Multifaceted strategy for the synthesis of diverse 2,2′-bithiophene derivatives

Article abstract of DOI:10.3390/molecules20034565

New catalytically or high pressure activated reactions and routes, including coupling, double bond migration in allylic systems, and various types of cycloaddition and dihydroamination have been used for the synthesis of novel bithiophene derivatives. Tha

Full text of DOI:10.3390/molecules20034565

Molecules 2015, 20, 4565-4593; doi:10.3390/molecules20034565
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Multifaceted Strategy for the Synthesis of Diverse
,2'-Bithiophene Derivatives
2
1,
1
1
1
1
Stanisław Krompiec *, Michał Filapek , Iwona Grudzka-Flak , Aneta Slodek , Sławomir Kula ,
1
1
1
1
Jan Grzegorz Malecki , Joanna Malarz , Grażyna Szafraniec-Gorol , Mateusz Penkala ,
1
2
2
1
1
Ewa Schab-Balcerzak , Marian Paluch , Michał Mierzwa , Marek Matussek , Agata Szlapa ,
1
1
1
3
4
Michał Pajak , Dariusz Blach , Beata Marcol , Witold Danikiewicz , Bartosz Boharewicz ,
and Agnieszka Iwan 4
1
Institute of Chemistry, Faculty of Mathematics, Physics and Chemistry, University of Silesia,
Szkolna 9, Katowice 40-007, Poland; E-Mails: filus.lc@interia.pl (M.F.);
iwonagrudzka@gmail.com (I.G.-F.); a.slodek@wp.pl (A.S.); kula.slawek@gmail.com (S.K.);
gmalecki@us.edu.pl (J.G.M.); joanna.malarz@gmail.com (J.M.); grazyna.szafraniec@wp.pl (G.S.-G.);
mateusz.penkala@us.edu.pl (M.P.); ewa.schab-balcerzak@us.edu.pl (E.S.-B.);
marmat89@interia.pl (M.M.); agataszlapa@o2.pl (A.S.); spider1989@gmail.com (M.P.);
dariusz2lo@o2.pl (D.B.); beata_marcol@wp.pl (B.M.)
2
Institute of Physics, Faculty of Mathematics, Physics and Chemistry, University of Silesia,
Uniwersytecka 4, Katowice 40-007, Poland; E-Mails: marian.paluch@us.edu.pl (M.P.);
michal.mierzwa@us.edu.pl (M.M.)
3
Polish Academy of Science, Institute of Organic Chemistry Kasprzaka 44/52, PO Box 58,
Warsaw 01-224, Poland; E-Mail: witold.danikiewicz@icho.edu.pl
4
Electrotechnical Institute, Division of Electrotechnology and Materials Science,
M. Skłodowskiej-Curie 55/61, Wrocław 50-369, Poland; E-Mails: b.boharewicz@iel.wroc.pl (B.B.);
a.iwan@iel.wroc.pl (A.I.)
*
Author to whom correspondence should be addressed; E-Mail: stanislaw.krompiec@us.edu.pl;
Tel.: +48-32-359-1646; Fax: +48-32-259-9978.
Academic Editor: Derek J. McPhee
Received: 13 January 2015 / Accepted: 26 February 2015 / Published: 12 March 2015
Abstract: New catalytically or high pressure activated reactions and routes, including
coupling, double bond migration in allylic systems, and various types of cycloaddition and
dihydroamination have been used for the synthesis of novel bithiophene derivatives.
Thanks to the abovementioned reactions and routes combined with non-catalytic ones, new

Molecules 2015, 20
acetylene, butadiyne, isoxazole, 1,2,3-triazole, pyrrole, benzene, and fluoranthene
4566
derivatives with one, two or six bithiophenyl moieties have been obtained. Basic sources of
crucial substrates which include bithiophene motif for catalytic reactions were
2
,2'-bithiophene, gaseous acetylene and 1,3-butadiyne.
Keywords: bithiophene derivatives; coupling; cycloaddition; high pressure; homogeneous
catalysis; isomerization; PTC
1
. Introduction
Compounds containing thiophene, bithiophene or oligothiophene motifs are particularly popular
because they are used in various fields of science and technology, ranging from organic chemistry and
synthesis to material science, technology, medicine and pharmaceutical science. Therefore, new
structures containing the abovementioned motifs are still being synthesized and the possibilities of
their practical application intensively tested. Various organic and organometallic systems containing
thiophene, bithiophene or oligothiophene moieties (and other essential structural elements, i.e., highly
conjugated aromatic and heteroaromatic systems, coordinated metal centers, diimide or triphenylamine
moiety and others) are used in organic electronics [1–4] and are still intensively investigated in
OLED [1–4], organic field-effect transistor [1,5] and solar cell [1,6,7] technology.
As far as examples of application in medicine and pharmaceutical science are concerned,
5
-(4-hydroxyphenyl)-5'-dicyanoethenyl-2,2'-bithiophene was tested as a marker of cell lesions in
Alzheimer’s disease [8]. Moreover, 5'-mercapto-2,2'-bithiophene-5-carboxylic acid was tested as a
potential biosensor detecting antigen-antibody connection [9], and a series of 5-(E)-styryl-2,2'-
bithiophenes were tested as potential β-amyloid probes [10]. The starting substances for the synthesis
of these compounds are simple derivatives of thiophene, bithiophene or oligothiophene substituted by
Li, Br, I, C≡CH, MgCl, SnBu
of their structures. The bithiophene derivatives, such as bromo- [11,12] and iodobithiophene [13–15],
-trialkylstannyl-2,2'-bithiophene [16], 5-ethynyl-2,2'-bithiophene [17], 2,2'-bithiophene-5-boronic
3
, B(OH)
2
, B(OR)
2
, or ZnCl, which facilitate the chemical modification
5
acid and its esters [12], and (2,2'-bithiophen-5-yl)magnesium bromide, are frequently used [18]. The
abovementioned thiophene derivatives were obtained in the catalytic processes, mostly with the aid of
transition metal catalysts.
However, in many cases such catalytic systems are inactive due to strong coordination of the
substrate by a transition metal catalytic center [19]. This fact ought to be taken into consideration when
planning catalytic systems to be used for transformations of strongly coordinated reagents, for instance
thiophene or oligothiophene [19]. There are a number of stable neutral and cationic transition metal
(Cr, Ru, Ir, Rh, Mn, Re, Ti, Cu, Fe etc.) complexes with thiophene. The issue of transition metal
complexation with thiophene and oligothiophenes has been intensively studied in view of the
hydrodesulfurization (HDS) process [20]. Thiophene coordinates transition metals in many ways, but
1
1
5
the most common are the η -S, η -C, and η - coordination modes [21,22], and furthermore, it forms
neutral complexes with Re and Mn, involving C-, S- and π-coordinated ligands [23]. Moreover, it
5
forms stable cationic complexes, e.g., [Mn(CO)
3
(η -thiophene)][BF
4
], which precursor is [Mn(CO) Br].
5

Molecules 2015, 20
4567
5
In addition, exchange of CO-ligand to η -thiophene in the reaction of [Cr(CO)
6
] with various
5
thiophene derivatives [Cr(CO)
RuCl (p-cymene)]
3
(η -substituted-thiophenes)] took place [24]. Furthermore, reaction of
[
2
2
with tetramethylthiophene resulted in a very stable [(tetramethyl-thiophene)RuCl
]
2 2
complex, indicating that thiophene coordinates a Ru atom stronger than p-cymene [25]. The above
analysis indicates that strong coordination of a transition metal with thiophene and oligothiophene may
interfere with some reactions involving substrates containing a thiophene moiety.
The synthesis of pyridine [26], bipyridine, terpyridine [27], carbazole [28] and benzene [29]
derivatives containing 2-thienyl, 3,4-methylenedioxothien-2-yl and/or 2,2'-bithiophen-5-yl moieties in
Stille cross-coupling reactions has been recently reported. Herein, we present a novel strategy for the
synthesis of many bithiophene derivatives via new catalytically or high pressure activated reactions
and catalytic routes combined with non-catalytic ones (Scheme 1).
2
2 R = C H
8 17
2
2
3 R = Bz
4 R = C10H21
7
R=CH3
R 8 R=Ph
2
1
2
5
2
2 - 24
bt
CO
Et
2
bt
[MnBr(CO)5]
N
21 10
H C
N
bt
bt
N
N
bt
bt
bt
N
N
bt
bt
bt
R
bt
bt
[
[
Cu]
or
Ru]
4
[
Ru]
[PdCl (PPh ) ]
2
3
2
[
RhCl(PPh ) ]
3
3
or hp
[
PdCl (PPh ) ]
[PdCl (PPh ) ]
2 3 2
2
3 2
bt
bt
bt
I
bt
bt
5
3
6
[
RhCl(PPh ) ]
[RhCl(PPh ) ]
3 3
3
3
I2
CuCl
n-BuLi
bt
bt
bt
S
S
(
bt-Li)
bt
bt
Ph
Ph
Ph
(
bt-H)
1
N
bt
2
Ar
Ph
Br- allyl
2
6 -28
Ar = Ph
Ar = -(n-C10H21O)C H
2
2
2
6
7
8
p
6
4
Ar = N-ethylcarbazo-3-yl
1
9
bt
9
[
RuClH(CO)(PPh ) ]
3 3
20
N
N
Ar
Ar
O
DDQ
ArCNO, T,hp
O
bt
bt
Me
bt
Me
Me
1
0
1
1 - 15
Ar = 2,6-Cl C H
3
16 - 18
16 Ar = 2,6-Cl C H
3
1
1
2
6
2
6
1
1
1
1
2
3
4
5
Ar = 4-Me NC H
4
Ar = 2-py
Ar = p-ONC-C6H4-CNO
Ar = bt
17 Ar = 2,2'-bitiophene-5-yl
18 Ar = p-ONC-C H -CNO
2
6
6
4
Scheme 1. Synthetic pathways to various 2,2'-bithiophene derivatives from
,2'-bithiophene (bt-H). Compounds marked as 7, 8, 10–28 are new.
2

