Synthesis of 2-aryl and 3-aryl benzo[b]furan thioethers using aryl sulfonyl hydrazides as sulfenylation reagents

Article abstract of DOI:10.1021/acs.joc.5b00146

An efficient, metal-free protocol used to synthesize aryl benzo[b]furan thioethers based on the I₂-catalyzed cross-coupling of benzo[b]furans as well as the electrophilic cyclization of 2-alkynylphenol derivatives with aryl sulfonyl hydrazides

Full text of DOI:10.1021/acs.joc.5b00146

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Note
Synthesis of 2-Aryl and 3-Aryl Benzo[b]furan Thioethers
Using Aryl Sulfonyl Hydrazides as Sulfenylation Reagents
Xia Zhao, Lipeng Zhang, Xiaoyu Lu, Tianjiao Li, and Kui Lu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00146 • Publication Date (Web): 12 Feb 2015
Downloaded from http://pubs.acs.org on February 18, 2015
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Synthesis of 2-Aryl and 3-Aryl Benzo[b]furan Thioethers
Using Aryl Sulfonyl Hydrazides as Sulfenylation Reagents
Xia Zhao,†,∗ Lipeng Zhang, † Xiaoyu Lu, † Tianjiao Li † and Kui Lu‡,∗
†College of Chemistry, Tianjin Key Laboratory of Structure and Performance for
Functional Molecules, Tianjin Normal University, Tianjin 300387, China
‡College of Biotechnology, Tianjin University of Science & Technology, Tianjin
300457, China
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∗Eꢀmail: hxxyzhx@mail.tjnu.edu.cn; lukui@tust.edu.cn
Abstracts: An efficient, metalꢀfree protocol used to synthesize aryl benzo[b]furan
thioethers based on the I2ꢀcatalysed crossꢀcoupling of benzo[b]furans as well as the
electrophilic cyclization of 2ꢀalkynylphenol derivatives with aryl sulfonyl hydrazides
was developed. Various 2ꢀaryl and 3ꢀaryl benzo[b]furan thioethers were obtained in
moderate to good yields.
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Benzofurans constitute basic units that frequently occur in natural products and
represent the most important type of heterocycles in drug discovery,1 as they have
been reported to exhibit anticancer,2 antiviral,3 antifungal,4 antiinflammatory5 and
immunosuppressive activities.6 Therefore, significant efforts have been put forth
towards the efficient construction of benzofuran scaffolds. To the best of our
knowledge, only a few methods have been reported to prepare 2ꢀsulfenyl or 3ꢀsulfenyl
benzo[b]furans including (i) electrophilic cyclisation of 2ꢀ(phenylethynyl)anisole with
4ꢀnitrophenyl hypochlorothioite (Scheme 1, Eq 1),7 (ii) electrophilic cyclisation of
2ꢀsulfenylꢀalkynylanisoles with electrophiles sources such as I2, ICl, Br2 and PhSeBr
(Scheme 1, Eq 2),8 (iii) PdCl2ꢀcatalysed annulation of 2ꢀalkynylphenol derivatives
with disulfides in the presence of 2 equivalents of I2 (Scheme 1, Eq 3),9 (iv)
FeCl3ꢀpromoted annulation of 2ꢀalkynylanisoles with disulfides (Scheme 1, Eq 4),10
and (v) I2ꢀmediated cyclisation of 2ꢀalkynylanisoles with diaryl disulfides (Scheme 1,
Eq 5).11 However, these methods require either expensive and airꢀsensitive metal
catalysts or foulꢀsmelling, toxic and unstable sulfur sources such as sulfenyl halides
and disulfides. Hence, a direct and concise method to synthesize 2ꢀsulfenyl or
3ꢀsulfenyl benzo[b]furans using stable and environmentally friendly reagents remains
a significant challenge for organic chemists.
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Scheme 1. Synthesis 2ꢀ or 3ꢀsulfenyl benzo[b]furans via different methods
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In the past two years, sulfonyl hydrazides, which are readily accessible,
nonꢀodorous, and stable solids, have emerged as novel sulfenylation reagents.
Specifically, they have been used in the sulfenylation of iodoles,12 alkanes, 13 ethers, 13
naphthols and naphthylamines,14 as well as in the oxysulfenylation of alkenes,15
hydrothiolation of alkynes,16 and in the synthesis of unsymmetrical sulfides.17
Recently, we reported the I2ꢀcatalysed sulfenylation of pyrazolones with aryl sulfonyl
hydrazides promoted by pꢀtoluenesulfonic acid (PTSA).18 Inspired by the
aforementioned background and our interest in the chemistry of sulfonyl hydrazides,
we envisaged that sulfenyl benzo[b]furans could be produced via the direct
sulfenylation of benzofuran by sulfonyl hydrazides and electrophilic cyclization of
2ꢀalkynylphenol derivatives with sulfonyl hydrazides. Herein, we disclose concise
and convenient methods to synthesize 2ꢀaryl and 3ꢀaryl benzo[b]furan thioethers
using aryl sulfonyl hydrazides as sulfenylation reagents via catalysis with iodine.
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To
begin
our
investigation,
benzofuran
was
reacted
with
3ꢀchlorobenzenesulfonohydrazide 2a using Tian’s protocol (I2 10 mol%, ethanol, 70
oC). Unfortunately, the sulfenylation reaction did not occur at all, and benzofuran
o
decomposed at higher temperatures (120 C). To circumvent this issue, a more stable
o
benzofuran derivative, 2ꢀphenylbenzofuran 1a, was reacted with 2a at 120 C in
ethanol (EtOH). To our delight, the desired sulfenylation product 3aa was obtained in
o
75% yield in the presence of 0.1 equivalent of I2 as the catalyst at 120 C (Table 1,
Entry 1). To identify the optimal reaction conditions, various solvents such as EtOH,
1,4ꢀdioxane, toluene, 1,2ꢀdichloroethane (DCE), N,Nꢀdimethylformamide (DMF), and
water were tested (Table 1, Entry 2ꢀ6). 1,4ꢀDioxane gave the best result, in that 83%
yield was obtained. Next, a few reaction temperatures and concentration were
screened. Increasing the reaction temperature to 130 oC led to a slightly diminished
yield (Table 1, Entry 7). However, when the reaction was carried out at 100 oC and 80
oC, the yield decreased to 71% and 58%, respectively (Table 1, Entries 8 and 9). It
was noteworthy that decreasing the concentration led to a decrease of the yield (Table
1, Entry 10). Finally, the effects of catalyst loading and equivalents of 2a were
investigated (Table 1, Entry 11ꢀ14). The results suggested that 0.1 equivalent of the I2
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catalyst was required to obtain a suitable product yield. When the catalyst loading was
decreased to 1%, only a trace amount of the desired product was obtained (Table 1,
Entry 12). For sulfonyl hydrazide, 1.8 equivalents of 2a were sufficient to produce a
suitable yield (Table 1, Entry 13). Further decrease in the amount of 2a led to a
decrease in the yield (Table 1, Entry 14). Notably, unlike in the sulfenylation of
naphthols, naphthylamines, and pyrazolones, the addition of an acid did not facilitate
the transformation.14, 18 In contrast, the presence of PTSA could accelerate the
decomposition of 2ꢀphenylbenzofuran (1a) which led to a diminished yield (Table 1,
Entry 15). Therefore, the optimized reaction conditions were determined to be as
follows: 1a (1.0 mmol), 2a (1.8 mmol), I2 (0.1 mmol), and 1,4ꢀdioxane (0.5 mL), at
120 °C.
