I2-Mediated Intramolecular C-H Amidation for the Synthesis of N-Substituted Benzimidazoles

Article abstract of DOI:10.1021/acs.joc.7b00142

A practical intramolecular C-H amidation methodology has been developed using molecular iodine under basic conditions. The required imine substrates were readily obtained by condensation of simple o-phenylenediamine derivatives and aldehydes. The transition-metal-free cyclization reaction described here works well with crude imines and allows for the sequential synthesis of N-protected benzimidazoles without purification of the less stable condensation intermediates. This operationally simple synthetic approach is broadly applicable to a variety of aromatic, aliphatic, and cinnamic aldehydes to produce diverse 1,2-disubstituted benzimidazole derivatives in an efficient and scalable fashion.

Full text of DOI:10.1021/acs.joc.7b00142

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Article
I2-Mediated Intramolecular C–H Amidation for
the Synthesis of N-Substituted Benzimidazoles
Zhiyuan Hu, Ting Zhao, Manman Wang, Jie Wu, Wenquan Yu, and Junbiao Chang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b00142 • Publication Date (Web): 24 Feb 2017
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I2ꢀMediated Intramolecular C–H Amidation for the Synthesis of
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NꢀSubstituted Benzimidazoles
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Zhiyuan Hu, Ting Zhao, Manman Wang, Jie Wu, Wenquan Yu,* and Junbiao Chang*
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College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, Henan
Province 450001, People's Republic of China
Abstract: A practical intramolecular C–H amidation methodology has been
developed using molecular iodine under basic conditions. The required imine
substrates were readily obtained by condensation of simple oꢀphenylenediamine
derivatives and aldehydes. The transition metalꢀfree cyclization reaction described
here works well with crude imines, and allows for the sequential synthesis of
Nꢀprotected benzimidazoles without purification of the less stable condensation
intermediates. This operationally simple synthetic approach is broadly applicable to a
variety of aromatic, aliphatic, and cinnamic aldehydes to produce diverse
1,2ꢀdisubstituted benzimidazole derivatives in an efficient and scalable fashion.
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ꢀ Introduction
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C−N bond formation via direct oxidative coupling of C‒H and N‒H bonds features
atomꢀ and stepꢀeconomy, and has received considerable attention in recent years.
Such transformations have been successfully achieved through transition
metalꢀcatalyzed1 and hypervalent iodineꢀmediated C‒H amination.2 Alternatively,
molecular iodine, commercially available, inexpensive, and ecoꢀfriendly, was widely
used as the sole oxidant for the oxidative C‒N bond construction.3 In particular, a
number of I2ꢀmediated amination reactions have been developed for the construction
of nitrogenꢀcontaining heterocyclic skeletons.3c, 4 However, examples of the formation
of a C−N bond through direct C‒H amidation has been reported only rarely,4d, 5
probably due to the weak nucleophilicity of the nitrogen in the amide substrates. As a
continuation of our previous work,3c, 4c we describe such an intramolecular method for
benzimidazole synthesis (Scheme 1).
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Scheme 1. Proposed route for direct synthesis of Nꢀprotected benzimidazoles
through C‒H amidation based on previously reported C‒H amination reactions
Benzimidazole is a privileged structural unit present in many biologically active
compounds.6 Among these, Nꢀprotected benzimidazole derivatives possess important
pharmaceutical properties (Figure 1). For example, Nꢀnitrobenzenesulfonyl
benzimidazole 4 can inhibit HBV DNA replication in vitro with low cytotoxicity7 and
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5ꢀbromobenzimidazoles such as 5 exhibit significant activity against the H37Rv strain
of mycobacterium tuberculosis.8 NꢀPhenylsulfonylꢀ5ꢀaminobenzimidazoles 6 display
moderate to good antiꢀinflammatory and analgesic activity in animal models9 and the
Nꢀisopropoxycarbonyl derivative 7 is an moderate antiviral agent which inhibits
replication of coxsackie virus B2.10 Nevertheless, of the numerous methods
established for benzimidazole synthesis,11 only a few provide direct access to
Nꢀprotected benzimidazoles.12,13 In 2011, Zeng12a reported the synthesis of Nꢀtosyl
benzimidazoles by PdCl2ꢀcatalyzed intramolecular sulfonamidation and oxidation of
imines employing PhI(OAc)2 as the oxidant. Subsequently, Mal12b achieved an
iodine(III)ꢀmediated cyclization reaction in the absence of a palladium catalyst. In
2013, Punniyamurthy2c synthesized a series of 1,2ꢀdisubstituted benzimidazoles
through mCPBA/PhIꢀmediated oxidative cyclization of N',N''ꢀdisubstituted amidines.
In this paper, we report a sequential approach to the synthesis of Nꢀprotected
benzimidazoles via I2ꢀmediated direct C–H amidation, omitting purification of the
less stable imine intermediates.
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Figure 1. Representative biologically active Nꢀprotected benzimidazoles.
ꢀ Results and Discussion
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The imine intermediate 3a necessary for benzimidazole synthesis can be readily
prepared by the condensation of Nꢀtosylꢀ1,2ꢀphenylenediamine (2a) with
benzaldehyde in EtOH at the reflux temperature (Table 1). In view of the poor
stability of imines, we initially investigated the I2ꢀmediated oneꢀpot synthesis without
isolation of 3a in the absence of base,4e which only resulted in the trace amount of the
benzimidazole 1a (entry 1). Upon completion of the firstꢀstep condensation, the
reaction mixture was treated directly with molecular iodine and K2CO3 in sequence,
which gave the desired product in 7% yield (entry 2). We continued to optimize the
reaction conditions using the crude imine 3a obtained by removing the EtOH under
reduced pressure. Screening demonstrated that CH2Cl2 is the optimal solvent for the
second annulation step and 1.2 equiv. of the oxidant is sufficient for the
transformation. In the presence of K2CO3, the I2ꢀpromoted oxidative cyclization of
crude 3a at room temperature was completed within 1 h, affording product 1a in 90%
overall yield (entry 7). With weaker (entry 9) or organic bases (entry 10), yields of the
expected benzimidazole were significantly reduced. Moreover, oneꢀpot reaction of 2a
and benzaldehyde in either EtOH or CH2Cl2 also formed the expected product 1a, but
in lower yields (entries 11−12).
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Table 1. Reaction Conditions Optimization for the Synthesis of 1ꢀTosyl
Benzimidazole 1a.
entry I2 (equiv.)
1c
1.2
base
–
solvent
EtOH
temp. timea yieldb
reflux 6 h trace
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1.2
1.2
1.2
1.2
1.0
1.2
1.4
1.2
1.2
1.2
1.2
K2CO3
K2CO3
EtOH
reflux 1.5 h
rt 2 h
7%
MeCN
63%
51%
78%
86%
90%
90%
49%
43%
38%
82%
4
K2CO3 1,4ꢀdioxane 60 °C 1 h
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5
K2CO3
K2CO3
K2CO3
K2CO3
NaHCO3
DBU
toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
EtOH
rt
rt
rt
rt
rt
rt
2 h
2 h
1 h
1 h
1 h
1 h
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7d
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9
10
11c
12c
K2CO3
reflux 4 h
rt 1 h
K2CO3
CH2Cl2
aReaction time for the cyclization step. Isolated yields are given. The reaction mixture was
directly treated with iodine and then heated to reflux. Optimal reaction conditions: 1) 2a (0.5
b
c
d
mmol), PhCHO (0.55 mmol), EtOH, reflux; 2) iodine (0.6 mmol), K2CO3 (1.5 mmol), CH2Cl2, rt.
