Dissymmetrization of Benzothiadiazole by Direct C–H Arylation: A Way to Symmetrical and Unsymmetrical Elongated π-Conjugated Molecules

Article abstract of DOI:10.1002/ejoc.201701382

5-(7-Bromo-2,1,3-benzothiadiazol-4-yl)-2-thiophenecarbaldehyde is a small building block of great interest for its use in the elaboration of symmetrical or unsymmetrical donor–acceptor π-conjugated molecules for optoelectronic applications. Herein, a convenient, one-pot, two-component synthesis of this intermediate is reported, based upon a palladium-catalysed, phosphine- and additive-free, direct C–H arylation process. The synthesis has been studied in depth to obtain optimum yields and selectivity by an efficient and environmentally friendly strategy for sustainable synthesis.

Full text of DOI:10.1002/ejoc.201701382

A Journal of
Accepted Article
Title: Dissymetrisation of benzothiadiazole by direct C-H arylation: a
way to symmetrical and unsymmetrical elongated π-conjugated
molecules
Authors: Kathleen Isabelle Moineau-Chane Ching, Chunxiang
Dall'Agnese, Daniel Hernández Maldonado, and Damien Le
Borgne
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10.1002/ejoc.201701382
European Journal of Organic Chemistry
Dissymetrisation of benzothiadiazole by direct C-H
arylation: a way to symmetrical and unsymmetrical
elongated π-conjugated molecules
Chunxiang Dall'Agnese1,2, Daniel Hernández Maldonado1,2, Damien Le Borgne1,2, Kathleen I.
Moineau-Chane Ching1,2*
1CNRS; LCC (Laboratoire de Chimie de Coordination); 205, route de Narbonne, 31077
Toulouse, France
2Université de Toulouse; UPS, INP; LCC; 31077 Toulouse, France
Email: Kathleen Isabelle Moineau-Chane Ching – kathleen.chane@lcc-toulouse.fr, homepage
URL : https://www.lcc-toulouse.fr/auteur6.html
* Corresponding author
Abstract
5-(7-Bromo-2,1,3-benzothiadiazol-4-yl)-2-thiophenecarboxaldehyde is a small building block
of great interest for its use in the elaboration of symmetrical or unsymmetrical donor-acceptor
π-conjugated molecules, for optoelectronic applications. Herein, a convenient, one-pot, two-
component synthesis of this intermediate is reported, based upon palladium-catalysed,
phosphine and additive-free, direct C-H arylation process. The synthesis is studied in depth to
obtain optimum yields and selectivity, according to an efficient and environmentally friendly
strategy for sustainable synthesis.
Keywords
1
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European Journal of Organic Chemistry
4,7-Dibromobenzo-2,1,3-thiadiazole; Direct C-H arylation; Phosphine-free Palladium
catalyst; Mono-arylation; Thiophene
Introduction
Organic semiconductors for optoelectronics are often based on alternating electron donor and
electron acceptor (D-A) moieties [1-7]. The classical synthetic approaches toward these D-A
structural materials rely on traditional cross-coupling reactions, such as Suzuki coupling using
arylene diboronic acids/esters [8,9] and Stille coupling using stannyl reagents [10]. Such
transition metal-catalysed cross couplings are still considered as powerful tools for C-C bond
formation. However, they involve the use of boron- or tin-aromatic derivatives that are
potentially costly and toxic, respectively, with the probable production of stoichiometric
amounts of environmentally risky by-products such as stannylated compounds. Therefore,
transition-metal (Palladium, Rhodium, Ruthenium) catalysed coupling methods of non-
preactivated aryl C-H bonds with aryl halides, belonging to the so-called direct arylation, have
become a focus of interest [11-19]. These methods have emerged as sustainable synthetic
protocols of π-conjugated materials using simplified reaction steps and reduced undesirable
organometallic reagents [12,17-23]. In the field of photovoltaics, there have been fruitful
successes in using thiophene-based molecules and polymers [27]. But so far, these materials
are mostly obtained via Suzuki [28-30] or Stille [31-33] coupling. However, as demonstrated
recently by M. Leclerc and co-workers [34], direct arylation assisted with phosphine ligands is
a promising method to synthesize high molecular weight conjugated thiophene-based polymers
with suitable yields in a faster and more environmentally friendly way. In the same time, H.
