A new convenient synthetic route towards 2-(hetero)aryl-substituted thieno[3,2-b]indoles using Fischer indolization

Article abstract of DOI:10.1039/C8OB01110A

A number of 2-(hetero)aryl-substituted thieno[3,2-b]indoles have been successfully prepared using an efficient transition-metal-free strategy, involving the Fiesselmann synthesis of methyl 5-(hetero)aryl-3-hydroxythiophene-2-carboxylates from 2-bromo-3-(hetero)arylacrylates and methyl thioglycolate, and the transformation of the synthesized 3-hydroxyesters into the corresponding thiophen-3(2H)-ones, followed by their treatment with arylhydrazines to directly form the targeted structures via Fischer indolization. At the same time, structural variety of the obtained thieno[3,2-b]indoles has been achieved due to a wide range of available starting materials, including both 2-bromo-3-(hetero)arylacrylates and arylhydrazines. In addition, two π-extended molecules, namely 1,4-bis(4H-thieno[3,2-b]indol-2-yl)benzene and 2,5-bis(4H-thieno[3,2-b]indol-2-yl)thiophene, have been synthesized in line with the current approach towards 2-(hetero)arylated thieno[3,2-b]indoles.

Full text of DOI:10.1039/C8OB01110A

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Graphical abstract
_____________________________________________________________________________
A new convenient synthetic route towards 2-(hetero)aryl-substituted thieno[3,2-b]indoles using the
Fischer indolization
Roman A. Irgashev,* Alexander S. Steparuk, Gennady L. Rusinov
____________________________________________________________________________________________________________________

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A new convenient synthetic route towards 2-(hetero)aryl-substituted
thieno[3,2-b]indoles using the Fischer indolization
Roman A. Irgashev,a,b,* Alexander S. Steparuk,a Gennady L. Rusinova,b
a
Postovsky Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences, S.
Kovalevskoy Str., 22, Ekaterinburg, 620990, Russia
*Corresponding author: Fax: +7 343 369 30 58; e-mail: irgashev@ios.uran.ru
b
Ural Federal University named after the First President of Russia B. N. Yeltsin, Mira Str., 19,
Ekaterinburg, 620002, Russia
Keywords: Thieno[3,2-b]indole; Thiophen-3(2H)-one; Arylhydrazines; π-Conjugated molecules; the
Fischer indole synthesis; the Fiesselmann thiophene synthesis
________________________________________________________________________________
A number of 2-(hetero)aryl-substituted thieno[3,2-b]indoles has been successfully prepared using an
efficient transition-metal-free strategy, involved the Fiesselmann synthesis of methyl 5-(hetero)aryl-
3-hydroxythiophene-2-carboxylates from 2-bromo-3-(hetero)arylacrylates and methyl thioglycolate,
and transformation of the synthesized 3-hydroxyesters into corresponding thiophen-3(2H)-ones,
followed by their treatment with arylhydrazines to directly form the targeted structures via the
Fischer indolization. At the same time, structural variety of the obtained thieno[3,2-b]indoles has
been achieved due to a wide range of available starting materials, both 2-bromo-3-
(hetero)arylacrylates and arylhydrazines. In addition, two π-extended molecules, namely 1,4-bis(4H-
thieno[3,2-b]indol-2-yl)benzene and 2,5-bis(4H-thieno[3,2-b]indol-2-yl)thiophene, have been
synthesized in line with the current approach towards 2-(hetero)arylated thieno[3,2-b]indoles.
________________________________________________________________________________

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Introduction
Indole ring system as well as its [b]-annelated analogues is a basic structural motif of a large number
of naturally occurring and synthetic substances, which have been found to be useful for modern
pharmacology, agriculture and materials science.1–3 Thus, it is not surprising, that today various
classes of indole-based compounds attract considerable attention of researchers in terms of
elaborating new sustainable methods for their synthesis and their properties study.4–7 In this context,
thieno[3,2-b]indoles (TIs) represent an important family of fused N,S-containing heterocycles, since
some TI species have exhibited promising biological properties, such as anti-osteoarthritis,8
antitumor,9 antitubercular10 and antibacterial9,11 activities. Besides, over the past decade thieno[3,2-
b]indole has been widely and successfully utilized as electron-rich heteroaromatic subunits for
engineering of various linear π-conjugated and fused molecules for organic electronics applications.
Indeed, a number of organic dyes, both small molecules12–16 and polymers,17–19 e.g., MKZ 39-41
and PTITBT in Figure 1, bearing thieno[3,2-b]indole moiety as electron-donating part of their push-
pull structures, have been regarded as light-harvesting materials for high performance organic
photovoltaics (OVPs). Additionally, it has recently been reported an interesting application of near-
infrared dyes, bearing thieno[3,2-b]indole and diketopyrrolopyrrole (DPP) scaffolds, e.g., DPP-r-TI
in Figure 1, as effective photosensitizes for both photodynamic and photothermal therapies.20
n-C6H13
n-C11H23
CN
S
S
CO2H
N
N
n-C11H23
S
n
N
S
N
S
C2H5
x
PTITBT
MKZ 39-41 (n = 2-4)
n-C8H17
n-C6H13
N
S
O
S
N
N
S
O
S
N
n-C6H13
n-C8H17
DPP-r-TI
Figure 1. Thieno[3,2-b]indole-containing push-pull chromophores
It is important to note, that synthetic approaches towards these π-extended TI-based molecules are
included (hetero)aryl-linked thieno[3,2-b]indoles as the key intermediates, which, in their turn, are
obtained via Pd-catalyzed processes, such as the Suzuki-Miyaura or the Stille cross-coupling
reactions. Therefore, the elaboration of convenient and robust synthetic approaches, that ensure an
easy access to (hetero)arylated thieno[3,2-b]indoles, is an important challenge, since such
compounds are in-demand as building blocks for optoelectronic materials engineering. Herewith, the

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published methods for the construction of TI framework include both thermal and catalytic
cyclization of 2-(2-azidoaryl)thiophenes A1,21–24 the Cadogan reductive cyclization of 2-(2-
nitroaryl)thiophenes A2,25,26 Cu-catalyzed C-H / N-H oxidative cyclization of 2-(2-
aminoaryl)thiophenes B1,27 as well as the Buchwald-Hartwig amination of 2-(2-bromoaryl)-3-
bromothiophenes C1,28–30 and intramolecular amination of 2-(2-aminoaryl)-3-bromothiophenes D131
or isomeric molecules D232,33 (Scheme 1). Nevertheless, the application of above mentioned routes
for synthesis of (hetero)aryl-substituted TIs requires additional steps, mostly Pd-catalyzed cross-
coupling reactions, to prepare the functionalized in appropriate manner intermediates A-D. As
compared with these methods, the Fischer indole synthesis34–36 seems to be more attractive and
convenient chemical tool for construction of thieno[3,2-b]indole ring system, including its
(hetero)arylated derivatives. Indeed, in the frame of this strategy, the desired thieno[3,2-b]indoles
can be easy obtained from corresponding thiophen-3(2H)-ones and arylhydrazines,10 since such
transformation of thiophen-3(2H)-one fragment into thieno[3,2-b]indole ring system proceeds
smoothly and without isolation of the intermediate arylhydrazones. In particular, we have recently
communicated
a
convenient
approach
towards
N,S-heteroacenes,
namely
6H-
benzo[4',5']thieno[2',3':4,5]thieno[3,2-b]indoles, using the Fischer indole synthesis as the key
reaction.37 Continuing our research, we wish to report herein an efficient and convenient method for
synthesis of 2-(hetero)arylated thieno[3,2-b]indoles in line with the Fischer indolization strategy.
NO2
N3
Ar
Ar
or
S
S
A1
A2
nitrene-type
cyclizations
R
R
N
Ar
H
NH
oxidative C-N
cyclization
the Fischer
indole synthesis
HN
Ar
H2N
Ar
R = H, Alk, Ar
S
+
S
S
B1
O
the Buchwald-Hartwig
amination reactions
R
R
Br
Br
HN
NH
Br
Br
or
or
Ar
Ar
D2
Ar
S
S
S
D1
C1
Scheme 1. Retrosynthetic map of thieno[3,2-b]indole framework construction
Results and discussion
The purpose of our investigation has been to elaborate synthetic approach towards 2-(hetero)aryl-
linked thieno[3,2-b]indoles using the Fischer indolization as the key step, to provide structural

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variety of these compounds. Therefore, we have focused on the 5-(hetero)arylthiophen-3(2H)-ones,
the main precursors of the TIs, to find optimal way for their preparation based on available
(hetero)aromatic sources. Generally, 2-unsubstituted thiophen-3(2H)-ones can be easily obtained by
the ester hydrolysis and the in situ decarboxylation of alkyl 3-hydroxythiophene-2-carboxylates (2-
thenoates). In its turn, a convenient method for preparation of the latter 2-thenoates is the
Fiesselmann thiophene synthesis, which represents a reaction of 1,3-C,C-dielectrophilic substrates
with alkyl thioglycolates under basic conditions.38,39 To this way, few 5-(hetero)aryl-3-hydroxy-
substituted 2-thenoates have previously been synthesized either in two steps from 2-
(hetero)aroylacetates 140–42 or directly from 3-(hetero)arylpropiolates 2,43–45 in accordance with the
Fiesselmann method (Scheme 2).
Scheme 2. The selected route to 2-(hetero)aryl-substituted thieno[3,2-b]indoles, based on the
Fischer and the Fiesselmann methods
At the same time, 2-bromo-3-(hetero)arylacrylates 3 (α-bromocinnamates or their hetero analogues),
being easily obtainable chemicals, are also attractive as 1,3-dielectrophilic three-carbon units for the
Fiesselmann thiophene synthesis (Scheme 2), since these compounds can be considered as synthetic
equivalents of 3-(hetero)arylpropiolates 2 in a context of their reactivity as the Michael acceptors for
nucleophilic addition.46,47 For this reason, we have selected the former substrates for the preparation
of 3-hydroxy-2-thenoates, bearing (hetero)aromatic fragments at C-5. To this end, methyl α-
bromocinnamates 3a-k (mixtures of Z-E stereoisomers) have readily been obtained in 87-98%
yields, using the one-pot procedure for bromination/dehydrobromination of methyl cinnamates (for
more experimental details see ESI). Next, species 3a-k have successfully been involved in the
reaction with methyl thioglycolate (2 equiv.) in the presence of NaOMe (4 equiv.) in a methanol
solution to form methyl 5-aryl-3-hydroxythiophene-2-carboxylates 4a-k in 29-84% yields (Scheme
3, Table 1). In regard to practical aspects of this procedure, the best results have been achieved,
when substrate 3, together with methyl thioglycolate, has gradually been added to NaOMe in dry
MeOH, followed by reflux of a reaction mixture for 5 h. However, 2-thenoates 4h-k have been

