A green and efficient approach for the synthesis of 3-chalcogen Benzo[b]Furans via i 2-mediated cascade annulation reaction of 2-alkynylanisoles at room temperature in water

Article abstract of DOI:10.1080/10426507.2013.770738

An efficient and green aqueous protocol to access 3-chalcogen benzo[b]furan derivatives has been developed. The reaction can proceed via I ₂-mediated intramolecular annulation reaction of 2-alkynylanisoles with diaryl disulfides (diselenides) i

Full text of DOI:10.1080/10426507.2013.770738

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Phosphorus, Sulfur, and Silicon and the Related
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A green and efficient approach for the synthesis of
3-chacogen benzo[b]furans via I2-mediated cascade
annulation reaction of 2-alkynylanisoles at room
temperature in water
Jiang-Sheng Han a , Yin-Lin Shao a , Xiao-Hong Zhang a & Ping Zhong a b
a College of Chemical and Materials Engineering, Wenzhou University, Wenzhou, 325035,
China
b Oujiang College, Wenzhou University, Wenzhou, 325035, China
Accepted author version posted online: 05 Apr 2013.
To cite this article: Phosphorus, Sulfur, and Silicon and the Related Elements (2013): A green and efficient approach for the
synthesis of 3-chacogen benzo[b]furans via I2-mediated cascade annulation reaction of 2-alkynylanisoles at room temperature
in water, Phosphorus, Sulfur, and Silicon and the Related Elements, DOI: 10.1080/10426507.2013.770738
To link to this article: http://dx.doi.org/10.1080/10426507.2013.770738
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A green and efficient approach for the synthesis of 3-chacogen benzo[b]furans via
I2-mediated cascade annulation reaction of 2-alkynylanisoles at room temperature in water
Jiang-Sheng Han,a Yin-Lin Shao,a Xiao-Hong Zhang,*a Ping Zhong*a,b
a College of Chemical and Materials Engineering, Wenzhou University, Wenzhou 325035, China
b Oujiang College, Wenzhou University, Wenzhou 325035, China
Author to whom correspondence should be addressed; E-Mail: kamenzxh@163.com;
zhongp0512@163.com;
Tel.:+86-0577-86689338; Fax: +86-0577-86689338.
Abstract: An efficient and green aqueous protocol to access 3-chalcogen benzo[b]furan
derivatives has been developed. The reaction can proceed via I2-mediated intramolecular
annulation reaction of 2-alkynylanisoles with diaryl disulfides (diselenides) in water or under
solvent-free conditions at room temperature. With the participation of I2, a variety of
3-chalcogen benzo[b]furan derivatives were obtained in good to excellent yields. This
reaction was considered to work via an iodocyclization cascade mechanism and the
intermediate 3-iodo-2-phenylbenzofuran was detected by GC-MS.
Keywords: 3-chalcogen benzo[b]furans; I2-mediated intramolecular annulation;
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<AQ>Author, confirm all tables are numbered and placed correctly<AQ>
INTRODUCTION
Benzofuran moieties are an important class of heterocyclic compounds1-4 and have shown a
broad range of biological activities, such as anticancer,5-8 antimicrobial,9-11
anti-inflammatory,12-15 antiviral,16-17 and antifungal activities.18-21 Therefore, many efficient
and versatile strategies to construct benzofuran scaffolds have been developed during the past
few years.22-25 However, to the best of our knowledge, little attention has been devoted to the
synthesis of 3-chalcogen benzofurans such as 3-sulfenyl benzo[b]furans and 3-selenenyl
benzo[b]furans.26-28 The conventional methods for the synthesis of these compounds typically
involve either the electrophilic cyclisation of 2-chalcogenealkynyl anisoles using I2, ICl, Br2,
or PhSeBr as the electrophilic sources29 (a, Scheme 1) or the electrophilic cyclisation of
2-(arylethynyl)anisole with 4-NO2C6H4SCl (PhSeCl)30 (b, Scheme 1). Alternatively,
Pd-catalyzed or Fe-promoted intramolecular cyclisation of 2-alkynylanisoles with diaryl
disulfides have been developed by Li31 and Zeni’s groups32, respectively (c and d, Scheme 1).
However, transition-metal-based protocols usually have several limitations, such as moisture
sensitivity, expensive metal catalysts, environmental toxicity. And a stoichiometric amount of
FeCl3 was required in Zeni’s preparative process, thus lots of toxic waste would be generated.
