Oxidant- And Catalyst-Free Synthesis of Sulfonated Benzothiophenes via Electrooxidative Tandem Cyclization

Article abstract of DOI:10.1021/acs.joc.0c02679

A green and practical electrochemical method for the synthesis of C-3-sulfonated benzothiophenes from 2-alkynylthioanisoles and sodium sulfinates was developed under oxidant- and catalyst-free conditions. Moderate to good yields of sulfonated benzothiophenes bearing important and useful functional groups have been achieved at a constant current. Preliminary mechanistic studies indicated a tandem radical addition-cyclization pathway. Moreover, the protocol is easy to scale up and exhibits good reaction efficiency.

Full text of DOI:10.1021/acs.joc.0c02679

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Oxidant- and Catalyst-Free Synthesis of Sulfonated
Benzothiophenes via Electrooxidative Tandem Cyclization
Dong Zhang,∥ Jinlin Cai,∥ Jinze Du, Xujia Wang, Wei He, Zhao Yang, Chengkou Liu,* Zheng Fang,*
and Kai Guo
Cite This: J. Org. Chem. 2021, 86, 2593−2601
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ABSTRACT: A green and practical electrochemical method for
the synthesis of C-3-sulfonated benzothiophenes from 2-alkynylth-
ioanisoles and sodium sulfinates was developed under oxidant- and
catalyst-free conditions. Moderate to good yields of sulfonated
benzothiophenes bearing important and useful functional groups
have been achieved at a constant current. Preliminary mechanistic
studies indicated a tandem radical addition−cyclization pathway.
Moreover, the protocol is easy to scale up and exhibits good reaction efficiency.
Scheme 1. Synthesis of 3-Arylsulfonylbenzothiophenes from
2-Alkynylthioanisoles
INTRODUCTION
■
Benzothiophene and its derivatives are an important class of
heterocyclic compounds that attracted tremendous attention
due to their wide application in medicinal chemistry, natural
products, and materials science.1−3 Among them, C-3-
substituted benzothiophenes are especially important because
of their wide applications in many pharmaceuticals and as drug
candidates.4−6 A variety of synthetic methods have been
developed for the construction of C-3-substituted benzothio-
phenes; among them, 2-alkynylthioanisoles are confirmed as
the most convenient substrates, and different functional groups
such as halogen, silyl, alkoxyalkyl, and benzyl were introduced
to the C-3 position of benzothiophenes.7−15 Even so, it is still
urgent to develop practical and general protocols to construct
structurally diverse functional benzothiophenes.
The sulfonyl group represents not only one of the more
versatile intermediates in organic synthesis,16,17 but also one of
a widely found motif in biologically active compounds and
drug molecules.18−20 In the past few years, oxidative tandem
cyclization has become one of the most practical and efficient
strategies in organic synthesis.21−26 Among the diverse
oxidative tandem synthetic methodologies, the activated
alkynes have proven to be highly valuable for the synthesis
of complex carbo- and heteropolycyclic skeletons via radical-
mediated cyclization and it also avoided the prefunctionaliza-
tion process.27−31 Recently, reactions of sulfonyl-containing
substrates with 2-alkynylthioanisoles via oxidative or photo-
redox-catalyzed radical tandem cyclization have been demon-
strated to be efficient methods to synthesize 3-arylsulfonyl-
benzothiophenes (Scheme 1a).32,33 However, these reported
methods still suffer from some drawbacks, such as the need to
use explosive oxidants and transition-metal catalysts to
generate sulfonyl radical. Therefore, there is still a need to
develop an efficient and environmentally friendly strategy to
synthesize diverse, multisubstituted benzothiophenes.
In this regard, electrochemistry provides an ideal alternative
method. In the past few years, due to its environmental
friendliness and economy, electrochemistry has gradually
become a popular topic in the field of organic synthesis.34−41
With the increasing attention on electrochemistry, the anodic
oxidation C−H functionalization proved to be an efficient
alternative method for classic oxidation-promoted free radical
reactions.42−50 The use of anodic oxidation to generate a
Received: November 10, 2020
Published: January 11, 2021
https://dx.doi.org/10.1021/acs.joc.0c02679
© 2021 American Chemical Society
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radical via direct electron transfer between a substrate and
electrode to achieve tandem cyclization of alkynes has also
been confirmed as an efficient method. Many reactions for
constructing sulfonyl-substituted indoles, isoquinolines, and
indenones via electrochemistry oxidation have been reported
by Sun,51 Guan,52 Lei53 and other groups. Our groups also
successfully achieved the sulfonylation/heteroarylation of
alkenes via distal heteroaryl ipso-migration using anodic
oxidation.54 Inspired by these pioneering studies on synthetic
electrochemistry, herein, we develop a direct sulfonylation of
2-alkynylthioanisoles to achieve intramolecular cyclization
through electrochemical oxidation (Scheme 1b). To the best
of our knowledge, this is the first example of constructing
sulfonated benzothiophenes via electrooxidative tandem
cyclization of 2-alkynylthioanisoles.
investigation focused on the electrochemical parameters;
both increasing and decreasing the constant current would
lead to decreased reaction efficiency (Table 1, entries 14−16).
Then, the effect of the electrode material was probed. It
seemed that replacing the graphite rod anode and Pt plate
cathode with other electrode materials resulted in lower yields
(Table 1, entries 17−19). Therefore, the conditions used in
Table 1, entry 1, were selected as the best reaction conditions.
With the set of optimized reaction conditions in hand, we
first investigated the substrate scope of various 2-alkynylth-
ioanisoles motifs in this electrochemical protocol, and the
results are shown in Table 2. First, the 2-alkynylthioanisoles
a b
,
Table 2. Substrate Scope for 2-Alkynylthioanisoles
RESULTS AND DISCUSSION
■
We initiated our studies by employing 2-alkynylthioanisole
(1a) and sodium p-tolylsulfinate (2a) as model substrates to
optimize the reaction conditions under a constant current
(Table 1).
a
Table 1. Optimization of the Reaction Conditions
b
entry
variation from standard conditions
none
Et4NClO4 as an electrolyte
Et4NBF4 as an electrolyte
nBu4NPF6 as an electrolyte
Piv-ONa as an electrolyte
CH3CN
CH3CN/HFIP
CH3CN/TFE
CH3CN/DCE
CH3CN/H2O (4/1)
CH3CN/H2O (1/1)
25 °C instead of 30 °C
40 °C instead of 30 °C
4 mA
yield (%, 3a)
c
1
2
3
88 (85)
31
66
59
45
36
42
30
21
a
4
Reaction conditions: Pt plate cathode (10 mm × 10 mm × 0.1 mm),
graphite rod anode (Φ 6 mm), I = 8 mA, 1 (0.2 mmol), 2a (0.4
5
6
7
8
n
mmol), Bu4NBF4 (0.1 mmol), CH3CN/H2O (6 mL, v/v = 2/1),
stirred at 30 °C for 3.5 h (5.2 F mol−1) at an undivided cell in air.
b
Isolated yield.