Doucet and co-workers proposed the use of phosphine-free low loading Palladium catalyst at
high temperature to yield highly selective 2- or 5-arylated heteroaromatics [35-39]. In a general
manner, this last strategy offers great advantages: due to the reduced number of reactants, the
workup is simplified and production cost is even reduced. Thus, it may be considered
2
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environmentally and economically attractive as well as efficient. In this spirit, we recently
performed the synthesis of benzothiadiazole- (Bz) based symmetrical molecules by using
dibromobenzothiadiazole (diBrBz) and 2-thiophenecarboxaldehyde (ThCHO) as starting
materials (Figure 1 top), through phosphine and additive-free direct C-H arylation [40].
In the present study, we investigated the disymmetrisation of the Bz unit by the synthesis of the
monoadduct 5-(7-bromo-2,1,3-benzothiadiazol-4-yl)-2-thiophenecarboxaldehyde (molecule 1,
Scheme 1). Note that the synthesis of the difluorobenzothiadiazole (DFBT) analogue in 74%
yield using a palladium redox catalytic cycle has been recently reported, where Pd(TFA)2 and
Ag2O were used as the catalyst and the oxidant, respectively [41]. These reactions conditions
lead satisfactorily via dual C–H functionalization to the thienylation of DFBT with various
thiophene derivatives. However, they were not applicable to non-fluorinated benzothiadiazole
and we never succeeded in obtaining molecule 1 in that way. As molecule 1 is not yet
commercially available but constitutes a unique building block for creating symmetrical or
unsymmetrical π-conjugated D-A molecules [42-48], the suggestion for an effective and simple
synthesis protocol should be of interest to many chemists. So far, there are a few reports about
the synthesis of 1 in good yields (i.e. more than 40%), and the related synthetic protocols are
based on Suzuki [43-47] or Stille [48] couplings (see Scheme 1).
Scheme 1: use of diBrBz in synthetic pathways leading to molecule 1 with related yields
3
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X. Yang et al. recently proposed its synthesis in two steps, first a Suzuki coupling providing
the intermediate 4-bromo-7(-thiophen-2-yl)benzo[1,2,5]thiadiazole (54% intermediate yield),
which was then formylated through a classical way to afford 1. Note that this pathway offers a
low overall yield of 6.24% [43]. At almost the same time, Y. Geng and co-workers proposed
the synthesis of 1 from diBrBz and 5-carboxythiophene-2-boronic acid as reagents through
Suzuki coupling using microwaves. They obtained the desired molecule in 40% yield [44].
More recently, K. Seo et al. employed Stille coupling with diBrBz and (5-(1,3-dioxolan-2-
yl)thiophen-2-yl)tributylstannane in tetrahydrofuran (THF) for getting 1 in 49% yield [48].
These examples involve the purchase or preparation of intermediate organometallic reactants.
Thus considering the simplest possible starting materials, namely diBrBz and ThCHO, the
overall yield in molecule 1 is still low, if one takes into account the preparation of the building
blocks. To our knowledge, the direct C-H activation approach has never been described for the
synthesis of molecule 1, maybe because of the difficulty of dissymetrisation, and the eventual
occurring of side reactions like homocoupling [49]. This work is thus expected to benefit the
synthesis of 1 simply based on diBrBz and ThCHO via direct C-H activation (see Scheme 2)
for the purpose of constructing extended π-conjugated D-A molecules such as 4 or 5, as shown
in Scheme 2.
4
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European Journal of Organic Chemistry
Scheme 2: Formation of molecule 1 via direct arylation and subsequent possible symmetrical
(4) and unsymmetrical (5) π-conjugated D-A molecules. The di-adduct 2 and homocoupling
derivative 3 are probable by-products of direct arylation.
