Facile synthesis of benzo[: B] thiophenes via metal-free radical-triggered intramolecular C-S bond formation

Article abstract of DOI:10.1039/c7ob01515a

A facile method for the synthesis of benzo[b]thiophenes with good to excellent yields via metal-free intramolecular C-S bond formation has been developed by utilizing I₂ as a catalyst and O₂ from air as an oxidant (20 examples). Its notable features such as catalytic I₂, intramolecular C-S bond formation, short reaction times, and broad functional group tolerance make this strategy highly attractive. The purification of products only needs washing with solvents, thereby avoiding traditional chromatography and recrystallization, which belongs to group-assisted purification (GAP) chemistry.

Full text of DOI:10.1039/c7ob01515a

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Facile synthesis of benzo[b]thiophenes via metal-free radical-
triggered intramolecular C-S bond formation
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
,a, b
,c
Wei Fan, Kwong-Yuen Chen, Qi-Peng Chen, Guigen Li,* and Bo Jiang*
A facile synthesis of benzo[b]thiophenes with good to excellent yields via metal-free intramolecular C-S bond formation
has been developed by utilizing I as the catalyst and O from air as the oxidant (20 Examples). Notable features such as
catalytic I , intramolecular C-S bond formation, short reaction times, and broad functional group tolerance make this
DOI: 10.1039/x0xx00000x
2
2
www.rsc.org/
2
strategy highly attractive. The purification of products only needs to be washed by solvents, thereby avoiding traditional
chromatography and recrystallization, which belongs to group-assisted purification (GAP) chemistry.
fundamental reactions since it represents a key step in the
7
synthesis of complex molecules. Despite the aforementioned
Introduction
success of C-S coupling reactions, however, metal-free
Among diverse heterocycles, benzo[b]thiophenes commonly
catalyzed intramolecular C-S bond formation still provides a
great challenge in modern organic synthesis. Recently, our
exist in a myriad of bioactive compounds, represented by
1
benocyclidine, zileuton, sertaconazole (Figure 1), which have
groups have been heavily involved in the development of C-S
8
forming reaction. For example, we have established an I
been found to show a broad range of biological activities such
2
/O
2
-
2
3
4
as anti-fungal, anti-tumor, anti-inflammatory. Therefore,
these derivatives have attracted special attention in organic
and medicinal fields. As a result, many approaches toward
enabled intermolecular N-S bond-formation to access
functionalized 1,2,3-thiadiazoles via a formal [3 + 2] annulation
of triethylammonium thiolates with aryl hydrazines under
5
benzo[b]thiophenes have been developed. However, these
9
metal-free condition (Scheme 1a). As a continuation of our
reactions still have some inherent limitations such as moisture
sensitivity, costly metal catalysts, and environmental toxicity.
project, we found that radical-enabled intramolecular C-S
2
bond formation via C(sp )-H functionalization could be
O
Cl
NH2
realized, providing a new and straightforward cyclization
O
Cl
N
approach to benzo[b]thiophenes (Scheme 1b). Under air
N
OH
conditions the preformed triethylammonium thiolates
preferentially reacts with I to form S-I bond, followed by its
homolysis to give S-radical, which is trapped by phenyl ring to
generate benzo[b]thiophenes due to the combination of
I2/O2 could serve as an efficient radical catalytic system.
Notably, the synthesis followed the group-assisted purification
On the other hand, metal-free catalyzed carbon-heteroatom (GAP) chemistry/technology, in which pure
bond formation has drawn considerable interests over the past benzo[b]thiophenes could be readily isolated by washing the
1
N
S
S
S
2
Cl
N
Benocyclidine
Zileuton
Sertaconazole
2
1
0
Figure 1. Several representative benzo[b]thiophenes
2
several decades due to its wide range of practical applications crude products with common 95% EtOH.
Our previous work
in constructing organic molecules as well as in the
6
pharmaceutical industry and process development. The
formation of C-S bonds is one of the most useful and
Ar2
O
HNEt
S
N
3
N
S
Ar1
Ar1
Ar2
NH
2 2
I , O
+
(a)
1,4-dioxane, 100 o
C
H
2
N
R
O
R
O
N
N
H
H
This work
R
O
HNEt
S
3
O
Ar
I
2
(20 mol %)
Ar
GAP (b)
R
O
1,4-dioxane
HN
S
N
H
air, 120 o
C
O
2
A radical process
1
2
0 Examples
Up to 92% yield
Scheme 1 Metal-free synthesis of benzo[b]thiophenes
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J. Name., 2013, 00, 1-3 | 1
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The results are summarized in Scheme 2. Firstly, the influence
of substituents in the phenyl ring (Ar moiety) of
Results and discussion
Initially, we carried out the tentative reaction of
triethylammonium thiolate
1 was investigated. The variants of
triethylammonium thiolate 1a in MeCN at 100 °C using 20
substituents bearing both electron-donating and electron-
withdrawing groups under the optimized conditions did not
hamper the reaction process. Substituents resided at different
positions on the phenyl ring (Ar), such as Cl, Br, Me, and MeO,
were compatible. For instance, more sterically demanding 2-
chloro-substituent was well-suited for this present
transformation, delivering the corresponding product 2d in
mol% of
I
2
as a catalyst under air conditions. This
transformation hardly proceeded, giving a trace amount of the
expected product 2a which failed to be isolated (entry 1).
