I2-Mediated transition-metal-free aromatic C-H amination for the synthesis of benzimidazol-2-ones and related heterocycles

Article abstract of DOI:10.1039/c8nj03166e

A practical iodine-mediated direct aromatic C-H amination reaction has been established for benzimidazol-2-one synthesis under transition-metal-free conditions. The required 1,3-diarylurea substrates are readily accessible by the addition of N-substituted arylamines to the corresponding isocyanates. This versatile and operationally simple synthetic process is broadly applicable to a wide range of 1,3-diarylureas and provides facile access to benzimidazol-2-ones and related heterocycles. Moreover, the present C-H amination reaction can also be performed directly from disubstituted amines and isocyanates without the purification of the urea intermediates in a scalable fashion.

Full text of DOI:10.1039/c8nj03166e

View Article Online
View Journal
NJC
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Y. Meng, B. Wang,
L. Ren, Q. Zhao, W. Yu and J. Chang, New J. Chem., 2018, DOI: 10.1039/C8NJ03166E.
This is an Accepted Manuscript, which has been through the
Volume 40 Number
1 January 2016 Pages 1–846
Royal Society of Chemistry peer review process and has been
accepted for publication.
NJC
Accepted Manuscripts are published online shortly after
New Journal of Chemistry
www.rsc.org/njc
A journal for new directions in chemistry
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
rsc.li/njc

Please do not adjust margins
New Journal of Chemistry
Page 1 of 8
View Article Online
DOI: 10.1039/C8NJ03166E
Journal Name
ARTICLE
I2-Mediated Transition-Metal-Free Aromatic C−H Aminaꢀon for
the Synthesis of Benzimidazol-2-ones and Related Heterocycles†
Yinggao Meng,a Bingnan Wang,a Linning Ren,a Qiongli Zhao,b Wenquan Yu*a and Junbiao Chang*a,b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
A practical iodine-mediated direct aromatic C−H aminaꢀon reacꢀon has been established for benzimidazol-2-one synthesis
under transition-metal-free conditions. The required 1,3-diarylurea substrates are readily accessible by the addition of N-
substituted arylamines to corresponding isocyanates. This versatile and operationally simple synthetic process is broadly
applicable to a wide range of 1,3-diarylureas and provide a facile access to benzimidazol-2-ones and related heterocycles.
Moreover, the present C−H aminaꢀon reacꢀon can also be performed directly from disubstituted amines and isocyanates
without purification of the urea intermediates in a scalable fashion.
www.rsc.org/
C−H funcꢀonalizaꢀon/C−N bond formaꢀon processes.
Previously, Liang12 and Huang13 described I2-mediated
intermolecular C-2 amination of indoles with morpholine in
Introduction
Benzimidazol-2-one is a privileged structural motif widely
distributed in many biologically active1 and functional
molecules.2 There are two general and classical synthetic
pathways to access benzimidazol-2-one derivatives: (a)
annulations of o-phenylenediamine derivatives with reagents
such as (tri)phosgene,3 carbonyldiimidazole,4 dimethyl
carbonate5 or CO2,6 and (b) transition-metal catalyzed
intramolecular7/intermolecular8 C−N coupling of ortho-
haloanilines (with amines). Yet, limitations associated with
existing methods include the use of toxic reagents, limited
scope and/or availability of substrates. Owing to the readily
accessibility and structural diversity, N,N'-diarylureas are ideal
substrates for benzimidazol-2-one synthesis through direct
aromatic C−H aminaꢀon. However, efficient approaches via
this synthetic strategy are only rarely achieved.9 Thus, it is of
great importance to develop practical and eco-friendly
approaches to access benzimidazol-2-ones and related
heterocycles from 1,3-disubstituted urea precursors.
the presence of base and with azoles in aqueous media. In
2015, Antonchick group14 achieved a regioselective amination
of chromones at C2-position with non-functionalized azoles.
Later, Sekar and coworkers15 developed a such transformation
to prepare indole-fused tetracycles in an intramolecular
manner. In 2012, Batra et al.16 reported an I2-promoted
electrophilic aromatic cyclization of allylamines for quinoline
synthesis. Recently, we accomplished the synthesis of
benzimidazole17 and 1H-indazole18 derivatives employing
molecular iodine under transition-metal free conditions. As a
part of our interest in this research area, herein we disclose an
I2-mediated C−H aminaꢀon reaction of 1,3-diarylureas to
access benzimidazol-2-ones and related heterocycles.
Results and discussion
Initially, we took 1-methyl-1,3-di-p-tolylurea (2b) as the model
substrate to investigate the I2-mediated aromatic C−H
amination for benzimidazol-2-one synthesis. The required
substrate 2b were readily obtained via the addition of N,4-
dimethylaniline and 4-methylphenyl isocyanate in CH2Cl2.19
Initial solvent screening (Table 1, entries 1−6) suggested that
1,2-dichloroethane (DCE) is the ideal medium for this
transformation (entry 6). Complete conversion of substrate 2b
into product 1b required at least 3 equiv of iodine with the
same amount of base (entries 6−7), but extra base resulted in
decreased yields of 1b (entries 8−10). Replacement of Cs2CO3
with other inorganic bases (entries 11−13) or DBU (entry 14)
affected the formation of the expected product.
Direct aromatic C−H aminaꢀon reactions featuring step- and
atom-economy has emerged as a valuable tool for the
construction of nitrogen-containing frameworks from the rich
source of precursors. Such transformations have been
achieved predominantly under transition-metal-catalyzed
conditions10 or in the presence of hypervalent iodine
reagents11 in these years. Moreover, commercially available
and inexpensive molecular iodine was also used in these aryl
a.College of Chemistry and Molecular Engineering, Zhengzhou University,
Zhengzhou, Henan Province 450001, China.
E-mail: wenquan_yu@zzu.edu.cn; changjunbiao@zzu.edu.cn
b.Collaborative Innovation Centre of New Drug Research and Safety Evaluation,
Henan Province, and School of Pharmaceutical Sciences, Zhengzhou University,
Zhengzhou, Henan Province 450001, China.
†Electronic Supplementary Information (ESI) available: 1H and 13C NMR spectra of
products 1. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 2 of 8
View Article Online
DOI: 10.1039/C8NJ03166E
ARTICLE
Journal Name
Table 1. Reaction Conditions Optimization for the Synthesis of Benzimidazol-2-one 1ba
I2
base
(equiv)
Cs2CO3
(3.0)
time
(h)
entry
solvent
DMSO
temp.
