Metal-Free Oxidative C-H Amidation of N,N′-Diarylureas with PhI(OAc)2: Synthesis of Benzimidazol-2-one Derivatives

Article abstract of DOI:10.1002/ejoc.201500726

Benzimidazol-2-ones have various biological functions and are usually prepared by reactions of substituted benzene-1,2-diamines with carbonyl-containing compounds or intramolecular N-arylations using substrates with carbon-halogen bonds. However, the star

Full text of DOI:10.1002/ejoc.201500726

FULL PAPER
DOI: 10.1002/ejoc.201500726
Metal-Free Oxidative C–H Amidation of N,NЈ-Diarylureas with PhI(OAc)2:
Synthesis of Benzimidazol-2-one Derivatives
Jipan Yu,[a] Chang Gao,[a,b] Zhixuan Song,[a] Haijun Yang,[a] and Hua Fu*[a,b]
Keywords: Synthetic methods / Nitrogen heterocycles / C–H activation / Iodine
Benzimidazol-2-ones have various biological functions and
are usually prepared by reactions of substituted benzene-1,2-
been developed that takes place at room temperature. This
protocol uses readily available N,NЈ-diarylureas as the start-
diamines with carbonyl-containing compounds or intramo- ing materials and inexpensive PhI(OAc)2 as the oxidant with-
lecular N-arylations using substrates with carbon-halogen
bonds. However, the starting materials of these protocols are
often not readily available. Herein, a simple and practical
metal-free oxidative C–H amidation of N,NЈ-diarylureas has
out the need of a catalyst, ligand, or the exclusion of air. The
present method has a wide functional group tolerance and
affords a new and practical strategy for the synthesis of N-
heterocycles.
Benzimidazol-2-ones have various biological functions.
For example, they are used as inhibitors of respiratory syn-
cytial virus (RSV) fusion,[13] non-nucleoside reverse tran-
scriptase (NNRT),[14] and farnesyltransferase (FTase)[15] as
well as antagonists of the progesterone receptor.[16] Corre-
spondingly, methods for the synthesis of these compounds
have been developed. Common approaches include reac-
tions between substituted benzene-1,2-diamines and phos-
gene,[17] triphosgene,[18] and carbonyldiimidazole (CDI).[19]
However, substituted benzene-1,2-diamines are often not
readily available. Recently, some alternative protocols have
been developed for the transformation of carbon-halogen
bonds into C–N bonds by transition-metal catalysis[20] or
base promotion.[21] To the best of our knowledge, the aryl
C–H amidation of N,NЈ-diarylureas has not been reported.
Herein, we describe a metal-free oxidative C–H amidation
reaction of readily available N,NЈ-diarylureas by using
PhI(OAc)2 at room temperature to prepare the correspond-
ing benzimidazol-2-one derivatives.
Introduction
Nitrogen-containing heterocycles are ubiquitous struc-
tures that exhibit a variety of biological activities[1] and have
been assigned as privileged motifs in drug development.[2]
The formation of C–N bonds is a key step in synthesis of
N-heterocycles,[3] so it is of great value to develop new, ef-
ficient, and practical methods for their construction. Com-
mon approaches include the copper-catalyzed Ullmann-
type coupling[4] and palladium-catalyzed Buchwald–Hart-
wig amination,[5] which occur between compounds that
contain NH and aryl halides, and some N-heterocycles have
been synthesized through coupling reactions by us[6] as well
as other groups.[7] Recently, success has been achieved in
the transition-metal-catalyzed formation of C–N bonds
through direct C–H activation,[8] and various N-hetero-
cycles have been constructed in this manner by us[9] and
other groups.[10] Very recently, protocols for the formation
of C–N bonds through C–H bond activation have been de-
veloped by using hypervalent iodine(III) reagents under
metal-free conditions.[11] However, methods for the
synthesis of N-heterocycles by using this strategy are
limited.[12]
Results and Discussion
We began by optimizing the reaction conditions for the
oxidative C–H amidation of 1-methyl-1,3-diphenylurea (1a)
with PhI(OAc)2 to lead to 1-methyl-3-phenyl-1H-benzo[d]-
imidazol-2(3H)-one (2a) and screened different solvents at
room temperature without the exclusion of air (Table 1, En-
tries 1–10). The highest yield was obtained by carrying out
the reaction in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)
for 12 h (Table 1, Entry 1). Other oxidants were then exam-
ined (Table 1, Entries 11–16), but they were inferior to
PhI(OAc)2. When the amount of PhI(OAc)2 was reduced
(Table 1, Entry 17), the yield of 2a decreased. Finally, we
[a] Key Laboratory of Bioorganic Phosphorus Chemistry and
Chemical Biology (Ministry of Education), Department of
Chemistry, Tsinghua University,
Beijing 100084, P. R. China
E-mail: fuhua@mail.tsinghua.edu.cn
http://chem.tsinghua.edu.cn
[b] Key Laboratory of Chemical Biology (Guangdong Province),
Graduate School of Shenzhen, Tsinghua University,
Shenzhen 518057, P. R. China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500726.
