Decarboxylative Coupling of α-Keto Acids with ortho-Phenylenediamines Promoted by an Electrochemical Method in Aqueous Media

Article abstract of DOI:10.1002/adsc.201501167

An electrochemical method for the decarboxylative coupling of α-keto acids with ortho-phenylenediamines was developed. The reaction proceeded smoothly in aqueous solution under air and metal catalyst-free conditions to afford 2-substituted benzimidazoles in good yields. Benzothiazoles could also be synthesized by this protocol. (Figure presented.) .

Full text of DOI:10.1002/adsc.201501167

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DOI: 10.1002/adsc.201501167
Decarboxylative Coupling of a-Keto Acids with ortho-Phenylene-
diamines Promoted by an Electrochemical Method in Aqueous
Media
Hai-Bin Wanga and Jing-Mei Huanga,*
a
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong 510640,
People’s Republic of China
Fax: (+86)-20-8711-0622; phone: (+86)-20-8711-0695; e-mail: chehjm@scut.edu.cn
Received: December 25, 2015; Revised: March 27, 2016; Published online: June 2, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201501167.
Abstract: An electrochemical method for the decar- benzimidazoles in good yields. Benzothiazoles could
boxylative coupling of a-keto acids with ortho-phe- also be synthesized by this protocol.
nylenediamines was developed. The reaction pro-
ceeded smoothly in aqueous solution under air and Keywords: aqueous media; decarboxylative cou-
metal catalyst-free conditions to afford 2-substituted pling; electrochemical reaction; 2-substituted benz-
oxazoles
Introduction
report the first highly efficient electrochemical decar-
boxylative coupling of a-keto acids with o-phenylene-
The decarboxylative coupling reaction has recently diamines to form 2-substituted benzimidazoles in
À
À
emerged as a powerful tool to construct C C or C
heteroatom bonds in synthetic organic chemistry. This
reaction typically involves transition metal catalytic
aqueous solution.
systems and high reaction temperatures are necessa- Results and Discussion
ry.[1] A Kolbe-type reaction through anodic oxidative
decarboxylation of a carboxylic acid represents the We commenced our study with benzoylformic acid
seminal study of electroorganic synthesis that allows (1a) and ortho-phenylenediamine (2a) as model sub-
À
À
one-step C C or C heteroatom bond formation, strates. The two compounds were treated with TFA
which is difficult to be attained through other (trifluoroacetic acid, 0.5 mmol) and DIPEA (N,N-di-
routes.[2] Despite the convenience and clean chemistry isopropylethylamine, 1.0 mmol) in 4.0 mL DMF (N,N-
that electrochemistry could bestow in the field of con- dimethylformamide)–0.2M NH4ClO4 solution in
temporary organic synthesis,[3,4] its applications in de- a one-compartment cell under a constant current
carboxylative cross-coupling reactions remain chal- (5 mA) for 15 h at room temperature. The desired
lenging and the reported methods are nonetheless product 3a was obtained in 48% isolated yield
limited.
