Synthesis of [1]benzothiopheno[2,3-b][1]benzothiophene derivatives through iodine-mediated sulfuration reaction of 1,1-diarylethylenes

Article abstract of DOI:10.1016/j.tetlet.2019.151476

Acceleration of the reaction for the synthesis of [1]benzothiopheno[2,3-b][1]benzothiophenes (BTBTs) from 1,1-diarylethylenes was accomplished by the addition of molecular iodine. Postulated intermediates 3-arylbenzo[b]thiophenes were also selectively prepared by simply changing the amount of iodine and the reaction time.

Full text of DOI:10.1016/j.tetlet.2019.151476

Journal Pre-proofs
Synthesis of [1]benzothiopheno[2,3-b][1]benzothiophene derivatives through
iodine-mediated sulfuration reaction of 1,1-diarylethylenes
Shuta Sakai, Kazuki Sato, Kazuhiro Yoshida
PII:
S0040-4039(19)31275-4
DOI:
https://doi.org/10.1016/j.tetlet.2019.151476
TETL 151476
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
11 October 2019
23 November 2019
2 December 2019
Please cite this article as: Sakai, S., Sato, K., Yoshida, K., Synthesis of [1]benzothiopheno[2,3-b][1]benzothiophene
derivatives through iodine-mediated sulfuration reaction of 1,1-diarylethylenes, Tetrahedron Letters (2019), doi:
https://doi.org/10.1016/j.tetlet.2019.151476
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Graphical Abstract
Synthesis of [1]benzothiopheno[2,3-
b][1]benzothiophene derivatives through
iodine-mediated sulfuration reaction of 1,1-
diarylethylenes
Leave this area blank for abstract info.
Shuta Sakai, Kazuki Sato, Kazuhiro Yoshida*

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Synthesis of [1]benzothiopheno[2,3-b][1]benzothiophene derivatives through iodine-
mediated sulfuration reaction of 1,1-diarylethylenes
Shuta Sakaia , Kazuki Satoa, Kazuhiro Yoshidaa,b,

aDepartment of Chemistry, Graduate School of Science, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
bMolecular Chirality Research Center, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
———
ARTICLE INFO
ABSTRACT
 Corresponding author. Tel.: +0-000-000-0000; fax: +0-000-000-0000; e-mail: author@university.edu
Article history:
Received
Acceleration of the reaction for the synthesis of [1]benzothiopheno[2,3-b][1]benzothiophenes
(BTBTs) from 1,1-diarylethylenes was accomplished by the addition of molecular iodine.
Received in revised form
Accepted
Postulated intermediates 3-arylbenzo[b]thiophenes were also selectively prepared by simply
changing the amount of iodine and the reaction time.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
3-Arylbenzo[b]thiophenes
[1]Benzothiopheno[2,3-b][1]benzothiophene
[1]Benzothiopheno[3,2-b][1]benzothiophene
Iodine
Sulfuration
reacting with elemental sulfur,3 which was reported more than
half a century ago (Scheme 2).4 Because BTBT containing TT
structure 15 was obtained from simple materials by quadruple C-
Introduction
Thiophene-containing -conjugated molecules have been
attracting considerable attention because they can be used as
diverse functional materials, such as organic field-effect
transistors (OFETs).1 Thienothiophenes (TTs) containing two
annulated thiophene rings are known to be one of the most
important core frameworks that constitute such molecules. TTs
have four isomers, thieno[2,3-b]thiophene 1, thieno[3,2-
b]thiophene 2, thieno[3,4-b]thiophene 3, and thieno[3,4-
c]thiophene 4 (Figure 1). Whereas little attention has been given
to 4 by reason of its instability, research of TTs 1–3 has made
much progress.
S bond formation via the cleavage of C–H bonds,6,7 the reaction
caught our eye. At the same time, we were aware that little
attention has been given to the reaction so far. Because we
considered that the harsh reaction conditions, namely, solvent-
free reaction and a high reaction temperature (240 °C), are
probably the main reason for this, we decided to search for mild
reaction conditions for this interesting transformation.
Consequently, we found that the reaction could be promoted by
the addition of molecular iodine,8 and report herein the details of
our findings.
S
S
S
S
S
S
S
S
2
1
3
4
Fig. 1. Structures of thienothiophenes (TTs) 1–4.
Scheme 1. Our previous work: synthesis of 1,1-diarylethylenes 6 from 5
using RCEM.
In the course of our studies on aromatic ring construction, we
developed new approach for the synthesis of 1,1-
a
diarylethylenes 6 from 5, which involves ruthenium-catalyzed
ring-closing enyne metathesis (RCEM) (Scheme 1).2 Thereafter,
we tried to devise ways to utilize products 6 as building blocks
for attractive compounds. Literature search revealed
transformation of 1,1-diphenylethylene 6a into
[1]benzothiopheno[2,3-b][1]benzothiophene (BTBT) 7a by
a