Eur. J. Org. Chem. 2015, 5869–5875
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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J. Yu, C. Gao, Z. Song, H. Yang, H. Fu
FULL PAPER
employed several bases as additives (Table 1, Entries 18–20)
and found that Cs2CO3 gave the best result (Table 1, En-
try 18).
After the optimized reaction conditions were deter-
mined, the scope for oxidative C–H amidation of N,NЈ-di-
arylureas 1 with PhI(OAc)2 was investigated. The substrates
that were examined provided moderate to good yields
(Table 2). The N,NЈ-diarylureas 1 with a neutral or electron-
donating group for R1 provided higher yields than those
with electron-withdrawing substituents. With the exception
of ethyl 4-(1-methyl-3-phenylureido)benzoate (1y), the
other substrates afforded moderate to good yields at room
temperature. However, the reaction of 1y, which contained
an ester group, did not work under the reaction conditions,
and a higher temperature (80 °C) was required, which af-
forded only 40% yield. The N,NЈ-diarylureas 1 with an al-
phatic substituent for R2 afforded lower yields as the sub-
strate became more sterically hindered. 1-Benzyl-1,3-di-
phenylurea (1h) yielded two products 2h and 2hЈ. 1-Allyl-
1,3-diphenylurea (1g) afforded a low yield of 2g along with
some unknown products (Table 2, Entry 7). Compound 1z,
in which R2 = Ph, afforded a high yield of 88% (Table 2,
Entry 26). The reaction of 1-methyl-3-phenyl-1-m-tolylurea
(1t) gave major product 2t. Because of steric hindrance,
only a trace amount of 2tЈ was observed (Table 2, Entry 20).
The N,NЈ-diarylureas 1 that contain electron-donating
groups for R3 showed higher reactivity than those with elec-
tron-withdrawing groups. The oxidative C–H amidation of
N,NЈ-diarylureas 1, which led to benzimidazol-2-one deriv-
atives 2, could tolerate various functional groups including
a C–F bond (Table 2, Entries 12 and 22), a C–Cl bond
(Table 2, Entries 13–15 and 23), a C–Br bond (Table 2, En-
tries 16 and 24), a CF3 group (Table 2, Entry 17), and an
ester group (Table 2, Entries 18 and 25).
Table 1. Optimization of reaction conditions for intramolecular C–
H oxidative amidation of 1-methyl-1,3-diphenylurea (1a).[a]
Entry Oxidant
(equiv.)
Solvent Additive Time
[h]
Yield
[%][b]
1
2
3
4
5
6
7
8
PhI(OAc)2 (1.5)
HFIP
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
12
12
24
24
24
24
24
24
24
24
24
24
24
24
24
63
50
17
47
0
trace
trace
0
39
23
55
0
0
0
0
0
51
71
57
68
PhI(OAc)2 (1.5)
PhI(OAc)2 (1.5)
PhI(OAc)2 (1.5)
PhI(OAc)2 (1.5)
PhI(OAc)2 (1.5)
PhI(OAc)2 (1.5)
PhI(OAc)2 (1.5)
PhI(OAc)2 (1.5)
PhI(OAc)2 (1.5)
TFE[c]
CF3CO2H
CH3CN
THF[c]
DMF[c]
DMSO[c]
iPrOH
9
DCM[c]
DCE[c]
10
11
12
13
14
15
16
17
18
19
20
PhI (0.2) + m-CPBA[c] (1.5) HFIP
PhI (0.2) + TBHP[c] (1.5)
K2S2O8 (1.5)
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
NIS[c] (1.5)
NBS[c] (1.5)
NCS[c] (1.5)
PhI(OAc)2 (1.1)
PhI(OAc)2 (1.5)
PhI(OAc)2 (1.5)
PhI(OAc)2 (1.5)
24
12
12
12
Cs2CO3
K2CO3
Na2CO3
A possible mechanism for the oxidative C–H amidation
of N,NЈ-diarylureas, which is in agreement with the results
above and previous references,[12] is presented in Scheme 1.