Having established the optimal reaction conditions, we sought to probe the
substrate scope and the generality of this synthetic approach. A range of aromatic
aldehydes were subjected to these sequential synthesis conditions (Scheme 2) and all
were smoothly transformed into the expected benzimidazoles by condensation with
Nꢀtosylꢀoꢀphenylenediamine (2a) followed by I2ꢀmediated intramolecular C–H
amidation. Using the synthesis of product 1e as an example, the reaction was
successfully conducted on the gram scale. This method is compatible with either
electronꢀdonating groups (EDG) or electronꢀwithdrawing groups (EWG) at the para,
meta, and ortho positions of the phenyl ring of the aldehydes (1a–1l). The good
functional group tolerance allows for the presence of a phenolic hydroxy group in the
substrate, as in 1d. 2,4,6ꢀTrimethylbenzaldehyde was efficiently cyclized to the
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expected product (1l), whose structure was confirmed by Xꢀray crystallography14 (see
Supporting Information). 2ꢀPyridylꢀ (1m) and 1ꢀnaphthylꢀsubstituted benzimidazoles
(1n) were prepared from the corresponding aldehydes in excellent yields.
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Scheme 2. Scope of Aromatic Aldehydes (ArCHO)a
aOptimal reaction conditions: 1) 2a (0.5 mmol), ArCHO (0.55 mmol), EtOH, reflux; 2) iodine (0.6
mmol), K2CO3 (1.5 mmol), CH2Cl2, rt (isolated yields are given). The yield of gramꢀscale
b
synthesis (4 mmol) is given in parentheses.
Encouraged by the successful synthesis of Nꢀtosylꢀ2ꢀaryl benzimidazoles, we
continued to explore the substrate scope of nonꢀaromatic aldehydes (Scheme 3) and
found that both cinnamic and aliphatic aldehydes were converted into the deisred
products through the reaction with the oꢀphenylenediamine derivative 2a under the
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optimal reaction conditions. It is worth to mention that benzimidazole 1o could be
used as a substrate for aza Michaelꢀtype addition, which was previously prepared
from a Bocꢀprotected precursor over three steps.15 Condensation of ethyl glyoxylate
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with 2a followed by I2ꢀmediated oxidative cyclization afforded
2ꢀcarbethoxylꢀsubstituted benzimidazole 1t.
a
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Scheme 3. Scope of NonꢀAromatic Aldehydes (R2CHO)a
aOptimal reaction conditions: 1) 2a (0.5 mmol), R2CHO (0.55 mmol), EtOH, reflux; 2) iodine (0.6
b
mmol), K2CO3 (1.5 mmol), CH2Cl2, rt (isolated yields are given). Anhydrous CH2Cl2 was used.
c1.5 mmol of the aldehyde was used.
The scope of oꢀphenylenediamine derivatives was also examined (Scheme 4), and it
was found that substrates bearing both EDGs and EWGs were transformed into the
expected benzimidazoles (1u–w). Notably, even the nitroꢀsubstituted substrate (2u)
was cyclized into the corresponding product in 90% yield. Furthermore, a variety of
benzimidazoles bearing different Nꢀprotecting groups (1x–ad) and no Nꢀsubstituents
(1ae–ah) were successfully synthesized from the corresponding oꢀphenylenediamine
derivatives. The relatively lower yield of the antiviral agent 710 might be caused by
the side reactions of the methylthio moiety, as both its 2ꢀphenyl (1aa) and 2ꢀpyridyl
analogs (1ab) were obtained in satisfactory yields.
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Scheme 4. Scope of oꢀPhenylenediamine Derivatives 2a
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NH2
N
1) R2CHO, EtOH, reflux
2) I2, K2CO3, CH2Cl2, rt
R1
R1
R2
N
PG
NH
PG
2
1
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Me
N
Br
Br
N
N
N
Ts
N
N
O2N
Me
Ts
Ts
1w
, 96%
b
1u
1v
, 99%
, 90%
N
N
N
N
N
N
O
S
Ph
Ph
OtBu
1z
, 70%
O
O
O
c
1x, 95%
1y
, 90%
SMe
N
N
N
N
N
N
N
OiPr
OiPr
OiPr
O
O
O
1ab, 87%c
1aa, 85%c
7, 33%
N
N
N
N
N
Ph
1ad, 91%
N
Me
1ac, 97%
H
1ae, 90%
Me
Me
Br
Br
N
N
N
N
N
N
H
1af, 88%
H
H
1ag, 93%
1ah, 86%
aOptimal reaction conditions: 1) 2 (0.5 mmol), PhCHO (0.55 mmol), EtOH, reflux; 2) iodine (0.6
mmol), K2CO3 (1.5 mmol), CH2Cl2, rt (isolated yields are given). bThe reaction was performed at
reflux temperature in CH2Cl2. cThe reaction was performed at reflux temperature in
1,2ꢀdichloroethane (DCE).
Based on these experimental results along with our previous work of I2ꢀmediated
C–H amination,3c, 4c a tentative reaction mechanism for this intramolecular C–H
amidation reaction is proposed (Scheme 5). Taking the formation of 1a as an example,
condensation of 2a and benzaldehyde formed imine 3a (path a), of which the
1
structure has been confirmed by H and 13C NMR. Then the iodineꢀmediated
iodocyclization of intermediate 3a generates a plausible iodo species C. Finally, the
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subsequent elimination of one molecule of HI promoted by base produces the
benzimidazole framework 1a. Another possible intermediate 3a' (path b) was not
observed, probably because the presence of Nꢀsulfonyl group reduces the
nucleophilicity of the nitrogen in intermediate A.16
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Scheme 5. Proposed Mechanism for the Formation of 1ꢀTosyl Benzimidazole 1a
via I2ꢀMediated C–H Amidation
ꢀ Conclusion
We have established a practical and transition metalꢀfree intramolecular C–H
amidation reaction using molecular iodine as the sole oxidant. The sequential
synthetic approach described here is operationally simple and requires no isolation of
the less stable imine intermediates. Under the optimal cyclization conditions, crude
imines obtained from readily available oꢀphenylenediamine derivatives and aldehydes
were directly cyclized into Nꢀprotected benzimidazoles. This versatile methodology is
broadly applicable to a variety of aromatic, aliphatic, and cinnamic aldehydes, and
provides facile access to diverse 1,2ꢀdisubstituted benzimidazole derivatives in an
efficient and scalable fashion.
ꢀ Experimental Section
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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 parts per million
(ppm) relative to the internal standard, tetramethylsilane (TMS). 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; tt,
triplet of triplets. The coupling constants (J) are reported in Hertz (Hz). Melting
points were determined on a micromelting point apparatus and are uncorrected.