Results and Discussion
Suzuki coupling
As a reference, and inspired by the work of Y. Geng and co-workers [44], the Suzuki
coupling reaction was first tested in modified conditions (see ESI): we used diBrBz and 5-
formyl-2-thiopheneboronic acid pinacol ester as reagents and Pd(PPh3)4/K2CO3 as the
catalyst/base system. This reaction is established to occur by oxidative addition,
transmetallation and reductive elimination. The oxidative addition on the bromo-compound is
often the rate-determining step [50-52], so the main difficulty here is linked to the likely high
reactivity of ThCHO with regard to that of diBrBz. We were unable to get the desired product
with acceptable yields under microwave irradiation, but better results were obtained in classical
conditions at 80°C, and in adding drop-wisely ThCHO to the reactive medium. At best a 30%
yield was reached, which can be considered as a minimum value for an acceptable alternative
protocol.
Direct arylation
As a preliminary screening, we tested direct arylation with and without phosphine ligand,
using diBrBz and ThCHO as the reactants (Table 1). Phosphine-assisted direct arylation was
adapted from conditions defined by Marder et al. [53], using Pd(OAc)2 and PtBu2Me.HBF4 as
the catalytic system in toluene, with pivalic acid (PivOH) as the additive and K2CO3 as the base.
We tested various diBrBz/ThCHO ratios, the amount of catalyst, phosphine and pivalic acid,
and the time of reaction (see Supporting Information). At best, the desired product was isolated
in 20% yield for a use of 5% catalyst. The main by-product is the symmetrical di-adduct 2 (See
5
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European Journal of Organic Chemistry
Scheme 1). It is worth to note that this di-adduct may be synthesized in quantitative yield by
using a diBrBz/ThCHO ratio of 0.45 (see SI). For comparison, a phopsphine-free process was
tested, following a procedure similar to that suggested by Doucet et al. who used a reduced
amount of base in order to decrease the amount of wastes [54]. We engaged the two reactants
with 1 mol% of Pd catalyst and 1 base equivalent in dimethylacetamide (DMAc) as the solvent.
We obtained similar yields than with phosphine-assisted arylation (Table1).
Table 1: Reaction of diBrBz with ThCHO following two direct arylation procedures.
base
(eq)
diBrBz/
ThCHO
Pd(OAc)2
(%)
ligand
(mol %) (mol %)
PivOH
temp
(°C)
time
(h)
yield
(%)*
entry
solvent
1
2
1.4
5
10%
0
30%
0
3a
toluene
DMAc
110°C
24
24
24 (20)
17 (14)
1
1
1b
115°C
a base = K2CO3; b base = KOAc; * NMR and isolated (in parentheses) yields
We decided to explore further the phosphine-free procedure because it offers several
potential advantages making it particularly attractive [54,55]: i) it is efficient for electron-
deficient aryl bromide such as diBrBz, ii) it needs neither phosphine ligand nor additive, iii) it
uses a little amount of catalyst. Moreover, we highlighted that this reaction is rather clean:
mostly the target molecule 1, the di-adduct 2, and molecule 3 arising from the 5,5’-
homocoupling of ThCHO, were present in significant amounts in the crude, along with the
eventual presence of non-reacted starting reactants diBrBz and ThCHO (see NMR spectra in
SI). This renders easy the analysis of the course of the reaction and makes it possible to evaluate
the reaction yield by a simple NMR analysis.
We first tested various temperatures for a 24 h reaction as shown in Table 2. Note that when
the temperature of the reaction mixture reached 130°C, only molecule 2 was formed. As stated
by de Vries [56], Pd(OAc)2 catalysed reactions (Heck or Suzuki couplings) proceed through
the formation of soluble palladium(0) colloids or nanoparticles formed at elevated temperature.