(Table 1, entry 1). The solvent effect was then studied
2-Substituted benzimidazoles are important build- (entries 2–4). To our delight, the desired product was
ing blocks for pharmaceutical agents, natural products formed in 88% yield (entry 3) by using DMSO (di-
and functional materials.[5] Hence, tremendous efforts methyl sulfoxide, AR grade, water content ꢀ0.2%) as
have been made to explore efficient methods for the the solvent. However, when the reaction was carried
construction of this type of heterocyclic ring.[6] How- out in anhydrous DMSO, the product was only ob-
ever, the preparation of benzimidazoles from a-keto tained in 53% yield (Table 1, entry 4). When the com-
acids has received less attention. Very recently, Lei bination DMSO/H2O (3/1, v/v) was employed, the
et al. demonstrated an elegant photocatalyzed decar- yield could be further increased to 94% (Table 1,
boxylation of a-keto acids with amines to form entry 5). Switching the Pt foils with graphite electro-
amides and benzazoles by visible light.[7] In continua- des led to a yield of 85% (Table 1, entry 6). Studies
tion of our interest in the development of new elec- on the effect of current density revealed that an in-
trochemical process in aqueous solution,[8] herein we crease or decrease of the current led to a decrease of
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Table 1. Optimization of the reaction conditions.[a]
Table 2. Scope of substrates.[a]
Entry Anode-Cathode Solvent
Yield [%][b]
1
2
Pt-Pt
Pt-Pt
Pt-Pt
Pt-Pt
Pt-Pt
C-C[d]
Pt-Pt
Pt-Pt
Pt-Pt
Pt-Pt
DMF
48
54
88
53
CH3OH
DMSO
DMSO
DMSO/H2O (3/1, v/v) 94
DMSO/H2O (3/1, v/v) 85
DMSO/H2O (3/1, v/v) 63
DMSO/H2O (3/1, v/v) 68
DMSO/H2O (3/1, v/v) 40
DMSO/H2O (3/1, v/v) 48
3
4[c]
5
6
7[e]
8[f]
9[g]
10[h]
[a]
the mixture of 1a (0.4 mmol), 2a (1.2 mmol), TFA
(0.5 mmol) and DIPEA (1.0 mmol) in solvent (4.0 mL)
with 0.2M NH4ClO4 as supporting electrolyte was elec-
trolyzed at constant current (5 mA) in an undivided cell
at room temperature for 15 h under air, anode: Pt foil
(1”1.5 cm2), cathode: Pt foil (1”1.5 cm2).
Yields of isolated products.
Anhydrous DMSO (4.0 mL).
Graphite rod electrode (diameter=0.5 cm, height=
1.8 cm).
[b]
[c]
[d]
[e]
[f]
The current was 3 mA.
The current was 8 mA.
In the absence of TFA.
In the absence of DIPEA.
[g]
[h]
the product yield (Table 1, entries 7 and 8). Hence,
5 mA was the optimal current for this reaction. Also,
the absence of TFA or DIPEA both led to decreases
of the chemical yield (Table 1, entries 9 and 10).
The reaction scope was explored by employing the
optimized reaction conditions. First, the reactivities of
various substituted aromatic diamines under our reac-
tion protocol were examined. As can be seen in
Table 2, most of the phenylenediamines, which bore
electron-deficient or electron-rich groups on the aro-
matic rings, gave the corresponding products in good
to excellent yields. It is noteworthy that the halide
substituents could be well tolerated under the electro-
chemical conditions and could thus provide an oppor-
tunity for further transformations at the halide posi-
tion. However, the reaction of 4-nitro-o-phenylenedi-
amine yielded only 30% of respective product, 3j. It
was speculated that the reduction of the nitro group
[a]
Reaction conditions: 1 (0.4 mmol), 2 (1.2 mmol), DMSO
(3.0 mL), H2O (1.0 mL), TFA (0.5 mmol), DIPEA
(1.0 mmol), 0.2M NH4ClO4 as supporting electrolyte,
15 h at room temperature under air, anode: Pt foil (1”
1.5 cm2), cathode: Pt foil (1”1.5 cm2), constant current
(5 mA), undivided cell. Yields of isolated products.
[b]
DMSO (3.5 mL) and H2O (0.5 mL).
After 22 h.
[c]
could have occurred on the cathode. Next, the reac- good yields (3k–o). The 2-thiopheneglyoxylic acid was
tions of different a-keto acids, including aliphatic and not compatible for this transformation under the stan-
heteroaromatic a-keto acids were studied. Besides the dard conditions (3p). Finally, this method was extend-
aromatic keto acids, the aliphatic keto acids under- ed to the synthesis of benzothiazoles and it was found
went decarboxylative coupling with 2a smoothly to that these useful compounds could also be synthesized
afford the desired benzimidazoles in moderate to in good yields (3q–w).
