An efficient route for the synthesis of N-(1H-benzo[d]imidazol-2-yl)benzamide derivatives promoted by CBr4 in one pot

Article abstract of DOI:10.1016/j.tet.2020.130977

A metal-free one-pot method for the synthesis of N-(1H-benzo[d]imidazol-2-yl)benzamide derivatives was proposed mediated by CBr₄. The reaction went through ring formation and opening processes with only two protons leaving and the thermodynamically favorable products were selectively formed in moderate to good yields.

Full text of DOI:10.1016/j.tet.2020.130977

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An efficient route for the synthesis of N-(1H-benzo[d]imidazol-2-yl)benzamide
derivatives promoted by CBr in one pot
4
Caixia Xie, Songhua Li, Yunyi Li, Chen Ma
PII:
S0040-4020(20)30072-7
https://doi.org/10.1016/j.tet.2020.130977
TET 130977
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 4 November 2019
Revised Date: 20 January 2020
Accepted Date: 22 January 2020
Please cite this article as: Xie C, Li S, Li Y, Ma C, An efficient route for the synthesis of N-(1H-
benzo[d]imidazol-2-yl)benzamide derivatives promoted by CBr in one pot, Tetrahedron (2020), doi:
4
https://doi.org/10.1016/j.tet.2020.130977.
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Tetrahedron
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An efficient route for the synthesis of N-(1H-benzo[d]imidazol-2-yl)benzamide
derivatives promoted by CBr4 in one pot
Caixia Xie a, b, Songhua Li a, Yunyi Li a, Chen Ma a, 
a School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, P. R. China.
b School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo, 255049, P. R. China
ARTICLE INFO
ABSTRACT678
Article history:
Received
Received in revised form
Accepted
A metal-free one-pot method for the synthesis of N-(1H-benzo[d]imidazol-2-yl)benzamide
derivatives was proposed mediated by CBr4. The reaction went through ring formation and
opening processes with only two protons leaving and the thermodynamically favorable products
were selectively formed in moderate to good yields.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
CBr4
1H-benzo[d]imidazol-2-amine
Synthesis
N-(1H-benzo[d]imidazol-2-yl)benzamide
Atom economy
many defects, such as multi-step reactions10, harsh conditions like
strong bases11 and transition metal catalysts12. To our knowledge,
1. Introduction
Benzimidazole derivatives are common crucial structures in
numerous naturally occurring products and hundreds of drugs1.
N-(1H-benzo[d]imidazol-2-yl)benzamide derivatives have been
proved to be effective drugs for a long time. For instance,
Albendazole and Mebendazole (Scheme 1, A and B)2 are existing
drugs used for anti-parasitism, and a highly water-soluble
prodrug of anthelmintic benzimidazole carbamate (Scheme 1, C)3
has been reported in 2008. Moreover, the antimicrobial and
the formation of carbon-nitrogen bonds should be an effective
strategy to build this skeleton. Despite the complex catalytic
system used in the oxidative coupling of the C-N bond13, carbon
tetrabromide (CBr4) has been proved to be an efficient catalyst in
the construction of C-N bond until very recently14. Huo et al
reported a C-N bond formation reaction mediated by CBr4 to
synthesize imidazo[1,2-a]pyridines in 201614(a). Chen et al put the
CBr4 applied in the synthesis of 1,2,4,5-tetra substituted
imidazole derivatives14(b). Taking advantage of this strategy, we
attempt to synthesize N-(1H-benzo[d]imidazol-2-yl)benzamide
derivatives with readily accessible starting materials mediated by
CBr4 under simple and mild conditions.
molluscicidal
activities
of
N-(1H-benzo[d]imidazol-2-
yl)benzamide derivatives have been carried out4. And its
potential drug activities have been reported, such as H4 receptor
antagonists5, TNF-α inhibitors6, kinase inhibitors7, antitumors8
and other interesting biological activities9.
2. Results and discussion
We commenced our experiment of one-pot synthesis of N-(1H-
benzo[d]imidazol-2-yl)benzamides with 1H-benzo[d]imidazol-2-
amine, ethyl 3-oxo-3-phenylpropanoate and CBr4 (3 equiv) at 80
oC in CH3CN (2 mL). Surprisingly, the desired product was
obtained in a yield of 78% (Table 1, entry 1). Inspired by this
result, several additives were screened under the same conditions
and CBr4 proved to be the most effective one (Table 1, entries 2-
8). The screening of different solvents of H2O, toluene, DMSO,
DMF, CH2Cl2 and EtOH suggested that CH3CN was the most
Scheme 1. Selected examples of N-(1H-benzo[d]imidazol-2-
yl)benzamide containing drugs.
Obviously, rich drug activities lead to lots of interests in
synthesizing this skeleton. Existing ways to synthesize N-(1H-
benzo[d]imidazol-2-yl)benzamide derivatives typically involved
———
 Corresponding author.
E-mail address: chenma@sdu.edu.cn

2
a 1a (1.5 mmol), 2a (0.5 mmol), additive (1.5 mmol), solvent (2 mL),
in a sealed tube, 6-8 h (TLC monitored), under air atmosphere.
b Isolated yields.
suitable choice than others (Table 1, entries 9-14). Additionally,
o
lower yields were obtained as the temperature increased to 90 C
o
o
and 100 C or decreased to 70 C (Table 1, entries 15-17). For
further investigation, the dosages of CBr4 were also tested and
the reaction with 3 equivalents of CBr4 gave the highest yield
(Table 1, entries 18-19). Hence, we continued our experiment
c DBDMH = 1,3-dibromo-5,5-dimethylhydantoin.
d CBr4 (1 mmol).
e CBr4 (2 mmol).
The versatilities and limitations of the reaction were
examined by employing 1H-benzo[d]imidazol-2-amine (1a) and
various substituted ethyl 3-oxo-3-phenylpropanoates (2). In
general, compounds 2 with different substituents on the aromatic
ring transformed smoothly into the corresponding products. And
compounds 2 with electron-withdrawing groups gave a little
better yield than those with electron-donating groups (Table 2,
3b-3j). And steric hindrance had no effect on the yields of the
products (3b-3c). It was noteworthy that ethyl 2-(2-(1-
naphthamido)-1H-benzo[d]imidazol-1-yl)acetate, ethyl 2-(2-(2-
naphthamido)-1H-benzo[d]imidazol-1-yl)acetate and ethyl 2-(2-
(benzo[d][1,3]dioxole-5-carboxamido)-1H-benzo[d]imidazol-1-
yl)acetate also proceeded well under the optimized conditions,
and very favorable yields were obtained (Table 2, 3l-3n). Then
o
with 3 equivalents of CBr4 as additive in 2 mL CH3CN at 80 C
under air atmosphere.