Molecules 2015, 20
4568
The substrates containing a bithiophene motif were prepared from commercially available
,2'-bithiophene, which during the first stage was lithiated according to the procedure developed by us
2
(
Scheme 1). Next, the 5-lithio-2,2'-bithiophene (“the first generation” substrate) was converted into
-iodo- and 5-allyl-2,2'-bithiophenes and in situ into 5-azido-2,2'-bithiophene (“the second generation”
substrates). In the subsequent step, the abovementioned compounds were catalytically transformed into
-ethynyl-2,2'-bithiophene, 1,2-bis(2,2'-bithiophene-5-yl)acetylene, 5-(1-propenyl)-2,2'-bithiophene,
5
5
and 1,4-bis(2,2'-bithiophene-5-yl)buta-1,3-diyne (“the third generation” substrates).
It is worth noting that the reactions leading to new 2,2'-bithiophene derivatives have not been
reported so far (or are significantly improved). Since our work is a multifaceted one, i.e., it concerns a
series of different reactions, relevant literature is presented in each subsection.
2
. Results and Discussion
2
.1. Synthesis of Substrates (for Catalytic Reactions) Containing 2,2'-Bithiophene Moiety from
,2'-Bithiophene
2
The initial step for the strategy presented in Scheme 1 was selective synthesis of 5-lithio-2,2'-
bithiophene (2). Compound 2 was then used for a direct or multi-step preparation of the following
compounds: 5-iodobithiophene (3), 5-ethynyl-2,2'-bithiophene (4), 1,2-bis(2,2'-bithiophen-5-yl)ethyne (5),
and 1,4-bis(2,2'-bithiophen-5-yl)-1,3-butadiyne (6), 5-allyl-2,2'-bithiophene (9), 5-(1-propenyl)-2,2'-
bithiophene (10) The selective synthesis of 2 via reaction of 2,2'-bithiophene with n-BuLi, and then
synthesis of 3 and 4 was reported in detail in our previous paper [29] and patents [30,31]. Despite the
fact that the synthesis of 5-iodo-2,2'-bithiophene (3) was highly selective and less than 0.5% of
5
,5'-diiodo-2,2'-bithiophene was obtained, it was possible to obtain monocrystals of 5,5'-diiodo-2,2'-
bithiophene which structure was determined by X-ray diffraction (Supplementary Table S3 in
Supporting Information). From the practical point of view, it is very important that any bithiophene
lithiation product used for the synthesis of 3, 4, 5, 6, 9 and 10, contains 80% of 2, less than 0.5% of
dilithiobithiophene, and ~19.5% unreacted bithiophene. Low concentration of the dilithioderivative
was crucial for the selectivity and yields of subsequent reactions, including the catalytic ones. In
particular, thanks to the abovementioned selectivity, the formation of polymeric products was not
observed in practice. Additionally, unreacted bithiophene turned out to be inert, did not disturb
catalytic reactions, and was finally recovered in the pure product separation procedure.
Compounds 5 and 6 were synthesized from gaseous acetylene or gaseous butadiyne using
new methods (Scheme 2) [14,15]. Previously, ArC≡CAr type compounds, including 1,2-bis(2-thienyl)-
acetylene, were obtained [32] using acetylene generated in situ from CaC
2
and H O in MeCN [11].
2
Compound 5 was previously obtained via three-step synthesis from iodobithiophene (coupling of 3
with TMS, distillation to 4 and finally coupling 3 with 4) [33]. Compound 6 was synthesized via
homocoupling of 4 in the presence of CuCl/TMEDA [34]. Additionally, various ArC≡CC≡CAr type
compounds (but not 6) were synthesized from ArI via Sonogashira-Glaser coupling [35]. On the other
hand, the synthesis of compounds ArC≡CC≡CAr type from gaseous butadiyne is unknown.
The strategy of synthesis of some bithiophene-motif containing substrates from gaseous acetylene
or gaseous butadiyne corresponds well with observed butadiyne rebirth in chemical technology [36]. It

Molecules 2015, 20
4569
is well known that butadiyne is created as a side product of acetylene production [36]. Due to this fact,
the application of the both gaseous reagents in our strategy, instead of protected forms of these
compounds, is rational and modern. Additionally, commercially available trimethylsilylacetylene used
by us for the synthesis of 5-ethynyl-2,2'-bithiophene was also prepared from acetylene [37].
H
H
acetone, NEt
3
S
S
[
PdCl (PPh ) ], CuI, 24h, rt
2
3 2
S
S
5
S
I
S
3
[
PdCl (PPh ) ], CuI, 24h, rt
2 3 2
S
S
I2
H
H
acetone, NEt3
6
S
S
S
Li
S
2
Scheme 2. Synthesis of 5-iodo-2,2'-bithiophene (3), 1,2-bis(2,2'-bithiophen-5-yl)ethyne
5), and 1,4-bis(2,2'-bithiophen-5-yl)-1,3-butadiyne (6). The generation of buta-1,3-diyne
(
has been previously described [11].
In order to improve the yield of 5 and 6 we applied a cascade consisting of three reactors. The
reactions were carried out in acetone due to a high solubility of acetylene and butadiyne therein. Other
authors have used MeCN as solvent [32], but MeCN appears to be a much worse solvent (the solubility
of acetylene therein is much lower), and in addition it is toxic. Gaseous acetylene (generated from
CaC
2
[34] or more conveniently supplied from a bottle gas) and butadiyne (generated from
1
,4-dichloro-2-butyne) were dried before the introduction into the reaction system and additionally
dispersed with a stream of argon. It is of particular importance in the case of butadiyne for safety
reasons (high concentrated butadiyne is explosive). Moreover, in the procedure leading to 5
[PdCl
2
(PPh
3
)
2
] was applied, which was much more effective than Pd(OAc)
2
+ PPh catalytic system
3
used by Chuentragool et al. in the synthesis of 1,2-bis(2-thienyl)acetylene [32]. Compound 6 was
obtained as yellow crystals and its structure was confirmed using X-ray crystallography (Table 2 in
Supporting Information). The [PdCl
2
(PPh
3
)
2
]/CuI catalytic system appeared to be more effective and
] used by McCormick et al., in the synthesis
convenient (due to its stability and price) than [Pd(PPh
)
3 4
of different ArC≡CC≡CAr from 1,4-bis(trimethylsilyl)-1,3-butadiyne [38].
Additionally, a new method of preparation of 6 via homocoupling of 5-ethynyl-2,2'-bithiophene (4)
in the presence of ethyl iodide, catalyzed by CuI/[PdCl
2
(PPh
3
2
) ] was developed (Scheme 3). This
method turned out to be very simple and effective (isolated yield was 97%).
It was found that the absence of alkyl iodide or bromide resulted in extremely low yield
(
approximately 10%). In addition, the influence of different alkyl bromides and iodides on the yield of
this reaction was tested. It was confirmed that the yield of homocoupling depends on the type of the
halide as follows: decyl bromide (60%), ethyl bromide (70%), decyl iodide (80%), and ethyl iodide
(97%). Moreover, no heterocoupled products of reaction of alkyl halides with 5-ethynyl-2,2'-bithiophene
(
to bt-≡-R) were observed.

Molecules 2015, 20
4570
[
PdCl (PPh ) ], CuI
2 3 2
S
S
S
S
S
S
EtI, PhMe, rt.24h
4
6
Scheme 3. Homocoupling of 5-ethynyl-2,2'-bithiophene (4) to 1,4-bis(2,2'-bithiophen-5-
yl)-buta-1,3-diyne (6) in the presence of ethyl iodide mediated by CuI/[PdCl (PPh ].
2
)
3 2
2
.2. Benzene Derivatives with Two bt Moieties Prepared via Manganese-Catalyzed Reaction
We synthesized 1,4-bis(2,2'-bithiophen-5-yl)-2-methyl-3-etoxycarbonylobenzene (7) and
,4-bis(2,2'-bithiophen-5-yl)-2-phenyl-3-etoxycarbonylobenzene (8) from 4 and ethyl acetoacetate or
1
benzoylacetate via [MnBr(CO) ]-catalyzed dehydrative [2 + 2 + 2] cycloaddition (Scheme 4).
5
O
R
O
O
O
Et
R
O
Et
+
[
MnBr(CO) ], MS4A
5
o
S
S
S
S
S
80 C, 48h, neat
S
7 R=CH3
8 R= Ph
4
Scheme 4. Synthesis of 1,4-bis(2,2'-bithiophen-5-yl)-2-methyl-3-ethoxycarbonylbenzene (7)
and 1,4-bis(2,2'-bithiophen-5-yl)-2-phenyl-3-ethoxycarbonylbenzene (8) via manganese-
catalyzed reactions of acetyl- or benzoylacetate with 5-ethynyl-2,2'-bithiophene (4).
The manganese-catalyzed dehydrative [2 + 2 + 2] cycloaddition of 1,3-dicarbonyl compounds to
terminal alkynes leading to 2,3,6-trisubstituted methyl or ethyl benzoate is known from the literature.
However, heteroaromatic substituents are unknown [39–41]. A slight modification of this method
allowed us to obtain compounds 7 and 8 with electron-rich heteroaromatic substituents such a
2
,2'-bithiophen-5-yl. We did not observe any desulfurization side reactions or other transformations of
the bithiophene systems, even though the catalytic reactions (using Mn, Pd, Rh, Ru, and Cu
complexes) were carried out at high temperatures. However, the procedures applied by us for the
synthesis of 7 and 8 did not cause the deactivation of the catalytic system. Due to this fact, one should
assume that the reaction with 5-ethynyl-2,2'-bithiophene proceeds according to the mechanism
proposed for other terminal alkynes [39–41].
2
.3. Isoxazolines With bt Motifs
Five new isoxazolines containing one or two bithienyl moieties were obtained via [Ru]- or
1
5-crown-5/NaOH catalyzed isomerization of 5-allyl-2,2'-bithiophene 9 to 5-(1-propenyl)-2,2'-
bithiophene and then 1,3-DC of nitrile oxide to 10 (Scheme 5). The range of reviews on the synthesis
of isoxazolines via the addition of nitrile oxides to alkenes is very extensive and includes many
monographic reports [42–45], and our papers [46–48]. The methods of preparation of numerous pure,
stable nitrile oxides [49] or generated in situ [50,51] have been also described. The synthesis of

Molecules 2015, 20
4571
2
-allyl-thiophene in the reaction of 2-lithiothiophene (obtained by the lithiation of bithiophene with
n-BuLi in THF at −78 °C) with allyl bromide has been reported [52,53]. However, our attempts to apply
this method to the synthesis of 9 were inefficient due to low regioselectivity (lithiation of bithiophene
produced more than 35% dilithiobithiophene). Moreover, the synthesis of 9 via reaction of 2-thienyl-
magnesium chloride with allyl bromide was described in the literature [54]. However, our attempts to
use this method to obtain 5-allyl-2,2'-bithiophene in the reaction of (2,2'-bithiophen-5-yl)magnesium
iodide or bromide with allyl bromide were not successful in spite of testing various reaction conditions
and various catalysts ([Pd(PPh
3
)
4
], [PdCl
2
(PPh
3
)
2
], [NiCl
2
(dppe)], [NiCl (dppp)]). The application of
2
our procedure of bithiophene lithiation [29] in the hexane-diethyl ether mixture allowed us to obtain
high lithiation regioselectivity (less than 0.5% of the dilithio product). Compound 9 was conveniently
and effectively obtained in the reaction of 2 with allyl bromide without the catalyst (Scheme 5).
Practically quantitative isomerization of 5-allyl-2,2'-bithiophene (9) to (E + Z)-5-(1-propenyl)-2,2'-
1
bithiophene (10) (determined by H-NMR: E/Z = 9/1) using [RuClH(CO)(PPh
3
3
) ] was performed. This
catalyst is well-known and has been intensively studied by us and used by others [19,55,56].
Additionally, the abovementioned isomerization was realized with a new catalytic system, i.e.,
1
5-crown-5/NaOH/PhMe. The latter catalytic system allowed the quantitative transformation of 9 into
-propenyl derivative 10 even at room temperature (E/Z = 10/1). We also verified that this catalytic
1
system is equally efficient in the isomerization of N-allylimidazole to N-(1-propenyl)imidazole and
allylphenyl sulphide to phenyl-(1-propenyl) sulphide (in each case a mixture of E and Z isomers was
formed). The reactions reached equilibrium Qallyl-Q(1-propenyl), where Q = 1-imidazolyl or PhS at room
temperature within 24h in PhMe. Among the catalysts of crown ether-base type, applied for the double
bond migration, only 18-crown-6/t-BuOK (for the isomerization of 1-phenyl-2-aza-1,4-pentadiene) [57]
and 18-crown-6/KOH/benzene (for the isomerization of N-allylimidazole, PhXCH
X = O, S, Se and several ArCH=NCH CH=CH ) have been described so far [46,58].
Compound 10 was used in the synthesis of five new isoxazolines 11–15, containing one or two
bithiophene motifs. The compounds 11–15 were obtained via 1,3-DC of two stable (2,6-Cl CNO
and p-(ONC) ), two low stable nitrile oxides (2-pyridinecarbonitrile oxide and p-dimethylamino-
2
CH=CH
2
, where
2
2
2
C
6
H
4
2
C
6
H
4
benzenecarbonitrile oxide) and extremely unstable 2,2'-bithiophen-5-carbonitrile oxide. It is known
that sterically hindered nitrile oxides and those containing substituents decreasing the dipole moment
of this dipole are stable [59]. The last three oxides (two low stable and one unstable) were generated
in situ from the proper oxymoyl chlorides using triethylamine (added dropwise) in order to achieve high
concentration of the dipolarophile (E + Z)-5-(1-propenyl)-2,2'-bithiophene. However, the dimerization
of these oxides, mainly 2,2'-bithiophen-5-carbonitrile oxide, was observed. Therefore, a 3-fold excess
of oxymoyl chloride in relation to the dipolarophile was used and consequently, the quantitative
conversion of the latter was attained. When the ratio nitrile oxide/dipolarophile = 1/1, the conversion
of 10 was low, e.g., for 2-pyridinecarbonitrile oxide it was 40% and the E/Z ratio in the unreacted 10, i.e.,
after 1,3-DC, was significantly different from that for 10 before 1,3-DC (4/2 and 9/1, respectively).
This means that (E)-(10) underwent cycloaddition much faster than (Z)-(10). We obtained stable
2
-pyridine oxymoyl chloride (described in the literature) and 2,2'-bithiophen-5-carbamoyl chloride
from the respective oximes in the reaction with NCS in DMF at room temperature via a typical or
modified procedure [60]. Interestingly, in the case of the synthesis of 2,2'-bithiophen-5-carbamoyl
chloride via the typical procedure (NCS, HCl in DMF) [60], chlorination of the bithiophene ring takes

