Synthesis of Benzimidazolones via One-Pot Reaction of Hydroxylamines, Aldehydes, and Trimethylsilyl Cyanide Promoted by Diacetoxyiodobenzene

Article abstract of DOI:10.1021/acs.joc.6b02781

A novel and efficient PhI(OAc)₂-promoted one-pot reaction of aromatic hydroxylamines, aldehydes, and TMSCN in the presence of BF₃·Et₂O is described. A wide variety of N-substituted benzimidazolones are obtained with satisfactory yields under mild reaction conditions. The method was proven to be efficient for the synthesis of benzimidazolone derivatives from readily available starting materials.

Full text of DOI:10.1021/acs.joc.6b02781

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Article
Synthesis of Benzimidazolones via One-Pot Reaction of Hydroxylamines,
Aldehydes and Trimethylsilyl Cyanide Promoted by Diacetoxyiodobenzene
Huaiyuan Zhang, Danfeng Huang, Ke-Hu Wang, Jun Li, Yingpeng Su, and Yulai Hu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02781 • Publication Date (Web): 05 Jan 2017
Downloaded from http://pubs.acs.org on January 6, 2017
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Synthesis of Benzimidazolones via One-Pot Reaction of
Hydroxylamines, Aldehydes and Trimethylsilyl Cyanide
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Promoted by Diacetoxyiodobenzene
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Huaiyuan Zhang,† Danfeng Huang,† Ke-Hu Wang,† Jun Li,† Yingpeng Su,† and Yulai Hu*†‡
†College of Chemistry and Chemical Engineering, Northwest Normal University, 967 Anning East Road, Lanzhou
730070, P. R. China.
‡State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. China
E-mail: huyl@nwnu.edu.cn.
Abstract
A novel and efficient PhI(OAc)2-promoted one-pot reaction of aromatic hydroxylamines, aldehydes
and TMSCN in the presence of BF3ꢀEt2O is described. A wide variety of N-substituted
benzimidazolones are obtained with satisfactory yields under mild reaction conditions. The method was
proved to be efficient for the synthesis of benzimidazolone derivatives from readily available starting
materials.
INTRODUCTION
Benzimidazolones, important derivatives of benzimidazoles, were found to exhibit wide range of
biological activities such as antidiabetic,1 antiulcer,2 anti-infective,3 and analgesic agents.4 Many
benzimidazolone-containing organic molecules, such as Oxatomide, Droperidol and others, have been
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successfully developed as clinical drugs (Figure 1).5-8 Furthermore, benzimidazolones have also been
widely used in material science.9-13 For instance, Pigment Yellow 151, a greenish shade yellow
pigment,14 is widely applied in plastics, inks and industrial paint because of its high color strength,
excellent heat stability, warping resistance and good fastness.
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Thus, considerable attention has been paid to the development of methods for the construction of
benzimidazolone-containing organic compounds.15-17 Up to now, many synthetic approaches have been
developed for the synthesis of benzimidazolone and its derivatives (Scheme 1, a-d). The conventional
methods are based on phosgenation of o-phenylenediamine,18 which are being gradually discarded since
phosgene is highly toxic. Recently, several nonphosgene approaches have been reported, including
condensation of o-phenylenediamines or 2-nitroaniline with urea,19 dimethyl carbonate,20 carbon
dioxide21 or carbon monoxide.22 Benzimidazolones can also be generated by the reaction of 2-amino-
benzamide with iodosylbenzene,23 ionic-liquid-catalyzed carbonylation of o-phenylenediamines with
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CO2 and cascade C−N coupling of monosubstituted ureas.24 Although much progress has been made
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for the synthesis of benzimidazolones, it is still necessary to develop more effective methods for the
synthesis of benzimidazolone and its derivatives.
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Figure 1. Representative clinical drugs containing benzimidazolones
Scheme 1. Preparation of Benzimidazolones
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On the other hand, diacetoxyiodobenzene (PhI(OAc)2), one of the most popular hypervalent iodine
reagents, is widely used in organic synthesis due to their low toxicity, high stability, ease of handling,
and commercial availability. Except for its traditional application as oxidative reagent in organic
synthesis, PhI(OAc)2 has also been applied in other transformations,25 including α-functionalization of
carbonyl compounds,26 C−C bond forming reactions,27 C−O bond forming reactions,28 cyclizations,29
and etc. In this paper, we report the first example of PhI(OAc)2-promoted one-pot reaction of
hydroxylamines, aldehydes and trimethylsilyl cyanide in the presence of Lewis acids to afford the
biologically interesting N-monosubstituted benzimidazolones in good yields (Scheme 1, e).
RESULTS AND DISCUSSION
We initiated our study with N-phenyl hydroxylamine 1a and benzaldehyde 2a as subsatrates, 1 equiv
of PhI(OAc)2 3a as oxidant, 3 equiv of TMSCN 4 as N-source, and 4 equiv of BF3ꢀEt2O 5a as Lewis
acid. The reaction was carried out in dry CH2Cl2 under nitrogen atmosphere at room temperature. The
desired product 6a was obtained with 30% yield. Next, the reaction conditions were examined in detail
in order to improve the yield, and the results were summarized in Table 1. When the molar ratio of N-
phenyl hydroxylamine 1a and benzaldehyde 2a was fixed to 1:1,30 the molar ratio of the substrate 3a, 4,
5a was examined (Table 1, entries 1−9). It was found that the yield of 6a increased from 30% to 61%
when the molar ratio of PhI(OAc)2 increased from 1 equiv to 2 equiv(Table 1, entries 1−3). Continuing
raise of the ratio of PhI(OAc)2 did not lead to increase of the yield of 6a (Table 1, entry 4). The molar
ratio of the TMSCN and BF3ꢀEt2O was also examined. When the amount of TMSCN decreased from 3
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to 2 equiv, the yield of 6a dropped from 61% to 44%, but increasing of its amount to 4 equiv did not
influence the result too much (Table 1, entries 3, 5 and 6). Moreover, when BF3ꢀEt2O was used above 4
equiv, the yield of 6a did not increase (Table 1, entries 3, 7 and 8). Especially, the reaction could not
occur in the absence of BF3ꢀEt2O, which shows that BF3ꢀEt2O plays an important role to initiate the
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reaction
(Table
1,
entry
9).
