N-Substituted Formamides as C1-Sources for the Synthesis of Benzimidazole and Benzothiazole Derivatives by Using Zinc Catalysts

Article abstract of DOI:10.1055/s-0035-1560319

An efficient and convenient one-pot protocol has been developed for the synthesis of a variety of benzimidazole, benzoxazole, and benzothiazole derivatives. This novel approach uses various o-phenylenediamines and N-substituted formamides (C₁ sources) in a zinc-catalyzed cyclization in the presence of poly(methylhydrosiloxane) to afford the corresponding derivatives as sole products in moderate to excellent yields.

Full text of DOI:10.1055/s-0035-1560319

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©
Georg Thieme Verlag Stuttgart · New York
2015, 26, 2835–2842
2835
letter
Synlett
D. B. Nale, B. M. Bhanage
Letter
N-Substituted Formamides as C -Sources for the Synthesis of Ben-
1
zimidazole and Benzothiazole Derivatives by Using Zinc Catalysts
Deepak B. Nale
Bhalchandra M. Bhanage*
Zn(OAc)2•2H2O
5 mol%)
O
NH2
XH
(
N
X
R2
R1
R1
H
Department of Chemistry, Institute of Chemical Technology,
N. Parekh Marg, Matunga, Mumbai 400 019, India
bm.bhanage@gmail.com
+
H
N
R2
PMHS, 120 °C
18 h
bm.bhanage@ictmumbai.edu.in
1
solventless
conv. 100%
yield up to 95%
4 examples
R = H, Me, OMe, OH, Cl, Br, NO2
2
R = H, Me, Et, Ph, n-Bu, cyclic
3
Ar = heteroaromatic, X = NH, S, O
9
Received: 11.07.2015
methods. These include a synthesis of benzimidazoles by
using 1,2-arylenediamines and N,N-dimethylformamide in
a highly acidic medium.9
Accepted after revision: 23.08.2015
Published online: 22.09.2015
DOI: 10.1055/s-0035-1560319; Art ID: st-2015-d0534-l
m
However, most of the existing methods have disadvan-
tages, such as a requirement for toxic or air-sensitive re-
agents, harsh conditions, or highly acidic media. Others
show poor atom economy or involve multistep syntheses of
prefunctionalized precursors, with limited success in terms
of yield and selectivity.
Much effort has been devoted to the development of
less-expensive and cleaner protocols and, in this respect,
zinc emerges as an interesting catalyst in the view of its
abundance and low cost.10 Here, we report an economical
protocol for the synthesis of benzimidazoles, benzoxazoles,
and benzothiazoles or substituted benzothiazole scaffolds
by using zinc and poly(methylhydrosiloxane) (PMHS) as a
catalytic system.
Abstract An efficient and convenient one-pot protocol has been de-
veloped for the synthesis of a variety of benzimidazole, benzoxazole,
and benzothiazole derivatives. This novel approach uses various o-
phenylenediamines and N-substituted formamides (C1 sources) in a
zinc-catalyzed cyclization in the presence of poly(methylhydrosiloxane)
to afford the corresponding derivatives as sole products in moderate to
excellent yields.
Key words formamides, benzenediamines, cyclizations, heterocycles,
zinc, catalysis
Benzimidazoles and benzothiazoles have attracted con-
siderable interest from organic chemists because of their
occurrence in a wide variety of pharmaceutically important
scaffolds in medicinal chemistry. They are also key struc-
tures in various biologically active compounds that show
antifungal, antileukemic, antihypertensive, antiulcerative,
antihistaminic, antitumor, antiviral, antidiabetic, or anthel-
mintic activities, examples of which are shown in Figure 1.1
Various methods have been developed for the synthesis
of benzimidazoles, benzoxazoles, benzothiazoles, or substi-
tuted benzothiazole scaffolds. However, these methods in-
volve condensation–dehydration of o-phenylenediamines
N,N-Dimethylformamide (DMF) is a versatile reagent
that can act as a source of –CO, –Me, –NMe , –CONMe ,
2
2
–CHO, or –CN groups, depending on the reaction condi-
tions.11 However, the synthetic utility of DMF as a source of
formyl (–CHO) groups is prominent among the reported
procedures. Some recent protocols include the formylation
of N–H functional group by DMF with copper(II) acetate
and tert-butyl hydroperoxide in an oxidative C–N bond-
forming reaction.12 PMHS is also used in many organic reac-
tions because it is an inexpensive, air stable, and nontoxic
2
or 2-aminobenzenethiol with carbonyl compounds, formic
acid, derivatives of carboxylic acids, or alcohols5 in the
3
4
reagent.
