Synthesis of aryl-substituted thieno[3,2-b]thiophene derivatives and their use for N,S-heterotetracene construction

Article abstract of DOI:10.3762/bjoc.15.261

Fiesselmann thiophene synthesis was applied for the convenient construction of thieno[3,2-b]thiophene derivatives. Thus, new 5- or 6-aryl-3-hydroxythieno[3,2-b]thiophene-2-carboxylates were obtained by condensation of 5- or 4-aryl-3-chlorothiophene-2-carb

Full text of DOI:10.3762/bjoc.15.261

Synthesis of aryl-substituted thieno[3,2-b]thiophene
derivatives and their use for N,S-heterotetracene construction
Nadezhda S. Demina1,2, Nikita A. Kazin1,2, Nikolay A. Rasputin1,2,
Roman A. Irgashev*1,2 and Gennady L. Rusinov1,2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 2678–2683.
1Postovsky Institute of Organic Synthesis, Ural Division, Russian
Academy of Sciences, S. Kovalevskoy St., 22, Ekaterinburg, 620990,
Russia and 2Ural Federal University named after the first President of
Russia B. N. Yeltsin, Mira St., 19, Ekaterinburg, 620002, Russia
doi:10.3762/bjoc.15.261
Received: 26 August 2019
Accepted: 31 October 2019
Published: 12 November 2019
Email:
Roman A. Irgashev* - irgashev@ios.uran.ru
Associate Editor: T. J. J. Müller
* Corresponding author
© 2019 Demina et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
Fiesselmann thiophene synthesis; Fischer indole synthesis;
N,S-heteroacene; thieno[3,2-b]thiophene;
thieno[2',3':4,5]thieno[3,2-b]indole
Abstract
Fiesselmann thiophene synthesis was applied for the convenient construction of thieno[3,2-b]thiophene derivatives. Thus, new 5- or
6-aryl-3-hydroxythieno[3,2-b]thiophene-2-carboxylates were obtained by condensation of 5- or 4-aryl-3-chlorothiophene-2-carbox-
ylates, respectively, with methyl thioglycolate in the presence of potassium tert-butoxide. The saponification of the resulting esters,
with decarboxylation of the intermediating acids, gave the corresponding thieno[3,2-b]thiophen-3(2H)-ones. The latter ketones
were used to synthesize new N,S-heterotetracenes, namely 9H-thieno[2',3':4,5]thieno[3,2-b]indoles by their treatment with aryl-
hydrazines in accordance with the Fischer indolization reaction.
Introduction
The thieno[3,2-b]thiophene (TT) unit is highly demanded in ment, the bicyclic TT subunit has been used to architect various
modern organic synthesis since TT-based compounds have a ring-fused S-heteroacenes, which have been studied extensive-
variety of applications, e.g., in the field of organic electronics. ly [8-10] due to their better characteristics compared to hetero-
Indeed, TT-based polymers and small molecules are used as atom-free acenes. For instance, S-heteroacenes have a better ox-
light-harvesting dyes for dye-sensitized solar cells [1], electron- idation stability due to lower-lying HOMO levels, as well as
donating materials for bulk heterojunction solar cells [2-4], and more efficient charge transfer because of their tendency to
p-type semiconductors for organic field-effect transistors [5-7]. π-stack, with non-bonded sulfur–sulfur interactions in the solid
Within the same context of organic semiconductor develop- state, which results in large intermolecular orbital coupling of
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HOMOs and, as a consequence, enhanced carrier transport ported procedures. For example, our attempt to diazotizate
properties [10]. However, there is a problem of poor solubility methyl 3-amino-5-phenylthiophene-2-carboxylate (1a) with so-
of a number of S-heteroacenes, which can limit the effective- dium nitrite in aqueous HCl or HBr solution failed due to the
ness of semiconducting films in the case of solution-process- poor solubility of its hydrohalide salts, while when 3-amino
able electronics [11]. Introducing the NH-containing moieties, ester 1a was treated with tert-butyl nitrite and CuBr2 in aceto-
e.g., pyrrole rings, followed by attaching solubilizing substitu- nitrile solution, we observed only significant decomposition of
ents is one of the ways to solve this problem. Thus, different starting compound.
types of N,S-heteroacenes, including ones with TT-scaffold
(Figure 1), which have promising electronic features, have been In this respect, we elaborated our own procedure for the prepa-
developed and are further investigated [12-14].
ration of aryl-substituted methyl 3-chlorothiophene-2-carboxyl-
ates 2, which consists of diazotization of the corresponding
3-aminothiophene-2-carboxylates 1 in acetonitrile solution with
an aqueous sodium nitrite (1.1 equiv) solution in the presence of
p-toluenesulfonic acid (4.0 equiv) followed by the addition of
the formed solution of diazonium salts to a warm suspension of
CuCl (5.0 equiv) in acetonitrile. Thus, compounds 2a–k were
obtained in 43–83% yield (Scheme 1, see Supporting Informa-
tion File 1 for more experimental details). It should be noted
that the initial 3-aminoesters 1 are known compounds and can
be obtained by the Fiesselmann thiophene synthesis from aryl-
substituted acrylonitriles bearing a good leaving group at the
C-3 position [22-24].
Figure 1: An example of an earlier developed S,N-heterohexacene
[13] and general structure of compounds synthesized in this work.
At present, the challenge is to develop effective ways of con- Methyl 3-chlorothiophene-2-carboxylates 2a–k were further
structing the TT-based compounds, such as S- and N,S-hetero- involved in the Fiesselmann reaction with methyl thioglycolate
acenes, in order to effectively tune their physical characteristics in the presence of potassium tert-butoxide in THF, which
and also reduce production costs since the routine synthesis of afforded aryl-substituted methyl 3-hydroxythieno[3,2-b]thio-