So
the
best
molar
ratio
of
N-phenyl
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hydroxylamine/PhCHO/PhI(OAc)2/TMSCN/BF3ꢀEt2O was determined to be 1/1/2/3/4. Afterwards,
different solvents were screened (Table 1, entries 10−15). The reaction could occur in dichloromethane,
acetonitrile, chloroform and nitromethane, but the yields of 6a in THF, DMF and toluene were lower.
Consequently, CH2Cl2 was chosen as the solvent in the following studies. In order to improve the
product yield further, the reactions were carried out in the presence of Lewis acid such as ZnCl2, FeCl3,
AlCl3, SnCl4, Mg(ClO4)2, Cu(AcO)2 (Table 1. entries 16−21). The results revealed that the use of Lewis
acid led to the formation of 6a’ in reaction besides 6a. Especially, when Mg(ClO4)2 or Cu(AcO)2 was
used, 6a’ became the sole product (Table 1, entries 20 and 21). We envisioned that the formation of 6a’
was due to the oxidative rearrangement reaction. Finally, the investigation of temperature on the
reaction showed that the yield of 6a at 0 oC or reflux was lower than that at room temperature (Table 1,
entries 22−23).
Table 1. Optimization of the Reaction Conditionsa
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Products (%)b
Entry
1a:2a:3a:4:5 mole ratio
Lewis acid
Solvent
6a
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0
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1:1:1:3:4
1:1:1.5:3:4
1:1:2:3:4
1:1:3:3:4
1:1:2:2:4
1:1:2:4:4
1:1:2:3:3
1:1:2:3:5
1:1:2:3:0
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1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
1:1:2:3:4
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
ZnCl2
FeCl3
AlCl3
SnCl4
Mg(ClO4)2
Cu (AcO)2
BF3ꢀEt2O
BF3ꢀEt2O
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
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DMF
PhMe
MeCN
CHCl3
MeNO2
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CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
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0
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aReactions were carried out on a scale of 1a (0.46 mmol) and 2a (0.46 mmol) in DCM (5 mL). Nitrone
formed from 1a and 2a was added under nitrogen atmosphere into a mixture of 3a (0.92 mmol), 4 (1.38
mmol) and 5 (1.84 mmol), which was stirred in new solvent (5 mL) for 30 minutes beforehand. bIsolated
yields. cThe reaction was conducted at 0 oC. dThe reaction was conducted under reflux.
Next, different hypervalent iodine reagents such as [bis-(trifluoroacetoxy)iodo]benzene and
[hydroxy(tosyloxy)iodo]benzene were investigated in the reactions (Table 2). Unfortunately, the
corresponding benzimidazolones could not be obtained when the other hypervalent iodine reagents were
used instead of PhI(OAc)2. Thus, the best reaction conditions were treatment of N-phenyl
hydroxylamine with 1 equiv of benzaldehyde in CH2Cl2 at room temperature for overnight. The reaction
mixture was then added into another mixture of 2 equiv of PhI(OAc)2, 3 equiv of TMSCN and 4 equiv
of BF3ꢀEt2O to give the target product.
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Table 2. Screening of Hypervalent Iodine Reagentsa
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Yield (%)b
Products
3a: R1 = R2 = Ac
6a: R = Ac
61
0
3b: R1 = R2 = COCF3
3c: R1 = R2 = 4-methoxycinnamoyl
3d: R1 = H; R2 = Ts
7: R = COCF3
8: R = 4-methoxycinnamoyl
9: R = H
0
0
3d: R1 = H; R2 = Ts
9': R = Ts
0
aReactions were carried out on a scale of 1a (0.46 mmol) and 2a (0.46 mmol) in DCM (5 mL). Nitrone
formed from 1a and 2a was added into a mixture of 3 (0.92 mmol), 4 (1.38 mmol) and 5a(1.84 mmol),
which was stirred in DCM for 30 minutes beforehand. bIsolated yields.
Under the optimized reaction conditions, the generality of aldehydes was firstly checked. As shown in
Table 3, most of the aromatic aldehydes gave the corresponding benzimidazolones in reasonable to
good yields. The aromatic aldehydes with electron-withdrawing groups on the phenyl rings usually gave
the products in higher yields than those with electron-donating groups on the phenyl rings. For instance,
when p-nitro or p-nitrile benzaldehyde was used, the corresponding products could be obtained in 63%
and 59% yields (Table 3, 6i and 6k), but p-methoxybenzaldehyde gave the corresponding product in
only 17% yield.
The positions of the substituents on the phenyl rings of aldehydes had little influence on the product
yields. For instance, the yield of the product from o-nitrobenzaldehyde was slightly lower than that from
p-nitrobenzaldehyde (Table 3, 6j and 6i). Unfortunately, heterocyclic aromatic aldehydes such as furan-
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2-carbaldehyde or picolinaldehyde, and aliphatic aldehyde such as n-butylaldehyde or i-butyl aldehydes,
could not afford the desired products (Table 3, 6m to 6p).
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Table 3. Reactions of Different Aldehydes for the Synthesis of Benzimidazolonesa
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aReactions were carried out on a scale of 1a (0.46 mmol) and 2 (0.46 mmol) in DCM (5 mL). Nitrones
formed from 1a and 2 were added into a mixture of 3a (0.92 mmol), 4 (1.38 mmol) and 5a (1.84 mmol),
which was stirred in DCM for 30 minutes beforehand. Isolated yields.