13a
6
In a continuation of our ongoing research,13 we report
an efficient, mild, and environmentally benign protocol for
the synthesis of benzimidazole derivatives by using a zinc
catalyst under solvent-free conditions (Scheme 1). This pro-
tocol was also applied to the synthesis of various benzothi-
azole and benzoxazole derivatives.
presence of oxidants, or cyclization of thioanilides. The
three-component reactions of 2-iodoaniline, aldehydes, and
elemental sulfur, and an intramolecular cross-coupling8
using transition metal-catalysts have been reported for the
synthesis of benzothiazole derivatives. Likewise, benzimid-
azoles and benzoxazoles have been synthesized by various
7
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Synlett
D. B. Nale, B. M. Bhanage
Letter
Me
N
H
N
N
N
Me
n-Pr
S
N
HOOC
N
O
OMe
MeO
N
omeprazole
antiulcer drug
micardis
antihypertention drug
CO2H
N
N
X
R1
H
H
N
N
O
X = NH, S, O
OMe
N
S
N
N
HN
F3C
pimobendan
calcium-sensitizer drug
O
Me
zopolrestat
antidiabetes drug
O
Me
OH
N
Cl
N
N
bendamustine
antileukemia drug
Cl
Figure 1 Representative drugs containing benzimidazole or benzothiazole skeletons
Zn(OAc)2•2H2O
5 mol%)
products were accompanied by minor amounts of the N-
methylation product 2a′ in the cases of zinc(II) nitrate hexa-
hydrate (entry 4) and zinc(II) sulfate heptahydrate (entry
5).
O
NH2
XH
(
N
X
R2
R1
R1
+
H
N
R2
H
PMHS, 120 °C
8 h
1
1
3
2
conv. 100%
yield up to 95%
Table 1 Screening of Various Catalystsa
Scheme 1 Approach to benzimidazole, benzothiazole, and benzoxaz-
b
Entry
Catalyst
Yield (%) of 2a
ole derivatives in the presence of N-substituted formamides as C sourc-
1
es
1
2c
3
4
5
6
7
–
–
Zn(OAc)
2
·2H
2
2
O
O
93
91
Zn(OTf)
Zn(NO
ZnSO
Zn(acac)
ZnCl
Zn(OH)
2
To optimize the reaction conditions, we screened vari-
ous catalysts, catalyst loadings, times, temperatures, and
the effect of PMHS on the synthesis 1H-benzimidazole (2a)
from benzene-1,2-diamine (1a) and DMF (3) as a model
system. In an initial study conducted in the absence of any
catalyst, the desired product was not obtained (Table 1, en-
try 1), indicating that the presence of a catalyst was neces-
sary for the progress of reaction. We then screened a range
of zinc catalysts (Table 1, entries 2–8). Among these, zinc(II)
acetate dihydrate provided the expected 1H-benzimidazole
91d
3
)
2
·6H
90e
4
2
·7H O
2
82
20
38
2
8
2
a
Reaction conditions: benzene-1,2-diamine (2 mmol), catalyst (5.0 mol%),
DMF (10.0 mmol), PMHS (5.0 mmol), 120 °C, 18 h.
b
By GC–GC/MS analysis with 1H-benzimidazole as an external standard.
Isolated yield after column chromatography.
2
2
c
d
a′ (9%) was also obtained.
a′ (10%) was also obtained.