100 °C
100 °C
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
yieldb
71%
58%
64%
81%
80%
87%
75%
79%
70%
65%
(equiv)
1
2
3.0
3.0
3.0
3.0
3.0
3.0
2.5
3.0
3.0
3.0
5
5
Cs2CO3
(3.0)
DMF
MeCN
toluene
CH2Cl2
DCE
Cs2CO3
(3.0)
3
4
Cs2CO3
(3.0)
4
8
Cs2CO3
(3.0)
5
24
4
Cs2CO3
(3.0)
6
Cs2CO3
(2.5)
7
DCE
16
8
Cs2CO3
(4.0)
8
DCE
Cs2CO3
(5.0)
9
DCE
12
12
Cs2CO3
(6.0)
10
DCE
Scheme 1. Substrate scope of Ar1 group. Reaction conditions:
(1.5 mmol), Cs2CO3 (1.5 mmol), DCE (5 mL), reflux.
2 (0.5 mmol), I2
11
12
13
14
3.0
3.0
3.0
3.0
K2CO3 (3.0)
K3PO4 (3.0)
KOH (3.0)
DBU (3.0)
DCE
DCE
DCE
DCE
reflux
reflux
reflux
reflux
9
85%
0%
24
24
24
0%
trace
with 24% of a byproduct 1t' formed via sequential benzylic
iodination and amination.20 Moreover, 3,4-dihydroquinoline-
1(2H)-carboxamides were also successfully cyclized into the
aOptimal reaction conditions (entry 6): 2b (0.5 mmol), I2 (1.5 mmol), Cs2CO3 (1.5
mmol), DCE (5 mL), reflux. bIsolated yields.
corresponding products (1u−w), while this reaction failed with
N-isopropyl substrate (1x). Unlike the effect on the Ar1 ring,
incorporation of EWGs to the Ar2 position favored the
Then, various 1,3-diarylurea substrates were subjected to
the optimal reaction conditions (Table 1, entry 6). The Ar1 ring
can tolerate both the electron-donating and electron-
formation of the benzimidazol-2-one products (1y−ad) (cf. 1ac
vs 1d). The structure of 1aa was further confirmed by X-ray
crystallography.21 To verify the practicality of the present
synthetic method, we carried out the reaction directly from
amines and isocyanates without purification of the urea
intermediate. The reaction of N-methylaniline and 4-
chlorophenyl isocyanate at the 5 mmol scale afforded the
desired benzimidazol-2-one (1z) on a gram scale via sequential
addition and I2-mediated oxidative cyclization (Scheme 3). To
avoid the use of highly toxic phenyl isocyanate, the 1,3-
diphenylurea substrate were prepared via PhI(OCOCF3)2-
mediated oxidative cross coupling of N-phenyl formamide with
aniline,22 which was then converted into the expected product
withdrawing groups (EDGs and EWGs) (Scheme 1, 1b
the presence of EWGs decreased the yields of the products
1d ). In the case of meta- (1f and 1f') and 3,4-di-methyl (1g
and 1g' substituted substrates two regioisomeric
−h), while
(
−e
)
benzimidazol-2-ones were formed. Replacement of the phenyl
group at Ar1 position with other aromatic substituents such as
α-naphthyl, β-naphthyl and 3-pyridyl also yielded the
corresponding products (1i−n).
In light of these encouraging results, we further explore the
substrate scope by replacing the N-methyl group at R position
with other aliphatic ones (Scheme 2). All these urea substrates
were smoothly transformed into the desired products under
the above reaction conditions. It is worth to mention that the
present reaction is compatible with functional groups such as
(
1ae) under the standard reaction conditions.
cyano, carboxylic acid ester and azide (1q−s). The N-phenethyl
substrate led to benzimidazol-2-one 1t in a moderate yield
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 3 of 8
View Article Online
DOI: 10.1039/C8NJ03166E
Journal Name
ARTICLE
R
N
R
N
O
I2, Cs2CO3
DCE, reflux
O
N
Ar2
HN
Ar2
2
1
CN
O
CO2Me
O
N
O
N
N
N
N
N
N
O
N
Me
1o, 76%
1p, 74%
1q, 87%
1r, 74%
Me
Scheme 4. Proposed mechanism for the formation of benzimidazol-2-one
I2-mediated aromatic C−H amination.
1 via
Me
Me
N3
Ph
O
Ph
N
N
O
N
+
N
Experimental
N
Me
N
O
General Information. 1H and 13C NMR spectra were recorded
on a 400 MHz (100 MHz for 13C NMR) spectrometer. Chemical
shift values are given in ppm (parts per million) with
tetramethylsilane (TMS) as an internal standard. The peak
patterns are indicated as follows: s, singlet; d, doublet; t,
triplet; q, quartet; quint, quintet; sext, sextet; hept, heptet; m,
multiplet; dd, doublet of doublets; dt, doublet of triplets. The
coupling constants (J) are reported in Hertz (Hz). Melting
points were determined on a micromelting point apparatus
without corrections. High-resolution mass spectra (HRMS)
were obtained on a Q-TOF Mass Spectrometer equipped with
an electrospray ion source (ESI), operated in the positive
1t', 24%
1s, 80%
Me
O
1t, 55%
Me
Me
N
N
N
N
N
O
O
N
1u (X = Me), 54%
1v (X = Cl), 59%
1w (X = OMe), 60%
1x, 0%
Me
1y, 90%
F
X
Me
Me
Me
N
N
O
N
N
O
O
N
N
mode. Most of substrates
2 were obtained by simple addition
of disubstituted amines to corresponding isocyanates in
CH2Cl2.19 Substrate 2ae was prepared via PhI(OCOCF3)2-
mediated oxidative cross coupling of N-phenyl formamide with
aniline22 to avoid the use of highly toxic phenyl isocyanate.
Flash column chromatography was performed over silica gel
200–300 mesh, and the solvents were distilled prior to use.
1,2-Dichloromethane (DCE) was dried over and distilled from
CaH2 under an atmosphere of dry nitrogen.
1z, 94%
1aa, 94%
Br
CF3
Cl
1ab, 92%
Me
N
Me
Me
N
O
N
N
O
N
O
N
Cl
Cl
CF3
1ac, 95%
1ad, 96%
1ae, 79%
Scheme 2. Substrate scope of R and Ar2 groups. Reaction conditions:
mmol), I2 (1.5 mmol), Cs2CO3 (1.5 mmol), DCE (5 mL), reflux.
2 (0.5
General Procedure for the Synthesis of Products 1. A stirred
solution of the N,N'-diarylurea substrate
2 (0.5 mmol) in DCE
(5 mL) was treated with iodine (1.5 mmol) and Cs2CO3 (1.5
mmol) in sequence, and then heated to reflux until TLC
indicated that the conversion was complete. After cooling to
room temperature, the reaction was quenched with 5%
Na2S2O3 (5 mL), diluted with brine (10 mL), and extracted with
EtOAc (3 × 15 mL). The combined organic layer was dried over
anhydrous Na2SO4, concentrated, and then purified through
silica gel column chromatography using a mixture of EtOAc and
Scheme 3. Gram-scale synthesis of benzimidazol-2-one 1z omitting the isolation
of the urea intermediate.