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Next, various aromatic and aliphatic hydroxylamines were reacted with benzaldehyde 2a to exam the
generality of the reaction (Table 4). The hydroxylamines bearing an electron-withdrawing group on
their phenyl rings usually gave the corresponding products in yields higher than those with electron-
donating groups. The reason was that the electron-withdrawing groups on the phenyl rings of aromatic
hydroxylamines could increase the eletrophilicity of in-situ formed nitrone by an inductive effect. The
positions of substituents on the phenyl rings of aromatic hydroxylamines greatly influenced the reaction
results. The para-substituted aromatic hydroxylamines usually gave the corresponding products in good
yields whatever the substituents were electron-donating or electron-withdrawing groups (Table 4, 6s, 6v
and 6y to 6aa). However, if the meta-substituted hydroxylamines were used, no product could be
obtained (Table 4, 6r, 6u and 6x). Unfortunately, aliphatic hydroxylamines did not afford the products
(Table 4, 6ab and 6ac).
Table 4. Reactions of Different Hydroxylamines for the Synthesis of Benzimidazolonesa
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aReactions were carried out on a scale of 1 (0.46 mmol) and 2a (0.46 mmol) in DCM (5 mL). Nitrones
formed from 1 and 2a were added into a mixture of 3a (0.92 mmol), 4 (1.38 mmol) and 5a (1.84 mmol),
which was stirred in DCM for 30 minutes beforehand. Isolated yields.
Further investigation for generality of substrates was conducted between various benzaldehydes and
various hydroxylamines. As shown in Table 5, the reaction could smoothly occur to afford the
corresponding products when different aromatic aldehydes reacted with different aromatic
hydroxylamines. When ketones were used as substrates instead of aldehydes, the reactions did not occur
(Scheme 2).
Table 5. Reactions of Different Aldehydes with Different Hydroxylamines for the Synthesis of
Benzimidazolonesa
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aReactions were carried out on a scale of 1 (0.46 mmol) and 2 (0.46 mmol) in DCM (5 mL). Nitrones
formed from 1 and 2 were added into a mixture of 3a (0.92 mmol), 4 (1.38 mmol) and 5a (1.84 mmol),
which was stirred in DCM for 30 minutes beforehand. Isolated yields.
Scheme 2. Diacetoxyiodobenzene-Promoted Reactions of Hydroxylamine, Ketones and
Trimethylsilyl Cyanide
Finally, the application of products 6 in organic synthesis was briefly investigated. As showed in
Figure 2, nitrogen at position a in the products is protected by hemiaminal group, and nitrogen at
position b is a free amino group. Thus, the hemiaminal group could be hydrolyzed to release the amino
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group to give benzimidazolones. In addition, nitrogen at position b could be manipulated at first, and
then the nitrogen at position a was released. For instance, when product 6a was exposed to concentrated
HCl, benzimidazolone 10 could be obtained in 76% yield (Scheme 3, a). The product 6a could react at
first with benzyl bromide in the presence of potassium carbonate to afford compound 11, which was
then hydrolyzed to product 12 in 80% yield (Scheme 3, b). Furthermore, acetoxy group in the product
6c could be exchanged to more stable ethoxy groups to give compound 13 in 82% yield (Scheme 3, c).
b
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R1
NH
O
N
a
R2
O
O
6
Figure 2 Different properties of nitrogen atoms at position a and b
Scheme 3. Synthetic Applications of 6
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To investigate the mechanism, some nitrones were prepared firstly, and then reacted with PhI(OAc)2
and TMSCN in the presence of BF3ꢀEt2O. It was found that the desired products were also obtained
(Table 6), which confirmed that nitrones were firstly formed at the beginning of the reaction. Based on
the literature31-33 and experimental results, a possible mechanism was proposed in Scheme 4. Firstly, N-
phenyl hydroxylamine 1a reacted with benzaldehyde 2a to give nitrone 14. PhI(OAc)2 was activated by
BF3ꢀEt2O through coordination to the oxygen atoms of the ligands on iodine,32 and then ligand exchange
between PhI(OAc)2 and TMSCN afforded intermediate 15. Second ligand exchange between 14 and 15
produced intermediate 16, which was attached by AcO- anion to afford intermediate 17. Decomposition
of intermediate 17 gave the intermediate 18, which conducted [3,3] rearrangement to afford isocyanate
19. Intramolecular addition and proton migration produced final product 6a.
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Table 6. Diacetoxyiodobenzene-Promoted Reactions of Nitrones and Trimethylsilyl Cyanidea
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aReactions were carried out on a scale of 3a (0.92 mmol), 4 (1.38 mmol) and 5a (1.84 mmol) in DCM
(5 mL), after stirred for 30 minutes under nitrogen atmosphere, 14 (0.46 mmol) was added. Isolated
yields.
Scheme 4. Plausible Mechanism
CONCLUSIONS
In summary, we have developed the first PhI(OAc)2-promoted one-pot reaction of aromatic
hydroxylamines, aldehydes and TMSCN to give benzimidazolones in the presence of BF3ꢀEt2O. Under
the reaction conditions, aromatic aldehydes bearing different functional groups on their phenyl rings
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could be easily converted into the corresponding products with satisfactory yields, while heterocylic
aldehydes, aliphatic aldehydes and ketones did not work. This novel protocol provided an efficient
method for the construction of benzimidazolones.
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Experimental section
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General methods. All isolated new compounds were characterized on the basis of 1H NMR and 13C
1 13
NMR spectroscopic data and HRMS data. H NMR and C NMR chemical shifts are reported in ppm
using tetramethylsilane (TMS) as an internal standard.
General Procedure for the Synthesis of Compounds 6 from 1, 2, 3a, 4 and 5a. N-
Phenylhydroxylamines 1 (0.46 mmol, 1 equiv) and aldehydes 2 (0.46 mmol, 1 equiv) were mixed in
DCM (5 mL) at room temperature, and stirred overnight for the formation of nitrone. This nitrone-
containing mixture was added into another mixture of PhI(OAc)2 3a (0.92 mmol, 2 equiv), TMSCN 4
(1.38 mmol, 3 equiv) and BF3ꢀEt2O 5a (1.84 mmol, 4 equiv) in DCM, which has been stirred for 30
minutes in another round-bottom flask beforehand under nitrogen atmosphere. After the reaction was
completed, saturated NaHCO3 solution (10 mL) were added to the reaction mixture and stirred for 10
min. The mixture was extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried
(MgSO4) and concentrated. Purification of the residue by silica gel column chromatography using PE :
EA (4:1) as the eluent afforded the products 6.