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Table 1. Optimization of I2ꢀcatalysed reaction of 1a with 2a.a
Entry
1
I2 (equiv)
0.1
t (h)
24
24
24
24
24
24
24
24
24
24
48
48
24
24
24
T (°C)
120
120
120
120
120
120
130
100
80
Solvent
EtOH
Yield (%)
75
2
0.1
H2O
35
3
0.1
DCE
79
4
0.1
Toluene
61
5
0.1
DMF
0
6
0.1
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
1,4ꢀDioxane
83
7
0.1
81
8
0.1
71
9
0.1
58
72b
10
11
12
13
14
15
0.1
120
120
120
120
120
120
0.05
0.01
0.1
69
trace
84c
75d
25e
0.1
0.1
a Reaction conditions: 1a (1.0 mmol), 2a (2.0 mmol), solvent (0.5 mL). b 1a
c
(1.0 mmol), 2a (2.0 mmol), solvent (1.0 mL). 1a (1.0 mmol), 2a (1.8
mmol), solvent (0.5 mL). d 1a (1.0 mmol), 2a (1.5 mmol), solvent (0.5 mL).
e 1a (1.0 mmol), 2a (1.8 mmol), PTSA (1.0 mol), solvent (0.5 mL).
With the optimized reaction conditions in hand, the generality and substrate scope
of 2ꢀsubstituted benzofurans and sulfonyl hydrazides were examined in the
sulfenylation reaction. The results are illustrated in Table 2. A variety of substituted
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aryl sulfonyl hydrazides could be coupled with various 2ꢀsubstituted benzofurans to
afford the corresponding benzofuran thioethers in moderate to excellent yields.
However, when aliphatic sulfonyl hydrazides such as methanesulfonohydrazide and
butaneꢀ1ꢀsulfonohydrazide were employed as substrates, the desired coupling
products were not detected under the optimized reaction conditions.
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Table 2. I2ꢀcatalysed cross coupling with a series of 2ꢀsubstituted benzofurans and
aryl sulfonyl hydrazides.a
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For aromatic sulfonyl hydrazides, both electronꢀwithdrawing and electronꢀdonating
groups, as well as meta-, orthoꢀ, and paraꢀsubstitutions (2aꢀ2f) were tolerated under
the optimized conditions. Notably, the identity of the substituent on the benzofuran
had a significant effect on the sulfenylation reaction. In regard to substituents in the
2ꢀposition, alkylꢀsubstituted benzofuran (1d) resulted in lower yields compared with
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the
corresponding
phenyl
substrate
(1a)
when
using
4ꢀmethylbenzenesulfonohydrazide (2b) or 4ꢀmethoxybenzenesulfonohydrazide (2d)
as the sulfenylation reagent. Moreover, electronꢀwithdrawing groups in the 2ꢀposition
of the aryl substituent (1c) and 5ꢀposition of benzofuran (1f and 1i) resulted in lower
yields as compared to that with substrates containing electronꢀdonating groups.
Interestingly, when benzofuranꢀ2ꢀyltrimethylsilane (1j) was utilized as a substrate,
the diꢀsulfenylation product (3jb) was obtained in 40% yield (Scheme 2).
Scheme 2. Sulfenylation of benzofuranꢀ2ꢀyltrimethylsilane.
Notably, when 2‒phenylbenzo[b]thiophene (1k) was coupled with
4ꢀmethylbenzenesulfonohydrazide (2b) under the optimized condition, the desired
product 2ꢀphenylꢀ3ꢀ(pꢀtolylthio)benzo[b]thiophene (3kb) was obtained in 24% yield.
Table 3. I2ꢀcatalysed cross coupling with a series of 3ꢀsubstituted benzofurans and
aryl sulfonyl hydrazides.a
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In order to extend the scope of this transformation, 3ꢀsubstituted benzofurans were
tested under the optimized conditions. The results are summarized in Table 3. Both
3ꢀphenyl and 3ꢀmethyl substituted benzofurans reacted with various aryl sulfonyl
hydrazides (2b, 2d, and 2e) smoothly and were converted to the sulfenylation
products in moderate to good yields. Notably, when 5ꢀmethoxyꢀ3ꢀphenylbenzofuran
(4b) was treated with 4ꢀmethylbenzenesulfonohydrazide (2b) under the catalysis of I2,
diꢀsulfenylation product (5bb) was obtained in 54% yield.
As mentioned previously, 2ꢀsulfenyl or 3ꢀsulfenyl benzo[b]furans can be
synthesised by the annulation of 2ꢀalkynylphenol derivatives.7ꢀ11 Hence,
2ꢀ(phenylethynyl)phenol
6
was
evaluated
in
the
reaction
with
4ꢀmethylbenzenesulfonohydrazide (2b). As expected, the desired product 3ab was
formed in 30% yield (Table 4, Entry 1) under the standard conditions (I2 10 mol%,
o
1,4ꢀdioxane, 120 C). To improve the yield, various conditions were screened;
addition of 0.5 equivalents of PTSA greatly increased the yield (Table 4, Entry 2).
Other 2ꢀalkynylphenol derivatives and aryl sulfonyl hydrazides were subjected to this
tandem reaction, and fortunately provided the desired products in poor to good yields
(Table 4, Entry 3ꢀ6).