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obtained in moderate yields. This fact can probably be explained by steric hindrances for S-
nucleophile addition to activated C=C double bond of α-bromocinnamates 3h-k, having bulky o-
substituted aryls (Table 1, entries 8-11). At the same time, due to the rather small radius (1.47 Å)48
of fluorine atom, 2-fluorophenyl-containing substrate 3g (Table 1, entry 7) has given corresponding
2-thenoate 4g in 60% yield, which is comparable with 62% yield of 2-thenoate 4a, having a simple
phenyl substituent at C-5 (Table 1, entry 1).
Scheme 3. Synthesis of methyl 5-aryl-3-hydroxythiophene-2-carboxylates 4
Table 1. Substrate scope of methyl 5-aryl-3-hydroxythiophene-2-carboxylates 4
4
%)
(yield
entry methyl α-bromocinnamate 3 (Ar)
1
2
3
4
5
6
7
8
3a (phenyl)
4a (62)
4b (84)
4c (75)
4d (72)
4e (65)
4f (79)
4g (60)
4h (31)
4i (29)
4j (35)
4k (43)
3b (4-fluorophenyl)
3c (4-bromophenyl)
3d (4-methoxyphenyl)
3e (4-hexyloxyphenyl)
3f (3,4,5-trimethoxyphenyl)
3g (2-fluorophenyl)
3h (2-chlorophenyl)
3i (2-bromophenyl)
3j (2-methoxyphenyl)
3k (1-naphthyl)
9
10
11
Besides, to build thien-2-yl-linked thieno[3,2-b]indoles, methyl [2,2'-bithiophene]-5-carboxylates
4l,m have been prepared from methyl 2-bromo-3-(thien-2-yl)acrylates 3l,m, which obtained by
esterification of corresponding 2-bromoacrylic acids49 (for more experimental details see ESI). To
show compatibility of the current strategy with others synthetic techniques, Br-containing ester 4m
has been converted into corresponding 5-phenylthien-2-yl-linked derivatives 4n using the Suzuki-
Miyaura cross-coupling reaction (Scheme 4). Importantly, the main 5-(hetero)aryl-3-hydroxy-
substituted 2-thenoates 4a-m have been produced in gram scales, thanks to easy procedure of their
preparation and high availability of source compounds 3.

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Scheme 4. Synthesis of methyl [2,2'-bithiophene]-5-carboxylates 4l,m and 4n
Construction of the target TI frameworks has been carried out by the next two steps. Saponification
of the synthesized esters 4 has been performed by their treatment with excess of NaOH in aqueous
DMSO solution at 140 °C for 1.5 h under an argon atmosphere, followed by acidic workup of the
reaction mixtures to obtain thiophen-3(2H)-ones 5 in 88-95% yields (Scheme 5, Table 2). Along
with good results in this synthetic step, saponification of ester 4m has totally failed under these
alkali reaction conditions, apparently due to a cleavage of 5-bromothien-2-yl part (Table 2, entry
13). Clearly, the preliminary replacement of bromine atom in substrate 4m, before its conversion to
thiophen-3(2H)-one, is more preferable way to perform the necessary modifications. Nevertheless,
the treatment of ester 4m with a mixture of trifluoroacetic and methanesulfonic acids at 80 °C for 2
h has allowed us to receive crude ketone 5m in 29% yield, that has been used in the next step
without purification. Unsubstituted at benzene ring thieno[3,2-b]indoles 7a-n, bearing
(hetero)aromatic moieties at C-2, have been obtained in 38-72% yields by reaction of thiophen-
3(2H)-ones 5a-n with phenylhydrazine 6a (1.5 equiv.) in the solution of glacial acetic acid at 120 °C
for 1 h (Scheme 5, Table 2). At the same time, the use of phenylhydrazine hydrochloride instead of
its base form 6a in the reaction with ketone 5a under the same conditions has reduced the yield of
thieno[3,2-b]indole 7a to 28% because of significantly increased decomposition of starting substrate
5a.
Scheme 5. Synthetic route to 2-(hetero)aryl-substituted thieno[3,2-b]indoles 7a-n
Table 2. Substrate scope of (het)arylated thiophen-3(2H)-ones 5 and thieno[3,2-b]indoles 7
entry 2-thenoate 4 (Ar or Het)
5 (yield %)
5a (95)
5b (92)
5c (95)
5d (88)
5e (95)
5f (90)
5g (91)
5h (95)
5i (89)
7 (yield %)
7a (58 / 28b)
7b (65)
7c (61)
1
2
4a (phenyl)
4b (4-fluorophenyl)
4c (4-bromophenyl)
4d (4-methoxyphenyl)
4e (4-hexyloxyphenyl)
4f (3,4,5-trimethoxyphenyl)
4g (2-fluorophenyl)
4h (2-chlorophenyl)
4i (2-bromophenyl)
4j (2-methoxyphenyl)
4k (1-naphthyl)
3
4
5
6
7
8
9
10
11
7d (70)
7e (70)
7f (41)
7g (53)
7h (56)
7i (38)
5j (95)
5k (88)
7j (66)
7k (44)

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12
13
14
4l (thien-2-yl)
4m (5-bromothien-2-yl)
4n (5-phenylthien-2-yl)
5l (90)
5m (0 / 29a)
5n (95)
7l (72)
7m (61)
7n (66)
a A mixture of CF3CO2H and MeSO3H (v/v, 3:1) has been used in this case.
b In the case of the use of PhNHNH2·HCl.
During this study, thieno[3,2-b]indoles, functionalized at both thiophene and benzene rings of their
framework, have also been obtained in the same manner using the Fischer indolization process. Two
thiophen-3(2H)-ones 5a and 5l, bearing phenyl and thien-2-yl at C-5, have been treated with 4-
bromo-, 4-methyl-, 4-cyano-, and 4-carboxyphenylhydrazine 6b-e or 1-naphtylhydrazine 6f
hydrochlorides (1.5 equiv.) and NaOAc (1.5 equiv.), added to neutralize hydrochloric acid, under
the similar reaction conditions, to afford 2,7-disubstituted thieno[3,2-b]indoles 7o-r and 7t-w or 8-
substituted benzo[g]thieno[3,2-b]indoles 7s and 7x, respectively (Scheme 6).
Scheme 6. Synthesis of thiophene-benzene-functionalized TIs 7o-x, substrate scope and yields
Thus, formation of the desired thieno[3,2-b]indoles has been reached in all studied by us reactions of
thiophene-3(2H)-ones 5 with arylhydrazines 6, that provides access to a wide range of new TI
compounds 7. However, derivatives 7f,i,k (Scheme 5, Table 2) and 7q,r,t,v,w (Scheme 6) have been
isolated in 38-44% and 17-43% yields, respectively, although we have observed full consumption of
source materials 5 in these experiments. It can be assumed, that a decrease in the yield of these
products is caused by undesirable transformations of the reaction intermediates, such as N-N bond
cleavage in the ene-hydrazines, that leads to side processes.50,51 Moreover, the indolization slows
down when using arylhydrazines, bearing electron-withdrawing groups,52 which explains poor
yields of compounds 7q,v and 7r,w, obtained from 4-cyano- and 4-carboxy-substituted
phenylhydrazines 6d and 6e, respectively.
Furthermore, the application of the present synthetic strategy to the construction of some more π-
extended thieno[3,2-b]indole-based molecules has been also investigated. To this end, diethyl bis(2-

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bromoacrylates) 8a and 8b have been synthesized starting from the corresponding bis(acrylates), by
analogy with the synthesis of α-bromocinnamates 3 from cinnamates (for more experimental details
see ESI). Substrates 8 have been used as ethyl diester forms to provide their sufficient solubility in
the next step. Dimethyl bis(3-hydroxy-2-thenoates) 9a and 9b have been obtained in 33% and 17%
yield, respectively, by condensation of bis(2-bromoacrylates) 8a,b with methyl thioglycolate (4
equiv.) in the presence of NaOMe (8 equiv.) in a methanol solution. Note that the low yields of
derivatives 9 can be explained by a successive transformation of 2-bromoacrylate units of starting
molecules 8 into thiophene moieties during the reaction. In this context, average yields per the
formation of one thiophene ring of 9a and 9b are respectively 57% and 41%, which is comparable
with the yields of similar 2-thenoates 4a (62%, Table 1, entry 1) and 4l (38%, Scheme 4). Further
cleavage of diesters 9a,b under the same reaction conditions as for esters 4 has readily given the key
precursors 10a,b, that have been successfully converted into the target twin TI derivatives 11a,b
according to the Fischer indolization procedure (Scheme 7). In this case, analytically pure forms of
products 11 have been obtained by their sublimation at high temperature under reduced pressure
(280 °C / 3 mbar), due to low solubility of these bulky TI molecules in the majority of organic
solvents. It should be also noted, that an appreciable tendency to sublimation at close to the melting
point temperature, even under atmospheric pressure, has been observed for most of the synthesized
thieno[3,2-b]indoles.
Scheme 7. Synthesis of π-extended thieno[3,2-b]indole-based molecules 11