(
2a) as the sole product in 93% isolated yield (entry 2); the
e
structure of the product was confirmed by NMR and mass
analysis. Zinc(II) chloride and zinc(II) hydroxide gave the
desired product in lower yields (entries 7–8). Zinc(II) tri-
flate, zinc(II) nitrate hexahydrate, zinc(II) sulfate hepta-
hydrate, and bis(acetylacetonato)zinc gave the desired
product 2a in good to excellent yields (entries 3–6), but the
Encouraged by these results, we investigated the effects
of catalyst loading on the reaction yield (Table 2, entries 1–
4). The yield increased marginally on increasing the amount
of catalyst to 15 mol%. We observed that 5 mol% of catalyst
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Synlett
D. B. Nale, B. M. Bhanage
Letter
provided the highest yield (93%) of the desired product 2a.
Next, we examined the effect of reaction time on the reac-
tion outcome (entries 5–7). Initially, we carried out the re-
action for 16 hours, which gave the desired product in 80%
yield (entry 7). An excellent 93% yield of 2a with complete
conversion of the reactants was obtained after 18 hours.
Table 2 Effect of Reaction Parameters on the Synthesis of Benzimidaz-
oles 2a and 2a′
N
N
H
O
NH2
NH2
2
a
catalyst
(entry 6). No notable effect was observed on increasing the
Me
+
+
H
N
time to 20 hours (entry 5). We then examined the reaction
at various temperatures (entries 8 and 9). At 120 °C, a 93%
yield of the desired product 2a was obtained within 18
hours. The yield of the desired product decreased with de-
creasing reaction temperature. Finally, we focused on the
effect of PMHS loading on the reaction yield (entries 10–
reductant, temp,
time
solventless
N
N
Me
3
1a
Me
2a'
Entry
Catalyst
(mol%)
PMHS
(mmol)
Temp
(°C)
Time
(h)
Conversiona Yielda
14). The reaction did not proceed in the absence of PMHS
(%)
(%)
(entry 14). Furthermore, when we increased the amount of
Effect of catalyst loading
PMHS from 10 to 25 mmol, there was a decrease in the yield
of the desired product 2a, accompanied by an increase in
the yield of the methylated byproduct 2a′ (entries 10–13).
Hence, the optimized reaction conditions were established
as benzene-1,2-diamine (1a) (2 mmol), zinc(II) acetate di-
hydrate catalyst (5 mol%), DMF (3; 10 mmol), and PMHS (5
1
2
3
4
–
5
5
5
5
120
120
120
120
18
18
18
18
–
NR
15
10
5
100
94
100
100
94
93b
Effect of time
14
mmol) at 120 °C for 18 hours.
5
6
7
5
5
5
5
5
5
120
120
120
20
18
16
100
100
100
93
93
80
Because of the importance of benzimidazoles, benzothi-
azoles, and substituted benzothiazole scaffolds, these reac-
tions conditions were used to explore the substrate scope.
The reactions of a variety of substituted o-phenylenedi-
amines 1 with various N-substituted formamides and thio-
formamides 3 were examined under the optimized condi-
tions (Table 3). To identify the optimal C1 source (–CHO
group), we turned our attention to other N-substituted for-
mamides, such N,N-diethylformamide, N-phenylforma-
mide, N-formylmorpholine, N,N-dibutylformamide, N-
methylformanilide, and N,N-dimethylthioformamide (Table
Effect of temperature
8
9
5
5
5
5
130
100
18
18
100
90
93
82
Effect of PMHS
10
5
5
5
5
5
25
20
15
10
0
120
120
120
120
120
18
18
18
18
18
100
100
100
100
–
90b,c
11
92b,d
93b,e
12
13
14
3, entries 1–7). Note that all the N-substituted formamides
94
–
provided good to excellent yields of the desired product 2a.
Among the formamides, DMF provided an excellent yield of
the desired product and was used in all subsequent studies
to demonstrate the general applicability of the reaction to
various substrates. Benzene-1,2-diamines bearing methyl,
methoxy, or chloro substituents on the phenyl ring (1b–d,
a
b
c
Based on GC/MS analysis with 1H-benzimidazole as an external standard.
Isolated yield after column chromatography.
2a′ (10%) was also obtained.
2
2
d
e
a′ (8%) was also obtained.
a′ (7%) was also obtained.