To avoid using any metal catalysts, a metal-free synthesis of 3-chalcogen benzofurans in
toluene at 110°C has been reported by our group recently33 (e, Scheme 1).
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However, toluene is toxic to the environment and human health. And high temperature
(110°C) has also limited the application of this method. In recent years, in view of the great
demand for green chemistry which is economic and sustainable, much efforts have been paid
to ensure these criterias are met.34 Among the various green methods, the application of
environmentally friendly solvents, such as water, is the most important concern.35-40
In this context, we herein demonstrate I2-mediated intramolecular annulation reaction of
2-alkynylanisoles with diaryl disulfides (diselenides) to give 3-chalcogen benzo[b]furan
derivatives in water or under solvent-free conditions at room temperature (f, Scheme 1). This
approach contains some interesting advantages: (1) the reaction proceeds well without using
any metal catalysts or other additives; (2) since water is a safe, harmless, and environmentally
benign solvent, it is used instead of organic solvents; (3) the reaction system worked well for
many substrates in good to excellent yields at room temperature.
Results and discussion
2-(phenylethynyl)anisole (1a) and diphenyl disulfide (2a) were chosen as model substrates
to determine the optimal reaction conditions (Table 1). The amount of I2 was evaluated using
water as solvent at room temperature. It can be seen that the amount of I2 greatly affected the
reaction. For example, only 26% conversion of the target compound 3, as well as 32%
3-iodo-2-phenylbenzofuran 3a, can be obtained when the amount of I2 was 0.5 equiv, keeping
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40% substrate 1a intact (entry 1, Table 1 ). When the amount of I2 was increased to 1.0 equiv,
the conversion of 3 was sharply enhanced to 80% associated with 15% conversion of 3a
(entry 2, Table 1). Notably, 1.5 equiv I2 gave similar results as 2.0 equiv I2 (entry 3, 4, Table
1). Thus, the combination of 1.0 equiv 2-alkynylanisoles, 0.5 equiv diaryl disulfides, 1.5 equiv
I2 in water at room temperature for overnight was chosen as the optimal conditions for further
exploration.
With the optimal reaction conditions in hand, the scope of both 2-alkynylanisoles and diaryl
disulfides as reaction partners was explored for the annulation reaction. The results are
summarized in Table 2. Initially, a series of diaryl disulfides were chosen to react with
2-phenylethynylanisole (entry 1-6). The results reveal that the reactions are insensitive to
electronic effect of the substituents on the aryl moiety of diaryl disulfides and various diaryl
disulfides worked well under the optimal conditions, affording the desired products in good
yields. For example, disulfide with CH3 group (entry 2) gave the same high yield as those
with electron-withdrawing moieties, such as F, Cl and Br (entries 3-5). However, no desired
product but, only the intermediate 3-iodo-2-phenylbenzofuran (3a) was obtained in good
yields when 2-(phenylethynyl)anisole reacted with 2,2’-dithiobisthiazole and
2,2’-dithiobisthiophene, respectively (entry 6). Notably, diaryl disulfide bearing CH3, F, Cl
groups can occur smoothly under solvent-free conditions, also giving the corresponding
products in good yields (entries 2-4). Subsequently, a variety of 2-alkynylanisoles were
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examined (Table 2, entries 7-21). It was found that the environmentally friendly protocol was
compatible with 2-alkynylanisoles bearing 4-CH3C6H4, 4-ClC6H4 and 4-FC6H4 groups at the
terminal of the 1-ethynyl-2-methoxybenzene and those with 4-Cl and 4-CH3 groups on the
anisole moiety. More than 80% yields of the corresponding products were obtained when
these 2-alkynylanisoles reacted with various disulfides. For instance, treatment of
2-(4-methylphenylethynyl)anisole with diphenyl disulfide afforded the product 8 in 90% yield
(entry 7), whose structure was confirmed by X-ray crystallography (Fig. 1).
As expected, the reactions of various 2-alkynylanisoles with diphenyl diselenide proceed
successfully to afford the desired products in good yields (Table 3). In the presence of I2,
2-alkynylanisoles, bearing 4-CH3C6H4 and 4-FC6H4 group at the terminal
1-ethynyl-2-methoxybenzene, smoothly underwent the reaction to give the target products 24,
26, 27 and 28 in 83%, 85%, 93% and 85% yields, respectively (entries 2, 4, 5, 6).
