One-pot synthesis of benzo[b]thiophenes and benzo[b]selenophenes from o-halo-substituted ethynylbenzenes: convenient approach to mono-, bis-, and tris-chalcogenophene-annulated benzenes

Article abstract of DOI:10.1021/ol900809w

A convenient one-pot procedure for the synthesis of benzo[b]thiophenes and selenophenes from readily available o-halo-ethynylbenzene precursors is described. Regardless of the substituent on the acetylene terminus or the number of cyclization moieties on the precursors, various benzo[b]thiophenes and selenophenes, including not only the parent, alkyl-, and phenyl-substituted derivatives but also benzo[1,2-b:4,5-b']dithiophenes and diselenophenes and benzo[1,2-b:3,4-b':5,6-b'']trithiophenes and triselenophenes can be prepared in good to high yields.

Full text of DOI:10.1021/ol900809w

ORGANIC
LETTERS
2009
Vol. 11, No. 11
2473-2475
One-pot Synthesis of Benzo[b]thiophenes
and Benzo[b]selenophenes from
o-Halo-Substituted Ethynylbenzenes:
Convenient Approach to Mono-, Bis-, and
Tris-Chalcogenophene-Annulated
Benzenes
Tomoya Kashiki,† Shoji Shinamura,† Masahiro Kohara,† Eigo Miyazaki,†
Kazuo Takimiya,*,†,‡ Masaaki Ikeda,§ and Hirokazu Kuwabara§
Department of Applied Chemistry, Graduate School of Engineering, Hiroshima
UniVersity, Higashi-Hiroshima 739-8527, Japan, Institute for AdVanced Materials
Research, Hiroshima UniVersity, Higashi-Hiroshima 739-8530, Japan, and Functional
Chemicals R&D Laboratories, Nippon Kayaku Co. Ltd., Shimo,
Kita-ku, Tokyo 115-8588, Japan
ktakimi@hiroshima-u.ac.jp
Received April 13, 2009
ABSTRACT
A convenient one-pot procedure for the synthesis of benzo[b]thiophenes and selenophenes from readily available o-halo-ethynylbenzene precursors
is described. Regardless of the substituent on the acetylene terminus or the number of cyclization moieties on the precursors, various benzo[b]thiophenes
and selenophenes, including not only the parent, alkyl-, and phenyl-substituted derivatives but also benzo[1,2-b:4,5-b′]dithiophenes and diselenophenes
and benzo[1,2-b:3,4-b′:5,6-b′′]trithiophenes and triselenophenes can be prepared in good to high yields.
Benzo[b]thiophene and its related derivatives represent an
important class of fused-thiophene compounds in the field
of bioactive materials as well as optoelectronic materials.1
In particular, multithiophene fused-aromatic compounds are
attracting current interest as promising electronic materials
for organic conductors,2 organic light-emitting diodes,3
photovoltaic cells,4 and field-effect transistors.5
For the further development of new materials based on
benzo[b]thiophenes, it is of primary importance to devise
effective synthetic methods. To this end, much work has been
done to develop new and convenient synthetic approaches
† Department of Applied Chemistry, Graduate School of Engineering,
Hiroshima University.
‡ Institute for Advanced Materials Research, Hiroshima University.
§ Functional Chemicals Research Laboratories, Nippon Kayaku Co. Ltd.
(1) (a) Zhang, T. Y.; O’Toole, J.; Proctor, C. S. J. Sulfur Chem. 1999,
22, 1–47. (b) Engel, E.; Oepen, G. In Methoden der Organischen Chemie
(Houben-Weyl); Kreher, R. P., Ed.; Georg Thieme Verlag: Stuttgart, NY,
1994; Vol. E6b, pp 217-274.
(2) (a) Wudl, F.; Haddon, R. C.; Zellers, E. T.; Bramwell, F. B. J. Org.
Chem. 1979, 44, 2491–2493. (b) Takimiya, K.; Yashiki, F.; Aso, Y.; Otsubo,
T.; Ogura, F. Chem. Lett. 1993, 365–367. (c) Takimiya, K.; Otsubo, T.;
Ogura, F. J. Chem. Soc., Chem. Commun. 1994, 1859–1860. (d) Takimiya,
K.; Kato, K.; Aso, Y.; Ogura, F.; Otsubo, T. Bull. Chem. Soc. Jpn. 2002,
75, 1795–1805.