9
c
with different substituents on the aromatic ring of 2-
phenylethynyl were used as substrates to react with sodium
p-tolylsulfinate (2a). As expected, the substrates bearing both
electron-donating and electron-withdrawing groups on the aryl
ring of 2-phenylethynyl were suitable for this transformation,
and the corresponding products (3b−3q) were obtained in
good to excellent yields (43−87%). Substituent screening
showed that the reaction efficiency of the substrates with
electron-withdrawing groups (1p-1q) was significantly re-
duced, and the corresponding products 3p and 3q were
obtained only in 51 and 43% yield, respectively. Moreover,
heterocycles such as thiophene were also well accommodated
under electrocatalytic conditions, furnishing the sulfonated
benzothiophene in good yields (3r-3s). Finally, different
substituents on the aromatic ring of o-methylthio-aryl alkyne
were studied. Gratifyingly, the electronic characteristics of
these groups have no significant influence in this reaction, and
the target products (3t-3w) were obtained in 72−83% yield.
Meanwhile, 2-alkynylanisoles were also subjected to optimized
reaction conditions. Unfortunately, this reaction only afforded
the corresponding product 3x in a trace yield. This discrepancy
suggested that further work is required to generalize the
reaction conditions.
10
11
12
13
14
15
16
17
18
19
85 (81)
67
c
80 (76)
87 (81)
c
47
56
78
27
43
23
6 mA
10 mA
Pt (+) | C (−) instead of C (+) | Pt (−)
C (+) | C (−) instead of C (+) | Pt (−)
Pt (+) | Pt (−) instead of C (+) | Pt (−)
a
Reaction conditions: Pt plate cathode (10 mm × 10 mm × 0.1 mm),
graphite rod anode (Φ 6 mm), I = 8 mA, 1a (0.2 mmol), 2a (0.4
n
mmol), Bu4NBF4 (0.1 mmol), CH3CN/H2O (6 mL, v/v = 2/1),
b
stirred at 30 °C for 3.5 h at an undivided cell in air. 1H NMR yield
c
using CH2Br2 as an internal standard. Isolated yield.
First, different kinds of electrolytes were examined. The
results showed that nBu4NBF4 performed better than the
others, affording the desired product 3a in 85% isolated yield
(Table 1, entries 1−5). Then, the effect of solvent was
n
explored with Bu4NBF4 as the electrolyte under an 8 mA
constant current; the results indicated that the cosolvent of
CH3CN/H2O (v/v = 2/1) was the best one (Table 1, entries
6−11). Screening the temperature showed that 30 °C might be
a suitable choice (Table 1, entries 12−13). Further
Next, the substrate scope for sodium sulfinates was also
studied (Table 3). To our delight, the reaction of 2-
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a b
,
Table 3. Substrates Scope For Sodium Sulfinates
Scheme 3. Control Experiments
a
Reaction conditions: Pt plate cathode (10 mm × 10 mm × 0.1 mm),
graphite rod anode (Φ 6 mm), I = 8 mA, 1a (0.2 mmol), 2 (0.4
n
mmol), Bu4NBF4 (0.1 mmol), CH3CN/H2O (6 mL, v/v = 2/1),
stirred at 30 °C for 3.5 h (5.2 F mol−1) at an undivided cell in air.
b
Isolated yield.
alkynylthioanisole 1a with a variety of sodium sulfinates 2
under the standard conditions offered the corresponding
sulfonated benzothiophenes in good to excellent yields. The
substrates with electron-donating or electron-withdrawing
substituents at the benzene ring were good candidates,
affording the desired benzothiophenes (3aa−3am) in 45−
79% yield. Moreover, other aromatic sodium sulfinates such as
naphthalene- or thiophene-2-sodium sulfinate can also
generate the target products in good yields (3an-3ao). We
also found that several alkyl sodium sulfinates reacted
smoothly, delivering products (3ap-3ar) in 47−64% yield.
To verify the practical application of the electrochemical
protocol for synthesizing sulfonated benzothiophene, a gram-
scale reaction was carried out using 1a (5 mmol, 1.12 g) and
2a (2 equiv) under standard reaction conditions (Scheme 2).
We were pleased to discover that product 3a could be obtained
in 68% isolated yield, which highlights the great potential in
the industrial application of this transformation.
the results showed that the formation of 3a was completely
suppressed. In addition, when ethene-1,1-diyldibenzene (3
equiv) was added into the model reaction under standard
conditions, the formation of 3a was also completely suppressed
and the sulfonyl radical addition elimination product 4 was
obtained in 41% yield. The results suggested the involvement
of a radical pathway in the reaction.
Furthermore, cyclic voltammetry (CV) experiments were
performed to investigate the redox potential of the substrates
(Figure 1). The oxidation peaks of 1a and 2a were observed at
Scheme 2. Gram-Scale Synthesis
To shed light on the mechanism of this reaction, a series of
control experiments were performed (Scheme 3). First, the
reaction of 1a with 2a was conducted under the standard
conditions without the current; as expected the desired
product could be detected. Second, the substituent on the S
atom was investigated and the results showed that sterically
bulkier ethyl (1a′) could also react smoothly; the substrate
(1a″) with an alkene moiety instead of an alkyne was also
tested under standard conditions but no cyclization product
(3a′) was detected. Then, 1a and 2a were treated with 2,2,6,6-
tetramethyl-1-piperidinyloxy (Tempo) or butylated hydrox-
ytoluene (BHT) (3 equiv) under standard reaction conditions;
Figure 1. Cyclic voltammograms of 1a and 2a.
1.60 and 1.40 V, respectively. This phenomenon illustrated
that sodium p-tolylsulfinate 2a was oxidized preferentially at
the anode.
According to the experimental results and previous literature
reports,55−59 a plausible mechanistic pathway for the electro-
catalytic sulfonylation reaction is depicted in Scheme 4. The
reaction sequence begins with sodium p-tolylsulfinate 2a,
which loses one electron at the anode to give the radical
intermediate II or III. The arylsulfonyl radicals III and II are
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chromatography using EtOAc/n-hexane as an eluent to afford the
product.
Scheme 4. Plausible Mechanism
A 50 mL vial was charged with substrate 1a (0.2 mmol, 1.0 equiv),
n
2 (2.0 equiv), Bu4NBF4 (0.5 equiv), CH3CN/H2O (6 mL, v/v = 2/
1) and a magnetic stir bar. The vial was equipped with platinum
electrodes (1 cm × 1 cm × 0.1 mm) as a cathode and a graphite rod
(Φ 6 mm) as an anode. The whole cell was an undivided cell. The
reaction mixture was stirred and electrolyzed at a constant current of
8 mA without a reference electrode in an oil bath under 30 °C for 3.5
h (5.2 F mol−1). After completion of the reaction, it was monitored
with TLC. Then, the reaction mixture was diluted with EtOAc (10
mL) and filtered through a silica gel pad. The vial and silica gel were
washed with an additional volume of EtOAc (20 mL). The filtrate was
concentrated in vacuo, and the resulting residue was purified by flash
column chromatography using EtOAc/n-hexane as an eluent to afford
the product.