A tentative mechanism is proposed for this I2-mediated
aromatic C−H amination reaction (Scheme 4). The base-
petroleum ether (PE) as the eluent to afford the product 1.
1-Methyl-3-(p-tolyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one
(1a). 6 h; eluent: EtOAc/PE 20:80; yield: 104 mg, 87%; white
solid, mp 106-107 ºC (lit.9b mp 107-108 ºC); 1H NMR (400 MHz,
CDCl3): δ 7.40-7.38 (m, 2H), 7.30 (d, J = 8.0 Hz, 2H), 7.14-7.09
(m, 1H), 7.06-7.00 (m, 3H), 3.46 (s, 3H), 2.40 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 153.7, 137.5, 132.1, 130.1, 129.6, 125.9,
121.8, 121.4, 108.6, 107.6, 27.3, 21.2; HRMS (m/z) [M + Na]+
calcd for C15H14N2NaO 261.0998, found 261.1005.
promoted oxidative iodination of 1,3-diarylurea substrate
generates an N-iodo species . Then the cleavage of the N−I
bond and consequent cyclization of iodide form intermediate
. Finally, the subsequent deprotonation by base affords the
benzimidazol-2-one framework
2
B
B
C
1.
1,5-Dimethyl-3-(p-tolyl)-1,3-dihydro-2H-benzo[d]imidazol-2-
one (1b). 4 h; eluent: EtOAc/petroleum ether(PE) 20:80; yield:
1
110 mg, 87%; white solid, mp 84-85 ºC; H NMR (400 MHz,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 4 of 8
View Article Online
DOI: 10.1039/C8NJ03166E
ARTICLE
Journal Name
CDCl3): δ 7.38 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 6.95- 128.3, 127.7, 125.8, 109.7, 108.8, 27.2, 21.2, 19.94, 19.88;
6.89 (m, 2H), 6.84 (s, 1H), 3.45 (s, 3H), 2.41 (s, 3H), 2.34 (s, 3H); HRMS (m/z) [M + Na]+ calcd for C17H18N2NaO 289.1311, found
13C NMR (100 MHz, CDCl3): δ 153.9, 137.6, 132.3, 131.3, 130.2, 289.1318.
129.9, 128.1, 126.1, 122.4, 109.3, 107.3, 27.4, 21.6, 21.3; 1,4,5-Trimethyl-3-(p-tolyl)-1,3-dihydro-2H-benzo[d]imidazol-
HRMS (m/z) [M + Na]+ calcd for C16H16N2NaO 275.1155, found 2-one (1g'). 4 h; eluent: EtOAc/PE 17:83; yield: 51 mg, 38%;
1
white solid, mp 104-105 ºC; H NMR (400 MHz, CDCl3): δ 7.29-
275.1163.
5-Methoxy-1-methyl-3-(p-tolyl)-1,3-dihydro-2H-
7.22 (m, 4H, overlapped with the peak of chloroform), 6.95 (d,
benzo[d]imidazol-2-one (1c). 5 h; eluent: EtOAc/PE 17:83; J = 8.0 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 3.43 (s, 3H), 2.42 (s, 3H),
1
yield: 101 mg, 75%; light yellow solid, mp 150-151 ºC; H NMR 2.25 (s, 3H), 1.76 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.9,
(400 MHz, CDCl3): δ 7.38 (m, 2H), 7.31 (d, J = 8.4 Hz, 2H), 6.90 138.4, 134.1, 130.8, 129.8, 129.0, 128.7, 128.2, 122.9, 119.0,
(d, J = 8.4 Hz, 1H), 6.69 (dd, J = 8.4, 2.4 Hz, 1H), 6.64 (d, J = 2.4 104.7, 27.2, 21.3, 20.0, 14.0; HRMS (m/z) [M + Na]+ calcd for
Hz, 1H), 3.75 (s, 3H), 3.44 (s, 3H), 2.41 (s, 3H); 13C NMR (100 C17H18N2NaO 289.1311, found 289.1319.
MHz, CDCl3): δ 155.6, 154.0, 137.6, 132.1, 130.4, 130.2, 125.9, 1,4,6-Trimethyl-3-(p-tolyl)-1,3-dihydro-2H-benzo[d]imidazol-
124.3, 107.8, 107.2, 95.9, 56.0, 27.3, 21.2; HRMS (m/z) [M + 2-one (1h). 4 h; eluent: EtOAc/PE 25:75; yield: 120 mg, 90%;
Na]+ calcd for C16H16N2NaO2 291.1104, found 291.1105.
1
white solid, mp 158-160 ºC; H NMR (400 MHz, CDCl3): δ 7.27-
5-Chloro-1-methyl-3-(p-tolyl)-1,3-dihydro-2H-
7.22 (m, 4H), 6.70 (s, 1H), 6.62 (s, 1H), 3.42 (s, 3H), 2.41 (s, 3H),
benzo[d]imidazol-2-one (1d). 7 h; eluent: EtOAc/PE 17:83; 2.37 (s, 3H), 1.82 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.8,
1
yield: 80 mg, 59%; white solid, mp 152-153 ºC; H NMR (400 138.5, 133.7, 131.2, 130.7, 129.7, 128.9, 125.7, 125.2, 119.8,
MHz, CDCl3): δ 7.37-7.31 (m, 4H), 7.10 (dd, J = 8.4, 2.0 Hz, 1H), 106.1, 27.3, 21.3, 18.0; HRMS (m/z) [M + Na]+ calcd for
7.01 (d, J = 2.0 Hz, 1H), 6.92 (d, J = 8.4 Hz, 1H), 3.46 (s, 3H), C17H18N2NaO 289.1311, found 289.1310.
2.42 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.6, 138.1, 131.5, 1-Methyl-3-(p-tolyl)-1,3-dihydro-2H-naphtho[1,2-d]imidazol-
130.5, 130.3, 128.7, 127.0, 125.9, 121.7, 109.0, 108.2, 27.4, 2-one (1i). 6 h; eluent: EtOAc/PE 17:83; yield: 117 mg, 81%;
21.2; HRMS (m/z) [M + Na]+ calcd for C15H13ClN2NaO 295.0609, white solid, mp 178-181 ºC; H NMR (400 MHz, CDCl3): δ 8.38
1
found 295.0602.