General Procedure for the Synthesis of Compounds 6 from 14, 3a, 4 and 5a. A mixture of
PhI(OAc)2 3a (0.92 mmol, 2 equiv), TMSCN 4 (1.38 mmol, 3 equiv) and BF3ꢀEt2O 5a (1.84 mmol, 4
equiv) was stirred in DCM (5 mL) for 30 minutes under nitrogen atmosphere, and then, nitrones 14
(0.46 mmol, 1 equiv) were added. After the reaction was completed, saturated NaHCO3 solution (10 mL)
were added to the reaction mixture and stirred for 10 min. The mixture was extracted with CH2Cl2 (3 ×
10 mL). The combined organic layers were dried (MgSO4) and concentrated. Purification of the residue
by silica gel column chromatography using PE : EA (4:1) as the eluent afforded the products 6.
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(2-Oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(phenyl)methyl acetate (6a). White solid; mp 165−166
oC; yield 79.1 mg (61%). 1H NMR (600 MHz, CDCl3) δ 10.06 (s, 1H), 8.07 (s, 1H), 7.43−7.36 (m, 5H),
7.13 (d, J = 7.8 Hz, 1H), 7.04 (td, J = 7.8, 1.2 Hz, 1H), 6.92−6.89 (m, 1H), 6.82 (d, J = 7.8 Hz, 1H),
2.22 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 168.9, 154.9, 134.9, 133.7, 129.0, 128.4, 127.4, 127.1,
122.5, 121.4, 110.6, 110.3, 75.2, 20.7; HRMS (ESI) calcd for C16H14N2O3Na [M + Na]+ 305.0897,
found 305.0894.
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o
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N-acetoxy-N-phenylbenzamide(6a’).34 White solid; mp 53−54 C; yield 41.1 mg (35%). H NMR
(600 MHz, CDCl3) δ 7.53−7.52 (m, 2H), 7.38−7.35 (m, 1H), 7.33−7.25 (m, 7H), 2.18 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ 167.9, 166.8, 140.6, 133.2, 131.0, 129.2, 128.8, 128.4, 128.1, 126.9, 18.4; HRMS
(ESI) calcd for C15H14NO3 [M + H]+ 256.0968, found 256.0970
(2-Oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(o-tolyl)methyl acetate (6b). White solid; mp 144−145
oC; yield 72.2 mg (53%). 1H NMR (600 MHz, CDCl3) δ 10.73 (s, 1H), 8.08 (s, 1H), 7.65−7.64 (m, 1H),
7.30−7.28 (m, 2H), 7.18−7.14 (m, 2H), 7.03 (t, J = 7.2 Hz, 1H), 6.87 (t, J = 7.8 Hz, 1H), 6.82 (d, J = 7.8
13
Hz, 1H), 2.24 (s, 3H), 2.19 (s, 3H); C NMR (150 MHz, CDCl3) δ 168.8, 154.8, 136.4, 132.8, 131.4,
129.1, 128.4, 127.8, 125.9, 125.8, 122.2, 121.3, 110.5, 110.2, 74.9, 20.7, 19.1; HRMS (ESI) calcd for
C17H16N2O3Na [M + Na]+ 319.1053, found 319.1058.
(2-Oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(m-tolyl)methyl acetate (6c). White solid; mp
o
1
154−155 C; yield 108.9 mg (80%). H NMR (600 MHz, CDCl3) δ 10.63 (br, 1H), 8.05 (s, 1H),
7.28−7.21 (m, 3H), 7.15 (d, J = 7.8 Hz, 2H), 7.03 (t, J = 7.8, 1H), 6.90 (t, J = 7.8, 1H), 6.85 (d, J = 7.8
13
Hz, 1H), 2.34 (s, 3H), 2.21 (s, 3H); C NMR (150 MHz, CDCl3) δ 169.0, 155.1, 138.5, 135.0, 129.6,
128.6, 128.4, 127.5, 126.5, 122.9, 122.2, 121.3, 110.8, 110.1, 75.7, 21.5, 20.7; HRMS (ESI) calcd for
C17H16N2O3Na [M + Na]+ 319.1053, found 319.1057.
(2-Oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(p-tolyl)methyl acetate (6d). White solid; mp 191−192
oC; yield 59.9 mg (44%). 1H NMR (600 MHz, CDCl3) δ 10.80 (s, 1H), 8.08 (s, 1H), 7.32 (d, J = 7.8 Hz,
2H), 7.20 (d, J = 7.8 Hz, 2H), 7.17 (d, J = 7.8 Hz, 1H), 7.04 (t, J = 7.8 Hz, 1H), 6.91 (t, J = 7.8 Hz, 1H),
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6.85 (d, J = 7.8 Hz, 1H), 2.35 (s, 3H), 2.22 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.0, 155.1, 138.6,
132.1, 129.3, 128.4, 127.5, 125.8, 122.2, 121.2, 110.8, 110.2, 75.7, 21.1, 20.7; HRMS (ESI) calcd for
C17H16N2O3Na [M + Na]+ 319.1053, found 319.1059.
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(3-Methoxyphenyl)(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl acetate (6e). White solid;
mp 143−144 oC; yield 27.3 mg (19%). 1H NMR (600 MHz, CDCl3) δ 10.88 (s, 1H), 8.07 (s, 1H), 7.29 (t,
J = 7.8 Hz, 1H), 7.16 (d, J = 7.8 Hz, 1H), 7.04−6.98 (m, 3H), 6.91−6.86 (m, 3H), 3.76 (s, 3H), 2.20 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 168.9, 159.8, 155.0, 136.6, 129.8, 128.4, 127.3, 122.2, 121.2, 118.1,
113.8, 112.0, 110.6, 110.2, 75.4, 55.2, 20.6; HRMS (ESI) calcd for C17H16N2O4Na [M + Na]+ 335.1002,
found 335.1007.