Gram-Scale Synthesis of 3a. 2-Alkynylthioanisole 1a (5 mmol,
n
1.12g), sodium p-tolylsulfinate 2a (10 mmol), Bu4BF4 (2.5 mmol),
and CH3CN/H2O (150 mL, v/v = 2/1) were mixed and added to an
oven-dried undivided three-necked bottle (250 mL) equipped with a
stir bar. The bottle was equipped with platinum electrodes (1 cm × 1
cm × 0.1 mm) as a cathode and a graphite rod (Φ 6 mm) as an
anode. The whole cell was an undivided cell. The reaction mixture
was stirred and electrolyzed at a constant current of 8 mA without a
reference electrode in an oil bath under 30 °C for 15 h. When the
reaction was completed, the reaction mixture was washed with water
and extracted with CH2Cl2 (100 mL × 3). The organic layers were
combined, dried over Na2SO4, and concentrated. The crude product
was purified by column chromatography on silica gel using EtOAc/n-
hexane (1:15) as an eluent to afford product 3a in 68% yield.
Cyclic Voltammetry Experiment. Cyclic voltammograms of 1a
and 2a were performed in a three-electrode cell connected to a
Schlenk line under nitrogen at room temperature. The working
electrode was a steady glassy carbon disk electrode, while the counter
electrode was a platinum wire. The reference was an Ag/AgCl
electrode submerged in saturated aqueous KCl solution. (1) 1a (0.2
mmol) and a mixed solvent CH3CN/H2O (6 mL, v/v = 2/1)
containing nBu4NBF4 (0.1 mmol) were poured into the electro-
chemical cell in cyclic voltammetry experiments. The scan rate was
0.10 V s−1, ranging from 0 to 2.5 V. (2) 2a (0.2 mmol) and a mixed
resonance structures. Subsequently, the sulfonyl radical III
undergoes intermolecular radical addition to the alkynyl
moiety of 1a to give the vinyl radical intermediate IV. Then,
the intermediate IV is attacked by the methylthio moiety to
afford the desired product 3a along with the release of the
methyl radical.60−62 The methyl radical is then converted into
methane with the hydrogen from the reaction mixture.
CONCLUSIONS
■
In summary, we have developed a simple and efficient
electrooxidative-mediated tandem radical addition−cyclization
reaction of 2-alkynylthioanisoles with sodium sulfinates. This
electrochemical protocol avoids the use of external catalysts
and chemical oxidants and provides environmentally friendly
access to various sulfonated functionalized benzothiophenes.
Moreover, this reaction is easy to scale up and exhibits good
reaction efficiency, which demonstrates its potential for
practical applications.
n
EXPERIMENTAL SECTION
General Information. Unless otherwise indicated, all commer-
solvent CH3CN/H2O (6 mL, v/v = 2/1) containing Bu4NBF4 (0.1
■
mmol) were poured into the electrochemical cell in cyclic
voltammetry experiments. The scan rate was 0.10 V s−1, ranging
from 0 to 2.5 V.
1
cially available chemicals were used without purification. H NMR
(400 MHz), 13C NMR (100 MHz), and 19F NMR (376 MHz) were
measured on a 400 M spectrometer. The chemical shifts are given in
2-Phenyl-3-tosylbenzo[b]thiophene (3a). Light yellow solid
(61.89 mg, 85%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.62 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H),
7.59−7.36 (m, 9H), 7.13 (d, J = 8.0 Hz, 2H), 2.34 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 152.5, 143.9, 139.4, 138.2, 136.1, 131.7,
130.5, 130.3, 129.5, 129.4, 127.7, 127.0, 125.9, 125.6, 124.6, 121.8,
21.6. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H17O2S2,
365.0664; found: 365.0658.
2-(o-Tolyl)-3-tosylbenzo[b]thiophene (3b). Light yellow solid
(59.74 mg, 79%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.66 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H),
7.54 (t, J = 8.4 Hz, 3H), 7.44 (t, J = 7.6 Hz, 1H), 7.37 (t, J = 8.2 Hz,
1H), 7.28−7.18 (m, 2H), 7.12−7.16 (m, 3H), 2.35 (s, 3H), 2.09 (s,
3H). 13C{1H} NMR (100 MHz, CDCl3) δ 151.6, 144.0, 139.1, 138.5,
138.1, 135.8, 131.1, 131.0, 130.1, 129.8, 129.6, 129.4, 127.2, 125.8,
125.5, 124.9, 124.4, 121.8, 21.5, 20.2. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C22H19O2S2, 379.0821; found: 379.0817.
1
parts per million (ppm) on the delta (δ) scale. H NMR chemical
shifts were determined relative to internal tetramethylsilane (TMS) at
δ 0.0 ppm. 13C NMR chemical shifts were determined relative to
CDCl3 at δ 77.00 ppm. The following abbreviations are used to
explain multiplicities: s = singlet, d = doublet, dd = doublet of
doublet, t = triplet, td = triplet of doublet, q = quartet, m = multiplet,
and br = broad. Analytical thin-layer chromatography (TLC) was
performed on 0.2 mm coated silica gel plates, and the course of the
reactions was visualized using a UV light 254 nm. High-resolution
mass spectra (HRMS) were obtained on an Agilent mass
spectrometer using electrospray ionization-time-of-flight (ESI-TOF).
General Procedure for the Synthesis of Sulfonated
Benzothiophenes. A 50 mL vial was charged with substrate 1
(0.2 mmol, 1.0 equiv), 2a (2.0 equiv), nBu4NBF4 (0.5 equiv.),
CH3CN/H2O (6 mL, v/v = 2/1) and a magnetic stir bar. The vial was
equipped with platinum electrodes (1 cm × 1 cm × 0.1 mm) as a
cathode and a graphite rod (Φ 6 mm) as an anode. The whole cell
was an undivided cell. The reaction mixture was stirred and
electrolyzed at a constant current of 8 mA without a reference
electrode in an oil bath under 30 °C for 3.5 h (5.2 F mol−1). After
completion of the reaction, it was monitored with TLC. Then, the
reaction mixture was diluted with EtOAc (10 mL) and filtered
through a silica gel pad. The vial and silica gel were washed with an
additional volume of EtOAc (20 mL). The filtrate was concentrated
in vacuo, and the resulting residue was purified by flash column
2-(2-Fluorophenyl)-3-tosylbenzo[b]thiophene (3c). Light yellow
solid (52.72 mg, 69%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.47 (d, J = 8.2 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H),
7.67 (d, J = 8.3 Hz, 2H), 7.54−7.36 (m, 4H), 7.28−7.21 (m, 1H),
7.21−7.06 (m, 3H), 2.35 (s, 3H). 19F NMR (376 MHz, CDCl3) δ
−110.49 (s, 1F). 13C{1H} NMR (100 MHz, CDCl3) δ 159.8 (C−F,
1JC−F = 249.4 Hz), 144.9, 144.1, 138.8 (C−F, 3JC−F = 11.6 Hz), 135.5,
3
132.4, 131.8, 131.7, 131.6, 129.5, 127.1, 127.1, 125.8 (C−F, JC−F
=
4
10.2 Hz), 124.3, 123.5 (C−F, JC−F = 3.7 Hz), 121.9, 119.7 (C−F,
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2JC−F = 15.6 Hz), 115.5 (C−F, JC−F = 21.6 Hz), 21.5. HRMS (ESI-
(ESI-TOF) m/z: [M + H]+ calcd for C22H19O2S2, 379.0821; found:
379.0813.