6
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The conversion rate of diBrBz indicates that for the present case, the optimum reaction
temperature for allowing the catalytic system to effectively take place is of around 105°C. At
higher temperature, the selectivity dramatically decreases in such a way that we obtained the
exclusive formation of 2 at 130°C. In rising the reaction temperature, we faced a compromise
between selectivity (in favour to 1 at low temperature) and conversion rate (which decreases
when significant amount of 2 is formed), thus a quantitative yield for molecule 1 cannot be
awaited. The optimal conditions correspond to an operating temperature of 105°C giving a
selectivity of 2.5 for a conversion rate of 33.4% (Table 2, entry 3).
Table 2: Effect of temperature on phosphine-free direct arylation of ThCHO with diBrBz in
DMAc. Fixed parameters: 1 to 1 eq. of engaged ThCHO and diBrBz; catalyst = 1% Pd(OAc)2,
base = 2 eq. KOAc, and time of reaction = 24h.
molar ratios in the crudea
temp
(°C)
conv. rate c
(%)
yield in
entry
selectivityb
1 (%)d
diBrBz
15
2
3
-
1
2
3
4
60
95
0.1
0.1
0.4
0.8
10
10
6.8
6
5.85
2.8
0.09
-
15.9
33.4
24.6
14.5
24
105
115
2.5
1.25
5.5
0.05
13.7
a relative to 1 and according to 1H NMR analysis; b 1:2 molar ratio according to NMR analysis;
c % of reacted diBrBz; d isolated yield.
One way to improve the yield was to adapt the optimal conditions by involving a default of
ThCHO. By means of 0.5 equivalent of ThCHO for 1 equivalent of diBrBz, a better yield of
35% in 1 (related to the involved ThCHO) was reached. This is however not fully satisfactory
because a significant amount of diBrBz (up to 85%) remained non-reacted.
Another way was to raise the amount of catalyst up to 5% (entry 2, Table 3). This proved
however to be unfruitful since the selectivity dramatically decreased despite very similar
obtained yields. Finally, we found that increasing the time of reaction was the simplest way for
improving the yield. A duration of up to 3 days played a decisive role in achieving an optimum
45% yield for a selectivity of 2.7, i.e. the best results we have ever reached. It is also noted that,
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by doubling the amount of starting materials (without changing the co-reagent ratios), the yield
is unchanged. The relevant details are summarized in the following table:
Table 3: Optimization of Pd(OAc)2-catalysed direct arylation of ThCHO with diBrBz in
DMAc at 105°C.
molar ratios in the crudea
time
(h)
conv. Rate c
(%)
yield in 1
entry % Pd
Selectivityb
(%)d
diBrBz
2. 8
2
3
1
2
3
1
5
1
24
24
72
0.4
-
2.5
1.0
2.7
33.4
46.4
62
24
23
45
1
2.3
0.25
0.37
0.85
0.06
1
b
a relative to 1 and according to H NMR analysis; Selectivity = 1/2 molar ratio according to
NMR analysis; c % of reacted diBrBz; d isolated yield.
As initially proposed, we used molecule 1 for elaborating symmetrical and unsymmetrical
π-conjugated molecules. The two elongated molecules, 4 and 5 were obtained through Suzuki
coupling in good yields, of around 60%. Their synthesis via direct arylation is not
straightforward, and is currently under investigations. These new molecules are end-capped by
aldehyde functions that will be later engaged in Knoevenagel condensations for the generation
of new materials for organic photovoltaics, opening the way to new families of donor-acceptor
π-conjugated molecules based on the benzothiadiazole-thiophene fragment.
Conclusion
In summary, we have demonstrated that phosphine-free direct arylation is a convenient tool
for obtaining the mono-adduct 1, despite its pronounced ability to undergo a second arylation
leading to the symmetrical molecule 2. By using 1 mol% of Pd(Ac)2 at a moderate reaction
temperature of 105°C in DMAc under argon atmosphere, the direct 5-arylation via C-H bond
activation of thiophene derivative proceeds in satisfactory yields, up to 45%. When the amount
of catalyst is increased up to 5 mol%, no improvement in the yield was observed, and the
selectivity of the reaction is decreased. This low catalyst loading procedure is easy to carry out,
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as well as the purification process and may be applied to a variety of coupling reactions when
mono-adduct is preferred.