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(4-Methoxyphenyl)(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl acetate (6f). White solid;
yellow oil; yield 24.4 mg (17%). 1H NMR (600 MHz, CDCl3) δ 10.03 (s, 1H), 8.00 (s, 1H), 7.33 (d, J =
8.4 Hz, 2H), 7.12 (d, J = 7.8 Hz, 1H), 7.04 (t, J = 7.2 Hz, 1H), 6.93−6.89 (m, 3H), 6.85 (d, J = 7.8 Hz,
1H), 3.80 (s, 3H), 2.20 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.1, 159.9, 154.8, 128.3, 127.5, 127.2,
127.0, 122.2, 121.3, 114.1, 110.9, 110.0, 75.7, 55.3, 20.7; HRMS (ESI) calcd for C17H16N2O4Na [M +
Na]+ 335.1002, found 335.1006.
(2-Chlorophenyl)(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl acetate (6g). White solid; mp
o
1
202−204 C; yield 62.6 mg (43%). H NMR (600 MHz, CDCl3) δ 10.44 (br, 1H), 8.08 (s, 1H),
7.70−7.68 (m, 1H), 7.40−7.38 (m, 1H), 7.36−7.32 (m, 2H), 7.13 (d, J = 7.2, 1H), 7.05 (t, J = 7.2, 1H),
6.94-6.89 (m, 2H), 2.20 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 168.7, 154.6, 133.3, 132.4, 130.5, 128.4,
128.1, 128.0, 126.6, 122.3, 121.3, 110.2, 110.1, 74.5, 20.6; HRMS (ESI) calcd for C16H13ClN2O3Na [M
+ Na]+ 339.0507, found 339.0511.
(4-Chlorophenyl)(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl acetate (6h). White solid; mp
o
1
198−199 C; yield 58.3 mg (40%). H NMR (600 MHz, CDCl3) δ 10.67 (s, 1H), 8.03 (s, 1H), 7.36 (s,
4H), 7.15 (d, J = 7.8 Hz, 1H), 7.05 (t, J = 7.8 Hz, 1H), 6.92 (t, J = 7.8 Hz, 1H), 6.82 (d, J = 8.4 Hz, 1H),
2.21 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 168.9, 154.9, 134.9, 133.7, 129.0, 128.4, 127.4, 127.1,
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122.5, 121.4, 110.6, 110.3, 75.2, 20.7; HRMS (ESI) calcd for C16H13ClN2O3Na [M + Na]+ 339.0507,
found 339.0512.
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(4-Nitrophenyl)(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl acetate (6i). White solid; mp
233−234 oC; yield 94.8 mg (63%). 1H NMR (600 MHz, DMSO-d6) δ 11.21 (s, 1H), 8.26 (d, J = 9.0 Hz,
2H), 7.84 (s, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.03−6.98 (m, 2H), 6.87 (t, J = 7.8 Hz, 1H), 6.74 (d, J = 7.8
Hz, 1H), 2.22 (s, 3H); 13C NMR (150 MHz, DMSO-d6) δ 167.0, 153.1, 147.8, 142.5, 128.7, 127.4, 127.0,
123.9, 122.1, 120.9, 109.7, 109.5, 74.5, 20.4; HRMS (ESI) calcd for C16H13N3O5Na [M + Na]+
350.0747, found 350.0750.
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(2-Nitrophenyl)(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl acetate (6j). White solid; mp
235−237 oC; yield 85.7 mg (57%). 1H NMR (600 MHz, DMSO-d6) δ 11.20 (s, 1H), 8.16 (s, 1H), 8.07 (d,
J = 7.8 Hz, 1H), 7.82 (t, J = 7.2 Hz, 1H), 7.75 (t, J = 7.8 Hz, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.06−7.02
(m, 2H), 6.89 (t, J = 7.2 Hz, 1H), 6.59 (d, J = 7.8 Hz, 1H), 2.14 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
δ 168.8, 152.9, 147.9, 133.6, 131.0, 128.7, 128.5, 128.2, 127.3, 125.4, 122.2, 121.0, 109.6, 109.4, 73.1,
19.9; HRMS (ESI) calcd for C16H13N3O5Na [M + Na]+ 350.0747, found 350.0744.
(4-Cyanophenyl)(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl acetate (6k). White solid; mp
217−218 oC; yield 83.3 mg (59%). 1H NMR (600 MHz, CDCl3) δ 10.57 (s, 1H), 8.08 (s, 1H), 7.71 (d, J
= 8.4 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 7.8 Hz, 1H), 7.08 (t, J = 7.8 Hz, 1H), 6.95 (t, J = 7.8
Hz, 1H), 6.79 (d, J = 7.8 Hz, 1H), 2.25 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 168.7, 154.7, 140.3,
132.6, 128.3, 126.9, 126.8, 122.7, 121.6, 118.1, 113.0, 110.4, 110.3, 74.8, 20.6; HRMS (ESI) calcd for
C17H13N3O3Na [M + Na]+ 330.0849, found 330.0845.
Naphthalen-1-yl(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)methyl acetate (6l). White solid; mp
223−224 oC; yield 73.3 mg (48%). 1H NMR (400 MHz, CDCl3) δ 10.47 (s, 1H), 8.65 (s, 1H), 8.15 (d, J
= 8.0 Hz, 1H), 7.94−7.84 (m, 3H), 7.56−7.44 (m, 3H), 7.13 (d, J = 7.6 Hz, 1H), 7.01−6.97 (m, 2H),
6.88−6.84 (m, 1H), 2.23 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.8, 154.7, 133.9, 130.4, 130.2,
130.1, 128.8, 128.4, 128.0, 127.2, 126.2, 124.5, 124.3, 123.0, 122.2, 121.3, 110.8, 110.1, 74.6, 20.8;
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HRMS (ESI) calcd for C20H16N2O3Na [M + Na]+ 355.1053, found 355.1049.