2
TOF) m/z: [M + H]+ calcd for C21H16FO2S2, 383.0570; found:
383.0564.
2-(4-Ethylphenyl)-3-tosylbenzo[b]thiophene (3k). Light yellow
solid (64.30 mg, 82%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.60 (d, J = 8.3 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H),
7.61−7.45 (m, 3H), 7.42 (d, J = 8.1 Hz, 1H), 7.35 (d, J = 8.1 Hz,
2H), 7.23 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 8.1 Hz, 2H), 2.73 (d, J =
7.6 Hz, 2H), 2.33 (s, 3H), 1.31 (t, J = 7.6 Hz, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 152.9, 145.8, 143.7, 139.5, 138.1, 136.2, 130.5,
129.94, 129.3, 128.9, 127.2, 127.0, 125.8, 125.4, 124.6, 121.7, 28.8,
21.5, 15.4. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C23H21O2S2,
393.0977; found: 393.0971.
2-(2-Chlorophenyl)-3-tosylbenzo[b]thiophene (3d). Light yellow
solid (57.31 mg, 72%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.53 (d, J = 8.3 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H),
7.67 (d, J = 8.4 Hz, 2H), 7.56−7.49 (m, 1H), 7.47−7.40 (m, 4H),
7.40−7.31 (m, 1H), 7.18 (d, J = 8.1 Hz, 2H), 2.35 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 148.4, 144.1, 138.8, 138.7, 135.3, 134.2,
132.5, 131.6, 130.8, 130.8, 129.5, 129.3, 127.3, 126.0, 125.8, 125.8,
124.4, 122.1, 21.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C21H16ClO2S2, 399.0275; found: 399.0270.
2-(2-Bromophenyl)-3-tosylbenzo[b]thiophene (3e). Light yellow
solid (53.92 mg, 61%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.54 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 8.1 Hz, 1H),
7.68 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.9 Hz, 1H), 7.51 (dd, J = 8.3,
1.1 Hz, 1H), 7.44 (ddd, J = 13.9, 7.3, 1.4 Hz, 3H), 7.35 (td, J = 7.6,
1.9 Hz, 1H), 7.19 (d, J = 8.1 Hz, 2H), 2.36 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 150.1, 144.2, 138.7, 138.7, 135.2, 132.8, 132.5,
132.5, 131.3, 130.9, 129.5, 127.4, 126.5, 125.9, 125.8, 124.5, 124.1,
122.1, 21.6. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C21H16BrO2S2, 442.9770; found: 442.9763.
2-(m-Tolyl)-3-tosylbenzo[b]thiophene (3f). Light yellow solid
(62.00 mg, 82%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.63 (d, J = 10.1 Hz, 1H), 7.79 (d, J = 9.8 Hz, 1H),
7.59−7.48 (m, 3H), 7.45−7.38 (m, 1H), 7.33−7.26 (m, 2H), 7.23 (d,
J = 8.3 Hz, 1H), 7.18−7.06 (m, 3H), 2.38 (s, 3H), 2.34 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 152.7, 143.8, 139.4, 138.1,
137.3, 136.1, 131.5, 131.1, 130.1, 129.3, 127.5, 127.1, 125.9, 125.5,
124.6, 121.7, 21.5, 21.3. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C22H19O2S2, 379.0821; found: 379.0815.
2-(4-Methoxyphenyl)-3-tosylbenzo[b]thiophene (3l). Light yel-
1
low solid (52.81 mg, 67%), (hexane/ethyl acetate = 10:1). H NMR
(400 MHz, CDCl3) δ 8.60 (d, J = 8.3 Hz, 1H), 7.78 (d, J = 8.0 Hz,
1H), 7.62−7.43 (m, 3H), 7.45−7.35 (m, 3H), 7.14 (d, J = 8.2 Hz,
2H), 6.94 (d, J = 8.7 Hz, 2H), 3.89 (s, 3H), 2.33 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 160.6, 152.8, 143.8, 139.5, 138.1, 136.2,
131.9, 129.7, 129.7, 126.9, 125.8, 125.4, 124.5, 123.7, 121.7, 113.1,
55.4, 21.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C22H19O3S2,
395.0770; found: 395.0766.
2-(4-Fluorophenyl)-3-tosylbenzo[b]thiophene (3m). Light yellow
solid (55.78 mg, 73%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.61 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H),
7.63−7.47 (m, 3H), 7.47−7.38 (m, 3H), 7.20−7.01 (m, 4H), 2.34 (s,
3H). 19F NMR (376 MHz, CDCl3) δ −111.24 (s, 1F). 13C{1H} NMR
1
(100 MHz, CDCl3) δ 163.5 (C−F, JC−F = 249.9 Hz), 151.2, 144.0,
139.2, 138.0, 136.1, 132.4 (C−F, 3JC−F = 8.5 Hz), 130.5, 129.8, 129.5,
127.8, 127.5 (C−F, 4JC−F = 3.4 Hz), 126.9, 126.0, 125.7, 124.6, 121.7,
2
114.8 (C−F, JC−F = 21.9 Hz), 21.5. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C21H16FO2S2, 383.0570; found: 383.0563.
2-(4-Chlorophenyl)-3-tosylbenzo[b]thiophene (3n). Light yellow
solid (48.56 mg, 61%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.60 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.1 Hz, 1H),
7.54 (dd, J = 14.0, 8.2 Hz, 3H), 7.48−7.33 (m, 5H), 7.17 (d, J = 8.2
Hz, 2H), 2.35 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 150.8,
144.1, 139.2, 138.1, 135.9, 135.8, 131.8, 130.1, 129.8, 129.5, 127.9,
127.1, 126.1, 125.8, 124.6, 121.8, 21.6. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C21H16ClO2S2, 399.0275; found: 399.0267.
2-(4-Bromophenyl)-3-tosylbenzo[b]thiophene (3o). Light yellow
solid (46.85 mg, 53%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.60 (d, J = 8.3 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H),
7.62−7.47 (m, 5H), 7.45 (t, J = 8.1 Hz, 1H), 7.31 (d, J = 8.4 Hz, 2H),
7.17 (d, J = 8.1 Hz, 2H), 2.35 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 150.8, 144.1, 139.2, 138.1, 135.9, 132.0, 130.9, 130.6, 130.6,
129.5, 127.1, 126.1, 125.8, 124.6, 124.1, 121.8, 21.6. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C21H16BrO2S2, 442.9770; found:
442.9762.