Gratifyingly, the reaction of 2-alkynylanisoles, having 4-Cl and 4-CH3 groups on the anisole
moiety, with diphenyl diselenide was also conducted smoothly in good yield under the
standard conditions (entries 3-6). The structure of compound 25 was also confirmed by
X-Ray crystallography (Fig. 2).
Table 4 details the X-ray structural parameters of compounds 8 and 25
[Insert Table 4]
The reaction process was monitored by GC-MS and the reaction mixture was sampled every
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3h. It was found that intermediate 3-iodo-2-phenylbenzofuran (3a) was first formed from the
reaction of 1a and I2. Then intermediate 3a was reacted with diphenyl disulfide to give
compound 3 in 93% yield with the aid of I2. To elucidate the reaction pathway, controlled
reactions between 1a, 2a, 3a and I2 were carried out, respectively (a, b, Scheme 2). In the
absence of 2a, 1a could react with stoichiometric amount of I2 to give 3a quantitatively.
Meanwhile, no target product 3 was observed by GC-MS in the absence of I2, whereas 3 was
obtained in good yield when I2 was added to the mixture of 3a and 2a. The results suggested
that the reaction proceeded via an iodocyclization cascade process though the competitive
process was reported in our previous paper.[13] Based on the present results, a possible
mechanism was proposed as outlined in Scheme 3.
Initially, the direct electrophilic addition of 2-(phenylethynyl)anisole (1a) with I2 occurred
to give the intermediate A, after the annulation and the removal of CH3 group from A with the
aid of I- nucleophile, the intermediate 3a was formed. Besides, the reaction of diphenyl
disulfide 2a with I2 would yield PhSI in situ, which was reacted with 3a to give the target
compound 3.
Conclusion
We would like to conclude that we have developed an efficient and environmentally friendly
approach for the synthesis of 3-chalcogen benzo[b]furan derivatives in water with good to
excellent yields at room temperature. The reaction can proceed well without using any organic
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solvent, metal-catalyst or other additives. Adopting this protocol, a number of 3-chacogen
benzo[b]furan derivatives were synthesized at room temperature in view of green chemistry
by avoiding to use the highly volatile and toxic organic solvents. The reaction mechanism has
been intensively studied in detail and was proposed to proceed via an iodocyclization cascade
process. The structures were unambiguously determined by the analytic tools, such as
1
GC-MS, HRMS, H and 13C NMR. Compounds 8 and 25 were further confirmed by X-Ray
crystallographic analysis.
Experimental Section
General procedure for the synthesis of 3-chalcogen benzo[b]furans
2-(phenylethynyl)anisoles (0.5 mmol), I2 (0.75 mmol), diphenyl disulfides (0.25 mmol), water (1.0 ml)
were added to a test tube. The mixture was allowed to stir at room temperature for 12 h, and the resulting
mixture was washed with saturated sodium thiosulfate (5 ml), and then extracted with ethyl acetate (2 x 5
mL). The combined organic fractions were concentrated under vacuum to yield the crude product. The
crude product was purified by flash chromatography on silica gel using Petroleum ether as the eluent.
3-iodo-2-phenylbenzo[b]furan (3a)30
2-phenyl-3-(phenylthio)benzofuran (3)33
2-phenyl-3-(p-tolylthio)benzofuran (4)30
3-(4-fluorophenylthio)-2-phenylbenzofuran (5)30
3-(4-chlorophenylthio)-2-phenylbenzofuran (6)30
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3-(4-bromophenylthio)-2-phenylbenzofuran (7). The product was obtained as a white solid in 95% yield.
º
m.p. 116-117 C. 1H NMR (CDCl3, 500 MHz): δ 8.18-8.20 (m, 2H), 7.56 (d, J = 10 Hz, 1H), 7.43-7.46 (m,
13
3H), 7.38-7.41 (m, 1H), 7.32-7.35 (m, 1H), 7.28-7.30 (m, 2H), 7.21-7.25 (m, 1H), 7.03-7.05 (m, 2H). C
NMR (125 MHz, CDCl3); δ (ppm): 157.8, 154.0, 135.5, 132.1, 130.9, 130.5, 129.6, 128.7, 128.0, 127.4,
125.5, 123.7, 120.3, 119.3, 111.5, 104.1, IR (KBr, cm-1): 3007, 2358, 1222, 1079, 1006, 801, 739, 683.