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Control experiments were carried out in order to
obtain useful insights into the mechanism. The stan-
dard conditions include the presence of electric
supply, water together with air, as listed in entry 1,
Table 3. The reaction yield was decreased to 85%
under a nitrogen atmosphere (Table 3, entry 2). Only
a trace amount of product was obtained in the ab-
sence of the power supply (Table 3, entry 3). When
anhydrous DMSO was used without addition of
water, the reaction gave a 53% yield of product
(Table 3, entry 4). Furthermore, it was observed that
if the conditions listed in entry 4 were repeated under
a nitrogen atmosphere instead of air, a lower yield of
product was observed (Table 3, entry 5). Some other
control reactions were also carried out by using the
preformed imine from benzaldehyde and ortho-phe-
nylenediamine 2a. The imine was subjected to the
cyclization and dehydrogenation reactions under dif-
ferent control conditions (see the Supporting Infor-
mation, Scheme S1 for the results and discussion).
Very recently, Cheon and co-workers had verified
that water could act as a nucleophilic catalyst for the
synthesis of benzimidazoles.[9] Hence, in our reaction
Scheme 1. Studies on the mechanism of the reaction.
system, it was demonstrated that electrochemical cur- MS and LC-MS analysis. On the other hand, when
rent, oxygen and water have all played important only benzoylformic acid 1a was added to the reaction
roles in this decarboxylative coupling process.
mixture under the standard conditions, 12% conver-
Further studies on the mechanism of the reaction sion of benzoylformic acid 1a was observed with 6%
were performed. When two equivalents of 2,2,6,6-tet- of benzaldehyde and 6% benzoic acid being formed
ramethylpiperidine N-oxyl (TEMPO) were added (Scheme 1B). The Kolbe coupling product, benzil was
into the reaction mixture under the standard condi- not detected by TLC and GC-MS post reaction.[10]
tions, the desired product was obtained in 58% yield Cyclic voltammetry (CV) experiments were carried
(Scheme 1A). However, the (2,2,6,6-tetramethylpiper- out (Figure 1, for more details, please refer to the
idin-1-yl) benzoate was not detected by NMR, GC- Supporting Information). An obvious oxidative peak
(peak potential at 1.01 V vs. Ag/AgNO3, curve b) was
detected in the solution of PhCOCOOK, but the cor-
Table 3. Control experiments.[a]
responding reductive peak was not detected. These
experimental results showed that PhCOCOOÀ could
be oxidized to form PhCOCOOC followed by an irre-
versible extrusion of CO2. The CV studies on the
effect of CF3COOH were also carried out. In the ab-
sence of CF3COOH, the oxidation peak of 1,2-phenyl-
enediamine was observed at Ep =0.41 V vs. SCE
Entry
Current
Water
Air
Yield [%][b]
(Supporting Information, Figure S1, curve f) and at
Ep =0.63 V vs. SCE (Supporting Information, Fig-
ure S1, curve g) in its presence. This implies that in
our reaction system the acid could have partially pro-
tonated the 1,2-phenylenediamine and hampered its
oxidation.[11]
1
+
+
-
+
+
+
+
+
–
+
–
+
+
–
94
85
12
53
47
2[c]
3
4[d]
5[c,d]
–
Based on the above described results and reported
works,[12] we proposed two mechanistic pathways for
the reaction (Scheme 2, Paths A and B). In Path A,
according to the cyclic voltammetry (CV) experi-
ments (Figure 1), a-keto acid anion[13] loses an elec-
tron to generate radical 5. 5 then undergoes decarbox-
ylation to produce the acyl radical 6, which couples
with partially protonated diamine 2a and a hydrogen
atom transfers from the electrogenerated amine radi-
[a]
Reaction conditions: 1a (0.4 mmol), 2a (1.2 mmol),
DMSO (3.0 mL), H2O (1.0 mL), TFA (0.5 mmol),
DIPEA (1.0 mmol), 0.2M NH4ClO4 as supporting elec-
trolyte, 15 h at room temperature, anode: Pt foil (1”
1.5 cm2), cathode: Pt foil (1”1.5 cm2), constant current
(5 mA), undivided cell.
Yields of isolated products.
Reaction was carried out under N2.
Anhydrous DMSO (4.0 mL).