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(7-Methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(phenyl)methyl acetate (6q). White solid; mp
264−265 oC; yield 73.5 mg (54%). 1H NMR (600 MHz, CDCl3) δ 10.68 (s, 1H), 8.07 (s, 1H), 7.42−7.35
(m, 5H), 6.86 (d, J = 7.8 Hz, 1H), 6.82 (t, J = 7.8 Hz, 1H), 6.67 (d, J = 7.8 Hz, 1H), 2.41 (s, 3H), 2.21 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 169.0, 155.2, 135.2, 128.8, 128.7, 127.5, 127.1, 125.9, 123.4, 121.2,
120.0, 108.3, 75.8, 20.7, 16.2; HRMS (ESI) calcd for C17H16N2O3Na [M + Na]+ 319.1053, found
319.1059.
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(5-Methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(phenyl)methyl acetate (6s). White solid; mp
208−209 oC; yield 88.5 mg (65%). 1H NMR (600 MHz, CDCl3) δ 10.61 (s, 1H), 8.06 (s, 1H), 7.42−7.34
13
(m, 5H), 6.99 (s, 1H), 6.71−6.67 (m, 2H), 2.31 (s, 3H), 2.21 (s, 3H); C NMR (150 MHz, CDCl3) δ
169.0, 155.2, 135.1, 132.1, 128.8, 128.7, 128.6, 125.9, 125.2, 121.9, 110.8, 110.4, 75.7, 21.2, 20.7;
HRMS (ESI) calcd for C17H16N2O3Na [M + Na]+ 319.1053, found 319.1058.
(5-Chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(phenyl)methyl acetate (6v). White solid; mp
198−199 oC; yield 90.3 mg (62%). 1H NMR (600 MHz, CDCl3) δ 10.84 (s, 1H), 8.04 (s, 1H), 7.40−7.37
13
(m, 5H), 7.17 (d, J = 1.8 Hz, 1H), 6.88−6.86 (m, 1H), 6.72 (d, J = 8.4 Hz, 1H), 2.22 (s, 3H); C NMR
(150 MHz, CDCl3) δ 168.9, 155.1, 134.6, 129.3, 129.0, 128.8, 128.0, 126.0, 125.8, 121.4, 111.4, 110.6,
75.6, 20.7; HRMS (ESI) calcd for C16H13ClN2O3Na [M + Na]+ 339.0507, found339.0510.
(5-Bromo-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(phenyl)methyl acetate (6y). White solid; mp
o
1
202−203 C; yield 129.5 mg (78%). H NMR (600 MHz, CDCl3) δ 10.83 (s, 1H), 8.03(s, 1H),
7.40−7.36 (m, 5H), 7.31 (d, J = 1.8 Hz, 1H), 7.02 (dd, J = 8.4, 1.8 Hz, 1H), 6.68 (d, J = 9.0 Hz, 1H),
2.22 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.1, 155.1, 134.8, 129.8, 129.2, 129.0, 126.6, 125.9,
124.4, 115.3, 113.5, 112.0, 75.7, 20.8; HRMS (ESI) calcd for C16H13BrN2O3Na [M + Na]+ 383.0002,
found 382.9999.
(5-Acetyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(phenyl)methyl acetate (6z). White solid; mp
210−211 oC; yield 67.1 mg (45%). 1H NMR (600 MHz, CDCl3) δ 10.87 (s, 1H), 8.09 (s, 1H), 7.81 (d, J
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= 1.2 Hz, 1H), 7.61 (dd, J = 8.4, 1.8 Hz, 1H), 7.45−7.37 (m, 5H), 6.90 (d, J = 8.4 Hz, 1H), 2.56 (s, 3H),
2.25 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 197.0, 168.9, 155.1, 134.5, 131.9, 131.3, 129.1, 128.8,
128.5, 125.8, 122.8, 110.2, 110.1, 75.6, 26.5, 20.6; HRMS (ESI) calcd for C18H16N2O4Na [M + Na]+
347.1002, found 347.1000.
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Ethyl 1-(acetoxy(phenyl)methyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-5-carboxylate (6aa).
White solid; mp 195−196 oC; yield 99.3 mg (61%). 1H NMR (400 MHz, CDCl3) δ 10.93 (s, 1H), 8.09 (s,
1H), 7.88 (s, 1H), 7.70 (dd, J = 8.4, 1.2 Hz, 1H), 7.44−7.38 (m, 5H), 6.89 (d, J = 8.4 Hz, 1H), 4.35 (q, J
= 7.2 Hz, 2H), 2.24 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.9, 166.3, 155.2,
134.6, 131.0, 129.0, 128.8, 128.2, 125.7, 124.7, 123.7, 111.3, 110.1, 75.6, 60.9, 20.6, 14.2; HRMS (ESI)
calcd for C19H18N2O5Na [M + Na]+ 377.1108, found 377.1110.
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(5-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(o-tolyl)methyl acetate (6ad). White solid;
o
1
mp 191−193 C; yield 85.6 mg (60%). H NMR (600 MHz, CDCl3) δ 10.76 (s, 1H), 8.05 (s, 1H),
7.64−7.63 (m, 1H), 7.29−7.27 (m, 2H), 7.17−7.16 (m, 1H), 6.99 (s, 1H), 6.67 (s, 2H), 2.30 (s, 3H), 2.23
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(s, 3H), 2.19 (s, 3H); C NMR (150 MHz, CDCl3) δ 168.8, 155.0, 136.3, 132.9, 132.1, 131.3, 129.1,
128.5, 125.9, 125.8, 125.6, 121.9, 110.7, 110.2, 74.9, 21.2, 20.7, 19.1; HRMS (ESI) calcd for
C18H18N2O3Na [M + Na]+ 333.1210, found 333.1208.
(5-Methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(4-(trifluoromethyl)phenyl)methyl
acetate
(6ae). White solid; mp 206−208 oC; yield 107.2 mg (64%). 1H NMR (600 MHz, CDCl3) δ 10.73 (s, 1H),
8.09 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H), 7.00 (s, 1H), 6.74 (d, J = 8.4 Hz, 1H),
6.68 (d, J = 8.4 Hz, 1H), 2.32 (s, 3H), 2.24 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 168.9, 155.1, 139.2,
132.6, 131.1 (q, JC-F = 31.5 Hz), 128.6, 126.5, 125.7 (q, JC-F = 4.5 Hz), 124.8, 122.8 (q, JC-F = 270 Hz),
122.1, 111.0, 110.1, 75.1, 21.2, 20.6; HRMS (ESI) calcd for C18H15F3N2O3Na [M + Na]+ 387.0927,
found 387.0930.