Experimental Section
General: Solvents: All reactions and manipulations were carried out under Ar, with degassed
solvents, by the use of standard inert atmosphere and Schlenk techniques. All the synthetic
procedures were repeated at least five times, the reported results were averaged. Anhydrous
toluene, potassium carbonate and potassium acetate were purchased from Aldrich. Pd(OAc)2
(99+%) was purchased from Strem Chemicals. Pivalic acid was purchased from Acros. 2-
Thiophenecarboxaldehyde (ThCHO), and PtBu2Me.HBF4 were purchased from Alfa Aesar.
N,N-Dimethylacetamide, 99.5%, Extra Dry over Molecular Sieve, AcroSeal® was purchased
from Acros Organics. 4,7-Dibromo-2,1,3-benzothiadiazole (diBrBz) and 5-formyl-2-
thiopheneboronic acid pinacol ester were bought from Interchim. 9-(Tributylstannyl)-
1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinoline was synthesized in a similar way as the
preparation of N,N-diphenyl-4-(tributylstannyl)aniline [57]. 4,4’-Dioctyl-5,5’-bis(tributyltin)-
dithieno[3,2-b:2',3'-d]silole was synthesized according to literature procedure [58].
1H and 13C NMR spectra were acquired in CDCl3 and DMSO-d6 using Bruker Avance 300 and
Avance 400 spectrometers and the signals were referenced using the corresponding solvent
peaks. The splitting patterns are designated as follows: s (singlet); d (doublet); t (triplet); q
(quartet); m (multiplet).
Chromatographic separations were performed using standard column chromatography methods
using silica gel purchased from Sigma-Aldrich (60 Å, 63-200 μm).
Suzuki coupling for the synthesis of molecule 1:
Method a, microwave: diBrBz (706 mg, 2.4 mmol), 5-formyl-2-thiopheneboronic acid pinacol
ester (381 mg, 1.6 mmol), and Pd(PPh3)4/K2CO3 (92 mg/11 mg, 5% mol) were mixed in dry
9
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toluene (4 ml) and dry methanol (1 ml) under argon atmosphere. The solution was irradiated
using microwaves (T= 100°C, 2 cycles of 30 minutes at 25 W). The red mixture was filtered
and washed with toluene and dichloromethane. The combined organic phases were evaporated
and purified by column chromatography first using dichloromethane and pentane (1:1) and then
using petroleum ether and ethyl acetate (4:1) as eluent, giving rise to 13 mg of pure orange
mono-arylated product (3%).
Method b, drop-wise method: All solvents and basic solutions were previously degassed by
bubbling through argon for 20 min. diBrBz (500 mg, 1.7 mmol) was placed in an oven dried
three-necked flask under an inert atmosphere. Toluene (30 mL), K2CO3 (2.0 M, 2 mL), H2O (6
mL) and Aliquat 336 (4–5 drops) were sequentially added under argon and the mixture was
vigorously stirred for 10 min at room temperature. Pd(PPh3)4 (3 mol%) was then added and the
reaction was maintained under strong stirring until it reached 80°C. Then, 5-formyl-2-
thiopheneboronic acid pinacol ester (365 mg, 1.55 mmol) previously dissolved in 10 mL
toluene and degassed for 15 min, was added drop-wisely for 3 hours. The mixture was allowed
to react at 80°C until TLC reveal that 5-formyl-2-thiopheneboronic acid pinacol ester
disappeared, i.e. after 14 h. After cooling down to room temperature, the mixture was extracted
twice with dichloromethane. The organic extracts were gathered, dried over MgSO4, filtered,
combined and concentrated under vacuum. The residue was purified by column
chromatography on silica (eluent = petroleum ether: ethyl acetate, from 4:1 to 0:1) to give 150
mg of molecule 1 as a yellow-orange powder (30% yield). TLC (pentane:dichloromethane 1:1):
Rf = 0.63. IR (Neat): max = 3098, 3084, 2882, 2788, 2722, 2156, 1660, 1652, 1512, 1440, 1386
cm-1. HRMS (TOF-ESI) (m/z): calcd. for (M+H)+ C11H6N2OS2Br: 324.9105, found: 324.9102.