Table 4. I2ꢀcatalysed electrophilic cyclization of 2ꢀalkynylphenols with aryl sulfonyl
hydrazides.a
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Entry
6, Ar1 =
6a,Ph
2, Ar2 =
Yield (%)
3ab, 30b
3ab, 80
3ac, 66
3ad, 35
3ag, 39
3bb, 78
1
2
3
4
5
6
2b, pꢀMeC6H4
2b, pꢀMeC6H4
2c, oꢀMeC6H4
2d, pꢀMeOC6H4
2g, pꢀBrC6H4
2b, pꢀMeC6H4
6a,Ph
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6a,Ph
6a,Ph
6a,Ph
6b, pꢀMeOC6H4
a Reaction conditions: 6 (1.0 mmol), 6 (2.0 mmol), I2 (0.1 mmol), PTSA (0.5
mmol), 1,4ꢀdioxane (0.5 mL), 120 °C, 24 h. b PTSA was not added.
On the basis of the experimental and previously reported results,12, 15 a plausible
mechanism for these transformations is proposed in Scheme 3. Initially, aryl sulfonyl
hydrazide 2 is converted to thiodiazonium iodide 7, which is attacked by benzofuran 1
and 4 to give sulfenylation products 3 and 5, respectively. For the tandem reaction,
electrophilic addition of thiodiazonium iodide 7 to alkyne 6 gives thiirenium ion 8.
Subsequently, intramolecular ringꢀopening of the thiirenium ion with the phenol
moiety affords compound 3.
O
Ar
I2
S
NHNH2
O
2
R1
ref 12
HI, HOI
R2
R2
SAr
R1
R2
SAr
R1
O
O
4
1
Ar
S
N
NI
R1
R2
O
O
7
HI
HI
3
5
R1
Ar
-HI
S
R1
ref 15
I
R2
OH
R2
6
OH
8
Scheme 3. Possible reaction pathways
In conclusion, we developed concise and efficient methods for the synthesis of
2ꢀaryl and 3ꢀaryl benzofuran thioethers by the I2ꢀcatalysed crossꢀcoupling reaction of
3ꢀ and 2ꢀsubstituted benzo[b]furans with aryl sulfonyl hydrazides via direct C–H
functionalization, as well as the electrophilic cyclization of 2ꢀalkynylphenol
derivatives with aryl sulfonyl hydrazides. This study not only broadened the substrate
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scope of sulfonyl hydrazides as novel and environmentally friendly reagents with
sulfenylate electronꢀrich heterocycles, but also facilitated the synthesis of benzofuran
thioethers via the oxysulfenylation of alkynes.
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EXPERIMENTAL SECTION
General experimental methods.
All solvents were distilled prior to use. Aryl benzo[b]furans were prepared according
to the literature procedure.19 2ꢀAlkynylphenol derivatives were prepared according to
the literature procedure.20 Unless otherwise noted, chemicals were used as received
without further purification. For chromatography, 200−300 mesh silica gel was
1
employed. H and 13C{1H} NMR spectra were recorded at 400 MHz and 100 MHz
respectively. Chemical shifts are reported in ppm using tetramethylsilane as internal
standard. IR spectra were recorded in wave numbers (cm−1) with a FTꢀIR
spectrometer. HRMS was performed on an FTMS mass instrument. Melting points
are reported as uncorrected.
General Procedure I: The I2-catalyzed reactions between aryl benzo[b]furans
1a-g; 5a-c and aryl sulfonyl hydrazides 2a-f (Table 2, 3; Schemes 2). Aryl
benzo[b]furan (1.0 mmol), aryl sulfonyl hydrazides (1.8 mmol) and I2 (25.4 mg, 0.1
mmol) and 1,4ꢀdioxane (0.5 mL) were mixed in a sealed tube. The mixture was stirred
at 120 oC until the aryl benzo[b]furan disappeared detected by TLC. Then, the solvent
was evaporated under reduced pressure and the residue was purified by silica gel
column chromatography to afford the pure product.
General Procedure II: The I2-catalyzed reactions between 2-alkynylphenol
derivatives 6a, 6b and aryl sulfonyl hydrazides 2b, 2d, 2c, 2f (Table 4).
2ꢀAlkynylphenol derivatives (1.0 mmol), aryl sulfonyl hydrazides (2.0 mmol), I2
(25.4 mg, 0.1 mmol), 4ꢀmethylbenzenesulfonic acid (86 mg, 0.5 mmol) and
o
1,4ꢀdioxane (0.5 mL) were mixed in a sealed tube. The mixture was stirred at 120 C
for 24 hours. Then, the solvent was evaporated under reduced pressure and the residue
was purified by silica gel column chromatography to afford the pure product.
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3-(3-chlorophenylthio)-2-phenylbenzofuran (3aa): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE, PE = petroleum ether), compound 3aa was isolated as a white
o
solid (281 mg, 84%): mp (melting point) = 60ꢀ61 C; Rf (PE) = 0.3; IR (film): 1576,
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1460, 1442, 1086, 1069, 772, 744, 688 cm−1; 1H NMR (400 MHz, CDCl3): δ 8.20 (d,
J = 8.8 Hz, 2H), 7.58 (d, J = 8.0 Hz, 1H), 7.34ꢀ7.49 (m, 5H), 7.24ꢀ7.27 (m, 1H), 7.17
(d, J = 1.6 Hz, 1H), 7.02ꢀ7.12 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 157.8,
153.9, 138.4, 134.9, 130.4, 130.0, 129.5, 129.4, 128.6, 127.3, 125.9, 125.6, 125.4,
124.3, 123.6, 120.1, 111.4, 103.5,; HRMS (ESI, m/z): calcd for C20H14ClOS [M + H]+
337.0448, found 337.0453.
2-phenyl-3-(p-tolylthio)benzofuran (3ab):9 The crude compound was prepared
through the general procedure I or procedure II. After purification by silica gel
column chromatography (PE), compound 3ab was isolated as a pale yellow solid (281
1
mg, 89% for procedure I) (253 mg, 80% for procedure II): Rf (PE) = 0.5; H NMR
(400 MHz, CDCl3): δ 8.24 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.4 Hz, 1H), 7.44ꢀ7.49 (m,
3H), 7.38ꢀ7.41 (m, 1H), 7.31ꢀ7.35 (m, 1H), 7.20ꢀ7.24 (m, 1H), 7.11 (d, J = 8.0 Hz,
2H), 7.01 (d, J = 8.0 Hz, 2H), 2.26 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ
157.1, 153.8, 135.3, 132.4, 130.8, 129.8, 129.2, 128.5, 127.3, 126.8, 125.1, 123.3,
120.4, 111.2, 105.2, 20.8.