Table 1.
Optimization of Reaction Conditions.a
Entry
1
Additive
CBr4
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
H2O
Temp (oC)
80
Yield (%) b
78
2
NBS
80
54
3
NIS
80
7
4
TBAB
LiBr
DBDMH c
80
NR
NR
14
methyl
2-(2-(benzo[d][1,3]dioxole-5-carboxamido)-1H-
benzo[d]imidazol-1-yl)acetates with different substituents
transformed smoothly into the corresponding products in
moderate to excellent yields (Table 2, 3o-3s). Besides, 1,3-
diphenylpropane-1,3-dione and 1-phenylbutane-1,3-dione could
be applied to the reaction to produce the desired products 3t and
3u. It was worth mentioning that compound 2 bearing an alkyl
substituent smoothly worked in this reaction, giving the product
3v in a yield of 41%.
Encouraged by these results, 2-aminoimidazole sulfate (4)
was used as reactant with different β-keto ester derivatives as
shown in Table 3. And Na2CO3 (0.75 mmol) was added to
consume the 1/2H2SO4 of compounds 4. As previously noted, the
target products 5 were obtained in moderate to good yields
(Table 3). And reactions worked smoothly to give the products
ethyl 2-(2-(1-naphthamido)-1H-imidazol-1-yl)acetate (5g) and
ethyl 2-(2-(benzo[d][1,3]dioxole-5-carboxamido)-1H-imidazol-1-
yl)acetate (5h).
5
80
6
80
7
CuBr
80
NR
NR
43
8
CCl4
80
9
CBr4
80
10
11
12
13
14
15
16
17
18
19
CBr4
Toluene
DMSO
DMF
80
NR
60
CBr4
80
CBr4
80
57
CBr4
CH2Cl2
CH3CH2OH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
80
37
CBr4
80
51
CBr4
70
73
CBr4
90
70
CBr4
100
70
67
CBr4 (2:1) d
CBr4 (4:1) e
47
70
54
Table 2
Reaction of 1H-benzo[d]imidazol-2-amineethyl and 3-oxo-3-phenylpropanoate.a,b

a 1 (1.5 mmol), 2 (0.5 mmol), CBr4 (1.5 mmol), CH3CN (2 mL), in a sealed tube, TLC monitored the end of the reaction, under
air atmosphere.
b Isolated yields.
Table 3
Reaction of 1H-imidazol-2-amine and 3-oxo-3-phenylpropanoate.a,b
a 4 (1.5 mmol), 2 (0.5 mmol), Na2CO3 (0.75 mmol), CBr4 (1.5 mmol), CH3CN (2 mL), in a sealed tube, TLC monitored the end of the reaction,
under air atmosphere.
b Isolated yields.
Subsequently, to further investigate the reaction mechanism,
several control experiments were carried out (Scheme 2).
Initially, radical inhibitors (TEMPO and BHT) were added to the
reaction. However, no significant decrease in yield was found.
Thus, it appeared that a radical process can be excluded in this
reaction (Scheme 2, a, b). Then, we succeeded in detecting the
intermediate M by HRMS when the reaction continued for 0.5 h
under standard conditions (Scheme 2, c). And then the reaction
was proceeded at room temperature under standard conditions.
Stopping this reaction after 5 h, M was isolated in a yield of 15%
(Scheme 2, d). Finally, intermediate M was used and the
corresponding product was obtained smoothly in a yield of 87%,
which indicated that M was very likely to be the intermediate of
the transformation (Scheme 2, e).
On the basis of the control experiments above and the
previous literatures14-15, a possible mechanism was proposed for
this transformation in Scheme 3. Mediated by CBr4, intermediate
M was produced with ethyl 3-oxo-3-phenylpropanoate (2a).
Next, two possible pathways might be included. In path a,
nucleophilic reaction afforded the intermediate F and a five-
membered ring intermediate G was obtained by intramolecular
nucleophilic substitution. Alternatively, path b was also a
reasonable explanation. Intermolecular nucleophilic substitution

4
Tetrahedron
was first occurred and gave the intermediate E. Then, E
transformed
Scheme 2. Control experiments.
into G. Lastly, a 1,3-proton transfer provided the desired product
3a instead of a dehydration of intermediate G. As was reported15,
this behavior could be understood that a thermodynamically
favorable product 3a was obtained in priority in the presence of
HBr.
1-yl) acetate derivatives as well as ethyl 2-(2-benzamido-1H-
imidazol-1-yl)acetate derivatives. A variety of desired products
were obtained in moderate to good yields. In particular, almost
100% utilization of reactant atoms was able to be realized with
only two protons leaving in the reaction. Easily accessible
starting materials, simply operations and high atom economy
made this strategy a potential and useful method in organic and
pharmaceutical chemistry.
3. Conclusion
In summary, we have developed an effective, mild and simple
method to construct ethyl 2-(2-benzamido-1H-benzo[d]imidazol-
Scheme 3. Proposed mechanism.
4. Experimental section
4.1 General procedure
1H NMR and 13C NMR spectra were recorded with a 300 MHz
Bruker instrument, a 400 MHz Bruker or 500 MHz Bruker
instrument in CDCl3 or DMSO-d6 and tetramethylsilane (TMS)
was used as the internal standard. HRMS spectra were obtained
using a Q-TOF spectrograph. Compounds 2 were prepared
according to the literature16. The other reagents were
commercially available and were used without further

purification. All the reactions were monitored by thin-layer
chromatography (TLC).
4.2 Preparation of starting materials
Scheme 4. General procedure for the synthesis of compounds 2.
Compounds
2
were prepared according to the previous
5.6 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 176.88, 168.36,
152.65, 138.64, 138.00, 131.55, 130.45, 130.20, 129.85, 129.41,
125.74, 123.18, 112.54, 110.00, 61.66, 43.59, 22.08, 14.51.