(d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.57-7.52 (m, 2H),
7.45-7.39 (m , 3H), 7.36 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.8 Hz,
1-Methyl-3-(p-tolyl)-5-(trifluoromethyl)-1,3-dihydro-2H-
benzo[d]imidazol-2-one (1e). 7 h; eluent: EtOAc/PE 17:83; 1H), 4.02 (s, 3H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
1
yield: 95 mg, 62%; white solid, mp 107-108 ºC; H NMR (400 153.9, 137.9, 132.0, 130.4, 130.2, 129.5, 126.34, 126.27, 125.5,
MHz, CDCl3): δ 7.42 (d, J = 8.4 Hz, 1H), 7.39-7.34 (m, 4H), 7.24 123.6, 122.8, 122.1, 120.8, 120.1, 109.9, 31.1, 21.2; HRMS
(s, 1H), 7.09 (d, J = 8.0 Hz, 1H), 3.52 (s, 3H), 2.43 (s, 3H); 13C (m/z) [M + Na]+ calcd for C19H16N2NaO 311.1155, found
NMR (100 MHz, CDCl3): δ 153.8, 138.3, 132.6, 131.3, 130.4, 311.1154.
129.7, 125.9, 124.4 (q, JC–F = 270.0 Hz), 123.8 (q, JC–F = 32.5 Hz), 3-Methyl-1-(p-tolyl)-1,3-dihydro-2H-naphtho[1,2-d]imidazol-
119.3 (q, JC–F = 4.0 Hz), 107.3, 105.6 (q, JC–F = 4.0 Hz), 27.5, 2-one (1j). 5 h; eluent: EtOAc/PE 25:75; yield: 138 mg, 96%;
1
21.2; HRMS (m/z) [M + Na]+ calcd for C16H13F3NaN2O 329.0872, white solid, mp 165-166 ºC; H NMR (400 MHz, CDCl3): δ 7.86
found 329.0876.
(d, J = 8.4 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.39 (s, 4H), 7.34 (d, J
3,5-Dimethyl-1-(p-tolyl)-1,3-dihydro-2H-benzo[d]imidazol-2-
= 8.4 Hz, 1H), 7.31-7.27 (m, 1H), 7.20-7.19 (m, 2H), 3.59 (s, 3H),
one (1f). 6 h; eluent: EtOAc/PE 13:87; yield: 55 mg, 44%; white 2.50 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.6, 139.0, 133.9,
1
solid, mp 124-125 ºC; H NMR (400 MHz, CDCl3): δ 7.38 (d, J = 130.4, 130.1, 129.2, 128.5, 126.2, 125.8, 123.3, 122.7, 122.3,
8.0 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.8 Hz, 1H), 6.85 120.4, 120.1, 108.8, 27.5, 21.4; HRMS (m/z) [M + Na]+ calcd for
(d, J = 7.6 Hz, 2H), 3.45 (s, 3H), 2.41 (d, J = 5.6 Hz, 6H); 13C NMR C19H16N2NaO 311.1155, found 311.1160.
(100 MHz, CDCl3): δ 153.8, 137.3, 132.3, 131.7, 130.3, 130.1, 1-(4-Bromophenyl)-3-methyl-1,3-dihydro-2H-naphtho[1,2-
127.5, 125.8, 121.9, 108.3, 108.2, 27.2, 21.5, 21.2; HRMS (m/z) d]imidazol-2-one (1k). 5 h; eluent: EtOAc/PE 20:80; yield: 167
[M + Na]+ calcd for C16H16N2NaO 275.1155, found 275.1151.
1
mg, 95%; brown solid, mp 182-183 ºC; H NMR (400 MHz,
1,4-Dimethyl-3-(p-tolyl)-1,3-dihydro-2H-benzo[d]imidazol-2-
CDCl3): δ 7.86 (d, J = 8.4 Hz, 1H), 7.70 (dd, J = 8.8, 2.4 Hz, 3H),
one (1f'). 6 h; eluent: EtOAc/PE 13:87; yield: 63 mg, 50%; white 7.40-7.36 (m, 2H), 7.35-7.29 (m, 2H), 7.23-7.17 (m, 2H), 3.58 (s,
1
solid, mp 148-150 ºC; H NMR (400 MHz, CDCl3): δ 7.29-7.24 3H); 13C NMR (100 MHz, CDCl3): δ 154.2, 135.6, 132.9, 130.25,
(m, 4H, overlapped with the peak of chloroform), 7.02 (t, J = 130.19, 129.4, 126.5, 126.1, 123.5, 123.2, 122.8, 121.6, 120.2,
8.0 Hz, 1H), 6.88 (d, J = 7.6 Hz, 1H), 6.80 (d, J = 8.0 Hz, 1H), 3.45 119.9, 108.8, 27.6; HRMS (m/z) [M + Na]+ calcd for
(s, 3H), 2.42 (s, 3H), 1.86 (s, 3H); 13C NMR (100 MHz, CDCl3): δ C18H13BrN2NaO 375.0103, found 375.0107.
154.7, 138.6, 133.5, 130.5, 129.7, 128.9, 127.8, 124.6, 121.4, 1-Methyl-3-(p-tolyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-
120.1, 105.4, 27.3, 21.3, 18.1; HRMS (m/z) [M + Na]+ calcd for one (1l). 9 h; eluent: EtOAc/PE 33:67; yield: 100 mg, 83%;
1
C16H16N2NaO 275.1155, found 275.1155.
white solid, mp 126-127 ºC; H NMR (400 MHz, CDCl3): δ 8.05
(dd, J = 5.2, 1.2 Hz, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.0
1,5,6-Trimethyl-3-(p-tolyl)-1,3-dihydro-2H-benzo[d]imidazol-
2-one (1g). 4 h; eluent: EtOAc/PE 17:83; yield: 75 mg, 56%; Hz, 2H), 7.22 (dd, J = 7.6, 1.6 Hz, 1H), 7.07-7.04 (m, 1H), 3.49 (s,
white solid, mp 164-165 ºC; 1H NMR (400 MHz, CDCl3): δ 7.40- 3H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.1, 143.5,
7.37 (m, 2H), 7.31 (d, J = 8.4 Hz, 2H), 6.81 (d, J = 4.8 Hz, 2H), 140.9, 137.7, 130.6, 129.9, 125.9, 124.4, 117.5, 113.5, 27.0,
3.44 (s, 3H), 2.41 (s, 3H), 2.32 (s, 3H), 2.24 (s, 3H); 13C NMR 21.2; HRMS (m/z) [M + Na]+ calcd for C14H13N3NaO 262.0951,
(100 MHz, CDCl3): δ 153.7, 137.3, 132.4, 130.03, 129.97, 129.5, found 262.0948.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 5 of 8
View Article Online
DOI: 10.1039/C8NJ03166E
Journal Name
ARTICLE
3-(4-Chlorophenyl)-1-methyl-1,3-dihydro-2H-imidazo[4,5-
δ 7.41-7.39 (m, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.17-7.11 (m, 1H),
b]pyridin-2-one (1m). 9 h; eluent: EtOAc/PE 33:67; yield: 109 7.09-7.05 (m, 3H), 4.03 (t, J = 6.8 Hz, 2H), 3.43 (t, J = 6.4 Hz,
1
mg, 84%; white solid, mp 160-161 ºC; H NMR (400 MHz, 2H), 2.41 (s, 3H), 2.08 (m, 2H); 13C NMR (100 MHz, CDCl3): δ
CDCl3): δ 8.05 (dd, J = 5.2, 1.2 Hz, 1H), 7.72-7.70 (m, 2H), 7.48- 153.4, 137.6, 131.9, 130.1, 129.6, 129.4, 125.8, 121.9, 121.5,
7.46 (m, 2H), 7.27-7.23 (m, 1H), 7.10-7.06 (m, 1H), 3.48 (s, 3H); 108.8, 107.6, 48.8, 38.4, 27.8, 21.2; HRMS (m/z) [M + Na]+
13C NMR (100 MHz, CDCl3): δ 152.6, 142.9, 140.8, 133.0, 132.0, calcd for C17H17N5NaO 330.1325, found 330.1326.