[b]
[c]
[d]
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amine with a-oxocarboxylate which is catalyzed by
TFA.[15] Then the decarboxylation of 9 was assisted by
the anodic oxidation followed by H atom abstraction
from (i-Pr)2NEtC+ to form 7. Subsequent transforma-
tion of intermediate 7 to final product 3a follows the
same process as described in Path A. Noteworthily, a-
iminocarboxylate 10 was detected during the reaction
(see the Supporting Information for details). It had
been reported that the activation barrier of the decar-
boxylation of 9 would be reduced after condensation
of o-phenylenediamine with a-oxocarboxylate. Hence,
it could extrude CO2 more easily than a-oxocarboxyl-
ate.[15e] Therefore, we propose that Path B is the more
favorable process for our reaction.
Figure 1. Cyclic voltammograms in DMSO–0.1M NH4ClO4
solution at room temperature: (a) 0.05M ferrocene, (b)
0.01M PhCOCOOK. The voltammogram was obtained with
Pt wire as auxiliary electrode and Ag/AgNO3 as reference
electrode. The scan rate was 0.1 VsÀl on a platinum disk
electrode (d=2 mm).
Conclusions
In summary, a novel electrochemical-promoted decar-
boxylative coupling of a-keto acids with o- benzimi-
dazoles has been developed. This reaction protocol
accommodates the use of undivided-cell equipment,
aqueous media without the need of inert atmosphere,
rendering it a mild and easily-operated reaction pro-
+
cal cation [(i-Pr)2NEtC )] to afford the product 7.[14]
7
is then transformed to the intermediate benzimidazo- tocol. Under metal catalyst-free conditions, the reac-
line 8. Subsequent dehydrogenation of 8 has proceed- tion afforded the desired products in good to excel-
ed through a synergistic action of O2 and anodic oxi- lent yields with a wide substrate scope. Further inves-
dation (Path A). Alternatively, in Path B, hemiaminal tigations on the mechanism and the synthetic applica-
9 is formed by the condensation of o-phenylenedi- tions are in progress.
Scheme 2. Proposed reaction mechanism.
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1H), 7.24–7.20 (m, 1H); 13C NMR (100 MHz, DMSO-d6):
d=152.1, 130.2, 129.6, 128.9, 126.8, 123.2, 121.7.
Experimental Section
5-Chloro-2-phenyl-1H-benzo[d]imidazole (3c):[16a] The
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3c as
a yellow solid; yield: 86.7 mg (95%); Rf =0.54 (PE/EA=2/
1); 1H NMR (400 MHz, DMSO-d6): d=13.12 (br s, 1H),
8.19 (d, J=7.6 Hz, 2H), 7.66–7.66 (m, 1H), 7.62–7.49 (m,
4H), 7.23 (d, J=8.4 Hz, 1H); 13C NMR (100 MHz, DMSO-
d6): d=152.6, 130.2, 129.7, 129.0, 126.7, 126.6, 122.3.
General Information
Cyclic voltammetric (CV) experiments were carried out in
a classical undivided cell in the presence of a supporting
electrolyte. A platinum disk electrode (d=2 mm) and a plati-
num wire electrode (d=0.2 mm) were employed as the
anodic electrode and cathodic electrode, respectively. An
Ag/AgNO3 electrode was used as the reference electrode in
the CV experiments. Analytical thin-layer chromatography
(TLC) plates and the silica gel for column chromatography
were commercially available.
5,6-Dichloro-2-phenyl-1H-benzo[d]imidazole (3d):[16a] The
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3d as
a yellow solid; yield: 80.7 mg (77%); Rf =0.50 (PE/EA=2/
1); 1H NMR (400 MHz, DMSO-d6): d=13.20 (br s, 1H),
8.17–8.17 (m, 2H), 7.83–7.83 (m, 2H), 7.56–7.54 (m, 3H);
13C NMR (100 MHz, DMSO-d6): d=153.8, 130.4, 129.3,
128.9, 126.7, 124.5.
Commercial solvents and reagents were used without fur-
ther purification, and tap water was used for the reaction.