Molecules 2015, 20
4572
place. When the procedure was changed, i.e., when HCl was no longer used as an initiator, the desired
oxymoyl chloride was obtained in high yield (95%) without the chlorination of thiophene ring.
Furthermore, the generation of oxides in situ in DMF proceeds at room temperature (2-pyridine- and
p-dimethylaminobenzenecarbonitrile oxides) and in THF at −20 °C (2,2'-bithiophen-5-carbonitrile oxide).
2
1
3
N
N
S
S
O
Li
Me
S
Ar
Me
S
N
O
S
S
Br
S
S
1
1
2
Ar = 2,6-Cl C H
9
NEt3, DMF,
°
40 C
2
6
3
1
Ar = 4-Me
2
NC
6
H
4
S
OH
S
N
rt, CH
2 2
Cl
N
ArCNO
Cl
[
RuClH(CO)(PPh
or 15-Crown5/NaOH
in PhMe)
3 3
) ]
Me
O
S
(
N
S
NEt3, THF, -20 C
°
N
S
S
1
4
OH
N
N
O
Me
O
1
5
Me
Me
Cl
S
10
S
S
S
S
S
Scheme 5. Synthesis of isoxazolines (E + Z)-(10): cis + trans 3-(2,6-dichlorophenyl-4-
methyl-5-(2,2'-bithiophen-5-yl)isoxazoline (11); 3-(p-dimethylaminophenyl)-5-(2,2'-
bithiophen-5-yl)-4-methylisoxazoline (12); 3,5-bis(2,2'-bithiophen-5-yl)-4-methylisoxazoline
15); 5-(2,2'-bithiophen-5-yl)-4-methyl-3-(2-pyridyl)isoxazoline (13); 1,4-bis(5-(2,2'-
(
bithiophen-5-ylo)-4-methylisoxazoline-3-ylo)benzene (14).
In the case of the cycloaddition reactions activated by high pressure, it is very important to take into
consideration the stability and reactivity of ArCNO, and in addition the solubility of ArCNO in organic
solvents (Scheme 5). In the case of terephthaloyldinitrile dioxide, which is a low reactivity oxide,
performance of the cycloaddition under high pressure gave a good result, i.e., with practically quantitative
conversion (Scheme 5). It was very important to reach such a conversion since it facilitated the
separation of the pure product, which would have been difficult if the product had been a mixture of
mono- and diisoxazoline. At room temperature the reaction between p-(ONC)
2
C
6
4
H and 10 practically
did not occur, whereas at 80 °C in a steel reactor (under equilibrium pressure) the yield of isoxazolines
was 60%, while 10% was the product of monoaddition. There is no doubt that considerable
enhancement of yield is caused by high pressure activation. The reaction shown in Scheme 5 leading to
1
4 was the first 1,3-DC of nitrile oxide to alkenes under high pressure. In the literature, there are many
examples reporting the beneficial, spectacular influence of high pressure on chemical reactions,
cycloaddition reactions in particular, due to their highly negative activation volume [60–63]. There are
many papers on diene-ene [4 + 2] cycloadditions but the number of papers on dipolar [3 + 2]
cycloaddition is limited, furthermore, most of them concern the cycloaddition of nitrones to alkenes [62],
and azides to alkynes [61,63]. There are no reports on the beneficial effects of high pressure on the

Molecules 2015, 20
4573
cycloaddition reaction of nitrile oxide to alkenes. All five 1,3-DC reactions shown in Scheme 5 were
concerted, since the trans/cis ratio for the isoxazolines obtained was the same as the E/Z ratio for the
dipolarophile (9/1). On the other hand, the regioselectivity of the cycloaddition presented in Scheme 5
was slightly different. In the case of dipolarophiles of MeCH=CHQ type (as 10), the regioselectivity was
very high or complete when Q was a strong donor, as it has been shown in our previous papers [46–48].
The content of the second regioisomer, i.e., 3-Ar, 4-bithienyl-5-methylisoxazolines depended on the
type of Ar is 5%, 2%, 2% 1% and 1% for 2,6-Cl
2
C
6
H
3
, p-Me
2
NC
6
H
4
, bt, C
6
4
H , 2-Py, respectively. It
means that the reactions are highly regioselective, allowing one to obtain pure 5-bithienyl isoxazolines.
In the case of the reaction with 2-pyridinecarbonitrile oxide, a side product, i.e., oxide dimer was
isolated, which structure was confirmed by X-ray spectroscopy (Table S1 in Supporting Information).
This dimer is a known compound [64], however, its X-ray structure is not known.
The obtained 5-(2,2'-bithiophen-5-yl)-3-(2,6-dichlorophenyl)-4-methylisoxazoline (11) and
5
-(2,2'-bithiophen-5-yl)-3-(p-dimethylaminophenyl)-4-methylisoxazoline (12) were assumed as model
compounds for 1,3-DC and aromatization. Compounds 1,4-bis(5-(2,2'-bithiophen-5-yl)-4-
methylisoxazoline-3-ylo)benzene (14) and 3,5-bis(2,2'-bithiophen-5-yl)-4-methylisoxazoline (15) are
the precursors of conducting polymers of bt-A-bt type, where the spacer A contains an isoxazole ring.
However, aromatization before polymerization is necessary. Isoxazoline 12 containing a 2-pyridyl-
substituent is particularly interesting—it is a bidendate N,N-donor ligand and a precursor of a ligand
which is an analogue of 2,2'-bipyridine (after aromatization). Both the dihydro form (isoxazoline) and,
particularly, the fully aromatic form (isoxazole) may be used for the synthesis of molecular materials
and conducting polymers. In the literature only a few transition metal (Pd, Pt, Re) complexes with
3
-(2-pyridyl)isoxazolines, and also a few Ir and Re complexes with diisoxazoles [65] have been
described. Importantly, such conducting polymers from the polythiophene group with isoxazole motif
connecting the terthiophene fragments have not been reported. The obtained isoxazolines may be
easily transformed into respective isoxazoles via oxidative dehydrogenation by DDQ, as it has been
shown for two of them, i.e., 16, 17 (Scheme 6). The aromatization of isoxazolines shown in Scheme 6
was performed using a typical procedure [66].
Me
Ar
Me
Ar
S
DDQ
S
S
N
S
PhMe, rfx, 24h
N
O
O
1
6 Ar = 2,6-Cl C H
2 6 3
'
1
7 Ar = 2,2-bitiophene-5-yl
Scheme 6. Aromatization of isoxazolines using DDQ to: 3-(2,6-dichlorophenyl)-4-methyl-5-
2,2'-bithiophen-5-yl)isoxazole (16) and 3,5-bis(2,2'-bithiophen-5-yl)-4-methylisoxazole (17).
(
The alternative route for the synthesis of isoxazoles via addition nitrile oxide to double bond and
then aromatization can be the direct addition of RCNO into triple bond—see Scheme 7.
According to us, the reaction shown in Scheme 7 is a particularly spectacular example of the
beneficial influence of high pressure on 1,3-DC. The conversion and the selectivity were practically
quantitative, whereas under atmospheric or equilibrium pressure, in a steel reactor, this reaction does
not take place even at 100 °C (in CH
2
Cl or DMF).
2

Molecules 2015, 20
4574
N
N
O
O
S
1
GPa
-
+
+
-
S
S
O N
N O
+
CH Cl , 100
°
C
S
2
2
S
1
8
S
Scheme 7. Synthesis of 1,4-bis[5-(2,2'-bithiophen-5-yl)isoxazol-3-yl]benzene (18) via high
pressure activated 1,3-DC cycloaddition of terephthaloyldinitrile to 5-ethynyl-2,2'-bithiophene.
2
.4. Rh-Mediated [2 + 2 + 2] Cycloaddition for Synthesis of Fluoranthene and Benzene Derivatives
with a bt Motif
Two new 7,8,9,10-tetrasubstituted fluoranthenes 19, 20 were obtained from
1
,8-diethynylnaphthalene and 1,2-bis(2,2'-bithiophen-5-yl)ethyne (5) or 1,4-bis(2,2'-bithiophen-5-yl)-
,3-butadiyne (6) derivatives via [RhCl(PPh ]-mediated formal [2 + 2 + 2] cycloaddition (Scheme 8).
1
)
3 3
S
S
S
S
S
S
S
S
5
o
[
RhCl(PPh ) ], 130 C, 72h
3 3
Xylene
19
Ph
Ph
S
S
S
S
S
S
S
6
S
o
[
RhCl(PPh ) ], 130 C, 72h
3 3
Xylene
2
0
Scheme 8. Rh-mediated synthesis of fluoranthene derivatives containing 2,2'-bithiophen-5-
yl moiety: di(2,2'-bithienyl-5-yl)diphenylfluoranthene (19) and (2,2'-bithiophen-5-yl)[(2,2'-
bithiophen-5-yl)ethynyl]diphenylfluoranthene (20).
[RhCl(PPh
3
)
3
] was applied as a catalyst since, together with [Co
2
(CO) ], it is the most frequently
8
applied and effective catalyst for both inter- and intramolecular [2 + 2 + 2] cycloadditions [67–69]. In
the literature there are only a few papers devoted to the synthesis of 7,8,9,10-tetrasubstituted
fluoranthenes from derivatives of 1,8-diethynylnaphthalene and alkynes, except for conjugated diynes,
or NBD which can act as an acetylene equivalent catalyzed by various rhodium complexes [67–69]. To
date, fluoranthenes with alkyl or phenyl substituents, except for the ones with heteroaryl substituent,
have been obtained in this way. Recently, several fluoranthenes with substituted thiophene motifs (except
for the ones with a bithiophene one) and two fluoranthenes with a 6H-indolo[2,3-b]quinazoline