129.3, 126.9, 124.4, 118.0, 113.8, 27.1; HRMS (m/z) [M + Na]+ 1-Phenethyl-3-(p-tolyl)-1,3-dihydro-2H-benzo[d]imidazol-2-
calcd for C13H10ClN3NaO 282.0405, found 282.0405.
one (1t). 6 h; eluent: EtOAc/PE 10:90; yield: 90 mg, 55%; light
yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.38 (d, J = 8.4 Hz, 2H),
imidazo[4,5-b]pyridin-2-one (1n). 9 h; eluent: EtOAc/PE 33:67; 7.32-7.20 (m, 7H, overlapped with the peak of chloroform),
1-Methyl-3-(4-(trifluoromethyl)phenyl)-1,3-dihydro-2H-
1
yield: 116 mg, 79%; white solid, mp 98-99 ºC; H NMR (400 7.10-7.00 (m, 3H), 6.93 (d, J = 7.6 Hz, 2H), 4.15 (t, J = 8.0 Hz,
MHz, CDCl3): δ 8.08 (dd, J = 5.2, 1.2 Hz, 1H), 7.98 (d, J = 8.4 Hz, 2H), 3.09 (t, J = 8.0 Hz, 2H), 2.41 (s, 3H); 13C NMR (100 MHz,
2H), 7.78 (d, J = 8.4 Hz, 2H), 7.28-7.26 (m, 1H), 7.14-7.10 (m, CDCl3): δ 153.3, 138.3, 137.5, 132.1, 130.1, 129.7, 129.4, 128.9,
1H), 3.50 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 152.4, 142.6, 128.7, 126.7, 125.9, 121.7, 121.2, 108.7, 107.7, 42.8, 34.7,
140.9, 136.8, 129.0 (q, JC–F = 32.6 Hz), 126.2 (q, JC–F = 3.8 Hz), 21.2; HRMS (m/z) [M + Na]+ calcd for C22H20N2NaO 351.1468,
125.4, 124.5, 123.9 (q, JC–F = 270.5 Hz), 118.3, 114.0, 27.1; found 351.1467.
HRMS (m/z) [M + Na]+ calcd for C14H10F3N3NaO 316.0668, 1,4-Diphenyl-3-(p-tolyl)imidazolidin-2-one (1t'). 6 h; eluent:
1
found 316.0664.
EtOAc/PE 10:90; yield: 40 mg, 24%; light yellow oli; H NMR
(400 MHz, CDCl3): δ 7.77 (d, J = 7.6 Hz, 2H), 7.39-7.34 (m, 8H),
1-Ethyl-3-(p-tolyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one
(1o). 7 h; eluent: EtOAc/PE 13:87; yield: 96 mg, 76%; white 7.06 (m, 5H), 5.55 (t, J = 7.6 Hz, 1H), 4.33 (t, J = 8.4 Hz, 1H),
1
solid, mp 87-88 ºC; H NMR (400 MHz, CDCl3): δ 7.41-7.39 3.94-3.90 (m, 1H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
(m, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.15-7.11 (m, 1H), 7.06-7.03 148.5, 144.4, 139.7, 138.5, 131.7, 129.2, 128.94, 128.88, 128.8,
(m, 3H), 4.01 (q, J = 7.2 Hz, 2H), 2.41 (s, 3H), 1.39 (t, J = 7.2 Hz, 125.9, 123.2, 122.9, 118.8, 76.4, 53.8, 20.9; HRMS (m/z) [M +
3H); 13C NMR (100 MHz, CDCl3): δ 153.1, 137.5, 132.1, 130.1, H]+ calcd for C22H21N2O 329.1648, found 329.1656.
129.7, 129.2, 125.9, 121.7, 121.2, 108.7, 107.6, 36.0, 21.2, 1-(p-Tolyl)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2(1H)-
13.6; HRMS (m/z) [M + Na]+ calcd for C16H16N2NaO 275.1155, one (1u). 8 h; eluent: EtOAc/PE 17:83; yield: 71 mg, 54%; light
found 275.1159.
yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.44-7.42 (m, 2H), 7.30
(d, J = 8.0 Hz, 2H), 6.97-6.88 (m, 3H), 3.92 (t, J = 6.0 Hz, 2H),
1-Butyl-3-(p-tolyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one
(1p). 8 h; eluent: EtOAc/PE 13:87; yield: 104 mg, 74%; white 2.88 (t, J = 6.0 Hz, 2H), 2.40 (s, 3H), 2.18-2.12 (m, 2H); 13C NMR
1
solid, mp 67-68 ºC; H NMR
(
400 MHz, CDCl3): δ 7.41-7.39 (100 MHz, CDCl3): δ 152.6, 137.1, 132.6, 130.0, 128.0, 126.6,
(m, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.13-7.09 (m, 1H), 7.06-7.03 125.3, 120.9, 119.9, 119.7, 106.5, 39.2, 24.0, 21.9, 21.2; HRMS
(m, 3H), 3.94 (t, J = 7.2 Hz, 2H), 2.41 (s, 3H), 1.82-1.75 (m, 2H), (m/z) [M + Na]+ calcd for C17H16N2NaO 287.1155, found
1.49-1.39 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, 287.1149.
CDCl3): δ 153.4, 137.4, 132.1, 130.0, 129.7, 129.6, 125.9, 121.7, 1-(4-Chlorophenyl)-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-
121.1, 108.7, 107.8, 41.0, 30.5, 21.2, 20.2, 13.8; HRMS (m/z) 2(1H)-one (1v). 6 h; eluent: EtOAc/PE 17:83; yield: 84 mg, 59%;
[M + Na]+ calcd for C18H20N2NaO 303.1468, found 303.1470.