HRMS (ESI): Calcd 380.9894 for C20H14BrOS+, Found 380.9906 (M+H+).
3-(phenylthio)-2-p-tolylbenzofuran (8)30
3-(4-methylphenylthio)-2-(4-methyphenyl)benzofuran (9)1
3-(4-fluorophenylthio)-2-(4-methyphenyl)benzofuran (10)30
3-(4-chlorophenylthio)-2-(4-methyphenyl)benzofuran (11). The product was obtained as a white solid in
88% yield. m.p.120-122 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.09 (d, J = 10 Hz, 2H), 7.55 (d, J = 10 Hz, 1H),
7.44 (d, J = 10 Hz, 1H), 7.43-7.45 (m, 1H), 7.31-7.35 (m, 1H), 7.21-7.27 (m, 4H), 7.09-7.16 (m, 4H), 2.39 (s,
13
3H). C NMR (125 MHz, CDCl3) δ (ppm): 158.0, 153.9, 139.9, 135.0, 131.4, 130.6, 129.4, 129.2, 127.7,
127.3, 126.8, 125.2, 123.6, 120.1, 111.4, 103.4, 21.5. IR (KBr, cm-1): 2921, 1424, 1361, 1228, 1089, 806,
749. LRMS (EI, 70 eV) m/z (%): 350 (M+, 100). HRMS (ESI): Calcd 351.0605 for C21H16OSCl+, Found:
351.0613 (M+H+).
3-(4-bromophenylthio)-2-(4-methyphenyl)benzofuran (12). The product was obtained as a white solid in
97% yield. m.p. 138-139 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.09 (d, J = 10 Hz, 2H), 7.55 (d, J = 10 Hz, 1H),
7.44 (d, J = 10 Hz, 1H), 7.21-7.35 (m, 6H), 7.03 (d, J = 5 Hz, 2H), 2.39 (s, 3H). 13C NMR (125 MHz, CDCl3)
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δ (ppm): 158.1, 153.9, 139.9, 135.7, 132.1, 130.6, 129.4, 128.0, 127.3, 126.8, 125.2, 123.6, 120.1, 119.1,
111.4, 103.2, 21.5. IR (KBr, cm-1): 3007, 2358, 2153, 1417, 1361, 1222, 1089, 1003, 814, 799, 744. LRMS
(EI, 70 eV) m/z (%): 396 (M+, 100), 395 (23.5), 397 (21.6). HRMS (ESI): Calcd 395.0100 for C21H16OSBr+,
Found: 395.0113 (M+H+).
3-(phenylthio)-2-(4-chlorophenyl)benzofuran (13). The product was obtained as a white solid in 90% yield.
m.p. 79-81 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.19 (d, J = 10 Hz, 2H), 7.54 (d, J = 5 Hz, 1H), 7.48 (d, J = 10
Hz, 1H), 7.41 (d, J = 10 Hz, 2H), 7.34 (t, J = 10 Hz, 1H), 7.17-7.24 (m, 5H), 7.10-7.13 (m, 1H). 13C NMR
(125 MHz, CDCl3) δ (ppm): 156.3, 154.0, 135.8, 135.4, 130.8, 129.1, 128.9, 128.6, 128.3, 126.7, 125.8,
125.6, 123.6, 120.5, 111.4, 105.4. IR (KBr, cm-1): 1218, 1092, 1003, 827, 738, 685. LRMS (EI, 70 eV) m/z
(%): 336 (M+,100), 337 (26.3). HRMS (ESI): Calcd 337.0448 for C20H14OSCl+, Found: 337.0438 (M+H+).
