], methanol [10], benzimidazole [11,12] were syn-
thesized by the formation of CAN, CAO, CAH, and CAN bond. Gen-
erally, a catalyst is required for CO2 conversion due to the
thermodynamic and kinetic stability of CO2, and many studies have
been developed for efficient conversion of CO2.
Benzimidazoles and its derivatives are vital intermediates and
widely used in synthesizing important pharmaceutical com-
pounds. Benzimidazoles are synthesized via condensation reac-
tions of o-phenylenediamine with formic acid or its derivatives
(esters, nitriles) in the presence of strong acidic conditions with
relatively high temperatures or under microwave irradiation
[13,14].
ence of CO2 atmosphere. Hao et al. reported Au/TiO2 catalyst for the
synthesis of benzimidazoles from o-nitroaniline and H2 as a reduc-
ing agent in the presence of CO2 (CO2 and H2 = 8 MPa) at 100 °C for
12 h (Scheme 1a) [15]. Recently, the synthesis of formamides and
benzimidazoles from amines, nitrobenzene and o-nitroaniline cat-
alyzed by Ru@PSIL has been reported (Scheme 1b) [16]. Previously,
N-formylation of amines was obtained by using Pd-NC-800 catalyst
in presence of 7 MPa pressure (H2:CO2 – 4:3) at 130 °C [17]. It is an
interesting route for the direct synthesis of benzimidazole from
nitroaniline with CO2 and silane as a reducing agent. Previously
hydrogen gas was used as a reducing agent [15]. H2 is one of the
clean source of energy and economical hydrogen source but require
high pressure and temperature, handling of H2 at high temperature
limits its broad application. Hydrosilanes and H2 having similar
reduction potential (H2 and Si-H bond). The Si-H bond kinetically
more active due to its lower bond dissociation energy and polarity.
Additionally, hydrosilanes are air-stable and less moisture sensitive
compare to boron hydride. TBD (1,5,7-Triazabicyclo [4.4.0] dec-5-
ene) was selected as a base as it activates CO2 and helps to insertion
of CO2. TBD is the most common super base used in organic synthe-
sis due to its high Pka value [18].
There are only a few reports available to synthesize benzimida-
zoles from o-nitroaniline and CO2 as a carbon source in literature.
⇑
Corresponding author.
E-mail address: bm.bhanage@ictmumbai.edu.in (B.M. Bhanage).
https://doi.org/10.1016/j.tetlet.2021.152940
0040-4039/Ó 2021 Elsevier Ltd. All rights reserved.

V.V. Phatake and B.M. Bhanage
Tetrahedron Letters 68 (2021) 152940
Scheme 1. Comparison of previous reports of synthesis of benzimidazole from o-nitroaniline and CO2.
There is a need to develop a more efficient, simple and sustainable
route for the synthesis of benzimidazoles from o-nitroaniline.
Herein, we report the efficient synthesis of benzimidazole directly
from ortho nitroaniline, phenyl silane as a reductant, ACN (acetoni-
trile) as a solvent in the presence of CO2 atmosphere at 70 °C for 15 h.
solvents, including polar and non-polar solvents were studied for
the synthesis of benzimidazole out of which Acetonitrile (ACN)
and DMSO gave the 90 and 88% yield and ACN selected as a solvent
for the further experiments (Table 1, entries 1–5). This is due to the
excellent solubility of carbon dioxide in the polar aprotic solvent
(ACN and DMSO). Next, we screen various palladium catalysts such
as PdCl2 and Pd(OAC)2 gave the lower yield compared to Pd/C cat-
alyst (Table 1, entries 6, 7 and 1). Furthermore, we examined other
silanes such as PhSiH3 and PMHS (Polymethylhydrosiloxane).
PhSiH3 and PMHS gave an excellent yield compare to Et3SiH
(Table 1, entries 8 and 9). PhSiH3 is selected as a reducing agent
for further experiments. Next, the effect of various bases has been
Result and discussion
We have selected 2-nitroaniline with CO2 and different reduc-
ing agents as a model reaction for the synthesis of benzimidazole.
We examined various parameters such as a solvent, temperature,
pressure, time, CO2 pressure, base, palladium catalyst, etc. Several
Table 1
Optimization study.
