Improved synthesis of a terthiophene-based monomeric ligand that forms a highly active polymer for the carbon dioxide reduction

Article abstract of DOI:10.2174/1570178614666170503122330

Background: The carbon-dioxide reduction to obtain important chemicals such as fuels is a topic of high current interest. Recently, monomeric thiophenes and terthiophenes linked to a bipyridine ligand were designed and their polymeric films achieved very high turnover numbers during electrocatalytic CO2 reduction. In this paper we improved the protocol to access the ligand that shows the best performances, in view of opening the way to a general method to obtain side-functionalized terthiophenes. Methods: Several reactions were attempted to improve the synthetic pathway. Different approaches were attempted to convert the 3-bromothiophene into its 3-iodo analog and to brominate it to obtain the 2,5-dibromo-3-iodothiophene. The synthetic pathway was completed by using Pd-catalyzed crosscoupling reactions such as Sonogashira and Suzuki. The removal of a trimethylsilyl protection was attempted by common methods. However, with the use of a one-pot reaction, both the alkyne deprotection and the final Sonogashira coupling were performed as the key point of the pathway to obtain the final product. Results: The key intermediate 2,5-dibromo-3-iodothiophene was obtained by a CuI assisted electrophilic aromatic substitution, followed by a bromination with NBS in ethyl acetate. This compound was reacted with TMS-acetylene to obtain the ((2,5-dibromothiophen-3-yl)ethynyl)trimethylsilane which, by a Suzuki reaction, afforded the ([2,2':5',2''-terthiophen]-3'-ylethynyl)trimethylsilane. Using a onepot reaction for the last step, the deprotection of the TMS-protected alkyne and its coupling with 4- bromo-2,2'-bipyridine was accomplished easily. A final 52% yield was achieved over 5 steps. Conclusion: The ligand 4-([2,2':5',2''-terthiophen]-3'-ylethynyl)-2,2'-bipyridine was prepared in a 52% yield, over 5 steps, improving the previous protocol (17% yield over 4 steps). The rhenium complex of this ligand is still under study for CO2 reduction. This novel protocol can be used to produce a series of analog terthiophene monomers bearing side-attached ligands.

Full text of DOI:10.2174/1570178614666170503122330

472
Send Orders for Reprints to reprints@benthamscience.ae
Letters in Organic Chemistry, 2017, 14, 472-478
LETTER ARTICLE
ISSN: 1570-1786
eISSN: 1875-6255
Improved Synthesis of a Terthiophene-Based Monomeric Ligand That
Forms a Highly Active Polymer for the Carbon Dioxide Reduction
Impact
Factor:
0.664
BENTHAM
S
CIENCE
Pierluigi Quagliotto*, Simona Prosperini and Guido Viscardi
Dipartimento di Chimica, Università di Torino, Torino, Italy
Abstract: Background: The carbon-dioxide reduction to obtain important chemicals such as fuels is a
topic of high current interest. Recently, monomeric thiophenes and terthiophenes linked to a bipyridine
ligand were designed and their polymeric films achieved very high turnover numbers during electro-
catalytic CO2 reduction. In this paper we improved the protocol to access the ligand that shows the best
performances, in view of opening the way to a general method to obtain side-functionalized terthio-
phenes.
Methods: Several reactions were attempted to improve the synthetic pathway. Different approaches
were attempted to convert the 3-bromothiophene into its 3-iodo analog and to brominate it to obtain the
2,5-dibromo-3-iodothiophene. The synthetic pathway was completed by using Pd-catalyzed cross-
coupling reactions such as Sonogashira and Suzuki. The removal of a trimethylsilyl protection was at-
A R T I C L E H I S T O R Y
tempted by common methods. However, with the use of a one-pot reaction, both the alkyne deprotec-
tion and the final Sonogashira coupling were performed as the key point of the pathway to obtain the
final product.
Received: November 24, 2016
Revised: February 20, 2017
Accepted: April 08, 2017
Results: The key intermediate 2,5-dibromo-3-iodothiophene was obtained by a CuI assisted electro-
philic aromatic substitution, followed by a bromination with NBS in ethyl acetate. This compound was
DOI:
10.2174/1570178614666170503122330
reacted with TMS-acetylene to obtain the ((2,5-dibromothiophen-3-yl)ethynyl)trimethylsilane which,
by a Suzuki reaction, afforded the ([2,2':5',2''-terthiophen]-3'-ylethynyl)trimethylsilane. Using a one-
pot reaction for the last step, the deprotection of the TMS-protected alkyne and its coupling with 4-
bromo-2,2’-bipyridine was accomplished easily. A final 52% yield was achieved over 5 steps.
Conclusion: The ligand 4-([2,2':5',2''-terthiophen]-3'-ylethynyl)-2,2'-bipyridine was prepared in a 52%
yield, over 5 steps, improving the previous protocol (17% yield over 4 steps). The rhenium complex of
this ligand is still under study for CO2 reduction. This novel protocol can be used to produce a series of
analog terthiophene monomers bearing side-attached ligands.
Keywords: Carbon dioxide reduction, catalysis, Suzuki cross-coupling, Sonogashira cross-coupling, monomeric ligand, polymer.
1. INTRODUCTION
giving good results [6, 7]. Electrochemical CO2 reduction
was originally developed to study the activity of rhenium
complexes in solution [6, 7]. The immobilization of the cata-
lyst was tried with different approaches, one of which is
based on the electropolymerization of monomers having a
pendant organometallic catalytically active moiety onto an
electrode [8]. With the aim to give a contribution to this last
topic, recently we studied the electrochemical carbon dioxide
reduction to carbon monoxide, using rhenium complexes [9].