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Conclusion
In summary, we have successfully applied the Fischer indolization process to the construction of
thieno[3,2-b]indole frameworks, having aromatic or heteroaromatic units at C-2. The necessary 5-
(hetero)arylthiophen-3(2H)-ones have been obtained by two-step route included condensation of
easily accessible α-bromocinnamates or their heteroanalogues with methyl thioglycolate according
to the Fiesselmann method and alkali treatment of the afforded 5-(hetero)aryl-3-hydroxy-substituted
2-thenoates. The advantages of present methodology are available starting substrates and convenient
reactions based on transition metal-free processes, thereby it provides an easy access to a variety of
(hetero)aryl-linked thieno[3,2-b]indoles, with optional functions at benzene ring of their system. In
this context, the current approach has a high synthetic utility for further engineering of new
thieno[3,2-b]indole-based both (photo)electronic materials and pharmaceuticals.
Experimental
General information. Analytical studies were carried out using equipment of the Center for Joint
Use “Spectroscopy and Analysis of Organic Compounds” at Postovsky Institute of Organic
Synthesis (Ural Division, RAS). 1H, 13C and 19F NMR spectra were obtained on a Bruker DRX-400
and AVANCE-500 spectrometers with Me4Si as an internal standard for 1H and 13C NMR or C6F6 as
an internal standard for 19F NMR. 13С NMR spectra of compounds 11a,b were not recorded because
of poor solubility of these substances in a majority of deuterated solvents. Elemental analysis was
carried on a Eurovector EA 3000 automated analyzer. High-resolution mass spectrometry was
performed using a Bruker maXis Impact HD spectrometer. Melting points were determined on
Boetius combined heating stages and were not corrected. Silica gel 0.040–0.063 mm (230–400
mesh) was used to purify compounds. All used solvents were dried and distilled per standard
procedures.
General procedure for synthesis of methyl 5-(hetero)aryl-3-hydroxythiophene-2-carboxylates
(4a-m). A mixture of appropriate methyl 2-bromoacrylate 3 (50 mmol) and methyl thioglycolate
(9.15 ml, 100 mmol) in dry MeOH (30 ml) (dry THF (30 ml) was used in the case of substrate 3m)
was added dropwise to a stirred solution of NaOMe, prepared from sodium (4.6 g, 200 mmol) and
dry MeOH (70 ml), at 0 °C during 20 min and the formed suspension was vigorously stirred and
heated at reflux for 5 h. Then, the reaction mixture was poured into ice-cold water (100 ml) and the
obtained turbid pale-green solution was immediately acidified with conc. HCl (13 ml) to form
precipitate of the product. The obtained solid was collected by filtration, washed with water (5×30

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ml), MeOH (15 ml) and dried at room temperature. Crude products 4a,b,l were purified by
crystallization from 50% aqueous EtOH (50 ml), while other crude materials 4 were crystallized
from a mixture of toluene and MeOH (60 ml, v/v 1:3), to afford the analytically pure forms.
Methyl 3-hydroxy-5-phenylthiophene-2-carboxylate (4a). White needles, m.p. 97-98 °C (from
1
50% aqueous EtOH); yield 7.26 g (62%); H NMR (400 MHz, DMSO-d6) δ 10.42 (s, 1H), 7.74 –
7.66 (m, 2H), 7.52 – 7.38 (m, 3H), 7.19 (s, 1H), 3.78 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ
162.9, 161.5, 147.1, 132.5, 129.3, 129.2, 125.5, 116.7, 104.0, 51.5. Anal. Calcd for C12H10O3S: C,
61.52; H, 4.30. Found: C, 61.63; H, 4.22.
Methyl 5-(4-fluorophenyl)-3-hydroxythiophene-2-carboxylate (4b). White fleecy crystals, m.p.
1
156-157 °C (from 50% aqueous EtOH); yield 10.59 g (84%); H NMR (500 MHz, DMSO-d6) δ
19
10.42 (s, 1H), 7.79 – 7.72 (m, 2H), 7.34 – 7.25 (m, 2H), 7.17 (s, 1H), 3.78 (s, 3H). F NMR (471
MHz, DMSO-d6) δ 50.75 – 50.68 (m). 13C NMR (126 MHz, DMSO-d6) δ 162.9, 162.6 (d, JCF
=
247.4 Hz), 161.5, 145.9, 129.1 (d, JCF = 3.1 Hz), 127.7 (d, JCF = 8.5 Hz), 116.9, 116.2 (d, JCF = 21.9
Hz), 104.0, 51.5. Anal. Calcd for C12H9FO3S: C, 57.14; H, 3.60. Found: C, 57.03; H, 3.61.
Methyl 5-(4-bromophenyl)-3-hydroxythiophene-2-carboxylate (4c). Pink powder, m.p. 147-148
1
°C (from toluene-MeOH, v/v 1:3); yield 11.74 g (75%); H NMR (500 MHz, DMSO-d6) δ 10.46 (s,
1H), 7.67 – 7.63 (m, 4H), 7.22 (s, 1H), 3.79 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 162.7,
161.3, 145.5, 132.1, 131.7, 127.4, 122.5, 117.3, 104.5, 51.5. Anal. Calcd for C12H9BrO3: C, 46.02;
H, 2.90. Found: C, 45.92; H, 2.79.
Methyl 3-hydroxy-5-(4-methoxyphenyl)thiophene-2-carboxylate (4d). White needles, m.p. 138-
1
139 °C (from toluene-MeOH, v/v 1:3); yield 9.51 g (72%); H NMR (500 MHz, DMSO-d6) δ 10.32
13
(s, 1H), 7.77 – 7.47 (m, 2H), 7.08 (s, 1H), 7.04 – 6.98 (m, 2H), 3.80 (s, 3H), 3.78 (s, 3H). C NMR
(126 MHz, DMSO-d6) δ 163.0, 161.7, 160.2, 147.4, 127.0, 125.1, 115.4, 114.6, 102.8, 55.3, 51.4.
Anal. Calcd for C13H12O4S: C, 59.08; H, 4.58. Found: C, 59.15; H, 4.50.
Methyl 5-[4-(hexyloxy)phenyl]-3-hydroxythiophene-2-carboxylate (4e). Pale pink powder, m.p.
1
96-97 °C (from toluene-MeOH, v/v 1:3); yield 10.87 g (65%); H NMR (500 MHz, DMSO-d6) δ
10.32 (s, 1H), 7.61 (d, J = 8.8 Hz, 2H), 7.07 (s, 1H), 6.99 (d, J = 8.8 Hz, 2H), 4.00 (t, J = 6.5 Hz,
2H), 3.77 (s, 3H), 1.75 – 1.66 (m, 2H), 1.45 – 1.37 (m, 2H), 1.34 – 1.27 (m, 4H), 0.88 (t, J = 7.0 Hz,
3H). 13C NMR (126 MHz, DMSO-d6) δ163.0, 161.7, 159.7, 147.4, 126.9, 124.9, 115.3, 115.0,

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102.7, 67.6, 51.4, 31.0, 28.5, 25.1, 22.0, 13.9. Anal. Calcd for C18H22O4S: C, 64.65; H, 6.63. Found:
C, 64.78; H, 6.67.
Methyl 3-hydroxy-5-(3,4,5-trimethoxyphenyl)thiophene-2-carboxylate (4f). Beige powder, m.p.
1
152-153 °C (from toluene-MeOH, v/v 1:3); yield 12.81 g (79%); H NMR (500 MHz, DMSO-d6) δ
10.29 (s, 1H), 7.21 (s, 1H), 6.94 (s, 2H), 3.85 (s, 6H), 3.78 (s, 3H), 3.69 (s, 3H). 13C NMR (126
MHz, DMSO-d6) δ163.0, 161.5, 153.3, 147.4, 138.6, 128.2, 116.8, 103.7, 103.2, 60.1, 56.1, 51.5.
Anal. Calcd for C15H16O6S: C, 55.55; H, 4.97. Found: C, 55.54; H, 4.93.
Methyl 5-(2-fluorophenyl)-3-hydroxythiophene-2-carboxylate (4g). White powder, m.p. 139-140
1
°C (from toluene-MeOH, v/v 1:3); yield 7.57 g (60%); H NMR (400 MHz, DMSO-d6) δ 10.51 (s,
1H), 7.81 (td, J = 8.0, 1.6 Hz, 1H), 7.51 – 7.44 (m, 1H), 7.41 – 7.35 (m, 1H), 7.34 – 7.27 (m, 1H),
19
13
7.24 (d, J = 0.5 Hz, 1H), 3.79 (s, 3H). F NMR (471 MHz, DMSO-d6) δ 49.34 – 49.25 (m). C
NMR (126 MHz, DMSO-d6) δ 162.6, 160.7, 158.7 (d, JCF = 250.2 Hz), 139.8 (d, JCF = 3.1 Hz),
131.0 (d, JCF = 8.7 Hz), 128.5 (d, JCF = 2.6 Hz), 125.3 (d, JCF = 3.2 Hz), 120.1 (d, JCF = 11.7 Hz),
119.4 (d, JCF = 5.4 Hz), 116.6 (d, JCF = 22.0 Hz), 105.1 (d, JCF = 5.4 Hz), 51.5. Anal. Calcd for
C12H9FO3S: C, 57.14; H, 3.60. Found:C, 57.20; H, 3.57.
Methyl 5-(2-chlorophenyl)-3-hydroxythiophene-2-carboxylate (4h). Beige needles, m.p. 136-137
1
°C (from toluene-MeOH, v/v 1:3); yield 4.17 g (31%); H NMR (400 MHz, DMSO-d6) δ 10.54 (s,
13
1H), 7.68 – 7.64 (m, 1H), 7.63 – 7.59 (m, 1H), 7.49 – 7.42 (m, 2H), 7.12 (s, 1H), 3.78 (s, 3H). C
NMR (126 MHz, DMSO-d6) δ 162.5, 160.2, 143, 131.2, 131.04, 131.00, 130.7, 130.6, 127.9, 121.2,
105.8, 51.5. Anal. Calcd for C12H9ClO3S: C, 53.64; H, 3.38. Found: C, 53.53; H, 3.51.
Methyl 5-(2-bromophenyl)-3-hydroxythiophene-2-carboxylate (4i). Pale orange needles, m.p.
118-119 °C (from toluene-MeOH, v/v 1:3); yield 4.54 g (29%); 1H NMR (400 MHz, CDCl3) δ 10.55
(s, 1H), 7.78 (dd, J = 8.0, 1.0 Hz, 1H), 7.59 (dd, J = 7.7, 1.7 Hz, 1H), 7.49 (td, J = 7.6, 1.1 Hz, 1H),
13
7.38 (td, J = 7.7, 1.7 Hz, 1H), 7.04 (s, 1H), 3.79 (s, 3H). C NMR (126 MHz, DMSO-d6) δ 162.5,
160.1, 144.9, 133.8, 133.4, 131.5, 130.8, 128.3, 121.5, 121.4, 105.7, 51.5. Anal. Calcd for
C12H9BrO3S: C, 46.02; H, 2.90. Found: C, 46.03; H, 2.77.
Methyl 3-hydroxy-5-(2-methoxyphenyl)thiophene-2-carboxylate (4j). Yellowish needles, m.p.
1
104-105 °C (from toluene-MeOH, v/v 1:3); yield 4.63 g (35%); H NMR (400 MHz, DMSO-d6) δ