Infrared (IR) spectra were obtained on an FTꢀIR spectrometer. Highꢀresolution mass
spectra (HRMS) were obtained on a TOFꢀQ mass spectrometer equipped with an
electrospray ion source (ESI) and operated in the positive mode. Flash column
chromatography was performed over 200‒300 mesh silica gel and the solvents were
distilled prior to use. EtOH, for the firstꢀstep condensation, was analytical reagent
(AR) grade and used was without any pretreatment. CH2Cl2 and 1,2ꢀdichloroethane
(DCE), used in the sequential oxidative cylization, were dried over 4 Å molecular
sieves (for the synthesis of 1p–r, CH2Cl2 was distilled from calcium hydride) prior to
use.
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General Procedure for the Synthesis of NꢀSubstituted Benzimidazoles 1. A
mixture of oꢀphenylenediamine derivative (2, 0.5 mmol) and the corresponding
aldehyde (0.55 mmol) in EtOH (6 mL) was refluxed for 1 h. Then the solvent was
evaporated under reduced pressure to give the crude imine 3 [The structure of 3a was
1
characterized by NMR: H NMR (400 MHz, CDCl3): δ 8.19 (s, 1H), 7.79ꢀ7.77 (m,
1H), 7.72 (s, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.0 Hz, 2H), 7.53ꢀ7.47 (m,
3H), 7.21 (t, J = 8.0 Hz, 1H), 7.09 (t, J = 8.0 Hz, 1H), 7.04ꢀ7.02 (m, 2H), 2.26 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 159.6, 143.5, 140.9, 136.1, 135.6, 132.3, 132.1, 129.4,
129.0, 128.9, 127.7, 127.1, 125.4, 121.2, 116.9, 21.5], which was redissolved in
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CH2Cl2 (6 mL), followed by the sequential addition of iodine (152 mg, 0.6 mmol) and
K2CO3 (207 mg, 1.5 mmol). The reaction mixture was stirred at room temperature
(for the synthesis of 1u, the reaction was performed in CH2Cl2 at reflux temperature;
for 1y and 1aa–ab in DCE at reflux temperature) for the indicated time. Upon
completion of the reaction, it was quenched with 5% Na2S2O3 (15 mL), and then
extracted with CH2Cl2 (10 mL × 3). The combined organic layer was washed with
brine (20 mL), dried over anhydrous Na2SO4, concentrated, and then purified through
silica gel column chromatography to afford the desired product 1.
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2ꢀPhenylꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1a).17 1 h; eluent: EtOAc/petroleum
1
ether (PE) 5:95; yield: 156 mg, 90%; white solid, mp 103 ºC; H NMR (400 MHz,
CDCl3): δ 8.21 (d, J = 8.0 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.61 (d, J = 7.2 Hz, 2H),
7.55 (t, J = 7.2 Hz, 1H), 7.48ꢀ7.37 (m, 4H), 7.33 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 8.0
Hz, 2H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.1, 145.7, 142.6, 135.0,
133.9, 130.9, 130.5, 130.0, 129.7, 127.7, 127.0, 125.5, 125.3, 120.4, 115.2, 21.6; IR
(film) 3056(w), 1597(w), 1449(w), 1387(m), 1176(s), 1119(m), 1083(m), 1010(w),
816(w), 768(m), 740(vs), 701(s), 668(s); HRMS (m/z) [M + H]+ calcd for
C20H17N2O2S 349.1005, found 349.1005.
2ꢀ(pꢀTolyl)ꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1b). 1 h; eluent: EtOAc/PE 5:95; yield:
162 mg, 90%; white solid, mp 127ꢀ128 ºC; 1H NMR (400 MHz, CDCl3): δ 8.20ꢀ8.18
(m, 1H), 7.72ꢀ7.70 (m, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.44ꢀ7.33 (m, 4H), 7.28ꢀ7.26 (m,
2H, overlapped with the peak of chloroform), 7.09 (d, J = 8.4 Hz, 2H), 2.47 (s, 3H),
2.32 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 154.4, 145.6, 142.7, 140.8, 135.0, 133.9,
130.8, 129.7, 128.4, 127.1, 127.0, 125.31, 125.27, 120.3, 115.2, 21.7, 21.6; IR (film)
2921(w), 1596(w), 1497(w), 1445(w), 1374(s), 1253(w), 1174(vs), 1118(w), 1062(m),
996(m), 823(m), 805(m), 767(s), 757(s), 703(w), 669(s); HRMS (m/z) [M + H]+ calcd
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for C21H19N2O2S 363.1162, found 363.1151.
2ꢀ(4ꢀMethoxyphenyl)ꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1c).12b 0.5 h; eluent:
7
8
1
EtOAc/PE 15:85; yield: 178 mg, 94%; white solid, mp 132ꢀ133 ºC; H NMR (400
9
MHz, CDCl3): δ 8.20ꢀ8.18 (m, 1H), 7.71ꢀ7.68 (m, 1H), 7.61ꢀ7.57 (m, 2H), 7.43ꢀ7.35
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(m, 2H), 7.31 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 7.00ꢀ6.97 (m, 2H), 3.91 (s,
13
3H), 2.31 (s, 3H); C NMR (100 MHz, CDCl3): δ 161.5, 154.3, 145.6, 142.8, 134.9,
134.0, 132.5, 129.7, 126.9, 125.3, 125.2, 122.2, 120.2, 115.3, 113.1, 55.4, 21.6; IR
(film) 2966(w), 1609(w), 1494(m), 1441(w), 1376(s), 1304(m), 1251(m), 1175(vs),
1117(w), 1063(m), 1010(m), 833(s), 807(w), 769(s), 750(m), 704(w), 676(s); HRMS
(m/z) [M + H]+ calcd for C21H19N2O3S 379.1111, found 379.1104.
4ꢀ(1ꢀTosylꢀ1Hꢀbenzo[d]imidazolꢀ2ꢀyl)phenol (1d). 1 h; eluent: EtOAc/PE 25:75;
yield: 130 mg, 71%; light brown solid, mp 163ꢀ164 ºC; 1H NMR (400 MHz, CDCl3):
δ 8.22 (d, J = 7.6 Hz, 1H), 7.74 (d, J = 7.2 Hz, 1H), 7.47ꢀ7.37 (m, 4H), 7.30 (d, J =
8.0 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.74 (d, J = 8.4 Hz, 2H), 2.30 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 159.1, 154.7, 145.9, 141.6, 134.8, 133.7, 132.6, 129.7, 127.1,
125.50, 125.49, 120.5, 119.7, 115.4, 115.1, 21.6; IR (film) 1594(w), 1486(w),
1452(w), 1386(m), 1274(m), 1179(s), 1128(w), 1083(m), 837(m), 809(w), 745(s),
675(vs); HRMS (m/z) [M + H]+ calcd for C20H17N2O3S 365.0954, found 365.0948.