GC-MS analyses were carried out on a GC apparatus cou-
pled with a single quadrupole mass spectrometer (EI,
70 eV) and a TG-5MS (30 m”0.25 mm i.d.”0.25 mm) capil-
1
lary column. H NMR and 13C NMR spectra were recorded
5-Bromo-2-phenyl-1H-benzo[d]imidazole (3e):[16b] The
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3e as
a yellow solid; yield: 100.1 mg (92%); Rf =0.54 (PE/EA=2/
1); 1H NMR (400 MHz, DMSO-d6): d=13.13 (br s, 1H),
8.19 (d, J=7.6 Hz, 2H), 7.81 (s, 1H), 7.58–7.50 (m, 4H),
7.36–7.32 (m, 1H); 13C NMR (100 MHz, DMSO-d6): d=
152.5, 130.2, 129.6, 129.0, 126.6, 124.9.
at 400 and 100 MHz, respectively. Chemical shifts of
1H NMR and 13C NMR spectra are reported in units of parts
per million (ppm) downfield from SiMe4 (d=0.0 ppm) and
1
relative to the signal of CDCl3 (d=7.26 ppm for H NMR
and d=77.1 ppm for 13C NMR) and (CD3)2SO (d=2.50 ppm
for 1H NMR and d=39.5 ppm for 13C). Multiplicities are
given as s (singlet); br s (broad singlet); d (doublet); t (trip-
let); q (quartet); dd (doublet of doublets); m (multiplets),
etc. The number of protons (n) for a given resonance is indi-
cated by nH.
4-Methyl-2-phenyl-1H-benzo[d]imidazole (3f):[16a] The
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3f as
a yellow solid; yield: 74.9 mg (90%); Rf =0.63 (PE/EA=2/
1); 1H NMR (400 MHz, DMSO-d6): d=12.68 (br s, 1H),
8.24 (d, J=7.6 Hz, 2H), 7.58–7.56 (m, 2H), 7.54–7.48 (m,
1H), 7.42 (d, J=7.7 Hz, 1H), 7.13–7.09 (m, 1H), 7.02–7.00
(m, 1H), 2.60 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d=
150.7, 130.3, 129.6, 128.8, 126.5, 122.4, 122.1, 16.9.
General Procedure for the Electrochemical Decarboxyla-
tive Coupling of a-Keto Acids with ortho-Phenylenedi-
amines
In a round-bottom flask cell, a-keto acid (0.4 mmol), o-
phenylenediamine (1.2 mmol), TFA (0.5 mmol) and DIPEA
(1.0 mmol) were dissolved in 4 mL DMSO/H2O (v/v=3:1)
with NH4ClO4 (0.2M) as electrolyte. The reaction flask was
equipped with Pt foils as anode and cathode (1.5 cm2). The
solution was electrolyzed at a constant current (5 mA) for
15 h (270 C of charge passed based on the standard condi-
tions) at ambient temperature. After electrolysis, the mix-
ture was quenched by water and extracted with ethyl acetate
(3”15 mL). The combined organic layer was washed with
brine (5 mL) and dried over MgSO4. Pure product was ob-
tained after column chromatography on silica gel using a sol-
vent mixture of petroleum ether and ethyl acetate.
5-Methyl-2-phenyl-1H-benzo[d]imidazole (3g):[16a] The
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3g as
a yellow solid; yield: 77.4 mg (93%); Rf =0.44 (PE/EA=2/
1
1); H NMR (400 MHz, DMSO-d6): d=12.79 (s, 1H), 8.20
(d, J=7.4 Hz, 2H), 7.57–7.53 (m, 3H), 7.50–7.48 (m, 1H),
7.41 (m, 1H), 7.05–7.03 (m, 1H), 2.44 (s, 3H); 13C NMR
(100 MHz, DMSO-d6): d=150.9, 131.3, 130.3, 129.6, 128.9,
126.3, 123.5, 21.3.