The treatment of 1 with PhI(OAc)2 gives I, and heterolysis
of the N–I bond of I results in the leaving of PhI and AcO–
to provide cation II. An intramolecular electrophilic ad-
dition of II leads to III, and the deprotonation of III in the
presence of AcO– affords target product 2.
[a] Reagents and conditions: 1-methyl-1,3-diphenylurea (1a)
(0.2 mmol), PhI(OAc)2 (0.3 mmol), additive (0.24 mmol), and solvent
(2.0 mL) at r.t. (approximately 25 °C) for 12 or 24 h in a sealed
Schlenk tube without the exclusion of air. [b] Isolated yield. [c] TFE
= 2,2,2-trifluoroethanol, THF = tetrahydrofuran, DMF = N,N-di-
methylformamide, DMSO = dimethyl sulfoxide, DCM = 1,2-dichloro-
methane, DCE = 1,2-dichloroethane, m-CPBA = meta-chloroper-
oxybenzoic acid, TBHP = tert-butyl hydroperoxide, NIS = N-iodosuc-
cinimide, NBS = N-bromosuccinimide, NCS = N-chlorosuccinimide.
Scheme 1. Possible mechanism for the oxidative C–H amidation of N,NЈ-diarylureas.
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Metal-Free Oxidative C–H Amidation of N,NЈ-Diarylureas
Table 2. Oxidative C–H amidation of N,NЈ-diarylureas (1) to lead to benzimidazol-2-one derivatives (2).[a]
[a] Reagents and conditions: N,NЈ-diarylureas 1 (0.2 mmol), PhI(OAc)2 (0.3 mmol), Cs2CO3 (0.24 mmol), HFIP (2.0 mL), at r.t. (approximately
25 °C) for 12 or 24 h in a sealed Schlenk tube without the exclusion of air. [b] Isolated yield. [c] The reaction was performed at 80 °C.
Eur. J. Org. Chem. 2015, 5869–5875
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1
light yellow gum. H NMR (400 MHz, CDCl3): δ = 7.56–7.49 (m,
4 H), 7.38 (t, J = 6.9 Hz, 1 H), 7.15–7.03 (m, 4 H), 3.95 (t, J =
7.2 Hz, 2 H), 1.84–1.76 (m, 2 H), 1.50–1.40 (m, 2 H), 0.98 (t, J =
7.3 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.4, 134.9,
129.7, 129.5, 127.6, 126.0, 121.9, 121.3, 108.8, 107.9, 41.1, 30.5,
20.2, 13.9 ppm. MS (ESI): m/z = 267.5 [M + H]+.
Conclusions
We have developed a simple, efficient, and practical
metal-free oxidative C–H amidation of N,NЈ-diarylureas.
The corresponding benzimidazol-2-one derivatives were
prepared in moderate to good yields. This protocol uses
readily available N,NЈ-diarylureas as the starting materials
and inexpensive PhI(OAc)2 as the oxidant without the need
for a catalyst, ligand, or the exclusion of air. The reactions
performed well with wide tolerance for various functional
groups. Therefore, the present method provides a new strat-
egy for the synthesis of N-heterocycles.
1-Pentyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2e): Purification
of the crude product by flash chromatography on silica gel (petro-
leum ether/ethyl acetate, 5:1) afforded 2e (61% isolated yield) as a
1
light yellow gum. H NMR (400 MHz, CDCl3): δ = 7.56–7.49 (m,
4 H), 7.40–7.36 (m, 1 H), 7.15–7.02 (m, 4 H), 3.94 (t, J = 7.3 Hz,
2 H), 1.85–1.78 (m, 2 H), 1.44–1.36 (m, 4 H), 0.91 (t, J = 7.0 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.4, 134.9, 129.7,
129.5, 127.6, 126.0, 121.9, 121.3, 108.8, 107.9, 41.1, 29.1, 28.1, 22.5,
14.1 ppm. MS (ESI): m/z = 281.1 [M + H]+.