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10.18 (s, 1H), 7.77 (dd, J = 7.8, 1.6 Hz, 1H), 7.40 (ddd, J = 8.6, 7.4, 1.6 Hz, 1H), 7.29 (s, 1H), 7.22
– 7.13 (m, 1H), 7.05 (td, J = 7.8, 1.0 Hz, 1H), 3.94 (s, 3H), 3.78 (s, 3H). 13C NMR (126 MHz,
DMSO-d6) δ 163.4, 160.8, 155.9, 142.9, 130.4, 127.7, 121.0, 120.7, 117.5, 112.4, 104.3, 55.7, 51.4.
Anal. Calcd for C13H12O4S: C, 59.08; H, 4.58. Found: C, 59.07; H, 4.65.
Methyl 3-hydroxy-5-(naphthalen-1-yl)thiophene-2-carboxylate (4k). Cream needles, m.p. 133-
1
134 °C (from toluene-MeOH, v/v 1:3); yield 6.11 g (43%); H NMR (500 MHz, DMSO-d6) δ 10.58
(s, 1H), 8.19 – 8.13 (m, 1H), 8.08 – 8.00 (m, 2H), 7.67 – 7.55 (m, 4H), 7.03 (s, 1H), 3.81 (s, 3H).
13C NMR (126 MHz, DMSO-d6) δ 162.7, 160.6, 145.3, 133.4, 130.7, 130.3, 129.5, 128.6, 127.7,
127.3, 126.5, 125.5, 124.5, 121.1, 105.2, 51.5. Anal. Calcd for C16H12O3S: C, 67.59; H, 4.25. Found:
C, 67.42; H, 4.08.
Methyl 4-hydroxy-[2,2'-bithiophene]-5-carboxylate (4l). Cream crystals, m.p. 70-71 °C (from
50% aqueous EtOH); yield 4.69 g (39%); 1H NMR (400 MHz, DMSO-d6) δ 10.54 (s, 1H), 7.65 (dd,
J = 5.1, 1.0 Hz, 1H), 7.48 (dd, J = 3.6, 1.1 Hz, 1H), 7.14 (dd, J = 5.0, 3.7 Hz, 1H), 6.97 (s, 1H), 3.77
13
(s, 3H). C NMR (126 MHz, DMSO-d6) δ 162.5, 161.0, 140.4, 135.4, 128.7, 127.6, 126.0, 116.4,
103.2, 51.5. Anal. Calcd for C10H8O3S2: C, 49.98; H, 3.36. Found: C, 49.73; H, 3.13.
Methyl 5'-bromo-4-hydroxy-[2,2'-bithiophene]-5-carboxylate (4m). Yellow needles, m.p. 138-
1
139 °C (from toluene-MeOH, v/v 1:3); yield 7.50 g (47%); H NMR (400 MHz, DMSO-d6) δ 10.58
(s, 1H), 7.34 (d, J = 3.9 Hz, 1H), 7.28 (d, J = 3.9 Hz, 1H), 6.96 (s, 1H), 3.76 (s, 3H). 13C NMR (126
MHz, DMSO-d6) δ 162.4, 160.8, 138.8, 137.0, 131.9, 126.6, 117.0, 112.6, 103.8, 51.5. Anal. Calcd
for C10H7BrO3S2: C, 37.63; H, 2.21. Found: C, 37.54; H, 2.20.
Procedure for synthesis of methyl 4-hydroxy-5'-phenyl-[2,2'-bithiophene]-5-carboxylate (4n).
Methyl 5'-bromo-4-hydroxy-[2,2'-bithiophene]-5-carboxylate 4m (640 mg, 2 mmol), phenylboronic
acid (488 mg, 4 mmol), Pd(PPh3)4 (116 mg, 0.1 mmol) together with 2M aqueous K2CO3 solution (3
ml), THF (12 ml) and EtOH (8 ml) were placed in a 50 ml Schlenk tube, equipped with a magnetic
stir bar and reflux condenser. The resulting mixture was deoxygenated by several cycles (4 – 5
times) of vacuum pumping and flushing with argon at room temperature, and then it was stirred and
heated at reflux for 7 h under an argon atmosphere. After this time, the reaction mixture was treated
with AcOH (4 ml) and evaporated to dryness under reduced pressure. The obtained residue was
extracted with warm CHCl3 (3×20 ml) and the resulting CHCl3 solution was eluted through a short

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silica gel plug (1 cm×1.5 cm) with CHCl3 (15 ml). The filtrate was concentrated in vacuum to afford
the crude product, which was purified by crystallization from a mixture of toluene and MeOH (10
ml, v/v 1:1) to obtain analytically pure compound 4n.
Methyl 4-hydroxy-5'-phenyl-[2,2'-bithiophene]-5-carboxylate (4n). Pale yellow powder, m.p.
1
121-122 °C; yield 468 mg (74%); H NMR (400 MHz, DMSO-d6) δ 10.57 (s, 1H), 7.70 (d, J = 7.4
Hz, 2H), 7.56 (d, J = 3.9 Hz, 1H), 7.52 (d, J = 3.8 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.4
13
Hz, 1H), 7.00 (s, 1H), 3.77 (s, 3H). C NMR (126 MHz, DMSO-d6) δ 162.5, 161.1, 144.3, 140.0,
134.5, 132.8, 129.2, 128.3, 127.2, 125.4, 125.0, 116.4, 103.3, 51.5. Anal. Calcd for C16H12O3S2: C,
60.74; H, 3.82. Found: C, 60.70; H, 3.87.
General procedure for synthesis of 5-(hetero)arylthiophen-3(2H)-ones (5a-l,n). NaOH (5.04 g,
126 mmol) in water (24 ml) was added in one portion to appropriate methyl 2-thenoate 4 (6.3 mmol)
in DMSO (15 ml) and the obtained solution was flushed with argon, then it was stirred and heated at
140 °C for 1.5 h under an argon atmosphere. The reaction mixture was cooled to room temperature,
poured into water (75 ml) with conc. HCl (12 ml) and extracted with benzene (50 ml). The benzene
extract was washed with saturated aqueous NaHCO3 solution (15 ml), water (2×25 ml) and dried
with Na2SO4. The solvent was removed under reduced pressure and the residue was purified by
crystallization from 50% aqueous EtOH (25 ml). Crude substances 5g-k were purified as follows:
the residue obtained after evaporation of benzene extract was dissolved in CHCl3 (30 ml) and eluted
through a short silica gel plug (2 cm×1.5 cm) with CHCl3 (10 ml). The filtrate was concentrated in
vacuum to afford analytically pure product.
1
13
To obtain single-valued H and C spectra of products 5g-k, the NMR measurements were carried
out in DMSO-d6 solution, where the exclusively enol (3-hydroxythiohene) form of these compounds
was detected, since a tautomeric mixture, both thiophen-3(2H)-one and 3-hydroxythiophene forms,
were observed for their 1H NMR spectra recorded in CDCl3 solution.
5-Phenylthiophen-3(2H)-one (5a). Beige powder, m.p. 74-75 °C (from 50% aqueous EtOH); yield
1.06 g (95%); 1H NMR (500 MHz, CDCl3) δ 7.70 – 7.62 (m, 2H), 7.55 – 7.40 (m, 3H), 6.56 (s, 1H),
13
3.80 (s, 2H). C NMR (126 MHz, CDCl3) δ 202.2, 178.5, 132.6, 132.1, 128.9, 126.5, 118.4, 40.6.
Anal. Calcd for C10H8OS: C, 68.15; H, 4.58. Found: C, 67.98; H, 4.59.
5-(4-Fluorophenyl)thiophen-3(2H)-one (5b). Beige powder, m.p. 112-113 °C (from 50% aqueous
EtOH); yield 1.13 g (92%); 1H NMR (500 MHz, CDCl3) δ 7.70 – 7.62 (m, 2H), 7.55 – 7.40 (m, 3H),
19
6.56 (s, 1H), 3.80 (s, 2H). F NMR (471 MHz, CDCl3) δ 55.30 (s). 13C NMR (126 MHz, CDCl3) δ