Similar inferior outcomes were observed when both 1,2-
dichloroethane (DCE) and ethyl acetate (EA) served as reaction
media (entries 2-3) whereas the reaction did not work in EtOH
and the starting materials remained completely unconsumed
7
8% isolated yield. It is worth mentioning that both 3-
(
entry 4). To our delight, exchanging EtOH for tetrahydrofuran
chlorophenyl and 2-naphthyl counterparts enabled their
regioselective C-S coupling to access product 2h and 2i in 83%
and 84% yields, respectively. After the successful utilization of
various substituents in the phenyl ring (Ar moiety), we next
extended our investigation to the electronic properties of
indolin-2-one moiety (R). Functional groups like fluoride,
chloride, bromide and methyl situated in 5- or 6-position of
indolin-2-one ring were well tolerated, affording the
(THF) led to an 80% yield of product 2a (entry 5). The higher
yield (83%) was obtained using 1,4-dioxane as a solvent (entry
). It was found that the reaction temperature affected the
6
reaction efficiency (entries 6-7). The increase of reaction
o
temperature to 120 C resulted in a higher 91% yield (entry 7).
o
However, the higher reaction temperature (130 C) was
adverse to the improvement of chemical yield of 2a (entry 8).
Afterward, we turned our attention to investigate the loading
corresponding benzo[b]thiophenes 2j
-2t in excellent yields
of I
(entry 9) whereas the yield leveled off when the loading of
was increased to 30 mol% (entry 10). Without I catalyst, the
desired product 2a was not observed (entry 11), confirming
that I is essential for the success of this transformation. The
identical performed under O conditions resulted in a flat yield
as compared with air conditions (entry 12), suggestion that O
2 2
-catalyst. Decreasing the loading of I lowered the yield of
(
79%-88%). The structural elucidation of the products was
1
13
2
a
determined from its IR, H, C NMR, and HRMS spectra. In the
case of 2d, its structure was unequivocally confirmed by X-ray
analysis (Figure 2).
I
2
2
2
2
2
from air as a green oxidant could thoroughly oxidize this
reaction process to complete the construction of C-S bond.
a
Table 1. Optimization of reaction conditions for forming 2a
o
b
entry cat. (mol%)
solvent
t ( C)
yield (%)
1
2
3
4
5
6
7
8
9
1
1
I
I
I
I
I
I
I
I
I
I
2
2
2
2
2
2
2
2
2
2
(20)
(20)
(20)
(20)
(20)
(20)
(20)
(20)
(10)
(30)
MeCN
DCE
EA
EtOH
100
100
100
100
100
100
120
130
120
120
120
120
trace
trace
trace
c
ND
THF
80
83
91
80
82
90
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
0
1
2
c
-
I
ND
d
1
2
(20)
91
a
Reaction conditions: all the reactions were performed with 1a
(
1.0 mmol), solvent (2.0 mL) in the sealed reaction tube under
b
c
microwave conditions for 30 min. Isolated yield. ND (Not
Detected). Under O (1.0 atm) conditions.
2
d
Scheme 2 Substrate scope for synthesis of 2. Reaction conditions: all the
reactions were performed with 1 (1.0 mmol), I (0.2 mmol), and 1,4-dioxane
2
With the established optimal conditions, we then set out to
explore the scope of this transformation by employing a
o
(
2.0 mL) in the sealed reaction tube at 120 C under air conditions for 30
b
min. Isolated yield.
variety of structurally diverse triethylammonium thiolate 1.
2
| J. Name., 2012, 00, 1-3
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Orga Pn l ie ca s&e Bd oi o nmo to al ed cj uu sl ta mr Ca rhg ei nms istry
final benzo[b]thiophenes
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DOI: 10.1039/C7OB01515A
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ARTICLE
2
via deprotonation. I
2
is regenerated
2
by reacting with iodine anion and molecular O .
O
O
I
Ar
Ar
S HNEt3
O
heat
S
O
N
H
1
I
2
N
H
A
HI
heat
Ar
H O
O2
2
O
I
S
O
IH
I
Ar
O
H
O
N
H
Ar
S
HN
S
Figure 2. The ORTEP Drawing of 2d
B
O
O
2
N
H
C
To understand the mechanism, several control experiments
were conducted (Scheme 3). Substrate 1a was treated with
Scheme 4 Proposed mechanisms for forming products 2
2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO)
or
butylhydroxytoluene (BHT) (2.0 equiv.) under the standard
conditions (Scheme 3a), and a complex mixture was detected
without observation of 2a, suggesting a possible radical
process. The reaction of 1a under Ar conditions gave a trace
Conclusions
In summary, we have developed
a new metal-free
amount of 2a (Scheme 3b), indicating that O play a key role in
2
intramolecular C-S bond formation that offers a facile
synthesis of benzo[b]thiophenes. The reaction pathway
involved a radical coupling/SET sequence, allowing us to access
blocks of benzo[b]thiophenes with a wide diversity of
substituents. Eco-friendly oxidant, flexible structural
modification and broad functional group compatibility as well
as mild reaction conditions make this strategy highly viable for
future applications. Besides, the purification of products could
avoid traditional chromatography and recrystallization, which
provide a valuable complement for group-assisted purification
the success of this reaction. An intermolecular competitive
experiment between 1b and 1f revealed that electron-rich
group of phenyl ring (Ar) is beneficial to the transformation
(Scheme 3c). A significant primary kinetic isotope effect was
observed (K / K = 3.65), showing that the cleavage of C-H
H
D
bond is a rate-limiting step (Scheme 3d).
O
HNEt3
S
Ph
O
standard conditions
(
a)
(GAP) chemistry.
O
TEMPO or BHT
HN
S
N
H
O
1a
2
a (Not observed)
Experiment
standard conditions
Ar
(
b)
1a
2a (Trace)
General Information
standard conditions
1
b + 1f
2b + 2f
(c)
Melting points were determined in open capillaries and were
uncorrected. IR spectra were taken on a FT-IR-Tensor 27
2
b / 2f = 1 / 2.5
O
HNEt3
O
HNEt
-1
1
13
3
spectrometer in KBr pellets and reported in cm . H NMR ( C
NMR) spectra were measured on a Bruker DPX 400 MHz
[D
5
]-Ph
S
Ph
S
standard
+
2
a + [D ]-2a (d)
4
6 7
spectrometer in DMSO-d or DMF-d with chemical shift (δ)
conditions
O
O
N
given in ppm relative to TMS as internal standard [(s = singlet,
d = doublet, t = triplet, brs = broad singlet, m = multiplet),
coupling constant (Hz)]. HRMS (ESI) was determined by using
N
H
1a
H
H D
K / K = 3.65
[
D
5
]-1a
Scheme 3 Control Experiments
microTOF-Q
crystallographic analysis was performed with a Siemens
On the basis of the above analysis and literature survey , a SMART CCD and a Siemens P4 diffractometer.