Element. Anal. Found: C, 40.56; H, 1.45; N, 8.80 %; molecular formula C11H5N2OS2Br
1
requires C, 40.59; H, 1.54; N, 8.61 %. NMR analyses on molecule 1: H NMR (400 MHz,
Chloroform-d, 25°C): δ = 10.01 (s, 1H, CHO), 8.21 (d, 3J = 4 Hz, 1H, H thiophene), 7.95 (d, 3J
= 7.7 Hz, 1H, H benzothiadiazole), 7.88 (d, 3J = 4 Hz, 1H, H thiophene), 7.87 (d, J = 3J = 7.7
10
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13
Hz, 1H, H benzothiadiazole) ppm. C NMR (101 MHz, Chloroform-d, 25°C) δ = 182.97,
147.54, 143.97, 136.65, 134.03, 132.12, 131.33, 128.53, 127.37, 125.75, 115.11 ppm. 1H NMR
3
(400 MHz, DMSO-d6, 25°C) δ = 10.01 (s, 1H, CHO), 8.28 (d, J = 4 Hz, 1H, H thiophene),
8.22 (d, 3J = 7.7 Hz, 1H, H benzothiadiazole), 8.15 (d, 3J = 7.7 Hz, 1H, H benzothiadiazole),
8.14 (d, 3J = 4 Hz, 1H, H thiophene) ppm. 13C NMR (101 MHz, DMSO-d6, 25°C) δ = 185.08,
144.55, 138.43, 135.29, 132.98, 131.03, 129.00, 128.45, 125.23, 119.96, 114.59 ppm.
Direct C-H arylation methods:
1) Phosphine ligand-assisted reaction
Synthesis of molecule 1: In an oven-dried three-necked flask containing a stirring bar,
equipped with a thermometer, a condenser and septum cap, palladium acetate (Pd(OAc)2),
PtBu2Me.HBF4, PivOH, diBrBz (500 mg, 1.7 mmol), K2CO3 (705 mg, 3 eq), and ThCHO (r eq,
where “r” stands for the diBrBz/ThCHO molar ratio) were sequentially added under Ar flow.
Dry toluene (7.5 mL) was added under argon atmosphere. The reaction mixture was refluxed
for a given reaction time (See Table S1). The resulting mixture was cooled down to room
temperature and filtered through a layer of Celite® using dichloromethane (DCM). The filtrate
was concentrated under reduced pressure, and the residue was dried under vacuum. The reaction
1
yield was estimated using HNMR results in DMSO-d6 (see Table 4). For the best estimated
yield (the case of entry 6), the desired product was isolated by column chromatography (silica
gel, ethyl acetate/pentane = 30:70) affording 80 mg of 1 (20 % yield of isolated product).
Table 4: Optimization of ligand-assisted direct arylation of ThCHO with diBrBz.
Pd(OAc)2
(mole %)*
Ligand
(eq)*
PivOH Time
1H NMR
Yield (%)
Entry
r
1/2**
(eq)*
(h)
1
2
1
1
10
0.2
0.2
1
4
16
10
3
5
10
1
4
3
4
2
1
10
10
0.2
0.2
1
6
11
12
10
0.3
24
1.6
11
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5
6
7
1.1
1.4
1.4
5
5
1
0.1
0.1
0.1
0.3
0.3
0.3
24
24
18
13
24
22
2.5
0.4
1
* % and equivalents are relative to the molar amount of diBrBz; ** evaluated (molecule
1/molecule 2) ratio according to 1H NMR analysis of the crude in DMSO-d6.