Entry
Solvent
Reducing agent
Catalyst
Base
CO2 (MPa)
Temperature (°C)
Time (h)
Yieldb (%)
Effect of Solvent
1
2
3
4
5
Toluene
Et3SiH
Et3SiH
Et3SiH
Et3SiH
Et3SiH
10% Pd/C
10% Pd/C
10% Pd/C
10% Pd/C
10% Pd/C
TBD
TBD
TBD
TBD
TBD
2
2
2
2
2
80
80
80
80
80
20
20
20
20
20
–
1,4-dioxane
CH3CN
ACN
35
67
78
72
DMSO
Effect of other Palladium catalyst
6
7
ACN
ACN
Et3SiH
Et3SiH
PdCl2
Pd(OAC)2
TBD
TBD
2
2
80
80
20
20
35
62
Effect of reducing agent
8
9
ACN
ACN
PhSiH3
PMHS
10% Pd/C
10% Pd/C
TBD
TBD
2
2
80
80
20
20
92
86
Effect of Base
10
11
12
ACN
ACN
ACN
PhSiH3
PhSiH3
PhSiH3
10% Pd/C
10% Pd/C
10% Pd/C
DBU
DMAP
DABCO
2
2
2
80
80
80
20
20
20
76
54
49
Effect of Temperature
13
14
ACN
ACN
PhSiH3
PhSiH3
10% Pd/C
10% Pd/C
TBD
TBD
2
2
70
60
20
20
92
70
Effect of Time
15
16
ACN
ACN
PhSiH3
PhSiH3
10% Pd/C
10% Pd/C
TBD
TBD
2
2
70
70
15
10
88
67
Effect of Pressure
17
18
ACN
ACN
PhSiH3
PhSiH3
10% Pd/C
10% Pd/C
TBD
TBD
1
0.5
70
70
15
15
89
61
Effect of PhSiH3 loading
19c
20d
ACN
ACN
PhSiH3
PhSiH3
10% Pd/C
10% Pd/C
TBD
TBD
1
1
70
70
15
15
91
63
a – Reaction condition: o-nitroanlines (0.5 mmol), catalyst (10 mg, 0.01 mmol Pd), PhSiH3 (4 equi.), Base (5 mol%), ACN (7 mL), Temperature (70 °C) for 15 h. b – GC and
GCMS Yield. c – PhSiH3 (3 equi.). d – PhSiH3 (2 equi.).
2

V.V. Phatake and B.M. Bhanage
Tetrahedron Letters 68 (2021) 152940
Table 2
Substrate study.a
Entry
1
Substrate
Product
Yieldb (%)
94
2
85
3
4
5
95
94
92
6
7
88
07 (78)c
8
9
82
95
10
94
11
12
72
70
13
84
a – Reaction condition: Substrate (1 mmol), catalyst (10 mg, 0.01 mmol of Pd), PhSiH3 (3 equi.), TBD (5 mol%), CO2 (1 MPa), ACN (7 mL), Temperature (70 °C) for 15 h. b –
Isolated yield (%). c – benzimidazole
3

V.V. Phatake and B.M. Bhanage
Tetrahedron Letters 68 (2021) 152940
benzimidazole was decreased (Table 1, entries 15 to 16). After this,
the influence of CO2 pressure was also examined and 1.0 MPa of
CO2 pressure was sufficient to give 89% yield of benzimidazole, fur-
ther reducing the CO2 pressure to 0.5 MPa significant decrease in
the yield of benzimidazole was observed (Table 1, entries 17 to
18). Next, the influence of PhSiH3 loading was also examined, three
equivalents of PhSiH3 is enough to obtained benzimidazole in
excellent yield (Table 1, entries 19 to 20).
The final optimized reaction condition is 2-nitroaniline
(0.5 mmol), CO2 (1 MPa), Pd/C (10 mg, 0.01 mmol of Pd), PhSiH3
(3 equi.), TBD (5 mol%), ACN (7 mL) at 70 °C for 15 h.