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201.9, 176.9, 164.9 (d, JCF = 255.6 Hz), 129.0), 128.7 (d, JCF = 8.2 Hz), 118.3, 116.2 (d, JCF = 22.1
Hz), 40.7. Anal. Calcd for C10H7FOS: C, 61.84; H, 3.63. Found: C, 61.60; H, 3.55. HRMS (APCI)
m/z calcd for C10H8FOS [M+H]+: 195.0274, found: 195.0273.
5-(4-Bromophenyl)thiophen-3(2H)-one (5c). Pale brown powder, m.p. 127-128 °C (from 50%
aqueous EtOH); yield 1.53 g (95%); 1H NMR (500 MHz, CDCl3) δ 7.61 (d, J = 8.3 Hz, 2H), 7.55 (d,
J = 8.3 Hz, 2H), 6.55 (s, 1H), 3.82 (s, 2H). 13C NMR (126 MHz, CDCl3) δ 202.0, 176.9, 132.3,
131.7, 128.0, 126.8, 118.9, 40.8. Anal. Calcd for C10H7BrOS: C, 47.08; H, 2.77. Found: C, 46.89; H,
2.67.
5-(4-Methoxyphenyl)thiophen-3(2H)-one (5d). Pale brown powder, m.p. 123-124 °C (from 50%
aqueous EtOH); yield 1.15 g (88%); 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.8 Hz, 2H), 6.97 (d,
J = 8.9 Hz, 2H), 6.49 (s, 1H), 3.88 (s, 3H), 3.80 (s, 2H). 13C NMR (126 MHz, CDCl3) δ 202.0,
177.9, 162.8, 128.3, 125.2, 116.6, 114.3, 55.5, 40.5. Anal. Calcd for C11H10O2S: C, 64.05; H, 4.89.
Found: C, 63.81; H, 4.84.
5-[4-(Hexyloxy)phenyl]thiophen-3(2H)-one (5e). Pink powder, m.p. 92-93 °C (from 50% aqueous
EtOH); yield 1.65 g (95%); 1H NMR (400 MHz, CDCl3) δ 7.67 – 7.60 (m, 2H), 6.98 – 6.92 (m, 2H),
6.49 (s, 1H), 4.02 (t, J = 6.6 Hz, 2H), 3.80 (s, 2H), 1.86 – 1.75 (m, 2H), 1.52 – 1.42 (m, 2H), 1.40 –
13
1.30 (m, 4H), 0.91 (t, J = 7.0 Hz, 3H). C NMR (126 MHz, CDCl3) δ 201.9, 177.9, 162.4, 128.3,
124.9, 116.4, 114.7, 68.2, 40.4, 31.4, 28.9, 25.5, 22.5, 13.9. Anal. Calcd for C16H20O2S: C, 69.53; H,
7.29. Found: C, 69.21; H, 7.61.
5-(3,4,5-Trimethoxyphenyl)thiophen-3(2H)-one (5f). Reddish needles, m.p. 128-129 °C (from
1
50% aqueous EtOH); yield 1.51 g (90%); H NMR (400 MHz, CDCl3) δ 6.90 (s, 2H), 6.50 (s, 1H),
3.92 (s, 6H), 3.92 (s, 3H), 3.83 (s, 2H). 13C NMR (126 MHz, CDCl3) δ 201.8, 178.3, 153.3, 141.4,
128.2, 118.1, 103.9, 60. 9, 56.2, 40.7. Anal. Calcd for C13H14O4S: C, 58.63; H, 5.30. Found: C,
58.51; H, 5.25.
5-(2-Fluorophenyl)thiophen-3(2H)-one (5g). Pale brown powder, m.p. 66-67 °C; yield 1.11 g
(91%); for enol form: 1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 7.71 (td, J = 8.0, 1.6 Hz, 1H),
13
7.37 – 7.28 (m, 2H), 7.27 – 7.23 (m, 1H), 7.20 – 7.15 (m, 1H), 6.43 (d, J = 1.6 Hz, 1H). C NMR
(126 MHz, DMSO-d6) δ 158.3 (d, JCF = 248.3 Hz), 155.2, 133.9 (d, JCF = 3.2 Hz), 129.1 (d, JCF
=

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8.6 Hz), 127.9 (d, JCF = 3.2 Hz), 125.0 (d, JCF = 3.3 Hz), 121.6 (d, JCF = 12.0 Hz), 119.2 (d, JCF
=
5.8 Hz), 116.3 (d, JCF = 22.0 Hz), 99.7 (d, JCF = 5.0 Hz). Anal. Calcd for C10H7FOS: C, 61.84; H,
3.63. Found: C, 61.70; H, 3.71.
5-(2-Chlorophenyl)thiophen-3(2H)-one (5h). Beige needles, m.p. 80-81 °C; yield 1.26 g (95%);
1
for enol form: H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 7.57 (dd, J = 7.7, 1.8 Hz, 1H), 7.54
(dd, J = 7.8, 1.5 Hz, 1H), 7.38 (td, J = 7.8, 1.5 Hz, 1H), 7.34 (td, J = 7.7, 1.8 Hz, 1H), 7.04 (d, J =
1.7 Hz, 1H), 6.42 (d, J = 1.7 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 154.7, 137.0, 132.6, 130.7,
130.7, 130.5, 129.1, 127.6, 120.7, 100.1. Anal. Calcd for C10H7ClOS: C, 57.01; H, 3.35. Found: C,
56.98; H, 3.57.
5-(2-Bromophenyl)thiophen-3(2H)-one (5i). Beige powder, m.p. 64-65 °C; yield 1.43 g (89%); for
enol form: 1H NMR (500 MHz, DMSO-d6) δ 9.67 (s, 1H), 7.73 (dd, J = 7.8, 1.2 Hz, 1H), 7.52 (dd, J
= 7.7, 1.7 Hz, 1H), 7.43 (td, J = 7.8, 1.2 Hz, 1H), 7.28 (td, J = 7.7, 1.7 Hz, 1H), 6.99 (d, J = 1.7 Hz,
1H), 6.43 (d, J = 1.7 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 154.5, 138.7, 134.7, 133.7, 131.3,
129.5, 128.1, 121.4, 120.8, 99.8. Anal. Calcd for C10H7BrOS: C, 47.08; H, 2.77. Found: C, 47.21; H,
2.75.
5-(2-Methoxyphenyl)thiophen-3(2H)-one (5j). Beige powder, m.p. 89-90 °C (from 50% aqueous
EtOH); yield 1.23 g (95%); for enol form: 1H NMR (500 MHz, DMSO-d6) δ 9.47 (s, 1H), 7.61 (dd,
J = 7.8, 1.6 Hz, 1H), 7.29 – 7.24 (m, 1H), 7.17 (d, J = 1.7 Hz, 1H), 7.11 – 7.08 (m, 1H), 6.99 (td, J =
13
7.6, 1.0 Hz, 1H), 6.29 (d, J = 1.7 Hz, 1H), 3.88 (s, 3H). C NMR (126 MHz, DMSO-d6) δ 155.3,
154.6, 136.7, 128.5, 127.2, 122.4, 120.9, 118.2, 112.2, 98.9, 55.6. Anal. Calcd for C11H10O2S: C,
64.05; H, 4.89. Found: C, 64.08; H, 4.71.
5-(Naphthalen-1-yl)thiophen-3(2H)-one (5k). Beige powder, m.p. 88-89 °C (from 50% aqueous
1
EtOH); yield 1.25 g (88%); for enol form: H NMR (500 MHz, DMSO-d6) δ 9.76 (s, 1H), 8.29 –
8.25 (m, 1H), 8.02 – 7.98 (m, 1H), 7.97 – 7.93 (m, 1H), 7.61 – 7.53 (m, 4H), 6.98 (d, J = 1.7 Hz,
1H), 6.50 (d, J = 1.7 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 154.8, 138.9, 133.5, 132.3, 130.7,
128.4, 128.3, 127.4, 126.8, 126.2, 125.5, 125.0, 120.6, 99.1. Anal. Calcd for C14H10OS: C, 74.31; H,
4.45. Found: C, 74.30; H, 4.46.

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[2,2'-Bithiophen]-4(5H)-one (5l). Pale brown powder, m.p. 117-118 °C (from 50% aqueous EtOH);
yield 1.03 g (90%); 1H NMR (500 MHz, CDCl3) δ 7.63 – 7.50 (m, 2H), 7.19 – 7.09 (m, 1H), 6.41 (s,
13
1H), 3.82 (s, 2H). C NMR (126 MHz, CDCl3) δ 201.2, 169.8, 136.1, 130.9, 129.1, 128.4, 117.2,
40.5. Anal. Calcd for C8H6OS2: C, 52.72; H, 3.32. Found: C, 52.82; H, 3.24.
5'-Bromo-[2,2'-bithiophen]-4(5H)-one (5m). Compound 5m was prepared as follows: ester 4m
(480 mg, 1.5 mmol) was added to a mixture of CF3CO2H (4.5 ml) and MeSO3H (1.5 ml) at room
temperature. The resulting mixture was stirred and heated at 80 °C for 2 h, then it was poured into
water (50 ml) and neutralized by addition of NaHCO3 (6 g). The obtained suspension was treated
with CHCl3 (30 ml), intensively shacked and filtered to remove insoluble black gum. The CHCl3
layer was separated, washed with water (2×25 ml) and dried with Na2SO4. Solvent was evaporated
in vacuum to yield crude product 5m (yield 115 mg, about 29%) as greenish-black solid, which was
1
used in the next step without purification. H NMR (500 MHz, CDCl3) δ 7.30 (d, J = 4.0 Hz, 1H),
7.11 (d, J = 4.0 Hz, 1H), 6.33 (s, 1H), 3.80 (s, 2H).
5'-Phenyl-[2,2'-bithiophen]-4(5H)-one (5n). Brown powder, m.p. 127-128 °C (from 50% aqueous
EtOH); yield 245 mg (95%) was obtained from 4n (316 mg, 1 mmol); 1H NMR (400 MHz, CDCl3)
δ 7.66 – 7.61 (m, 2H), 7.53 (d, J = 4.0 Hz, 1H), 7.46 – 7.40 (m, 2H), 7.40 – 7.35 (m, 1H), 7.34 (d, J
= 4.0 Hz, 1H), 6.42 (s, 1H), 3.83 (s, 2H). 13C NMR (126 MHz, CDCl3) δ 201.1, 169.5, 150.3, 134.8,
132.9, 130.3, 129.1, 129.0, 126.1, 124.2, 116.7, 40.5. HRMS (ESI) m/z calcd for C14H11OS2
[M+H]+: 259.0246, found: 259.0248.
General procedure for synthesis of 2-(hetero)arylthieno[3,2-b]indoles (7a-n) from thiophen-
3(2H)-ones (5a-n) and phenylhydrazine (6a). Phenylhydrazine (0.15 ml, 1.5 mmol) was added to a
stirred solution of appropriate thiophen-3(2H)-one 5 (1 mmol) in AcOH (7 ml). The reaction
mixture was stirred and heated at 120 °C for 1 h, then it was cooled to room temperature and diluted
with MeOH (7 ml). The precipitate was filtered, washed with MeOH (3×4 ml) and dried at 120 °C
to afford product 7. Compounds 7a-n were obtained in analytically pure form without additional
purification.
2-Phenyl-4H-thieno[3,2-b]indole (7a). White plates, m.p. 320-321 °C (sub.); yield 145 mg (58%);
1H NMR (500 MHz, DMSO-d6) δ 11.48 (s, 1H), 7.76 (d, J = 7.4 Hz, 2H), 7.72 (d, J = 7.8 Hz, 1H),
7.65 (s, 1H), 7.51 – 7.41 (m, 3H), 7.32 (t, J = 7.4 Hz, 1H), 7.24 – 7.19 (m, 1H), 7.10 (t, J = 7.4 Hz,