Synthesis of molecule 2: In an oven-dried three-necked flask containing a stirring bar,
equipped with a thermometer, a condenser and septum cap, palladium acetate (Pd(OAc)2, 7.6
mg, 3.4 10-5 mol), PtBu2Me.HBF4 (16.9 mg, 6.8 10-5 mol), pivalic acid (PivOH, 35 mg, 0.34
mmol), diBrBz (100 mg, 0.34 mmol, 1 eq), potassium carbonate (K2CO3, 140 mg, 1.02 mmol),
and ThCHO (70 L, 0.75 mmol) were sequentially added under a flow of Ar. Dry toluene (7.5
mL) was added under argon atmosphere. The reaction mixture was refluxed for 5.5 h, then
cooled down to room temperature and filtered. The resulting solid was washed with water, ethyl
acetate, and then petroleum ether, affording molecule 2 as a red-orange powder which was dried
1
under vacuum (116 mg, 98% yield). NMR analyses on molecule 2: H NMR (400 MHz,
Chloroform-d, 25°C): δ = 10.02 (s, 2H, CHO), 8.29 (d, J = 4 Hz, 2H, H thiophene), 8.09 (s, 2H,
H benzothiadiazole) 7.90 (d, J = 4 Hz, 2H, H thiophene) ppm. (the molecule was too poorly
soluble to allow 13C NMR analysis)
1H NMR (400 MHz, DMSO-d6, 25°C) δ = 10.03 (s, 1H, CHO), 8.43 (s, 2H, H
benzothiadiazole), 8.38 (d, J = 4 Hz, 2H, H thiophene), 8.17 (d, J = 4 Hz, 2H, H thiophene)
ppm. (the molecule was too poorly soluble to allow 13C NMR analysis).
2) Phosphine-free reaction
Synthesis of molecule 1, using the procedure for reactions mentioned in Table 2: In an
oven-dried Schlenk containing a stirring bar and septum cap, diBrBz (500 mg, 1.7 mmol, 1 eq),
KOAc (330 mg, 3.4 mmol, 1.5 eq), Pd(OAc)2 (4 mg, 1.8 10-5 mol, 1 mol %), were sequentially
added under a flow of Ar. Dry and degassed dimethylacetamide (7.5 mL) was added under
argon atmosphere, then ThCHO, (320 L, 3.4 mmol, 1 eq) was added under stirring. The
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mixture was stirred for 24 h at a given temperature, between 60 and 130°C (see Table 2 of main
paper). After cooling down to 50°C, the solvent was evaporated and the crude dried under
1
reduced pressure. The reaction yield was estimated from the HNMR analysis of the crude
product, which was then purified by column chromatography (silica gel, EtOAc/pentane =
30:70) for recovering the non-reacted diBrBz and isolating the pure molecule 1.
Synthesis of molecule 1, using the procedure for reactions mentioned in Table 3: The same
procedure as above was applied, but by starting from 1 g of diBrBz and, i) by using an amount
of Pd(OAc)2 of 40 mg, i.e. 5 mol % (instead of 1 mol %), and ii) with increasing the reaction
time to 72 h (instead of 24 h). Surprisingly, it appeared that operating either in Schlenk or in
three-necked flask had an impact on the results. Working in Schenk flask led to similar yields
of 1, but with a better selectivity than in a three-necked flask.
3) Synthesis of the extended π-conjugated D-A molecules.
Synthesis of molecule 4: A solution of 4,4’-dioctyl-5,5’-bis(tributyltin)-dithieno[3,2-b:2',3'-
d]silole (0.613 g, 0.61 mmol) and molecule 1 (0.4 g, 1.23 mmol) in dry toluene (20 ml) was
bubbled with argon for 25 min, then Pd(PPh3)4 (35 mg, 3 10-5 mol) was added to the mixture.
After stirring under reflux for 17 h, the reaction mixture was allowed to cool down to 50°C,
then the toluene was evaporated under vacuum. The crude product was dispersed in 10 ml
AcOEt under sonication, then filtered. The solid was washed with 20 ml of AcOEt, and dried
under vacuum, leading to 400 mg of pure molecule 4 as a black solid (52%). IR (Neat): max
=
3318, 2952, 2917, 2848, 1659, 1532, 1519, 1436, 1339 cm-1. 1H NMR (400 MHz, Chloroform-
d, 25°C) δ = 10.00 (s, 2H CHO) , 8.26 (s, 2H, thiophene), 8.25 (d, J = 4 Hz, 2H, thiophene),
8.02 (d, J = 8 Hz, 2H, benzothiadiazole), 7.94 (d, J = 8 Hz, 2H, benzothiadiazole), 7.88 (d, J =
4 Hz, 2H, thiophene), 1.52-1.49 (m, 4H, Si-CH2-), 1.41-1.36 (m, 4H, Si-CH2-CH2-), 1.32-1.22
(m, 16H, alkyles), 1.11-1.07 (m, 4H, -CH2-CH3), 0.87-0.82 (m, 6H, -CH2-CH3) ppm ; MS (CI-
NH3) : found: 907.00 [MH+] calculated for C46H47N4O2S6Si: 907.17. Element. Anal. Found:
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10.1002/ejoc.201701382
European Journal of Organic Chemistry
C, 60.01; H, 4.79; N, 6.27%; molecular formula C23H19N3OS2 + 0.45 H2O requires C, 60.35;
H, 5.16; N, 6.12 %.
Synthesis of molecule 5: A mixture of 9-(tributylstannyl)-1,2,3,5,6,7-hexahydropyrido[3,2,1-
ij]quinoline (0.470 g, 1.01 mmol), 1 (0.300 g, 0.923 mmol), Pd(PPh3)4 (30 mg, 2.3 10-5 mol) in
10 mL of dry toluene was heated at reflux overnight under Ar atmosphere. The solvent was
removed and the residue was extract with dichloromethane. The organic phase was washed with
water, dried over magnesium sulphate, and the solvent was evaporated. The target compound
was purified by two successive recrystallizations in ethyl acetate to give pure molecule 3 as a
deep purple solid (230mg, 60%). IR (Neat): max = 2952, 2938, 2938, 2830, 2793, 2156, 1662,
1602, 1537, 1506, 1461, 1440 cm-1. 1H NMR (400 MHz, Chloroform-d, 25°C) δ = 9.99 (1H, s,
CHO), 8.22 (1H, d, J = 4.1 Hz, thiophene), 8.02 (1H, d, J = 7.6 Hz, benzothiadiazole), 7.86
(1H, d, J = 4.1 Hz, thiophene), 7.68 (1H, d, J = 7.6 Hz, benzothiadiazole), 7.54 (2H, s, 8,10-H
julolidine), 3.27 (4H, t, J = 5.6 Hz, 1,7-H julolidine), 2.90 (4H, t, J = 6.5 Hz, 3,5-H julolidine),
2.05 (4H, m, 2,6-H julolidine) ppm.13C NMR (101 MHz, Chloroform-d, 25°C) δ = 182.95,
153.97, 152.81, 149.60, 143.68, 142.73, 136.90, 135.74, 128.00, 127.89, 127.24, 125.20,
123.48, 122.65, 121.34, 49.98, 27.92, 21.90 ppm. HRMS (TOF-ESI) (m/z): calcd. for (M+H)+
C23H20N3OS2: 418.1048, found: 418.1040. Element. Anal. Found: C, 64.45; H, 3.93; N, 9.75%;
molecular formula C23H19N3OS2 + 0.2 CH2Cl2 requires C, 64.13; H, 4.50; N, 9.67 %.
Supporting Information
1H and 13C NMR spectra are included in the Supporting Information.
Acknowledgements
The authors gratefully acknowledge financial support from Region Midi-Pyrénées, IDEX
Transversalité « dessine moi OPV », Consejo Nacional de Ciencia y Technologia (Mexico) and
China Scholarship Council (China).
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10.1002/ejoc.201701382
European Journal of Organic Chemistry
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