2
Tetrahedron
toluene. Then, we chose toluene as solvent and increased the
amount of I2 by twofold. To our delight, desired BTBT 7a was
produced at last (11% yield), along with 8a in 66% yield (entry
8). We next extended the reaction time from 4 h to 24 h or 48 h.
As a result, the yield of 7a increased with time (22% and 49%,
respectively), whereas the yield of 8a decreased (53% and 17%,
respectively) (entries 9 and 10). When we further increased the
amount of I2 from 2 equiv to 4 equiv and carried out the reaction
for 24 h, 7a was formed in the highest yield (52% yield) in this
study (entry 11). It should be mentioned that besides 8a, other
side products were identified in this reaction. For example, under
the optimum conditions, reduced side product 9a and self-
dimerized side product 10a13 were generated in 6% and 3%
yields, respectively. Although we tried to improve the yield of 7a
further from the best result by prolonging the reaction time
(entry 12), increasing the amount of I2 (entries 13 and 14), or
increasing the amount of S8 (entry 15), all these attempts met
with failure. It appeared that large amounts of undesired
polymerization side products were formed under these
conditions. Consequently, we determined that the conditions in
entry 4 are the best for 8a and those in entry 11 are the best for
7a.
Scheme 2. Known reaction: synthesis of [1]benzothiopheno[2,3-
b][1]benzothiophene 7a and 3-phenylbenzo[b]thiophene 8a from 6a.
Results and discussion
First, we chose toluene as the reaction solvent because it
reasonably dissolves sulfur,9 not to mention 6a.10 However,
simply stirring the toluene mixture of 6a and S8 (4 equiv) at
refluxing temperature for 4 h did not generate desired product 7a
(entry 1, Table 1). Because it is known that the use of additives
is effective for C-S bond formation,8,11 we next tried to introduce
some additives into the reaction. As a result, whereas metal
complexes, such as CuI and AlCl3 were ineffective (entries 2 and
3), molecular iodine (1 equiv) worked, giving 3-
phenylbenzo[b]thiophene 8a in high yield, which is naturally
considered to be the intermediate of BTBT 7a (entry 4).12
Encouraged by the result, we next investigated the preferred
solvent for the reaction (entry 4 vs. entries 5–7). Although some
solvents also afforded 8a at refluxing temperature in the
presence of I2, the yields of 8a were lower than that obtained in
Table 1. Optimization of reaction conditions.a
entry
1
S8 (equiv)
additive (equiv)
none
solvent
toluene
toluene
toluene
toluene
THF
time (h)
yield of 7a (%)b
yield of 8a (%)b
4
4
4
4
4
4
4
4
4
4
4
4
4
4
8
4
0
0
2
CuI (1)
AlCl3 (1)
I2 (1)
4
0
0
3
4
0
0
4c
5
4
0
82
0
I2 (1)
4
0
6
I2 (1)
CHCl3
DMF
4
0
37
40
66
53
17
36
0
7
I2 (1)
4
0
8
I2 (2)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
4
11
22
49
52
22
35
33
41
9
I2 (2)
24
48
24
48
24
24
24
10
11d
12
13
14
15
I2 (2)
I2 (4)
I2 (4)
I2 (5)
0
I2 (6)
0
I2 (4)
0
a The reaction was carried out with 6a, S8 (4 or 8 equiv), and additive (1–6 equiv) in solvent at refluxing temperature for 4–48 h under nitrogen. b The yield was
determined by 1H NMR analysis of the crude mixture using 1,4-bis(trimethylsilyl)benzene as the internal standard. c 9a (13% yield) was formed as the side
product. d 9a (6% yield) and 10a (3% yield) were formed as the side products.