5,6-Dimethyl-2-phenyl-1H-benzo[d]imidazole
(3h):[16a]
The crude product was purified by column chromatography
on silica gel (petroleum ether/ethyl acetate=2:1) to give 3h
as a yellow solid; yield: 54.2 mg (61%); Rf =0.46 (PE/EA=
Characterization Data of 2-Substituted Benzoxazoles
2-Phenyl-1H-benzo[d]imidazole (3a):[7] The crude product
was purified by column chromatography on silica gel (petro-
leum ether/ethyl acetate=2:1) to give 3a as a yellow solid;
yield: 72.9 mg (94%); Rf =0.44 (PE/EA=2/1); 1H NMR
(400 MHz, DMSO-d6): d=13.00 (br s, 1H), 8.23 (d, J=
7.3 Hz, 2H), 7.64–7.64 (m, 2H), 7.58–7.55 (m, 2H), 7.51–
7.50 (m, 1H), 7.24–7.23 (m, 2H); 13C NMR (100 MHz,
DMSO-d6): d=151.2, 130.2, 129.8, 128.9, 126.4, 122.1.
1
2/1); H NMR (400 MHz, DMSO-d6): d=12.33 (br s, 1H),
8.24 (d, J=7.5 Hz, 2H), 7.54–7.50 (m, 2H), 7.46–7.43 (m,
3H), 2.31 (s, 6H); 13C NMR (100 MHz, DMSO-d6): d=
150.5, 130.4, 129.4, 128.8, 126.3, 19.9.
5-Methoxy-2-phenyl-1H-benzo[d]imidazole (3i):[6b] The
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3i as
a yellow solid; yield: 73.5 mg (82%); Rf =0.33 (PE/EA=2/
4-Chloro-2-phenyl-1H-benzo[d]imidazole (3b):[16a] The
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3b as
a yellow solid; yield: 78.4 mg (86%); Rf =0.48 (PE/EA=2/
1); 1H NMR (400 MHz, DMSO-d6): d=13.30 (br s, 1H),
8.24 (d, J=6.5 Hz, 2H), 7.58–7.53 (m, 4H), 7.30–7.28 (m,
1
1); H NMR (400 MHz, CDCl3): d=9.83 (br s, 1H), 8.18–
8.16 (m, 2H), 7.46 (d, J=8.8 Hz, 1H), 7.34–7.33 (m, 3H),
6.97–6.97 (m, 1H), 6.86–6.84 (m, 1H), 3.69 (s, 3H);
13C NMR (100 MHz, CDCl3): d=156.7, 152.3, 139.4, 134.5,
130.1, 129.9, 129.1, 126.8, 116.2, 112.6, 97.5, 55.7.
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5-Nitro-2-phenyl-1H-benzo[d]imidazole
(3j):[16a]
The
13C NMR (100 MHz, CDCl3): d=168.1, 154.2, 135.1, 133.7,
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3j as
a brown solid; yield: 28.7 mg (30%); Rf =0.40 (PE/EA=2/
1); 1H NMR (400 MHz, DMSO-d6): d=13.44 (br s, 1H),
8.45 (s, 1H), 8.21–8.19 (m, 2H), 8.11–8.09 (m, 1H), 7.75–
7.73 (m, 1H), 7.59–7.57 (m, 3H); 13C NMR (100 MHz,
DMSO-d6): d=155.7, 142.7, 130.9, 129.1, 129.0, 126.9, 117.9.
2-Benzyl-1H-benzo[d]imidazole (3k):[16c] The crude prod-
uct was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate=2:1) to give 3k as a yellow
solid; yield: 60.8 mg (73%); Rf =0.39 (PE/EA=2/1);
1H NMR (400 MHz, DMSO-d6): d=12.36 (br s, 1H), 7.53–
7.53 (m, 2H), 7.36–7.32 (m, 4H), 7.25–7.23 (m, 1H), 7.16–
7.15 (m, 2H), 4.22 (s, 2H); 13C NMR (100 MHz, DMSO-d6):
d=153.5, 137.6, 128.7, 128.5, 126.5, 34.9.
131.0, 129.1, 127.6, 126.4, 125.2, 123.3, 121.7.
5-Chloro-2-phenylbenzo[d]thiazole (3r):[6b] The crude
product was purified by column chromatography on silica
gel (petroleum ether/ethyl acetate=10:1) to give 3r as
a white solid; yield: 68.6 mg (70%); Rf =0.75 (PE/EA=10/
1
1); H NMR (400 MHz, CDCl3): d=8.08–8.06 (m, 3H), 7.80
(d, J=8.8 Hz, 1H), 7.51–7.50 (m, 3H), 7.37–7.35 (m, 1H);
13C NMR (100 MHz, CDCl3): d=169.9, 150.0, 133.3, 133.2,
132.4, 131.3, 129.1, 127.6, 125.7, 123.1, 122.3.