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1H). 13C NMR (126 MHz, DMSO-d6) δ 144.3, 143.9, 140.9, 134.9, 129.1, 127.6, 125.1, 122.5,
121.2, 119.1, 118.3, 114.8, 112.3, 108.7. Anal. Calcd for C16H11NS: C, 77.07; H, 4.45; N, 5.62.
Found: C, 77.05; H, 4.34; N, 5.76.
2-(4-Fluorophenyl)-4H-thieno[3,2-b]indole (7b). Pink plates, m.p. 330-331 °C (sub.); yield 174
mg (65%); 1H NMR (500 MHz, DMSO-d6) δ 11.48 (s, 1H), 7.79 (dd, J = 8.7, 5.4 Hz, 2H), 7.71 (d, J
= 7.8 Hz, 1H), 7.62 (s, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.28 (t, J = 8.8 Hz, 2H), 7.21 (t, J = 7.3 Hz,
13
1H), 7.09 (t, J = 7.5 Hz, 1H). 19F NMR (471 MHz, DMSO-d6) δ 48.82 – 47.46 (m). C NMR (126
MHz, DMSO-d6) δ 161.6 (d, JCF = 245.1 Hz), 143.9, 143.1, 140.9, 131.5 (d, JCF = 3.1 Hz), 127.1 (d,
JCF = 8.0 Hz), 122.5, 121.2, 119.1, 118.27, 116.1 (d, JCF = 21.7 Hz), 114.7, 112.3, 108.9. Anal.
Calcd for C16H10FNS: C, 71.89; H, 3.77; N, 5.24. Found: C, 71.63; H, 3.60; N, 5.42.
2-(4-Bromophenyl)-4H-thieno[3,2-b]indole (7c). Beige powder, m.p. 339-340 °C (sub.); yield 200
1
mg (61%); H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 7.75 – 7.68 (m, 4H), 7.66 – 7.60 (m,
2H), 7.48 (d, J = 8.1 Hz, 1H), 7.25 – 7.20 (m, 1H), 7.13 – 7.07 (m, 1H). 13C NMR (126 MHz,
DMSO-d6) δ 143.9, 142.7, 141.0, 134.1, 132.0, 127.0, 122.7, 121.1, 120.3, 119.1, 118.4, 115.2,
112.3, 109.4. HRMS (APCI) m/z calcd for C16H11BrNS [M+H]+: 327.9790, found: 327.9789.
2-(4-Methoxyphenyl)-4H-thieno[3,2-b]indole (7d). Pale yellow crystals, m.p. 336-337 °C (sub.);
yield 196 mg (70%); 1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 7.68 (d, J = 8.8 Hz, 3H), 7.50
(s, 1H), 7.46 (d, J = 8.1 Hz, 1H), 7.22 – 7.15 (m, 1H), 7.12 – 7.05 (m, 1H), 7.04 – 6.99 (m, 2H), 3.80
13
(s, 3H). C NMR (126 MHz, DMSO-d6) δ 158.93, 144.5, 144.0, 140.7, 127.6, 126.5, 122.1, 121.3,
119.0, 118.0, 114.5, 113.8, 112.2, 107.5, 55.2. Anal. Calcd for C17H13NOS: C, 73.09; H, 4.69; N,
5.01. Found: C, 72.97; H, 4.79; N, 5.24.
2-[4-(Hexyloxy)phenyl]-4H-thieno[3,2-b]indole (7e). Beige plates, m.p. 318-319 °C; yield 245 mg
(70%); 1H NMR (500 MHz, DMSO-d6) δ 11.41 (s, 1H), 7.70 – 7.64 (m, 3H), 7.49 (s, 1H), 7.46 (d, J
= 8.1 Hz, 1H), 7.21 – 7.16 (m, 1H), 7.11 – 7.05 (m, 1H), 7.02 – 6.97 (m, 2H), 4.00 (t, J = 6.5 Hz,
13
2H), 1.77 – 1.69 (m, 2H), 1.47 – 1.39 (m, 2H), 1.36 – 1.28 (m, 4H), 0.89 (t, J = 7.1 Hz, 3H). C
NMR (126 MHz, DMSO-d6) δ 158.4, 144.5, 144.0, 140.7, 127.4, 126.5, 122.1, 121.3, 119.0, 118.0,
115.0, 113.8, 112.1, 107.4, 67.6, 31.0, 28.6, 25.2, 22.1, 13.9. Anal. Calcd for C22H23NOS: C, 75.61;
H, 6.63; N, 4.01. Found: C, 75.50; H, 6.71; N, 4.14.

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2-(3,4,5-Trimethoxyphenyl)-4H-thieno[3,2-b]indole (7f). Pink powder, m.p. 200-201 °C; yield
1
140 mg (41%); H NMR (500 MHz, DMSO-d6) δ 11.45 (s, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.65 (s,
1H), 7.48 (d, J = 8.2 Hz, 1H), 7.24 – 7.18 (m, 1H), 7.12 – 7.07 (m, 1H), 7.01 (s, 2H), 3.88 (s, 6H),
3.70 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 153.3, 144.5, 143.8, 140.9, 137.3, 130.7, 122.4,
121.3, 119.0, 118.2, 114.5, 112.2, 108.9, 102.8, 60.1, 56.0. Anal. Calcd for C19H17NO3S: C, 67.24;
H, 5.05; N, 4.13. Found: C, 67.14; H, 4.84; N, 4.10.
2-(2-Fluorophenyl)-4H-thieno[3,2-b]indole (7g). Pink powder, m.p. 206-207 °C; yield 142 mg
1
(53%); H NMR (500 MHz, DMSO-d6) δ 11.48 (s, 1H), 7.79 – 7.71 (m, 2H), 7.62 (d, J = 7.9 Hz,
1H), 7.56 (s, 1H), 7.51 (d, J = 8.2 Hz, 1H), 7.46 (t, J = 7.1 Hz, 1H), 7.40 (td, J = 7.7, 1.5 Hz, 1H),
19
7.24 (t, J = 7.6 Hz, 1H), 7.11 (t, J = 7.5 Hz, 1H). F NMR (471 MHz, DMSO-d6) δ 48.44 – 48.30
(m). 13C NMR (126 MHz, DMSO-d6) δ 158.2 (d, JCF = 248.4 Hz), 143.5, 141.1, 136.8 (d, JCF = 3.8
Hz), 129.1 (d, JCF = 8.5 Hz), 128.3 (d, JCF = 3.1 Hz), 125.2 (d, JCF = 3.0 Hz), 122.8, 122.4 (d, JCF
=
12.1 Hz), 121.0, 119.1 (s), 118.6, 116.5 (d, JCF = 22.3 Hz), 116.1 (d, JCF = 5.2 Hz), 112.3, 111.4 (d,
JCF = 6.5 Hz). HRMS (APCI) m/z calcd for C16H10FNS [M]+: 267.0512, found: 267.0513.
2-(2-Chlorophenyl)-4H-thieno[3,2-b]indole (7h). Beige powder, m.p. 159-160 °C; yield 160 mg
(56%); 1H NMR (500 MHz, DMSO-d6) δ 11.48 (s, 1H), 7.88 (t, J = 7.5 Hz, 1H), 7.76 (d, J = 7.9 Hz,
1H), 7.68 (s, 1H), 7.51 (d, J = 8.2 Hz, 1H), 7.40 – 7.28 (m, 3H), 7.26 – 7.22 (m, 1H), 7.11 (t, J = 7.4
Hz, 1H). 13C NMR (126 MHz, DMSO) δ 143.1, 140.9, 139.7, 133.2, 131.4, 130.9, 130.6, 129.2,
127.8, 122.8, 121.0, 119.0, 118.5, 116.4, 113.0, 112.3. HRMS (APCI) m/z calcd for C16H10ClNS
[M]+: 283.0217, found: 283.0216.
2-(2-Bromophenyl)-4H-thieno[3,2-b]indole (7i). Cream powder, m.p. 152-153 °C; yield 125 mg
1
(38%); H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 7.84 – 7.73 (m, 2H), 7.66 (dd, J = 7.7, 1.5
Hz, 1H), 7.56 – 7.45 (m, 3H), 7.33 (td, J = 7.8, 1.6 Hz, 1H), 7.28 – 7.20 (m, 1H), 7.11 (t, J = 7.2 Hz,
1H). 13C NMR (126 MHz, DMSO-d6) δ 143.0, 141.5, 140.8, 135.3, 133.7, 132.1, 129.7, 128.1,
122.7, 121.8, 121.0, 119.1, 118.5, 116.3, 113.1, 112.3. Anal. Calcd for C16H10BrNS: C, 58.55; H,
3.07; N, 4.27. Found: C, 58.35; H, 3.01; N, 4.23.
2-(2-Methoxyphenyl)-4H-thieno[3,2-b]indole (7j). White powder, m.p. 178-179 °C; yield 184 mg
(66%); 1H NMR (500 MHz, DMSO-d6) δ 11.36 (s, 1H), 7.80 (dd, J = 7.7, 1.6 Hz, 1H), 7.71 (d, J =
7.9 Hz, 1H), 7.68 (s, 1H), 7.47 (d, J = 8.1 Hz, 1H), 7.34 – 7.29 (m, 1H), 7.22 – 7.15 (m, 2H), 7.11 –