10.1021/ol900809w CCC: $40.75
Published on Web 05/11/2009
 2009 American Chemical Society

to benzo[b]thiophenes. In particular, the use of phenylacety-
lene-based precursors in cyclization reactions affording fused-
thiophene or selenophene moieties has emerged: Sashida et
al. reported that o-alkynylbromobenzenes react with elemen-
tal chalcogene (sulfur, selenium, or tellurium) upon lithium-
halogen exchange to afford benzo[b]chalcogenophenes in
good yields.6 On the other hand, Larock and co-workers
employed o-alkynyl-thioanisole or -selenoanisole in the
electrophilic cyclization reaction to give benzo[b]-thiophenes
and -selenophenes, respectively, where o-methylthio or
methylseleno groups are an excellent chalcogen source.7 The
superiority of these new methods was proved by the high
yields of the desired products, the tolerance for various
substituents, and successful applications to 2-fold cyclization
reactions to give benzo[1,2-b:4,5-b′]dithiophenes and benzo-
[1,2-b:5,4-b′]diselenophenes.8
nucleophiles can be accelerated by use of polar aprotic
solvents and/or by elevating the reaction temperature.11 We
thus examined a similar cyclization reaction using Na2S as
reagent and 1-bromo-2-trimethylsilylethynylbenzenes as
substrates in N-methyl-2-pyrrolidone (NMP) at 180 °C
(Scheme 1). After usual workup, unsubstituted benzo[b-
Scheme 1
.
Reaction of 1-Bromo-2-trimethylsilylethynylbenzene
with Na2S
During the course of our synthetic studies on heteroaro-
matic compounds for use as electronic materials,9 we have
pursued efficient methods to introduce sulfur functional
groups to aromatic rings and have focused on inorganic sulfur
sources, such as sodium sulfide (Na2S), in the aromatic
nucleophilic substitution (SNAr) reaction. To our knowledge,
very limited examples of the syntheses of benzo[b]thiophenes
using such inorganic reagents have been reported: Shvarts-
berg and co-workers reported the thiophene-annulation
reaction of 2-alkynyl-1-chloro- and 1-alkynyl-2-chloroan-
thraquinones with Na2S to yield anthra[1,2-b]thiophene-6,11-
diones and anthra[2,1-b]thiophene-6,11-diones, respec-
tively.10 In the reactions, electron-withdrawing anthraquinone
moieties in the substrates activate the initial substitution
reaction of Na2S with the substrate.
]thiophene was obtained in 70% isolated yield as the major
product. This indicates that Na2S acts as a nucleophile to
nonactivated bromobenzenes and the resulting phenylthiolate
intermediate attacks the adjacent acetylene moiety to form
the thiophene ring. Although the trimethylsilyl (TMS) group
was displaced during the reaction, probably due to the high
basicity of the reagent, we recognized that this one-pot
procedure for the synthesis of benzo[b]thiophene is very
useful because various kinds of precursors, not only o-
alkynylbromobenzenes with different substituents at the
acetylene terminus but also the potential precursors for
benzo[1,2-b:4,5-b′]dithiophenes (BDTs) and benzo[1,2-b:3,4-
b′:5,6-b′′]trithiophenes (BTTs), are easily available.
We thus carried out the reactions of n-hexyl- and phenyl-
substituted o-ethynylbromobenzenes under the same reaction
conditions (Table 1). As expected, corresponding 2-n-hexyl-
For nonactivated substrates without strong electron-
withdrawing groups, the SNAr reactions of sulfur-based
(3) (a) Mazzeo, M.; Vitale, V.; Sala, F. D.; Pisignano, D.; Anni, M.;
Barbarella, G.; Favaretto, L.; Zanelli, A.; Cingolani, R.; Gigli, G. AdV. Mater.
2003, 15, 2060–2063. (b) Huang, T.-H.; Lin, J. T.; Chen, L. Y.; Lin, Y. T.;
Wu, C. C. AdV. Mater. 2006, 18, 602–606.
Table 1. Synthesis of Benzo[b]thiophenes,
benzo[1,2-b:4,5-b′]dithiophenes, and
Benzo[1,2-b:3,4-b′:5,6-b′′]trithiophenes
(4) Bettignies, R. d.; Nicolas, Y.; Blanchard, P.; Levillain, E.; Nunzi,
J. M.; Roncali, J. AdV. Mater. 2003, 15, 1939–1943.
(5) (a) Laquindanum, G. L.; Katz, H. E.; Lovinger, A. J.; Dodabalapur,
A. AdV. Mater. 1997, 9, 36–39. (b) Sirringhaus, H.; Friend, R. H.; Wang,
C.; Leuningerb, J.; Mu¨llen, K. J. Mater. Chem. 1999, 9, 2095–2101. (c)
Laquindanum, J. G.; Katz, H. E.; Lovinger, A. J. J. Am. Chem. Soc. 1998,
120, 664–672. (d) Takimiya, K.; Kunugi, Y.; Konda, Y.; Niihara, N.; Otsubo,
T. J. Am. Chem. Soc. 2004, 126, 5084–5085. (e) Takimiya, K.; Kunugi,
Y.; Toyoshima, Y.; Otsubo, T. J. Am. Chem. Soc. 2005, 127, 3605–3612.
(f) Payne, M. M.; Parkin, S. R.; Anthony, J. E.; Kuo, C. C.; Jackson, T. N.
J. Am. Chem. Soc. 2005, 127, 4986–4987. (g) Ebata, H.; Miyazaki, E.;
Yamamoto, T.; Takimiya, K. Org. Lett. 2007, 9, 4499–4502. (h) Ebata, H.;
Izawa, T.; Miyazaki, E.; Takimiya, K.; Ikeda, M.; Kuwabara, H.; Yui, T.
J. Am. Chem. Soc. 2007, 129, 15732–15733. (i) Takimiya, K.; Ebata, H.;
Sakamoto, K.; Izawa, T.; Otsubo, T.; Kunugi, Y. J. Am. Chem. Soc. 2006,
128, 12604–12605. (j) Yamamoto, T.; Takimiya, K. J. Am. Chem. Soc.
2007, 129, 2224–2225. (k) Gao, J.; Li, R.; Li, L.; Meng, Q.; Jiang, H.; Li,
H.; Hu, W. AdV. Mater. 2007, 19, 3008–3011.
(6) Sashida, H.; Sadamori, K.; Tsuchiya, T. Synth. Commun. 1998, 28,
713–727.
a Isolated yields after purification by column chromatography and/or
recrystallization. b Trimethylsilyl group(s) were removed during the reaction
to give the parent benzo[b]thiophenes. Purified by vacuum gradient
sublimation.
(7) (a) Yue, D.; Larock, R. C. J. Org. Chem. 2002, 67, 1905–1909. (b)
Yue, D.; Yao, T.; Larock, R. C. J. Org. Chem. 2005, 70, 10292–10296.
(8) (a) Takimiya, K.; Konda, Y.; Ebata, H.; Niihara, N.; Otsubo, T. J.
Org. Chem. 2005, 70, 10569–10571. (b) Wang, C.-H.; Hu, R.-R.; Liang,
S.; Chen, J.-H.; Yang, Z.; Pei, J. Tetrahedron Lett. 2005, 46, 8153–8157.
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583.
and 2-phenyl-benzo[b]thiophenes were isolated in high
yields. Similarly, 2-fold cyclization using 1,4-dibromo-2,5-
bis(alkenyl)benzenes was examined. Dihexyl- and diphenyl-
(10) Ivanchikova, I. D.; Lebedeva, N. I.; Shvartsberg, M. S. Synthesis
2004, 2131–2134.
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Org. Lett., Vol. 11, No. 11, 2009

substituted precursors gave the corresponding disubstituted
BDTs in reasonable yields, whereas the TMS-substituted one
gave the parent BDT in 88% isolated yield (Table 1). For
the synthesis of BTTs, 1,3,5-trichloro-2,4,6-tris(alkenyl)ben-
zenes12 instead of the corresponding tribromobenzene were
used because of the ready availability of the former. Even
with the trichloride precursors, the reactions proceeded
smoothly to give corresponding BTTs; i.e., the parent,
trihexyl-, and triphenyl-BTTs were obtained in reasonable
isolated yields (Table 1).
Table 2. Synthesis of Benzo[b]selenophenes,
Benzo[1,2-b:4,5-b′]diselenophenes, and
Benzo[1,2-b:3,4-b′:5,6-b′′]triselenophenes
Three-fold cyclization on the benzene ring to afford BTTs
has not been attainable so far even with the recently
developed benzo[b]thiophene syntheses6,7 due to the lack of
suitable precursors and/or the difficulty of generating syn-
thetic intermediates. Therefore, BTTs were prepared by a
multistep synthesis using expensive starting materials and
tedious reactions including the oxidative photoinduced cy-
clization reaction.13 The present direct synthesis of BTTs
from easily available precursors will pave the way to the
chemistry of these intriguing heteroarenes with C3h sym-
metry.4,13,14
a Isolated yields after purification by column chromatography and/or
recrystallization. b Trimethylsilyl group(s) were removed during the reaction
to give the parent benzo[b]thiophenes. c Purified by vacuum gradient
sublimation.
not synthesizable. Using these heteroarene structures, the
development of new optoelectronic materials is now being
actively pursued.
In order to extend the present strategy to the synthesis of
benzo[b]selenophenes, we examined similar reactions of the
o-halo-ethynylbenzene precursors with sodium selenide
reagents that were generated in situ from sodium borohydride
(NaBH4) and selenium powder in ethanol. The results of
thesynthesisofbenzo[b]selenophenes,benzo[1,2-b:4,5-b′]dise-
lenophenes (BDSs), and benzo[1,2-b:3,4-b′:5,6-b′′]trise-
lenophenes (BTSs) are summarized in Table 2. Similar to
the syntheses of benzo[b]thiophenes, selenophene cyclization
on the benzene ring took place smoothly regardless of the
substituent on the acetylene terminus or the number of
cyclization moieties on the precursors to give various
benzo[b]selenophene derivatives in reasonable to good yields.
In particular, the first successful synthesis of BTSs should
be noted.15
Acknowledgment. This work was partially supported by
a Grant-in-Aid for Scientific Research (No. 20350088) from
the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
Supporting Information Available: Experimental details
for the synthesis and characterization of benzo[b]-thiophenes
and -selenophenes; X-ray crystallographic file (CIF). These
materials are available free of charge via the Internet at
http://pubs.acs.org.
OL900809W
In summary, we have successfully established a convenient
one-pot procedure for the synthesis of benzo[b]thiophenes
and benzo[b]selenophenes from o-halo-substituted ethynyl-
benzenes using sodium chalcogenides as reagents. Owing
to the accessibility of the precursors, the easy experimental
operation, and the reasonable yields of the products, the
present method for the synthesis will be beneficial for
developing new materials based on benzo[b]thiophenes and
benzo[b]selenophenes. In particular, the applicability to the
3-fold cyclization on the benzene ring affords straightforward
access to benzo[1,2-b:3,4-b′:5,6-b′′]-trithiophenes and -trise-
lenophenes, which are hitherto very tedious to synthesize or
(11) (a) Cogolli, P.; Maiolo, F.; Testaferri, L.; Tingoli, M.; Tiecco, M.
J. Org. Chem. 1979, 44, 2642–2646. (b) Shaw, J. E J. Org. Chem. 1991,
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2419–2421.
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13, 543–544. (b) Jayasuriya, N.; Kagan, J.; Owens, J. E.; Kornak, E. P.;
Perrine, D. M. J. Org. Chem. 1989, 54, 4203–4205. (c) Nicolas, Y.;
Blanchard, P.; Levillain, E.; Allain, M.; Mercier, N.; Roncali, J. Org. Lett.
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2060.
(15) All new compounds were characterized by spectroscopic and
combustion analyses. The structure of the parent benzo[1,2-b:3,4-b′:5,6-
b′′]triselenophene was also confirmed by X-ray structural analysis. See
Supporting Information for details.
Org. Lett., Vol. 11, No. 11, 2009
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