Experimental Section
1-Cyclohexyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2f): Purifi-
cation of the crude product by flash chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) afforded 2f (55% isolated yield)
as a light yellow solid; m.p. 94–95 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.54–7.49 (m, 4 H), 7.41–7.36 (m, 1 H), 7.24 (d, J =
7.7 Hz, 1 H), 7.12–7.00 (m, 3 H), 4.40–4.32 (m, 1 H), 2.26–2.17 (m,
2 H), 1.94 (d, J = 10.9 Hz, 4 H), 1.77 (d, J = 12.9 Hz, 1 H), 1.52–
1.42 (m, 2 H), 1.34–1.25 (m, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 152.9, 134.8, 129.7, 129.5, 128.8, 127.6, 126.3, 121.6,
120.9, 109.5, 108.8, 53.3, 30.2, 26.1, 25.5 ppm. MS (ESI): m/z =
293.1 [M + H]+.
1
General Methods: All reactions were carried out under air. The H
and 13C NMR spectroscopic data were recorded in CDCl3 with
1
tetramethylsilane as the internal standard (for H NMR: TMS at
δ = 0.00 ppm and CHCl3 at δ = 7.26 ppm; for 13C NMR: CDCl3
at δ = 77.26 ppm). Compounds 1a–1z were prepared according to
previously reported procedures.[22]
General Procedure for Synthesis of Compounds 2a–2z: A 25 mL
Schlenk tube was charged with a magnetic stirrer, N,NЈ-diarylurea
1 (0.2 mmol), PhI(OAc)2 (0.3 mmol), Cs2CO3 (0.24 mmol), and
1,1,1,3,3,3-hexafluoro-2-propanol (2.0 mL). The tube was sealed,
and the mixture was stirred at room temperature (approximately
25 °C; 80 °C for substrate 1y, see Table 2) until the reaction reached
completion (monitored by TLC). The mixture was concentrated by
rotary evaporation, and the residue was purified by column
chromatography on silica gel (petroleum ether/ethyl acetate) to give
the desired target product 2.
1-Allyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2g): Purification
of the crude product by flash chromatography on silica gel (petro-
leum ether/ethyl acetate, 5:1) afforded 2g (33% isolated yield) as a
1
light yellow gum. H NMR (600 MHz, CDCl3): δ = 7.55–7.51 (m,
4 H), 7.39 (t, J = 6.8 Hz, 1 H), 7.13–7.08 (m, 2 H), 7.05 (t, J =
7.9 Hz, 2 H), 5.99–5.93 (m, 1 H), 5.32–5.26 (m, 2 H), 4.58 (dd, J
= 5.5 Hz, J = 1.0 Hz, 2 H) ppm. 13C NMR (150 MHz, CDCl3): δ
= 153.2, 134.8, 132.0, 129.6, 129.3, 127.7, 126.1, 125.9, 122.0, 121.5,
117.9, 108.8, 108.5, 43.8 ppm. MS (ESI): m/z = 251.2 [M + H]+.
1-Methyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2a): Purifica-
tion of the crude product by flash chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) afforded 2a (71% isolated yield)
as a light yellow solid, m.p. 126–127 °C; ref.[21a] m.p. 127–129 °C.
1H NMR (400 MHz, CDCl3): δ = 7.54–7.49 (m, 4 H), 7.40–7.36
(m, 1 H), 7.17–7.13 (m, 1 H), 7.08–7.02 (m, 3 H), 3.49 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 153.6, 134.9, 130.3, 129.6, 129.5,
127.7, 126.1, 122.1, 121.5, 108.7, 107.7, 27.3 ppm. MS (ESI): m/z
= 225.3 [M + H]+.
1-Benzyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2h): Purification
of the crude product by flash chromatography on silica gel (petro-
leum ether/ethyl acetate, 5:1) afforded 2h (46% isolated yield) as a
1
light yellow solid, m.p. 99–100 °C; ref.[21b] m.p. 99.8–100.7 °C. H
NMR (400 MHz, CDCl3): δ = 7.59–7.51 (m, 4 H), 7.41–7.38 (m, 3
H), 7.34 (t, J = 7.9 Hz, 2 H), 7.28 (d, J = 7.3 Hz, 1 H), 7.11–7.07
(m, 1 H), 7.06–7.03 (m, 2 H), 6.96–6.94 (m, 1 H), 5.14 (s, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 153.6, 136.3, 134.8, 129.6, 129.4,
128.9, 127.9, 127.8, 127.7, 126.0, 122.1, 121.6, 108.9, 108.6,
45.1 ppm. MS (ESI): m/z = 301.3 [M + H]+.