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7.03 (m, 2H), 3.96 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 155.3, 143.4, 141.0, 140.1, 128.5,
127.7, 123.3, 122.3, 121.3, 121.0, 118.9, 118.3, 116.0, 112.3, 112.1, 110.3, 55.7. Anal. Calcd for
C17H13NOS: C, 73.09; H, 4.69; N, 5.01. Found: C, 73.11; H, 4.80; N, 4.71. HRMS (ESI) m/z calcd
for C17H14NOS [M+H]+: 280.0791, found: 280.0786.
2-(Naphthalen-1-yl)-4H-thieno[3,2-b]indole (7k). Cream powder, m.p. 199-200 °C (sub.); yield
1
132 mg (44%); H NMR (500 MHz, DMSO-d6) δ 11.51 (s, 1H), 8.38 – 8.32 (m, 1H), 8.08 – 7.98
(m, 2H), 7.77 (d, J = 7.8 Hz, 1H), 7.70 (d, J = 7.0 Hz, 1H), 7.61 (dd, J = 10.6, 4.9 Hz, 3H), 7.54 (d,
J = 8.2 Hz, 1H), 7.45 (s, 1H), 7.25 (t, J = 7.6 Hz, 1H), 7.13 (t, J = 7.5 Hz, 1H). 13C NMR (126 MHz,
DMSO-d6) δ 143.5, 141.7, 140.7, 133.6, 132.7, 130.9, 128.5, 128.1, 126.9, 126.3, 125.5, 125.1,
122.5, 121.2, 119.0, 118.4, 115.7, 112.9, 112.3. Anal. Calcd for C20H13NS: C, 80.23; H, 4.38; N,
4.68. Found: C, 80.37; H, 4.34; N, 4.93.
2-(Thiophen-2-yl)-4H-thieno[3,2-b]indole (7l). Beige crystals, m.p. 275-276 °C (sub.); yield 185
mg (72%); 1H NMR (500 MHz, DMSO-d6) δ 11.46 (s, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 5.1
Hz, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.44 – 7.38 (m, 2H), 7.21 (t, J = 7.6 Hz, 1H), 7.16 – 7.06 (m, 2H).
13C NMR (126 MHz, DMSO-d6) δ 143.4, 140.9, 137.9, 137.3, 128.4, 125.3, 123.7, 122.5, 121.1,
119.1, 118.3, 114.3, 112.3, 108.8. Anal. Calcd for C14H9NS2: C, 65.85; H, 3.55; N, 5.49. Found: C,
65.91; H, 3.45; N, 5.55.
2-(5-Bromothiophen-2-yl)-4H-thieno[3,2-b]indole (7m). Brown crystals, m.p. 219-220 °C (dec.);
1
yield 82 mg (61%) was obtained from 5m (105 mg, 0.4 mmol); H NMR (400 MHz, DMSO-d6) δ
11.50 (s, 1H), 7.71 (d, J = 7.9 Hz, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.43 (s, 1H), 7.27 – 7.20 (m, 3H),
7.09 (t, J = 7.5 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 143.3, 141.1, 139.6, 135.8, 131.6, 124.2,
122.8, 121.0, 119.2, 118.4, 114.7, 112.3, 109.9, 109.4. HRMS (APCI) m/z calcd for C14H8BrNS2
[M]+: 332.9276, found: 332.9277.
2-(5-Phenylthiophen-2-yl)-4H-thieno[3,2-b]indole (7n). Dark-yellow crystals, m.p. 318-319 °C
(sub.); yield 88 mg (66%) was obtained from 5n (103 mg, 0.4 mmol); 1H NMR (400 MHz, DMSO-
d6) δ 11.50 (s, 1H), 7.71 (t, J = 8.1 Hz, 3H), 7.54 (d, J = 3.8 Hz, 1H), 7.51 – 7.40 (m, 5H), 7.36 –
13
7.30 (m, 1H), 7.24 – 7.19 (m, 1H), 7.13 – 7.07 (m, 1H). C NMR (126 MHz, DMSO-d6) δ 143.5,
141.9, 141.0, 137.2, 137.0, 133.2, 129.2, 127.8, 125.1, 124.8, 122.6, 121.1, 119.2, 118.3, 114.5,

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112.3, 108.8. Anal. Calcd for C20H13NS2: C, 72.48; H, 3.95; N, 4.23. Found: C, 72.28; H, 3.86; N,
4.54.
General procedure for synthesis of 2-(hetero)arylthieno[3,2-b]indoles (7o-x) from thiophen-
3(2H)-ones (5a,l) and arylhydrazines hydrochlorides (6b-f). Anhydrous NaOAc (120 mg, 1.5
mmol) and appropriate arylhydrazine hydrochloride 6 (1.5 mmol) were added to a stirred solution of
thiophen-3(2H)-one 5a (176 mg, 1 mmol) or 5b (182 mg, 1 mmol) in AcOH (7 ml). The reaction
mixture was stirred and heated at 120 °C for 1 h, then it was cooled to room temperature and the
formed precipitate was filtered, washed with warm water (10 ml), MeOH (3×4 ml) and dried at 120
°C to afford product 7. Compounds 7o-x were obtained in analytically pure form without additional
purification.
7-Bromo-2-phenyl-4H-thieno[3,2-b]indole (7o). White crystals, m.p. 276-277 °C (sub.); yield 197
mg (60%); 1H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 7.98 (d, J = 1.6 Hz, 1H), 7.76 (d, J = 7.9
13
Hz, 2H), 7.66 (s, 1H), 7.46 (t, J = 7.9 Hz, 3H), 7.37 – 7.29 (m, 2H). C NMR (126 MHz, DMSO-
d6) δ 145.7, 145.0, 139.6, 134.6, 129.1, 127.8, 125.3, 124.8, 122.9, 120.6, 114.1, 114.0, 111.3,
108.6. Anal. Calcd for C16H10BrNS: C, 58.55; H, 3.07; N, 4.27. Found: C, 58.39; H, 2.92; N, 4.42.
7-Methyl-2-phenyl-4H-thieno[3,2-b]indole (7p). Beige powder, m.p. 273-274 °C (sub.); yield 140
1
mg (53%); H NMR (400 MHz, DMSO-d6) δ 11.33 (s, 1H), 7.75 (dd, J = 8.3, 0.9 Hz, 2H), 7.62 (s,
1H), 7.49 (s, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.36 (d, J = 8.3 Hz, 1H), 7.31 (t, J = 7.4 Hz, 1H), 7.03
(dd, J = 8.3, 1.0 Hz, 1H), 2.42 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 144.1, 144.0, 139.2,
134.9, 129.1, 127.7, 127.5, 125.1, 123.9, 121.4, 118.0, 114.4, 112.0, 108.7, 21.1. Anal. Calcd for
C17H13NS: C, 77.53; H, 4.98; N, 5.32. Found: C, 77.43; H, 4.88; N, 5.40.
2-Phenyl-4H-thieno[3,2-b]indole-7-carbonitrile (7q). Beige powder, m.p. 265-266 °C; yield 82
mg (30%); 1H NMR (400 MHz, DMSO-d6) δ 12.11 (s, 1H), 8.36 (d, J = 0.7 Hz, 1H), 7.79 (d, J = 7.6
Hz, 2H), 7.72 (s, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.57 (dd, J = 8.5, 1.6 Hz, 1H), 7.47 (t, J = 7.7 Hz,
13
2H), 7.36 (t, J = 7.4 Hz, 1H). C NMR (126 MHz, DMSO-d6) δ 146.7, 145.5, 142.7, 134.4, 129.2,
128.1, 125.4, 125.2, 123.7, 121.1, 120.5, 114.92, 113.2, 108.7, 100.9. Anal. Calcd for C17H10N2S: C,
74.43; H, 3.67; N, 10.21. Found: C, 74.42; H, 3.65; N, 10.19.

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2-Phenyl-4H-thieno[3,2-b]indole-7-carboxylic acid (7r). White powder, m.p. 334-335 °C; yield
1
117 mg (40%); H NMR (400 MHz, DMSO-d6) δ 12.56 (s, 1H), 11.90 (s, 1H), 8.39 (d, J = 0.5 Hz,
1H), 7.84 (dd, J = 8.6, 1.5 Hz, 1H), 7.78 (d, J = 7.4 Hz, 2H), 7.70 (s, 1H), 7.54 (d, J = 8.6 Hz, 1H),
13
7.46 (t, J = 7.7 Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H). C NMR (126 MHz, DMSO-d6) δ 168.0, 145.5,
145.0, 143.5, 134.6, 129.2, 127.8, 125.3, 123.7, 121.5, 120.8, 120.6, 115.5, 111.9, 108.8. Anal.
Calcd for C17H11NO2S: C, 69.61; H, 3.78; N, 4.78. Found: C, 69.76; H, 3.85; N, 4.89.
8-Phenyl-10H-benzo[g]thieno[3,2-b]indole (7s). Pale yellow powder, m.p. 308-309 °C (sub.);
yield 200 mg (67%); 1H NMR (400 MHz, DMSO-d6) δ 12.48 (s, 1H), 8.47 (d, J = 8.2 Hz, 1H), 7.98
(d, J = 8.0 Hz, 1H), 7.86 (d, J = 8.6 Hz, 1H), 7.80 (d, J = 7.8 Hz, 2H), 7.75 (s, 1H), 7.63 – 7.56 (m,
2H), 7.51 – 7.43 (m, 3H), 7.33 (t, J = 7.4 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 143.4, 142. 6,
135.5, 135.0, 130.1, 129.1, 128.5, 127.4, 125.6, 125.1, 124.2, 122.3, 121.1, 119.9, 118.6, 116.8,
116.6, 108.7. Anal. Calcd for C20H13NS: C, 80.24; H, 4.38; N, 4.68. Found: C, 80.39; H, 4.52; N,
4.45. HRMS (ESI) m/z calcd for C20H14NS [M+H]+: 300.0841, found: 300.0838.
7-Bromo-2-(thiophen-2-yl)-4H-thieno[3,2-b]indole (7t). Beige crystals, m.p. 259-260 °C (sub.);
yield 127 mg (38%); 1H NMR (500 MHz, DMSO-d6) δ 11.65 (s, 1H), 7.97 (d, J = 1.9 Hz, 1H), 7.55
(dd, J = 5.1, 1.0 Hz, 1H), 7.46 – 7.41 (m, 3H), 7.31 (dd, J = 8.7, 2.0 Hz, 1H), 7.13 (dd, J = 5.1, 3.6
13
Hz, 1H). C NMR (126 MHz, DMSO-d6) δ 144.5, 139.6, 138.7, 137.6, 128.4, 125.6, 124.8, 124.1,
122.8, 120.6, 114.1, 113.5, 111.4, 108.6. Anal. Calcd for C14H8BrNS2: C, 50.31; H, 2.41; N, 4.19;
Found: C, 50.38; H, 2.44; N, 4.26.
7-Methyl-2-(thiophen-2-yl)-4H-thieno[3,2-b]indole (7u). Beige powder, m.p. 243-244 °C (sub.);
yield 140 mg (52%); 1H NMR (500 MHz, DMSO-d6) δ 11.30 (s, 1H), 7.52 (dd, J = 5.1, 1.0 Hz, 1H),
7.47 (s, 1H), 7.39 – 7.34 (m, 3H), 7.11 (dd, J = 5.1, 3.6 Hz, 1H), 7.03 (dd, J = 8.3, 1.3 Hz, 1H), 2.41
13
(s, 3H). C NMR (126 MHz, DMSO-d6) δ 143.5, 139.3, 137.9, 137.1, 128.3, 127.8, 125.1, 124.0,
123.6, 121.3, 117.9, 113.9, 112.0, 108.8, 21.1. HRMS (ESI) m/z calcd for C15H12NS2 [M+H]+:
270.0406, found: 270.0404.
2-(Thiophen-2-yl)-4H-thieno[3,2-b]indole-7-carbonitrile (7v). Brown powder, m.p. 233-234 °C
1
(dec.); yield 121 mg (43%); H NMR (500 MHz, DMSO-d6) δ 12.08 (s, 1H), 8.34 (d, J = 0.6 Hz,
1H), 7.63 (d, J = 8.5 Hz, 1H), 7.57 (ddd, J = 10.1, 6.8, 1.2 Hz, 2H), 7.49 (s, 1H), 7.46 (dd, J = 3.5,
0.9 Hz, 1H), 7.15 (dd, J = 5.0, 3.7 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 145.0, 142.7, 139.7,