(5-Chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(4-methoxyphenyl)methyl acetate (6af).
1
yellow oil; yield 49.5 mg (31%). H NMR (600 MHz, CDCl3) δ 9.32 (s, 1H), 7.94 (s, 1H), 7.31 (d, J =
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8.4 Hz, 2H), 7.10 (d, J = 1.8 Hz, 1H), 6.91−6.88 (m, 3H), 6.74 (d, J = 8.4 Hz, 1H), 3.81 (s, 3H), 2.20 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 168.9, 160.1, 154.3, 128.9, 127.9, 127.2, 126.6, 126.2, 121.6, 114.2,
111.6, 110.2, 75.7, 55.3, 20.7; HRMS (ESI) calcd for C17H15ClN2O4Na [M + Na]+ 369.0613, found
369.0610.
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(5-Chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(o-tolyl)methyl acetate (6ag). White solid;
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mp 201−202 C; yield 68.5 mg (45%). H NMR (600 MHz, CDCl3) δ 10.81 (s, 1H), 8.03 (s, 1H), 7.62
(d, J = 6.6 Hz, 1H), 7.33−7.28 (m, 2H), 7.20−7.17 (m, 2H), 6.86 (dd, J = 9.0, 2.4 Hz, 1H), 6.71 (d, J =
9.0 Hz, 1H), 2.23 (s, 3H), 2.21 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 168.7, 154.8, 136.3, 132.4, 131.5,
129.3, 129.2, 127.9, 126.4, 125.9, 125.8, 121.4, 111.2, 110.6, 74.7, 20.7, 19.1; HRMS (ESI) calcd for
C17H15ClN2O3Na [M + Na]+ 353.0663, found 353.0668.
(5-Chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(4-nitrophenyl)methyl acetate (6ah). White
solid; mp 194−195 oC; yield 106.6 mg (64%). 1H NMR (600 MHz, CDCl3) δ 10.56 (s, 1H), 8.26 (d, J =
9.0 Hz, 2H), 8.05 (s, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 1.8 Hz, 1H), 6.92 (dd, J = 8.4, 1.8 Hz,
13
1H), 6.71 (d, J = 8.4 Hz, 1H), 2.27 (s, 3H); C NMR (150 MHz, CDCl3) δ 168.7, 154.7, 148.3, 141.6,
129.2, 128.5, 127.1, 125.4, 124.1, 121.8, 111.0, 110.9, 74.7, 20.6; HRMS (ESI) calcd for
C16H12ClN3O5Na [M + Na]+ 384.0358, found 384.0363.
(5-Chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(4-chlorophenyl)methyl acetate (6ai). White
solid; mp 174−175 oC; yield 117.9 mg (73%). 1H NMR (600 MHz, CDCl3) δ 10.69 (s, 1H), 7.97 (s, 1H),
7.37 (d, J = 9.0 Hz, 2H), 7.34 (d, J = 9.0 Hz, 2H), 7.16 (d, J = 2.4 Hz, 1H), 6.90 (dd, J = 8.4, 2.4 Hz,
13
1H), 6.71 (d, J = 8.4 Hz, 1H), 2.22 (s, 3H); C NMR (150 MHz, CDCl3) δ 168.8, 154.9, 135.1, 133.2,
129.3, 129.1, 128.2, 127.3, 125.7, 121.6, 111.3, 110.7, 75.1, 20.6; HRMS (ESI) calcd for
C16H12Cl2N2O3Na [M + Na]+ 373.0117, found 373.0125.
(5-Chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(2-chlorophenyl)methyl acetate (6aj). White
solid; mp 217−218 oC; yield 82.3 mg (51%). 1H NMR (400 MHz, CDCl3) δ 10.34 (s, 1H), 8.02 (s, 1H),
7.70−7.67 (m, 1H), 7.42−7.35 (m, 3H), 7.14 (s, 1H), 6.91 (d, J = 8.4 Hz, 1H), 6.80 (d, J = 8.8 Hz, 1H),
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2.21 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 168.6, 154.5, 133.2, 132.0, 130.6, 130.5, 129.2, 128.1,
128.0, 126.7, 121.4, 110.9, 110.5, 74.4, 20.6; HRMS (ESI) calcd for C16H12Cl2N2O3Na [M + Na]+
373.0117, found 373.0124.
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(5-Bromo-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(4-bromophenyl)methyl acetate (6ak). White
solid; mp 223−224 oC; yield 125.5 mg (62%). 1H NMR (400 MHz, CDCl3) δ 10.58 (s, 1H), 7.94 (s, 1H),
7.53 (d, J = 6.4 Hz, 2H), 7.31−7.26 (m, 3H), 7.05 (dd, J = 8.0, 1.6 Hz, 1H), 6.67 (d, J = 8.4 Hz, 1H),
2.22 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 168.8, 154.7, 133.8, 132.0, 129.5, 127.6, 126.1, 124.4,
123.3, 115.4, 113.5, 111.7, 75.1, 20.6; HRMS (ESI) calcd for C16H12Br2N2O3Na [M + Na]+ 460.9107,
found 460.9111.
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(5-Bromo-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(2-fluorophenyl)methyl acetate (6al). White
o
1
solid; mp 245−246 C; yield 94.1 mg (54%). H NMR (400 MHz, DMSO-d6) δ 11.35 (s, 1H), 7.86 (s,
1H), 7.67 (t, J = 7.6 Hz, 1H), 7.50−45 (m, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.25−7.20 (m, 1H), 7.15 (d, J =
2.0 Hz, 1H), 7.06 (dd, J = 8.4, 1.6 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 2.20 (s, 3H); 13C NMR (100 MHz,
DMSO-d6) δ 168.7, 159.3 (d, JC-F = 369.0 Hz), 152.4, 131.5 (d, JC-F = 13.5 Hz), 130.1, 127.9 (d, JC-F
=
3.0 Hz), 126.7, 124.6 (d, JC-F = 6.0 Hz), 123.4, 122.0 (d, JC-F = 16.5 Hz), 116.1 (d, JC-F = 31.5 Hz),
113.8, 112.0, 110.9, 71.5, 20.3; HRMS (ESI) calcd for C16H12BrFN2O3Na [M + Na]+ 400.9908 found
400.9913.