3
5
6c
6d
6e
6f
4-tBu
4-MeO
4-F
A
B
A
B
A
B
A
B
A
B
A
B
3
70
0
We named the two conditions A (entry 4, Table 1) and B
(entry 11, Table 1), and applied those conditions to the synthesis
of the derivatives of 7 and 8 (Table 2). In order to facilitate
comparison of results, the optimum conditions in Table 1 are
shown again in Table 2 (entries 1 and 2). When substrate 6b
having methyl groups was allowed to react under conditions A,
8b in 35% yield and 7b in 6% yield were obtained (entry 3). On
the other hand, the reaction of 6b under conditions B gave 7b in
28% yield (entry 4). In this case, no detectable amount of 8b was
obtained and instead, a large quantity of polymers, the formation
6
24
9
7
20
0
8
17
0
9
58
33
0
10
11
12
13
14
15
16
38
0
1
of which was presumed from the broadening of signals in H
4-CF3
2-Me
3,5-Me2
NMR spectrum, were produced (entry 4). It could be assumed
that the presence of electron-donating methyl groups accelerated
not only the C-S bond formation but also undesirable
intermolecular reactions. To support this, similar results were
obtained from the reaction of 6c having tert-butyl groups under
both conditions A and B (entries 5 and 6). The introduction of
methoxy groups worsened the situation and much more
significant signal broadening was observed with small signals of
7d and 8d in the crude 1H NMR spectra (entries 7 and 8). On the
contrary, the introduction of electron-withdrawing fluoro
substituents on the aromatic rings decreased the reaction rate.
When 6e was reacted under conditions A (entry 9), no 7e and 8e
in 58% yield were obtained with recovered substrate (20% yield).
The reaction of 6e under conditions B also proceeded slowly, but
7e in 38% yield and 8e in 33% yield were obtained together with
a relatively clean crude 1H NMR spectrum (entry10). The
introduction of more electron-withdrawing trifluoromethyl
groups decreased the reaction rate further. Neither 7f nor 8f was
obtained under conditions A with recovered substrate (98%
yield) (entry 11). Even in conditions B, 8f was obtained only in
29% yield with recovered substrate (45% yield) (entry 12). When
substrate 6g having ortho-methyl groups was reacted with
conditions A, 8g was obtained in 67% yield. In this case, 7g was
not observed at all (entry 13). It is obvious that severe steric
repulsion of two methyl groups prevented the formation of 7g.
Again, a large quantity of polymers was produced, when the
reaction of 6g was carried out under conditions B (entry 14).
Finally, substrate 6h having four meta-methyl groups was
allowed to react under conditions A and B. However, only a
small amount of desired products 7h and 8h was obtained with a
large quantity of polymers (entries 15 and 16).
0
29
67
<1
0
6g
6h
0
0
2
2
9
a The reaction was carried out with 6, S8 (4 equiv), and I2 (1 or 4 equiv) in
toluene at refluxing temperature for 4 or 24 h under nitrogen. b The yield was
determined by 1H NMR analysis of the crude mixture using 1,4-
bis(trimethylsilyl)benzene as the internal standard.
The result of X-ray diffraction analysis of a crystal of 7b
having methyl groups is shown in Figure 2.14 It is evident that the
compound has an extremely planar structure.
Table 2. Iodine-mediated sulfuration reaction of 1,1-
diarylethylenes 6. a
Fig. 2. Crystal structure of 7b. Selected bond lengths (Å) and angles
(deg): C1–S1 1.755(3), S1–C8 1.724(3), C8–C9 1.367(4), C9–C2 1.444(3),
C2–C1 1.402(3), C1–S1–C8 89.7(1), S1–C8–C9 115.1(2), C8–C9–C2
111.4(2), C9–C2–C1 111.3(2), C2–C1–S1 112.5(2).
entry
substrate
R
H
conditions
yield of 7 yield of 8
The BTBTs 7 mentioned earlier have cross-conjugated
systems with core structure 1. Therefore, in the field of OFETs,
much attention is being directed toward [1]benzothiopheno[3,2-
b][1]benzothiophenes 12 with core structure 2, which provide a
small HOMO-LUMO band gap.15 We were naturally interested in
the possibility of applying our new reaction conditions using I2 to
the synthesis of BTBT 12 (Table 3).16 Whereas the employment
of diphenylacetylene 11 as substrate under conditions B resulted
in a tragic failure (entry 1), harsher conditions in which larger
amounts of I2 (9 equiv) and S8 (24 equiv) were used afforded
(%)b
(%)b
82
36
35
0
1
2
3
4
6a
A
B
A
B
0
52
6
6b
4-Me
28