2-phenyl-3-(o-tolylthio)benzofuran (3ac): The crude compound was prepared
through the general procedure I or procedure II. After purification by silica gel
column chromatography (PE), compound 3ac was isolated as a white solid (225 mg,
71% for procedure I), (209 mg, 66% for procedure II): mp (melting point) = 67ꢀ68 oC;
Rf (PE) = 0.5; IR (film): 2932, 1590, 1453, 1442, 1067, 742, 689 cm−1; 1H NMR (400
MHz, CDCl3): δ 8.19 (d, J = 7.2 Hz, 2H), 7.56 (d, J = 8.4 Hz, 1H), 7.38ꢀ7.45 (m, 4H),
7.32 (t, J = 7.2 Hz, 1H), 7.22 (d, J = 8.0 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.01 (t, J =
13
7.2 Hz, 1H), 6.92 (t, J = 7.2 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 2.50 (s, 3H); C{1H}
NMR (100 MHz, CDCl3): δ 157.5, 154.0, 135.2, 135.1, 130.8, 130.2, 129.8, 129.3,
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128.5, 127.3, 126.6, 125.8, 125.3, 125.2, 123.4, 120.4, 111.3, 104.4, 20.0; HRMS
(ESI, m/z): calcd for C21H17OS [M + H]+ 317.0995, found 317.0999.
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3-(4-methoxyphenylthio)-2-phenylbenzofuran (3ad):9 The crude compound was
prepared through the general procedure I or procedure II. After purification by silica
gel column chromatography (PE : EA = 30 :1, PE = petroleum ether, EA = ethyl
acetate), compound 3ad was isolated as a pale yellow oil (226 mg, 68% for procedure
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I), (116 mg, 35% for procedure II): Rf (PE : EA = 30 :1) = 0.3; H NMR (400 MHz,
CDCl3): δ 8.26 (d, J = 8.8 Hz, 2H), 7.53 (d, J = 8.0 Hz, 1H), 7.45ꢀ7.48 (m, 3H),
7.38ꢀ7.41 (m, 1H), 7.31 (t, J = 8.0 Hz, 1H), 7.18ꢀ7.24 (m, 3H), 6.76 (d, J = 8.8 Hz,
2H), 3.73 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.3, 156.6, 153.8, 130.8,
129.9, 129.24, 129.19, 128.5, 127.3, 126.4, 125.1, 123.3, 120.4, 114.7, 111.2, 106.4,
55.2.
3-(3-methoxyphenylthio)-2-phenylbenzofuran (3ae): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE : EA = 30 :1), compound 3ae was isolated as a pale yellow solid
(183 mg, 55% for procedure I): mp (melting point) = 83ꢀ84 oC; Rf (PE : EA = 30 :1) =
0.5; IR (film): 2927, 1590, 1477, 1248, 1043, 768, 745, 687 cm−1; 1H NMR (400 MHz,
CDCl3): δ 8.22 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H),
7.38ꢀ7.48 (m, 3H), 7.34 (dt, J = 8.0 Hz, 1.2 Hz, 1H), 7.24 (t, J = 7.2 Hz, 1H), 7.12 (t,
J = 8.0 Hz, 1H) 6.77 (d, J = 8.0 Hz, 1H), 6.75 (t, J = 2.0 Hz, 1H), 6.66 (dd, J = 8.0 Hz,
2.0 Hz, 1H) 3.68 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 160.0, 157.6, 153.9,
137.6, 130.8, 129.9, 129.7, 129.4, 128.5, 127.4, 125.3, 123.5, 120.4, 118.7, 112.1,
111.3, 111.0, 104.4, 55.1; HRMS (ESI, m/z): calcd for C21H17O2S [M+H]+ 333.0944,
found 333.0949.
2-phenyl-3-(4-(trifluoromethyl)phenylthio)benzofuran (3af): The crude compound
was prepared through the general procedure I. After purification by silica gel column
chromatography (PE), compound 3af was isolated as a white solid (265 mg, 72%):
o
mp (melting point) = 77ꢀ79 C; Rf (PE) = 0.6; IR (film): 1606, 1325, 1166, 1123,
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1107, 1087, 1063, 1012, 827, 746, 689 cm−1; 1H NMR (400 MHz, CDCl3): δ 8.19 (d,
J = 8.4 Hz, 2H), 7.59 (d, J = 8.4 Hz, 1H), 7.41ꢀ7.47 (m, 6H), 7.35ꢀ7.39 (m, 1H),
7.23ꢀ7.26 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.2, 154.0, 141.5, 130.3,
129.7, 129.4, 128.7, 127.5 (q, J = 32 Hz, 1C), 127.4, 125.90 (q, J = 3.8 Hz, 1C),
125.85, 125.6, 124.1 (q, J = 270 Hz, 1C), 123.8, 120.1, 111.5, 102.9; HRMS (ESI,
m/z): calcd for C21H13F3OS [M]+ 370.0634, found 370.0632.
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3-(4-bromophenylthio)-2-phenylbenzofuran (3ag):11b The crude compound was
prepared through the general procedure II. After purification by silica gel column
chromatography (PE : EA = 50 : 1), compound 3ag was isolated as a pale yellow oil
(147 mg, 39%): Rf (PE : EA = 20 : 1) = 0.5; 1H NMR (400 MHz, CDCl3): δ 8.20 (d, J
= 8.0 Hz, 2H), 7.58 (d, J = 8.0 Hz, 1H), 7.41ꢀ7.49 (m, 4H), 7.29ꢀ7.38 (m, 3H), 7.25 (t,
J = 7.2 Hz, 1H), 7.05 (d, J = 8.8 Hz,2H); 13C{1H} NMR (100 MHz, CDCl3): δ 157.7,
153.9, 135.4, 132.0, 130.4, 129.6, 129.5, 128.6, 127.9, 127.3, 125.4, 123.6, 120.2,
119.2, 111.4, 103.9.