3-(4-methyphenylthio)-2-(4-chlorophenyl)benzofuran (14). The product was obtained as a white solid in
92% yield. m.p. 110-113 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.20 (d, J = 10 Hz, 2H), 7.53 (d, J = 10 Hz, 1H),
7.48 (d, J = 10 Hz, 1H), 7.41 (d, J = 10 Hz, 2H), 7.33 (t, J = 10 Hz, 1H), 7.20-7.25 (m, 1H), 7.09 (d, J = 10
Hz, 2H), 7.01 (d, J = 10 Hz, 2H), 2.26 (s, 3H). 13C NMR (125 MHz, CDCl3) δ (ppm): 155.9, 153.9, 135.8,
135.3, 132.1, 130.8, 129.9, 128.8, 128.6, 128.37, 127.0, 125.5, 123.6, 120.5, 111.3, 106.0, 20.9. IR (KBr,
cm-1): 3007, 2358, 1218, 1096, 1006, 883, 822, 796, 743, 719. LRMS (EI, 70 eV) m/z (%): 350 (M+,100),
351 (25.4). HRMS (ESI): Calcd 351.0605 for C21H16OClS +, Found: 351.0610 (M+H+).
3-(4-fluorophenylthio)-2-(4-chlorophenyl)benzofuran (15). The product was obtained as a white solid in
95% yield. m.p. 105-107 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.18 (d, J = 5 Hz, 2H), 7.54 (d, J = 5 Hz, 1H ),
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7.41-7.46 (m, 3H), 7.33-7.36 (m, 1H), 7.22-7.25 (m, 1H), 7.15-7.18 (m, 2H), 6.89-6.92 (m, 2H). 13C NMR
(125 MHz, CDCl3) δ (ppm): 161.4 (d, JC-F = 243.7 Hz), 156.0, 153.9, 135.4, 130.7 (d, JC-F = 2.5 Hz), 130.52,
128.9, 128.8 (d, JC-F = 8.8 Hz), 128.6, 128.2, 125.6, 123.7, 120.4, 116.3 (d, JC-F = 21.3 Hz), 111.4, 105.8. IR
(KBr, cm-1): 1222, 1096, 1009, 887, 829, 741, 724. LRMS (EI, 70 eV) m/z (%): 354 (M+,100), 355 (22.7).
HRMS (ESI) Calcd 355.0354 for C20H13OClFS +, Found: 355.0378.
3-(4-chlorophenylthio)-2-(4-chlorophenyl)benzofuran (16). The product was obtained as a white solid in
90% yield. m.p. 137-139 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.17 (d, J = 5 Hz, 2H), 7.56 (d, J = 10 Hz, 1H ),
7.42-7.46 (m, 3H), 7.35-7.38 (m, 1H), 7.23-7.26 (m, 1H), 7.16-7.18 (m, 2H), 7.09-7.10 (m, 2H), 13C NMR
(125 MHz, CDCl3) δ (ppm): 156.4, 153.9, 135.6, 134.4, 131.7, 130.4, 129.3, 128.9, 128.6, 128.1, 127.8,
125.7, 123.8, 120.3, 111.5, 104.8. IR (KBr, cm-1): 736, 802, 887, 1009, 2994, 2358, 2153. LRMS (EI, 70 eV)
m/z (%): 370 (M+,100), 371 (23). HRMS (ESI): Calcd 371.0059 for C20H13OClFS+, Found: 371.0068
(M+H+).
3-(4-bromophenylthio)-2-(4-chlorophenyl)benzofuran (17). The product was obtained as a white solid in
77% yield. m.p. 132-133 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.16 (d, J = 10 Hz, 2H), 7.56 (d, J = 10 Hz, 1H ),
7.42-7.46 (m, 3H), 7.30-7.38 (m, 3H), 7.23-7.26 (m, 1H), 7.02-7.04 (m, 2H), 6.89-6.92 (m, 2H). 13C NMR
(125 MHz, CDCl3) δ (ppm): 156.5, 154.0, 135.6, 135.1, 132.2, 130.4, 128.9, 128.6, 128.1, 125.7, 123.8,
120.3, 119.5, 111.5, 104.7. IR (KBr, cm-1): 3009, 1171, 1078, 1008, 932, 887, 834, 804, 742, 654. LRMS
(EI, 70 eV) m/z (%): 416 (M+,100), 415 (20.8). HRMS (ESI): Calcd 414.9554 for C20H13BrClOS+, Found:
414.9532 (M+H+).