4
Tetrahedron
desired compound 12 in 9% yield (entry 2). In this case, the use
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tetlet.xxxx
of dimethyl carbonate instead of toluene as solvent gave a better
result in terms of the yield of 12 (22% yield) (entry 5).
References
1.
(a) M. E. Cinar, T. Ozturk, Chem. Rev. 115 (2015), 3036-3140. (b)
L. Li, C. Zhao, H. Wang, Chem. Rec. 16 (2016), 797-809. (c) X.
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Table 3. Iodine-Mediated Sulfuration Reaction of
Diphenylacetylene 11.a
2.
(a) K. Yoshida, Y. Shishikura, H. Takahashi, T. Imamoto, Org.
Lett. 10 (2008), 2777-2780. (b) H. Takahashi, K. Yoshida, A.
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K. Yoshida, A. Yanagisawa, J. Org. Chem. 78 (2013), 3464-3469.
(d) K. Yoshida, K. Nishii, Y. Kano, S. Wada, A. Yanagisawa, J.
Org. Chem. 79 (2014), 4231-4239.
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For recent examples of reaction using elemental sulfur, see (a) M.
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419, and references cited therein.
entry
S8
(equiv)
I2
solvent
time
(h)
yield
yield
4.
5.
(equiv)
of 12 of 13
(%)b
(%)b
(a) M. Kienle, A. Unsinn, P. Knochel, Angew. Chem., Int. Ed. 49
(2010), 4751-4754. (b) V. G. Nenajdenko, E. S. Balenkova, K. Y.
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1462. (c) Y. Ogawa, E. Takiguchi, M. Mamada, D. Kumaki, S.
Tokito, H. Katagiri, Tetrahedron Lett. 58 (2017), 963-967.
For recent reviews on C–S bond formation, see (a) H. Liu, X. Jiang,
Chem. Asian J. 8 (2013), 2546-2563. (b) C. Shen, P. Zhang, Q.
Sun, S. Bai, T. S. A. Hor, X. Liu, Chem. Soc. Rev. 44 (2015), 291-
314. (c) T. B. Nguyen, Adv. Synth. Catal. 359 (2017), 1066-1130.
For recent examples of C–S bond formation, see (a) C. Xia, Z.
Wei, Y. Yang, W. Yu, H. Liao, C. Shen, P. Zhang, Chem. Asian J.
11 (2016), 360-366. (b) Y. Yang, W. Li, C. Xia, B. Ying, C. Shen,
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Huang, W. Wu, W. Yu, J. Li, Z. Zhu, H. Jiang, Org. Biomol. Chem.
17 (2019), 3424-3432.
1
4
9
9
9
9
4
toluene
toluene
DMF
24
15
15
15
15
0
0
2
24
24
24
24
9
13
0
6.
7.
3c
4c
5
0
DMSO
0
0
dimethyl
carbonate
22
0
a The reaction was carried out with 11, S8 (4 or 9 equiv), and I2 (4 or 24
equiv) in solvent at refluxing temperature for 15 or 24 h under nitrogen. b The
yield was determined by 1H NMR analysis of the crude mixture using 1,4-
bis(trimethylsilyl)benzene as the internal standard. c Benzil (21% yield (entry
3), 27% yield (entry 4)) was obtained with recovered 11.
8.
9.
(a) E. Knoevenagel, J. Prakt. Chem. 289 (1914), 11-12. (b) D.
Villemin, X. Vlieghe, Sulfur Lett. 21 (1998), 191-198, and