3-(3-chlorophenylthio)-2-(4-methoxyphenyl)benzofuran (3ba): The crude compound
was prepared through the general procedure I. After purification by silica gel column
chromatography (PE : EA = 40 :1), compound 3ba was isolated as a pale yellow solid
(283 mg, 77%): mp (melting point) = 84ꢀ85 oC; Rf (PE : EA = 30 :1) = 0.6; IR (film):
1609, 1576, 1499, 1460, 1452, 1256, 1177, 1081, 1033, 833, 774, 746 cm−1; 1H NMR
(400 MHz, CDCl3): δ 8.13ꢀ8.17 (m, 2H), 7.55 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 7.6 Hz,
1H), 7.33 (dt, J = 8.0 Hz, 1.2 Hz, 1H), 7.24 (t, J = 8.0 Hz, 1H), 7.16 (t, J = 1.6 Hz,
1H), 7.05ꢀ7.12 (m, 2H), 7.02 (dt, J = 7.6 Hz, 1.6 Hz, 1H), 6.95ꢀ6.99 (m, 2H), 3.84 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 160.7, 158.2, 153.7, 138.7, 134.9, 130.7,
130.1, 130.0, 125.8, 125.6, 125.0, 124.2, 123.6, 122.2, 119.8, 114.1, 111.3, 101.5,
55.3; HRMS (ESI, m/z): calcd for C21H16ClO2S [M+H]+ 367.0554, found 367.0563.
2-(4-methoxyphenyl)-3-(p-tolylthio)benzofuran (3bb): The crude compound was
prepared through the general procedure I or procedure II. After purification by silica
gel column chromatography (PE), compound 3bb was isolated as a pale yellow solid
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(288 mg, 83% for procedure I), (269 mg, 78% for procedure II): mp (melting point) =
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72ꢀ74 C; Rf (PE) = 0.3; IR (film): 1609, 1499, 1451, 1255, 1177, 1079, 1034, 833,
804, 745 cm−1; 1H NMR (400 MHz, CDCl3): δ 8.19 (dd, J = 8.8 Hz, 2H), 7.52 (d, J =
8.4 Hz, 1H), 7.45ꢀ7.47 (m, 1H), 7.28ꢀ7.32 (m, 1H), 7.19ꢀ7.22 (m, 1H), 7.01 (d, J = 8.4
Hz, 2H), 6.96ꢀ7.02 (m, 4H), 3.85 (s, 3H), 2.26 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3): δ 160.4, 157.5, 153.7, 135.3, 132.7, 131.1, 129.8, 128.9, 126.7, 124.7, 123.3,
122.5, 120.1, 114.0, 103.2, 55.3, 20.9; HRMS (ESI, m/z): calcd for C22H19O2S
[M+H]+ 347.1100, found 347.1107.
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3-(3-(p-tolylthio)benzofuran-2-yl)benzonitrile (3cb): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE : EA = 30 :1), compound 3cb was isolated as a pale yellow solid
o
(153 mg, 45%): mp (melting point) = 116ꢀ118 C; Rf (PE : EA = 30 :1) = 0.3; IR
(film): 2231, 1491, 1450, 1255, 1172, 1078, 1016, 865, 802, 747 cm−1; 1H NMR (400
MHz, CDCl3): δ 8.56 (s, 1H), 8.52 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H),
7.53ꢀ7.57 (m, 2H), 7.49 (d, J = 8.0 Hz, 1H), 7.38 (t, J = 8.0 Hz, 1H), 7.25 (t, J = 8.0
Hz, 1H), 7.11 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 2.27 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ 154.0, 153.9, 136.1, 132.1, 131.4, 131.2, 131.1, 130.6,
130.5, 130.0, 129.4, 127.3, 126.1, 123.8, 120.8, 118.5, 113.0, 111.5, 108.0, 20.9;
HRMS (ESI, m/z): calcd for C22H16NOS [M+H]+ 342.0947, found 342.0952.
2-butyl-3-(p-tolylthio)benzofuran (3db): The crude compound was prepared through
the general procedure I. After purification by silica gel column chromatography (PE),
compound 3db was isolated as a pale yellow oil (186 mg, 63%): Rf (PE) = 0.3; IR
1
(film): 2963, 2954, 1489, 1452, 1033, 1016, 803, 747 cm−1; H NMR (400 MHz,
CDCl3): δ 7.45 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.22ꢀ7.26 (m, 1H),
7.15ꢀ7.19 (m, 1H), 7.03 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 2.94 (t, J = 7.6
Hz, 2H), 2.25 (s, 3H), 1,72 (dt, J = 7.6 Hz, 7.6 Hz, 2H), 1,37 (dt, J = 7.6 Hz, 7.4 Hz,
2H), 0.91 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 163.7, 154.3,
135.2, 132.2, 129.6, 128.5, 126.7, 124.0, 123.0, 119.7, 111.0, 104.9, 30.2, 26.3, 22.3,
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20.9, 13.7; HRMS (ESI, m/z): calcd for C19H21OS [M+H]+ 297.1308, found
297.1312.
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2-butyl-3-(4-methoxyphenylthio)benzofuran (3dd): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE : EA = 30 :1), compound 3dd was isolated as a pale yellow oil
(128 mg, 41%): Rf (PE : EA = 30 :1) = 0.3; IR (film): 2955, 2924, 1591, 1493, 1452,
1244, 1173, 1032, 822, 747 cm−1; 1H NMR (400 MHz, CDCl3): δ 7.44 (d, J = 8.0 Hz,
1H), 7.40 (dd, J = 8.0 Hz, 0.8 Hz, 1H), 7.22ꢀ7.26 (m, 1H), 7.18 (dd, J = 8.0 Hz, 0.8
Hz, 1H), 7.14 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 2.96 (t, J =
7.6 Hz, 2H), 1,72 (dt, J = 7.6 Hz, 7.6 Hz, 2H), 1,38 (dt, J = 7.6 Hz, 7.6 Hz, 2H), 0.93
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(t, J = 7.6 Hz, 3H); C{1H} NMR (100 MHz, CDCl3): δ 163.2, 158.1, 154.2, 129.6,
129.2, 127.2, 124.0, 123.0, 119.7, 114.6, 111.0, 106.0, 55.3, 30.2, 26.3, 22.3, 13.7;
HRMS (ESI, m/z): calcd for C19H21O2S [M+H]+ 313.1257, found 313.1263.