Ⅱ
HRMS/MS instrument (BRUKER). X-Ray
9
reasonable mechanism is outlined in Scheme 4. Substrate
undergoes an S-I bond formation to generate intermediate
1
General Procedure for the Synthesis of Products 1.
A
,
Example for the synthesis of 1a: Indoline-2,3-dione (10.0 mmol,
followed by homolysis of S-I bond to yield radical intermediate 1.47 g) and 1-phenyl-2-thiocyanatoethanones (10.0 mmol,
. The intramolecular radical coupling/cyclization between S- 1.77 g) were introduced into a 50-mL reaction flask, ethyl
B
2
radical and C(sp )-H of Ar attached by carbonyls occurs, acetate (10.0 ml) and triethylamine (12.0 mmol, 1.22 g) were
allowing a single-electron transfer (SET) process to access the then successively added into this reaction mixture. The
reaction system was stirred at room temperature for
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overnight. After the completion of the reaction (monitored by (Z)-3-(4-Chloro-3-oxobenzo[b]thiophen-2(3H)-ylidene)indolin-
TLC), triethylamine and ethyl acetate were removed under 2-one (2d)
o
vacuum. The crude solid was purified by recrystallization from A red solid; 244 mg; 78% yield; Mp: >300 C; IR (KBr, ν, cm ):
-1
9
5% ethanol to afford the pure triethylammonium thiolates 3191, 1702, 1672, 1611, 1583, 1481, 1459, 1433, 1403, 1334;
1
1a
.
H NMR (400 MHz, DMSO-d
d, 1H, J = 8.0 Hz, ArH), 7.72 (d, 1H, J = 7.6 Hz, ArH), 7.67 (t, 1H,
J = 7.6 Hz, ArH), 7.43-7.39 (m, 2H, ArH), 7.09 (t, 1H, J = 8.0 Hz,
6
) (δ, ppm): 11.15 (s, 1H, NH), 8.98
(
General Procedure for the Synthesis of Products 2.
Example for the synthesis of 2a: In a typical experiment ArH), 6.95 (d, 1H, J = 7.6 Hz, ArH); C NMR (100 MHz, DMSO-
procedure, triethylammonium (Z)-2-oxo-1-(2-oxoindolin-3- ) (δ, ppm): 187.9, 169.7, 150.5, 144.2, 138.2, 137.1, 134.3,
ylidene)-2-phenylethanethiolate (1a, 1.0 mmol, 382 mg), and I 133.3, 128.6, 128.0, 127.7, 124.6, 124.0, 122.4, 121.1, 110.8;
0.2 mmol, 50.8 mg) were introduced into a 10-mL reaction HRMS (ESI): m/z calcd for: C16
vial. Then 1,4-dioxane (2.0 mL) were successively added, and found: 311.9892.
the mixture stirred at 120 °C under microwave conditions for (Z)-3-(6-Bromo-3-oxobenzo[b]thiophen-2(3H)-
0 min. After completion of the reaction (monitored by TLC), ylidene)indolin-2-one (2e)
the reaction mixture was down to room temperature. The A red-brown solid; 303 mg; 85% yield; Mp: 297-298 C; IR (KBr,
1
3
d
6
2
-
(
7 2
H ClNO S, 311.9886 [M-H] ;
3
o
-1
solid product was collected by Büchner filtration to give almost ν, cm ): 3179, 1705, 1675, 1616, 1585, 1458, 1389, 1340,
pure product 2a
.
1301;
1
(
Z)-3-(3-Oxobenzo[b]thiophen-2(3H)-ylidene)indolin-2-one
2a)
6
H NMR (400 MHz, DMSO-d ) (δ, ppm): 11.16 (s, 1H, NH), 9.00
(
(d, 1H, J = 8.4 Hz, ArH), 8.12 (d, 1H, J = 1.2 Hz, ArH), 7.77 (d,
o
A red solid; 254 mg; 91% yield; Mp: >300 C; IR (KBr, ν, cm ): 1H, J = 8.4 Hz, ArH), 7.61-7.58 (m, 1H, ArH), 7.43 (t, 1H, J = 8.0
-1
1
160, 1698, 1648, 1617, 1587, 1460, 1450, 1338, 1298; H Hz, ArH), 7.09 (t, 1H, J = 8.0 Hz, ArH), 6.96 (d, 1H, J = 7.6 Hz,
3
1
3
6 6
NMR (400 MHz, DMSO-d ) (δ, ppm): 11.12 (s, 1H, NH), 9.00 (d, ArH); C NMR (100 MHz, DMSO-d ) (δ, ppm): 189.5, 169.6,
1
H, J = 7.6 Hz, ArH), 7.84 (d, 1H, J = 7.6 Hz, ArH), 7.75-7.70 (m, 149.6, 144.3, 138.1, 133.4, 131.0, 129.9, 128.5, 128.4, 128.2,
H, ArH), 7.42-7.37 (m, 2H, ArH), 7.09-7.05 (m, 1H, ArH), 6.94 128.0, 127.7, 122.4, 121.2, 110.8; HRMS (ESI): m/z calcd for:
2
1
3
-
(
d, 1H, J = 7.6 Hz, ArH); C NMR (100 MHz, DMSO-d
6
) (δ, ppm):
90.5, 169.6, 147.5, 144.1, 138.5, 136.9, 133.2, 129.3, 127.9,
26.9, 126.8, 125.0, 122.3, 121.2, 110.8; HRMS (ESI): m/z calcd (Z)-3-(6-Methyl-3-oxobenzo[b]thiophen-2(3H)-
16 7 2
C H BrNO S, 355.9381 [M-H] ; found: 355.9374.