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5-chloro-2-phenyl-3-(phenylthio)benzofuran (18)33
5-chloro-2-(4-methylphenyl)-3-(phenylthio)benzofuran (19). The product was obtained as a white solid in
80% yield. m.p. 151-153 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.10-8.12 (d, J = 10 Hz, 2H), 7.44-7.46 (m, 2H),
13
7.11-7.28 (m, 9H), 2.38 (s, 3H). C NMR (125 MHz, CDCl3) δ (ppm): 159.4, 152.2, 140.1, 135.8, 132.6,
129.4, 129.2, 129.2, 127.4, 126.6, 126.5, 125.7, 125.3, 119.8, 112.3, 103.5, 21.5. IR (KBr, cm-1): 1715, 1443,
1362, 1222, 1088, 1067. HRMS (ESI): Calcd 350.0532 for C21H16OClS+, Found: 350.0527 (M+H+).
5-methyl-2-phenyl-3-(phenylthio)benzofuran (20)31
5-methyl-2-(4-methylphenyl)-3-(phenylthio)benzofuran (21). The product was obtained as a white solid in
92% yield. m.p. 128-130 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.09-8.11 (d, J = 10 Hz, 2H), 7.41-7.43 (d, J =
10 Hz, 1H), 7.23-7.24 (m, 3H), 7.17-7.21 (m, 4H), 7.08-7.13 (m, 2H), 2.38-2.39 (d, J = 5 Hz, 6H). 13C NMR
(125 MHz, CDCl3) δ (ppm): 158.2, 152.3, 139.5, 136.6, 133.1, 131.1, 129.3, 129.0, 127.3, 127.1, 126.4,
126.2, 125.3, 119.9, 110.8, 103.3, 21.4, 21.3. IR (KBr, cm-1): 1438, 1362, 1222, 1084, 819, 797, 736, 686.
HRMS (ESI): Calcd 331.1151 for C22H19OS +, Found: 331.1153 (M+H+).
5-methyl-2-(4-fluorophenyl)-3-(phenylthio)benzofuran (22). The product was obtained as a white solid in
85% yield. m.p. 104-106 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.18-8.21 (m, 2H), 7.40-7.42 (d, J = 10 Hz, 1H),
13
7.28 (s, 1H), 7.16-7.22 (m, 4H), 7.09-7.14 (m, 4H), 2.38 (s, 3H), C NMR (125 MHz, CDCl3) δ (ppm):
163.2(d, JC-F = 250 Hz), 156.9, 152.3, 136.2, 133.3, 130.9, 129.3 (d, JC-F = 12.5 Hz), 129.1, 126.7, 126.2,
125.5, 120.7, 120.0, 115.6 (d, JC-F = 12.5 Hz), 110.8, 103.8, 21.3. IR (KBr, cm-1): 1497, 1472, 1438, 1410,
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1361, 1233, 1158, 1079, 1023, 930, 872, 836, 798, 736, 687. HRMS (ESI): Calcd 335.0900 for C21H16OFS+,
Found: 335.0881 (M+H+).
2-phenyl-3-(phenylseleno)benzofuran (23)33
2-(4-methylPhenyl)-3-(phenylseleno)benzofuran (24)33
5-chloro-2-phenyl-3-(phenylseleno)benzofuran (25)33
5-chloro-2-(4-methyl-phenyl)-3-(phenylseleno)benzofuran (26). The product was obtained as a white solid
º
in 85% yield. m.p. 138-140 C. 1H NMR (CDCl3, 500 MHz) δ: 8.07-8.09 (d, J = 10 Hz, 2H), 7.47 (m, 1H),
13
7.43-7.45 (d, J = 10 Hz, 1H), 7.24-7.27 (m, 5H), 7.14-7.19 (m, 3H), 2.39 (s, 3H). C NMR (125 MHz,
CDCl3) δ (ppm): 159.1, 152.4, 140.0, 133.7, 131.1, 129.4, 129.3, 129.2, 127.8, 126.9, 126.5, 125.2, 120.7,
112.1, 98.5, 21.5. IR (KBr, cm-1): 3007, 2914, 1225, 1086, 907, 661. LRMS (EI, 70 eV) m/z (%): 318 (M+,
100), 398 (36). HRMS (ESI): Calcd 399.0048 for C21H16OClSe +, Found: 398.9996 (M+H+).