In order to facilitate the transfer of electrons from the elec-
trode to the catalytic centers and to the CO2 the polymer
should be able to be conductive. Few cases were found in
literature [6-8]. In our previous study about the preparation
of thiophene-based monomers, their electrochemical-driven
polymerization and their CO2 reduction activity, we synthe-
sized a terthiophene monomer in which the terthiophene was
One of the most important problems of our age is con-
nected with the overproduction of carbon dioxide, due to the
enhanced exploitation of fossil fuels to obtain energy. The
technological approaches to reduce carbon dioxide impact
span from the use of renewable sources to produce chemi-
cals, [1, 2] to the capture and storage of CO2, [3, 4] to the
attempt to reduce CO2 in order to convert it to useful chemi-
cals and, possibly, fuels [5]. The conversion of carbon diox-
ide into other compounds has been intensively studied over
the last few decades, with electrochemical CO2 reduction,
*Address correspondence to this author at Dipartimento di Chimica, Univer-
sità di Torino, via Pietro Giuria 7, 10125 Torino, Italy; Tel/Fax: +39-011-
670-7593, +39-011-670-7591; E-mail: pierluigi.quagliotto@unito.it
1875-6255/17 $58.00+.00
© 2017 Bentham Science Publishers

Improved Synthesis of a Terthiophene-Based Monomeric Ligand
Letters in Organic Chemistry, 2017, Vol. 14, No. 7 473
connected with the bipyridine ligand moiety, through an al-
posited on electrodes. The CO2 reduction tests performed on
these electrodes, gave a TONCO of 519, approaching the best
turnover numbers (TON) ever obtained with this approach
for the production of CO with the complex 2a (516-600)
(See Chart 1 for structures of the best performing compounds
2a-f and Table 1 for their TON data) [9]. See also the Elec-
tronic Supplementary Information of this reference for syn-
thesis details.
kyne bridge (compound 1) (Fig. 1).
N
N
S
S
As one can easily evidence, polythiophenes based on 2e-
2f complexes showed an important activity towards the CO2
reduction to CO [9]. Besides, those polythiophenes seemed
to reduce slightly the applied potential to obtain the reduc-
tion, with respect to polypyrroles 2b-d. Since these mono-
mers and the derived polymers showed very interesting re-
sults, the improvement of their synthetic pathway was an
interesting topic. We recently reported about the optimized
synthesis of the precursor ligand for 2e in almost green con-
ditions [10]. In this paper we describe an improved synthetic
S
1
Fig. (1). Terthiophene monomer, whose synthesis was improved in
this paper.
This compound was used to prepare a rhenium complex
which, by electropolymerization, gave a polymeric film de-
N
N
N
N
N
(CH2)4
Cl
Re
CO
Cl
Re
CO
Cl
Re
CO
Cl
Re
CO
N
N
N
N
N
N
N
N
CO
CO
CO
CO
OC
OC
OC
OC
2a
2b
2c
2d
CO
OC
N
Re CO
Cl
CO
Re CO
N
OC
N
Cl
N
S
S
S
S
S
S
2e
2f
Chart (1). Organometallic monomers employed in literature for the preparation and immobilization of polymers onto electrodes for CO2
reduction [6, 8, 9].
Table 1. Comparison of the CO2 reduction activity in CH3CN for the polymers obtained from monomers represented in Chart 1,
immobilized onto electrodes.
ηCO (%)
Comp.
E
(V)
TONco
Time (min)
Refs.
2a
2b
2c
2d
2e
2f
-1.93
-2.23
-2.23
-2.23
-2.10
-2.10
94
98.5
69
516-600
133-236
34
60
120
120
120
40
[6]
[8]
[8]
[8]
[9]
[9]
98
118
84.7
489
34.0
519
40
Conditions: MeCN solution (0.1 M TBAPF6 as supporting electrolyte). Potentials are in V vs. Fc/Fc+. E: potential applied to the electrode; ηCO: faradaic efficiency towards CO;
TONCO: Turnover number for CO.

474 Letters in Organic Chemistry, 2017, Vol. 14, No. 7
Quagliotto et al.
method for the ligand 1 from which 2f can be easily pre-
iodine in position 3 and a further Suzuki reaction on the
bromine atoms in 2 and 5 position to give the terthiophene 6.
The preparation of the intermediate 4 has been published
[12]. We used some insights taken from the literature to
build a novel protocol (Scheme 2) [12-14].
pared.
2. RESULTS AND DISCUSSION
The original method to prepare ligand 1 was derived
from the work of Manca et al., [11] who devised the synthe-
sis of a similar compound (Scheme 1). The method devised
in Scheme 1 showed two low-yield steps, the first and the
last one. The final total yield for 1 in the original synthesis
was about 17% [9]. Since the practical importance of ligand
1 and in view of the preparation of similar terthiophene-
based ligands, it seemed interesting to revise completely its
preparation method.