2ꢀ(4ꢀChlorophenyl)ꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1e). 1 h; eluent: EtOAc/PE
95:5; yield: 171 mg, 90% (0.5 mmol scale); 1.35 g, 88% (4 mmol scale); white solid,
1
mp 138ꢀ139 ºC (lit.18 mp 140ꢀ141 ºC); H NMR (400 MHz, CDCl3): δ 8.21ꢀ8.19 (m,
1H), 7.73ꢀ7.71 (m, 1H), 7.58 (dt, J = 8.4, 2.4 Hz, 2H), 7.46ꢀ7.38 (m, 4H), 7.33 (d, J =
8.4 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
153.0, 145.9, 142.6, 136.9, 134.9, 133.9,132.2, 129.8, 128.5, 128.0, 126.9, 125.7,
125.5, 120.5, 115.2, 21.7; IR (film) 1596(w), 1480(w), 1453(w), 1373(s), 1304(w),
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1175(s), 1116(w), 1092(m), 1063(s), 1013(m), 994(m), 834(m), 808(m), 758(s),
702(w), 666(vs); HRMS (m/z) [M + H]+ calcd for C20H16ClN2O2S 383.0616, found
383.0603.
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2ꢀ(4ꢀFluorophenyl)ꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1f). 2 h; eluent: EtOAc/PE
10
11
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1
10:90; yield: 168 mg, 92%; white solid, mp 118ꢀ119 ºC (lit.12b mp 118ꢀ120 ºC); H
NMR (400 MHz, CDCl3): δ 8.20 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 7.2 Hz, 1H),
7.64ꢀ7.60 (m, 2H), 7.46ꢀ7.38 (m, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.18ꢀ7.09 (m, 4H),
2.32 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 164.3 (d, JCꢀF = 249.8 Hz), 153.1, 145.9,
142.5, 134.9, 133.9, 133.0 (d, JCꢀF = 8.7 Hz), 129.8, 126.9, 126.1 (d, JCꢀF = 3.4 Hz),
125.6, 125.4, 120.4, 115.2, 115.0 (d, JCꢀF = 21.9 Hz), 21.6; IR (film) 1593(w),
1494(m), 1447(w), 1372(m), 1303(w), 1223(m), 1175(s), 1158(m), 1117(m), 1060(s),
997(m), 840(s), 798(s), 756(vs), 703(w), 668(s); HRMS (m/z) [M + H]+ calcd for
C20H16FN2O2S 367.0911, found 367.0905.
4ꢀ(1ꢀTosylꢀ1Hꢀbenzo[d]imidazolꢀ2ꢀyl)benzonitrile (1g). 0.5 h; eluent: EtOAc/PE
1
15:85; yield: 180 mg, 96%; white solid, mp 147ꢀ149 ºC (lit.12b mp 146ꢀ148 ºC); H
NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8.0 Hz, 1H), 7.78 (s, 4H), 7.74 (d, J = 7.6 Hz,
1H), 7.50ꢀ7.40 (m, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 2.34 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 151.9, 146.2, 142.6, 134.7, 134.6, 133.8, 131.6,
131.4, 130.0, 126.8, 126.2, 125.7, 120.8, 118.3, 115.2, 114.2, 21.7; IR (film) 2231(w),
1599(w), 1495(w), 1448(w), 1382(m), 1303(w), 1174(s), 1119(w), 1070(m), 1005(w),
852(s), 807(w), 748(s), 676(vs); HRMS (m/z) [M + H]+ calcd for C21H16N3O2S
374.0958, found 374.0952.
2ꢀ(4ꢀNitrophenyl)ꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1h). 1.5 h; eluent: EtOAc/PE
1
15:85; yield: 185 mg, 94%; yellow solid, mp 168ꢀ170 ºC; H NMR (400 MHz,
CDCl3): δ 8.34 (d, J = 8.8 Hz, 2H), 8.20 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 8.8 Hz, 2H),
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7.75 (d, J = 7.6 Hz, 1H), 7.51ꢀ7.41 (m, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4
Hz, 2H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 151.6, 149.0, 146.3, 142.6,
136.3, 134.7,133.8, 132.0, 130.0, 126.8, 126.3, 125.8, 122.8, 120.8, 115.1, 21.7; IR
(film) 1599(w), 1515(m), 1450(w), 1381(m), 1350(s), 1275(w), 1172(s), 1122(w),
1076(m), 1011(w), 855(s), 812(m), 747(m), 701(w), 670(vs); HRMS (m/z) [M + H]+
calcd for C20H16N3O4S 394.0856, found 394.0852.
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1ꢀTosylꢀ2ꢀ(3ꢀ(trifluoromethyl)phenyl)ꢀ1Hꢀbenzo[d]imidazole (1i). 0.5 h; eluent:
1
EtOAc/PE 5:95; yield: 197 mg, 95%; white solid, mp 62ꢀ63 ºC; H NMR (400 MHz,
CDCl3): δ 8.23 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H),
7.75 (d, J = 7.6 Hz, 1H), 7.71 (s, 1H), 7.63 (t, J = 8.0 Hz, 1H), 7.50ꢀ7.41 (m, 2H),
7.30 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 2.34 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 152.2, 146.2, 142.4, 134.9, 134.4, 133.9, 130.9, 130.3 (q, JCꢀF = 32.7 Hz),
129.9, 128.3, 127.5 (q, JCꢀF = 3.8 Hz), 127.2 (q, JCꢀF = 3.7 Hz), 126.9, 126.0, 125.5,
123.7 (q, JCꢀF = 271.1 Hz), 120.6, 115.1, 21.6; IR (film) 1597(w), 1431(w), 1384(m),
1335(s), 1300(w), 1269(m), 1230(w), 1174(s), 1117(s), 1074(m), 1035(w), 908(w),
855(w), 813(m), 742(m), 702(vs), 674(m); HRMS (m/z) [M + H]+ calcd for
C21H16F3N2O2S 417.0879, found 417.0871.
2ꢀ(2ꢀChlorophenyl)ꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1j). 1.5 h; eluent: EtOAc/PE
1
5:95; yield: 176 mg, 92%; white solid, mp 145ꢀ146 ºC (lit.17 mp 147ꢀ148 ºC); H
NMR (400 MHz, CDCl3): δ 8.16 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.53 (d,
J = 8.4 Hz, 2H), 7.50ꢀ7.45 (m, 3H), 7.43ꢀ7.37 (m, 3H), 7.19 (d, J = 8.0 Hz, 2H), 2.37
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 149.6, 146.0, 142.3, 135.2, 135.0, 132.9,
132.3, 131.6, 130.0, 129.9, 129.4, 127.4, 126.0, 125.7, 125.0, 120.8, 114.2, 21.7; IR
(film) 1596(w), 1450(w), 1366(s), 1251(w), 1174(s), 1126(m), 1088(m), 1054(m),
806(m), 766(vs), 749(s), 678(s); HRMS (m/z) [M + H]+ calcd for C20H16ClN2O2S
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383.0616, found 383.0613.
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2ꢀ(2,4ꢀDichlorophenyl)ꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1k). 1.5 h; eluent:
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8
1
EtOAc/PE 10:90; yield: 207 mg, 99%; white solid, mp 139ꢀ140 ºC; H NMR (400
9
MHz, CDCl3): δ 8.15 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.54ꢀ7.51 (m, 3H),
7.49ꢀ7.35 (m, 4H), 7.21 (d, J = 8.4 Hz, 2H), 2.37 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 148.6, 146.2, 142.2, 137.2, 136.1, 134.9, 133.1, 132.9, 130.0, 129.4, 128.6,
127.3, 126.5, 125.9, 125.2, 120.8, 114.2, 21.7; IR (film) 1596(w), 1446(w), 1381(m),
1307(w), 1280(w), 1245(w), 1176(vs), 1123(m), 1085(m), 1051(m), 1013(w), 823(m),
785(m), 770(w), 753(w), 743(m), 669(s); HRMS (m/z) [M + H]+ calcd for
C20H15Cl2N2O2S 417.0226, found 417.0213.