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137.3, 128.5, 126.0, 125.2, 124.4, 123.6, 121.0, 120.5, 114.4, 113.3, 108.7, 101.0. HRMS (ESI) m/z
calcd for C15H9N2S2 [M+H]+: 281.0202, found: 281.0199.
2-(Thiophen-2-yl)-4H-thieno[3,2-b]indole-7-carboxylic acid (7w). Greenish powder, m.p. 313-
1
314 °C; yield 51 mg (17%); H NMR (500 MHz, DMSO-d6) δ 12.55 (s, 1H), 11.86 (s, 1H), 8.41 –
8.34 (m, 1H), 7.83 (dd, J = 8.6, 1.6 Hz, 1H), 7.58 – 7.51 (m, 2H), 7.46 (s, 1H), 7.44 (dd, J = 3.6, 1.1
Hz, 1H), 7.14 (dd, J = 5.1, 3.6 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 168.0, 144.5, 143.5,
138.5, 137.6, 128.4, 125.6, 124.1, 123.7, 121.6, 120.7, 120.6, 115.1, 111.9, 108.8. Anal. Calcd for
C15H9NO2S2: C, 60.18; H, 3.03; N, 4.68. Found: C, 59.91; H, 3.07; N, 4.48.
8-(Thiophen-2-yl)-10H-benzo[g]thieno[3,2-b]indole (7x). Cream powder, m.p. 256-257 °C (sub.);
yield 189 mg (62%); 1H NMR (500 MHz, DMSO-d6) δ 12.45 (s, 1H), 8.44 (d, J = 8.2 Hz, 1H), 7.98
(d, J = 8.1 Hz, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.62 – 7.56 (m, 2H), 7.53 (dd, J = 5.1, 1.0 Hz, 1H),
7.51 (s, 1H), 7.49 – 7.45 (m, 1H), 7.43 (dd, J = 3.6, 1.0 Hz, 1H), 7.14 (dd, J = 5.0, 3.6 Hz, 1H). 13C
NMR (126 MHz, DMSO-d6) δ 142.0, 138.0, 136.5, 135.5, 130.1, 128.6, 128.3, 125.6, 125.1, 124.3,
123.7, 122.3, 121.0, 120.0, 118.6, 116.7, 116.2, 108.7. HRMS (ESI) m/z calcd for C18H12NS2
[M+H]+: 306.0406, found: 306.0402.
General procedure for synthesis of 5,5'-bis(3-hydroxythiophene-2-carboxylate) compounds
(9a,b). A mixture of bis(2-bromoacrylate) 8a (6.48 g, 15 mmol) or 8b (6.57 g, 15 mmol) and methyl
thioglycolate (5.5 ml, 60 mmol) in dry MeOH (35 ml) was added dropwise to a solution of NaOMe,
prepared from sodium (2.8 g, 122 mmol) and dry MeOH (35 ml), at 0 °C during 20 min with
continuous stirring and the formed suspension was stirred and heated at reflux for 8 h. The reaction
mixture was poured into ice-cold water (70 ml) and acidified with conc. HCl (8 ml). The formed
precipitate was filtered, washed with water (3×10 ml), MeOH (10 ml), dried at room temperature
and purified by crystallization from a mixture of MeOH and DMF (15 ml, v/v 1:14) to yield
analytically pure product 9a or 9b, respectively.
Dimethyl 5,5'-(1,4-phenylene)bis(3-hydroxythiophene-2-carboxylate) (9a). Brownish needles,
1
m.p. 287-288 °C; yield 1.93 g (33%); H NMR (500 MHz, DMSO-d6) δ 10.46 (s, 2H), 7.77 (s, 4H),
7.26 (s, 2H), 3.79 (s, 6H). 13C NMR (101 MHz, DMSO-d6) δ 162.9, 161.5, 146.0, 133.1, 126.2,
117.2, 104.6, 51.5. Anal. Calcd for C18H14O6S2: C, 55.38; H, 3.61. Found: C, 55.27; H, 3.88.

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Dimethyl 4,4''-dihydroxy-[2,2':5',2''-terthiophene]-5,5''-dicarboxylate (9b). Brownish fleecy
crystals, m.p. 231-232 °C; yield 1.02 g (17%); 1H NMR (500 MHz, DMSO-d6) δ 10.61 (s, 2H), 7.51
13
(s, 2H), 7.03 (s, 2H), 3.77 (s, 6H). C NMR (101 MHz, DMSO-d6) δ 162.6, 161.1, 139.2, 136.1,
127.1, 117.1, 104.1, 51.5. Anal. Calcd for C16H12O6S3: C, 48.47; H, 3.05. Found: C, 48.36; H, 2.95.
General procedure for synthesis of 5,5'-bis(thiophen-3(2H)-one) compounds (10a,b). NaOH
(1.2 g, 30 mmol) in water (5 ml) was added in one portion to diester 9a (391 mg, 1 mmol) or 9b
(400 mg, 1 mmol) in DMSO (10 ml), the obtained solution was flushed with argon, then it was
stirred and heated at 140 °C for 1.5 h under an argon atmosphere. The reaction mixture was cooled
to room temperature and poured into water (20 ml) with conc. HCl (2.6 ml). The precipitate was
filtered, washed with water (4×5 ml) and dried at room temperature. The obtained solid was
extracted with hot EtOAc (5×15 ml), every time at triturating and heating. The EtOAc extract was
eluted through a short silica gel plug (1 cm×4 cm) with hot EtOAc (15 ml). The filtrate was
concentrated under reduced pressure to afford analytically pure product 10a or 10b, respectively.
5,5'-(1,4-Phenylene)bis(thiophen-3(2H)-one) (10a). Brownish powder, m.p. 256-257 °C (dec.);
1
yield 212 mg (77%); for enol form: H NMR (500 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.59 (s, 2H),
7.09 (d, J = 1.6 Hz, 1H), 6.29 (d, J = 1.6 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 155.6, 140.4,
133.0,
[2,2':5',2''-Terthiophene]-4,4''(5H,5''H)-dione (10b). Brownish powder, m.p. 196-197 °C (dec.);
1
yield 243 mg (86%); for enol form: H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 7.18 (s, 1H),
6.88 (d, J = 1.6 Hz, 1H), 6.26 (d, J = 1.6 Hz, 1H). 13C NMR (126 MHz, DMSO-d6) δ 155.2, 135.6,
133.9, 124.2, 116.7, 98.1. HRMS (ESI) m/z calcd for C12H9O2S3 [M+H]+: 280.9759, found:
280.9761.
General procedure for synthesis of thieno[3,2-b]indole twin derivatives (11a,b). Bis(thiophen-
3(2H)-one) 10a (137 mg, 0.5 mmol) or 10b (140 mg, 0.5 mmol) was dissolved in AcOH (10 ml) and
phenylhydrazine (0.15 ml, 1.5 mmol) was added to this solution. The reaction mixture was stirred
and heated at 120 °C for 2 h, then it was cooled to room temperature and the formed precipitate was
filtered, washed with MeOH (3×4 ml) and dried at 120 °C. This crude substance was purified by
sublimation at 280 °C in vacuum (3 mbar) to afford analytically pure product 11a or 11b,
respectively.

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DOI: 10.1039/C8OB01110A
1,4-Bis(4H-thieno[3,2-b]indol-2-yl)benzene (11a). Pale yellow powder, m.p. ˃360 °C; yield 172
1
mg (82%); H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 2H), 7.82 (s, 4H), 7.73 (d, J = 7.8 Hz, 2H),
7.68 (s, 2H), 7.50 (d, J = 8.1 Hz, 2H), 7.26 – 7.20 (m, 2H), 7.16 – 7.09 (m, 2H). Anal. Calcd for
C26H16N2S2: C, 74.26; H, 3.83; N, 6.66. Found: C, 74.57; H, 3.91; N, 6.56.
2,5-Bis(4H-thieno[3,2-b]indol-2-yl)thiophene (11b). Orange microcrystals, m.p. ˃360 °C; yield
190 mg (89%); 1H NMR (400 MHz, DMSO-d6) δ 11.39 (s, 2H), 7.72 (d, J = 7.8 Hz, 2H), 7.50 (d, J
= 8.1 Hz, 2H), 7.45 (s, 2H), 7.39 (s, 2H), 7.27 – 7.19 (m, 2H), 7.15 – 7.07 (m, 2H). Anal. Calcd for
C24H14N2S3: C, 67.58; H, 3.31; N, 6.57. Found: C, 67.52; H, 3.25; N, 6.44.
Conflicts of interest
There are no conflicts to declare
Acknowledgments
This work was supported by the Scientific Council of the President of the Russian Federation (grant
no. МК-1460.2018.3).
Supporting Information
Electronic supplementary information (ESI) available: Procedures for preparation of starting
materials 3a-m and 8a,b, copies of 1H, 19F and 13C NMR spectra of new compounds (PDF).
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