(ii a) Yield 80%
Yield 85%
(i a)
Br
I
I
(i b)
(ii b)
Br
Br
Yield 98%
S
S
S
Yield 53%
3
4
(i c)
Yield 46%
TMS
(iii a)
(iii b)
Yield 70%
Yield 82%
Br
Br
Br
(i)
TMS
S
Br
S
S
S
(43%)
(iv)
S
Br
S
Br
S
S
Yield (80 %)
(ii)
5
6
OH
(v)
Yield (95 %)
(iii)
N
N
S
S
S
S
S
S
(85%)
(56%)
(iv)
S
S
S
1
N
N
Scheme (2). Novel protocol for the synthesis of 1. (i a) NaI, CuI,
N,N-dimethylethylenediamine, toluene:dioxane 4:1, 110°C, 24 h; (i
b) NaI, CuI, N,N-dimethylethylenediamine, n-butanol, 120°C, 3 h;
(i c) NaI, Cu2O, L-Proline, ethanol, 110°C, 21 h; (ii a) NBS, DMF,
60°C, 24 h; (ii b) NBS, ethyl acetate, 60°C, 30 h; (iii a)
Pd(PPh3)2Cl2, CuI, trimethylsilylacetylene (TMS-acetylene), TEA,
0°C, 6 h; (iii b) Pd(PPh3)4, CuI, TMS-acetylene, TEA, 0°C, 3 h; (iv)
2-thiopheneboronic acid, Pd(PPh3)4, 1M NaHCO3, DME, 80°C, 2 h;
(v) 4-bromo-2,2’-bipyridine, 1,8-Diazabicyclo[5.4.0]undec-7-ene
(DBU), Pd(PPh3)2Cl2, CuI, water (40% with respect to the limiting
reagent), benzene, 80°C, 18 h.
S
S
S
(30%)
1
Scheme (1). Original synthetic method for compound 1. (i) 2-
thiopheneboronic acid, Pd(PPh3)4, 1.5M NaHCO3, DME, micro-
waves (MW), 130°C, 30 min; (ii) 2-methyl-3-butyn-2-ol,
Pd(PPh3)4, CuI, diisopropylamine (DIPA), reflux, Ar, 20 h; (iii)
KOH, toluene:methanol 1:1, reflux, Ar; (iv) 4-bromo-2,2’-
bipyridine, Pd(PPh3)4, CuI, DIPA, reflux, Ar, 20 h.
The synthetic pathway started with the transformation of
the 3-bromothiophene into the 3-iodothiophene 3. We tried a
few protocols, based on two catalytic approaches. The first
one is based on the Buchwald findings [15] about a sort of
Finkelstein aromatic reaction. The reaction was performed
following the original protocol [12] with NaI, CuI and N,N-
dimethylethylenediamine using toluene:dioxane 4:1 as sol-
vents, at 110°C for 24 h (yield: 85%). We observed a slightly
improved yield, over the literature. We also substituted the
solvent with n-butanol, at 120°C for 24 h, as reported in the
literature, [16] obtaining a 53% yield. A second protocol was
In the original method the first step gave a low yield that
was due to the presence of three bromine atoms on the start-
ing material, whose substitution was occurring in sequence
and it was difficult to be stopped properly after the second
substitution [10, 11]. In order to avoid this problem, we tried
to prepare the 2,5-dibromo-3-iodothiophene. This intermedi-
ate could be used to perform a Sonogashira reaction on the

Improved Synthesis of a Terthiophene-Based Monomeric Ligand
Letters in Organic Chemistry, 2017, Vol. 14, No. 7 475
attempted to improve the yield, on the basis of a different
green method using Cu2O, L-proline in ethanol at 120°C
[17]. The application of this method gave a 46% yield.
a modification of the Sonogashira coupling, designed for
both symmetrical and unsymmetrical bisarylethynes [14],
using TMS-acetylene, DBU as a base, Pd(PPh3)2Cl2, CuI and
water (40% with respect to the starting material) in benzene
as a solvent. The method is quite general, since it can work
on both iodides and bromides, can be selectively used to
react iodides in the presence of bromides (iodides react at
60°C, while bromides require higher temperature, about 80°C)
and afford excellent yields for both symmetrical and un-
symmetrical alkynes. Besides, as a further key point, aryl
halides bearing electronwithdrawing groups (like our reagent
4-bromobipyridine) are the compounds most prone to react.
Since the protocol was originally designed to react two aryl
halides in sequence with TMS-acetylene, we needed to use
only the last part of it, starting with the TMS-protected het-
eroarylacetylene 6 and with 4-bromobipyridine. The reaction
was thus performed with DBU, Pd(PPh3)2Cl2, CuI and water
in benzene at 80°C for 18 h. The title compound 1 was ob-
tained easily and isolated by chromatography in 95% yield.
The whole process required 5 steps with a final yield of 52%.
If we compare the two protocols by starting both from a tri-
halothiophene, the 2,3,5-tribromothiophene for the original
protocol and the 2,5-dibromo-3-iodothiophene for the new
method, the novel protocol requires only 3 steps (4 steps are
required for the original protocol) to give 1 in a yield of
62%, about 3.5 times higher than in the original synthetic
pathway.
The main problem to be addressed to ensure a high re-
covery of the product is the evaporation of the solvent, since
3 shows a high volatility [17]. We avoided as much as possi-
ble the use of common laboratory evaporators and a Claisen
distillation apparatus, trying to evaporate the common sol-
vents used to help the material transfer into the flasks, such
as dichloromethane or hexane, directly at rt under the re-
duced pressure produced by a water pump. A further careful
and slow distillation of the reaction solvent, such as xylene,
not exceeding 65-70°C, afforded the best recoveries. Ethanol
could be distilled in the same way at rt, which made the
Cu2O catalyzed reaction attractive due to its simplicity, green
character and easiness of work-up.
The key intermediate 4 was first obtained by bromination
of 3 with NBS in DMF at 60°C for 5 h (yield: 80%), as from
the original protocol that developed part of this pathway
[12]. This second step was also attempted with a similar pro-
tocol, in which the solvent was ethyl acetate. In a recent pa-
per a fast bromination of thiophene was promoted by the use
of ultrasounds in different solvents [13]. When we optimized
the synthesis of the 4-([2,2':5',2''-terthiophen]-3'-yl)-2,2'-
bipyridine ligand, precursor of the 2e complex, we found that
the presence of the electronwithdrawing bipyridyl substituent
on the 3- position of the thiophene, prevented the reaction
under irradiation with ultrasounds [10]. However, when the
reaction was performed on the 4-(thiophen-3-yl)-2,2’-bipyridine
with NBS in ethyl acetate at rt over 5 days (no ultrasound),
the corresponding 2,5-dibromo compound was obtained in
quantitative yield [10]. The application of this bromination in
EtAc at room temperature on small quantities of 3 (0.5-1.0 g)
gave 90% yield after 5 days, while by raising the temperature
to 60°C, a 92% yield was obtained in 24 h, shortening con-
siderably the reaction time. When the reaction was per-
formed on larger quantities (5 g) the yield approached 98%.
The simple use of a different solvent raised some important
points. The yield was greatly improved, the ethyl acetate is
considered a green solvent, greener than DMF, [18] and it is
easier to be removed.
The title product 1 was thus obtained in a fast and rea-
sonable easy way with a good total yield over 5 steps. The
rhenium complex obtained from 1 was used to prepare
polymers immobilized onto electrodes for the selective car-
bon dioxide reduction to carbon monoxide [9]. Also, some
films of these conductive polymers are showing charge sepa-
ration under illumination, an interesting phenomenon that is
currently being studied [23].
3. MATERIALS AND METHODS
All chemicals were purchased from Aldrich or Fluka and
were used without further purification. All reactions were
performed under Argon atmosphere. The reactions were per-
formed in 20 mL vials or 100 mL reactors that were crimped
and sealed with PTFE septa caps. Some reactions were per-
formed in a 250 ml flask. The reactions were monitored by
GC-MS and/or thin layer chromatography (TLC) using silica
gel as stationary phase on plastic sheets and eluents as re-
ported for the purification in each procedure. The products
were purified using a Biotage Isolera automated medium
pressure purification system, equipped with UV detector
(using variable/fixed wavelength and a Diode array, from
200 to 400 nm), working with silica stationary phase. The
eluents used for the purifications are indicated, for every
product, in the proper synthetic procedure.
The difference in reactivity of the iodo- and bromo- func-
tionalities in the thiophene 4 was exploited to insert the
TMS-protected alkyne in the 3- position by a Sonogashira
reaction and two thiophenes in 2,5- positions by a Suzuki
reaction in two sequential steps. The compound 5 was thus
obtained by a Sonogashira reaction between 4 and trimethyl-
silylacetylene with Pd(PPh3)2Cl2 and CuI in TEA as a sol-
vent, at 0°C for 6 h (yield 70%) [12]. By simple substitution
of the catalyst with Pd(PPh3)4 in the same conditions the
reaction completed in 3 hours, giving 4 in 82% yield. A con-
ventional Suzuki reaction helped to obtain 6 from 5, in 80%
yield. The removal of the trimethylsilyl protective group was
attempted with different protocols [11, 19-22]. However the
yield was ranging between 70% and 80% and, in the best
case, an impurity was still present and could not be sepa-
rated, as also reported in literature [11]. In order to increase
the final total yield for 1 and to reduce the number of reac-
tion steps in the protocol, we looked for one pot protocols to
perform the transformation from 6 to 1. We were attracted by
NMR spectra were recorded in CDCl3 with a Brüker
Avance 200 NMR Spectrometer, working at 200 MHz for 1H
and 50 MHz for 13C. Chemical shifts were reported in parts
per million (δ) using TMS and residual solvent peaks as a
reference.
GC-MS were recorded with a Thermo Finningan Trace
GC instrument equipped with a Zebron-5MS fused silica

476 Letters in Organic Chemistry, 2017, Vol. 14, No. 7
Quagliotto et al.
column of Phenomenex (30 × 0.25 mm i.d., 0.25 µm film
tickness), injector temperature of 250°C, split flow of 10
mL/min, carrier gas Helium at constant flow of 1.2 mL/min.
with argon. The xylene (40 mL) and the dioxane (10 mL),
previously flushed with argon for 20 min, were introduced.
The N,N'-dimethylethylendiamine (0.541 g, 0.600 mL, 6.13
mmol, 0.1 eq.) and the 3-bromothiophene (10.00 g, 61.3
mmol, 1 eq.) were added. The suspension was degassed with
argon for 10 min and it was introduced into the oil bath,
warmed at 110°C. The reaction was checked by GC and
stopped after 24 h. The suspension was filtered on a Buchner,
and the solid was washed with dichloromethane. The most
volatile solvents were removed under vacuum with a Claisen
apparatus working at rt, and the highest boiling solvent (xy-
lene) was removed in the same apparatus by warming from rt
to 65-70°C as a maximum, to minimize product losses.
Microanalyses were performed with a CHNS-O Analyzer
Thermo flash 1112.
3.1. 4-([2,2':5',2''-terthiophen]-3'-ylethynyl)-2,2'-bipyri-
dine (1)
A 100 mL reactor was dried by keeping it in an oven
overnight; it was closed with a rubber stopper and was
purged with argon for 20 min. In the reactor, Pd(PPh3)2Cl2,
(44 mg, 0.063 mmol, 0.03 eq.) CuI (42 mg, 0.209 mmol,
0.10 eq.) were added and the reactor was purged with argon.
Compound 6 (0.720 g, 2.089 mmol, 1 eq.) was added as a
solution in benzene (10 mL). Further benzene (20 mL) was
added along with TEA (1.328 g, 0.726 mL, 13.128 mmol, 6
eq.) and the solution was left to stir at rt under argon. The 4-
bromo-2,2’-bipyridine, (0.540 g, 2.298 mmol, 1.10 eq.) DBU
(3.82 g, 3.75 mL, 25.07 mmol, 12 eq.) and water (16 mg, 16
µl, 0.875 mmol, 0.40 eq.) were finally added and the solution
was put in a pre-heated oil bath 60°C, and left to react under
vigorous stirring for 18 h. The reaction was stopped and the
benzene was removed under vacuum by distillation. The
residue was extracted with diethyl ether (3 × 50 mL) and
water (50 mL). The organic layer was washed with 10% HCl
(3 × 50 mL) and brine (1 × 50 mL) and the organic phase
was dried with Na2SO4, filtered and evaporated under vac-
uum. The crude was purified by chromatography on Biotage
on silica (100 g) with dichloromethane-TEA (0.5%) and after
with a gradient from dichloromethane to dichloromethane:
ethyl acetate 8:2. A yellow solid was finally obtained: 849.6
mg (95%).
m.p.: 153-156°C. 1H NMR (200 MHz, CDCl3) δ 8.70 (m,
2H, H6pyr and H6’pyr), 8.56 (s, 1H, H3pyr), 8.41 (d, J = 8.0
Hz, 1H, H3’pyr), 7.83 (td, J = 7.8, 1.8 Hz, 1H, H4pyr), 7.51
(dd, J = 3.7, 1.2 Hz, 1H, H3 or H3”), 7.44 (dd, J = 5.0, 1.5
Hz, 1H, H5 or H5”), 7.37 (dd, J = 5.1, 1.1 Hz, 1H, H5 or
H5”), 7.34-7.29 overlapping (m, J = 7.5 4.8, 1.1, 1H, H5pyr
or H5’pyr), 7.26 (dd, J = 5.1, 1.1 Hz, 1H, H3 or H3”), 7.20
(m (dd + s), 3.5, 1.2 Hz, 2H, H4’ and H5pyr or H5’pyr), 7.09
(dd, J = 5.1, 3.7 Hz, 1H, H4 or H4”).7.06 (dd, J = 5.1, 3.7
Hz, 1H, H4 or H4”). 13C NMR (50 MHz, CDCl3) δ 156.43
(C2q-pyr), 155.65 (C2’q-pyr), 149.38 (C6-pyr or C6’-pyr),
149.27 (C6-pyr or C6’-pyr), 139.97 (C3’th), 137.09 (C5’th),
136.08 (C4’pyr), 135.54 (C2th), 134.64 (C2”th), 132.41
(C4pyr), 128.10 (C4’th), 127.51 (C5th or C5”th), 127.07
(C5th or C5”th), 126.40 (C3’pyr), 126.11 (C3”th), 125.35
(C4th or C4”th), 125.16 (C4th or C”th), 124.53 (C3pyr),
124.14 (C2th), 122.96 (C3th), 121.32 (C5pyr or C5’pyr),
116.87 (C5pyr or C5’pyr), 91.77 (C≡C), 89.69 (C≡C). MS
(EI, m/z): 426.09. Elemental analysis: required for
C24H14N2S3, C 67.57, H 3.31, N 6.57, S 22.55, found: C
67.60, H 3.28, N 6.62, S 22.50.
A brownish oil was obtained, that was purified by Bio-
tage flash chromatography on silica with petroleum ether,
giving a faint yellow oil, 10.31 g (82%).
3.2.2. Method B
The same reaction was performed in a 100 mL reactor,
with CuI (0.584 g, 3.07 mmol, 0.05 eq.), KI (20.40 g, 123
mmol, 2 eq.), N,N'-dimethylethylendiamine (0.541 g, 0.600
mL, 6.13 mmol, 0.1 eq.) and 3-bromothiophene (10.00 g,
61.3 mmol, 1 eq.) using n-butanol (40 mL) as solvent, and
warming the reactor at 120°C for 3 h. The reactor was cooled
to rt and the mixture was filtered on a Buchner and washed
twice with little dichloromethane. The dichloromethane was
evaporated in a Claisen, under reduced pressure (water pump).
The n-butanol was evaporated in the same way, warming care-
fully and raising the temperature step by step from 40°C to
65°C by 5°C steps, until the distillation stopped. The residue
was purified by flash chromatography on Biotage KP Sil 100 g
silica column, with hexane, giving a faint yellow oil: 6.80 g
(53%).
3.2.3. Method C
In a 250 mL reactor, previously purged with argon, the
Cu2O (878 mg, 6.13 mmol, 0.1 eq.), the L-Proline (1.41 g,
12.3 mmol, 0.2 eq.), the 3-bromothiophene (10.00 g, 61.3
mmol, 1 eq.) and the potassium iodide (30.5 g, 184 mmol, 3
eq) were introduced along with ethanol (150 mL), working
under argon. The reactor was crimped. The suspension was
stirred for 16 h at 110°C. The ethanol was evaporated with
Claisen apparatus at rt under reduced pressure using a water
pump. The crude was purified by flash chromatography on
Biotage KP Sil 100 g silica column eluting with hexane. The
collected fractions were evaporated, giving a faint yellow oil:
5.95 g (46%). The NMR spectra are in agreement with the
literature [12].
1H NMR (200 MHz, CDCl3) δ 7.41 (dd, J = 3.0, 1.2 Hz,
1H, H-2), 7.20 (dd, J = 5.0, 3.0 Hz, 1H, H-4), 7.10 (dd, J =
5.0, 1.2 Hz, 1H, H-5). 13C NMR (50 MHz, CDCl3) δ 134.87
(C-4), 128.76 (C-2), 127.43 (C-5), 77.25 (C-3). MS (EI,
m/z): 209.18. Elemental analysis: required for C4H3IS, C
22.87, H 1.44, S 15.27, found: C 22.93, H 1.39, S 15.22.
3.2. 3-iodothiophene (3)
3.2.1. Method A
3.3. 2,5-dibromo-3-iodothiophene (4)
In a 100 mL reactor, stoppered with rubber septum and
flushed with argon, CuI (0.584 g, 3.07 mmol, 0.05 eq.) and
NaI (18.39 g 123 mmol, 2 eq.) were introduced and flushed
3.3.1. Method A
In a three necked Schlenk 250 mL flask the product 3
(4.77 g, 22.71 mmol, 1 eq.) was introduced as a solution in

Improved Synthesis of a Terthiophene-Based Monomeric Ligand
Letters in Organic Chemistry, 2017, Vol. 14, No. 7 477
DMF (30 mL), and sparged with argon for 10 min under
stirring. The NBS (19.77 g, 111 mmol, 4.89 eq.) and further
100 mL of DMF were added and the reactor was kept away
from light. After 1 h of stirring at room temperature, the
reactor was immersed in an oil bath warmed at 60°C and left
to react overnight. The reaction was checked by TLC and
GC. After 24 h, the reaction was stopped and left to cool at
rt, and it was quenched with about 150 mL of water, ex-
tracted with hexane (3 × 75 mL) and the organic phase was
washed with water (2 × 75 mL) and with brine (2 × 75 mL).
The organic phase was dried with sodium sulfate, filtered
and evaporated, thus giving about 12.24 g of crude. The
crude was purified with Biotage flash chromatography on a
silica cartridge (100 gr.) with hexane. A faint yellow oil was
obtained, 6.68 g (80%).
added. The reaction was run at 0°C. The reaction was
checked by GC, showing that after 3 h the residual 4 was still
present in low quantity (less than 5%). The reaction was
stopped after 6 h and the TEA was distilled under vacuum.
The residue was taken up with 70 mL of petroleum ether,
and filtered on a buchner to remove the solid, which was
washed twice with petroleum ether. The organic phase was
extracted with water (2 × 50 mL) and with brine (50 mL).
The organic phase was dried with Na2SO4, filtered and
evaporated, giving a reddish oil. The oil was purified by Bio-
tage flash chromatography on silica (100 g) with petroleum
ether, giving the pure product as a pale yellow oil: 4.34 g,
(70%).
3.4.2. Method B
The reaction was carried out as in Method (a) on a
slightly lower scale using 5.00 g of compound 4 (13.6 mmol,
1 eq) and replacing Pd(PPh3)2Cl2 with Pd(PPh3)4 (0.628 g,
0.544 mmol, 0.04 eq) as the catalyst.
3.3.2. Method B
In a 100 mL reactor, purged with argon for 10 min, the
compound 3 (5.00 g, mmol, 1 eq.) and NBS (12.74 g, mmol, 3
eq.) were introduced and the reactor was closed with a rubber
stopper and was purged with argon for 10 min. Ethyl acetate
(70 mL) was added and the reactor was introduced in an oil
bath warmed at 60°C and was left to react for 30 h. The reac-
tion was cooled to rt and the solution was extracted with
hexane and washed with water (2 × 50 mL) and brine
(1 × 50 mL). The organic phase was collected, dried with
sodium sulfate, filtered and evaporated, obtaining a reddish
oil. The crude was purified by flash chromatography on Bio-
tage KP Sil 100 g silica column, eluting with hexane. The
collected fractions were evaporated giving a faint pink oil:
8.54 g (98%). The same reaction was also performed at 25°C
for 5 days, giving nearly the same yield. The NMR spectra
are in agreement with the literature [12].
After Biotage flash chromatography on silica (100 g)
with petroleum ether, the product was isolated giving the
pure product as a pale yellow oil: 5.06 g, (82%). The NMR
spectra are in agreement with the literature [12].
1H NMR (200 MHz, CDCl3) δ 6.94 (s, 1H, Har), 0.25 (s,
9H, 3 CH3). 13C NMR (50 MHz, CDCl3) δ 132.30, 125.35,
116.86, 110.84, 99.86, 96.93, 0.03. MS (EI, m/z): 335.91.
Elemental analysis: required for C9H10Br2SSi, C 31.97, H
2.98, S 9.48, found: C 31.90, H 3.02, S 9.45.
3.5. ([2,2':5',2''-terthiophen]-3'-ylethynyl)trimethylsilane
(6)
A 100 mL vial, closed with a rubber stopper, was purged
with argon for 20 min. Compound 5 (1.4407 g, 4.26 mmol, 1
eq.), was introduced in the reactor with the Pd catalyst,
Pd(PPh3)2Cl2, (0.2461 g, 0.213 mmol, 0.05 eq.). The reac-
tants were degassed for a few minutes and DME (44 mL),
previously degassed, was added. The resulting solution was
degassed for a few minutes under stirring, while the Na-
HCO3 solution (1M in water) was degassed for at least 10-15
min. The 2-thiopheneboronic acid (2.204 g, 17.03 mmol, 4
eq.) was added and while the solution was still under argon
purging, the NaHCO3 solution was added (14.91 mL, 14.91
mmol, 3.5 equivalent). The degassing was continued for
about 10 min and the vial was introduced into the pre-heated
oil bath at 80°C. After 2 hours, the reaction was checked by
GC, showing the disappearance of the starting material. The
reaction was stopped and left to cool to rt. The mixture was
extracted with dichloromethane (3 ×100 mL). The organic
phase was dried with Na2SO4, filtered and evaporated, ob-
taining a deep red oil with some solid inside. The crude was
purified by Biotage flash chromatography, with petroleum
ether, giving a faint yellow liquid that sometimes can be-
come solid, for which however the m.p. could not be meas-
ured, being very close to room temperature: 1.17 g (80%).
1H NMR (200 MHz, CDCl3) δ 6.92 (s, 1H). 13C NMR (50
MHz, CDCl3) δ 137.17 (C-4), 116.41 (C-2), 113.55 (C-5),
85.28 (C-3). MS (EI, m/z): 365.80. Elemental analysis: re-
quired for C4HBr2IS, C 13.06, H 0.27, S 8.72, found: C
13.12, H 0.31, S 8.69.
3.4. ((2,5-dibromothiophen-3-yl)ethynyl)trimethylsilane
(5)
3.4.1. Method A
A 250 mL three-necked Schlenk flask, closed with stop-
pers and a joint with stopcock and a balloon for gases, was
purged with argon for 20 min. In the meantime triethylamine
(TEA) was purged with argon for 40 min.
The Pd catalyst, Pd(PPh3)2Cl2 (0.849 g 0.834 mmol, 0.04
eq.) and CuI (0.2089 g, 1.097 mmol, 0.06 eq.) were added
and the apparatus was continuously purged with argon for
about 15 min, until 80 mL of TEA was added. The suspen-
sion was stirred and cooled with ice bath to 0°C. The com-
pound 4 (6.75 g, 18.34 mmol, 1 eq.) was transferred into a 20
mL vial, previously purged with argon and TEA (10 mL)
was added to dissolve the oil, continuously purging with
argon. Compound 4 was transferred into the reaction flask by
a syringe and the vial was washed with further 2 × 5 mL of
TEA, that was transferred to the reaction flask. The flask was
purged with argon for further 10 min, and the trimethylsily-
lacetylene (1.98 g, 2.85 mL, 20.18 mmol, 1.10 eq.) was
1H NMR (200 MHz, CDCl3) δ 7.66 (d, J = 2.4 Hz, 1H, H-
3 or H3"), 7.44 (d, J = 4.5 Hz, 1H, H-5 or H5"), 7.37 (d, J =
5.1 Hz, 1H, H-5 or H5"), 7.30 (d, J = 3.4 Hz, 1H, H-3 or
H3"), 7.26 (s, 1H, H-4'), 7.17 (s, 2H, H-4 and H4"). 13C

478 Letters in Organic Chemistry, 2017, Vol. 14, No. 7
Quagliotto et al.
the production of light olefins. ChemSusChem, 2011, 4(9), 1265-
1273.
NMR (50 MHz, CDCl3) δ 139.43 (C3’-C≡C), 136.34 (C5 or
C5”), 135.88 (C2”), 134.04 (C5 or C5”), 128.04 (C2’),
127.48 (C4 or C4’), 127.45 (C4 or C4’), 127.29 (C2), 125.74
(C2’), 125.13 (C5’), 124.31 (C3, or C3”), 117.81 (C3, or
C3”), 100.39 (C≡C), 100.31 (C≡C), -0.10 (Si(CH3)3). MS
(EI, m/z): 344.06. Elemental analysis: required for
C17H16S3Si, C 59.25, H 4.68, S 27.92, found: C 59.21, H
4.75, S 27.88.
[5]
[6]
Smestad, G.P.; Steinfeld, A. Review: Photochemical and thermo-
chemical production of solar fuels from H2O and CO2 using metal
oxide catalysts. Ind. Eng. Chem. Res., 2012, 51(37), 11828-11840.
O'Toole, T.R.; Margerum, L.D.; Westmoreland, T.D.; Vining,
W.J.; Murray, R.W.; Meyer, T.J. Electrocatalytic reduction of CO2
at a Chemically Modified electrode. J. Chem. Soc. Chem. Com-
mun., 1985, 20, 1416.
[7]
[8]
Windle, C. D.; Reisner, E. Heterogenised molecular catalysts for
the reduction of CO2 to fuels. Chimia (Aarau), 2015, 69 (7-8), 435-
41.
Cosnier, S.; Deronzier, A.; Moutet, J. C. Electrocatalytic reduction
of CO2 on electrodes modified by Fac-Re(2,2'-Bipyridine)(Co)3Cl
complexes bonded to polypyrrole films. J. Mol. Catal., 1988, 45
(3), 381-391.
Sun, C.; Prosperini, S.; Quagliotto, P.; Viscardi, G.; Yoon, S. S.;
Gobetto, R.; Nervi, C. Electrocatalytic reduction of CO2 by thio-
phene-substituted rhenium (i) complexes and by their polymerized
films. Dalton Trans., 2016, 45(37), 14678-88.
Quagliotto, P.; Barbero, N.; Barolo, C.; Buscaino, R.; Carfora, P.;
Prosperini, S.; Viscardi, G. Water based surfactant-assisted synthe-
sis of thienylpyridines and thienylbipyridine intermediates. Dyes
Pigm., 2017, 137, 468-479.
Manca, P.; Pilo, M. I.; Casu, G.; Gladiali, S.; Sanna, G.; Scanu, R.;
Spano, N.; Zucca, A.; Zanardi, C.; Bagnis, D.; Valentini, L. A new
terpyridine tethered polythiophene: Electrosynthesis and charac-
terization. J. Polym. Sci. A Polym. Chem., 2011, 49(16), 3513-
3523.
Nagarjuna, G.; Yurt, S.; Jadhav, K. G.; Venkataraman, D. Impact
of pendant 1,2,3-triazole on the synthesis and properties of thio-
phene-based polymers. Macromolecules, 2010, 43(19), 8045-8050.
Arsenyan, P.; Paegle, E.; Belyakov, S. A novel method for the
bromination of thiophenes. Tetrahedron Lett., 2010, 5, 205-208.
Mio, M.J.; Kopel, L.C.; Braun, J.B.; Gadzikwa, T.L.; Hull, K.L.;
Brisbois, R.G.; Markworth, C.J.; Grieco, P.A. One-pot synthesis of
symmetrical and unsymmetrical bisarylethynes by a modification
of the sonogashira coupling reaction. Org. Lett., 2002, 4(19), 3199-
3202.
Klapars, A.; Buchwald, S.L. Copper-catalyzed halogen exchange in
aryl halides: An aromatic Finkelstein reaction. J. Am. Chem. Soc.,
2002, 124(50), 14844-14845.
Feng, R.; Chen, L.; Zhang, S.; Song, J. New synthesis process for
2-(3-thienyl) malonic acid. Shiyou Huagong, 2008, 37(6), 592-596.
Feng, X.; Li, L.; Yu, X.; Yamamoto, Y.; Bao, M. Copper-catalyzed
conversion of aryl and heteroaryl bromides into the corresponding
iodide. Catal. Today, 2016, 274, 129-132.
CONCLUSION
An alternative synthetic pathway to a bipyridine ligand
linked to a terthiophene through an alkyne moiety was
shown, obtaining a substantial yield improvement. The
pathway was a modification of literature protocols and af-
forded the title product in a total yield of 40% over 5 steps.
The compound and its rhenium complex is still under study.
Preliminary results show high activity towards carbon diox-
ide reduction and the possible formation of photoactive po-
lymeric films.
[9]
[10]
[11]
CONSENT FOR PUBLICATION
Not applicable.
[12]
CONFLICT OF INTEREST
[13]
[14]
The authors declare no conflict of interest, financial or
otherwise.
ACKNOWLEDGEMENTS
We gratefully acknowledge the financial support of the
Compagnia di San Paolo and Università di Torino (Progetti
di Ricerca di Ateneo 2012: project PHOTORECARB), the
Università di Torino (Ricerca Locale ex-60%, Bandi 2014
and 2015).
[15]
[16]
[17]
SUPPLEMENTARY MATERIAL
[18]
[19]
Prat, D.; Wells, A.; Hayler, J.; Sneddon, H.; McElroy, C. R.; Abou-
Shehada, S.; Dunn, P.J. CHEM21 selection guide of classical- and
less classical-solvents. Green Chem., 2016, 18, 288-296.
Boydston, A.J.; Haley, M.M.; Williams, R.V.; Armantrout, J.R.
Supplementary material is available on the publisher’s
website along with the published article.
REFERENCES
Diatropicity of 3,4,7,8,9,10,13,14-octadehydro[14]annulenes:
A
combined experimental and theoretical investigation. J. Org.
Chem., 2002, 67(25), 8812-8819.
Sugihara, Y.; Yagi, T.; Murata, I.; Imamura, A. 1-Phenylthieno
[3,4-d]borepin: A new 10 π electron system isoelectronic with az-
ulene. J. Am. Chem. Soc., 1992, 114(4), 1479-1481.
Solooki, D.; Kennedy, V. O.; Tessier, C. A.; Youngs, W. J. Synthe-
sis of a trithienocyclotriyne. Synlett, 1990, 7, 427-428.
Solooki, D.; Bradshaw, J.D.; Tessier, C.A.; Youngs, W.J. Synthesis
and characterization of trithienocyclotriyne (ttc) and its tetracobalt
complex. The first example of a dehydroannulene containing thio-
phene rings. Organometallics, 1994, 13(2), 451-455.
Sordello, F.; Minero, C.; Buscaino, R.; Viscardi, G.; Quagliotto, P.
Highly photoactive polythiophenes obtained by electrochemical
synthesis from bipyridine containing terthiophenes. J. Mater.
Chem., submitted.
[1]
Montoneri, P.E.; Rosso, D.; Bucci, G.; Berto, S.; Baglieri, A.;
Mendichi, R.; Quagliotto, P.; Francavilla, M.; Mainero, D.; Negre,
M. Ozonization to upgrade waste-derived soluble lignin-like sub-
stances to higher value products. Chem. Select., 2016, 1(8), 1613-
1629.
Montoneri, E.; Boffa, V.; Quagliotto, P.; Mendichi, R.; Gobetto,
R.; Medana, C. Humic acid-like matter isolated from green urban
wastes. Part I: Structure and surfactant properties. Bioresources,
2008, 3(1), 123-141.
Yu, K.M.; Curcic, I.; Gabriel, J.; Tsang, S.C. Recent advances in
CO2 capture and utilization. ChemSusChem, 2008, 1(11), 893-899.
Centi, G.; Iaquaniello, G.; Perathoner, S. Can we afford to waste
carbon dioxide? Carbon dioxide as a valuable source of carbon for
[20]
[21]
[22]
[2]
[3]
[4]
[23]
DISCLAIMER: The above article has been published in Epub (ahead of print) on the basis of the materials provided by the author. The Edito-
rial Department reserves the right to make minor modifications for further improvement of the manuscript.