5-chloro-2-phenyl-3-(p-tolylthio)benzofuran (3eb):11a The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE), compound 3eb was isolated as a pale yellow solid (249 mg,
71%): Rf (PE) = 0.4; 1H NMR (400 MHz, CDCl3): δ 8.23 (dd, J = 8.0 Hz, 1.2 Hz, 2H),
7.41ꢀ7.47 (m, 5H), 7.22 (dd, J = 8.8 Hz, 2.0 Hz, 1H), 7.09 (d, J = 8.0 Hz, 2H), 7.03 (d,
J = 8.0 Hz, 2H), 2.27 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.7, 152.2,
135.8, 132.5, 131.9, 130.0, 129.7, 129.4, 129.2, 128.6, 127.4, 126.9, 125.5, 120.0,
112.3, 105.0, 20.9.
5-chloro-2-phenyl-3-(o-tolylthio)benzofuran (3ec): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE), compound 3ec was isolated as a pale yellow solid (213 mg,
o
61%): mp (melting point) = 119ꢀ120 C; Rf (PE) = 0.4; IR (film): 1466, 1450, 1440,
1256, 1198, 1067, 804, 768, 744, 687 cm−1; 1H NMR (400 MHz, CDCl3): δ 8.18 (dd,
J = 8.0 Hz, 1.2 Hz, 2H), 7.39ꢀ7.49 (m, 5H), 7.29 (dd, J = 8.8 Hz, 2.0 Hz, 1H), 7.19 (d,
J = 7.2 Hz, 1H), 7.03 (dt, J = 7.2 Hz, 1.2 Hz, 1H), 6.96 (t, 7.2 Hz, 1H), 6.82 (d, 7.6 Hz,
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1H), 2.50 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 159.0, 152.3, 135.3, 134.6,
132.4, 130.4, 129.7, 129.3, 129.2, 128.6, 127.4, 126.7, 125.6, 125.5, 119.9, 112.3,
104.0, 20.4; HRMS (ESI, m/z): calcd for C21H15ClOS [M]+ 350.0527, found
350.0535.
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5-chloro-3-(4-methoxyphenylthio)-2-phenylbenzofuran (3ed): The crude compound
was prepared through the general procedure I. After purification by silica gel column
chromatography (PE : EA = 30 : 1), compound 3ed was isolated as a pale yellow solid
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(255 mg, 70%): mp (melting point) = 99ꢀ101 C; Rf (PE : EA = 30 : 1) = 0.5;IR
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(film):1596, 1493, 1450, 1440, 1246, 1067, 1032, 825, 804, 768, 717, 688 cm−1; H
NMR (400 MHz, CDCl3): δ 8.26 (d, J = 8.8 Hz, 2H), 7.43ꢀ7.50 (m, 5H), 7.27 (dd, J =
8.8 Hz, 2.0 Hz, 1H), 7.19 (dd, J = 6.8 Hz, 2.0 Hz, 2H), 6.79 (dd, J = 6.8 Hz, 2.0 Hz,
2H), 3.75 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 158.4, 158.1, 152.2, 132.4,
129.7, 129.4, 129.3, 129.1, 128.6, 127.4, 125.8, 125.4, 120.0, 114.9, 112.3, 106.0,
55.3; HRMS (ESI, m/z): calcd for C21H15ClO2S [M]+ 366.0476, found 366.0481.
5-fluoro-2-phenyl-3-(p-tolylthio)benzofuran (3fb): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE), compound 3fb was isolated as a pale yellow solid (228 mg,
o
68%): mp (melting point) = 81ꢀ82 C; Rf (PE : EA = 50 : 1) = 0.5; IR (film): 1491,
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1468, 1443, 1158, 1085, 1069, 947, 855, 802, 767, 689 cm−1; H NMR (400 MHz,
CDCl3): δ 8.21ꢀ8.24 (m, 2H), 7.40ꢀ7.47 (m, 4H), 7.09ꢀ7.13 (m, 3H), 7.00ꢀ7.04 (m,
3H); 13C{1H} NMR (100 MHz, CDCl3): δ 159.6 (d, J = 238 Hz, 1C), 158.9, 150.0,
135.8, 132.1 (d, J = 11 Hz, 1C), 131.9, 129.9, 129.6, 129.5, 128.6, 127.3, 127.0, 112.9
(d, J = 26 Hz, 1C), 112.0 (d, J = 9.4 Hz, 1C), 106.0 (d, J = 25 Hz, 1C), 105.6 (d, J =
3.9 Hz, 1C), 20.9; HRMS (ESI, m/z): calcd for C21H16FOS [M+H]+ 335.0900, found
335.0908
5-methyl-2-phenyl-3-(p-tolylthio)benzofuran (3gb): The crude compound was
prepared through the general procedure I. After purification by silica gel column
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chromatography (PE), compound 3gb was isolated as a pale yellow solid (282 mg,
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85%): mp (melting point) = 96ꢀ98 C; Rf (PE : EA = 50 : 1) = 0.4; IR (film): 2921,
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1491, 1473, 1444, 1202, 1085, 1068, 1016, 827, 801, 766, 689 cm−1; H NMR (400
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MHz, CDCl3): δ 8.21ꢀ8.23 (m, 2H), 7.35ꢀ7.46 (m, 4H), 7.29 (s, 1H), 7.13 (dd, J = 7.6
Hz, 1.2 Hz, 1H), 7.09 (d, J = 8.0 Hz, 2H), 7.01 (d, J = 8.0 Hz, 2H), 2.39 (s, 3H), 2.26
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 157.5, 152.3, 135.3, 133.0, 132.7, 131.0,
129.9, 129.8, 129.2, 128.5, 127.3, 126.5, 120.1, 110.8, 104.6, 21.4, 20.9; HRMS (ESI,
m/z): calcd for C22H19OS [M+H]+ 331.1151, found 331.1156.