1-Ethyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2b): Purification
of the crude product by flash chromatography on silica gel (petro-
leum ether/ethyl acetate, 5:1) afforded 2b (68% isolated yield) as a
1
light yellow gum. H NMR (300 MHz, CDCl3): δ = 7.60–7.49 (m,
4 H), 7.42–7.37 (m, 1 H), 7.18–7.03 (m, 4 H), 4.03 (q, J = 7.2 Hz,
2 H), 1.41 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 153.1, 134.8, 129.6, 129.3, 127.6, 126.1, 122.0, 121.3, 108.9,
107.8, 36.1, 13.7 ppm. MS (ESI): m/z = 238.3 [M + H]+.
1-Benzyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2hЈ): Purifica-
tion of the crude product by flash chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) afforded 2hЈ (10% isolated
yield) as a light yellow gum. 1H NMR (400 MHz, CDCl3): δ =
7.58–7.47 (m, 4 H), 7.42–7.28 (m, 6 H), 7.09–7.05 (m, 3 H), 6.98–
6.95 (m, 1 H), 5.14 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 153.4, 136.1, 133.4, 133.3, 129.8, 129.4, 129.2, 128.9, 127.9, 127.8,
127.2, 122.4, 121.8, 108.7, 45.2 ppm. MS (ESI): m/z = 301.2 [M +
H]+.
1-Isopropyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2c): Purifica-
tion of the crude product by flash chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) afforded 2c (64% isolated yield)
as a light yellow solid; m.p. 105–106 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.54–7.49 (m, 4 H), 7.42–7.36 (m, 1 H), 7.21 (d, J =
7.8 Hz, 1 H), 7.13–7.01 (m, 3 H), 4.81 (m, 1 H), 1.60 (d, J = 7.0 Hz,
6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 152.8, 134.8, 129.7,
129.5, 128.5, 127.6, 126.3, 121.7, 121.0, 109.2, 108.8, 45.3,
20.3 ppm. MS (ESI): m/z = 252.2 [M + H]+.
1-Methyl-3-(o-tolyl)-1H-benzo[d]imidazol-2(3H)-one (2i): Purifica-
tion of the crude product by flash chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) afforded 2i (42% isolated yield)
as a light yellow solid; m.p. 89–91 °C. 1H NMR (300 MHz,
1-Butyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2d): Purification CDCl3): δ = 7.41–7.27 (m, 4 H), 7.14 (t, J = 7.6 Hz, 1 H), 7.06–
of the crude product by flash chromatography on silica gel (petro-
leum ether/ethyl acetate, 5:1) afforded 2d (59% isolated yield) as a
7.01 (m, 2 H), 6.69 (d, J = 7.6 Hz, 1 H), 3.51 (s, 3 H), 2.18 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.6, 137.0, 133.2,
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Metal-Free Oxidative C–H Amidation of N,NЈ-Diarylureas
131.6, 130.4, 130.2, 129.2, 128.7, 127.2, 121.8, 121.5, 108.7, 107.6,
CDCl3): δ = 7.64 (d, J = 8.7 Hz, 2 H), 7.43 (d, J = 8.7 Hz, 2 H),
7.20–7.13 (m, 1 H), 7.11–7.03 (m, 3 H), 3.48 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 153.4, 134.0, 132.7, 130.3, 129.0,
127.5, 122.4, 121.7, 121.1, 108.9, 107.9, 27.4 ppm. MS (ESI): m/z
= 303.1 [M + H]+, 305.1.
27.4, 17.9 ppm. MS (ESI): m/z = 239.2 [M + H]+.
1-Methyl-3-(m-tolyl)-1H-benzo[d]imidazol-2(3H)-one (2j): Purifica-
tion of the crude product by flash chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) afforded 2j (56% isolated yield)
as a light yellow solid; m.p. 77–76 °C. 1H NMR (600 MHz,
CDCl3): δ = 7.40 (t, J = 7.7 Hz, 1 H), 7.34 (s, 1 H), 7.31 (d, J =
7.9 Hz, 1 H), 7.20 (d, J = 7.6 Hz, 1 H), 7.15–7.12 (m, 1 H), 7.06–
7.02 (m, 3 H), 3.48 (s, 3 H), 2.42 (s, 3 H) ppm. 13C NMR
(150 MHz, CDCl3): δ = 153.7, 139.6, 134.7, 130.2, 129.6, 129.3,
128.5, 126.8, 123.1, 121.9, 121.5, 108.8, 107.6, 27.3, 21.5 ppm. MS
(ESI): m/z = 239.2 [M + H]+.