5-methyl-2-(4-methylphenyl)-3-(phenylseleno)benzofuran (27). The product was obtained as a white solid
in 93% yield. m.p. 117-119 ºC. 1H NMR (CDCl3, 500 MHz) δ: 8.07-8.09 (d, J = 10 Hz, 2H), 7.40-7.42 (d, J
= 10 Hz, 1H), 7.23-7.30 (m, 5H), 7.11-7.17 (m, 4H), 2.38 (s, 3H), 2.40 (s, 3H). 13C NMR (125 MHz, CDCl3)
δ (ppm): 157.9, 152.5, 139.4, 133.0, 132.1, 131.8, 129.3, 129.2, 128.9, 127.7, 127.5, 126.3, 126.1, 120.8,
110.6, 98.5, 21.4, 21.4. IR (KBr, cm-1): 1711, 1436, 1420, 1361, 1222, 1091, 1067. HRMS (ESI): Calcd
379.0597 for C22H19OSe+, Found: 379.0585 (M+H+).
5-methyl-2-(4-fluorophenyl)-3-(phenylseleno)benzofuran (28). The product was obtained as a white solid in
º
85% yield. m.p. 97-98 C. 1H NMR (CDCl3, 500 MHz) δ: 8.17-8.20 (m, 2H), 7.41-7.43 (d, J = 10 Hz, 1H),
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13
7.32 (s, 1H), 7.25-7.27 (m, 2H), 7.10-7.19 (m, 6H), 2.41 (s, 3H). C NMR (125 MHz, CDCl3) δ (ppm):
163.2 (d, JC-F = 250 Hz), 156.6, 152.5, 133.2, 132.0, 131.5, 129.7, 129.7, 129.4, 128.9, 126.6, 126.2, 120.9,
115.5 (d, JC-F = 12.5 Hz), 110.7, 99.0, 21.4. IR (KBr, cm-1): 1713, 1605, 1576, 1496, 1473, 1437, 1223, 1158,
1068, 1021, 983, 932, 835, 801, 732, 688, 667. HRMS (ESI): Calcd 383.0346 for C21H16OFSe+, Found:
383.0359 (M+H+).
CCDC 876672 and CCDC 876669 contain the supplementary crystallographic data for compounds 8 and
25, irrespectively. These data can be obtained free of charge from the Cambridge Crystallographic Data
Centre, via www.ccdc.cam.ac.uk/data_request.cif.
Acknowledgements
The authors thank the National Natural Science Foundation of China (No. 20972114) and the
Zhejiang Provincial Natural Science Foundation of China (Y4100578).
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YR1
a)
E
E+
CH2Cl2
YR1
R
R
O
O
Y=S,Se E=I2, ICl, PhSeBr, Br2
R1
YAr
b)
c)
CH2Cl2 25 oC
+
R
R
ArYCl
R1
O
O
O
Y=S,Se
R1
+
YR3
PdCl2/I2
R
R3YYR3
Y=S,Se
R1
R
R2
CH3CN, 80oC
O
Ar
d)
YR1
R1YYR1
Y=S,Se
FeCl3, 1.0 equiv
R
+
Ar
R
CH2Cl2, 45 o
C
O
O
e)
R
YR1
Ar
I2, toluene
110oC
R1YYR1
Y=S,Se
Ar
+
R
O
O
f) This work:
Ar
+
YAr1
I2, r.t.
Ar1YYAr1
Y=S,Se
R
Ar
R
water or solvent-free
O
O
heterogeneous reaction
Scheme 1 Strategies for the annulation reaction of 2-alkynylanisoles to 3-chalcogen benzofurans
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a)
I
S
I2
+
PhSSPh
+
O
O
I
O
1a
2a
3
3a
I2
I
b)
S
I2
+
PhSSPh
+
PhSSPh
O
O
O
3a
2a
3
3a
2a
Scheme 2 The reaction pathway
I
I
I
I2
O
O
O
O
A
CH3
CH3
3a
1a
I
PhSSPh 2a
I
I2
S
PhSI
O
O
3a
3
Scheme
3 Mechanism study for the annulation reaction of 2-alkynylanisoles to 3-chalcogen benzofurans
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Table 1 screening optimal conditionsa
I
S
I2, H2O
+
PhSSPh
+
r.t.
O
O
O
1a
2a
3
3a
Conversionb (%)
Entry
I2 (equiv)
3
3a
32
15
2
1
2
3
4
0.5
1.0
1.5
2.0
26
80
97
98
1.5
aReaction conditions: 1a (0.5 mmol, 1.0 equiv), 2a (0.25 mmol, 0.5 equiv), H2O (1.0 ml), rt, air,
overnight.
bThe conversion of 3 and 3a was analyzed by GC-MS.