Methyl 4-(3-Tosylbenzo[b]thiophen-2-yl)benzoate (3p). Light
yellow solid (43.05 mg, 51%), (hexane/ethyl acetate = 10:1). 1H
NMR (400 MHz, CDCl3) δ 8.61 (d, J = 8.3 Hz, 1H), 8.09 (d, J = 8.4
Hz, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.64−7.49 (m, 5H), 7.46 (t, J = 7.6
Hz, 1H), 7.16 (d, J = 8.1 Hz, 2H), 3.98 (s, 3H), 2.35 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 166.6, 150.8, 144.2, 139.1,
138.3, 136.4, 135.9, 130.9, 130.9, 130.6, 129.6, 128.8, 127.1, 126.1,
125.9, 124.6, 121.8, 52.4, 21.5. HRMS (ESI-TOF) m/z: [M + H]+
calcd for C23H19O4S2, 423.0719; found: 423.0715.
3-Tosyl-2-(4-(trifluoromethyl)phenyl)benzo[b]thiophene (3q).
Light yellow solid (37.16 mg, 43%), (hexane/ethyl acetate = 15:1).
1H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 8.3 Hz, 1H), 7.83 (d, J =
8.0 Hz, 1H), 7.67 (d, J = 8.2 Hz, 2H), 7.54−7.57 (m, 5H), 7.47 (t, J =
7.5 Hz, 1H), 7.16 (d, J = 8.2 Hz, 2H), 2.35 (s, 3H). 19F NMR (376
MHz, CDCl3) δ −62.71 (s, 3F). 13C{1H} NMR (100 MHz, CDCl3) δ
149.9, 144.3, 139.0, 138.2, 135.8, 135.5, 131.5, 131.2, 131.1, 130.9,
2-(3-Fluorophenyl)-3-tosylbenzo[b]thiophene (3g). Light yellow
solid (54.25 mg, 71%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.62 (d, J = 7.4 Hz, 1H), 7.81 (d, J = 7.8 Hz, 1H),
7.61−7.50 (m, 3H), 7.48−7.35 (m, 2H), 7.24 (dt, J = 7.7, 1.3 Hz,
1H), 7.20−7.13 (m, 3H), 7.10 (dt, J = 9.3, 2.0 Hz, 1H), 2.35 (s, 3H).
19F NMR (376 MHz, CDCl3) δ −113.14 (s, 1F). 13C{1H} NMR (100
MHz, CDCl3) δ 161.7 (C−F, 1JC−F = 247.2 Hz), 150.3, 144.1, 139.1,
138.1, 135.9, 133.6 (C−F, 3JC−F = 8.4 Hz), 130.8, 129.5, 129.2 (C−F,
4
3JC−F = 8.5 Hz), 127.0, 126.5 (C−F, JC−F = 3.0 Hz), 126.1, 125.8,
124.7, 121.8, 117.6 (C−F, 2JC−F = 23.0 Hz), 116.4 (C−F, 2JC−F = 20.8
Hz), 21.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H16FO2S2,
383.0570; found: 383.0566.
2-(3-Chlorophenyl)-3-tosylbenzo[b]thiophene (3h). Light yellow
solid (50.15 mg, 63%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.64 (d, J = 10.1 Hz, 1H), 7.82 (d, J = 9.0 Hz, 1H),
7.62−7.49 (m, 3H), 7.49−7.42 (m, 2H), 7.40−7.32 (m, 2H), 7.27
(m, 1H), 7.17 (d, J = 8.0 Hz, 2H), 2.36 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 150.0, 144.2, 139.1, 138.1, 135.9, 133.6, 133.3, 131.1,
130.1, 129.5, 128.9, 128.9, 127.1, 126.1, 125.8, 124.7, 121.8, 21.5.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H16ClO2S2,
399.0275; found: 399.0271.
2-(3-Bromophenyl)-3-tosylbenzo[b]thiophene (3i). Light yellow
solid (52.15 mg, 59%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.65 (d, J = 9.1 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H),
7.62−7.51 (m, 4H), 7.49−7.37 (m, 3H), 7.30 (t, J = 7.9 Hz, 1H),
7.17 (d, J = 8.0 Hz, 2H), 2.37 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 149.9, 144.2, 139.1, 138.1, 135.9, 133.6, 132.8, 132.4, 131.2,
129.5, 129.4, 129.2, 127.1, 126.1, 125.8, 124.7, 121.8, 121.6, 21.6.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H16BrO2S2,
442.9770; found: 442.9766.
2-(p-Tolyl)-3-tosylbenzo[b]thiophene (3j). Light yellow solid
(65.78 mg, 87%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.58 (d, J = 8.3 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H),
7.57 (d, J = 8.3 Hz, 2H), 7.50 (d, J = 7.2 Hz, 1H), 7.42 (d, J = 8.2 Hz,
1H), 7.34 (d, J = 8.1 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 7.14 (d, J =
8.0 Hz, 2H), 2.44 (s, 3H), 2.33 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 153.0, 143.8, 139.6, 139.5, 138.1, 136.2, 130.4, 129.9, 129.4,
128.8, 128.4, 127.0, 125.9, 125.5, 124.6, 121.7, 21.6, 21.5. HRMS
129.6, 127.0, 126.2, 126.1, 125.2, 124.7, 124.6 (q,
J = 3.7 Hz),
C−F
122.5, 121.8, 21.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C22H16F3O2S2, 433.0538; found: 433.0531.
2-(Thiophen-2-yl)-3-tosylbenzo[b]thiophene (3r). Light yellow
solid (55.50 mg, 75%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.67 (d, J = 8.3 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H),
2597
https://dx.doi.org/10.1021/acs.joc.0c02679
J. Org. Chem. 2021, 86, 2593−2601

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
7.60 (d, J = 8.3 Hz, 2H), 7.55−7.42 (m, 3H), 7.42 (t, J = 8.2 Hz, 1H),
7.19−7.06 (m, 3H), 2.33 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3)
δ 144.6, 144.1, 139.0, 138.2, 136.5, 132.2, 131.0, 130.6, 129.4, 129.3,
127.4, 126.9, 126.0, 125.8, 124.8, 121.5, 21.5. HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C19H15O2S3, 371.0229; found: 371.0223.
2-(Thiophen-3-yl)-3-tosylbenzo[b]thiophene (3s). Light yellow
solid (48.84 mg, 66%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.66 (d, J = 8.3 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H),
7.61−7.47 (m, 4H), 7.42 (t, J = 7.1 Hz, 1H), 7.36 (dd, J = 5.0, 3.0 Hz,
1H), 7.27 (d, J = 1.1 Hz, 1H), 7.13 (d, J = 8.0 Hz, 2H), 2.33 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 147.1, 143.9, 139.3, 137.8,
136.4, 131.1, 130.2, 130.1, 129.3, 127.8, 126.8, 125.9, 125.5, 125.0,
124.6, 121.6, 21.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C19H15O2S3 371.0229; found: 371.0225.