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Y. Ren, H. Shui, C. Peng, H. Liu, Y. Hu, Fluid Phase Equilib. 312
(2011), 31-36.
10. In this preliminary study, only readily available 1,1-diarylethylenes
6 which were prepared by classical methods were used, see (a) M.
N. Alberti, M. Orfanopoulos, Org. Lett. 11 (2008), 2465-2468. (b)
F. Gao, X.-J. Deng, Y. Tang, J.-P. Tang, J. Yang, Y.-M. Zhang,
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8276-8279.
12. When N-iodosuccinimide (NIS) (1 equiv) was used instead of I2, 8a
was generated in 65% yield. In this case, recovered substrate 6a
(4% yield) and 9a (2% yield) were also observed.
13. (a) A. G. Evans, E. D. Owen, J. Chem. Soc. (1959), 4123-4125. (b)
R. R. Thomas, V. Chebolu, A. Sen, J. Am. Chem. Soc. 108 (1986),
4096-4103.
Conclusion
In conclusion, we have investigated the sulfuration reaction of
1,1-diarylethylenes 6 for the synthesis of BTBTs 7, which were
reported more than half a century ago. Although the original
reaction was carried out in the absence of solvent and at a high
temperature (240 °C), we were able to improve the reaction
conditions (in refluxing toluene) by adding I2. Modification of
the new conditions using I2 enabled not only the selective
formation of BTBTs 7 and their intermediates 8, but also the
formation of other important BTBTs 12. Although there is still
room for improving yields, we believe that this multi C-S bond
formation shows great promise because valuable compounds are
generated at once from easily obtainable materials.
14. CCDC 1956668.
15. (a) K. Takimiya, H. Ebata, K. Sakamoto, T. Izawa, T. Otsubo, Y.
Kunugi, J. Am. Chem. Soc. 128 (2006), 12604-12605. (b) T.
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2225. (c) H. Ebata, T. Izawa, E. Miyazaki, K. Takimiya, M. Ikeda,
H. Kuwabara, T. Yui, J. Am. Chem. Soc. 129 (2007), 15732-15733.
(d) K. Takimiya, I. Osaka, T. Mori, M. Nakano, Acc. Chem. Res. 47
(2014), 1493-1502.
16. (a) H. Sashida, S. Yasuike, J. Heterocycl. Chem. 35 (1998), 725-
726. (b) L. Meng, T. Fujikawa, M. Kuwayama, Y. Segawa, K.
Itami, J. Am. Chem. Soc. 138 (2016), 10351-10355. (c) T.
Kitamura, K. Morita, H. Nakamori, J. Oyamada, J. Org. Chem. 84
(2019), 4191-4199.
Acknowledgments
This work was supported by Grant-in-Aid for Scientific
Research (C) from JSPS to K.Y. (Grant #18K05097) and Grant-
in-Aid for Scientific Research on Innovative Areas "Precisely
Designed Catalysts with Customized Scaffolding" from MEXT
to K.Y. (Grant #18H04236).
Appendix A. Supplementary data
2) The addition of molecular iodine accelerates the
formation of BTBTs.
3) 3-Arylbenzo[b]thiophenes are also prepared by
changing reaction conditions.
Highlights
1) BTBTs are generated at once by the Quadruple C-S
bond formation.

5