General Procedure for the Synthesis of Compound 10. Compound 6a (0.18 mmol, 1 equiv) was
dissolved in isopropanol (5 mL), and then concentrated hydrochloric acid (0.72 mmol, 4 equiv) was
added. The reaction mixture was stirred at 70 °C for 1 h, and then cooled to room temperature. Ethyl
acetate (5 mL) and aqueous sodium hydroxide solution were added and stirred for another 30 min. The
organic layer was separated, dried and evaporated under reduced pressure. Pure compound 10 as white
solid was produced via recrystallization in isopropanol (5 mL).
o
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1H-Benzo[d]imidazol-2(3H)-one (10).35 White solid; >312 C; yield 18.3 mg (76%). H NMR (400
13
MHz, DMSO-d6) δ 10.56 (s, 2H), 6.90 (s, 4H); C NMR (150 MHz, DMSO-d6) δ 155.7, 130.1, 120.8,
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108.9.
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General Procedure for the Synthesis of Compound 11. A mixture of 6a (0.32 mmol, 1 equiv),
benzyl bromide (0.48 mmol, 1.5 equiv), potassium carbonate (0.26 mmol, 0.8 equiv), and DMF (6 mL)
was stirred at room temperature overnight. Water (10 mL) was added. The mixture was extracted with
ethyl acetate (2 × 6 mL). The organic layer was dried (MgSO4) and concentrated. Purification of the
residue by silica gel column chromatography using PE : EA (6:1) as the eluent afforded the product 11.
(3-Benzyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)(phenyl)methyl acetate (11). White solid; mp
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141−142 C; yield 72.6 mg (61%). H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.43−7.25 (m, 10H),
6.96 (td, J = 7.6, 1.2 Hz, 1H), 6.90−6.81 (m, 3H), 5.10 (d, J = 2.0 Hz, 2H), 2.20 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 168.8, 153.5, 136.0, 135.2, 129.6, 128.8, 128.7, 128.6, 127.7, 127.5, 126.7, 125.9, 121.9,
121.4, 110.6, 108.5, 76.3, 45.0, 20.7; HRMS (ESI) calcd for C23H20N2O3Na [M + Na]+ 395.1366, found
395.1362.
General Procedure for the Synthesis of Compound 12. Compound 11 (0.13 mmol, 1 equiv) was
dissolved in THF (5 mL), and concentrated hydrochloric acid (2.5 mL) was added. The reaction mixture
was stirred at 70 °C for 1 h. After cooling of the solution, ethyl acetate (5 mL) and aqueous sodium
hydroxide solution were added and stirred for 30 min. The organic layer was dried (MgSO4) and
concentrated. Purification of the residue by silica gel column chromatography using PE : EA (1.5:1) as
the eluent afforded the product 12.
1-Benzyl-1H-benzo[d]imidazol-2(3H)-one (12).36 White solid; mp 211−213 oC; yield 23.3 mg (80%).
1H NMR (600 MHz, DMSO-d6) δ 10.95 (s, 1H), 7.34−7.31 (m, 4H), 7.27−7.24 (m, 1H), 7.02−6.93 (m,
13
4H), 5.00 (s, 2H); C NMR (150 MHz, DMSO-d6) δ 159.6, 142.4, 135.2, 133.8, 133.5, 132.5, 126.2,
125.7, 114.0, 113.3, 48.4; HRMS (ESI) calcd for C14H12N2ONa [M + Na]+ 247.0842, found 247.0838.
General Procedure for the Synthesis of Compound 13. Compound 6c (0.17 mmol, 1 equiv) and p-
toluenesulfonic acid (0.20 mmol, 1.2 equiv) were added into EtOH (5 mL). The reaction mixture was
stirred at reflux temperature for 1 h. After cooling of the solution, the residue was purified by silica gel
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column chromatography using PE : EA (15:1) as eluent to give the product 13.
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3
o
1-(Ethoxy(m-tolyl)methyl)-1H-benzo[d]imidazol-2(3H)-one (13). White solid; mp 120−121 C; yield
4
5
6
1
39.3 mg (82%). H NMR (600 MHz, CDCl3) δ 10.48 (s, 1H), 7.33−7.30 (m, 2H), 7.25−7.21 (m, 1H),
7
8
9
7.13−7.10 (m, 2H), 7.03−7.00 (m, 1H), 6.93 (d, J = 7.8 Hz, 1H), 6.89 (t, J = 7.8 Hz, 1H), 6.76 (s, 1H),
3.76−3.71 (m, 1H), 3.68-3.63 (m, 1H), 2.33 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz,
CDCl3) δ 156.3, 138.1, 137.5, 129.1, 128.3, 128.1, 127.7, 126.8, 123.2, 121.8, 121.3, 111.6, 109.6, 82.4,
64.2, 21.5, 14.8; HRMS (ESI) calcd for C17H18N2O2Na [M + Na]+ 305.1260, found 305.1258.
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
Copies of the 1H NMR, 13C NMR and HRMS spectra of 6, 10, 11, 12, 13 and crystallography of 6a
(PDF).
Crystallographic date for 6a (CIF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: huyl@nwnu.edu.cn.
Notes
The authors declare no competing financial interest.
Acknowledgment.
We are thankful for financial support from the National Natural Science Foundation of China (Grant No.
21462037 and 21362033); Key Laboratory Polymer Materials of Gansu Province (Northwest Normal
University); Bioactive Product Engineering Research Center for Gansu Distinctive Plants; and State
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Key Laboratory of Applied Organic Chemistry, Lanzhou University.
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