6-Methyl-2-phenyl-3-tosylbenzo[b]thiophene (3t). Light yellow
solid (62.76 mg, 83%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.48 (d, J = 8.5 Hz, 1H), 7.58 (s, 1H), 7.53 (d, J =
8.2 Hz, 2H), 7.48−7.36 (m, 5H), 7.33 (d, J = 8.6 Hz, 1H), 7.12 (d, J
= 8.3 Hz, 2H), 2.47 (s, 3H), 2.32 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 151.3, 143.7, 139.5, 138.4, 135.8, 133.9, 131.8, 130.5, 130.0,
129.3, 129.3, 127.6, 127.6, 127.0, 124.2, 121.4, 21.5, 21.4. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C22H19O2S2, 379.0821; found:
379.0815.
3-((2-Chlorophenyl)sulfonyl)-2-phenylbenzo[b]thiophene (3ac).
Light yellow solid (60.67 mg, 79%), (hexane/ethyl acetate = 15:1).
1H NMR (400 MHz, CDCl3) δ 8.63 (d, J = 8.4 Hz, 1H), 7.83 (d, J =
7.9 Hz, 1H), 7.64 (dd, J = 8.0, 1.3 Hz, 1H), 7.54−7.48 (m, 1H),
7.47−7.40 (m, 1H), 7.32−7.26 (m, 4H), 7.25−7.18 (m, 3H), 7.07−
7.00 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ 152.1, 139.1,
137.7, 136.9, 133.7, 132.8, 131.1, 131.0, 130.3, 130.3, 129.3, 128.9,
127.6, 126.2, 125.8, 125.4, 124.9, 121.6. HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C20H13ClO2S2, 385.0118; found: 385.0113.
3-((2-Bromophenyl)sulfonyl)-2-phenylbenzo[b]thiophene (3ad).
Light yellow solid (52.21 mg, 61%), (hexane/ethyl acetate = 15:1).
1H NMR (400 MHz, CDCl3) δ 8.68 (d, J = 8.4 Hz, 1H), 7.84 (d, J =
8.0 Hz, 1H), 7.63 (dd, J = 7.9, 1.5 Hz, 1H), 7.56−7.49 (m, 1H), 7.45
(t, J = 7.0 Hz, 2H), 7.27 (d, J = 2.1 Hz, 2H), 7.25 (s, 1H), 7.17 (t, J =
7.7 Hz, 3H), 7.04 (t, J = 8.2 Hz, 1H). 13C{1H} NMR (100 MHz,
CDCl3) δ 151.7, 140.7, 137.7, 137.3, 134.6, 133.5, 131.0, 130.7, 130.2,
129.3, 128.7, 127.6, 126.8, 125.8, 125.4, 125.1, 121.7, 121.0. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C20H14BrO2S2, 428.9613; found:
428.9609.
3-((4-Methoxyphenyl)sulfonyl)-2-phenylbenzo[b]thiophene
(3ae). Light yellow solid (47.89 mg, 63%), (hexane/ethyl acetate =
10:1). 1H NMR (400 MHz, CDCl3) δ 8.63 (d, J = 8.3 Hz, 1H), 7.79
(d, J = 8.0 Hz, 1H), 7.57 (d, J = 9.0 Hz, 2H), 7.52 (t, J = 7.8 Hz, 1H),
7.48−7.38 (m, 6H), 6.78 (d, J = 9.0 Hz, 2H), 3.78 (s,3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 163.1, 152.0, 138.1, 136.1, 134.01, 131.8,
130.7, 130.5, 129.4, 129.2, 127.6, 125.9, 125.5, 124.6, 121.7, 113.9,
55.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H16O3S2,
381.0614; found: 381.0608.
3-((4-(Tert-butyl)phenyl)sulfonyl)-2-phenylbenzo[b]thiophene
(3af). Light yellow solid (59.29 mg, 73%), (hexane/ethyl acetate =
15:1). 1H NMR (400 MHz, CDCl3) δ 8.66 (d, J = 8.3 Hz, 1H), 7.79
(d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 7.8 Hz, 1H),
7.45−7.37 (m, 6H), 7.33 (d, J = 8.2 Hz, 2H), 1.26 (s, 9H). 13C{1H}
NMR (100 MHz, CDCl3) δ 156.7, 152.3, 139.2, 138.1, 136.2, 131.7,
130.4, 129.3, 127.6, 126.8, 126.2, 125.9, 125.7, 125.5, 124.7, 121.7,
35.1, 31.0. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C24H23O2S2,
407.1134; found: 407.1129.
6-Fluoro-2-phenyl-3-tosylbenzo[b]thiophene (3u). Light yellow
solid (59.60 mg, 78%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.61 (dd, J = 9.2, 5.1 Hz, 1H), 7.55−7.43 (m, 4H),
7.37−7.41 (m, 4H), 7.31−7.20 (m, 1H), 7.12 (d, J = 8.4 Hz, 2H),
2.33 (s, 3H). 19F NMR (376 MHz, CDCl3) δ −114.88 (s, 1F).
13C{1H} NMR (100 MHz, CDCl3) δ 160.8 (C−F, 1JC−F = 247.9 Hz),
3
152.0 (C−F, JC−F = 3.2 Hz), 144.0, 139.2, 139.0, 132.6 (C−F, 4JC−F
= 1.4 Hz), 131.3, 130.5, 130.1, 129.5, 129.4, 127.7, 127.0, 126.10 (C−
3
2
2
F, J = 9.0 Hz), 114.9 (C−F, JC−F = 23.7 Hz), 107.8 (C−F, JC−F
=
25.5 Hz), 21.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C21H16FO2S2, 383.0570; found: 383.0561.
6-Chloro-2-phenyl-3-tosylbenzo[b]thiophene (3v). Light yellow
solid (62.89 mg, 79%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.57 (d, J = 8.9 Hz, 1H), 7.77 (d, J = 1.9 Hz, 1H),
7.53−7.44 (m, 4H), 7.38−7.42 (m, 4H), 7.12 (d, J = 8.0 Hz, 2H),
2.33 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 152.7, 144.1,
139.1, 139.1, 134.6, 131.9, 131.2, 130.5, 130.2, 129.6, 129.4, 127.7,
127.0, 126.7, 125.6, 121.3, 21.5. HRMS (ESI-TOF) m/z: [M + H]+
calcd for C21H15ClO2S2, 399.0275; found: 399.0267.
6-Bromo-2-phenyl-3-tosylbenzo[b]thiophene (3w). Light yellow
solid (63.64 mg, 72%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.51 (d, J = 8.9 Hz, 1H), 7.93 (d, J = 1.8 Hz, 1H),
7.62 (dd, J = 8.9, 1.9 Hz, 1H), 7.48 (d, J = 8.3 Hz, 3H), 7.40 (d, J =
4.4 Hz, 4H), 7.12 (d, J = 8.0 Hz, 2H), 2.33 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 152.7, 144.1, 139.4, 139.1, 135.0, 131.1, 130.4,
130.3, 129.6, 129.4, 129.4, 127.7, 127.0, 125.8, 124.2, 119.7, 21.5.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H16BrO2S2,
442.9770; found: 442.9761.
3-((4-Fluorophenyl)sulfonyl)-2-phenylbenzo[b]thiophene (3ag).
Light yellow solid (55.21 mg, 75%), (hexane/ethyl acetate = 15:1).