1f) were well tolerated under the present reaction condi-
tions and provided the corresponding products 2a–d and 2f
in excellent yields (entries 1–10 and entry 12). Unfortu-
nately, 2,3-diaminophenol (1e) did not provide the desired
product (entry 11).
Substrates possessing an electron-withdrawing nitro
group and substrates containing heterocyclic rings provid-
ed good yields of the corresponding N-methylated cyclized
products 2g (79%), 2h (89%), 2i (75%), and 2j (81%) (Table 3,
entries 13–16, respectively). Note that the reactions of
naphthalene-2,3-diamine and naphthalene-1,8-diamine
also gave the corresponding products 2k and 2l, albeit in
slightly lower yields of 45% and 41%, respectively (entries
17 and 18). However, in the case of 2k, 20% of N-methyla-
tion also took place. We also applied our method to N-sub-
stituted benzene-1,2-diamines, such as N-methylbenzene-
1,2-diamine, N-phenylbenzene-1,2-diamine, and we ob-
tained the corresponding products in good yields (entries
19 and 20). When we extended our protocol to 2-amino-
phenol, 5-methyl-2-aminophenol, and 2-aminobenzen-
ethiol, we obtained 2o (70%), 2p (81%), and 2q (83%), re-
spectively (entries 21–23). In the reaction of 2-nitroaniline
(1r) with DMF, only N-methylation occurred, giving the
product 2r in 94% yield (entry 24). Biphenyl-3,3′,4,4′-
tetraamine (1s) also gave a moderate 38% yield of product
2s (entry 25).
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D. B. Nale, B. M. Bhanage
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Table 3 Synthesis of Various Benzimidazole Derivatives under Solvent-Free Conditionsa
NH2
Zn(OAc)2•2H2O
N
N
R1
(thio)formamide
R1
+
PMHS, 120 °C
3
NH2
18 h
R
solventless
1a
2a/2a'
b
Entry
1
Substrate
(Thio)formamide
DMF
Product
Yield (%)
NH2
NH2
N
93
N
H
1
a
2a
2
3
4
5
6
7
Et
2
NCHO
85
92
90
89
70
72
PhNHCHO
morpholine-4-carbaldehyde
Bu
PhN(Me)CHO
Me NCH=S
2
NCHO
2
NH2
NH2
NH2
NH2
N
8
DMF
DMF
DMF
91
92
95
N
H
Me
Me
1
b
2b
Me
Me
N
9
N
H
Me
Me
1
c
2c
NH2
N
1
0
1
N
MeO
NH2
MeO
H
1
d
2d
OH
OH
NH2
NH2
N
1
DMF
–
N
H
1
e
2e
NH2
N
1
2
3
DMF
DMF
93
79
N
H
Cl
Cl
NH2
1
f
2f
N
NH2
1
N
O2N
O2N
NH2
Me
1
g
2
g
N
N
NH2
NH2
14
DMF
89
N
N
Me
1
h
2
h
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D. B. Nale, B. M. Bhanage
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Table 3 (continued)
b
Entry
Substrate
(Thio)formamide
Product
Yield (%)
Br
N
N
N
N
Br
N
N
NH2
15
DMF
75
NH2
Me
1
i
2
i
Cl
Cl
NH2
NH2
N
N
1
6
7
DMF
DMF
81
N
N
Me
1
1
j
2
j
NH2
N
1
45c
N
H
NH2
k
2k
NH2 NH2
N
NH
18
DMF
41
1
1
l
2
l
NH2
N
N
1
9
0
Me
DMF
DMF
95
88
N
H
Me
m
2m
2n
NH2
N
N
2
Ph
N
H
Ph
1
1
n
o
NH2
OH
N
O
21
22
23
DMF
DMF
DMF
70
81
83
2
o
NH2
OH
N
O
Me
Me
2p
1
1
p
q
NH2
SH
N
S
2
2
q
r
H
N
NH2
NO2
Me
2
2
4
DMF
DMF
94
38
NO2
1
r
H2N
H2N
NH2
NH2
HN
NH
5
N
N
1
s
2s
a
b
c
Reaction conditions: substrate (2 mmol), Zn(OAc)
Isolated yield after column chromatography.