1
pink solid, mp 99-101 ºC; H NMR (400 MHz, CDCl3): δ 7.54-
3-(2-Oxo-3-(p-tolyl)-2,3-dihydro-1H-benzo[d]imidazol-1-
7.51 (m, 2H), 7.48-7.46 (m, 2H), 7.00-6.96 (m, 1H), 6.93-6.90
yl)propanenitrile (1q). 7 h; eluent: EtOAc/PE 33:67; yield: 120 (m, 2H), 3.92 (t, J = 6.0 Hz, 2H), 2.89 (t, J = 6.0 Hz, 2H), 2.16 (dt,
1
mg, 87%; light yellow oil; H NMR (400 MHz, CDCl3): δ 7.40- J = 12.0, 6.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 152.3, 133.9,
7.37 (m, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.17-7.13 (m, 2H), 7.11- 132.5, 129.6, 127.3, 126.6, 126.4, 121.1, 120.4, 119.9, 106.4,
7.04 (m, 2H), 4.24 (t, J = 6.8 Hz, 2H), 2.88 (t, J = 6.8 Hz, 2H), 39.2, 24.0, 21.8; HRMS (m/z) [M
2.42 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.0, 137.9, 131.5, C16H13ClN2NaO 307.0609, found 307.0602.
+
Na]+ calcd for
130.2, 129.7, 128.5, 125.9, 122.2, 122.1, 117.4, 109.2, 107.6, 1-(4-Methoxyphenyl)-5,6-dihydro-4H-imidazo[4,5,1-
37.4, 21.2, 17.2; HRMS (m/z) [M + Na]+ calcd for C17H15N3NaO ij]quinolin-2(1H)-one (1w). 8 h; eluent: EtOAc/PE 17:83; yield:
1
84 mg, 60%; pink oil; H NMR (400 MHz, CDCl3): δ 7.46-7.42
300.1107, found 300.1114.
Methyl-3-(2-oxo-3-(p-tolyl)-2,3-dihydro-1H-benzo[d]imidazol- (m, 2H), 7.04-7.00 (m, 2H), 6.95 (t, J = 8.0 Hz, 1H), 6.90-6.88
1-yl)propanoate (1r). 6 h; eluent: EtOAc/PE 33:67; yield: 115 (m, 1H), 6.85 (d, J = 7.6 Hz, 1H), 3.92 (t, J = 6.0 Hz, 2H), 3.85 (s,
mg, 74%; light yellow oil; 1H NMR (400 MHz, CDCl3): δ 7.39 (d, 3H), 2.89 (t, J = 6.0 Hz, 2H), 2.16 (dt, J = 12.0, 6.0 Hz, 2H); 13C
J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.15-7.12 (m, 2H), 7.04- NMR (100 MHz, CDCl3): δ 158.6, 152.7, 128.2, 127.9, 126.9,
7.03 (m, 2H), 4.24 (t, J = 7.2 Hz, 2H), 3.67 (s, 3H), 2.85 (t, J = 7.2 126.5, 120.9, 119.9, 119.6, 114.7, 106.3, 55.5, 39.2, 24.0, 21.9;
Hz, 2H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 171.7, HRMS (m/z) [M + Na]+ calcd for C17H16N2NaO2 303.1104, found
153.2, 137.6, 131.9, 130.1, 129.7, 129.1, 125.9, 121.9, 121.5, 303.1111.
108.8, 108.0, 51.9, 37.2, 32.9, 21.2; HRMS (m/z) [M + Na]+ 1-(4-Fluorophenyl)-3-methyl-1,3-dihydro-2H-
calcd for C18H18N2NaO3 333.1210, found 333.1214..
benzo[d]imidazol-2-one (1y). 5 h; eluent: EtOAc/PE 17:83;
yield: 109 mg, 90%; white solid, mp 129-131 ºC (lit.9a mp 127-
1-(3-Azidopropyl)-3-(p-tolyl)-1,3-dihydro-2H-
1
benzo[d]imidazol-2-one (1s). 6 h; eluent: EtOAc/PE 17:83; 129 ºC); H NMR (400 MHz, CDCl3): δ 7.51-7.48 (m, 2H), 7.24-
yield: 123 mg, 80%; light yellow oil; 1H NMR (400 MHz, CDCl3): 7.14 (m, 3H), 7.09-7.00 (m, 3H), 3.48 (s, 3H); 13C NMR (100
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 6 of 8
View Article Online
DOI: 10.1039/C8NJ03166E
ARTICLE
Journal Name
MHz, CDCl3): δ 161.6 (d, JC–F = 245.8 Hz), 153.5, 130.7, 130.1, 126.1, 124.0, 122.4, 121.6, 108.6, 107.8, 27.3; HRMS (m/z) [M
129.4, 127.8 (d, JC–F = 8.6 Hz), 122.1, 121.5, 116.4 (d, JC–F = 22.5 + Na]+ calcd for C14H11ClNaN2O 281.0452, found 281.0456.
Hz), 108.4, 107.7, 27.3; HRMS (m/z) [M + Na]+ calcd for 1-Methyl-3-phenyl-1,3-dihydro-2H-benzo[d]imidazol-2-one
C14H11FNaN2O 265.0748, found 265.0759.
(1ae). 4 h; eluent: EtOAc/PE 25:75; yield: 89 mg, 79%; white
solid, mp 123-125 ºC (lit.9a mp 121-123ºC); 1H NMR (400 MHz,
1-(4-Chlorophenyl)-3-methyl-1,3-dihydro-2H-
benzo[d]imidazol-2-one (1z). The 0.5 mmol scale reaction was CDCl3): δ 7.54-7.49 (m, 4H), 7.42-7.36 (m, 1H), 7.17-7.13 (m,
carried out according to the General Procedure using purified 1H), 7.09-7.03 (m, 3H), 3.49 (s, 3H); 13C NMR (100 MHz, CDCl3):
substrate 2z. 5 h; yield: 122 mg, 94%. For the 5 mmol scale δ 153.5, 134.7, 130.1, 129.4, 129.3, 127.5, 125.9, 121.9, 121.4,
sequential synthesis, a reaction mixture of N-methylaniline 108.6, 107.6, 27.2; HRMS (m/z) [M + H]+ calcd for C14H13N2O
(536 mg, 5 mmol) and 1-chloro-4-isocyanatobenzene (768 mg, C14H13N2O 225.1022, found 225.1027.