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4,6-dichloro-2-phenyl-3-(p-tolylthio)benzofuran (3hb): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE), compound 3hb was isolated as a white solid (116 mg, 30%):
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mp (melting point) = 147ꢀ148 C; Rf (PE : EA = 50 : 1) = 0.4; IR (film): 2921, 2846,
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1723, 1575, 1491, 1455, 1398, 1325, 1176, 1081, 1068, 965, 839, 799, 682 cm−1; H
NMR (400 MHz, CDCl3): δ 8.16ꢀ8.19 (m, 2H), 7.50 (d, J = 1.6 Hz, 1H), 7.44ꢀ7.47 (m,
3H), 7.23 (d, J = 1.6 Hz, 1H), 7.03ꢀ7.07 (m, 4H), 2.28 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ 159.9, 154.6, 135.4, 134.0, 130.8, 130.1, 129.9, 128.8, 128.6, 127.9,
127.5, 126.2, 126.0, 125.5, 110.8, 104.8, 20.9; HRMS (ESI, m/z): calcd for
C21H15Cl2OS [M+H]+ 385.0215, found 385.0219.
methyl 2-phenyl-3-(p-tolylthio)benzofuran-5-carboxylate (3ib): The crude
compound was prepared through the general procedure I. After purification by silica
gel column chromatography (PE), compound 3ib was isolated as a pale yellow solid
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(85 mg, 30%): mp (melting point) = 116ꢀ117 C; Rf (PE : EA = 30 : 1) = 0.4; IR
(film): 2918, 2847, 1721, 1491, 1441, 1232, 1095, 767, 746, 690 cm−1; 1H NMR (400
MHz, CDCl3): δ 8.23ꢀ8.26 (m, 3H); 8.07 (dd, J = 8.4 Hz, 1.6 Hz, 1H), 7.58 (d, J = 8.4
Hz, 1H), 7.40ꢀ7.49 (m, 3H), 7.10 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 3.90 (s,
3H), 2.27 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 167.0, 158.7, 156.4, 135.8,
132.1, 131.2, 129.9, 129.7, 129.3, 128.6, 127.4, 127.0, 126.9, 125.9, 122.7, 111.2,
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105.9, 52.1, 20.9; HRMS (ESI, m/z): calcd for C23H19O3S [M+H]+ 375.1049, found
375.1057, calcd for C23H18NaO3S [M+Na]+ 397.0869, found 397.0875.
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2,3-bis(p-tolylthio)benzofuran (3jb): Benzofuranꢀ2ꢀyltrimethylsilane (190 mg,
1mmol), 4ꢀmethylbenzenesulfonohydrazide (335 mg, 1.8 mmol) and I2 (23.0 mg, 0.09
mmol) and 1,4ꢀdioxane (0.5 mL) were mixed in a sealed tube. The mixture was stirred
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at 120 C for 24 hours. Then, the solvent was evaporated under reduced pressure and
the residue was purified by silica gel column chromatography (PE), compound 3jb
was isolated as a pale yellow solid (130 mg, 40%): mp (melting point) = 60ꢀ61 oC; Rf
(PE : EA = 50 : 1) = 0.4; IR (film): 2920, 1597, 1491, 1443, 1083, 1029, 1016, 803,
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746 cm−1; H NMR (400 MHz, CDCl3): δ 7.41ꢀ7.43 (m, 1H), 7.35ꢀ7.38 (m, 1H),
7.26ꢀ7.32 (m, 3H), 7.15ꢀ7.19 (m, 1H), 7.13 (dd, J = 6.4 Hz, 1.6 Hz, 2H), 7.09 (d, J =
13
8.0 Hz, 2H), 7.01 (d, J = 8.0 Hz, 2H), 2.31 (s, 3H), 2.27 (s, 3H); C{1H} NMR (100
MHz, CDCl3): δ 155.9, 153.1, 137.9, 136.1, 131.6, 131.1, 130.0, 129.7, 129.2, 129.0,
128.4, 125.5, 123.4, 120.4, 116.4, 111.5, 21.1, 20.9; HRMS (ESI, m/z): calcd for
C22H19OS2 [M+H]+ 363.0872, found 363.0881.
2-phenyl-3-(p-tolylthio)benzo[b]thiophene (3kb): 2ꢀphenylbenzo[b]thiophene (210
mg, 1mmol), 4ꢀmethylbenzenesulfonohydrazide (335 mg, 1.8 mmol) and I2 (23.0 mg,
0.09 mmol) and 1,4ꢀdioxane (0.5 mL) were mixed in a sealed tube. The mixture was
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stirred at 120 C for 24 hours. Then, the solvent was evaporated under reduced
pressure and the residue was purified by silica gel column chromatography (PE),
compound 3kb was isolated as a pale yellow solid (80 mg, 24%): mp (melting point)
= 72ꢀ73 oC; Rf (PE) = 0.4; IR (film): 2949, 2918, 2846, 1738, 1491, 1430, 1082, 1015,
804, 752, 731, 694 cm−1; 1H NMR (400 MHz, CDCl3): δ 7.80ꢀ7.87 (m, 2H), 7.87 (dd,
13
J = 8.0 Hz, 1.6Hz, 2H), 7.33ꢀ7.44 (m, 5H), 6.94ꢀ6.99 (m, 4H), 2.25 (s, 3H); C{1H}
NMR (100 MHz, CDCl3): δ 149.2, 141.0, 138.3, 135.0, 133.9, 133.4, 129.8, 129.7,
128.8, 128.4, 126.3, 125.1, 125.0, 123.9, 122.1, 111.8, 20.9; HRMS (ESI, m/z): calcd
for C21H17S2 [M+H]+ 333.0766, found 333.0771.
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2-(3-chlorophenylthio)-3-phenylbenzofuran (5aa): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE), compound 5aa was isolated as a pale yellow oil (282 mg, 84%):
Rf (PE) = 0.4; IR (film): 2990, 2900, 1576, 1460, 1445, 1264, 1092, 1079, 965, 773,
739, 698 cm−1; 1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 7.6 Hz, 1H), 7.60 (d, J =
7.6 Hz, 2H), 7.45ꢀ7.52 (m, 3H), 7.36ꢀ7.41(m, 2H), 7.29 (t, J = 7.6 Hz, 1H), 7.21 (s,
1H), 7.13ꢀ7.15 (m, 2H), 7.06ꢀ7.09 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ
156.1, 142.1, 137.0, 135.0, 131.1, 130.2, 129.2, 129.0, 128.7, 128.2, 127.8, 127.6,
126.8, 126.1, 126.0, 123.3, 120.7, 111.6; HRMS (ESI, m/z): calcd for C20H14ClOS
[M+H]+ 337.0448, found 337.0452.