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2ꢀMesitylꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1l).12b 1 h; eluent: EtOAc/PE 10:90;
yield: 179 mg, 92%; white solid, mp 161ꢀ162 ºC; 1H NMR (400 MHz, CDCl3): δ 8.27
(d, J = 8.0 Hz, 1H), 7.77 (d, J = 7.6 Hz, 1H), 7.48ꢀ7.39 (m, 4H), 7.18 (d, J = 8.0 Hz,
2H), 6.88 (s, 2H), 2.39 (s, 3H), 2.37 (s, 3H), 1.76 (s, 6H); 13C NMR (100 MHz,
CDCl3): δ 151.8, 145.9, 142.3, 139.9, 138.7, 135.2, 133.1, 129.7, 127.9, 127.7, 126.8,
125.2, 124.6, 120.5, 114.2, 21.7, 21.4, 20.0; IR (film) 2920(w), 1611(w), 1545(w),
1449(w), 1381(s), 1296(w), 1251(m), 1179(s), 1125(w), 1092(w), 1061(m), 1014(m),
861(w), 812(m), 741(s), 678(vs); HRMS (m/z) [M + H]+ calcd for C23H23N2O2S
391.1475, found 391.1471.
2ꢀ(Pyridinꢀ2ꢀyl)ꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1m). 0.5 h; eluent: EtOAc/PE
1
20:80; yield: 170 mg, 98%; white solid, mp 136ꢀ138 ºC (lit.12b mp 129ꢀ131 ºC); H
NMR (400 MHz, CDCl3): δ 8.68 (d, J = 4.8 Hz, 1H), 8.09 (d, J = 8.0 Hz, 1H), 8.03 (d,
J = 8.4 Hz, 2H), 7.88ꢀ7.86 (m, 2H), 7.79 (d, J = 7.6 Hz, 1H), 7.46ꢀ7.38 (m, 3H), 7.31
(d, J = 8.0 Hz, 2H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 151.7, 149.6, 148.5,
145.6, 142.3, 136.4, 135.8, 133.5, 129.7, 127.9, 125.7, 125.6, 125.0, 124.7, 120.9,
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114.3, 21.7; IR (film) 1591(w), 1449(w), 1436(w), 1365(s), 1254(w), 1174(s),
1132(w), 1088(m), 1012(w), 811(w), 766(m), 750(m), 669(vs); HRMS (m/z) [M +
H]+ calcd for C19H16N3O2S 350.0958, found 350.0954.
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2ꢀ(Naphthalenꢀ1ꢀyl)ꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1n).12b
1
h; eluent:
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1
EtOAc/PE 10:90; yield: 184 mg, 92%; white solid, mp 125ꢀ126 ºC; H NMR (400
MHz, CDCl3): δ 8.30 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.4 Hz,
1H), 7.83ꢀ7.81 (m, 1H), 7.62ꢀ7.55 (m, 2H), 7.53ꢀ7.42 (m, 3H), 7.27ꢀ7.22 (m, 2H，
overlapped with the peak of chloroform), 7.19 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.0 Hz,
13
2H), 2.22 (s, 3H); C NMR (100 MHz, CDCl3): δ 151.4, 145.6, 142.3, 134.7, 133.5,
133.0, 132.5, 130.8, 130.0, 129.5, 128.1, 127.2, 126.7, 126.0, 125.6, 125.2, 125.0,
124.3, 120.6, 114.7, 21.5; IR (film) 3056(w), 1594(w), 1449(w), 1371(s), 1302(w),
1256(w), 1173(s), 1131(m), 1085(m), 1043(m), 1014(w), 801(m), 778(m), 743(vs),
701(m), 682(s), 659(s); HRMS (m/z) [M + H]+ calcd for C24H19N2O2S 399.1162,
found 399.1156.
(E)ꢀ2ꢀStyrylꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1o).19 0.5 h; eluent: EtOAc/PE 10:90;
1
yield: 157 mg, 84%; white solid, mp 155ꢀ157 ºC; H NMR (400 MHz, CDCl3): δ
8.09ꢀ8.07 (m, 1H), 7.93 (s, 2H), 7.78 (d, J = 8.4 Hz, 2H), 7.70ꢀ7.65 (m, 3H),
7.46ꢀ7.39 (m, 3H), 7.36ꢀ7.34 (m, 2H), 7.22 (d, J = 8.4 Hz, 2H), 2.33 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 151.2, 145.9, 142.7, 139.8, 135.8, 135.3, 133.2, 130.2,
129.6, 129.0, 127.8, 126.8, 125.3, 125.1, 119.9, 114.4, 114.0, 21.6; IR (film) 1623(w),
1506(w), 1448(w), 1374(s), 1342(w), 1232(w), 1198(m), 1162(s), 1089(m), 1050(m),
976(w), 925(w), 817(m), 760(m), 741(s), 672(vs), 645(m); HRMS (m/z) [M + H]+
calcd for C22H19N2O2S 375.1162, found 375.1160.
2ꢀPropylꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1p). 0.5 h; eluent: EtOAc/PE 10:90;
1
yield: 88 mg, 56%; white solid, mp 99ꢀ100 ºC (lit.20 mp 102ꢀ104 ºC); H NMR (400
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MHz, CDCl3): δ 8.04ꢀ8.02 (m, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.67ꢀ7.65 (m, 1H),
7.35ꢀ7.31 (m, 2H), 7.30ꢀ7.26 (m, 2H, overlapped with the peak of chloroform), 3.13 (t,
J = 7.6 Hz, 2H), 2.38 (s, 3H), 1.94 (sext, J = 7.6 Hz, 2H), 1.06 (t, J = 7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3): δ 155.2, 145.9, 142.0, 135.6, 133.2, 130.2, 126.7, 124.7,
124.6, 119.8, 113.7, 31.8, 21.7, 21.2, 14.0; IR (film) 2962(w), 1595(w), 1543(w),
1452(w), 1367(s), 1303(w), 1231(w), 1197(m), 1169(s), 1147(m), 1086(m), 1053(w),
878(w), 823(w), 764(w), 745(s), 667(vs); HRMS (m/z) [M + H]+ calcd for
C17H19N2O2S 315.1162, found 315.1161.
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2ꢀIsopropylꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1q).12b 0.5 h; eluent: EtOAc/PE 10:90;
1
yield: 145 mg, 92%; white solid, mp 102ꢀ103 ºC; H NMR (400 MHz, CDCl3): δ
8.06ꢀ8.04 (m, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.70ꢀ7.66 (m, 1H), 7.36ꢀ7.29 (m, 2H),
7.27 (d, J = 8.0 Hz, 2H, overlapped with the peak of chloroform), 3.83 (hept, J = 6.8
Hz, 1H), 2.38 (s, 3H), 1.39 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3): δ 160.7,
145.8, 142.0, 135.9, 133.0, 130.2, 126.6, 124.7, 124.6, 119.8, 114.0, 28.5, 22.3, 21.6;
IR (film) 2970(w), 1595(w), 1534(w), 1454(w), 1383(s), 1257(w), 1175(vs), 1139(m),
1087(s), 1035(m), 817(w), 768(w), 746(s), 692(s), 659(s); HRMS (m/z) [M + H]+
calcd for C17H19N2O2S 315.1162, found 315.1161.