1
1
-
for: C16
H
8
NO
2
S, 278.0276 [M-H] ; found: 278.0285.
ylidene)indolin-2-one (2f)
A red solid; 264 mg; 90% yield; Mp: >300 C; IR (KBr, ν, cm ):
o
-1
1
Z)-3-(6-Fluoro-3-oxobenzo[b]thiophen-2(3H)-ylidene)indolin- 3166, 1703, 1676, 1654, 1618, 1597, 1461, 1399, 1339; H
(
2
-one (2b)
6
NMR (400 MHz, DMSO-d ) (δ, ppm): 11.12 (s, 1H, NH), 9.03 (d,
o
A red solid; 247 mg; 83% yield; Mp: >300 C; IR (KBr, ν, cm ): 1H, J = 7.6 Hz, ArH), 7.76 (d, 1H, J = 7.6 Hz, ArH), 7.57 (s, 1H,
-1
3
187, 1711, 1662, 1610, 1538, 1495, 1433, 1418, 1401, 1343; ArH), 7.41 (t, 1H, J = 7.6 Hz, ArH), 7.23 (d, 1H, J = 7.6 Hz, ArH),
1
H NMR (400 MHz, DMSO-d
6
) (δ, ppm): 11.16 (s, 1H, NH), 9.01 7.08 (t, 1H, J = 7.6 Hz, ArH), 6.95 (d, 1H, J = 7.6 Hz, ArH), 2.43
1
3
(d, 1H, J = 6.8 Hz, ArH), 7.94 (t, 1H, J = 5.2 Hz, ArH), 7.74 (d, 1H, (s, 3H, CH ); C NMR (100 MHz, DMSO-d ) (δ, ppm): 189.9,
3 6
J = 8.4 Hz, ArH), 7.42 (t, 1H, J = 6.8 Hz, ArH), 7.25 (t, 1H, J = 6.8 169.6, 148.3, 147.8, 144.0, 139.0, 133.0, 127.9(5), 127.8(9),
Hz, ArH), 7.09 (t, 1H, J = 7.2 Hz, ArH), 6.96 (d, 1H, J = 7.6 Hz, 127.7, 127.2, 126.7, 125.0, 122.2, 121.2, 110.7, 22.2; HRMS
1
ArH); C NMR (100 MHz, DMSO-d
3
-
6
+DMF-d
7
) (δ, ppm): 188.7, (ESI): m/z calcd for: C17
2
H10NO S, 292.0432 [M-H] ; found:
4
69.5, 144.3, 138.2, 133.2, 129.4 ( JCF = 1.6 Hz), 129.3, 128.0 292.0426.
1
2
3
JCF = 11.3 Hz), 126.2 ( JCF = 1.7 Hz), 122.2, 121.1, 114.7, 114.5,
(
5
14.3 ( JCF = 1.2 Hz), 111.9 ( JCF = 25.8 Hz), 110.7;HRMS (ESI): (Z)-3-(6-Methoxy-3-oxobenzo[b]thiophen-2(3H)-
1
1
-
S, 296.0182 [M-H] ; found: 296.0190.
m/z calcd for: C16
H
7
FNO
2
ylidene)indolin-2-one (2g)
A red solid; 284 mg; 92% yield; Mp: >300 C; IR (KBr, ν, cm ):
o
-1
1
Z)-3-(6-Chloro-3-oxobenzo[b]thiophen-2(3H)-ylidene)indolin- 3186, 1702, 1667, 1617, 1593, 1488, 1461, 1414, 1336; H
(
2
-one (2c)
6
NMR (400 MHz, DMSO-d ) (δ, ppm): 11.08 (s, 1H, NH), 9.02 (d,
o
A red-brown solid; 275 mg; 88% yield; Mp: >300 C; IR (KBr, ν, 1H, J = 8.0 Hz, ArH), 7.76 (d, 1H, J = 8.4 Hz, ArH), 7.40-7.36 (m,
-1
cm ): 3179, 1702, 1675, 1616, 1590, 1459, 1394, 1340, 1302;
1H, ArH), 7.31 (d, 1H, J = 2.4 Hz, ArH), 7.08-7.04 (m, 1H, ArH),
1
13
H NMR (400 MHz, DMSO-d
d, 1H, J = 8.0 Hz, ArH), 7.96 (d, 1H, J = 1.6 Hz, ArH), 7.85 (d, DMSO-d
H, J = 8.4 Hz, ArH), 7.46-7.40 (m, 2H, ArH), 7.08 (t, 1H, J = 8.0 132.7, 128.5, 128.0, 127.1, 122.7, 122.1, 121.2, 114.3, 110.5,
6
) (δ, ppm): 11.15 (s, 1H, NH), 9.00 6.94-6.89 (m, 2H, ArH), 3.90 (s, 3H, OCH
3
); C NMR (100 MHz,
(
6
) (δ, ppm): 188.3, 169.5, 166.5, 150.6, 143.9, 139.5,
1
1
3
3
Hz, ArH), 6.95 (d, 1H, J = 7.6 Hz, ArH); C NMR (100 MHz, 108.7, 56.6; HRMS (ESI): m/z calcd for: C17H10NO S, 308.0382
-
DMSO-d
6
) (δ, ppm): 189.2, 169.5, 149.5, 144.3, 141.7, 138.1, [M-H] ; found: 308.0377.
33.4, 128.4, 128.2, 128.1, 128.0, 127.1, 124.8, 122.4, 121.2,
10.8;
1
1
(Z)-3-(7-Chloro-3-oxobenzo[b]thiophen-2(3H)-ylidene)indolin-
S, 311.9886 [M-H] ; 2-one (2h)
A red-brown solid; 260 mg; 83% yield; Mp: >300 C; IR (KBr, ν,
-
HRMS (ESI): m/z calcd for: C16
found: 311.9893.