Several o-nitroanilines were evaluated by using optimized reac-
tion conditions. The o-nitroanilines bearing electron-withdrawing
and -donating groups were well tolerated except bromo and iodo
substituted benzimidazole under the optimized reaction condition
to obtain various benzimidazoles in good to excellent yields
(Table 2). O-nitroaniline gave the benzimidazole in 94% yield
(Table 2, entry 1). Furthermore, the steric effect on o-nitroaniline
was also examined. O-nitroanilines having donating groups
(methyl, methoxy groups) gave the excellent yield of the corre-
sponding benzimidazole compare to the withdrawing substrate
(Table 2, entries 2 to 6). When we performed the reaction with
5-bromo-2-nitroaniline gave the corresponding benzimidazole
only 7% and benzimidazole 78% (Table 2 entry 7). Then we
Scheme 2. Controlled experiments.
studied. DBU, DABCO, DMAP gave the lower yield compare to TBD
(Table 1, entries 10–12). Next, the effect of temperature was stud-
ied from 80 to 60 °C and 70 °C temperature is optimum for this
reaction (Table 1, entries 13 to 14). Then, the effect of time was
performed and 15 h of reaction time was gave the 88% yield of ben-
zimidazole. Further decrease in the reaction time to 10 h yield of
Fig. 1. Plausible reaction mechanism based on the previous report and experimental data.
Fig. 2. Recyclability of Pd/C for the synthesis of benzimidazole.
4

V.V. Phatake and B.M. Bhanage
Tetrahedron Letters 68 (2021) 152940
performed a reaction with 4-iodo-2-nitroaniline as a substrate
gave only benzimidazole instead of 5-iodo-1H-benzimidazole
(Table 2 entry 8). Additionally, N-substituted nitroaniline having
methyl and ethyl groups (Table 2, entries 9 and 10) gave the excel-
lent yield compare to N-substituted nitroaniline having phenyl
group (Table 2, entries 11 and 12), this is due to the steric hin-
drance of the phenyl group. Next, 4,5-dimethyl benzimidazole
was also synthesized in good yield from 4,5-dimethyl-2-nitroani-
line (Table 2 entry 13).
source compare to boranes. The synthesis of benzimidazole
involves the hydrogenation of 2-nitroaniline to o-phenylenedi-
amine, which further reacted with CO2 to obtained formamide
intermediate which undergo cyclization followed by dehydration
to delivered benzimidazole. Furthermore, this catalyst can be recy-
cled up to five recycled runs without a significant decrease in the
yield of benzimidazole.
Declaration of Competing Interest
Next, we performed controlled experiments (Scheme 2). First,
we tried the reaction with an optimized reaction condition and
benzimidazole obtained as a product (Scheme 2a). Then we per-
formed the reaction without reducing agent (PhSiH3), and no
reduction of the nitro group, as well as CO2 insertion was observed
(Scheme 2b). Next, the reaction was performed without CO2; only
the reduction of the nitro group was observed (Scheme 2c). To con-
firm the N-formamide as an intermediate after CO2 insertion, we
performed the reaction with nitrobenzene instead of o-nitroaniline
and formanilide was observed in good yield (Scheme 2d).
On the basis of controlled experiments and previous reports, a
plausible reaction mechanism has been proposed for the synthesis
of benzimidazole from nitroaniline, CO2 and PhSiH3 as a reducing
agent and Pd/C as a catalyst (Fig. 1) [19–22]. Intermediate A is
obtained from ortho nitroaniline by in situ reduction of nitro group
using Pd/C as a catalyst and PhSiH3 as a reductant. Next, the
hydride transfer reaction occurs between phenyl silane and CO2
led to the formation of intermediate C. The nucleophilic attack of
A on the carbonyl group of intermediate C to delivered formamide
intermediate D. Finally, benzimidazole (E) was obtained by cycliza-
tion followed by dehydration.
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgement
The author Vishal Phatake acknowledges the university grant
commission (UGC) for providing UGC SRF fellowship.
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Recyclability
The recyclability of any catalyst is an important aspect to con-
firm the heterogeneous nature of catalysts (Fig. 2). For the recycle
run, the 2-nitroaniline (0.5 mmol), PhSiH3 (3 equi.), catalyst
(10 mg, 0.01 mmol of Pd), TBD (5 mol %), CO2 (1 MPa), ACN
(7 mL), for 15 h at 70 °C. After completion of the reaction, the cat-
alyst was recovered by centrifugation and used for the next recy-
cled run. The Pd/C catalyst shows excellent performance, and it
can be recycled up to five recycled runs without a noteworthy
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We have developed a simple and efficient route for the synthe-
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a heterogeneous recyclable catalyst. A series of benzimidazoles
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5