HRMS (ESI) calcd for C19H19N3O3 [(M+H)+]: 338.1499; found,
338.1498.
literature.16 A mixture of compound 7 (66 mmol), toluene (20 mL)
and NaH (3.7g, 60% in mineral oil, 92 mmol) was added to a
dried 250 mL RBF under N2 atmosphere. The mixture was heated
to reflux and a solution of compound 6 (33 mmol) in toluene (20
mL) was added into the mixture dropwise. After 1h, the mixture
was cooled to room temperature. Glacial acetic acid (10 mL) was
added dropwise and a heavy pasty solid separated. Ice-cold water
(150 mL) was slowly added until the solid was dissolved
completely. Then, the reaction system was diluted with 200 mL
of EtOAc. The organic layer was separated, washed with water
(20 mL) and brine (20 mL) and dried over Na2SO4. And the
combined extracts were concentrated under reduced pressure and
purified by column chromatography to afford the pure product β-
keto esters 2.
Ethyl
2-(2-(4-methoxybenzamido)-1H-benzo[d]imidazol-1-
o
1
yl)acetate (3d), 68%, White solid, MP: 163-165 C, H NMR
(500 MHz, DMSO-d6) δ: 12.70 (s, 1H), 8.16 (d, J = 8.5 Hz, 2H),
7.53-7.48 (m, 2H), 7.24 (dd, J = 5.5 Hz, 2.0 Hz, 2H), 7.00 (d, J =
8.5 Hz, 2H), 5.11 (s, 2H), 4.22 (q, J = 6.8 Hz, 2H), 3.82 (s, 3H),
1.24 (t, J = 6.0 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) δ:
173.65, 168.45, 162.23, 152.79, 131.14, 130.92, 129.91, 129.48,
123.10, 123.06, 113.61, 112.37, 109.94, 61.64, 55.74, 43.67,
14.58. HRMS (ESI) calcd for C19H19N3O4 [(M+H)+]: 354.1448;
found, 354.1447.
1.3 General experimental procedure for Ethyl 2-(2-
Ethyl 2-(2-(3,4-dimethylbenzamido)-1H-benzo[d]imidazol-1-
benzamido-1H-benzo[d]imidazol-1-yl)acetate
o
1
yl)acetate (3e), 59%, White solid, MP: 159-161 C, H NMR
(500 MHz, DMSO-d6) δ: 12.72 (s, 1H), 7.97 (m, 2H), 7.54 (m,
2H), 7.24 (m, 3H), 5.11 (s,2H), 4.22 (q, J = 7.0 Hz, 2H), 2.29 (s,
3H), 2.27 (s, 3H), 1.24 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz,
DMSO-d6) δ: 174.13, 168.44, 152.82, 140.17, 136.02, 130.32,
129.91, 129.54, 129.48, 126.96, 123.09, 112.43, 109.96, 61.61,
40.49, 20.01, 19.96, 14.58. HRMS (ESI) calcd for C20H21N3O3
[(M+H)+]: 352.1656; found, 352.1655.
A mixture of 1H-benzo[d]imidazol-2-amine (1.5 mmol), ethyl 3-
oxo-3-phenylpropanoate (0.5 mmol) and CBr4 (1 mmol) in
CH3CN (2 mmol) was stirred in 80 oC in a tube under air
atmosphere. TLC monitored the end of the reaction. Then the
mixture was cooled to room temperature and saturated brine (100
ml) was poured into the solution. The mixture was extracted with
EtOAc (3 × 50 mL). The organic phase was combined and dried
by anhydrous Na2SO4. Finally, the product was separated by
flash chromatography on silica gel (petroleum ether / EtOAc = 3:
1) and obtained after vacuum-rotary evaporation.
Ethyl
2-(2-(3-fluorobenzamido)-1H-benzo[d]imidazol-1-
o
1
yl)acetate (3f), 65%, White solid, MP: 166-167 C, H NMR
(500 MHz, DMSO-d6) δ: 12.84 (s, 1H), 8.04 (d, J = 7.0 Hz, 1H),
7.93 (d, J = 10.0 Hz, 1H), 7.57-7.50 (m, 3H), 7.39-7.35 (m, 1H),
7.28-7.24 (m, 2H), 5.16 (s, 2H), 4.23 (q, J = 5.6 Hz, 2H), 1.25 (t,
J = 7.5 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 172.34,
Ethyl 2-(2-benzamido-1H-benzo[d]imidazol-1-yl)acetate (3a),
78%, White solid, MP: 139-141 oC. 1H NMR (500 MHz, CDCl3),
δ: 12.35 (s, 1H), 8.33-8.31 (m, 2H), 7.51-7.47 (m, 1H), 7.45-7.42
(m, 2H), 7.32 (dd, J = 7.0 Hz, 3.0 Hz, 1H), 7.27-7.23 (m, 2H),
7.16-7.14 (m, 1H), 5.00 (s, 2H), 4.29 (q, J = 7.0 Hz, 2H), 1.29 (t,
J = 8.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 176.65, 167.25,
154.00, 137.65, 131.45, 129.46, 129.32, 128.39, 127.94, 123.43,
123.33, 111.42, 109.02, 62.03, 43.27, 14.17. HRMS (ESI) calcd
for C18H17N3O3 [(M+H)+]: 324.1343; found, 324.1349 .
1
168.40, 163.50 (d, JC,F = 242 Hz, 1C), 152.68, 141.02, 130.50
3
(d, JC,F = 8 Hz, 1C), 129.86, 129.39, 125.17, 123.37, 118.52 (d,
2
2JC,F = 21 Hz, 1C), 115.64 (d, JC,F = 22 Hz, 1C), 112.66, 110.19,
61.68, 43.83, 14.53. HRMS (ESI) calcd for C18H16FN3O3
[(M+H)+]: 342.1248; found, 342.1247.