7 2
H ClNO
o
-1
cm ): 3231, 1702, 1674, 1617, 1585, 1459, 1413, 1385, 1340;
4
| J. Name., 2012, 00, 1-3
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Orga Pn l ie ca s&e Bd oi o nmo to al ed cj uu sl ta mr Ca rhg ei nms istry
View Article Online
DOI: 10.1039/C7OB01515A
Journal Name
ARTICLE
1
H NMR (400 MHz, DMSO-d
6
) (δ, ppm): 11.23 (s, 1H, NH), 9.01 150.6, 142.7, 141.5, 131.7, 128.6, 127.3, 126.1, 125.9, 122.6,
(
d, 1H, J = 7.6 Hz, ArH), 7.89-7.86 (m, 2H, ArH), 7.49-7.42 (m, 122.4, 114.3, 111.8, 108.8, 56.4; HRMS (ESI): m/z calcd for:
-
2
H, ArH), 7.11 (t, 1H, J = 8.0 Hz, ArH), 6.97 (d, 1H, J = 8.0 Hz,
1
17 9 3
C H ClNO S, 341.9992 [M-H] ; found: 341.9988.
3
6
ArH); C NMR (100 MHz, DMSO-d ) (δ, ppm): 189.7, 169.5,
1
1
C
46.0, 144.5, 137.4, 136.1, 133.7, 131.6, 129.0, 128.9, 128.5, (Z)-5-Bromo-3-(3-oxobenzo[b]thiophen-2(3H)-
28.1, 125.5, 122.4, 121.1, 111.0; HRMS (ESI): m/z calcd for: ylidene)indolin-2-one (2m)
-
S, 311.9886 [M-H] ; found: 311.9896.
o
A red solid; 303 mg; 85% yield; Mp: 295-296 C; IR (KBr, ν, cm
-
16
H
7
ClNO
2
1
1
)
: 3175, 1702, 1676, 1615, 1585, 1451, 1382, 1316, 1284; H
NMR (400 MHz, DMSO-d ) (δ, ppm): 11.27 (s, 1H, NH), 9.20 (d,
1H, J = 2.0 Hz, ArH), 7.89 (d, 1H, J = 7.6 Hz, ArH), 7.77-7.74 (m,
A red solid; 276 mg; 84% yield; Mp: >300 C; IR (KBr, ν, cm ): 2H, ArH), 7.60-7.57 (m, 1H, ArH), 7.45-7.41 (m, 1H, ArH), 6.93
(Z)-3-(3-Oxonaphtho[1,2-b]thiophen-2(3H)-ylidene)indolin-2-
6
one (2i)
o
-1
1
13
3
204, 1690, 1667, 1590, 1573, 1513, 1459, 1435, 1358; H (d, 1H, J = 8.4 Hz, ArH); C NMR (100 MHz, DMSO-d
NMR (400 MHz, DMSO-d ) (δ, ppm): 11.21 (s, 1H, NH), 9.11 (d, 190.7, 169.2, 147.2, 143.1, 140.4, 137.2, 135.1, 129.9, 129.1,
H, J = 8.0 Hz, ArH), 8.13 (d, 2H, J = 8.4 Hz, ArH), 7.90 (d, 1H, J = 127.1, 127.0, 126.5, 125.1, 122.9, 113.8, 112.6; HRMS (ESI):
6
) (δ, ppm):
6
1
8
-
7 2
.8 Hz, ArH), 7.83 (t, 2H, J = 6.4 Hz, ArH), 7.76 (t, 1H, J = 7.2 Hz, m/z calcd for: C16H BrNO S, 355.9381 [M-H] ; found: 355.9374.
ArH), 7.44 (t, 1H, J = 7.6 Hz, ArH), 7.11 (t, 1H, J = 8.0 Hz, ArH),
1
.97 (d, 1H, J = 8.0 Hz, ArH); C NMR (100 MHz, DMSO-d
3
6
6
) (δ, (Z)-5-Bromo-3-(6-chloro-3-oxobenzo[b]thiophen-2(3H)-
ppm): 190.3, 169.6, 149.8, 144.5, 137.6, 137.0, 133.6, 131.3, ylidene)indolin-2-one (2n)
o
29.7, 128.9, 128.5, 128.3, 128.0, 127.1, 126.6, 124.6, 122.4, A red solid; 324 mg; 83% yield; Mp: >300 C; IR (KBr, ν, cm ):
-1
1
1
3
1
21.5, 121.2, 110.8; HRMS (ESI): m/z calcd for: C20
H
10NO
2
S, 3179, 1702, 1675, 1655, 1615, 1585, 1453, 1402, 1385; H
NMR (400 MHz, DMF-d ) (δ, ppm): 11.49 (s, 1H, NH), 9.46 (d,
H, J = 2.0 Hz, ArH), 8.16 (d, 1H, J = 1.6 Hz, ArH), 8.12 (d, 1H, J =
Z)-5-Fluoro-3-(3-oxobenzo[b]thiophen-2(3H)-ylidene)indolin- 8.4 Hz, ArH), 7.83-7.81 (m, 1H, ArH), 7.71-7.68 (m, 1H, ArH),
-
28.0432 [M-H] ; found: 328.0443.
7
1
(
1
3
2
-one (2j)
7
7.22 (d, 1H, J = 8.4 Hz, ArH); C NMR (100 MHz, DMF-d ) (δ,
o
-1
A red solid; 258 mg; 87% yield; Mp: >300 C; IR (KBr, ν, cm ): ppm): 189.4, 169.2, 149.6, 143.5, 142.2, 140.0, 135.2, 130.2,
170, 1694, 1677, 1648, 1587, 1490, 1469, 1451, 1312, 1284; 128.2, 128.1, 127.2, 127.0, 124.7, 123.0, 113.9, 112.5; HRMS
3
1
-
H NMR (400 MHz, DMSO-d
.81 (m, 1H, ArH), 7.89 (d, 1H, J = 7.6 Hz, ArH), 7.79-7.74 (m, 389.8985.
H, ArH), 7.45-7.41 (m, 1H, ArH), 7.31-7.26 (m, 1H, ArH), 6.97-
6 6 2
) (δ, ppm): 11.16 (s, 1H, NH), 8.84- (ESI): m/z calcd for: C16H BrClNO S, 389.8991 [M-H] ; found:
8
2
6
1
1
1
1
3
.94 (m, 1H, ArH); C NMR (100 MHz, DMSO-d
6
) (δ, ppm): (Z)-5-Bromo-3-(6-bromo-3-oxobenzo[b]thiophen-2(3H)-
1
90.7, 169.5, 157.8 ( JCF = 233.0 Hz), 147.3, 140.5, 140.1, ylidene)indolin-2-one (2o)
6
5
o
-1
37.1, 129.1, 127.3 ( JCF = 3.0 Hz), 127.0 ( JCF = 5.3 Hz), 125.0, A red solid; 350 mg; 80% yield; Mp: >300 C; IR (KBr, ν, cm ):
3
21.7 ( JCF = 10.2 Hz), 119.5, 119.3, 114.4 ( JCF = 27.5 Hz), 111.4 3171, 1701, 1675, 1615, 1583, 1452, 1388, 1315, 1267; H
2
1
4
(
JCF = 8.3 Hz); HRMS (ESI): m/z calcd for: C16
H
7
FNO
2
S, NMR (400 MHz, DMSO-d
9.28 (d, 1H, J = 2.0 Hz, ArH), 8.17 (d, 1H, J = 1.6 Hz, ArH), 7.87
d, 1H, J = 8.4 Hz, ArH), 7.70-7.65 (m, 2H, ArH), 7.04 (d, 1H, J =
6 7
+DMF-d ) (δ, ppm): 11.37 (s, 1H, NH),
-
96.0182 [M-H] ; found: 296.0188.
2
(
1
3
(
Z)-5-Chloro-3-(3-oxobenzo[b]thiophen-2(3H)-ylidene)indolin- 8.4 Hz, ArH); C NMR (100 MHz, DMSO-d
-one (2k) 189.7, 169.3, 149.6, 143.5, 140.0, 135.3, 131.3, 130.2, 130.1,
A red solid; 269 mg; 86% yield; Mp: >300 C; IR (KBr, ν, cm ): 128.5, 128.2, 127.7, 127.1, 123.0, 113.9, 112.6; HRMS (ESI):
6 7
+DMF-d ) (δ, ppm):
2
o
-1
1
-
3
180, 1694, 1678, 1645, 1616, 1586, 1458, 1450, 1307; H m/z calcd for:
NMR (400 MHz, DMSO-d ) (δ, ppm): 11.25 (s, 1H, NH), 9.05 (d, 435.8477.
H, J = 2.0 Hz, ArH), 7.88 (d, 1H, J = 7.6 Hz, ArH), 7.62-7.50 (m,
H, ArH), 7.47-7.40 (m, 2H, ArH), 6.96 (d, 1H, J = 8.4 Hz, ArH); (Z)-5-Bromo-3-(6-methoxy-3-oxobenzo[b]thiophen-2(3H)-
16 6 2 2
C H Br NO S, 435.8466 [M-H] ; found:
6
1
2
1
3
6
C NMR (100 MHz, DMSO-d ) (δ, ppm): 190.7, 169.3, 147.2, ylidene)indolin-2-one (2p)
o
42.7, 140.4, 137.2, 132.3, 129.1, 127.2, 127.0, 126.9(9), A red solid; 317 mg; 82% yield; Mp: >300 C; IR (KBr, ν, cm ):
-1
1
1
C
26.6, 126.0, 125.1, 122.4, 112.1; HRMS (ESI): m/z calcd for: 3176, 1698, 1673, 1650, 1616, 1594, 1486, 1452, 1402, 1317;
-
S, 311.9886 [M-H] ; found: 311.9872.
1
16
H
7
ClNO
2
H NMR (400 MHz, DMSO-d
s, 1H, ArH), 7.82 (d, 1H, J = 8.4 Hz, ArH), 7.57 (d, 1H, J = 6.8 Hz,
ArH), 7.37 (s, 1H, ArH), 6.97-6.91 (m, 2H, ArH), 3.93 (s, 3H,
6
) (δ, ppm): 11.24 (s, 1H, NH), 9.23
(
(
Z)-5-Chloro-3-(6-methoxy-3-oxobenzo[b]thiophen-2(3H)-
ylidene)indolin-2-one (2l)
A red solid; 271 mg; 79% yield; Mp: >300 C; IR (KBr, ν, cm ): 166.8, 150.5, 142.9, 141.5, 134.7, 130.1, 128.9, 125.8, 122.8,
199, 1695, 1671, 1655, 1584, 1476, 1467, 1426, 1385, 1326; 122.6, 114.6, 113.7, 112.5, 109.1, 56.8; HRMS (ESI): m/z calcd
1
3
3 6
OCH ); C NMR (100 MHz, DMSO-d ) (δ, ppm): 188.5, 169.2,
o
-1
3
1
-
H NMR (400 MHz, DMF-d
d, 1H, J = 2.0 Hz, ArH), 7.89 (d, 1H, J = 8.8 Hz, ArH), 7.52-7.49
m, 1H, ArH), 7.39 (d, 1H, J = 2.4 Hz, ArH), 7.09 (d, 1H, J = 8.4 (Z)-5-Methyl-3-(3-oxobenzo[b]thiophen-2(3H)-
7 9 3
) (δ, ppm): 11.24 (s, 1H, NH), 9.22 for: C17H BrNO S, 385.9487 [M-H] ; found: 385.9479.
(
(
1
3
3
Hz, ArH), 7.03-7.00 (m, 1H, ArH), 4.03 (s, 3H, OCH ); C NMR ylidene)indolin-2-one (2q)
6 7
(100 MHz, DMSO-d +DMF-d ) (δ, ppm): 188.5, 169.3, 167.0,
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Organic & Biomolecular Chemistry
Page 6 of 7
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DOI: 10.1039/C7OB01515A
ARTICLE
A red solid; 256 mg; 88% yield; Mp: >300 C; IR (KBr, ν, cm ):
Journal Name
o
-1
Notes and references
1
3
179, 1694, 1672, 1619, 1586, 1472, 1451, 1408, 1322; H
NMR (400 MHz, DMSO-d ) (δ, ppm): 11.02 (s, 1H, NH), 8.87 (s,
H, ArH), 7.86 (d, 1H, J = 7.6 Hz, ArH), 7.76-7.73 (m, 2H, ArH),
.43-7.39 (m, 1H, ArH), 7.23-7.21 (m, 1H, ArH), 6.83 (d, 1H, J =
1
2
3
S. Kim, N. Dahal and T. Kesharwani, Tetrahedron Lett., 2013,
, 4373.
6
5
4
1
7
7
M. Raga, C. Palacin, J. M. Castello, J. A. Ortiz, M. R. Cuberes
and M. Moreno-Manas, Eur. J. Med. Chem., 1986, 21, 329.
R. Romagnoli, P. G. Baraldi, M. K. Salvador, D. Preti, M. A.
Tabrizi, M. Bassetto, A. Brancale, E. Hamel, I. Castagliuolo,
R. Bortolozzi, G. Basso and G. Viola, J. Med. Chem., 2013,
1
3
3 6
.6 Hz, ArH), 2.34 (s, 3H, CH ); C NMR (100 MHz, DMSO-d )
(δ, ppm): 190.5, 169.6, 147.5, 142.0, 138.2, 136.8, 133.7,
1
30.9, 129.4, 128.3, 128.2, 126.8, 126.7(6), 125.0, 121.3,
10.5, 21.4; HRMS (ESI): m/z calcd for: C17 S, 292.0432
56, 2606.
1
H
10NO
2
4
5
M. R. Bleavins, F. A. de la Igelsia, J. A. McCay, L. White, L.
Kimber, Jr. and A. E. Munson, Toxicology, 1995, 98, 111.
(a) I. Nakamura, T. Sato and Y. Yamamoto, Angew. Chem.,
Int. Ed., 2006, 45, 4473. (b) T. Mori, T. Nishimura, T.
Yamamoto, I. Doi, E. Miyazaki, I. Osaka and K. Takimiya, J.
Am. Chem. Soc., 2013, 135, 13900. (c) H. Huang, P. Dang, L.
Wu, Y. Liang and J. Liu, Tetrahedron Lett., 2016, 57, 574. (d)
Y.-S. Kim, S. H. Kwak and Y.-D. Gong, ACS Comb. Sci., 2015,
17, 365. (e) R. Samanta and A. P. Antonchick, Angew. Chem.
Int. Ed., 2011, 50, 5217. (f) S. Sangeetha and G. Sekar, Org.
Lett., 2017, 19, 1670. (g) S. Yugandar, S. Konda and H. Ila,
Org. Lett., 2017, 19, 1512. (h) L.-M. Ye, L. Qian, Y.-Y. Chen,
X.-J. Zhang and M. Yan, Org. Biomol. Chem., 2017, 15, 550.
-
M-H] ; found: 292.0443.
[
(Z)-3-(6-Methoxy-3-oxobenzo[b]thiophen-2(3H)-ylidene)-5-
methylindolin-2-one(2r)
A red solid; 268 mg; 83% yield; Mp: >300 C; IR (KBr, ν, cm ):
o
-1
1
3
174, 1702, 1675, 1589, 1468, 1397, 1316, 1269; H NMR (400
MHz, DMSO-d ) (δ, ppm): 10.99 (s, 1H, NH), 8.89 (s, 1H, ArH),
.79 (d, 1H, J = 8.8 Hz, ArH), 7.34 (d, 1H, J = 2.0 Hz, ArH), 7.22-
.20 (m, 1H, ArH), 6.95-6.93 (m, 1H, ArH), 6.83 (d, 1H, J = 8.0
6
7
7
1
3
3 3
Hz, ArH), 3.91 (s, 3H, OCH ), 2.34 (s, 3H, CH ); C NMR (100
MHz, DMSO-d
6
) (δ, ppm): 188.5, 169.7, 166.6, 150.7, 141.7,
39.3, 133.3, 130.9, 128.7, 128.4, 127.5, 122.8, 121.3, 114.5,
10.4, 108.8, 56.7, 21.4; HRMS (ESI): m/z calcd for:
(
2016, , 1619. (j) H. Zang, J.-G. Sun, X. Dong, P. Li and B.
i) X. Wang, T. Gensch and F. Glorius, Org. Chem. Front.,
3
1
1
Zhang, Adv. Synth. Catal., 2016, 358, 1746. (k) L. Gao, B.
Chang, W. Qiu, L. Wang, X. Fu and R. Yuan, Adv. Synth.
Catal., 2016, 358, 1202. (l) V. Guilarte, M. A. Fernández-
Rodríguez, P. García-García, E. Hernando and R. Sanz, Org.
Lett., 2011, 13, 5100. (m) R. Sanz, V. Guilarte, E. Hernando
and A. M. Sanjuán, J. Org. Chem., 2010, 75, 7443.
(a) Y. Zhang and C.-J. Li, J. Am. Chem. Soc., 2006, 128, 4242.
(b) G. C. Senadi, W.-P. Hu, T.-Y. Lu, A. M. Garkhedkar, J. K.
Vandavasi and J.-J. Wang, Org. Lett., 2015, 17, 1521. (c) J.
Chen, Y. Shao, H. Zheng, J. Cheng and X. Wan, J. Org. Chem.,
-
18 3
C H12NO S, 322.0538 [M-H] ; found: 322.0543.
(
Z)-6-Chloro-3-(3-oxobenzo[b]thiophen-2(3H)-ylidene)indolin-
-one (2s)
A red solid; 266 mg; 85% yield; Mp: >300 C; IR (KBr, ν, cm ):
2
o
-1
6
1
3
164, 1707, 1657, 1623, 1588, 1442, 1378, 1310, 1276; H
NMR (400 MHz, DMF-d ) (δ, ppm): 11.45 (s, 1H, NH), 9.27 (d,
H, J = 8.8 Hz, ArH), 8.10 (d, 1H, J = 7.6 Hz, ArH), 7.96-7.95 (m,
H, ArH), 7.65-7.62 (m, 1H, ArH), 7.37-7.35 (m, 1H, ArH), 7.25
7
1
2
2
015, 80, 10734. (d) S.-R. Guo, Y.-Q. Yuan and J.-N. Xiang,
Org. Lett., 2013, 15, 4654. (e) B. Jiang, J. Li, Y.-Y. Pan, W.-J.
Hao, G. Li and S.-J. Tu, Chin. J. Chem., 2017, 35, 323. (f) T.-S.
Zhang, Y.-J. Xiong, W.-J. Hao, X.-T. Zhu, S.-L. Wang, G. Li, S.-J.
Tu and B. Jiang, J. Org. Chem., 2016, 81, 9350.
(a) X. Zhao, T. Li, L. Zhang and K. Lu, Org. Biomol. Chem.,
016, 14, 1131. (b) S. K. R. Parumala and R. K. Peddinti,
1
3
(d, 1H, J = 2.0 Hz, ArH); C NMR (100 MHz, DMF-d
7
) (δ, ppm):
90.4, 169.5, 147.4, 145.4, 139.1, 137.0, 136.6, 129.3, 129.0,
26.5, 126.5, 124.6, 121.8, 120.2, 110.5; HRMS (ESI): m/z calcd
1
1
7
-
7 2
for: C16H ClNO S, 311.9886 [M-H] ; found: 311.9890.
2
Green Chem., 2015, 17, 4068. (c) X. Zhao, L. Zhang, X. Lu, T.
Li and K. Lu, J. Org. Chem., 2015, 80, 2918. (d) M. A.
Fernández-Rodríguez, Q. Shen and J. F. Hartwig, J. Am.
Chem. Soc., 2006, 128, 2180. (e) M. A. Fernández-Rodríguez
and J. F. Hartwig, Chem. Eur. J., 2010, 16, 2355.
(
Z)-6-Bromo-3-(3-oxobenzo[b]thiophen-2(3H)-
ylidene)indolin-2-one (2t)
A red solid; 286 mg; 80% yield; Mp: >300 C; IR (KBr, ν, cm ):
o
-1
1
3
175, 1696, 1667, 1617, 1587, 1572, 1472, 1452, 1356; H
NMR (400 MHz, DMF-d ) (δ, ppm): 11.30 (s, 1H, NH), 9.05 (d,
H, J = 8.4 Hz, ArH), 7.95 (d, 1H, J = 7.6 Hz, ArH), 7.82-7.80 (m,
H, ArH), 7.50-7.46 (m, 1H, ArH), 7.38-7.36 (m, 1H, ArH), 7.25
8
(a) Z.-Z. Chen, S. Liu, W.-J. Hao, G. Xu, S. Wu, J.-N. Miao, B.
Jiang, S.-L. Wang, S.-J. Tu and G. Li, Chem. Sci., 2015, 6,
7
1
2
6654. (b) Y.-L. Zhu, B. Jiang, W.-J. Hao, A.-F. Wang, J.-K. Qiu,
P. Wei, D. Wang, G. Li and S.-J. Tu, Chem. Commun., 2016,
52, 1907. (c) W.-J. Hao, Y. Du, D. Wang, B. Jiang, Q. Gao, S.-J.
Tu and G. Li, Org. Lett., 2016, 18, 1884. (d) Y.-N. Wu, R. Fu,
N.-N. Wang, W.-J. Hao, G. Li, S.-J. Tu and B. Jiang, J. Org.
Chem., 2016, 81, 4762. (e) R. Fu, W.-J. Hao, Y.-N. Wu, N.-N.
1
3
(d, 1H, J = 1.6 Hz, ArH); C NMR (100 MHz, DMF-d
7
) (δ, ppm):
90.4, 169.3, 147.4, 145.4, 139.3, 136.5, 129.2, 129.1,
26.5(4), 126.5(2), 126.4(7), 125.6, 124.7, 124.5, 120.5, 113.3;
1
1
-
HRMS (ESI): m/z calcd for: C16
found: 355.9376.
H
7
BrNO
2
S, 355.9381 [M-H] ;
Wang, S.-J. Tu, G. Li and B. Jiang, Org. Chem. Front., 2016,
452. (f) W. Fan, Z. Yang, B. Jiang, and G. Li, Org. Chem.
Front., 2017, , 1091.
W. Fan, Q. Li, Y. Li, H. Sun, B. Jiang and G. Li, Org. Lett., 2016,
, 1258.
3,
1
4
9
1
8
Acknowledgements
10 (a) W.-J. Hao, J.-Q. Wang, X.-P. Xu, S.-L. Zhang, S.-Y. Wang
and S.-J. Ji, J. Org. Chem., 2013, 78, 12362. (b) T. B. Nguyen,
M. Corbin, P. Retailleau, L. Ermolenko and A. Al-Mourabit,
Org. Lett., 2015, 17, 4956. (c) J. Dhineshkumar, M. Lamani,
K. Alagiri and K. R. Prabhu, Org. Lett., 2013, 15, 1092.
We are grateful for financial support from the NSFC (No. 21332005
and 21672100), Robert A. Welch Foundation (D-1361, USA), PAPD
of Jiangsu Higher Education Institutions, and NSF of Jiangsu
Province (BK20151163).
6
| J. Name., 2012, 00, 1-3
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Page 7 of 7
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C7OB01515A
Facile synthesis of benzo[b]thiophenes via metal-free
radical-triggered intramolecular C-S bond formation
Wei Fan, Kwong-Yuen Chen, Qi-Peng Chen, Guigen Li, and Bo Jiang