Molecules 2015, 20
4575
chromophore [70] have been obtained. The compounds were obtained via [4 + 2], but not via [2 + 2 + 2]
cycloaddition. The novel compounds 19 and 20 are the first bithiophene derivatives of the bt-A-bt type,
where the fluoroanthene fragment plays a role of a spacer. The polymers obtained from them are
expected to have interesting conducting and luminescence properties.
The methods known from the literature were applied for the synthesis of diiodonaphthalene [71],
was obtained from commercially available 1,8-diaminonaphthalene, which was further used to obtain a
phenyl derivative via Sonogashira coupling [72]. The trimerization of the acetylene derivative 5, both
in the reaction shown in Scheme 9 and during heating of 5 in xylene at 130 °C in the presence of
1
5
0 mol% [RhCl(PPh
3
)
3
] was observed. The latter reaction allowed to obtain pure hexa(2,2'-bithiophen-
-yl)benzene (21) with 40% yield (Scheme 9). In the literature, there is only one work devoted to the
trimerization of ArC≡CAr (Ar is alkyl-substituted- thienyl, bithienyl or terthienyl) to
hexakis(alkylthienyl-, bithienyl and terthienyl)benzenes catalyzed by [Co (CO) ] [73].
Our result, i.e., the trimerization of 5, corresponds to the results of other authors, who used
RhCl(PPh ] with very good results for fully intermolecular [2 + 2 + 2] cycloaddition [67]. However,
2
8
[
)
3 3
trimerization of 1,4-bis(2,2'-bithiophen-5-yl)-1,3-butadiyne was not observed despite the fact that such
a reaction is known for 1,4-diphenyl-1,3-butadiyne [67]. It probably results from the steric effects
being greater for the 2,2-bitihophen-5-yl substituent than for the phenyl one, which have a major
influence on the course of the studied cycloaddition reactions. One should remember that this reaction
probably proceeds via a metalacyclopentadiene intermediate and steric hindrance plays a crucial role in
this transformation [67]. Moreover, in accordance with the results of Wu et al., the thermal,
intramolecular transformation of 1,8-di(phenylethyl)naphthalene to 7-phenylbenzo[k]fluoranthene
described by Bossenbroek et al., was not observed by us [74].
S
S
S
S
S
S
S
0
[
RhCl(PPh ) ],130 C, 72h
3 3
S
S
S
S
Xylene
5
S
S
S
S
S
2
1
Scheme 9. Cyclotrimerization of 1,2-bis(2,2'-bithiophen-5-yl)acetylene (5) to hexa(2,2'-
bithiophen-5-yl)benzene (21) catalyzed by [RhCl(PPh ].
)
3 3
2
.5. Catalytically or High Pressure Activated 1,3-DC of Azides to Triple Bond for Synthesis of
Triazoles with bt Moiety
Using 5-iodobithiophene (3), 5-ethynylbithiophene (4), 1,2-bis(2,2'-bithiophen-5-yl)acetylene (5)
and Cu-catalyst or Ru-catalyst or high pressure mediated 1,3-dipolar cycloaddition of azides to
alkynes, four novel triazole derivatives 22–25 containing one or two bt moieties were obtained
(
Scheme 10). In these syntheses, typical catalytic systems, i.e., CuSO /sodium ascorbate [75–77] or
4

Molecules 2015, 20
4576
[
RuClcp(PPh ] [78,79] or high pressure activation were used. The use of high pressure in the 1,3-DC
3 2
)
of azides to alkynes has already been described [63,80], although not for heteroaryl-substituted
alkynes. Decyl, benzyl, and bithienyl azides [13] were synthesized using the methods known from the
literature (the latter was generated in situ).
NaN , CuI,
3
S
DMEDA
EtOH/H O
2
S
5
0
°
C, 24h
S
18 17
C H
I
+
S
H
N
OH
N
O
N
O
H
-
+
Na
22
HO
O
17 18
H C
N
N
1
S
R
a or b
N
S
S
RN3
R
+
S
2
3
4
R = PhCH2
R = n-C H
21
2
1
0
1
2
a) sodium ascorbate, CuSO *5H O, K CO , t- BuOH/H O, rt, 48h when R = SiMe and R = PhCH ;
4
2
2
3
2
3
2
o
1
2
b) 1.0 GPa, 80 C, 24h when R = H and R = n-C H ;
1
0
21
N
N
N
+
-
H
21
C
10
S
N N N [CpRuCl(PPh ) ]
S
S
S
S
3 2
+
21 10
H C
benzene,
C, 24h
S
80
°
S
S
25
Scheme 10. Cu- or Ru-catalyst or hp-mediated synthesis of triazoles 22–25 with a bt moiety.
It should be noted that the reaction carried out under high pressure is fully regioselective—only
-(2,2'-bithiophen-5-yl)triazole is formed. The obtained triazoles may play the role as cyclometalating
4
ligands or monomers for the synthesis of polythiophenes, where the triazole ring is the linker
connecting tetrathiophene fragments. Up till now, this type of conducting polythiophenes has not been
known. Moreover, there are a lot of triazoles which play a vital role of ligands in the molecular
catalysis described in the literature [75]. Additionally, a triazole motif is present in the structure of
many pharmaceuticals, in particular antifungal ones [81].
2
.6. Synthesis of Pyrroles with two bt Moieties via CuCl-Mediated Dihydroamination of 1,4-Bis(2,2'-
bithiophene-5-yl)buta-1,3-diyne
Three new pyrrole derivatives 26–28 were also obtained via CuCl-mediated hydroamination of
1
,4-bis(2,2'-bithiophen-5-yl)buta-1,3-diyne (6) (Scheme 11). The addition of RNH to 1,3-diynes
2

Molecules 2015, 20
4577
(
hydroamination of 1,3-diynes) catalyzed with transition metal complexes leading to pyrrole
derivatives is an alternative to classical Knorr, Paal-Knorr, and Hantzsch methods. The effective
catalysts of these reactions are complexes of Au(I) [82,83], Au(I)-H PO -12WO [84], and
3
4
3
CuCl [85–87]—the yields of these reactions range from moderate to very high. Convenient procedures
for many disubstituted diynes, even for 1,4-bis(2-thienyl)-1,3-butadiyne are known [85–88]. Moreover,
several aromatic and aliphatic amines were used for the abovementioned procedures [85–88].
S
S
S
S
S
CuCl
10 °C, 48 h
N
S
H
H
1
N
S
S
+
Ar
1
10 癈, 48h
Ar
26) Ar = Ph
2
7) Ar = p-(n-C10H21O)C H4
6
28) Ar = N-ethylcarbazo-3-yl
Scheme 11. Synthesis of: N-phenyl-2,5-bis(2,2'-bithiophen-5-yl)pyrrole (26); N-(p-
decyloxyphenyl)-2,5-bis(2,2'-bithiophen-5-yl)pyrrole (27) and N-[2-(N-carbazo-3-
yl)ethyl]-2,5-bis(2,2'-bithiophen-5-yl)pyrrole (28) via CuCl-catalyzed dihydroamination of
1
,4-bis(2,2'-bithiophen-5-yl)-1,3-butadiyne (6).
It was shown that it is possible to obtain pyrroles with 2,2'-bithiophen-5-yl substituents in positions
and 5, and most of all, that aminoheteroarenes may also serve as substrates in this synthesis.
2
Importantly, the synthesis yield of the derivative substituted with N-ethylcarbazo-3-yl was much
higher than for phenyl and p-decyloxyphenyl substituents. The synthesized compounds 26–28 will be
certainly very interesting as nanomaterials due to the π-excessive character of the pyrrole and
bithiophene fragments, luminescence, and solubility in organic solvents. There are only two similar
systems known in the literature [89]. Nevertheless, these systems contain a thiophene (not bithiophene)
motif, i.e., 3,6-bis(2,5-di-2-thienyl-1H-pyrrol-1-yl)-9-ethyl(or dodecyl)-9H-carbazole, which were
classically obtained from 1,4-bis(2-thienyl)buta-1,4-dione [89]. The mechanism of dihydroamination
of conjugated diynes catalysed by CuCl has not been described in detail so far. Nevertheless, it is
probably similar to the well-known addition of amines to disubstituted acetylenes catalyzed by various
transition metal complexes [90].
3. Experimental Section
3.1. General Methods
All starting materials and reagents were purchased from commercial sources and were used as
received, unless otherwise stated. All reactions were carried out under argon atmospheres
undernhydrous conditions. Solvents were dried and purified using usual methods before use. Thin
layer chromatography was performed on silica gel (TLC silica gel 60, Merck, Darmstadt, Germany).
1
13
NMR spectra were recorded on an Avance 400 instrument (400 MHz for H and 100 MHz for C) or
Ascend 500 instrument (500 MHz for H and 125 MHz for 13C) (Bruker, Billerica, MA, USA).
Chemical shifts were referenced to the residual proton signal of the solvent. Melting point
measurements were conducted on Stuart automatic melting point SMP40 apparatus (Bibby Scientific
1

Molecules 2015, 20
4578
Limited Group, Staffordshire, United Kingdom). Low resolution mass spectra were recorded in
methanol on a Varian LC-920 instrument (Varian, Palo Alto, CA, USA). HRMS-ESI spectra were
recorded in methanol on a Synapt G2-S HDMS mass spectrometer (Waters Inc., Milford, MA, USA)
equipped with an electrospray ion source and q-TOF type mass analyzer. HRMS-EI spectra were
recorded on an AutoSpec Premier magnetic sector mass spectrometer (Waters Inc.) equipped with an
electron impact (EI) ion source and the EBE double focusing geometry mass analyzer. The setup for
reactions under high pressure conditions was built for high pressure dielectric measurements by
UNIPRESS (Warsaw, Poland) and described by Paluch et al. [91].
The crystals of compounds were mounted in turn on a Gemini Ultra Oxford Diffraction automatic
diffractometer (Agilent, Santa Clara, CA, USA) equipped with a CCD detector, and used for data
collection. X-ray intensity data was collected with graphite monochromated MoK
α
radiation
(
λ = 0.71073 Å) at a temperature of 295.0(2) K, with ω scan mode. Ewald sphere reflections were
collected up to 2θ 50.10. Details concerning crystal data and refinement is gathered in Tables S1–S3.
Lorentz, polarization and empirical absorption corrections using spherical harmonics implemented in
SCALE3 ABSPACK scaling algorithm [92]. The structures were solved by the direct method and
subsequently completed by difference Fourier recycling. All the non-hydrogen atoms were refined
anisotropically using full-matrix, least-squares techniques. The Olex2 [93] and SHELXS97,
SHELXL97 [94] programs were used for all the calculations. Atomic scattering factors were
incorporated in the computer programs.
3
1
.2. Synthesis of 1,2-Bis(2,2'-bithiophene-5-yl)acetylene (5) and 1,4-Bis(2,2'-bithiophene-5-yl)buta-
,3-diyne (6)
A cascade of three reactors, each containing a mixture of substrates consisting of 5-iodo-2,2'-
bithiophene (15.0 g, 51.3 mmol), CuI (1.125 g, 5.9 mmol), [PdCl
2
(PPh
3
)
2
] (0.75 g, 1.1 mmol), acetone
(
500 mL), triethylamine (11.25 mL, 81 mmol), was saturated with a steady stream of acetylene (for 5)
or buta-1,3-diyne (generated from 1,4-dichloro-2-butyne (12.64 g, 0.1 mol), according to the procedure
described in literature [95] in temperature range from 70 to 75 °C for 30 min, 1 mol/6 h for 6),
mixed with argon (1:10 v/v) at room temperature for 6 h. After the flow of gas was finished, the
content of the reactors was left to stir for 24 h at room temperature. Then the volatile fractions from
the combined mixtures were evaporated on a rotary evaporator. Crude product was purified using
column chromatography (SiO
2
, hexane). A yellow solid was obtained in 60% and 75% yield for 5 and
6
, respectively.
Compound 5:
S
S
S
S
1H-NMR (CDCl
d, J = 3.8 Hz, 2H), 7.07 (d, J = 3.8 Hz, 2H), 7.03 (dd, J = 5.1 Hz, J = 3.6 Hz, 2H). C-NMR (CDCl
δ 139.53, 136.79, 133.15, 128.12, 125.17, 124.50, 123.77, 121.55, 87.43. HRMS (EI) calcd. for
353.96654 found 353.93537.
): δ 7.25 (dd, J = 5.1 Hz, J = 3.6 Hz, 2H), 7.20 (dd, J = 3.6 Hz, J = 1.1 Hz, 2H), 7.18
3
1
3
(
3
):
C
18
H S
10 2

Molecules 2015, 20
Compound 6:
4579
S
S
S
S
1H-NMR (CDCl
J = 1.1 Hz, 2H), 7.05 (d, J = 3.8 Hz, 2H), 7.03 (dd, J = 5.1 Hz, J = 3.6 Hz, 2H). C-NMR (100 MHz,
): δ 7.26 (dd, J = 5.1 Hz, J = 1.1 Hz, 2H), 7.25 (d, J = 3.8 Hz, 2H), 7.21 (dd, J = 3.6 Hz,
3
1
3
CDCl
3
): δ 140.82, 136.56, 135.52, 128.19, 125.69, 124.92, 123.74, 120.66, 79.16, 77.59. HRMS (EI)
+
calcd for C20
H
10
S
4
[M] 377.9665 found 377.9669.
3
.3. Synthesis of 1,4-Bis(2,2'-bithiophene-5-yl)-3-methyl-2-ethoxycarbonylbenzene (7) and 1,4-
Bis(2,2'-bithiophene-5-yl)-3-phenyl-2-ethoxycarbonylbenzene (8)
The mixture of ethyl acetoacetate (for synthesis of 7) or ethylbenzoyl acetate (for synthesis of 8)
(
1.28 mmol) with 5-ethynyl-2,2'-bithiophene (609 mg, 3.20 mmol), [MnBr(CO)
and powdered 4 Å molecular sieves (23 mg; 115 wt %-Mn cat.) was vigorously stirred and heated at
0 °C for 48 h. Crude product was purified using column chromatography (SiO , toluene-petroleum
5
] (20 mg, 0.0735 mmol),
8
2
ether 3:1). Compounds 7 and 8 were isolated in 60% and 70% yield, respectively, as yellow solids.
1
1
7
1
7
3
1
1
,4-Bis(2,2'-bithiophene-5-yl)-3-methyl-2-etoxycarbonylbenzene (7). H-NMR (400 MHz, CDCl
3
): δ
.48 (d, J = 8.0 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.25–7.23 (m, 2H), 7.21 (dd, J = 3.4 Hz, J =1.0 Hz,
H), 7.20 (dd, J = 3.4 Hz, J =1.0 Hz, 1H), 7.17 (d, J = 3.7 Hz, 1H), 7.13 (d, J = 3.7 Hz, 1H),
.06–7.02 (m, 3H), 6.97 (d, J = 3.7 Hz, 1H), 4.30 (q, J = 7.1 Hz, 2H), 2.45 (s, 1H), 1.24 (t, J = 7.1 Hz,
1
3
H). C-NMR (125 MHz, CDCl ): δ 169.68, 140.63, 140.12, 138.22, 137.94, 137.10, 137.08, 134.74,
3
34.27, 133.44, 131.44, 131.18, 128.03, 127.90, 127.37, 127.07, 124.62, 124.59, 124.15, 123.88,
+
23.84, 61.62, 18.05, 13.96. HRMS (EI) calcd for C26
H
20
O
2
S
4
[M] 492.0346 found 492.0361.
1
1
7
1
7
6
,4-Bis(2,2'-bithiophene-5-yl)-3-phenyl-2-etoxycarbonylbenzene (8). H-NMR (400 MHz, CDCl
3
): δ
.67 (d, J = 8.2 Hz, 1H), 7.55 (d, J = 8.2 Hz, 1H), 7.36–7.27 (m, 5H), 7.23 (dd, J = 5.0 Hz, J =0.7 Hz,
H), 7.20 (dd, J = 3.6 Hz, J =0.8 Hz, 1H), 7.17 (dd, J = 5.1 Hz, J =0.9 Hz, 1H), 7.12 (d, J = 3.7 Hz, 1H),
.09 (d, J = 3.8 Hz, 1H), 7.05 (dd, J = 3.5 Hz, J =0.8 Hz, 1H), 7.03 (dd, J = 5.0 Hz, J =3.6 Hz, 1H),
.97 (dd, J = 5.0 Hz, J =3.6 Hz, 1H), 6.89 (d, J = 3.8 Hz, 1H), 6.50 (d, J = 3.8 Hz, 1H), 3.90 (q,
1
3
J = 7.1 Hz, 2H), 0.89 (t, J = 7.1 Hz, 3H). C-NMR (125 MHz, CDCl
3
): δ 168.55, 140.72, 139.72,
1
1
38.31, 138.02, 138.00, 137.87, 137.16, 137.11, 134.85, 133.25, 130.49, 130.30, 130.26, 129.14,
28.09, 128.00, 127.89, 127.79, 127.31, 124.64, 124.41, 124.30, 123.90, 123.69, 123.61, 61.23, 13.56.
+
HRMS (EI) calcd for C31
H
22
O
2
S
4
[M] 554.0503 found 554.0482.
3
.4. Synthesis of 5-Allyl-2,2'-bithiophene (9)
.6 M solution of n-BuLi in hexane (60.2 mL, 96.2 mmol) was injected through septum with a
1
syringe (for about 30 min.) to vigorously stirred solution of 2,2'-bithiophene (1, 20 g, 120.3 mmol) in
the mixture of hexane (1 L) and diethyl ether (350 mL) cooled down to below −5 °C. It was necessary
to keep the temperature of reaction mixture below −5 °C during the injection of n-BuLi solution. After
all n-BuLi was added, the cooling bath was removed and reaction mixture was left to reach room

Molecules 2015, 20
4580
temperature. In the next step, allyl bromide (14.5 g, 120.3 mmol) was added dropwise through septum
with a syringe. The reaction mixture was stirred for 72 h at room temperature and the progress of the
reaction was monitored with TLC. After that, the post-reaction mixture was filtered and the solvents
were evaporated from the filtrate using a rotary evaporator. The crude product was purified using
column chromatography (SiO , hexane). Product 9 was obtained as yellowish liquid in 85% yield.
2
Isomerization of 5-Allyl-2,2'-bithiophene (9), N-allylimidazole and Allyl-phenyl sulfide to 1-propenyl
derivatives catalysed by 15-crown-5/NaOH
Allyl substrate (10 mmol), 15-crown-5 (10 mmol), micronized NaOH (10 mmol) and toluene
(
1 mL) were vigorously stirred at room temperature for 24 h. After that, toluene (10 mL) was added
and the mixture was washed with water (3 times 10 mL) and dried over anhydrous MgSO . After
drying an agent was filtered out, activated carbon (20 mg) was added and the mixture was stirred for
h at room temperature. After that, activated carbon was filtered out and the solvent was evaporated
on a rotary evaporator. Pure (E + Z)-(1-propenyl) derivatives were obtained with 97% yield.
4
3
3
.5. Synthesis of (E) + (Z)-5-(1-Propenyl)-2,2'-bithiophene (10)
A mixture of 5-allyl-2,2'-bithiophene (9) (2 g, 10 mmol), [RuClH(CO)(PPh
3
3
) ] (10 mg, 0.1 mmol)
and toluene (1 mL) was stirred at 60 °C for 24 h. The solvent was evaporated using a rotary evaporator
and the solid residue was purified using column chromatography (SiO
2
, hexane). Ru-free 10 was
obtained with 97% yield (E/Z = 9) as a light-brown oil.
Compound (10):
S
S
Me
1H-NMR (400 MHz, C
H), 5.47 (dq, J = 11.4 Hz, J = 7.3 Hz, 1H), 5.89 (dq, J = 15.5 Hz, J = 6.7 Hz, 1H), 6.23 (dtd,
J = 15.5 Hz, J = 1.6 Hz, J = 1,1 Hz, 1H), 6.39 (ddd, J = 11.4 Hz, J = 1.7 Hz, J = 0.5 Hz, 1H), 6.50
d, J = 3,7 Hz, 1H), 6.52 (d, J = 3,7 Hz, 1H), 6.64 (dd, J = 5.1 Hz, J = 3.6 Hz, 1H), 6.65 (dd, J = 5.1 Hz,
J = 3.6 Hz, 1H), 6.71 (dd, J = 5.1 Hz, J = 1.1 Hz, 2H), 6.88 (d, J = 3.7 Hz, 1H), 6.93 (d, J = 3.7 Hz,
H), 6.08 (dd, J = 3.6 Hz, J = 1.2 Hz, 1H), 7.00 (dd, J = 3.6 Hz, J = 1.2 Hz, 1H). 13C-NMR
100 MHz, CDCl ): δ 142.26, 137.84, 137.53, 134.93, 127.93, 127.92, 127.92, 126.10, 126.10, 125.08,
6
6
D ): δ 1.54 (dd, J = 6.7 Hz, J = 1.7 Hz, 3H), 1.81 (dd, J = 7.3 Hz,J = 1.7 Hz,
3
(
1
(
3
1
25.08, 124.47, 124.46, 124.46, 124.20, 123.92, 123.92, 123.88, 123.88, 123.50, 18.52, 15.39. HRMS
+
(
EI) calcd for C11
H
10
S
2
[M] 206.02239 found 206.02162.
3
.6. General Procedure for 1,3-Dipolar Cycloaddition: Synthesis of 11–13
To a solution of aldoxime (1.29 mmol) and NCS (1.50 mmol) in CH Cl (or DMF for 13) (12 mL),
2
2
one drop of 36% hydrochloric acid was added. The reaction mixture was stirred at room temperature
for 24 h. After that time, (E + Z)-5-(1-propenyl)-2,2'-bithiophene (10) (266 mg, 1.29 mmol) and
triethylamine (0.10 mL, 1.41 mmol) were added and the reaction mixture was stirred at 40 °C for 24 h.
In the next step, solvent was removed using a rotary evaporator. The crude product was purified using

Molecules 2015, 20
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column chromatography (SiO
2
, CH
2
Cl
2
). Products 11 (61% yield, yellow solid), 12 (29% yield,
pale-red oil), and 13 (34% yield, pale-brown oil) were isolated. During isolation of the isoxazoline 13
the dimer of 2-pyridinecarbonitrile oxide 13a was additionally obtained (5% yield, pale yellow crystals).
5
-(2,2'-Bithiophen-5-yl)-3-(2,6-dichlorophenyl)-4-methylisoxazoline (11). 1H-NMR (400 MHz,
CDCl ): δ 7.44–7.31 (m, 3H), 7.26 (d, J = 5.1 Hz, 1H), 7.21 (d, J = 3.6 Hz, 1H), 7.10 (s, 2H), 7.05 (dd,
3
J = 4.6 Hz, J = 3.6 Hz, 1H), 6.08 (d, J = 10.3 Hz, 1H), 5.50 (d, J = 10.0 Hz, 1H), 4.98 (dq, J = 9.3 Hz,
J = 6.1 Hz, 1H), 4.87 (d, J = 9.4 Hz, 1H), 4.09–4.01 (m, 1H), 3.97 (dq, J = 10.0 Hz, J = 7.1 Hz, 1H), 1.65
13
(
d, J = 6.1 Hz, 1H), 1.31 (d, J = 7.1 Hz, 3H), 1.00 (d, J = 7.5 Hz, 1H). C-NMR (100 MHz, CDCl
3
): δ
1
1
60.88, 139.80, 136.38, 135.98, 131.32, 128.17, 128.10, 127.95, 127.72, 127.38, 125.46, 124.63,
24.23, 109.70, 77.35, 77.04, 76.72, 8.09. m.p. 149 ± 1.2°C. HRMS (EI) calcd for C18
H13Cl
2
NOS
2
+
[M] : 392.98156 found 392.98123.
1
4
-[5-(2,2'-Bithiophen-5-yl)-4-methyl-4,5-dihydroisoxazol-3-yl]-N,N-dimethylaniline (12). cis H-NMR
(400 MHz, CDCl
3
): δ 1.43 (d, J = 7.1 Hz, 3H), 2.88 (s, 6H), 3.77 (qd, J = 7.1 Hz, J = 4.8 Hz, 1H),
5
.45 (dd, J = 4.8 Hz, J = 0.5 Hz , 1H), 6.69 (dd, J = 8.4 Hz, J = 2.1 Hz, 1H), 6.96 (dd, J = 3.7 Hz,
J = 0.6 Hz, 1H), 6.99 (dd, J = 5.1 Hz, J = 3.6 Hz, 1H), 7.02 (d, J = 3.6 Hz, 1H), 7.12 (dd, J = 3.6 Hz,
J = 1.1 Hz, 1H), 7.20 (dd, J = 5.1 Hz, J = 1.1 Hz, 1H), 7.55 (dd, J = 8.4 Hz, J = 2.1 Hz, 1H), 7.72 (d,
1
J = 2.1 Hz, 1H). trans H-NMR (400 MHz, CDCl
3
): δ 1.44 (d, J = 7.1 Hz, 3H), 3.00 (s, 6H), 3.78 (dq,
J = 7.1 Hz, J = 4.4 Hz, 1H), 5.41 (dd, J = 4.4 Hz, J = 0.5 Hz , 1H), 6.70–6.73 (m, 2H), 6.96 (dd,
J = 3.7 Hz, J = 0.6 Hz, 1H), 6.98 (dd, J = 5.1 Hz, J = 3.6 Hz, 1 H), 7.01 (d, J = 3.6 Hz, 1H),7.11 (dd,
1
3
J = 3.6 Hz, J = 1.1 Hz, 1H), 7.18 (dd, J = 5.1 Hz, J = 1.1 Hz, 1H), 7.58–7.62 (m, 2H). cis C-NMR
(
100 MHz, CDCl ): δ 17.76, 43.45, 50.51, 85.76, 115.78, 122.88, 123.33, 124.02, 124.73, 125.82,
3
1
3
1
4
1
3
26.34, 129.51, 137.06, 137.74, 142.21, 151.93, 159.60. trans C-NMR (100 MHz, CDCl ): δ 17.99,
3
0.24, 50.89, 85.10, 111.95, 119.86, 123.28, 123.89, 124.57, 125.54, 127.87, 128.46, 137.24, 137.43,
+
OS
[M+H]+
43.05, 151.54, 160.80. MS (ESI) m/z 369.11 [M+H] , HRMS (ESI): calcd for C20
H
21
N
2
2
69.1095 found 369.1096.
1
2
-[5-(2,2'-Bithiophen-5-yl)-4-methyl-4,5-dihydroisoxazol-3-yl]pyridine (13). H-NMR (400 MHz, CDCl
3
):
δ 1.53 (d, J = 7.1 Hz, 3H), 4.09 (dq, J = 7.1 Hz, J = 5.7 Hz, 1H), 5.50 (dd, J = 5.6 Hz, J = 0.5 Hz , 1H),
.98 (dd, J = 5.1 Hz, J = 3.6 Hz, 1H), 6.99 (dd, J = 3.7 Hz, J = 0.7 Hz, 1H), 7.02 (d, J = 3.7 Hz, 1H),7.12
dd, J = 3.6 Hz, J = 1.1 Hz, 1H), 7.18 (dd, J = 5.1 Hz, J = 1.1 Hz, 1H), 7.29 (ddd, J = 7.5 Hz,
J = 4.9 Hz, J = 1.2 Hz, 1H), 7.72 (td, J = 7.8 Hz, J = 1.8 Hz, 1H), 8.04 (dt, J = 8.0 Hz, J = 1.0 Hz, 1H),
6
(
1
3
8
1
1
.61 (ddd, J = 4.9 Hz, J = 1.7 Hz, J = 0.9 Hz, 1H). C-NMR (125 MHz, CDCl ): δ 17.63, 50.30, 86.34,
3
22.51, 123.39, 124.00, 124.35, 124.71, 125.94, 127.88, 136.57, 137.10, 137.84, 142.02, 148.87, 149.35,
+
61.82. HRMS (EI): calcd for C17H N OS
14 2 2
[M+H] 326.0548 found 326.0555.
1
2
-Pyridinecarbonitrile Oxide Dimer (13a). H-NMR (400 MHZ, CDCl
3
) δ = 7.32–7.35 ppm (m, 1H,
C
Ar-H), 7.38–7.41 (m, 1H, CAr-H), 7.82–7.86 (m, 3H, CAr-H), 7.97 (d, J = 8.0 Hz, 1H, CAr-H), 8.53 (d,
1
3
J = 4.6 Hz, 1H, CAr-H), 8.56 (d, J = 4.8 Hz, 1H, CAr-H). C-NMR (100 MHz, CDCl
3
) δ = 114.6 ppm,
+
1
23.8, 124.3, 124.6, 125.0, 136.7, 136.8, 143.7, 146.8, 149.6, 149.7, 156.3 (CAr). MS (ESI ) m/z 240.0
+
+
+
[M] , HRMS (ESI ): calcd for C12
H N
8 4
O [M] 240.0647 found 240.0642. IR (KBr): 3051, 2925, 2853,
2
1598, 1567, 1487, 1403, 1341, 1285, 1135, 1090, 993, 965, 827, 792, 749.

Molecules 2015, 20
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3
.7. Synthesis of 1,4-Bis(5-(2,2'-bithiophen-5-ylo)-4-methylisoxazoline-3-yl)benzene (14) under
High Pressure
A solution of (E + Z) 5-(1-propenyl)-2,2'-bithiophene (10) (536 mg, 2.60 mmol) and terephthalo-
bis(nitrile N-oxide) (192 mg, 1.2 mmol) in CH Cl (2 mL) was placed in a Teflon capsule and heated
at 100 °C for 4h under pressure of 1 GPa. After that, volatile fractions were removed using a rotary
2
2
evaporator. Crude product was purified using column chromatography (SiO
2
, CH
2
Cl /hexane 1:3).
2
1
Product 14 was obtained as an orange solid with 99% yield. H-NMR (400 MHz, CDCl
3
): δ 7.77 (s,
4
3
1
1
H), 7.21 (d, J = 5.1 Hz, 2H), 7.13 (d, J = 3.4 Hz, 2H), 7.05–6.96 (m, 6H), 5.50 (d, J = 5.0 Hz, 2H),
.84 (dq, J = 6.9, 5.4 Hz, 2H), 1.46 (d, J = 7.1 Hz, 6H). 13C-NMR (100 MHz, CDCl
): δ 160.14,
3
60.13, 141.77, 137.87, 136.94, 130.14, 127.88, 127.57, 125.99, 124.77, 124.04, 123.30, 86.08, 50.23,
7.62. HRMS (EI) calcd for C30 [M]+ 572.0721 found 572.0737.
H
24
S
4
N
2
O
2
3
.8. Synthesis of 3,5-Bis(2,2'-bithiophen-5-yl)-4-methylisoxazoline (15)
To a stirred, cooled down to −25 °C solution of 2,2'-bithiophene-5-carbox-imidoyl chloride (2.37 g,
.72 mmol) and (E + Z) 5-(1-propenyl)-2,2'-bithiophene (10) (1.88 g, 9.19 mmol) in tetrahydrofuran
9
(
250 mL), triethylamine (1.65 mL, 13.67 mmol) was added dropwise. After all amine was added, the
reaction mixture was left to reach room temperature and the solvent was evaporated on a rotary
evaporator. Crude product was purified using column chromatography (SiO
2
, CHCl
3
). Product 15 was
1
isolated with 60% yield as a yellow solid. H-NMR (400 MHz, CDCl
3
): δ 7.30 (dd, J = 5.2 Hz,
J = 1.1 Hz, 1H), 7.27 (dd, J = 3.6 Hz, J = 1.1 Hz, 1H), 7.23 (dd, J = 5.2 Hz, J = 1.0 Hz, 1H), 7.21 (d,
J = 3.8 Hz, 1H), 7.16 (dd, J = 3.7 Hz, J = 1.5 Hz, 2H), 7.15 (d, J = 3.7 Hz, 2H), 7.07 (dd, J = 5.1 Hz,
J = 3.7 Hz, 1H), 7.05 (d, J = 3.8 Hz, 1H), 7.02 (dd, J = 5.1 Hz, J = 3.7 Hz, 1H), 7.00 (d, J = 3.8 Hz,
1
H), 5.48 (d, J = 5.3 Hz, 1H), 3.78 (qd, J = 7.1 Hz, J = 5.3 Hz, 1H), 1.55 (d, J = 7.1 Hz, 3H).
13C-NMR (125 MHz, CDCl
): δ 156.51, 141.79, 140.07, 138.55, 137.89, 135.71, 133.48, 129.00,
28.72, 127.82, 126.01, 125.72, 123.92, 123.51, 123.45, 123.26, 123.18, 85.84, 51.44, 15.98. HRMS
3
1
+
(
ESI) calcd for C20
H
15NOS Na ([M+Na ]: 435,99287 found 435,99415.
4
3
3
.9. Synthesis of 5-(2,2'-Bithiophen-5-yl)-3-(2,6-dichlorophenyl)-4-methylisoxazole (16) and
,5-Bis(2,2'-bithiophene-5-yl)-4-methylisoxazole (17)
DDQ (575 mg, 2.54 mmol) was added to a solution of isoxazoline (11) (for product 16) or (15) (for
product 17) (1.27 mmol) in toluene (140 mL), and the reaction mixture was heated under reflux for
4 h and vigorously stirred. After that time, the product was still observed in the reaction mixture with
2
TLC, thus two more loads of DDQ (2 × 575 mg, 2 × 2.54 mmol) were added at an interval of 24 h (the
progress of the reaction was monitored with TLC). After 72 h, the conversion was complete (TLC).
Post-reaction mixture was concentrated to a small volume and loaded on a chromatography column
(
SiO
2
, toluene). Products 16 and 17 were obtained with 95 and 90% yields respectively, 16 as an
orange-red solid, 17 as an orange solid.
1
5
-(2,2'-Bithiophene-5-yl)-3-(2,6-dichlorophenyl)-4-methylisoxazole (16). H-NMR (400 MHz, CDCl
3
):
δ 7.49–7.35 (m, 3H), 7.29 (dd, J = 5.1 Hz, J = 1.2 Hz, 1H), 7.28 (dd, J = 3.7 Hz, J = 1.2 Hz, 1H), 7.24

Molecules 2015, 20
4583
(
(
(
d, J = 3.9 Hz, 1H), 7.19 (dd, J = 5.1 Hz, J = 1.2 Hz, 1H), 7.09 (dd, J = 3.6 Hz, J = 1.2 Hz, 1H), 7.06
dd, J = 5.1 Hz, J = 3.7 Hz, 1H), 7.00 (d, J = 3.7 Hz, 1H), 6.98 (dd, J = 5.1 Hz, J = 3.6 Hz, 1H), 2.69
1
3
s, 1H), 2.09 (s, 3H). C-NMR (100 MHz, CDCl ): δ 160.88, 139.80, 136.38, 135.98, 131.32, 128.17,
3
1
28.10, 127.95, 127.72, 127.38, 125.46, 124.63, 124.23, 109.70, 77.35, 77.04, 76.72, 8.09. HRMS (EI)
+
calcd for C18
H
11
S
2
NOCl
2
[M] 390.9659 found 390.9663. m.p. 134.8 ± 0.5 °C.
1
3
1
7
1
1
,5-Bis(2,2'-bithiophene-5-yl)-4-methylisoxazole (17). H-NMR (400 MHz, CDCl
3
): δ 7.47 (d, J = 3.9 Hz,
H), 7.44 (d, J = 3.8 Hz, 1H), 7.34–7.29 (m, 2H), 7.26 (d, J = 3.9 Hz, 1H), 7.25 (d, J = 3.8 Hz, 1H),
1
3
.10–7.09 (m, 1H), 7.08 (dd, J = 5.3 Hz, J = 3.5 Hz, 1H), 2.48 (s, 3H). C-NMR (100 MHz, CDCl ): δ
3
57.95, 139.89, 139.52, 136.60, 136.33, 128.90, 128.29, 128.09, 128.02, 127.74, 127.57, 126.33,
25.49, 125.24, 124.66, 124.60, 124.16, 124.02, 107.81, 77.33, 77.01, 76.69, 9.27. HRMS (EI) calcd for
+
C
20
H13NOS
4
[M] 410.9880 found 410.9891.
3
.10. Synthesis of1,4-Bis[5-(2,2'-bithiophen-5-yl)isoxazol-3-yl]benzene (18) under high pressure
A solution of 5-ethynyl-2,2'-bithiophene (494 mg, 2.60 mmol) (4) and terephthalo-bis(nitrile
N-oxide) (192 mg, 1.2 mmol) in CH
2
Cl
2
(2 mL) was placed in a Teflon capsule and heated at 100 °C
for 4 h under pressure of 1 GPa. After that, volatile fractions were removed using a rotary evaporator.
Crude product was purified using column chromatography (SiO
obtained as an orange solid with 99% yield.
2
, CH
2
Cl /hexane 1:3). Product 18 was
2
3.11. Synthesis of 8,9-Bis(2,2'-bithiophen-5-yl)-7,10-(diphenyl)fluoranthene (19) and 9-(2,2'-
Bithiophene-5-yl)-8-(5-ethynyl-2,2'-bithiophen-5-yl)-7,10-(diphenyl)fluoranthene (20)
1,8-Bis(phenylethynyl)naphthalene (11 mg, 0.03 mmol) and 5,5'-ethyne-1,2-diylbis(2,2'-bithiophene)
(
(
5) (59 mg, 0.17 mmol) for the synthesis of 19 or 5,5'-buta-1,3-diyne-1,4-diylbis(2,2'-bithiophene) (6)
61 mg, 0.16 mmol) for the synthesis of 20, and Wilkinson’s catalyst (3 mg, 0.003 mmol) were placed
in a screw capped glass vial. Xylene (3 mL) was added, and the vial was tightly capped and placed in
thermostated oil bath in 130 °C and stirred for 72 h. After that, the vial was cooled down and xylene
was evaporated on a rotary evaporator. Crude solid residue was purified on chromatography column
(
SiO ) using petroleum ether (for 19) or hexane:dichloromethane 3:1 (for 20) as an eluent. Products 19
2
and 20 were obtained with 60 and 70% yield, respectively. 19 as a yellow solid, 20 as a yellowish oil.
1
8
,9-Bis(2,2'-bithiophene-5-yl)-7,10-(diphenyl)fluoranthene (19). H-NMR (400 MHz, CDCl
3
): δ 7.74
(
d, J = 8.2 Hz, 2H), 7.36–7.44 (m, 10H), 7.29–7.33 (m, 2H), 7.09 (dd, J = 5.0 Hz, J = 1.1 Hz, 2H), 6.95
dd, J = 3.6 Hz, J = 1.1 Hz, 2H), 6.90 (dd, J = 4.9 Hz, J = 3.6 Hz, 2H), 6.74 (d, J = 3.7 Hz, 2H), 6.59 (d,
(
13
J = 7.1 Hz, 2H), 6.51 (d, J = 3.7 Hz, 2H). C-NMR (100 MHz, CDCl
3
): δ 139.84, 139.49, 138.65,
1
1
37.98, 137.86, 137.71, 136.13, 133.89, 133.44, 130.25, 129.90, 129.76, 128.57, 127.87, 127.70, 127.62,
+
27.11, 123.84, 123.81, 123.21, 122.79. HRMS (EI) calcd for C44
-(2,2'-Bithiophene-5-yl)-8-(5-ethynyl-2,2'-bithiophene-5-yl)-7,10-(diphenyl)fluoranthene (20). 1H-NMR
): δ 7.75 (t, J = 7.7 Hz, 2H), 7.57–7.67 (m, 5H), 7.40–7.48 (m, 5H), 7.34–7.37 (m, 1H),
.29–7.33 (m, 1H), 7.18 (dt, J = 5.0 Hz, J = 1.0 Hz, 2H), 7.12 (dd, J = 3.6 Hz, J = 1.1 Hz, 1H), 7.02 (dd,
H
26
S
4
[M] 682.0917 found 682.0923.
9
(400 MHz, CDCl
3
7
J = 3.6 Hz, J = 1.2 Hz, 1H), 6.98–7.01 (m, 2H), 6.96 (dd, J = 5.0 Hz, J = 3.6 Hz, 1H),

Molecules 2015, 20
4584
6
1
1
1
9
.87–6.89 (m, 2H), 6.82 (d, J = 3.7 Hz, 1H), 6.59–6.61 (m, 2H). 13C-NMR (100 MHz, CDCl
3
): δ
39.72, 139.34, 139.16, 139.01, 138.27, 138.06, 137.94, 137.57, 137.18, 137.03, 136.16, 135.67,
34.90, 133.51, 132.38, 130.12, 129.95, 129.82, 129.77, 128.80, 128.73, 128.19, 127.97, 127.88,
27.26, 127.21, 124.90, 124.16, 124.12, 123.85, 123.83, 123.62, 123.54, 123.52, 123.03, 122.34,
+
4.44, 91.96. HRMS (ESI) calcd for C46
H
27
S
4
[M+H] 707.0996 found 707.1010.
3
.12. Synthesis of Hexa(2,2'-bithiophen-5-yl)benzene (21)
5
,5'-Ethyne-1,2-diylbis(2,2'-bithiophene) (5, 50 mg, 0.14 mmol) and Wilkinson’s catalyst (13 mg,
0
.014 mmol) were placed in a screw capped glass vial. Xylene (3 mL) was added, and the vial was
tightly capped and placed in a thermostated oil bath in 130 °C and was stirred for 72 h. During that
time, the precipitation of grey solid in the reaction mixture was observed. After heating, the vial was
cooled down, and the precipitate was filtered. Crude solid residue was washed with xylene and diethyl
ether, and dried overnight at room temperature. Product 21 was isolated with 40% yield as a grey solid.
1
.1 Hz, 6H), 6.99 (d, J = 3.7 Hz, 6H), 6.97 (dd, J = 5.1 Hz, J = 3.6 Hz, 6H), 6.77 (d, J = 3.7 Hz, 6H).
13C-NMR (125 MHz, DMSO-d
): δ 138.01, 137.78, 136.53, 135.99, 131.06, 128.25, 125.32, 123.80,
6
+
1
22.98. HRMS (EI) calcd for C54
H
30
S12 [M] 1061.8996 found 1061.8977.
3
.13. Synthesis of 1-(2,2'-Bithiophen-5-yl)-4-octyl-1,2,3-triazole (22)
A mixture of 5-iodo-2,2'-bithiophene (3, 0.29 g, 1 mmol), ethanol-water solution (4 mL, 7:3 v/v),
sodium azide (130 mg, 2 mmol), CuI (19 mg, 0.1 mmol), sodium ascorbate (20 mg, 0.1 mmol), 1-decyne
0.18 mL, 1 mmol) and N,N'-dimethylethylenediamine (20 μL, 0.2 mmol) was vigorously stirred at
(
5
2
0 °C for 24h. After that time, the post-reaction mixture was cooled down to room temperature and
5% solution of ammonia (10 mL) and ethyl acetate (15 mL) were added. Organic layer was washed
with water (3 times 15 mL) and dried over anhydrous MgSO . Volatile fractions were removed on a
4
rotary evaporator and a solid residue was purified on chromatography column (SiO
2
, CH
2
Cl ). Product
2
1
2
2 was obtained as a dark solid with 70% yield. H-NMR (400 MHz, CDCl
3
): δ 7.63 (s, 1H), 7.22 (dd,
J = 5.2 Hz, J = 1.1 Hz, 1H), 7.20 (dd, J = 3.6 Hz, J = 1.1 Hz, 1H), 7.09 (d, J = 4.0 Hz, 1H), 7.06 (d,
J = 4.0 Hz, 1H), 7.05 (dd, J = 5.1 Hz, J = 3.6 Hz, 1H), 2.78 (t, J = 7.7 Hz, 2H), 1.72 (dt, J = 15.3 Hz,
1
3
J = 7.8 Hz, 2H), 1.32 (m, 10H), 0.88 (t, J = 6.8 Hz, 3H). C-NMR (100 MHz, CDCl
3
): δ 149.36,
1
2
36.96, 136.19, 134.59, 128.12, 126.37, 124.53, 122.32, 119.79, 117.80, 31.96, 29.44, 29.42, 29.36,
+
9.32, 25.72, 22.77, 14.21. HRMS (ESI) calcd for C18
H
24
N
3
2
S [M+H] 346.1412 found 346.1412.
3
.14. Synthesis of 1-Benzyl-4-(2,2'-bithiophen-5-yl)-1,2,3-triazole (23)
A mixture of 5-(trimethylsilyl)ethynyl-2,2'-bithiophene (150 mg, 0.571 mmol), benzylazide (110 mg,
0
.857 mmol), K
2
CO
3
(87 mg, 0.063 mmol), CuSO
4
·5H O (110 mg, 0.046 mmol), sodium ascorbate
2
(
270 mg, 1.37 mmol), pyridine (0.6 mL, 7.46 mmol) and tert-butanol-water mixture (14 mL, 1:1 v/v)
was stirred at room temperature for 48h. After that time, 25% solution of ammonia (10 mL) and ethyl
acetate (15 mL) was added. Organic layer was washed with water (3 × 15 mL) and dried over
anhydrous MgSO
4
. Volatile fractions were removed on a rotary evaporator and a solid residue was
, CH Cl /CH Cl + 5% MeOH). Product 23 was obtained as
purified on chromatography column (SiO
2
2
2
2
2

Molecules 2015, 20
a dark solid with 50% yield. H-NMR (400 MHz, CDCl
4585
1
3
): δ 7.56 (s, 1H), 7.43–7.37 (m, 3H), 7.33–7.30
(
m, 2H), 7.23 (d, J = 8.8 Hz, 1H), 7.22 (dd, J = 5.1 Hz, J = 1.1 Hz, 1H), 7.18 (dd, J = 3.6 Hz, J = 1.1 Hz,
1
3
1
1
1
H), 7.11 (d, J = 3.8 Hz, 1H), 7.02 (dd, J = 5.1 Hz, J = 3.6 Hz, 1H). C-NMR (100 MHZ, CDCl ) δ
3
43.12, 137.22, 137.09, 134.53, 131.69, 129.33, 129.01, 128.24, 128.02, 124.84, 124.68, 124.21,
+
23.98 119.04, 53.43. HRMS (ESI) calcd for C17
H
14
N
3
S
2
[M+H] 324.0629 found 324.0629.
3
.15. Synthesis of 1-Decyl-4-(2,2'-Bithiophen-5-yl)-1,2,3-triazole (24) under High Pressure
A solution of 5-ethynyl-2,2'-bithiophene (4) (100 mg, 0.525 mmol) and decylazide (144 mg,
0
.788 mmol) in CH
2
Cl (2 mL) was placed in a teflon capsule and heated at 80 °C for 24h under
2
pressure of 1 GPa. After that, volatile fractions were removed using a rotary evaporator. Crude product
was purified using column chromatography (SiO
2
, CH
2
Cl ). Product 24 was obtained as a dark solid
2
1
with 60% yield. H-NMR (400 MHz, CDCl
3
): δ 7.65 (s, 1H), 7.26 (d, J = 3.8 Hz, 1H), 7.22 (dd,
J = 5.1 Hz, J = 1.1 Hz, 1H), 7.20 (dd, J = 3.6 Hz, J = 1.1 Hz, 1H), 7.13 (d, J = 3.8 Hz, 1H), 7.02 (dd,
J = 5.1 Hz, J = 3.6 Hz, 1H), 4.36 (t, J = 7.2 Hz, 2H), 1.93 (m, 2H), 1.29 (m, 14H), 0.87 (t, J = 6.8 Hz,
1
3
3
H). C-NMR (100 MHz, CDCl ): δ 142.57, 137.27, 136.93, 131.96, 127.99, 124.66, 124.62, 124.21,
3
1
23.92, 118.99, 50.63, 31.95, 30.39, 29.56, 29.48, 29.35, 29.10, 26.58, 22.76, 14.20. HRMS (ESI)
+
calcd for C20
H
28
N
3
S
2
[M+H] 374.1725 found 374.1727.
3
.16. Synthesis of 1-Decyl-4,5-bis(2,2'-bithiophen-5-yl)-1,2,3-triazole (25)
The mixture of decylazide (61 mg, 0.33 mmol), bbta(5) (150 mg, 0.42 mmol), benzene (7 mL) and
RuCl(cp)(PPh ] (8 mg, 0.011 mmol) was stirred at 80 °C for 24 h. After that, volatile fractions were
[
)
3 2
removed using a rotary evaporator. Crude product was purified using column chromatography (SiO
2
,
1
hexane:ethyl acetate 9:1). Product 25 was obtained as a dark solid with 60% yield. H-NMR (400
MHz, CDCl
J = 1.1 Hz, 1H), 7.20 (dd, J = 5.1 Hz, J = 1.1 Hz, 1H), 7.16 (dd, J = 3.6 Hz, J = 1.1 Hz, 1H),
.13–7.11 (m, 2H), 7.07 (dd, J = 5.1 Hz, J = 3.6 Hz, 1H), 7.04 (d, J = 3.8 Hz, 1H), 6.99 (dd, J = 5.1 Hz,
J = 3.6 Hz, 1H), 4.28 (m, 2H), 1.87 (m, 2H), 1.26 (m, 14H), 0.86 (t, J = 6.8 Hz, 3H). 13C-NMR
3
): δ 7.31 (dd, J = 5.1 Hz, J = 1.1 Hz, 1H), 7.29 (d, J = 3.7 Hz, 1H), 7.27 (dd, J = 3.6 Hz,
7
(100 MHz, CDCl
3
): δ 141.99, 141.71, 137.49, 137.27, 136.24, 131.94, 131.63, 128.23, 127.98, 125.69,
1
2
25.66, 125.56, 124.91, 124.66, 124.33, 124.26, 124.15, 124.08, 48.88, 31.99, 30.44, 29.60, 29.48,
+
9.40, 29.07, 26.59, 22.79, 14.25. HRMS(EI) calcd for C28
H
31
N
3
4
S [M] 537.14009 found: 537.13955.
3.17. Synthesis of N-phenyl-2,5-bis(2,2'-bithiophen-5-yl)pyrrole (26), N-(p-decyloxy)phenyl-2,5-bis(2,2'-
bithiophen-5-yl)pyrrole (27) and N-(2-carbazolylethyl)-2,5-bis(2,2'-bithiophen-5-yl)pyrrole (28)
A mixture of 1,4-bis(2,2'-bithiophen-5-yl)buta-1,3-diyne (6, 50 mg, 0.132 mmol), CuCl (1.31 mg,
0
.0132 mmol) and aniline (0.12 mL, 1.32 mmol) (for 26) or p-(decyloxyphenyl)aniline (330 mg,
.64 mmol) (for 27) or N-ethyl-3-aminocarbazole (560 mg, 2.64 mmol) (for 28) was stirred at 110 °C
2
for 48 h. After that time, post-reaction mixture was cooled down to room temperature and CH
2
Cl
2
(50 mL) was added. Mixture was filtered and the filtrate was washed with 0.5 M solution of NaCN in
water (3 × 20 mL). The organic layer was dried over anhydrous MgSO
4
and volatile fractions were
Cl mixture (5:1) and
removed using a rotary evaporator. Crude residue was dissolved in hexane:CH
2
2

Molecules 2015, 20
4586
loaded on chromatography column (SiO
2
). Compounds 26, 27 and 28 were isolated as yellow solids
with 30, 31 and 74% yield, respectively. For the isolation of pure products, the following eluents were
used: hexane:CH
2
Cl
2
(5:1) for 26 and 27; hexane:CHCl
3
(5:2) with 1% of triethylamine for 28.
1
N-phenyl-2,5-bis(2,2'-bithiophene-5-yl)pyrrole (26). H-NMR (400 MHz, CDCl
3
): δ 7.51 (m, 3H), 7.40
(dd, J = 8.1 Hz, J = 1.4 Hz, 2H), 7.17 (dd, J = 5.1 Hz, J = 1.1 Hz, 2H), 7.06 (dd, J = 3.6 Hz, J = 1.1 Hz,
2
H), 6.98 (dd, J = 5.1 Hz, J = 3.6 Hz, 2H), 6.89 (d, J = 3.8 Hz, 2H), 6.60 (s, 2H), 6.36 (d, J = 3.8 Hz, 2H).
13C-NMR (100 MHz, CDCl
): δ 138.44, 137.42, 135.67, 133.88, 130.25, 130.10, 129.63, 129.56, 127.89,
3
+
124.72, 124.23, 123.90, 123.45, 110.24. HRMS (EI) calcd for C26
H17NS
4
[M] 471.0244 found 471.02434.
1
N-(p-decyloxy)phenyl-2,5-bis(2,2'-bithiophene-5-yl)pyrrole (27). H-NMR (400 MHz, CDCl
3
): δ 7.27
(
(
(
m, 2H), 7.15 (dd, J = 5.1 Hz, J = 1.1 Hz, 2H), 7.04 (dd, J = 3.6 Hz, J = 1.1 Hz, 2H), 6.97 (m, 4H), 6.88
d, J = 3.8 Hz, 2H), 6.56 (s, 2H), 6.40 (d, J = 3.8 Hz, 2H), 4.03 (t, J = 6.6 Hz, 2H), 1.84 (m, 2H), 1.33
13
s, 15H), 0.88 (t, J = 6.6 Hz, 3H). C-NMR (100 MHz, CDCl
3
): δ 160.04, 137.53, 135.50, 134.11, 131.07,
1
2
30.76, 130.55, 127.88, 124.48, 124.17, 123.96, 123.42, 115.32, 109.88, 68.57, 32.06, 29.74, 29.72, 29.59,
+
9.48, 29.37, 26.21, 22.83, 14.26. HRMS (EI) calcd for C36
H
37NOS [M] 627.1758 found 627.1757.
4
1
N-(2-carbazolylethyl)-2,5-bis(2,2'-bithiophen-5-yl)pyrrole (28). H-NMR (400 MHz, CDCl
3
): δ 8.12
(
d, J = 1.8 Hz, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.50 (m, 5H), 7.09 (dd, J = 5.1 Hz, J = 1.1 Hz, 2H), 6.94
(
dd, J = 3.6 Hz, J = 1.1 Hz, 2H), 6.90 (dd, J = 5.0 Hz, J = 3.6 Hz, 2H), 6.77 (d, J = 3.9 Hz, 2H), 6.63 (s,
13
2
H), 6.30 (d, J = 3.9 Hz, 2H), 4.46 (q, J = 7.2 Hz, 2H), 1.53 (t, J = 7.2 Hz, 3H). C-NMR (100 MHz,
): δ 140.88, 140.17, 137.49, 135.15, 134.47, 130.98, 129.56, 127.80, 127.22, 126.57, 124.22,
24.04, 124.00, 123.57, 123.33, 122.83, 122.16, 121.16, 119.52, 109.74, 109.11, 109.05, 38.07, 14.05.
CDCl
3
1
+
HRMS (EI) calcd for C34
. Conclusions
This work reports several highly effective new catalytically or high-pressure-activated reactions and
H
24
N
2
S
4
[M] 588.0822 found 588.0837.
4
routes leading to diverse 2,2'-bithiophene derivatives. New Pd/Cu-mediated coupling reactions, Mn-, Rh-,
Cu- or Ru-catalyst mediated various type of cycloaddition, Ru-complex or 15-crown-5/NaOH promoted
double bond migration in allylic systems and Cu/NEt -mediated complexation of metal centre were
3
presented. Thanks to these new catalytic reactions and catalytic routes (combined with non-catalytic
processes), we obtained novel acetylene, butadiyne, isoxazole, 1,2,3-triazole, pyrrole, benzene and
fluoranthene derivatives bearing one, two or six 2,2'-bithiophen-5-yl (bt) moieties. The obtained
compounds are of general formulas: bt-A, bt-A-bt and (bt) A, where 2,2'-bithiophen-5-ylic fragments
6
are connected by -C≡C-, -C≡C-C≡C-, aryl and heteroaryl. The “first generation” substrate containing
bithiophene motif was 5-lithio-2,2'-bithiophene, which was converted into 5-iodo- and 5-allyl-2,2'-
bithiophenes (“the second generation” substrate). In the next step, the above mentioned compounds
were transformed catalytically to 5-ethynyl-2,2'-bithiophene, 1,2-bis(2,2'-bithiophene-5-yl)acetylene,
5-(1-propenyl)-2,2'-bithiophene, and 1,4-bis(2,2'-bithiophene-5-yl)buta-1,3-diyne (“the third generation”
substrates). Moreover, in situ generated 2,2'-bithiophen-5-carbonitrile oxide and 2,2'-bithiophen-5-yl azide
belonging to the third-generation substrates were used. For the synthesis of 1,2-bis(2,2'-bithiophene-5-
yl)acetylene and 1,4-bis(2,2'-bithiophene-5-yl)buta-1,3-diyne gaseous acetylene and butadiyne and very

Molecules 2015, 20
4587
effective cascade reactor systems were used. All the obtained compounds including bithiophene motif can
be applied in organic electronics as monomers for new conducting polythiophenes or as luminescence
materials. Moreover, some of them, for instance triazole derivatives, can play the role of cyclometalated
ligands, while others should interest scientists searching for new medical probes and pharmaceutics,
i.e., antifungal ones. Our preliminary examination, presented in the supporting information, has shown
that some of the obtained compounds have very interesting luminescence properties and the derivatives
which contain at least two bt motifs can be easily electropolymerized into conducting polymers.
Supplementary Materials
Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/20/03/4565/s1.
Acknowledgments
This work was supported by National Science Centre of Poland, Projects No.:
DEC-011/01/B/ST5/06309 and DEC-2012/05/N/ST5/00733, and by The National Centre of Research
and Development, Project No. PBS2/A5/40/2014. Moreover, J. Malarz acknowledges a scholarship
from the TWING project co-financed by the European Social Fund. S. Kula acknowledges a
scholarship from the Forszt project co-financed by the European Social Fund. I. Grudzka-Flak, M.
Filapek, G. Szafraniec-Gorol, B. Marcol, M. Matussek, A. Szlapa acknowledge a scholarships from the
DoktoRIS project co-financed by the European Social Fund.
Author Contributions
Stanisław Krompiec wrote the manuscript, developed the main idea of the work; Michał Filapek
performed electrochemical measurements, synthesized isoxazoles, co-author of the main idea of the
work; Iwona Grudzka-Flak synthesized pyrroles; Aneta Słodek wrote the experimental part, co-author
of the main idea of the work; Sławomir Kula synthesized benzene derivatives via Mn catalysis;
Jan Grzegorz Malecki performed X-ray measurements and calculations; Joanna Malarz synthesized
isoxazolines; Grażyna Szafraniec-Gorol synthesized triazoles; Mateusz Penkala performed [2 + 2 + 2]
cycloaddition reactions; Ewa Schab-Balcerzak co-author of the main idea of the work; Marian Paluch
performed reactions under high pressure; Michał Mierzwa performed reactions under high pressure;
Marek Matussek synthesized bis(bithienyl) derivatives of acetylene and buta-1,3-diyne; Agata Szłapa
performed NMR measurements and analysis; Michał Pająk synthesized some of the isoxazolines and
isoxazoles; Dariusz Błach performed aromatization of dihydroisoxazolines; Beata Marcol performed
isomerisation of allyl precursors; Witold Danikiewicz performed MS and HRMS measurements and
analysis; Bartosz Boharewicz co-author of part devoted to preliminary examination of novel
2
,2'-bithiophene derivatives in organic electronics; Agnieszka Iwan co-author of part devoted to
preliminary examination of novel 2,2'-bithiophene derivatives in organic electronics. All authors
discussed the results and commented on the manuscript.
Conflicts of Interest
The authors declare no conflict of interest.

Molecules 2015, 20
4588
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Sample Availability: Samples of the compounds (5)–(28) (except of compound 13a) are available from
the authors.
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