2-Methylbenzo[d]thiazole (3s):[16g] The crude product was
purified by column chromatography on silica gel (petroleum
ether/ethyl acetate=10:1) to give 3s as a yellow liquid;
yield: 38.1 mg (64%); Rf =0.72 (PE/EA=10/1); 1H NMR
(400 MHz, CDCl3): d=7.94–7.90 (m, 1H), 7.75–7.73 (m,
1H), 7.40–7.34 (m, 1H), 7.29–7.25 (m, 1H), 2.76–2.74 (m,
3H); 13C NMR (100 MHz, CDCl3): d=166.8, 153.4, 135.6,
125.8, 124.6, 122.3, 121.3, 20.0.
2-Methyl-2-phenyl-1H-benzo[d]imidazole (3l):[16d] The
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3l as
a brown liquid; yield: 30.6 mg (58%); Rf =0.61 (PE/EA=2/
1); 1H NMR (400 MHz, CDCl3): d=7.55–7.53 (m, 2H),
7.22–7.29 (m, 2H), 2.62 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=151.4, 138.6, 122.2, 114.5, 14.8.
2-Isobutylbenzo[d]thiazole (3t):[16h] The crude product
was purified by column chromatography on silica gel (petro-
leum ether/ethyl acetate=10:1) to give 3t as a yellow liquid;
yield: 51.2 mg (67%); Rf =0.69 (PE/EA=10/1); 1H NMR
(400 MHz, CDCl3): d=7.99–7.82 (m, 1H), 7.84–7.82 (m,
1H), 7.46–7.42 (m, 1H), 7.36–7.32 (m, 1H), 2.99 (d, J=
6.6 Hz, 2H), 2.28–2.18 (m, 1H), 1.04 (d, J=7.2 Hz, 6H);
13C NMR (100 MHz, CDCl3): d=171.3, 153.3, 135.3, 125.8,
124.6, 122.6, 121.4, 43.3, 29.7, 22.4.
2-Propyl-1H-benzo[d]imidazole (3m):[16e] The crude prod-
uct was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate=2:1) to give 3m as a yellow
liquid; yield: 42.3 mg (66%); Rf =0.58 (PE/EA=2/1);
1H NMR (400 MHz, CDCl3): d=9.51 (br s,1H), 7.58–7.51
(m, 2H), 7.24–7.22 (m, 2H), 2.97 (t, J=7.2 Hz, 2H), 1.97–
1.88 (m, 2H), 0.99 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=155.7, 138.7, 122.1, 114.6, 31.3, 21.8, 13.9.
5-Chloro-2-methylbenzo[d]thiazole (3u):[16i] The crude
product was purified by column chromatography on silica
gel (petroleum ether/ethyl acetate=10:1) to give 3u as
a yellow liquid; yield: 54.9 mg (75%); Rf =0.65 (PE/EA=
10/1); 1H NMR (400 MHz, CDCl3): d=7.91–7.90 (m, 1H),
7.70–7.68 (m, 1H), 7.31–7.29 (m, 1H), 2.81 (s, 3H);
13C NMR (100 MHz, CDCl3): d=169.0, 154.3, 133.9, 132.0,
125.2, 122.3, 122.1, 20.2.