1-Methyl-3-[4-(trifluoromethyl)phenyl]-1H-benzo[d]imidazol-2(3H)-
one (2q): Purification of the crude product by flash chromatography
on silica gel (petroleum ether/ethyl acetate, 5:1) afforded 2q (52%
isolated yield) as a light yellow solid; m.p. 146–148 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.79 (d, J = 8.5 Hz, 2 H), 7.71 (d, J =
8.5 Hz, 2 H), 7.19 (dt, J = 7.5 Hz, J = 1.4 Hz, 1 H), 7.11 (dq, J =
7.7 Hz, J = 1.1 Hz, 2 H), 7.06 (d, J = 8.1 Hz, 1 H), 3.49 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 152.1, 137.1, 129.3,
128.2 (d, J = 33.0 Hz), 125.6 (d, J = 3.6 Hz), 124.7, 122.4 (q, J =
272.0 Hz), 121.6, 120.7, 107.6, 106.9, 26.3 ppm. MS (ESI): m/z =
293.5 [M + H]+.
Methyl-3-(p-tolyl)-1H-benzo[d]imidazol-2(3H)-one (2k): Purifica-
tion of the crude product by flash chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) afforded 2k (67% isolated yield)
as a light yellow solid; m.p. 107–108 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.40 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 8.2 Hz, 2 H),
7.17–7.12 (m, 1 H), 7.06–7.02 (m, 3 H), 3.49 (s, 3 H), 2.42 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.8, 137.6, 132.2,
130.2, 129.7, 126.0, 121.9, 121.5, 108.7, 107.6, 27.3, 21.3 ppm. MS
(ESI): m/z = 239.1 [M + H]+.
Ethyl 3-(3-Methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-
benzoate (2r): Purification of the crude product by flash
chromatography on silica gel (petroleum ether/ethyl acetate, 5:1)
afforded 2r (35% isolated yield) as a light yellow solid; m.p. 90–
1
92 °C. H NMR (300 MHz, CDCl3): δ = 8.22 (d, J = 1.8 Hz, 1 H),
8.08 (dt, J = 7.8 Hz, J = 1.3 Hz, 1 H), 7.78–7.74 (m, 1 H), 7.61 (t,
J = 7.9 Hz, 1 H), 7.21–7.15 (m, 1 H), 7.09–7.04 (m, 3 H), 4.40 (q,
J = 7.1 Hz, 2 H), 3.50 (s, 3 H), 1.39 (t, J = 7.1 Hz, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 165.8, 153.5, 135.1, 132.1, 130.4,
130.3, 129.7, 129.1, 128.7, 126.9, 122.4, 121.7, 108.7, 107.9, 61.4,
27.4, 14.4 ppm. MS (ESI): m/z = 297.5 [M + H]+.
1-(4-Fluorophenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one
(2l):
Purification of the crude product by flash chromatography on silica
gel (petroleum ether/ethyl acetate, 5:1) afforded 2l (48% isolated
yield) as a light yellow solid; m.p. 132–133 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.51–7.47 (m, 2 H), 7.22–7.13 (m, 3 H), 7.09–7.00 (m,
3 H), 3.48 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.7
(d, J = 247.6 Hz), 153.6, 130.7 (d, J = 0.7 Hz), 130.2, 129.5, 127.9
(d, J = 8.6 Hz), 122.2, 121.6, 116.5 (d, J = 22.9 Hz), 108.5, 107.8,
27.4 ppm. MS (ESI): m/z = 243.2 [M + H]+.
1-Phenyl-5,6-dihydro-1H-imidazo[4,5,1-ij]quinolin-2(4H)-one (2s):
Purification of the crude product by flash chromatography on silica
gel (petroleum ether/ethyl acetate, 5:1) afforded 2s (74% isolated
yield) as a light yellow gum. 1H NMR (300 MHz, CDCl3): δ =
7.59–7.48 (m, 4 H), 7.38–7.34 (m, 1 H), 7.00–6.90 (m, 3 H), 3.94
(t, J = 5.8 Hz, 2 H), 2.91 (t, J = 6.0 Hz, 2 H), 2.22–2.14 (m 2
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 152.6, 135.4, 129.5,
127.8, 127.2, 126.8, 125.4, 121.0, 120.2, 119.8, 106.6, 39.3, 24.1,
21.9 ppm. MS (ESI): m/z = 251.1 [M + H]+.
1-(2-Chlorophenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one (2m):
Purification of the crude product by flash chromatography on silica
gel (petroleum ether/ethyl acetate, 5:1) afforded 2m (55% isolated
yield) as a light yellow solid; m.p. 124–126 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.61–7.57 (m, 1 H), 7.46–7.41 (m, 3 H), 7.15 (dt, J =
7.7 Hz, J = 1.0 Hz, 1 H), 7.06–7.02 (m, 2 H), 6.70 (d, J = 7.3 Hz,
1 H), 3.50 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.3,
133.4, 132.2, 130.9, 130.6, 130.4, 130.3, 129.6, 128.1, 122.1, 121.6,
108.9, 107.8, 27.4 ppm. MS (ESI): m/z = 259.3 [M + H]+, 261.3.
3,5-Dimethyl-1-phenyl-1H-benzo[d]imidazol-2(3H)-one (2t): Purifi-
cation of the crude product by flash chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) afforded 2t (63% isolated yield)
as a light yellow solid; m.p. 127–128 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.53–7.49 (m, 4 H), 7.39–7.34 (m, 1 H), 6.96 (d, J =
8.5 Hz, 1 H), 6.86 (d, J = 7.5 Hz, 2 H), 3.46 (s, 3 H), 2.42 (s, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.7, 135.1, 131.9,
130.4, 129.5, 127.4, 127.3, 125.9, 121.9, 108.5, 108.4, 27.3,
21.6 ppm. MS (ESI): m/z = 239.2 [M + H]+.
1-(3-Chlorophenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one (2n):
Purification of the crude product by flash chromatography on silica
gel (petroleum ether/ethyl acetate, 5:1) afforded 2n (82% isolated
yield) as a light yellow solid; m.p. 141–143 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.56 (s, 1 H), 7.48–7.42 (m, 2 H), 7.38–7.32 (m, 1 H),
7.18–7.14 (m, 1 H), 7.10–7.03 (m, 3 H), 3.48 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 153.3, 136.1, 135.1, 130.5, 130.3,
128.9, 127.8, 126.1, 124.1, 122.4, 121.7, 108.7, 107.9, 27.4 ppm. MS
(ESI): m/z = 259.3 [M + H]+, 261.3.
1,5-Dimethyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2u): Purifi-
cation of the crude product by flash chromatography on silica gel
(petroleum ether/ethyl acetate, 5:1) afforded 2u (79% isolated yield)
as a light yellow solid; m.p. 78–80 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.58–7.47 (m, 4 H), 7.44–7.36 (m, 1 H), 6.98–6.89 (m,
3 H), 3.47 (s, 3 H), 2.36 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 153.8, 135.0, 131.4, 129.6, 128.1, 127.6, 126.2, 122.6, 109.3,
107.4, 27.4, 21.6 ppm. MS (ESI): m/z = 239.3[M + H]+.
1-(4-Chlorophenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one (2o):
Purification of the crude product by flash chromatography on silica
gel (petroleum ether/ethyl acetate, 5:1) afforded 2o (87% isolated
yield) as a light yellow solid; m.p. 159–160 °C. 1H NMR (600 MHz,
CDCl3): δ = 7.48 (s, 4 H), 7.16 (dt, J = 7.7 Hz, J = 1.2 Hz, 1 H),
7.08–7.03 (m, 3 H), 3.48 (s, 3 H) ppm. 13C NMR (150 MHz,
CDCl3): δ = 153.4, 133.4, 133.2, 130.3, 129.8, 129.1, 127.2, 122.3,
121.7, 108.6, 107.9, 27.4 ppm. MS (ESI): m/z = 259.4 [M + H]+,
261.4.
5-Fluoro-1-methyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one
(2v):
Purification of the crude product by flash chromatography on silica
gel (petroleum ether/ethyl acetate, 5:1) afforded 2v (59% isolated
yield) as a light yellow solid; m.p. 145–147 °C. 1H NMR (300 MHz,
1-(4-Bromophenyl)-3-methyl-1H-benzo[d]imidazol-2(3H)-one (2p): CDCl3): δ = 7.54–7.49 (m, 4 H), 7.39 (t, J = 6.8 Hz, 1 H), 6.94–
Purification of the crude product by flash chromatography on silica
6.90 (m, 1 H), 6.87–6.80 (m, 2 H), 3.47 (s, 3 H) ppm. 13C NMR
gel (petroleum ether/ethyl acetate, 5:1) afforded 2p (66% isolated (75 MHz, CDCl3): δ = 160.5, 155.6 (d, J = 258.0 Hz), 134.5, 130.0
yield) as a light yellow solid; m.p. 160–162 °C. 1H NMR (400 MHz, (d, J = 12.4 Hz), 129.7, 127.9, 126.0, 125.9, 108.3 (d, J = 24.3 Hz),
Eur. J. Org. Chem. 2015, 5869–5875
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5873

J. Yu, C. Gao, Z. Song, H. Yang, H. Fu
FULL PAPER
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107.8 (d, J = 9.4 Hz), 97.2 (d, J = 29.2 Hz), 27.5 ppm. MS (ESI):
m/z = 243.2 [M + H]+.
5-Chloro-1-methyl-3-phenyl-1H-benzo[d]imidazol-2(3H)-one (2w):
Purification of the crude product by flash chromatography on silica
gel (petroleum ether/ethyl acetate, 5:1) afforded 2w (63% isolated
yield) as a light yellow solid; m.p. 150–152 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.55–7.47 (m, 4 H), 7.40 (t, J = 7.0 Hz, 1 H), 7.11 (dd,
J = 8.3 Hz, J = 1.5 Hz, 1 H), 7.04 (d, J = 1.6 Hz, 1 H), 6.93 (d, J
= 8.3 Hz, 1 H), 3.46 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 153.5, 134.3, 130.3, 129.8, 128.8, 128.1, 127.1, 126.0, 121.9,
109.1, 108.4, 27.5 ppm. MS (ESI): m/z = 259.3 [M + H]+, 261.3.
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Purification of the crude product by flash chromatography on silica
gel (petroleum ether/ethyl acetate, 5:1) afforded 2x (74% isolated
yield) as a light yellow solid, m.p. 175–176 °C; ref.[23] m.p. 175–
177 °C. 1H NMR (600 MHz, CDCl3): δ = 7.53 (t, J = 8.2 Hz, 2 H),
7.48 (d, J = 7.3 Hz, 2 H), 7.41 (t, J = 7.3 Hz, 1 H), 7.26–7.24 (m,
1 H), 7.17 (d, J = 1.3 Hz, 1 H), 6.89 (d, J = 8.3 Hz, 1 H), 3.46 (s,
3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 153.4, 134.3, 130.6,
129.8, 129.3, 128.1, 126.0, 124.8, 114.2, 111.8, 108.9, 27.5 ppm. MS
(ESI): m/z = 303.3 [M + H]+, 305.3.
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Ethyl 2,3-Dihydro-1-methyl-2-oxo-3-phenyl-1H-benzo[d]imidazole-5-
carboxylate (2y): Purification of the crude product by flash
chromatography on silica gel (petroleum ether/ethyl acetate, 5:1)
afforded 2y (40% isolated yield) as a light yellow solid; m.p. 127–
1
128 °C. H NMR (300 MHz, CDCl3): δ = 7.93 (dd, J = 8.2 Hz, J
= 1.6 Hz, 1 H), 7.74 (d, J = 1.5 Hz, 1 H), 7.58–7.51 (m, 4 H), 7.47–
7.41 (m, 1 H), 7.06 (d, J = 8.2 Hz, 1 H), 4.35 (q, J = 7.1 Hz, 2 H),
3.53 (s, 3 H), 1.37 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 166.6, 153.8, 134.3, 133.9, 129.8, 129.3, 128.1, 126.1,
124.6, 124.1, 109.9, 107.1, 61.1, 27.6, 14.5 ppm. MS (ESI): m/z =
297.3 [M + H]+.
1,3-Diphenyl-1H-benzo[d]imidazol-2(3H)-one (2z): Purification of
the crude product by flash chromatography on silica gel (petroleum
ether/ethyl acetate, 5:1) afforded 2z (88% isolated yield) as a light
yellow solid; m.p. 100–101 °C. 1H NMR (400 MHz, CDCl3): δ =
7.63–7.60 (m, 4 H), 7.59–7.53 (m, 4 H), 7.44–7.40 (m, 2 H), 7.16–
7.10 (m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 152.5, 134.6,
129.6, 127.9, 126.2, 122.2, 109.19 ppm. MS (ESI): m/z = 287.1 [M
+ H]+.
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of H and 13C NMR spectra of compounds 2a–2z.
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Acknowledgments
The authors wish to thank the National Natural Science Founda-
tion of China (NSFC) (grant numbers 21172128, 21372139, and
21221062) and the Ministry of Science and Technology of China
(grant number 2012CB722605) for financial support.
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Received: June 3, 2015
Published Online: July 31, 2015
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