2ꢀ(tertꢀButyl)ꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1r). 0.5 h; eluent: EtOAc/PE 5:95;
yield: 128 mg, 78%; white solid, mp 70ꢀ71 ºC; 1H NMR (400 MHz, CDCl3): δ 7.85 (d,
J = 7.6 Hz, 1H), 7.69 (d, J = 7.6 Hz, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.30ꢀ7.21 (m, 4H,
overlapped with the peak of chloroform), 2.36 (s, 3H), 1.66 (s, 9H); 13C NMR (100
MHz, CDCl3): δ 162.7, 145.2, 140.7, 136.6, 134.8, 129.9, 126.5, 124.8, 124.5, 120.1,
114.6, 37.0, 30.1, 21.6; IR (film) 2970(w), 1594(w), 1523(w), 1456(w), 1379(s),
1255(w), 1189(m), 1178(s), 1130(m), 1081(m), 1010(m), 817(w), 746(m), 704(w),
675(vs); HRMS (m/z) [M + H]+ calcd for C18H21N2O2S 329.1318, found 329.1316.
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2ꢀCyclohexylꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1s).12b 0.5 h; eluent: EtOAc/PE 5:95;
1
yield: 175 mg, 99%; white solid, mp 125ꢀ126 ºC; H NMR (400 MHz, CDCl3): δ
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8.07ꢀ8.03 (m, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.70ꢀ7.66 (m, 1H), 7.35ꢀ7.30 (m, 2H),
7.28ꢀ7.26 (m, 2H, overlapped with the peak of chloroform), 3.49 (tt, J = 11.6, 3.2 Hz,
1H), 2.38 (s, 3H), 1.94ꢀ1.84 (m, 4H), 1.78ꢀ1.66 (m, 3H), 1.47ꢀ1.30 (m, 3H); 13C NMR
(100 MHz, CDCl3): δ 159.7, 145.8, 142.0, 135.9, 132.9, 130.2, 126.6, 124.7, 124.6,
119.8, 114.0, 38.1, 32.6, 26.3, 25.8, 21.7; IR (film) 2922(w), 2846(w), 1448(w),
1370(m), 1247(w), 1194(m), 1162(s), 1120(m), 1087(m), 1047(m), 884(w), 805(w),
765(w), 748(s), 704(w), 669(vs); HRMS (m/z) [M + H]+ calcd for C20H23N2O2S
355.1475, found 355.1476.
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Ethyl 1ꢀtosylꢀ1Hꢀbenzo[d]imidazoleꢀ2ꢀcarboxylate (1t).12a 0.5 h; eluent:
1
EtOAc/PE 10:90; yield: 159 mg, 93%; white solid, mp 105ꢀ106 ºC; H NMR (400
MHz, CDCl3): δ 8.10 (d, J = 8.4 Hz, 2H), 8.00 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.0 Hz,
1H), 7.50ꢀ7.46 (m, 1H), 7.42ꢀ7.38 (m, 1H), 7.35 (d, J = 8.0 Hz, 2H), 4.56 (q, J = 7.2
Hz, 2H), 2.41 (s, 3H), 1.49 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 160.0,
146.3, 143.4, 141.5, 134.6, 132.2, 130.1, 128.1, 126.9, 125.3, 121.7, 113.7, 63.4, 21.8,
14.0; IR (film) 2981(w), 1732(s), 1596(w), 1524(w), 1380(m), 1370(m), 1328(w),
1255(w), 1200(s), 1171(s), 1087(m), 1050(w), 1010(m), 860(w), 817(w), 749(s),
670(vs); HRMS (m/z) [M + Na]+ calcd for C17H16N2NaO4S 367.0723, found
367.0726.
6ꢀNitroꢀ2ꢀphenylꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1u). 3 h; eluent: EtOAc/PE
10:90; yield: 178 mg, 90%; white solid, mp 164ꢀ166 ºC; 1H NMR (400 MHz, CDCl3):
δ 9.14 (d, J = 2.0 Hz, 1H), 8.32 (dd, J = 8.8, 2.0 Hz, 1H), 7.81 (d, J = 8.8 Hz, 1H),
7.63ꢀ7.59 (m, 3H), 7.50 (t, J = 7.6 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4
Hz, 2H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.4, 146.7, 146.6, 145.3,
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134.3, 133.5, 131.4, 130.9, 130.0, 129.0, 127.9, 127.3, 120.9, 120.6, 111.9, 21.7; IR
(film) 3067(w), 1594(w), 1516(m), 1435(w), 1380(m), 1337(m), 1272(m), 1235(w),
1170(s), 1123(w), 1082(m), 1019(m), 890(w), 835(m), 811(m), 762(m), 734(w),
698(s), 664(vs); HRMS (m/z) [M + H]+ calcd for C20H16N3O4S 394.0856, found
394.0856.
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5,6ꢀDimethylꢀ2ꢀphenylꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1v).
1
h; eluent:
1
EtOAc/PE 10:90; yield: 187 mg, 99%; white solid, mp 134ꢀ135 ºC; H NMR (400
MHz, CDCl3): δ 7.97 (s, 1H), 7.58 (d, J = 7.2 Hz, 2H), 7.52 (t, J = 7.6 Hz, 1H),
7.47ꢀ7.42 (m, 3H), 7.30 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 2.45 (s, 3H),
2.36 (s, 3H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.3, 145.5, 141.2, 135.2,
134.8, 134.3, 132.3, 130.9, 130.3, 130.2, 129.6, 127.6, 126.9, 120.4, 115.4, 21.6, 20.8,
20.2; IR (film) 2924(w), 1595(w), 1465(w), 1361(s), 1287(w), 1164(m), 1110(w),
1083(m), 1071(w), 1010(m), 867(w), 810(m), 771(s), 689(s), 663(vs); HRMS (m/z)
[M + H]+ calcd for C22H21N2O2S 377.1318, found 377.1316.
5,6ꢀDibromoꢀ2ꢀphenylꢀ1ꢀtosylꢀ1Hꢀbenzo[d]imidazole (1w).
2
h; eluent:
1
EtOAc/PE 5:95; yield: 243 mg, 96%; white solid, mp 182ꢀ183 ºC; H NMR (400
MHz, CDCl3): δ 8.53 (s, 1H), 7.98 (s, 1H), 7.59ꢀ7.55 (m, 3H), 7.48ꢀ7.44 (m, 2H),
7.28ꢀ7.26 (m, 2H, overlapped with the peak of chloroform), 7.12 (d, J = 8.0 Hz, 2H),
2.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 155.6, 146.3, 142.8, 134.5, 133.9, 131.0,
130.9, 129.9, 129.1, 127.8, 127.1, 124.7, 121.1, 121.0, 119.7, 21.7; IR (film) 1624(w),
1494(w), 1429(w), 1377(m), 1236(w), 1158(vs), 1082(w), 1031(w), 1010(m), 935(w),
810(w), 769(w), 740(w), 666(s); HRMS (m/z) [M + H]+ calcd for C20H15Br2N2O2S
504.9216, found 504.9200.