1H NMR (400 MHz, CDCl3) δ 8.64 (d, J = 8.3 Hz, 1H), 7.82 (d, J =
8.0 Hz, 1H), 7.66−7.59 (m, 2H), 7.55 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H),
7.51−7.38 (m, 6H), 6.98 (t, J = 8.6 Hz, 2H). 19F NMR (376 MHz,
CDCl3) δ −104.44 (s, 1F). 13C{1H} NMR (100 MHz, CDCl3) δ
165.2 (C−F, 1JC−F = 255.7 Hz), 152.8, 138.2 (C−F, 4JC−F = 3.2 Hz),
138.1, 136.0, 131.4, 130.5, 129.9, 129.8, 129.7, 129.6, 127.7, 125.9
(C−F, 2JC−F = 37.6 Hz), 124.5, 121.8, 116.0 (C−F, 3JC−F = 22.6 Hz).
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C20H13FO2S2, 369.0414;
found: 369.0408.
3-((4-Chlorophenyl)sulfonyl)-2-phenylbenzo[b]thiophene (3ah).
Light yellow solid (54.53 mg, 71%), (hexane/ethyl acetate = 15:1).
1H NMR (400 MHz, CDCl3) δ 8.63 (d, J = 8.3 Hz, 1H), 7.83 (d, J =
8.0 Hz, 1H), 7.58−7.39 (m, 9H), 7.31−7.27 (m, 2H). 13C{1H} NMR
(100 MHz, CDCl3) δ 153.1, 140.6, 139.5, 138.1, 136.0, 131.3, 130.5,
129.6, 129.6, 129.0, 128.4, 127.7, 126.1, 125.7, 124.4, 121.8. HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C20H14ClO2S2, 385.0118; found:
385.0111.
3-((4-Bromophenyl)sulfonyl)-2-phenylbenzo[b]thiophene (3ai).
Light yellow solid (53.07 mg, 62%), (hexane/ethyl acetate = 15:1).
1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.3 Hz, 1H), 7.82 (d, J =
8.0 Hz, 1H), 7.55 (ddd, J = 8.4, 7.2, 1.2 Hz, 1H), 7.51−7.38 (m,
10H). 13C{1H} NMR (100 MHz, CDCl3) δ 153.1, 141.2, 138.1,
135.9, 132.0, 131.3, 130.5, 129.6, 129.5, 128.5, 128.1, 127.7, 126.1,
125.7, 124.4, 121.8. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C20H14BrO2S2 428.9613; found: 428.9608.
3-((4-Iodophenyl)sulfonyl)-2-phenylbenzo[b]thiophene (3aj).
Light yellow solid (53.31 mg, 56%), (hexane/ethyl acetate = 15:1).
1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 8.4 Hz, 1H), 7.74 (d, J =
8.1 Hz, 1H), 7.59 (d, J = 8.6 Hz, 2H), 7.47 (t, J = 7.3 Hz, 1H), 7.42−
7.32 (m, 6H), 7.24 (d, J = 8.6 Hz, 2H). 13C{1H} NMR (100 MHz,
2-Phenyl-3-(phenylsulfonyl)benzo[b]thiophene (3aa). Light yel-
1
low solid (47.61 mg, 68%), (hexane/ethyl acetate = 15:1). H NMR
(400 MHz, CDCl3) δ 8.64 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 8.0 Hz,
1H), 7.65 (d, J = 7.2 Hz, 2H), 7.57−7.51 (m, 1H), 7.49−7.37 (m,
7H), 7.33 (t, J = 7.8 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ
152.9, 142.2, 138.1, 136.1, 132.9, 131.5, 130.5, 129.9, 129.5, 128.7,
127.7, 126.9, 126.0 125.6, 124.6, 121.7. HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd for C20H15O2S2 351.0508; found: 351.0503.
2-Phenyl-3-(o-tolylsulfonyl)benzo[b]thiophene (3ab). Light yel-
1
low solid (41.50 mg, 57%), (hexane/ethyl acetate = 15:1). H NMR
(400 MHz, CDCl3) δ 8.61 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 7.9 Hz,
1H), 7.56 (d, J = 8.0 Hz, 1H), 7.53−7.47 (m, 1H), 7.46−7.41 (m,
1H), 7.36−7.31 (m, 1H), 7.27 (dd, J = 7.6, 5.8 Hz, 3H), 7.23 (d, J =
8.3 Hz, 2H), 7.05 (d, J = 7.6 Hz, 1H), 6.97 (t, J = 7.7 Hz, 1H), 2.19
(s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 151.9, 140.0, 137.9
137.4, 136.7, 132.8, 131.9, 131.1, 130.5, 130.3, 129.7, 129.3, 128.6,
127.6, 125.9, 125.5, 124.9, 121.7, 19.6. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C21H17O2S2, 365.0664; found: 365.0659.
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CDCl3) δ 153.1, 141.9, 138.1, 138.0, 136.0, 131.4, 130.5, 129.6, 129.6,
128.3, 127.7, 126.1, 125.7, 124.5, 121.8, 100.7. HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C20H14IO2S2, 476.9474; found: 476.9468.
2-Phenyl-3-((4-(trifluoromethyl)phenyl)sulfonyl)benzo[b]-
thiophene (3ak). Light yellow solid (42.64 mg, 51%), (hexane/ethyl
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H15O2S2, 303.0508;
found: 303.0499.
(2-Tosylethene-1,1-diyl)dibenzene (4). Yellow liquid (54.79 mg,
1
41%), (hexane/ethyl acetate =25:1). H NMR (400 MHz, CDCl3) δ
7.47 (d, J = 8.3 Hz, 2H), 7.40−7.33 (m, 2H), 7.30 (t, J = 7.6 Hz, 4H),
7.22−7.17 (m, 2H), 7.15 (d, J = 8.0 Hz, 2H), 7.10 (dd, J = 8.2, 1.3
Hz, 2H), 6.99 (s, 1H), 2.38 (s, 3H). 13C NMR (100 MHz, CDCl3) δ
154.7, 143.7, 139.2, 138.6, 130.2, 129.8, 129.3, 129.0, 128.8, 128.5,
128.2, 127.8, 127.7, 21.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C21H18O2S, 335.1100; found: 335.1097.
1
acetate = 15:1). H NMR (400 MHz, CDCl3) δ 8.66 (d, J = 8.3 Hz,
1H), 7.81 (d, J = 8.1 Hz, 1H), 7.72 (d, J = 8.3 Hz, 2H), 7.59−7.53
(m, 3H), 7.51−7.29 (m, 7H). 19F NMR (376 MHz, CDCl3) δ −63.20
(s, 3F). 13C{1H} NMR (100 MHz, CDCl3) δ 153.6, 145.6, 138.1,
136.0, 134.4 (q, JC−F = 32.8 Hz), 125.8 (d, JC−F = 4.3 Hz), 131.2,
130.5, 129.7, 129.1, 127.8, 127.5, 126.2, 125.7−125.8 (m), 124.4,
121.9. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H13F3O2S2,
419.0382; found: 419.0377.