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3-phenyl-2-(p-tolylthio)benzofuran (5ab): The crude compound was prepared
through the general procedure I. After purification by silica gel column
chromatography (PE), compound 5ab was isolated as a pale yellow solid (221 mg,
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70%): mp (melting point) = 54ꢀ56 C; Rf (PE) = 0.3; IR (film): 1491, 1444, 1119,
1078, 964, 804, 770, 749, 698 cm−1; 1H NMR (400 MHz, CDCl3): δ 7.67 (d, J = 8.0
Hz, 1H), 7.62ꢀ7.64 (m, 2H), 7.45ꢀ7.49 (m, 3H), 7.32ꢀ7.40 (m, 2H), 7.27 (dt, J = 8.0
Hz, 0.8Hz, 1H), 7.18 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 2.28 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 156.0, 144.1, 136.9, 131.5, 130.1, 130.0, 129.3,
128.9, 128.6, 128.1, 127.9, 127.5, 125.6, 123.1, 120.5, 111.5, 21.0; HRMS (ESI, m/z):
calcd for C21H17OS [M+H]+ 317.0995, found 317.1002.
2-(4-methoxyphenylthio)-3-phenylbenzofuran (5ad): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE : EA = 30 : 1), compound 5ad was isolated as a pale yellow
solid (274 mg, 82%): mp (melting point) = 55ꢀ57 oC; Rf (PE : EA = 30 : 1) = 0.4; IR
1
(film): 1592, 1493, 1444, 1290, 1246, 1173, 1031, 964, 825, 770, 749, 698 cm−1; H
NMR (400 MHz, CDCl3): δ 7.63ꢀ7.66 (m, 3H), 7.46ꢀ7.51 (m, 3H), 7.41 (t, J = 7.2 Hz,
1H), 7.34 (dt, J = 8.0 Hz, 1.2 Hz, 1H), 7.27ꢀ7.31 (m, 2H), 7.24ꢀ7.26 (m, 1H), 6.81 (dd,
J = 6.8 Hz, 2.0 Hz, 2H), 3.76 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 159.3,
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155.8, 145.1, 131.9, 131.6, 129.4, 128.6, 128.1, 127.8, 126.3, 125.4, 124.4, 123.0,
120.4, 114.8, 111.4, 55.3; HRMS (ESI, m/z): calcd for C21H17O2S [M+H]+ 333.0944,
found 333.0952.
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2-(3-methoxyphenylthio)-3-phenylbenzofuran (5ae): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE : EA = 30 : 1), compound 5ae was isolated as a pale yellow solid
(198 mg, 60%): mp (melting point) = 77ꢀ79 oC; Rf (PE : EA = 30 : 1) = 0.5; IR (film):
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1590, 1477, 1444, 1248, 1232, 1041, 964, 770, 749, 698 cm−1; H NMR (400 MHz,
CDCl3): δ 7.68 (d, J = 7.6 Hz, 1H), 7.63 (d, J = 7.6 Hz, 2H), 7.45ꢀ7.52 (m, 3H), 7.40
(d, J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.15 (t, J = 8.0
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Hz, 1H), 6.79ꢀ6.82 (m, 2H), 6.71 (dd, J = 8.8 Hz, 1.2 Hz, 1H), 3.70 (s, 3H); C{1H}
NMR (100 MHz, CDCl3): δ 160.1, 156.1, 143.1, 136.2, 131.4, 130.0, 129.3, 128.6,
128.5, 128.0, 127.9, 125.8, 123.2, 120.6, 120.3, 113.6, 112.3, 111.6, 55.2; HRMS
(ESI, m/z): calcd for C21H17O2S [M+H]+ 333.0944, found 333.0948.
5-methoxy-3-phenyl-2,6-bis(p-tolylthio)benzofuran
(5bb):
5ꢀmethoxyꢀ3ꢀphenylbenzofuran (224 mg, 1mmol), 4ꢀmethylbenzenesulfonohydrazide
(558 mg, 3 mmol) and I2 (25.4 mg, 0.1 mmol) and 1,4ꢀdioxane (0.5 mL) were mixed
in a sealed tube. The mixture was stirred at 120 oC for 24 hours. Then, the solvent was
evaporated under reduced pressure and the residue was purified by silica gel column
chromatography (PE : EA = 30 : 1), compound 5bb was isolated as a pale yellow
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solid (252 mg, 54%): mp (melting point) = 120ꢀ122 C; Rf (PE : EA = 30 : 1) = 0.3;
1
IR (film): 1491, 1457, 1438, 1269, 1198, 1149, 955, 807, 765, 737, 699 cm−1; H
NMR (400 MHz, CDCl3): δ 7.59 (d, J = 8.4 Hz, 2H), 7.50 (t, J = 7.6 Hz, 2H),
7.40ꢀ7.43 (m, 3H), 7.21 (d, J = 7.6 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H), 7.03ꢀ7.05 (m,
13
3H), 6.88 (s, 1H), 3.92 (s, 3H), 2.39 (s, 3H), 2.28 (s, 3H); C{1H} NMR (100 MHz,
CDCl3): δ 152.7, 151.1, 143.7, 138.8, 136.7, 134.3, 131.5, 131.0, 130.4, 129.9, 129.1,
128.63, 128.60, 128.3, 127.9, 127.7, 127.4, 125.9, 110.8, 100.5, 56.4, 21.2, 20.9;
HRMS (ESI, m/z): calcd for C29H25O2S2 [M]+ 469.1290, found 469.1279.
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5-methoxy-3-phenyl-2-(p-tolylthio)benzofuran (5cb): The crude compound was
prepared through the general procedure I. After purification by silica gel column
chromatography (PE), compound 5cb was isolated as a pale yellow oil (137 mg, 54%):
Rf (PE) = 0.3; IR (film): 1492, 1448, 1233, 1073, 803, 745 cm−1; 1H NMR (400 MHz,
CDCl3): δ 7.50 (d, J = 7.6 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.30 (dt, J = 8.0 Hz, 1.2
Hz, 1H), 7.21ꢀ (t, J = 7.6 Hz, 1H), 7.14 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 8.0 Hz, 2H),
2.35 (s, 3H), 2.26 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 155.7, 143.8, 136.6,
131.4, 129.9, 129.3, 128.4, 125.3, 123.4, 122.5, 119.7, 111.3, 20.9, 9.3; HRMS (ESI,
m/z): calcd for C16H15OS [M+H]+ 255.0838, found 255.0842.
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AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: hxxyzhx@mail.tjnu.edu.cn; lukui@tust.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The authors sincerely thank the financial support from National Science Foundation
of China (Grants 21202119, 21202118).
ASSOCIATED CONTENT
Supporting Information
Spectroscopic for compounds 3aa-3kb and 5aa-5cb. This material is available free of
charge via the Internet at http://pubs.acs.org.
REFERENCES
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