2-Isobutyl-1H-benzo[d]imidazole (3n):[16a] The crude
product was purified by column chromatography on silica
gel (petroleum ether/ethyl acetate=2:1) to give 3n as
a yellow liquid; yield: 45.3 mg (65%); Rf =0.64 (PE/EA=2/
2-Propylbenzo[d]thiazole (3v):[16j] The crude product was
purified by column chromatography on silica gel (petroleum
ether/ethyl acetate=10:1) to give 3v as a yellow liquid;
yield: 56.6 mg (80%); Rf =0.71 (PE/EA=10/1); 1H NMR
(400 MHz, CDCl3): d=7.97 (d, J=8.1 Hz, 1H), 7.81 (d, J=
8.0 Hz, 1H), 7.43 (t, J=7.6 Hz, 1H), 7.32 (t, J=7.6 Hz, 1H),
3.08 (t, J=7.6 Hz, 2H), 1.95–1.86 (m, 2H), 1.05 (t, J=
7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=172.1, 153.3,
135.2, 125.8, 124.6, 122.5, 121.4, 36.2, 23.1, 13.7.
1
1); H NMR (400 MHz, CDCl3): d=9.16 (br s, 1H), 7.57–
7.56 (m, 2H), 7.23–7.21 (m, 2H), 2.86 (d, J=7.2 Hz, 2H),
2.29–2.25 (m, 1H), 0.98 (d, J=6.4 Hz, 6H); 13C NMR
(100 MHz, CDCl3): d=155.0, 138.6, 122.1, 114.6, 38.5, 28.6,
22.5.
6-Chloro-2-phenyl-1H-benzo[d]imidazole (3o):[16f] The
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3o as
a white solid; yieçld: 61.0 mg (63%); Rf =0.43 (PE/EA=2/
2-(Thiophen-2-yl)benzo[d]thiazole (3w):[6b] The crude
product was purified by column chromatography on silica
gel (petroleum ether/ethyl acetate=10:1) to give 3w as
a white solid; yield: 36.4 mg (42%); Rf =0.78 (PE/EA=10/
1
1); H NMR (400 MHz, DMSO-d6): d=12.51 (s, 1H), 7.57–
7.52 (m, 2H), 7.34–7.30 (m, 4H), 7.25–7.22 (m, 1H), 7.17–
7.15 (m, 1H), 4.21 (s, 2H); 13C NMR (100 MHz, DMSO-d6):
d=155.1, 137.3, 128.8, 128.5, 126.6, 125.8, 121.5, 34.9.
1
1); H NMR (400 MHz, DMSO-d6): d=8.10 (d, J=8.0 Hz,
2-(Thiophen-2-yl)-1H-benzo[d]imidazole (3p):[6b] The
crude product was purified by column chromatography on
silica gel (petroleum ether/ethyl acetate=2:1) to give 3p as
a white solid; yield: 16.0 mg (20%); Rf =0.74 (PE/EA=2/1);
1H NMR (400 MHz, DMSO-d6): d=12.93 (s, 1H), 7.84–7.84
(m, 1H), 7.74–7.72 (m, 1H), 7.61–7.61 (m, 1H), 7.52–7.52
(m, 1H), 7.24–7.20 (m, 3H); 13C NMR (100 MHz, DMSO-
d6): d=147.0, 133.6, 128.7, 128.2, 126.7, 122.2.
1H), 8.00 (d, J=8.1 Hz, 1H), 7.87 (d, J=5.0 Hz, 1H), 7.84
(d, J=3.6 Hz, 1H), 7.53 (t, J=7.7 Hz, 1H), 7.44 (t, J=
7.6 Hz, 1H), 7.25 (t, J=4.3 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6): d=160.8, 153.1, 136.3, 134.2, 129.6, 128.7, 128.6,
126.7, 125.5, 122.4, 122.2.
2-Phenylbenzo[d]thiazole (3q):[7] The crude product was
purified by column chromatography on silica gel (petroleum
ether/ethyl acetate=10:1) to give 3q as a white solid; yield:
65.0 mg (77%); Rf =0.72 (PE/EA=10/1); 1H NMR
(400 MHz, CDCl3): d=8.13–8.13 (m, 3H), 7.91 (d, J=
7.4 Hz, 1H), 7.52–7.51 (m, 4H), 7.42–7.41 (m, 1H);
Acknowledgements
We are grateful to the National Natural Science Foundation
of China (Grant Nos. 21172080 and 21372089) for financial
support.
Adv. Synth. Catal. 2016, 358, 1975 – 1981
1980
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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Adv. Synth. Catal. 2016, 358, 1975 – 1981
1981
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim