Construction of 2,3-disubstituted benzo[: B] thieno[2,3- d] thiophenes and benzo[4,5]selenopheno[3,2- b] thiophenes using the Fiesselmann thiophene synthesis

Article abstract of DOI:10.1039/d0ob00300j

A series of 3-(hetero)aryl-substituted benzo[b]thieno[2,3-d]thiophenes, bearing various electron withdrawing groups at C-2 position of their scaffolds, were obtained using a convenient approach based on the Fiesselmann thiophene synthesis. To realize this strategy, the Friedel-Crafts acylation of (hetero)arenes with easily accessible 3-chlorobenzo[b]thiophene-2-carbonyl chlorides was initially performed to afford 3-chloro-2-(hetero)aroylbenzo[b]thiophenes. The latter ketones were treated either with methyl thioglycolate in the presence of DBU and calcium oxide powder or successively with sodium sulfide, an alkylating agent, containing methylene active component, and also DBU and calcium oxide, to form the desired benzo[b]thieno[2,3-d]thiophene derivatives. In addition, similar benzo[4,5]selenopheno[3,2-b]thiophene derivatives were prepared in the same manner using 3-bromobenzo[b]selenophen-2-yl substrates. The obtained functional derivatives of both benzo[b]thieno[2,3-d]thiophene and benzo[4,5]selenopheno[3,2-b]thiophene are of interest for further elaboration of organic semiconductor materials.

Full text of DOI:10.1039/d0ob00300j

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Construction of 2,3-disubstituted benzo[b]thieno
[2,3-d]thiophenes and benzo[4,5]selenopheno
[3,2-b]thiophenes using the Fiesselmann
thiophene synthesis†
Cite this: DOI: 10.1039/d0ob00300j
Roman A. Irgashev,
*
a,b Nadezhda S. Demina a,b and Gennady L. Rusinova,b
A series of 3-(hetero)aryl-substituted benzo[b]thieno[2,3-d]thiophenes, bearing various electron with-
drawing groups at C-2 position of their scaffolds, were obtained using a convenient approach based on
the Fiesselmann thiophene synthesis. To realize this strategy, the Friedel–Crafts acylation of (hetero)
arenes with easily accessible 3-chlorobenzo[b]thiophene-2-carbonyl chlorides was initially performed to
afford 3-chloro-2-(hetero)aroylbenzo[b]thiophenes. The latter ketones were treated either with methyl
thioglycolate in the presence of DBU and calcium oxide powder or successively with sodium sulfide, an
alkylating agent, containing methylene active component, and also DBU and calcium oxide, to form the
desired benzo[b]thieno[2,3-d]thiophene derivatives. In addition, similar benzo[4,5]selenopheno[3,2-b]
thiophene derivatives were prepared in the same manner using 3-bromobenzo[b]selenophen-2-yl sub-
strates. The obtained functional derivatives of both benzo[b]thieno[2,3-d]thiophene and benzo[4,5]sele-
nopheno[3,2-b]thiophene are of interest for further elaboration of organic semiconductor materials.
Received 10th February 2020,
Accepted 2nd April 2020
DOI: 10.1039/d0ob00300j
rsc.li/obc
polymers,24,25 liquid crystals26 and photochromic materials.27
Few protocols of preparing the simple benzo[b]thieno[2,3-d]
Introduction
Over the past two decades, π-conjugated thiophene-based com- thiophene have been reported in the literature, including reac-
pounds with linear as well as ring-fused structures have tion of 1-(3-bromobenzo[b]thiophen-2-yl)-2-trimethyl-
received significant attention from researchers owing to the silylacetylene with sodium sulfide,20 Cu- or Fe-catalyzed reac-
prospect of their application for organic electronics area.1–5 In tion of benzo[b]thieno[2,3-d]iodolium triflate with sulfur
this context, a large number of photo- and electroactive sources,28,29 Pd-catalyzed C–S cyclization of 2-(2-acetylthiophe-
materials based on thienothiophenes and more π-extended nyl)thiohene30 or 2,2′-di(thiophen-2-yl)diphenyldisulfide.31 At
thieno-fused molecules have been synthesized, studied and uti- the same time, BTT scaffolds can be readily formed by the
lized for the manufacture of various thin-film electronic and Fiesselmann thiophene synthesis, which consists in reaction
optoelectronic devices.6–9 Among them, benzo[b]thieno[2,3-d] of thioglycolic acid derivatives or mercaptomethyl ketones
thiophene (BTT) framework, also named benzothieno[3,2-b] with appropriate 1,3-C,C-dielectrophiles,32 and is widely used
thiophene or thieno[3,2-b][1]benzothiophene, has been used for the construction of functional thiophenes.33–35 With regard
in the production of dyes for dye-sensitized solar cells,10–14 to BTTs synthesis, 3-unsubstituted and 3-hydroxy-substituted
π-conjugated donor–acceptor polymers for bulk heterojunction benzo[b]thieno[2,3-d]thiophene-2-carboxylates 3 and 4 have
solar cells,15–17 p-type semiconductors for organic field-effect been prepared from benzo[b]thiophene substrates 1 21,24 or
transistors18–22 as well as fluorescent materials,23 electroactive 2,23,36,37 respectively (Scheme 1). However, the scope of the
aPostovsky Institute of Organic Synthesis, Ural Division, Russian Academy of
Sciences, S. Kovalevskoy Str., 22, Ekaterinburg, 620990, Russia.
E-mail: irgashev@ios.uran.ru; Fax: +7 343 369 30 58
bUral Federal University named after the First President of Russia B. N. Yeltsin, Mira
Str., 19, Ekaterinburg, 620002, Russia
†Electronic supplementary information (ESI) available: Experimental pro-
cedures, copies of 1H, 19F and 13C NMR spectra of new compounds. CCDC
1981665, 1981666 and 1981668. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/d0ob00300j
Scheme 1 Construction of BTT compounds using the Fiesselmann
reaction.
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according to previously described procedure.38 Compounds
6a–m were obtained in 28–87% yields, wherein moderate
yields were observed for 6g (28%) and 6h (38%), bearing thien-
2-yl and 5-methylthien-2-yl part, respectively, due to the signifi-
cant degradation of thiophene and 2-methylthiophene during
their reaction with acyl chloride 5a. At the same time, our
attempts to use milder Lewis acids such as SnCl4 or TiCl4
instead of AlCl3 failed.
It should be noted, that an alternative synthesis of such
type ketones, consisting in the treatment of 3-chloro-6-methox-
ybenzo[b]thiophene-2-carbonyl chloride (5b) or the corres-
ponding Weinreb amide39 with (hetero)arylmagnesium bro-
mides in dry THF, has recently been reported.40 This method
can also be utilized for the preparation of compounds 6 in
some cases.
Next, we focused on determining optimal reaction con-
ditions for the conversion of compounds 6 to BTT derivatives
using the Fiesselmann method. To this end, we studied the
reaction of 6 with methyl thioglycolate. Thus, the treatment of
substrate 6a with methyl thioglycolate (1.3 equiv.) and DBU (2
equiv.) in THF–MeOH (10 : 1, v/v) under an argon atmosphere
at room temperature gave a mixture of the desired ester 7a and
the corresponding carboxylic acid, which formed due to the
partial saponification of 7a. At the same time, our attempts to
use NaH or NaOMe in THF or DMF solution were fruitless,
since the fast degradation of raw materials occurred, complex
mixture of compounds forming. To improve the result, we
redid the experiment with DBU adding CaO powder (5 equiv.)
to bind water released during reaction process. With this
change, the desired product 7a was obtained in 91% yield.
Furthermore, since the basic nature of CaO caused the regen-
eration of DBU freebase from its hydrochloride, we managed
to reduce the amount of DBU to 50 mol% without decrease in
yield of ester 7a (Table 1). Other BTT derivatives 7b–m were
Fig. 1 Substructure of compounds, obtained in this study.
Fiesselmann reaction application for the construction of 2,3-
disubstituted BTT molecules has not been fully disclosed yet.
Herein, we report synthetic strategy for the preparation of 3-
(hetero)aryl-substituted BTTs, bearing electron withdrawing
groups (EWG), such as carbomethoxy, cyano or acyl at C-2 posi-
tions, based on the Fiesselmann reaction. In addition, we have
also used this approach to obtain some similar benzo[4,5]sele-
nopheno[3,2-b]thiophene (BST) derivatives (Fig. 1). Both types
of these 2,3-disubstituted BTTs and BSTs have not been pre-
viously described in principle to the best of our knowledge.
Results and discussion
To perform the construction of the above mentioned BTT
molecules in accordance with our synthetic strategy, we
selected
2-(hetero)aroyl-substituted
3-chlorobenzo[b]thio-
phenes 6 as appropriate 1,3-C,C-dielectrophilic substrates
required for the Fiesselmann reaction. Thus, ketones 6a–i were
synthesized by the Friedel–Crafts acylation of various aro-
matic compounds as well as thiophenes with 3-chlorobenzo[b]
thiophene-2-carbonyl chloride 5a in the presence of AlCl3 in
dry CH2Cl2, and ketones 6j–m were similarly obtained by the
acylation of veratrole with acyl chlorides 5b–e (Scheme 2) in
28–87% yields. In turn, acyl chlorides 5 were readily obtained
by treatment of the corresponding cinnamic acids with excess
of thionyl chloride in the presence of DMF and pyridine
Scheme 2 Synthesis of BTT derivatives 7, substrate scope and yields. HSCH2CO2Me (1.3 equiv.), DBU (50 mol%) and CaO (5 equiv.) were used.
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Table 1 Reaction conditions for the synthesis of BTT 7a
and 2-acetyl BTTs from substrate 6i, bearing 5-bromothien-2-yl
unit, while carbonitrile 8d was obtained only in moderate yield
because of significant degradation of 6i during its initial reac-
tion with sodium sulfide in DMF solution.
Entrya
DBU (equiv.)
CaO (equiv.)
Yield of 7a (%)
1
2
3
2.0
2.0
0.5
—
5.0
5.0
79b
91
91
The structure of BTTs 7–11 was confirmed by the data of 1H
and 13C NMR spectroscopy, and HRMS. In addition, the mole-
a The experiments were performed with HSCH2CO2Me (1.3 equiv.) in cular structure of compounds 9b and 11 was proved unequivo-
THF–MeOH (10 : 1, v/v) at rt for 15 h. b Ester 7a was obtained in a
cally by XRD analysis (see ESI† for additional information).41
mixture with the corresponding carboxylic acid.
The synthesis of 2-formyl-substituted BTT derivatives 12
was also elaborated during this study. Initially, we tried to
prepare these compounds by treatment of substrates 5 with
either 2,5-dihydroxy-1,4-dithiane (dimer of 2-mercaptoacetal-
dehyde and its synthetic equivalent) or sodium sulfide and
2-chloroacethaldehyde using the described above reaction con-
ditions, but these attempts failed. In this respect, we per-
formed the preparation of compounds 12 by transformation of
carbomethoxy group in derivatives 7. To this end, esters 7a,b
were reduced with LiAlH4 in THF solution at room tempera-
ture, followed by mild oxidation of the obtained BTT carbinols,
which were isolated by alkali workup of the reaction mixtures
and used without further purification, with MnO2 in CHCl3
solution to give BTT carbaldehydes 12a,b in 45% and 42%
overall yields (Scheme 4).
The present approach was also applied to construct 3-(3,4-
dimethoxyphenyl)-substituted BST molecules. To this end, we
saponified easily accessible ethyl 3-bromobenzo[b]seleno-
phene-2-carboxylate42 to obtain carboxylic acid 13. The latter
acid was treated with excess of thionyl chloride to afford the
corresponding acyl chloride, which was further involved in the
Friedel–Crafts reaction without any purification. Thus, ketone 14
was prepared in 83% yield by acylation of veratrole (1.2 equiv.)
with this intermediate acyl chloride in the presence of AlCl3 (1.3
equiv.). Then, the reaction of substrate 14 with methyl thiogly-
smoothly prepared in the same manner in 51–89% yields
(Scheme 2).
To obtain BTT derivatives with other EWGs at C-2 position,
we realized the Fiesselmann-like reaction, wherein 1,3-C,C-die-
lectrophilic substrate was successively treated with alkali
sulfide and the alkylating agent. For instance, to substitute
chlorine atom at C-3 position of compound 6a, the latter one
was involved in the reaction with sodium sulfide (1.1 equiv.) in
DMF solution under an argon atmosphere at 60 °C for 45 min,
thus giving thiolate anion, which was alkylated with chloroace-
tonitrile (1.1 equiv.) next. The formed intermediate was
cyclized in situ under the reaction conditions similar to the
derivatives 7 formation, except for a larger excess of CaO (15
equiv.), to afford product 8a in 77% yield. Carbonitriles 8b–d
were prepared from substrates 6b,f,i according to this one-pot
procedure in 46–79% yields. In addition, 2-benzoyl- and 2-(4-
fluorobenzoyl)-BTTs 9a–c and 9d as well as 2-acetyl-BTTs 10a–
c were obtained in the same manner using phenacyl and
4-flourophenacyl chlorides or chloroacetone as the alkylating
agents, respectively (Scheme 3). Doubled BTT derivative 11 was
also synthesized from substrate 6a in 71% yield with the use of
1,3-dichloroacetone. To note, we failed to prepare 2-benzoyl
Scheme 3 Synthesis of BTT derivatives 8–11, substrate scope and yields. Na2S·9H2O (1.1 equiv.), ClCH2EWG (1.1 equiv.), DBU (50 mol%) and CaO
(15 equiv.) were used.
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Scheme 4 Synthesis of 2-formyl-substituted BTTs 12.
Scheme 5 Synthesis of BST derivatives 15–18.
colate (1.3 equiv.) in the presence of DBU (50 mol%) and CaO building blocks for the development of π-extended BTT- and
powder (5 equiv.) afforded ester 15 in 63% yield. In turn, BST-based compounds for material applications.
2-cyano-, 2-benzoyl-, 2-(4-fluorobenzoyl)- and 2-acetyl-substi-
tuted BSTs 16, 17a, 17b and 18 were prepared by reaction of
compound 14 with sodium sulfide (1.1 equiv.) to form the
intermediate thiolate anion, which was successively treated
Conflicts of interest
There are no conflicts to declare.
with chloroacetonitrile, phenacyl or 4-fluorophenacyl chloride,
or chloroacetone (1.1 equiv.), respectively, and with DBU
(50 mol%) and CaO (15 equiv.) in DMF solution (Scheme 5).
The molecular structure of BST derivatives 15–18 was addition- Acknowledgements
ally established by XRD analysis, carried out for a single crystal
This study was supported by the Russian Science Foundation,
Grant No. 19-13-00234.
of compound 17a (see ESI† for additional information).43
Conclusion
Notes and references
In summary, we have successfully applied the Fiesselmann
reaction to prepare benzo[b]thieno[2,3-d]thiophene derivatives,
bearing (hetero)aromatic units at C-3 position and EWGs at
C-2 position, from 3-chloro-2-(hetero)aroylbenzo[b]thiophenes.
Furthermore, the construction of the similar benzo[4,5]seleno-
pheno[3,2-b]thiophene molecules in accordance with this syn-
thetic approach has also been demonstrated. In general, being
readily available and conveniently modifiable on (hetero)aro-
matic moieties and functional groups to get enhanced fea-
tures, benzo[b]thieno[2,3-d]thiophenes and benzo[4,5]seleno-
pheno[3,2-b]thiophenes described herein are of interest as
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