5 mmol) in DCE (15 mL) was stirred at room temperature for
2.5 h. Upon the disappearance of N-methylaniline, it was
Conclusions
directly treated with iodine (3.81 g, 15 mmol) and Cs2CO3 (4.89
g, 15 mmol), and then heated to reflux for 9 h (TLC indicated
that the addition was complete). The pure product 1z was
obtained according to the General Procedure. Overall yield:
1.13 g, 88% (from N-methylaniline). Eluent: EtOAc/PE 17:83;
white solid, mp 156-157 ºC (lit.9a mp 153-155 ºC); 1H NMR (400
MHz, CDCl3): δ 7.49 (s, 4H), 7.19-7.15 (m, 1H), 7.10-7.03 (m,
3H), 3.48 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.3, 133.3,
133.1, 130.2, 129.7, 129.0, 127.1, 122.3, 121.6, 108.5, 107.8,
27.3; HRMS (m/z) [M + Na]+ calcd for C14H11ClNaN2O 281.0452,
found 281.0455.
In summary, we have developed an I2-mediated oxidative
cyclization reaction of 1,3-diarylureas into benzimidazol-2-one
derivatives via intramolecular aryl C−H aminaꢀon. This
transition-metal-free and operationally simple method is
compatible with various 1,3-diarylurea substrates to produce
benzimidazol-2-one and related heterocyclic products. The
reaction can be conveniently carried out from simple amines
and isocyanates on a gram scale omitting the isolation of the
urea intermediates.
1-(4-Bromophenyl)-3-methyl-1,3-dihydro-2H-
benzo[d]imidazol-2-one (1aa). 6 h; eluent: EtOAc/PE 17:83;
yield: 142 mg, 94%; white solid, mp 160-161 ºC (lit.9b mp 160-
1
162ºC); H NMR (400 MHz, CDCl3): δ 7.66-7.62 (m, 2H), 7.45-
Conflicts of interest
There are no conflicts to declare.
7.41 (m, 2H), 7.19-7.13 (m, 1H), 7.10-7.03 (m, 3H), 3.48 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 153.2, 133.9, 132.6, 130.2, 128.8,
127.4, 122.3, 121.6, 121.0, 108.5, 107.8, 27.3; HRMS (m/z) [M
+ Na]+ calcd for C14H11BrNaN2O 324.9947, found 324.9952.
1-Methyl-3-(4-(trifluoromethyl)phenyl)-1,3-dihydro-2H-
benzo[d]imidazol-2-one (1ab). 5 h; eluent: EtOAc/PE 17:83;
Acknowledgements
We thank the National Natural Science Foundation of China
(No. 81773570 and 81330075), the Outstanding Young Talent
Research Fund of Zhengzhou University (No. 1521316004) for
financial support.
1
yield: 135 mg, 92%; white solid, mp 147-149 ºC; H NMR (400
MHz, CDCl3): δ 7.79 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 8.4 Hz, 2H),
7.22-7.06 (m, 4H), 3.50 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
153.2, 138.1, 130.3, 129.2 (q, JC–F = 32.7 Hz), 128.5, 126.7 (q,
JC–F = 3.7 Hz), 125.7, 123.9 (q, JC–F = 270.4 Hz), 122.6, 121.7,
108.7, 108.0, 27.3; HRMS (m/z) [M + H]+ calcd for C15H12F3N2O
293.0896, found 293.0901.
Notes and references
1
(a) S. Ferro; M. R. Buemi; L. D. Luca; F. E. Agharbaoui; C.
Pannecouque and A.-M. Monforte, Bioorg. Med. Chem.
2017, 25, 3861-3870; (b) A. H. Miah; H. Abas; M. Begg; B. J.
Marsh; D. E. O'Flynn; A. J. Ford; J. M. Percy; P. A. Procopiou;
5-Chloro-1-methyl-3-(4-(trifluoromethyl)phenyl)-1,3-dihydro-
2H-benzo[d]imidazol-2-one (1ac). 8 h; eluent: EtOAc/PE 17:83;
S. A. Richards and S.-A. Rumley, Bioorg. Med. Chem. 2014
,
22, 4298-4311; (c) C. Mattsson; T. Andreasson; N. Waters
and C. Sonesson, J. Med. Chem. 2012, 55, 9735-9750; (d) M.
Bruncko; S. K. Tahir; X. Song; J. Chen; H. Ding; J. R. Huth; S.
Jin; R. A. Judge; D. J. Madar; C. H. Park; C.-M. Park; A. M.
Petros; C. Tse; S. H. Rosenberg and S. W. Elmore, Bioorg.
Med. Chem. Lett. 2010, 20, 7503-7506; (e) A.-M. Monforte;
P. Logoteta; L. D. Luca; N. Iraci; S. Ferro; G. Maga; E. D.
Clercq; C. Pannecouque and A. Chimirri, Bioorg. Med. Chem.
2010, 18, 1702-1710; (f) A. Samuele; E. Crespan; S. Vitellaro;
A.-M. Monforte; P. Logoteta; A. Chimirri and G. Maga,
Antiviral Res. 2010, 86, 268-275; (g) P. Zhang; E. A.
Terefenko; J. Bray; D. Deecher; A. Fensome; J. Harrison; C.
Kim; E. Koury; L. Mark; C. C. McComas; C. A. Mugford; E. J.
Trybulski; A. T. Vu; G. T. Whiteside and P. E. Mahaney, J.
Med. Chem. 2009, 52, 5703-5711.
1
yield: 155 mg, 95%; white solid, mp 134-135 ºC; H NMR (400
MHz, CDCl3): δ 7.81 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H),
7.17 (dd, J = 8.4, 2.0 Hz, 1H), 7.12 (d, J = 1.6 Hz, 1H), 6.97 (d, J =
8.4 Hz, 1H), 3.48 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.1,
137.5, 129.7 (q, JC–F = 32.8 Hz), 129.3, 128.9, 127.4, 126.8 (q,
JC–F = 3.8 Hz), 125.7, 123.8 (q, JC–F = 270.5 Hz), 122.5, 109.1,
108.7, 27.5; HRMS (m/z) [M + Na]+ calcd for C15H10ClF3N2NaO
349.0326, found 349.0329.
1-(3-Chlorophenyl)-3-methyl-1,3-dihydro-2H-
benzo[d]imidazol-2-one (1ad). 10 h; eluent: EtOAc/PE 10:90;
yield: 124 mg, 96%; white solid, mp 138-140 ºC (lit.9a mp 139-
1
141ºC); H NMR (400 MHz, CDCl3): δ 7.58-7.57 (m, 1H), 7.46-
2
(a) M. Mastalerz and I. Oppel, Angew. Chem. Int. Ed. 2012,
7.45 (m, 2H), 7.38-7.35 (m, 1H), 7.19-7.15 (m, 1H), 7.11-7.08
(m, 2H), 7.05 (d, J = 7.6 Hz, 1H), 3.49 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 153.2, 136.0, 135.0, 130.5, 130.2, 128.8, 127.7,
51, 5252-5255; (b) A. A. Mir; S. Matsumura; A. R. Hlil and A.