4-((2-Phenylbenzo[b]thiophen-3-yl)sulfonyl)benzonitrile (3al).
Light yellow solid (33.75 mg, 45%), (hexane/ethyl acetate = 10:1).
1H NMR (400 MHz, CDCl3) δ 8.63 (d, J = 8.3 Hz, 1H), 7.83 (d, J =
8.0 Hz, 1H), 7.67 (d, J = 8.6 Hz, 2H), 7.61−7.52 (m, 3H), 7.52−7.44
(m, 2H), 7.44−7.32 (m, 4H). 13C{1H} NMR (100 MHz, CDCl3) δ
154.0, 146.2, 138.1, 135.9, 132.4, 131.0, 130.5, 129.9, 128.7, 127.8,
127.5, 126.3, 125.9, 124.3, 121.9, 117.2, 116.5. HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C21H14NO2S2, 376.0460; found: 376.0452.
3-([1,1′-Biphenyl]-4-ylsulfonyl)-2-phenylbenzo[b]thiophene
(3am). Light yellow solid (40.90 mg, 48%), (hexane/ethyl acetate =
15:1). 1H NMR (400 MHz, CDCl3) δ 8.69 (d, J = 8.3 Hz, 1H), 7.82
(d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.5 Hz, 2H), 7.59−7.35 (m, 14H).
13C{1H} NMR (100 MHz, CDCl3) δ 152.7, 145.8, 140.8, 139.2,
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c02679.
■
sı
1
General information, H, 19F, and 13C NMR spectra of
all products (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Chengkou Liu − College of Biotechnology and Pharmaceutical
Engineering, Nanjing Tech University, Nanjing 211816,
China; Email: liuchengkou@njtech.edu.cn
Zheng Fang − College of Biotechnology and Pharmaceutical
Engineering, Nanjing Tech University, Nanjing 211816,
China; orcid.org/0000-0002-3209-4713; Email: fzcpu@
njtech.edu.cn
138.2, 136.2, 131.6, 130.5, 130.2, 129.5, 129.0, 128.5, 127.7, 127.5,
127.4, 127.3, 126.0, 125.6, 124.7, 121.8. HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C26H18O2S2, 427.0821; found: 427.0815.
3-(Naphthalen-2-ylsulfonyl)-2-phenylbenzo[b]thiophene (3an).
Light yellow solid (38.41 mg, 48%), (hexane/ethyl acetate = 12:1).
1H NMR (400 MHz, CDCl3) δ 8.74 (d, J = 8.4 Hz, 1H), 8.14 (s, 1H),
7.85−7.71 (m, 4H), 7.64−7.50 (m, 4H), 7.47−7.30 (m, 6H).
13C{1H} NMR (100 MHz, CDCl3) δ 152.9, 139.0, 138.1, 136.2,
134.9, 131.8, 131.5, 130.6, 130.1, 129.5, 129.4, 129.1, 128.9, 128.5,
127.8, 127.6, 127.3, 126.0, 125.6, 124.7, 122.1, 121.7. HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C24H17O2S2, 401.0664; found:
401.0657.
Authors
Dong Zhang − College of Biotechnology and Pharmaceutical
Engineering, Nanjing Tech University, Nanjing 211816,
China
Jinlin Cai − College of Biotechnology and Pharmaceutical
Engineering, Nanjing Tech University, Nanjing 211816,
China
2-Phenyl-3-(thiophen-2-ylsulfonyl)benzo[b]thiophene (3ao).
Light yellow solid (46.99 mg, 66%), (hexane/ethyl acetate = 15:1).
1H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 8.3 Hz, 1H), 7.82 (d, J =
8.1 Hz, 1H), 7.59−7.35 (m, 9H), 6.94 (dd, J = 4.9, 3.8 Hz, 1H).
13C{1H} NMR (100 MHz, CDCl3) δ 152.9, 143.9, 138.1, 135.7,
133.1, 132.8, 131.6, 130.3, 130.1, 129.5, 127.7, 127.3, 126.0, 125.7,
124.5, 121.8. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C18H13O2S3, 357.0072; found: 357.0068.
3-(Cyclopropylsulfonyl)-2-phenylbenzo[b]thiophene (3ap). Light
yellow solid (35.80 mg, 57%), (hexane/ethyl acetate = 15:1). 1H
NMR (400 MHz, CDCl3) δ 8.51 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 8.1
Hz, 1H), 7.64−7.55 (m, 2H), 7.55−7.48 (m, 1H), 7.49−7.38 (m,
4H), 2.46 (tt, J = 8.0, 4.8 Hz, 1H), 1.17 (qd, J = 5.9, 1.3 Hz, 2H), 0.85
(qd, J = 5.9, 1.3 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 151.9,
138.3, 136.4, 131.8, 130.5, 129.8, 129.6, 127.7, 125.9, 125.6, 124.4,
121.8, 33.7, 5.5. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C17H15O2S2, 315.0508; found: 315.0498.
Jinze Du − College of Biotechnology and Pharmaceutical
Engineering, Nanjing Tech University, Nanjing 211816,
China
Xujia Wang − College of Biotechnology and Pharmaceutical
Engineering, Nanjing Tech University, Nanjing 211816,
China
Wei He − College of Biotechnology and Pharmaceutical
Engineering, Nanjing Tech University, Nanjing 211816,
China
Zhao Yang − College of Engineering, China Pharmaceutical
University, Nanjing 210003, China
Kai Guo − College of Biotechnology and Pharmaceutical
Engineering, Nanjing Tech University, Nanjing 211816,
China; State Key Laboratory of Materials-Oriented Chemical
Engineering, Nanjing 211816, China; orcid.org/0000-
0002-0013-3263
3-(Methylsulfonyl)-2-phenylbenzo[b]thiophene (3aq). Light yel-
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02679
1
low solid (36.87 mg, 64%), (hexane/ethyl acetate = 15:1). H NMR
(400 MHz, CDCl3) δ 8.49 (d, J = 8.3 Hz, 1H), 7.88 (d, J = 8.0 Hz,
1H), 7.61−7.38 (m, 7H), 3.02 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 152.5, 138.2, 136.1, 131.4, 130.3, 129.8, 129.1, 128.0, 126.1,
125.8, 124.2, 121.9, 45.0. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C15H13O2S2, 289.0351; found: 289.0344.
Author Contributions
∥D.Z. and J.C. contributed to the work equally.
Notes
3-(Ethylsulfonyl)-2-phenylbenzo[b]thiophene (3ar). Light yellow
solid (28.39 mg, 47%), (hexane/ethyl acetate = 15:1). 1H NMR (400
MHz, CDCl3) δ 8.48 (d, J = 8.2 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H),
7.64−7.38 (m, 7H), 3.06 (qd, J = 7.4, 1.4 Hz, 2H), 1.19 (td, J = 7.4,
1.4 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 153.4, 136.6,
131.5, 130.5, 129.7, 127.8, 127.1, 126.0, 125.7, 124.4, 121.8, 50.9, 7.1.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by the National Natural Science
Foundation of China (Grant No. 21776130) and the Jiangsu
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