Ethyl
2-(2-(4-fluorobenzamido)-1H-benzo[d]imidazol-1-
o
1
Ethyl
2-(2-(4-methylbenzamido)-1H-benzo[d]imidazol-1-
yl)acetate (3g), 72%, White solid, MP: 160-161 C, H NMR
(500 MHz, DMSO-d6) δ: 12.79 (s,1H), 8.27 (dd, J = 8.0 Hz, 6
Hz, 2H), 7.55-7.51 (m, 2H), 7.30-7.23 (m, 4H), 5.14 (s, 2H), 4.22
(q, J = 7.0 Hz, 2H), 1.26 (t, J = 7.0 Hz, 3H); 13C NMR (125
MHz, DMSO-d6) δ: 172.75, 168.39, 165.59 (1JC,F = 247 Hz, 1C),
152.74, 134.88, 131.78 (3JC,F = 9 Hz, 1C), 129.86, 129.40, 123.28
(4JC,F = 4 Hz, 1C), 115.36 (2JC,F = 21 Hz, 1C), 112.57, 110.12,
61.68, 43.74, 14.56. HRMS (ESI) calcd for C18H16FN3O3
[(M+H)+]: 342.1248; found, 342.1242.
o
1
yl)acetate (3b), 62%, White solid, MP: 185-187 C. H NMR
(500 MHz, DMSO-d6), δ: 12.75 (s, 1H), 8.10 (d, J = 7.0 Hz, 2H),
7.54-7.49 (m, 2H), 7.27-7.22 (m, 4H), 5.12 (s, 2H), 4.22 (q, J =
7.0 Hz, 2H), 2.37 (s, 3H), 3.14 (t, J = 7.0 Hz, 3H); 13C NMR (125
MHz, DMSO-d6) δ: 173.92, 168.43, 152.83, 141.44, 135.71,
129.90, 129.46, 129.32, 129.00, 128.79, 123.13, 112.45, 110.01,
61.64, 43.71, 21.57, 14.57. HRMS (ESI) calcd for C19H19N3O3
[(M+H)+]: 338.1499; found, 338.1498.
Ethyl
2-(2-(2-methylbenzamido)-1H-benzo[d]imidazol-1-
Ethyl
2-(2-(4-(trifluoromethyl)benzamido)-1H-
o
1
yl)acetate (3c), 73%, White solid, MP: 106-108 C. H NMR
(500 MHz, DMSO-d6), δ: 12.79 (s, 1H), 8.00 (d, J = 7.0 Hz, 1H),
7.57 (dd, J = 29 Hz, 3.6 Hz, 2H), 7.34-7.31 (m, 1H), 7.24 (s, 4H),
5.08 (s, 2H), 4.20 (q, J = 5.6 Hz, 2H), 2.61 (s, 3H), 1.23 (t, J =
benzo[d]imidazol-1-yl)acetate (3h), 75%, White solid, MP:
o
1
227-229 C, H NMR (400 MHz, DMSO-d6) δ: 12.88 (s, 1H),
8.39 (d, J = 8.0 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H), 7.57 (m, 2H),
7.30 (m, 2H), 5.17 (s, 2H), 4.23 (q, J = 7.3 Hz, 2H), 1.24 (s, 3H);

6
Tetrahedron
13C NMR (100 MHz, DMSO-d6) δ: 172.35, 168.28, 152.75,
5.11 (s, 2H), 4.21 (dd, J = 7.0 Hz, 3.0 Hz, 2H), 1.24 (t, J = 7.5
Hz, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 173.04, 168.46,
152.70, 150.28, 147.54, 132.82, 129.89, 129.45, 124.35, 123.15,
123.13, 112.43, 109.97, 109.10, 108.03, 101.96, 61.64, 43.73,
14.56. HRMS (ESI) calcd for C19H17N3O5 [(M+H)+]: 368.1241;
found, 368.1249.
142.10, 131.58 (2JC,F = 31 Hz, 1C), 129.84, 129.36, 126.04 (d,
1JC,F = 271 Hz, 1C), 125.48, 125.45, 123. 48 (d, 3JC,F = 3 Hz, 1C),
112.75, 110.29, 61.72, 43.82, 14.55. HRMS (ESI) calcd for
C19H16F3N3O3 [(M+H)+]: 392.1217; found, 392.1222.
Ethyl
2-(2-(4-chlorobenzamido)-1H-benzo[d]imidazol-1-
o
1
yl)acetate (3i), 77%, White solid, MP: 207-209 C, H NMR
(500 MHz, DMSO-d6) δ: 12.82 (s, 1H), 8.21 (d, J = 7.5 Hz, 2H),
7.54 (d, J = 8.0 Hz, 4H), 7.26 (t, J = 3.0 Hz, 2H), 5.15 (s, 2H),
4.22 (q, J = 6.5 Hz, 2H), 1.24 (t, J = 7.0 Hz, 3H); 13C NMR (125
MHz, DMSO-d6) δ: 172.71, 168.36, 152.72, 137.17, 136.48,
131.03, 129.85, 129.38, 128.52, 123.35, 123.32, 112.62, 110.18,
61.70, 43.75, 14.57. HRMS (ESI) calcd for C18H16ClN3O3
[(M+H)+]: 358.0953; found, 358.0959.
Methyl
2-(2-benzamido-1H-benzo[d]imidazol-1-yl)acetate
o
1
(3o), 68%, White solid, MP: 181-183 C, H NMR (500 MHz,
DMSO-d6) δ: 12.81 (s, 1H), 8.22 (d, J = 7.0 Hz, 2H), 7.56-7.45
(m, 5H), 7.27 (m, 2H), 5.17 (s, 2H), 3.73 (s, 3H); 13C NMR (125
MHz, DMSO-d6) δ: 173.95, 168.91, 152.86, 138.33, 131.62,
129.85, 129.43, 129.24, 128.44, 123.27, 123.23, 112.53, 110.11,
52.85, 43.54. HRMS (ESI) calcd for C17H15N3O3 [(M+H)+]:
310.1186; found, 310.1184.
Ethyl
2-(2-(4-bromobenzamido)-1H-benzo[d]imidazol-1-
Methyl
2-(2-(4-methylbenzamido)-1H-benzo[d]imidazol-1-
o
1
o
1
yl)acetate (3j), 74%, White solid, MP: 237-239 C, H NMR
(500 MHz, DMSO-d6) δ: 12.81 (s, 1H), 8.13 (d, J = 8.0 Hz, 2H),
7.68 (d, J = 8.5 Hz, 2H), 7.56-7.51 (m, 2H), 7.26 (t, J = 3.5 Hz,
2H), 5.14 (s, 2H), 4.22 (q, J = 7.0 Hz, 2H), 1.23 (t, J = 7.0 Hz,
3H); 13C NMR (125 MHz, DMSO-d6) δ: 172.82, 168.35, 152.71,
137.54, 131.74, 131.48, 131.27, 129.85, 129.38, 125.54, 123.33,
112.63, 110.19, 61.70, 40.49, 14.57. HRMS (ESI) calcd for
C18H16BrN3O3 [(M+H)+]: 402.0448; found, 402.0444 .
yl)acetate (3p), 73%, White solid, MP: 179-180 C, H NMR
(500 MHz, DMSO-d6) δ: 12.76 (s, 1H), 8.10 (d, J = 8.0 Hz, 2H),
7.55-7.48 (m, 2H), 7.27-7.23 (m, 4H), 5.15 (s, 2H), 3.73 (s, 3H),
2.37 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 173.94, 168.92,
152.75, 141.47, 135.63, 129.92, 129.31, 129.03, 128.85, 123.19,
123.15, 112.54, 110.06, 52.83, 43.55, 21.57. HRMS (ESI) calcd
for C18H17N3O3 [(M+H)+]: 324.1343; found, 314.1343.
Methyl
2-(2-(4-fluorobenzamido)-1H-benzo[d]imidazol-1-
o
1
Ethyl
2-(2-(4-iodobenzamido)-1H-benzo[d]imidazol-1-
yl)acetate (3q), 76%, White solid, MP: 187-189 C, H NMR
(500 MHz, DMSO-d6) δ: 12.79 (s, 1H), 8.27 (dd, J = 8.5 Hz, 6.0
Hz, 2H), 7.56-7.50 (m, 2H), 7.30-7.23 (m, 4H), 5.17 (s, 2H), 3.73
(s, 3H); 13C NMR (125 MHz, DMSO-d6) δ: 172.82, 168.88,
165.60 (1JC,F = 248 Hz, 1C), 152.76, 134.89, 131.79 (2JC,F = 10
Hz, 1C), 129.83, 129.39, 123.32 (4JC,F = 6 Hz, 1C), 115.38 (2JC,F
= 21 Hz, 1C), 112.57, 110.15, 52.86, 43.55. HRMS (ESI) calcd
for C17H14FN3O3 [(M+H)+]: 328.1092; found, 328.1090.
o
1
yl)acetate (3k), 71%, White solid, MP: 226-228 C, H NMR
(500 MHz, DMSO-d6) δ: 12.81 (s, 1H), 7.97 (d, J = 8.5 Hz, 2H),
7.86 (d, J = 8.0 Hz, 2H), 7.56-7.51 (m, 2H), 7.26 (dd, J = 6.0 Hz,
2.5 Hz, 2H), 5.13 (s, 2H), 4.22 (q, J = 6.0 Hz, 2H), 1.23 (t, J =
7.0 Hz, 2H); 13C NMR (125 MHz, DMSO-d6) δ: 173.12, 168.35,
152.70, 137.89, 137.38, 131.20, 129.86, 129.39, 128.47, 123.32,
112.62, 110.17, 99.52, 61.70, 43.75, 14.58. HRMS (ESI) calcd
for C18H16IN3O3 [(M+H)+]: 450.0309; found, 450.0306.
Methyl 2-(2-(4-methoxybenzamido)-1H-benzo[d]imidazol-1-
o
1
Ethyl
2-(2-(1-naphthamido)-1H-benzo[d]imidazol-1-
yl)acetate (3r), 65%, White solid, MP: 190-192 C, H NMR
(500 MHz, DMSO-d6) δ: 12.70 (s, 1H), 8.16 (d, J = 8.5 Hz, 2H),
7.53-7.47 (m, 2H), 7.25-7.22 (m, 2H), 7.00 (d, J = 9.0 Hz, 2H),
5.14 (s, 2H), 3.82 (s, 3H), 3.73 (s, 3H); 13C NMR (125 MHz,
DMSO-d6) δ: 173.69, 168.94, 162.25, 152.79, 131.13, 130.92,
129.88, 129.48, 123.12, 123.07, 113.67, 112.38, 109.98, 55.75,
52.83, 43.50. HRMS (ESI) calcd for C18H17N3O4 [(M+H)+]:
340.1292; found, 340.1283.
o
1
yl)acetate (3l), 86%, White solid, MP: 128-129 C, H NMR
(500 MHz, DMSO-d6) δ: 12.90 (s, 1H), 9.07-9.05 (m, 1H), 8.24
(d, J = 7.0 Hz, 1H), 8.04-7.97 (m, 2H), 7.60-7.53 (m, 5H), 7.29-
7.26 (m, 2H), 5.12 (s, 2H), 4.22 (q, J = 7.0 Hz, 2H), 1.22 (t, J =
7.0 Hz, 2H); 13C NMR (125 MHz, DMSO-d6) δ: 176.71, 168.40,
152.61, 136.48, 134.01, 131.30, 131.19, 129.87, 129.40, 129.00,
128.77, 126.89, 126.83, 126.12, 125.36, 123.34, 123.30, 112.62,
110.14, 61.74, 40.49, 14.53. HRMS (ESI) calcd for C22H19N3O3
[(M+H)+]: 374.1499; found, 374.1493.
Methyl
2-(2-(4-chlorobenzamido)-1H-benzo[d]imidazol-1-
o
1
yl)acetate (3s), 91%, White solid, MP: 212-214 C, H NMR
(500 MHz, DMSO-d6) δ: 12.81 (s, 1H), 8.21 (d, J = 8.5 Hz, 2H),
7.56-7.50 (m, 4H), 7.27-7.23 (m, 2H), 5.17 (s, 2H), 3.73 (s, 3H);
13C NMR (125 MHz, DMSO-d6) δ: 172.79, 168.84, 152.74,
137.19, 136.49, 131.04, 129.82, 129.39, 128.55, 123.38, 123.33,
112.63, 110.20, 52.87, 43.57. HRMS (ESI) calcd for
C17H14ClN3O3 [(M+H)+]: 344.0796; found, 344.0791.
Ethyl
2-(2-(2-naphthamido)-1H-benzo[d]imidazol-1-
o
1
yl)acetate (3m), 71%, White solid, MP: 154-156 C, H NMR
(500 MHz, DMSO-d6) δ: 12.86 (s, 1H), 8.81 (s, 1H), 8.34 (d, J =
8.0 Hz, 1H), 8.08-7.98 (m, 3H), 7.60-7.54 (m, 4H), 7.28 (t, J =
3.5 Hz, 2H), 5.23 (s, 2H), 4.26 (q, J = 7.0 Hz, 2H), 1.272 (t, J =
6.5 Hz, 2H); 13C NMR (125 MHz, DMSO-d6) δ: 173.83, 168.48,
152.82, 134.90, 132.83, 129.92, 129.59, 129.51, 129.48, 128.07,
127.83, 126.82, 126.25, 123.25, 112.58, 110.11, 61.70, 43.81,
14.62. HRMS (ESI) calcd for C22H19N3O3 [(M+H)+]: 374.1499;
found, 374.1501.
N-(1-(2-oxo-2-phenylethyl)-1H-benzo[d]imidazol-2-
yl)benzamide (3t), 67%, White solid, MP: 177-179 oC, 1H NMR
(500 MHz, DMSO-d6) δ: 12.85 (s, 1H), 8.20 (d, J = 7.5 Hz, 2H),
8.11 (d, J = 7.5 Hz, 2H), 7.79 (t, J = 7.5 Hz, 1H), 7.67 (d, J = 7.5
Hz, 2H), 7.59 (d, J = 7.0 Hz, 1H), 7.49-7.43 (m, 2H), 7.37 (t, J =
7.5 Hz, 2H), 7.26-7.21 (m, 2H), 5.95 (s, 2H); 13C NMR (125
MHz, DMSO-d6) δ: 193.49, 173.88, 153.07, 135.06, 134.61,
131.50, 130.44, 129.49, 129.15, 128.76, 128.32, 123.16, 123.11,
Ethyl
2-(2-(benzo[d][1,3]dioxole-5-carboxamido)-1H-
benzo[d]imidazol-1-yl)acetate (3n), 59%, White solid, MP:
o
1
191-193 C, H NMR (500 MHz, DMSO-d6) δ: 12.70 (s, 1H),
7.82 (dd, J = 10.0 Hz, 5.0 Hz, 1H), 7.66 (s, 1H), 7.52-7.48 (m,
2H), 7.25-7.20 (m, 2H), 6.99 (d, J = 10.0 Hz, 1H), 6.10 (s, 2H),

112.51, 110.23, 48.82. HRMS (ESI) calcd for C22H17N3O2
[(M+H)+]: 356.1394; found, 356.1395.
149.78, 142.78, 131.30, 130.98 (2JC,F = 31 Hz, 1C), 130.36,
129.46, 129.30, 128.81, 126.10 (1JC,F = 271 Hz, 1C), 125.19,
120.69, 61.59, 46.20, 14.47. HRMS (ESI) calcd for
C15H14N3O3F3 [(M+H)+]: 342.1060; found, 342.1067.
N-(1-(2-oxopropyl)-1H-benzo[d]imidazol-2-yl)benzamide
o
1
(3u), 65%, White solid, MP: 202-204 C, H NMR (500 MHz,
DMSO-d6) δ: 12.79 (s, 1H), 8.23 (d, J = 7.5 Hz, 2H), 7.55-7.50
(m, 2H), 7.47-7.44 (m, 2H), 7.41 (dd, J = 6.0 Hz, 3.0 Hz, 1H),
7.23 (dd, J = 5.5 Hz, 3.0 Hz, 2H), 5.25 (s, 2H), 2.33 (s, 2H); 13C
NMR (125 MHz, DMSO-d6) δ: 202.32, 173.93, 152.95, 138.41,
131.54, 130.10, 129.37, 129.28, 128.39, 123.09, 112.54, 110.11,
51.39, 27.73. HRMS (ESI) calcd for C17H15N3O2 [(M+Na)+]:
316.1056; found, 316.1051.
Methyl 2-(2-benzamido-1H-imidazol-1-yl)acetate (5f), 54%,
o
1
White solid, MP: 129-131 C, H NMR (400 MHz, CDCl3) δ:
8.24 (dd, J = 8.0 Hz, 1.4 Hz, 2H), 7.46-7.37 (m, 3H), 6.73 (d, J =
2.4 Hz, 1H), 6.63 (d, J = 2.4 Hz, 1H), 4.82 (s, 2H), 3.79 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 74.43, 168.04, 150.94, 137.90,
130.85, 128.83, 127.85, 114.68, 111.75, 52.75, 45.53. HRMS
(ESI) calcd for C13H13N3O3 [(M+Na)+]: 282.0849; found,
282.0848.
Ethyl 2-(2-acetamido-1H-benzo[d]imidazol-1-yl)acetate (3v),
1
White solid, H NMR (500 MHz, CDCl3) δ: 7.36-7.34 (m, 1H),
Ethyl 2-(2-(1-naphthamido)-1H-imidazol-1-yl)acetate (5g),
64%, White solid, MP: 151-153 oC, 1H NMR (400 MHz, CDCl3)
δ: 8.87 (d, J = 7.6 Hz, 1H), 8.07 (d, J = 2.4 Hz, 1H), 7.88 (m,
2H), 7.49-7.41 (m, 3H), 6.64 (d, J = 2.4 Hz, 8.0 Hz, 1H), 4.76 (s,
2H), 4.27 (q, J = 7.2 Hz, 2H), 1.28 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ: 176.37, 167.59, 149.70, 131.11, 130.53,
128.19, 127.83, 126.72, 126.35, 125.62, 124.79, 115.31, 113.27,
61.99, 45.96, 14.14. HRMS (ESI) calcd for C18H17N3O3
[(M+H)+]: 324.1343; found, 324.1346.
7.27-7.23 (m, 2H), 7.13-7.11 (m, 1H), 4.90 (s, 2H), 4.29 (q, J =
7.5Hz, 2H), 2.26 (s, 3H), 1.31 (t, J = 7.5Hz, 3H); 13C NMR (125
MHz, CDCl3) δ: 182.70, 167.23, 152.94, 129.63, 123.26, 123.17,
111.85, 109.02, 61.96, 43.14, 27.36, 14.13. HRMS (ESI) calcd
for C13H15N3O3 [(M+H)+]: 262.1192; found, 262.1189.
Ethyl 2-(2-benzamido-1H-imidazol-1-yl)acetate (5a), 69%,
White solid, MP: 109-110 oC, 1H NMR (500 MHz, DMSO-d6) δ:
12.23 (s, 1H), 8.10 (d, J = 6.0 Hz, 2H), 7.44-7.41 (m, 3H), 7.04
(s, 1H), 6.84 (d, J = 1.6 Hz, 1H), 4.83 (s, 2H), 4.19 (q, J = 7.0
Hz, 2H), 1.23 (t, J = 7.0 Hz, 3H), 13C NMR (75 MHz, DMSO-d6)
δ: 172.04, 168.45, 150.34, 138.95, 130.97, 128.81, 128.20,
115.99, 111.89, 61.52, 46.24, 14.48; HRMS (ESI) calcd for
C14H15N3O3 [(M+H)+]: 274.1189; found, 274.1184.
Ethyl
2-(2-(benzo[d][1,3]dioxole-5-carboxamido)-1H-
o
imidazol-1-yl)acetate (5h), 51%, White solid, MP: 127-129 C,
1H NMR (400 MHz, CDCl3) δ: 7.86 (d, J = 8.0 Hz, 1H), 7.73 (s,
1H), 6.82 (d, J = 8.0 Hz, 1H), 6.70 (s, 1H), 6.62 (s, 1H), 5.99 (s,
2H), 4.77 (s, 2H), 4.28 (q, J = 6.8 Hz, 2H), 1.32 (t, J = 7.2 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ: 173.64, 167.63, 150.96,
149.85, 147.27, 132.64, 123.84, 114.60, 111.47, 109.20, 107.47,
101.29, 61.98, 45.67, 29.67, 14.14. HRMS (ESI) calcd for
C15H15N3O5 [(M+H)+]: 318.1084; found, 318.1083.
Ethyl
2-(2-(4-methylbenzamido)-1H-imidazol-1-yl)acetate
o
1
(5b), 71%, White solid, MP: 129-131 C, H NMR (300 MHz,
DMSO-d6) δ: 12.12 (s, 1H), 8.00 (d, J = 7.5 Hz, 2H), 7.22 (d, J =
7.8 Hz, 2H), 7.03 (s, 1H), 6.83 (d, J = 2.1 Hz, 1H), 4.81 (s, 2H),
4.19 (q, J = 6.9 Hz, 2H), 2.33 (s, 3H), 1.22 (t, J = 7.8 Hz, 3H);
13C NMR (75 MHz, DMSO-d6) δ: 172.45, 168.48, 150.36,
140.54, 136.27, 128.85, 115.80, 111.90, 61.50, 46.22, 21.46,
14.49. HRMS (ESI) calcd for C15H17N3O3 [(M+Na)+]: 310.1162;
found, 310.1154.
Ethyl 2-bromo-3-oxo-3-phenylpropanoate (M), 1H NMR (500
MHz, CDCl3) δ: 8.00 (d, J = 8.0 Hz, 2H), 7.64 (t, J = 7.5 Hz, 1H),
7.51 (t, J = 7.5 Hz, 1H), 5.68 (s, 1H), 4.30 (q, J = 7.0 Hz, 2H),
1.26 (t, J = 7.5 Hz, 3H).
Acknowledgments
Ethyl 2-(2-(4-methoxybenzamido)-1H-imidazol-1-yl)acetate
o
1
(5c), 59%, White solid, MP: 126-127 C, H NMR (500 MHz,
DMSO-d6) δ: 12.15 (s, 1H), 8.07 (d, J = 8.0 Hz, 2H), 7.04-6.95
(m, 3H), 6.84 (s, 1H), 4.82 (s, 2H), 4.19 (q, J = 7.0 Hz, 2H), 3.80
(s, 3H), 1.22 (t, J = 7.0 Hz, 3H), 13C NMR (75 MHz, DMSO-d6)
δ: 172.19, 168.48, 161.69, 150.38, 131.69, 130.59, 115.60,
113.43, 111.78, 61.48, 55.67, 46.17, 14.49. HRMS (ESI) calcd
for C15H17N3O4 [(M+Na)+]: 326.1111; found, 326.1106.
We are grateful to the National Science Foundation of China
(No. 21572117) and the State Key Laboratory of Natural and
Biomimetic Drugs of Peking University (No. K20140208) for
financial support of this research.
References
1. For selected examples, see: (a) Chandrika, N. T.; Shrestha,
S. K.; Ngo, H. X.; Garneau-Tsodikova, S. Bioorg. Med.
Chem. 2016, 24, 3680-3686; (b) Liang, Y.; Zheng, J.; Li, X.;
Zheng, W.; Chen, T. Eur. J. Med. Chem. 2014, 84, 335-342;
(c) Tantray, M. A.; Khan, I.; Hamid, H.; Alam, M. S.;
Dhulap, A.; Kalam, A. RSC Adv. 2016, 6, 43345-43355; (d)
Romero-Parra, J.; Mella-Raipan, J.; Palmieri, V.; Allara, M.;
Torres, M. J.; Pessoa-Mahana, H.; Iturriaga-Vasquez, P.;
Escobar, R.; Faundez, M.; V. Mzrzo, D.; Pessoa-Mahana,
C. D. Eur. J. Med. Chem. 2016, 124, 17-35. (e) Nanda, K.
K.; Henze, D. A.; Penna, K. D.; Desai, R.; Leitl, M.;
Lemaire, W.; White, R. B.; Yeh, S.; Brouillette, J. N.;
Hartman, G. D.; Bilodeau, M. T.; Trotter, B. W. Bioorg.
Med. Chem. Lett. 2014, 24, 1218-1221.
Ethyl
2-(2-(4-chlorobenzamido)-1H-imidazol-1-yl)acetate
o
1
(5d), 87%, White solid, MP: 143-144 C, H NMR (400 MHz,
CDCl3) δ: 8.19 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 6.74
(d, J = 2.8 Hz, 1H), 6.66 (d, J = 2.4 Hz, 2H), 4.79 (s, 2H), 4.30 (q,
J = 7.2 Hz, 2H), 1.33 (t, J = 7.2 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ: 167.99, 167.58, 143.19, 137.47, 133.66, 130.99,
128.80, 119.40, 115.33, 61.93, 40.50, 14.43. HRMS (ESI) calcd
for C14H14N3O3Cl [(M+H)+]: 308.0796; found, 308.0792.
Ethyl
2-(2-(4-(trifluoromethyl)benzamido)-1H-imidazol-1-
o
1
yl)acetate (5e), 72%, White solid, MP: 143-145 C, H NMR
(400 MHz, DMSO-d6) δ: 12.34 (s, 1H), 8.32 (d, J = 7.6 Hz, 2H),
7.79 (d, J = 7.6 Hz, 2H), 7.10 (d, J = 2.0 Hz, 1H), 6.91 (d, J = 2.4
Hz, 1H), 4.90 (s, 2H), 4.23 (q, J = 7.2 Hz, 2H), 2.53 (t, J = 6.8
Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ: 170.54, 168.40,
2. Mckellar, Q. A.; Scott, E. W. J. vet. Pharmacol. Therp.
1990, 13, 223-225.

8
Tetrahedron
3. Chassaing, C.; Berger, M.; Heckeroth, A.; Ilg, T.; Jaeger,
A. V.; Kucheryavenko, A. F. Pharm. Chem. J. 2006, 40, 261-
M.; Kern, C.; Schmid, K.; Uphoff, M. J. Med. Chem. 2008,
51, 1111-1114.