Table 2 I2-promoted annulation reaction of 2-alkynylanisoles with diaryl disulfidesa,b
R2
R3
S
1.5 equiv I2
r.t. H2O
+
R3
S
S
R3
R1
R2
R1
O
O
F
S
S
S
O
O
O
4c
entry 1, 3 (93%)
entry 3, 5c (94%)
entry 2, (95%)
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Cl
Br
S
S
I
O
O
O
entry 4, 6c (90%)
entry 5, 7 ( 95%)
entry 6, 3a ( 90%d )
F
S
S
S
O
O
O
entry 7, 8 (90%)
entry 8, 9 (82%)
10
entry 9,
(88%)
Br
Cl
S
S
S
Cl
O
O
O
entry 12, 13 (90%)
entry 10, 11 (97%)
12
entry 11,
(97%)
Cl
F
S
S
S
Cl
Cl
Cl
O
O
O
entry 13, 14 (92%)
16
entry 14, 15 (95%)
entry 15,
(90%)
Br
S
S
S
Cl
Cl
Cl
O
O
O
19
(80%)
entry 17, 18 (83%)
entry 18,
entry 16, 17 (86%)
S
S
S
F
O
O
O
entry 19, 20 (85%)
entry 20, 21 (92%)
entry 21, 22 (85%)
aReaction conditions: 2-alkynylanisole (0.5 mmol), diaryl disulfide (0.25 mmol), I2 (0.75
mmol), H2O (1.0 ml). The reaction mixture was stirred for 12 h at room temperature under air,
then isolated by column chromatography.
bYield of isolated products.
cThe reaction proceeded under solvent-free conditions.
dThe intermediate 3a was obtained from the reaction of 2,2’-dithiobisthiazole and
2,2’-dithiobisthiophene with 2-(phenylethynyl)benzofuran, respectively.
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Table 3 I2-promoted annulation reaction of 2-alkynylanisoles with diphenyl diselenide a
R2
SePh
1.5 equiv I2
+
R2
R1
R1
PhSeSePh
r.t. H2O
O
O
Se
Se
Se
Cl
O
O
O
entry 2, 24 (83%)
entry 1, 23 (89%)
entry 3, 25 (95%)
Se
O
Se
Se
Cl
F
O
O
entry 4, 26 (85%)
entry 5, 27 (93%)
entry 6, 28 (85%)
aReaction conditions: 2-alkynylanisole (0.5 mmol), diphenyl diselenide (0.25 mmol), I2 (0.75
mmol), H2O (1.0 ml). The reaction mixture was stirred for 12 hours at room temperature under
air, then isolated by column chromatography.
bIsolated yields
Table 4: Crystal Structure and Data Refinement Parameters
Compound
8
25
C20H13ClOSe
383.71
Empirical Formula
Formula Weight
C21H16OS
316.40
Crystal System / Space Group Monoclinic, P 21/c
Triclinic, P -1
9.4752(10)
9.7345(10)
10.5538(11)
63.692(2)
a / Å
b / Å
c / Å
α / °
12.268(4)
5.885(2)
22.907(8) A
90
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β / °
100.563(10)
90
1625.8(10)
4
1.293
0.201
71.369(2)
75.086(2)
819.17(15)
2
1.556
2.456
γ / °
V / Å3
Z
D calc (g/cm3)
ꢀ (mm-1)
Crystal size (mm)
Color / Shape
Temp (K)
0.23 x 0.15 x 0.12
white
298(2)
0.30 x 0.25 x 0.22
white
298(2)
Theta range for collection
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness of fit on F2
Final R indices [I > 2σ(I)]
1.69 to 25.50
9344
3003
3003 / 0 / 209
1.030
R1 = 0.0461, wR2 =
0.1209
2.22 to 25.50
6852
2986
2986 / 0 / 208
1.045
R1 = 0.0313, wR2 =
0.1131
R indices (all data)
R1 = 0.0905, wR2 =
0.1361
R1 = 0.0380, wR2 =
0.1460
Largest difference peak/hole
0.262 and -0.227
0.779 and -0.725
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Fig. 1 The X-ray crystal structure of compound 8
Fig. 2 The X-ray crystal structure of compound 25
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