2ꢀPhenylꢀ1ꢀ(phenylsulfonyl)ꢀ1Hꢀbenzo[d]imidazole (1x).21 0.5 h; eluent:
EtOAc/PE 10:90; yield: 158 mg, 95%; white solid, mp 64ꢀ66 ºC; 1H NMR (400 MHz,
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CDCl3): δ 8.23ꢀ8.21 (m, 1H), 7.75ꢀ7.72 (m, 1H), 7.60ꢀ7.57 (m, 2H), 7.55ꢀ7.49 (m,
2H), 7.47ꢀ7.38 (m, 6H), 7.33ꢀ7.29 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 154.0,
142.6, 138.0, 134.4, 133.9, 130.9, 130.6, 129.9, 129.1, 127.7, 127.0, 125.6, 125.4,
120.5, 115.2; IR (film) 3057(w), 1536(w), 1445(m), 1381(s), 1275(w), 1184(s),
1122(m), 1067(m), 1016(w), 826(w), 764(m), 750(s), 729(s), 687(vs); HRMS (m/z)
[M + Na]+ calcd for C19H15N2O2S 335.0849, found 335.0846.
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Phenyl(2ꢀphenylꢀ1Hꢀbenzo[d]imidazolꢀ1ꢀyl)methanone (1y).22 12 h; eluent:
1
EtOAc/PE 10:90; yield: 134 mg, 90%; white solid, mp 142ꢀ143 ºC; H NMR (400
MHz, CDCl3): δ 7.89 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 7.2 Hz, 2H), 7.62ꢀ7.60 (m, 2H),
7.51 (t, J = 7.6 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.41ꢀ7.27 (m, 7H); 13C NMR (100
MHz, CDCl3): δ 169.1, 154.0, 142.7, 134.9, 134.1, 133.1, 130.6, 130.3, 129.9, 129.3,
128.8, 128.4, 124.8, 124.6, 120.2, 113.1; IR (film) 3029(w), 1698(m), 1597(w),
1450(m), 1333(w), 1282(m), 1265(m), 1147(m), 1026(w), 932(w), 899(m), 839(w),
748(s), 696(vs); HRMS (m/z) [M + H]+ calcd for C20H15N2O 299.1179, found
299.1179.
tertꢀButyl 2ꢀphenylꢀ1Hꢀbenzo[d]imidazoleꢀ1ꢀcarboxylate (1z). 0.5 h; eluent:
1
EtOAc/PE 5:95; yield: 103 mg, 70%; brown oil; H NMR (400 MHz, CDCl3): δ
8.06ꢀ8.04 (m, 1H), 7.80 (dd, J = 5.6, 2.4 Hz, 1H), 7.64ꢀ7.62 (m, 2H), 7.48ꢀ7.45 (m,
3H), 7.42ꢀ7.36 (m, 2H), 1.40 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 153.8, 148.6,
142.5, 133.8, 132.4, 129.6, 129.2, 128.0, 125.0, 124.5, 120.1, 114.7, 85.3, 27.6; IR
(film) 2979(w), 2930(w), 1741(vs), 1539(w), 1452(m), 1327(s), 1262(m), 1221(m),
1149(s), 1059(m), 846(w), 764(m), 746(m), 697(m); HRMS (m/z) [M + H]+ calcd for
C18H19N2O2 295.1441, found 295.1453.
Isopropyl 2ꢀ((methylthio)methyl)ꢀ1Hꢀbenzo[d]imidazoleꢀ1ꢀcarboxylate (7).10 0.5 h;
eluent: EtOAc/PE 15:85; yield: 43 mg, 33%; brown oil; 1H NMR (400 MHz, CDCl3):
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δ 7.98ꢀ7.95 (m, 1H), 7.72ꢀ7.70 (m, 1H), 7.37ꢀ7.32 (m, 2H), 5.34 (hept, J = 6.4 Hz,
1H), 4.19 (s, 2H), 2.15 (s, 3H), 1.52 (d, J = 6.4 Hz, 6H); 13C NMR (100 MHz, CDCl3):
δ 152.5, 149.7, 141.9, 133.3, 124.9, 124.4, 119.9, 115.1, 73.1, 33.3, 21.9, 15.4; IR
(Film) 2920(w), 1743(s), 1533(w), 1453(m), 1367(s), 1339(m), 1323(m), 1287(m),
1259(m), 1211(s), 1147(m), 1103(s), 1089(vs), 908(w), 839(w), 765(m), 744(m);
HRMS (m/z) [M + Na]+ calcd for C13H16N2NaO2S, 287.0825, found 287.0833.
Isopropyl 2ꢀphenylꢀ1Hꢀbenzo[d]imidazoleꢀ1ꢀcarboxylate (1aa). 3 h; eluent:
EtOAc/PE 20:80; yield: 122 mg, 87%; white solid, mp 83ꢀ84ºC; 1H NMR (400 MHz,
CDCl3): δ 8.07ꢀ8.04 (m, 1H), 7.81ꢀ7.78 (m, 1H), 7.66ꢀ7.63 (m, 2H), 7.51ꢀ7.45 (m,
3H), 7.41ꢀ7.37 (m, 2H), 5.14 (hept, J = 6.4 Hz, 1H), 1.23 (d, J = 6.4 Hz, 6H). 13C
NMR (100 MHz, CDCl3): δ 153.9, 149.7, 142.7, 133.7, 132.1, 129.7, 129.4, 127.9,
125.1, 124.6, 120.3, 114.9, 72.8, 21.5; IR (film) 2983(w), 1738(s), 1538(w), 1454(m),
1364(m), 1328(m), 1311(m), 1280(m), 1208(m), 1154(w), 1145(w), 1098(s), 1059(m),
903(w), 846(w), 760(s), 743(vs), 696(s); HRMS (m/z) [M + H]+ calcd for C17H17N2O2,
281.1285, found 281.1283.
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Isopropyl 2ꢀ(pyridinꢀ2ꢀyl)ꢀ1Hꢀbenzo[d]imidazoleꢀ1ꢀcarboxylate (1ab). 1.5 h;
1
eluent: EtOAc/PE 25:75; yield: 120 mg, 85%; yellow oil; H NMR (400 MHz,
CDCl3): δ 8.71ꢀ8.69 (m, 1H), 8.02ꢀ8.00 (m, 1H), 7.90ꢀ7.82 (m, 3H), 7.45ꢀ7.37 (m,
3H), 5.15 (hept, J = 6.4 Hz, 1H), 1.23 (d, J = 6.4 Hz, 6H). 13C NMR (100 MHz,
CDCl3): δ 152.0, 150.7, 149.6, 149.0, 142.5, 136.5, 133.7, 125.6, 124.6, 124.2, 124.0,
120.5, 114.3, 72.8, 21.5; IR (film) 2983(w), 1746(s), 1589(w), 1449(s), 1365(s),
1322(s), 1291(m), 1218(vs), 1103(s), 1066(m), 849(w), 763(m), 746(m); HRMS (m/z)
[M + H]+ calcd for C16H16N3O2, 282.1237, found 282.1247.
1ꢀMethylꢀ2ꢀphenylꢀ1Hꢀbenzo[d]imidazole (1ac). NꢀMethylꢀ1,2ꢀbenzenediamine
dihydrochloride (98 mg, 0.5 mmol) was used as the substrate in the presence of
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NaOAc (82 mg, 1 mmol). 3 h; eluent: EtOA/PE 20:80; yield: 101 mg, 97%; white
solid, mp 93ꢀ94ºC (lit.11e mp 96ꢀ49 ºC); 1H NMR (400 MHz, CDCl3): δ 7.85ꢀ7.81 (m,
1H), 7.78ꢀ7.75 (m, 2H), 7.55ꢀ7.50 (m, 3H), 7.40ꢀ7.37 (m, 1H), 7.34ꢀ7.29 (m, 2H),
3.86 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 153.8, 143.0, 136.6, 130.3, 129.7, 129.5,
129.5, 128.7, 122.8, 122.5 119.9, 109.6, 31.7; IR (film) 1614(w), 1468(m), 1441(m),
1383(m), 1329(w), 1277(w), 1242(w), 1155(w), 1060(w), 1022(w), 927(w), 818(w),
754(vs), 700(s); HRMS (m/z) [M + H]+ calcd for C14H13N2, 209.1073, found
209.1077.
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1,2ꢀDiphenylꢀ1Hꢀbenzo[d]imidazole (1ad). 3 h; eluent: EtOA/PE 15:85; yield: 123
1
mg, 91%; white solid, mp 108ꢀ109 ºC (lit.11e mp 109ꢀ110 ºC); H NMR (400 MHz,
CDCl3): δ 7.89 (d, J = 8.0 Hz, 1H), 7.58ꢀ7.56 (m, 2H), 7.52ꢀ7.46 (m, 3H), 7.34ꢀ7.25
(m, 8H, overlapped with the peak of chloroform); 13C NMR (100 MHz, CDCl3): δ
152.4, 143.0, 137.2, 137.0, 130.0, 129.9, 129.5, 129.4, 128.6, 128.3, 127.4, 123.3,
123.0, 119.9, 110.5; IR (film) 3050(w), 1595(w), 1491(m), 1476(m), 1444(m),
1381(m), 1328(w), 1260(w), 1181(w), 1077(w), 1027(w), 996(w), 977(w), 932(w),
832(w), 763(s), 750(s), 698(vs); HRMS (m/z) [M + H]+ calcd for C19H15N2, 271.1230,
found 271.1245.
2ꢀPhenylꢀ1Hꢀbenzo[d]imidazole (1ae). Eluent: EtOAc/PE 30:70 (enriched with 3%
of MeOH); yield: 87 mg, 90%; white solid, mp 285ꢀ286 ºC (lit.4e mp 282ꢀ284 ºC); 1H
NMR (400 MHz, CD3OD): δ 8.10 (d, J = 6.8 Hz, 2H), 7.63ꢀ7.61 (m, 2H), 7.57ꢀ7.49
(m, 3H), 7.28ꢀ7.26 (m, 2H); 13C NMR (100 MHz, CD3OD): δ 152.0, 130.0, 129.6,
128.8, 126.4, 122.5, 114.5; IR (film) 1542(w), 1463(m), 1444(m), 1411(m), 1315(w),
1277(w), 1227(w), 1120(w), 971(m), 927(w), 764(w), 738(vs), 702(s), 686(m);
HRMS (m/z) [M + H]+ calcd for C13H11N2, 195.0917, found 195.0918.
2ꢀIsopropylꢀ1Hꢀbenzo[d]imidazole (1af). Eluent: EtOAc/PE 30:70 (enriched with 3%
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of MeOH); yield: 70 mg, 88%; white solid, mp 217ꢀ218 ºC (lit.23 mp 220ꢀ225 ºC); 1H
NMR (400 MHz, CD3OD): δ 7.52ꢀ7.50 (m, 2H), 7.21ꢀ7.19 (m, 2H), 3.24 (hept, J =
7.2 Hz, 1H), 1.44(d, J = 7.2 Hz, 6H); 13C NMR (100 MHz, CD3OD): δ 160.2, 137.8,
121.8, 113.9, 28.7, 20.3; IR (film) 2971(w), 1533(w), 1455(m), 1414(s), 1321(m),
1273(s), 1158(w), 1091(m), 1014(w), 995(m), 929(w), 879(w), 742(vs); HRMS (m/z)
[M + H]+ calcd for C10H13N2, 161.1073, found 161.1073.
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2ꢀIsopropylꢀ5,6ꢀdimethylꢀ1Hꢀbenzo[d]imidazole (1ag). Eluent: EtOAc/PE 20:80
(enriched with 3% of MeOH); yield: 87 mg, 93%; white solid, mp 204ꢀ206 ºC (lit.24
mp 210 ºC); 1H NMR (400 MHz, CDCl3): δ 7.31 (s, 2H), 3.24 (hept, J = 6.8 Hz, 1H),
2.33(s, 6H), 1.44(d, J = 6.8 Hz, 6H); 13C NMR (100 MHz, CD3OD): δ 159.2, 136.9,
130.9, 114.9, 29.0, 21.6, 20.3; IR (film) 2963(m), 1541(w), 1445(vs), 1377(w),
1309(s), 1238(w), 1166(m), 1111(m), 1087(m), 1071(w), 1000(s), 928(w), 850(s);
HRMS (m/z) [M + H]+ calcd for C12H17N2, 189.1386, found 189.1387.
5,6ꢀDibromoꢀ2ꢀisopropylꢀ1Hꢀbenzo[d]imidazole (1ah). Eluent: EtOAc/PE 25:75
1
(enriched with 3% of MeOH); yield: 136 mg, 86%; white solid, mp 203ꢀ205 ºC; H
NMR (400 MHz, CD3OD): δ 7.83 (s, 2H), 3.22 (hept, J = 7.2 Hz, 1H), 1.43(d, J = 7.2
Hz, 6H); 13C NMR (100 MHz, CD3OD): δ 162.9, 124.8, 116.4, 28.8, 20.1; IR (film)
2972(m), 1532(w), 1437(s), 1356(m), 1295(m), 1276(m), 1095(s), 1078(w), 1003(w),
928(w), 858(vs), 846(s), 609(w); HRMS (m/z) [M + H]+ calcd for C10H11Br2N2,
316.9283, found 316.9287.
ꢀ Associated Content
Supporting Information
1
Copies of H and 13C NMR spectra of products 1 and 7, and imine 3a, and Xꢀray
structures and data of compound 1l (CIF). This material is available free of charge via
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the Internet at http://pubs.acs.org.
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ꢀ Author Information
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Corresponding Authors
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*Eꢀmail: wenquan_yu@zzu.edu.cn
*Eꢀmail: changjunbiao@zzu.edu.cn
Notes
The authors declare no competing financial interest.
ꢀ Acknowledgements
We thank the Outstanding Young Talent Research Fund of Zhengzhou University (No.
1521316004) and the National Natural Science Foundation of China (Nos. 81330075
and 81302637) for financial support.
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