4. Nofal, Z. M.; Fahmy, H. H.; Mohamed, H. S. Arch. Pharm.
Res. 2002, 23, 28-38.
267.
16. Yang, P.; Xu, H.; Zhou, J. Angew. Chem. Int. Ed. 2014, 53,
12210-12213.
5. Terzioglu, N.; Rijn, R. M. V.; Bakker, R. A.; Esch I. J. P. D.;
Leurs, R. Bioorg. Med. Chem. Lett. 2004, 14, 5251-5256.
6. Kaur, G.; Silakari, O. Bioorganic. Chem. 2008, 80, 24-35.
7. (a) Hasegawa, M.; Nishigaki, N.; Washio, Y.; Kano, K.;
Harris, P. A.; Sato, H.; Mori, I.; West, R.; Shibahara, I. M.;
Toyoda, H.; Wang, L.; Nolte, R. T.; Veal, J. M.; Cheung, M.
J. Med. Chem. 2007, 50, 4453-4470; (b) Martin, M. W.;
Newcomb, J.; Nunes, J. J.; Boucher, C.; Chai, L.; Epstein, L.
F.; Faust, T. T.; Flores, S.; Gallant, P.; Gore, A.; Gu, Y.;
Hsieh, F.; Huang, X.; Kim, J. L.; Middleton, S.;
Morgenstern, K.; Oliveria-dos-Santord, A.; Patel, V. F.;
Pwers, D.; Rose, P.; Tudor, Y. S.; Turci, M.; Welcher, A.
A.; Zack, D.; Zhao, H.; Zhu, L.; Ghiron, C.; Ermann, M.;
Johnston, D.; Saluste, C. P. J. Med. Chem. 2008, 51, 1637-
1648; (c) Powers, J. P.; Li, S.; Jaen, J. C.; Liu, J.; Walker, N.
P. C.; Wang, Z.; Wesche, H. Bioorg. Med. Chem. Lett. 2006,
16, 2842-2845.
Supplementary Material
Supplementary material related to this article can be found at
http://
8. Zhang, S.; Zhan, T.; Cheng, K.; Xia, Y.; Yang, B. Eur. J.
Med. Chem. 2008, 43, 2778-2783.
9. (a) Moriarty, K. J.; Takahashi, H.; Pullen, S. S.; Khine, H.;
Sallati, R. H.; Raymond, E. L.; Woska, J. R.; Jeanfavre, D.;
Roth, G. P.; Winters, M. P.; Qiao, L.; Ryan, D.; Desjarlais,
R. D.; Robinson, M.; Wilson, M.; Bobko, B.; Cook, N.; Lo,
H. Y.; Nemoto, P. A.; Kashem, M. A.; Wolak, J. P.; White,
A.; Magolda, R. L.; Tomczuk, B. Bioorg. Med. Chem. Lett.
2008, 18, 5545-5549. (b) Zhao, G.; Miller, M.; Franzblau,
S.; Wan, B.; Mollmann, U. Bioorg. Med. Chem. Lett. 2006,
16, 5534-5537. (c) Feng, T.; Li, D.; Wang, H.; Zhuang, J.;
Liu, F.; Bao, Q.; Lei, Y.; Chen, W.; Zhang, X.; Xu, X.; Sun,
H.; You, Q.; Guo, X. Eur. J. Med. Chem. 2015, 105, 145-
155.
10. (a) Seth, P. P.; Robinson, D. E.; Jefferson, E. A.; Swayze, E.
E. Tetrahedron Lett. 2002, 43, 7303-7306; (b) Sasmal, P. K.;
Krishna, C. V.; Adabala, S. S.; Roshaiah, M.; Rawoof, K.
A.; Thadi, E.; Sukumar, K. P.; Cheera, S.; Abbineni, C.;
Narasimha, K. V. L.; Prasanthi, A.; Nijhawan, K.; Jaleel,
M.; Iyer, L. R.; Chaitanya, T. K.; Tiwari, N. K.; Krishna, N.
L.; Potluri, V.; Khanna, I.; Frimurer, T. M.; Luckmann, M.;
Rist, O.; Elater, L.; Hogberg, T. Bioorg. Med. Chem. Lett.
2015, 25, 887-892.
11. Beesu, M.; Malladi, S. S.; Fox, L. M.; Jones, C. D.; Dixit, A.;
David, S. J. Med. Chem. 2014, 57, 7325-7341.
12. (a) Wang, Q.; Schereiber, S. Org. Lett. 2009, 11, 5178-5180.
(b) Zhu, Y.; Sergeyev, S.; Franck, P.; Orru, R. V. A.; Maes,
B. U. W. Org. Lett. 2016, 18, 4602-4605.
13. (a) Ma, L. J.; Wang, X. P.; Yu, W.; Han, B. Chem. Commun.
2011, 47, 11333-11335. (b) Monir, K.; Bagdi, A. K.; Mishra,
S.; Majee, A.; Hajra, A. Adv. Synth. Catal. 2014, 356, 1105-
1112; (c) Vinogradova, E. V.; Fors, B. P.; Buchwald, S. L.
J. Am. Chem. Soc. 2012, 134, 11132-11135; (d) Bariwal, J.;
Eycken, E. V. Chem. Soc. Rev. 2013, 42, 9283-9303. (e) Zheng,
Z.; Tao, Q.; Ao, Y.; Xu, M.; Li, Y. Org. Lett. 2018, 20, 3907-
3910.
14. (a) Huo, C.; Tang, J.; Xie, H.; Wang, Y.; Dong, J. Org. Lett.
2016, 18, 1016-1019. (b) Zhang, X.; Wu, P.; Fu, Y.; Zhang,
F.; Chen, B. Tetrahedron Lett. 2017, 58, 870-873.
15. (a) Anisimova, V. A.; Tolpygin, I. E.; Borodkin, G. S. Russ. J.
Org. Chem. 2010, 46, 275-285; (b) Anisimova, V. A.;
Tolpygin, I. E.; Spasov, A. A.; Kosolapov, V. A.; Stepanov,

An efficient route for the synthesis of
N-(1H-benzo[d]imidazol-2-yl)benzamide
derivatives promoted by CBr4 in one pot
Caixia Xie, Songhua Li, Yunyi Li, Chen Ma *

Declaration of interests
The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.