heteroacene structures involves cross-coupling reactions cata- phene-2-carboxylates 3a–k in 41–78% yields (Scheme 1).
lyzed by expensive transition metals [15]. Thus, in this paper, Compounds 3 were obtained in analytically pure form after
we would like to present an efficient metal-free synthesis of the single recrystallization from a toluene/ethanol mixture (1:1,
aryl-substituted TT building blocks, which can be utilized for v/v), or pure toluene for compounds 3f,g,i.
the construction of various fused systems, including N,S-hetero-
acenes, e.g., substituted 9H-thieno[2',3':4,5]thieno[3,2-b]indoles Next, we performed saponification of esters 3a–k by their
(TTIs) (Figure 1).
treatment with an excess of sodium hydroxyde in an
aqueous DMSO solution at 120 °C for 3 hours, where the
intermediating acids underwent decarboxylation to give
Results and Discussion
Continuing our previous work in which we used the Fiessel- thieno[3,2-b]thiophen-3(2H)-ones 4a–k after neutralization of
mann thiophene synthesis [16], viz., the interaction of ethyl the reaction mixture with a mineral acid. It should be noted that
thioglycolate with ethyl 3-chlorobenzo[b]thiophene-2-carboxyl- the obtained ketones 4 were more sensitive to the presence of
ates, to form a benzo[b]thieno[2,3-d]thiophene scaffold [17,18], acids than their benzo-annelated counterparts [17,18]: when an
we have decided to apply a similar approach to the synthesis of excess of a mineral acid was used, we observed a decrease in
aryl-substituted TT derivatives. Thus, 3-chloro- or 3-bromothio- yields of products 4 because of their partial degradation. There-
phene-2-carboxylates bearing aryl moieties at the C-5 or C-4 fore, to neutralize the reaction mixtures, we used one equiva-
position were appropriate starting substrates to construct TT lent of sulfuric acid relative to the alkali salt used for saponifi-
scaffolds according to our strategy. Compounds 2a–k can be cation. The resulting precipitates were then isolated by filtra-
prepared either through direct palladium-catalyzed arylation of tion, and thoroughly washed with water. As a result, we were
methyl 3-chlorothiophene-2-carboxylate [19] or through able to isolate products in analytically pure form with yields of
replacement of the amino group in the corresponding 3-amino- 93–99% (Scheme 2).
thiophene-2-carboxylates with a halogen atom by the Sand-
meyer reaction [20,21]. The former transformation is prefer- Both compounds 3 and 4 are new functional TT-cored building
able for large-scale syntheses, but we failed to repeat the re- blocks, which can be useful for the development of various
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Beilstein J. Org. Chem. 2019, 15, 2678–2683.
Scheme 1: Synthesis of aryl-substituted TT derivatives 3a–k, product scope, and yields.
Scheme 2: Synthesis of thieno[3,2-b]thiophen-3(2H)-one 4a–k, product scope, and yields.
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Beilstein J. Org. Chem. 2019, 15, 2678–2683.
fused molecules, e.g., we used sources 4 to construct deriva- the range of the TTI derivatives, ketone 4d was similarly treated
tives of new TTI ring systems according to the Fisсher indoliza- with arylhydrazines 5b–d containing electron–acceptor substit-
tion protocol [25]. To this end, compounds 4a–k were treated uents or electron–donor ones. There was no obvious change in
with phenylhydrazine 5a in acetic acid, thus affording com- the yields of compounds 6l–o (78–84%, Scheme 3), which may
pounds 6a–k in 45–83% yields (Scheme 3). Notably, all the indicate that the starting ketones had a rather high reactivity.
indolization reactions proceeded smoothly, the formed prod-
ucts precipitated from hot solutions during the process, and ana- To confirm the structure of TTI derivatives 6, we attempted to
lytically pure forms of substances were isolated by simple filtra- grow crystals of some of these compounds, however, all of
tion of cooled reaction mixtures, which were diluted with meth- them formed powdery precipitates. Therefore, N-functionaliza-
anol. In order to test the reactivity of compounds 4 and expand tion of compound 6d was carried out with benzyl bromide in
Scheme 3: Synthesis of TTI derivatives 6a–o, substrate and product scopes, and yields.
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the presence of NaH (Scheme 4). The resulting benzyl deriva-
tive 7d was crystallized from ethyl acetate to give crystals,
which were suitable for XRD analysis (Figure 2).
Supporting Information
X-ray crystallographic data. Deposition number CCDC
1944913 for compound 7d contain the crystallographic data
for these structures. These data can be obtained free of
charge from the Cambridge Crystallographic Data Centre
via https://www.ccdc.cam.ac.uk/data_request/cif.
Supporting Information File 1
Experimental section and copies of 1H, 13C and 19F NMR
spectra of new compounds.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-261-S1.pdf]
Supporting Information File 2
Crystal data of 7d.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-261-S2.cif]
Scheme 4: Alkylation of TTI 6d.
Acknowledgements
This study was supported by the Russian Foundation for Basic
Research, Grant No. 18-33-20083.
ORCID® iDs
Nadezhda S. Demina - https://orcid.org/0000-0002-5475-134X
Nikolay A. Rasputin - https://orcid.org/0000-0002-4610-3617
Roman A. Irgashev - https://orcid.org/0000-0002-8428-1748
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Fiesselmann thiophene synthesis for the construction of new
aryl-substituted thieno[3,2-b]thiophene derivatives, namely the
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