The methylated product was also obtained in 20% yield.
2 2
·2H O (5 mol%), (thio)formamide (10 mmol), PMHS (10 mmol), 120 °C, 18 h.
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D. B. Nale, B. M. Bhanage
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We also examined this catalytic system for the synthesis
of a variety of substituted benzothiazole scaffolds from 2-
aminobenzenethiol and nitriles under solvent-free condi-
tions. Various aromatic nitriles bearing electron-donating
or electron-withdrawing groups on the phenyl ring were
well tolerated under the reaction conditions and provided
the corresponding products 2aa–ai (Table 4, entries 1–9).
Table 4 Synthesis of 2-Substituted Benzothiazole Derivatives under Solvent-Free Conditionsa
NH2
N
Zn(OAc)2•2H2O
R1
R1
R2
R2
+
N
S
SH
PMHS, 120 °C
18 h
solventless
1aa
4
2aa–ai
b
Entry
1
2-Aminothiophenol
Nitrile
Product
Yield (%)
NH2
N
S
N
Me
96
SH
4a
2
aa
1
aa
N
N
NH2
2
3
45
91
H2N
S
4
b
2
2
ab
ac
N
CN
S
4
c
N
CN
4
5
6
S
85
51
89
MeO
OMe
4
d
2ad
2ae
2af
N
CN
OMe
S
MeO
4
e
N
S
CN
Me
Me
4
f
Cl
CN
N
7
8
81
Cl
S
4
g
2
ag
t-Bu
CN
N
75
55
t-Bu
S
4
h
2
2
ah
ai
N
N
CN
N
9
S
4
i
a
2
Reaction conditions: 2-H
Isolated yield after column chromatography.
2
NC
6 4 2 2
H SH (1aa; 2 mmol), R CN (4; 10.0 mmol), Zn(OAc) ·2H O (5.0 mol%), PMHS (5.0 mmol), 120 °C, 18 h.
b
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D. B. Nale, B. M. Bhanage
Letter
In the model reaction, 2-aminobenzenethiol (1aa) and
acetonitrile (4a) were easily converted into 2-methylben-
zo[d]thiazole (2aa) in 96% isolated yield (Table 4, entry 1).
This protocol was applied to the synthesis of ben-
zo[d]thiazol-2-amine (2ab; Table 4, entry 2), an important
key intermediate in numerous biologically active drugs
such as Zopolrestat and Riluzole. Furthermore, benzo-
nitrile (4c) readily reacted with 2-aminobenzenethiol (1aa)
to give the desired product 2ac (entry 3). 3-Methoxybenzo-
nitrile, 3-methylbenzonitrile, and 4-chlorobenzonitrile also
provided excellent yields of the corresponding products
Acknowledgment
D.B.N. is grateful to the University Grants Commission, India, for pro-
viding financial support under the UGC-SAP-SRF program, Green
Technology Centre of Institute of Chemical Technology (ICT), Mumbai,
India.
16
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560319.
S
u
p
p
o
nrtIo
i
g
f
rm oaitn
S
u
p
p
ortioIgnfmr oaitn
2
ad, 2af, and 2ag (entries 4, 6, and 7). However, 2-methoxy-
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benzonitrile derivative bearing a tertiary alkyl group also
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Et
R2
1
2
1
2
2
2
2
a R , R = H, 93%
Me
N
b R = Me, R2 = H, 91%
1
O
1
2
g R = NO2, R = Me, 79%
Me
Me
(
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For the investigation of the reaction mechanism, re-
placement of DMF with other formamides afforded in the
table 3, entries 2–7 at relatively good to excellent yields, but
no reaction was observed when DMF was replaced by N,N-
dimethylacetamide (Scheme 2), so the formyl proton is nec-
essary for the desired product.
In summary, we have developed a simple, efficient, and
inexpensive catalytic protocol for the synthesis of benzim-
idazoles from various o-phenylene diamines in the pres-
ence of zinc and PMHS as a robust catalytic system under
solvent-free and mild reaction conditions. This catalytic
system provides an attractive method for the synthesis of
wide range of benzimidazoles by using N,N-dimethylforma-
172. (e) Grimmett, M. R. Imidazole and Benzimidazole Synthesis;
Academic Press: San Diego, 1997.
(
5) (a) Blacker, A. J.; Farah, M. M.; Marsden, S. P.; Saidi, O.; Williams,
J. M. J. Tetrahedron Lett. 2009, 50, 6106. (b) Su, F.; Mathew, S. C.;
Möhlmann, L.; Antonietti, M.; Wang, X.; Blechert, S. Angew.
Chem. Int. Ed. 2011, 50, 657. (c) Endo, Y.; Bäckvall, J.-E. Chem.
Eur. J. 2012, 18, 13609. (d) Nguyen, T. B.; Ermolenko, L.; Dean,
W. A.; Al-Mourabit, A. Org. Lett. 2012, 14, 5948. (e) Yu, J.; Xu, J.;
Lu, M. Appl. Organomet. Chem. 2013, 27, 606. (f) Khalafi-Nezhad,
A.; Panahi, F. ACS Catal. 2014, 4, 1686. (g) Mukhopadhyay, C.;
Ghosh, S.; Sengupta, S.; De, S. RSC Adv. 2011, 1, 1033.
mide as a C source. Further examinations of applications of
1
(6) (a) Ma, D.; Xie, S.; Xue, P.; Zhang, X.; Dong, J.; Jiang, Y. Angew.
Chem. Int. Ed. 2009, 48, 4222. (b) Cheng, Y.; Yang, J.; Qu, Y.; Li, P.
Org. Lett. 2012, 14, 98.
this active catalytic system and detailed mechanistic stud-
ies are underway.
(
(
7) Deng, H.; Li, Z.; Ke, F.; Zhou, X. Chem. Eur. J. 2012, 18, 4840.
8) (a) Vera, M. D.; Pelletier, J. C. J. Comb. Chem. 2007, 9, 569.
(b) Evindar, G.; Batey, R. A. J. Org. Chem. 2006, 71, 1802. (c) Bose,
D. S.; Idrees, M. J. Org. Chem. 2006, 71, 8261. (d) Kashiyama, E.;
Hutchinson, I.; Chua, M.-S.; Stinson, S. F.; Phillips, L. R.; Kaur, G.;
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2835–2842

2
842
Synlett
D. B. Nale, B. M. Bhanage
Letter
Sausville, E. A.; Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G.
J. Med. Chem. 1999, 42, 4172. (e) Saha, P.; Ramana, T.; Purkait,
N.; Ali, M. A.; Paul, R.; Punniyamurthy, T. J. Org. Chem. 2009, 74,
perature with vigorous stirring (600 rpm). During the course of
the reaction, an increase of pressure was observed, due to the
15
generation of Me NH and HCHO at 120 °C. (For this reason,
2
8
719.
the protocol needs to be performed in a sealed high-pressure
reactor.) When the reaction was complete, the autoclave was
cooled to r.t., and the pressure generated during the reaction
was carefully released. Basic hydrolysis was then carried out at
r.t. for 30 min to remove unreacted PMHS from the mixture.1
The mixture was then extracted with EtOAc (3 × 20 mL). The
combined organic layers were dried (Na SO ), filtered, and con-
(
9) (a) Shelkar, R.; Sarode, S.; Nagarkar, J. Tetrahedron Lett. 2013, 54,
6986. (b) Bahrami, K.; Khodaei, M. M.; Nejati, A. Green Chem.
2
010, 12, 1237. (c) Qiao, J. X.; Wang, T. C.; Hu, C.; Li, J.; Wexler, R.
3a
R.; Lam, P. Y. S. Org. Lett. 2011, 13, 1804. (d) Yu, B.; Zhang, H.;
Zhao, Y.; Chen, S.; Xu, J.; Huang, C.; Liu, Z. Green Chem. 2013, 15,
95. (e) Yu, H.; Kawanishi, H.; Koshima, H. Heterocycles 2003, 60,
2
4
1
457. (f) Sparke, A. E.; Fisher, C. M.; Mewis, R. E.; Archibald, S. J.
centrated in vacuo. The crude products were further purified by
column chromatography [silica gel (100–200 mesh), PE–EtOAc
(20:4 to 10:2)]. The spectroscopic data for the products were
Tetrahedron Lett. 2010, 51, 4723. (g) Mochona, M.; Le, L.;
Mateeva, N.; Gangapuram, M.; Ardley, T.; Kinfe, K. J. Heterocycl.
Chem. 2010, 47, 1367. (h) Bahrami, K.; Khodaei, M. M.;
Kavianinia, I. Synthesis 2007, 547. (i) Du, L.-H.; Wang, Y.-G. Syn-
thesis 2007, 675. (j) Bahrami, K.; Khodaei, M. M.; Naali, F. J. Org.
Chem. 2008, 73, 6835. (k) Saha, D.; Saha, A.; Ranu, B. C. Green
Chem. 2009, 11, 733. (l) Tang, L.; Guo, X.; Yang, Y.; Zha, Z.; Wang,
Z. Chem. Commun. 2014, 50, 6145. (m) Kattimani, P. P.; Kamble,
R. R.; Meti, G. Y. RSC Adv. 2015, 5, 29447. (n) Khemnar, A.;
Bhanage, B. M. RSC Adv. 2014, 4, 8939.
9
consistent with those reported in the literature.
6-Methyl-1H-benzimidazole (2b)
White solid; yield: 120 mg (91%). H NMR (CDCl , 400 MHz,
1
3
30 °C, TMS): δ = 8.00 (s, 1 H), 7.55 (d, J = 8 Hz, 1 H), 7.43 (s, 1 H),
13
7.11 (d, J = 8 Hz, 1 H), 6.16 (s, 1 H), 2.47 (s, 3 H). C NMR (CDCl3,
100 MHz, 30 °C, TMS): δ = 140.26, 137.13, 136.03, 132.92,
124.53, 115.44, 114.77, 21.63. GC-MS (EI): m/z (%) = 132 (89) [M
+
+
+ 1] , 131 (100) [M ], 104 (20), 77 (25), 66 (10), 51 (17).
(
10) (a) González, J.; López, L. A.; Vicente, R. Chem. Commun. 2014,
0, 8536. (b) Ding, G.; Lu, B.; Li, Y.; Wan, J.; Zhang, Z.; Xie, X. Adv.
1-Methyl-6-nitro-1H-benzimidazole (2g)
Yellowish solid; yield: 140 mg (79%). H NMR (CDCl , 400 MHz,
1
5
3
Synth. Catal. 2015, 357, 1013. (c) Legrave, N.; Couhert, A.;
Olivero, S.; Desmurs, J.-R.; Duñach, E. Eur. J. Org. Chem. 2012,
30 °C, TMS): δ = 8.39 (s, 1 H), 8.24–8.21 (d, J = 8, 12 Hz, 1 H),
8.12 (s, 1 H), 7.87 (d, J = 12 Hz, 1 H), 3.96 (s, 3 H). 13C NMR
2012, 901. (d) Das, S.; Addis, D.; Zhou, S.; Junge, K.; Beller, M. J.
(CDCl , 100 MHz, 30 °C, TMS): δ = 146.75, 142.86, 132.72,
3
Am. Chem. Soc. 2010, 132, 1770. (e) González, M. J.; López, L. A.;
Vicente, R. Tetrahedron Lett. 2015, 56, 1600.
11) (a) Muzart, J. Tetrahedron 2009, 65, 8313. (b) Ding, S.; Jiao, N.
Angew. Chem. 2012, 124, 9360; Angew. Chem. Int. Ed. 2012, 51,
123.35, 119.45, 117.03, 105.45, 28.68. GC-MS (EI): m/z (%) = 178
(12) [M + 1] , 177 (100) [M ], 147 (44), 131 (51), 116 (27), 104
(43), 90 (25), 77 (18), 63 (68), 51 (17).
+
+
(
1-Methyl-1H-benzimidazole (2m)
Brownish solid; yield: 125 mg (95%). H NMR (CDCl , 400 MHz,
1
9226. (c) Kim, J.; Choi, J.; Shin, K.; Chang, S. J. Am. Chem. Soc.
2012, 134, 2528. (d) Ding, S.; Jiao, N. J. Am. Chem. Soc. 2011, 133,
12374. (e) Zhang, G.; Ren, X.; Chen, J.; Hu, M.; Cheng, J. Org. Lett.
2011, 13, 5004. (f) Kim, J.; Chang, S. J. Am. Chem. Soc. 2010, 132,
10272. (g) Kennedy, G. L. Jr. Crit. Rev. Toxicol. 1986, 17, 129.
3
30 °C, TMS): δ = 7.82 (s, 1 H), 7.72–7.61 (m, 1 H), 7.34–7.22 (m,
13
2 H), 3.65 (s, 3 H). C NMR (CDCl , 100 MHz, 30 °C, TMS):
3
δ = 146.37, 143.11, 136.33, 131.87, 126.75, 115.20, 113.44,
+
+
29.74. GC-MS (EI): m/z (%) = 133 (9) [M + 1] , 132 (100) [M ],
118 (49), 104 (11), 91 (23), 77 (6), 65 (13), 64 (19), 63 (24), 52
(11).
(h) Sawant, D. N.; Wagh, Y. S.; Bhatte, K. D.; Bhanage, B. M. J. Org.
Chem. 2011, 76, 5489.
(12) Ali, W.; Rout, S. K.; Guin, S.; Modi, A.; Banerjee, A.; Patel, B. K.
Adv. Synth. Catal. 2015, 357, 515.
N-Methyl-2-nitroaniline (2r)
Orange solid; yield: 143 mg (94%). H NMR (CDCl , 400 MHz,
1
3
(
13) (a) Nale, D. B.; Bhanage, B. M. Green Chem. 2015, 17, 2480.
30 °C, TMS): δ = 8.11 (d, J = 8 Hz, 1 H), 7.77 (br s, 1 H), 7.46–7.38
(b) Nale, D. B.; Rana, S.; Parida, K. M.; Bhanage, B. M. Catal. Sci.
(m, 1 H), 6.79 (d, J = 8 Hz, 1 H), 6.61 (m, 1 H), 3.01 (s, 3 H). 13
C
Technol. 2014, 4, 1608. (c) Nale, D. B.; Rana, S.; Parida, K. M.;
Bhanage, B. M. Appl. Catal., A 2014, 469, 340. (d) Nale, D. B.;
NMR (CDCl , 100 MHz, 30 °C, TMS): δ = 146.43, 136.37, 131.96,
3
126.82, 115.25, 113.46, 29.78. GC-MS (EI) (%): m/z = 154 (9) [M
+
+
Saigaonkar, S. D.; Bhanage, B. M. J. CO Util. 2014, 8, 67.
+ 2] , 152 (100) [M ], 138 (20), 122 (13), 106 (59), 92 (21), 79
(61), 77 (66), 65 (59), 51 (13).
2
(
14) Benzimidazole Derivatives; General Procedure
Zn(OAc) ·2H O (5.0 mol%) was transferred to a 100 mL autoclave
(15) Petersen, T. P.; Larsen, A. F.; Ritzén, A.; Ulven, T. J. Org. Chem.
2013, 78, 4190.
(16) (a) Beyer, T. A.; Scott, P. J.; Aldinger, C. E.; Dee, M. F.; Siegel, T.
W.; Zembrowski, W. J.; Mylari, B. L. J. Med. Chem. 1992, 35, 457.
(b) Song, J.-H.; Huang, C.-S.; Nagata, K.; Yeh, J. Z.; Narahashi, T.
J. Pharmacol. Exp. Ther. 1997, 282, 707.
2
2
reactor equipped with an overhead stirrer and an automatic
temperature-control system. The appropriate benzene-1,2-
diamine 1 (2 mmol), DMF (10.0 mmol), and PMHS (5.0 mmol)
were successively introduced. The reactor was sealed, flushed
three times with N (10 atm), and heated to the required tem-
2
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2835–2842