S. Hay, ACS Macro Lett. 2012, 1, 194-197; (c) R. E. Ward and
T. Y. Meyer, Macromolecules 2003, 36, 4368-4373; (d) K. E.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 7 of 8
View Article Online
DOI: 10.1039/C8NJ03166E
Journal Name
ARTICLE
Schwiebert; D. N. Chin; J. C. MacDonald and G. M.
Whitesides, J. Am. Chem. Soc. 1996, 118, 4018-4029.
free of charge by The Cambridge Crystallographic Data
Centre.
(a) J. T. Kuethe; A. Wong and I. W. Davies, J. Org. Chem. 22 N. V. Reddy; P. S. Kumar; P. S. Reddy; M. L. Kantam and K. R.
3
2004, 69, 7752-7754; (b) D. J. Gustin; C. A. Sehon; J. Wei; H.
Cai; S. P. Meduna; H. Khatuya; S. Sun; Y. Gu; W. Jiang; R. L.
Thurmond; L. Karlsson and J. P. Edwards, Bioorg. Med. Chem.
Lett. 2005, 15, 1687-1691; (c) P. H. Elsinga; A. van Waarde; K.
A. Jaeggi; G. Schreiber; M. Heldoorn and W. Vaalburg, J.
Med. Chem. 1997, 40, 3829-3835; (d) A.-M. Monforte; P.
Logoteta; S. Ferro; L. D. Luca; N. Iraci; G. Maga; E. D. Clercq;
Reddy, New J. Chem. 2015, 39, 805-809.
C. Pannecouque and A. Chimirri, Bioorg. Med. Chem. 2009
17, 5962-5967.
,
4
5
(a) I. Tapia; L. Alonso-Cires; P. L. López-Tudanca; R.
Mosquera; L. Labeaga; A. Innératy and A. Orjales, J. Med.
Chem. 1999, 42, 2870-2880; (b) H. Kawamoto; H. Nakashima;
T. Kato; S. Arai; K. Kamata and Y. Iwasawa, Tetrahedron
2001, 57, 981-986.
D. B. Nale and B. M. Bhanage, Green Chem. 2015, 17, 2480-
2486.
6
7
E. Łukasik and Z. Wróbel, Synthesis 2016, 48, 1159-1166.
(a) J. An; H. Alper and A. M. Beauchemin, Org. Lett. 2016, 18,
3482-3485; (b) A. Beyer; C. M. M. Reucher and C. Bolm, Org.
Lett. 2011, 13, 2876-2879; (c) Z. Li; H. Sun; H. Jiang and H.
Liu, Org. Lett. 2008, 10, 3263-3266; (d) M. McLaughlin; M.
Palucki and I. W. Davies, Org. Lett. 2006, 8, 3311-3314; (e) N.
Barbero; M. Carril; R. SanMartin and E. Domínguez,
Tetrahedron 2008, 64, 7283-7288.
8
9
(a) X. Diao; Y. Wang; Y. Jiang and D. Ma, J. Org. Chem. 2009,
74, 7974-7977; (b) B. Zou; Q. Yuan and D. Ma, Org. Lett.
2007, 9, 4291-4294; (c) Q. Wang; J. An; H. Alper; W. J. Xiao
and A. M. Beauchemin, Chem. Commun. 2017, 53, 13055-
13058.
(a) S. W. Youn and Y. H. Kim, Org. Lett. 2016, 18, 6140-6143;
(b) J. Yu; C. Gao; Z. Song; H. Yang and H. Fu, Eur. J. Org.
Chem. 2015, 5869-5875; (c) A. G. Romero; W. H. Darlington;
E. J. Jacobsen and J. W. Mickelson, Tetrahedron Lett. 1996
,
37, 2361-2364; (d) M. L. Oftedahl; R. W. Radue and M. W.
Dietrich, J. Org. Chem. 1963, 28, 578-580.
10 (a) S. H. Cho; J. Y. Kim; J. Kwak and S. Chang, Chem. Soc. Rev.
2011, 40, 5068-5083; (b) F. Collet; R. H. Dodd and P. Dauban,
Chem. Commun. 2009, 5061-5074; (c) J. Jiao; K. Murakami
and K. Itami, ACS Catal. 2016, 6, 610-633; (d) Y. Park; Y. Kim
and S. Chang, Chem. Rev. 2017, 117, 9247-9301; (e) P.
Subramanian; G. C. Rudolf and K. P. Kaliappan, Chem.-Asian
J. 2016, 11, 168-192.
11 (a) C.-L. Sun and Z.-J. Shi, Chem. Rev. 2014, 114, 9219-9280;
(b) R. Narayan; S. Manna and A. P. Antonchick, Synlett 2015,
26, 1785-1803.
12 Y.-X. Li; K.-G. Ji; H.-X. Wang; S. Ali and Y.-M. Liang, J. Org.
Chem. 2011, 76, 744-747.
13 W.-B. Wu and J.-M. Huang, Org. Lett. 2012, 14, 5832-5835.
14 R. Samanta; R. Narayan; J. O. Bauer; C. Strohmann; S.
Sieversa and A. P. Antonchick, Chem. Commun. 2015, 51,
925-928.
15 S. Badigenchala; V. Rajeshkumar and G. Sekar, Org. Biomol.
Chem. 2016, 14, 2297-2305.
16 H. Batchu; S. Bhattacharyya and S. Batra, Org. Lett. 2012, 14,
6330-6333.
17 Z. Lv; J. Liu; W. Wei; J. Wu; W. Yu and J. Chang, Adv. Synth.
Catal. 2016, 358, 2759-2766.
18 W. Wei; Z. Wang; X. Yang; W. Yu and J. Chang, Adv. Synth.
Catal. 2017, 359, 3378-3387.
19 D. Yamauchi; T. Nishimura and H. Yorimitsu, Angew. Chem.
Int. Ed. 2017, 56, 7200-7204.
20 X. Yang and A. K. Yudin, Synlett 2007, 2912-2918.
21 CCDC 1835502
crystallographic data for this paper. These data are provided
(
1aa
)
contains the supplementary
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

New Journal of Chemistry
Page 8 of 8
View Article Online
DOI: 10.1039/C8NJ03166E
I2ꢀMediated TransitionꢀMetalꢀFree Aromatic C−H Amination for the Synthesis of
Benzimidazolꢀ2ꢀones and Related Heterocycles
Yinggao Meng, Bingnan Wang, Linning Ren, Qiongli Zhao, Wenquan Yu* and Junbiao Chang*
A practical I2-mediated aromatic C-H amination reaction was established for benzimidazol-2-one
synthesis under transition-metal-free conditions. The present reaction can be performed directly
from disubstituted amines and isocyanates without purification of the urea intermediates in a
scalable fashion.