Synthesis of 1,6-, 2,7-, 3,8-, and 4,9-isomers of didodecyl[1] benzothieno[3,2-b][1]benzothiophenes

Article abstract of DOI:10.1021/jo401134c

The synthesis of 1,6-, 2,7-, 3,8-, and 4,9-isomers of dibromo- and didodecyl[1]benzothieno[3,2-b][1]benzothiophenes, via the stilbene pathway, is described. Starting from the synthesis of bromo-2-(methylthio)benzaldehydes, a series of functionalization, McMurry coupling, and finalising cyclization reactions were explored. The stereochemistry of the cyclization mechanism was investigated. Using this methodology didodecyl[1]benzothieno[3,2-b][1] benzothiophenes were formed in overall yields of 5-32%.

Full text of DOI:10.1021/jo401134c

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Note
Synthesis of 1,6- 2,7- 3,8- and 4,9- Isomers of
Didodecyl[1]benzothieno[3,2-b][1]benzothiophenes
Christian Ruzié, Jolanta Karpinska, Alan R. Kennedy, and Yves Henri Geerts
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo401134c • Publication Date (Web): 12 Jul 2013
Downloaded from http://pubs.acs.org on July 13, 2013
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Synthesis of 1,6- 2,7- 3,8- and 4,9- Isomers of Didodecyl[1]benzothieno[3,2-
b][1]benzothiophenes
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Christian Ruzié†, Jolanta Karpinska†, Alan R. Kennedy‡ and Yves H. Geerts*†
† Laboratoire de Chimie des Polymères
CP 206/01, Faculté des Sciences
Université Libre de Bruxelles (ULB)
Boulevard du Triomphe
1050 Brussels, Belgium
Email: ygeerts@ulb.ac.be
‡ Department of Pure and Applied Chemistry
University of Strathclyde
295 Cathedral Street
Glasgow G1 1XL, Scotland
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TOC
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C12H25
C12H25
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S
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S
S
C12H25
C12H25
C12H25
S
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C12H25
C12H25
S
S
C12H25
Abstract
The synthesis of 1,6- 2,7- 3,8- and 4,9- isomers of dibromo and
didodecyl[1]benzothieno[3,2-b][1]benzothiophenes, via the stilbene pathway, is described.
Starting from the synthesis of bromo-2-(methylthio)benzaldehydes, a series of functionalization,
McMurry coupling, and finalising cyclization reactions were explored. The stereochemistry of
the
cyclization
mechanism
was
investigated.
Using
this
methodology
didodecyl[1]benzothieno[3,2-b][1]benzothiophenes were formed in overall yields of 5 to 32 %.
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The most recently studied conjugated π-systems for charge transport are the diacene-
fused thienothiophenes1,2,3, among which [1]benzothieno[3,2-b][1]benzothiophene (BTBT)
derivatives are probably the best known for several reasons. They were the first systems to be
synthesized,4 are readily soluble in organic solvents5, easily crystallize6, and are available in
large quantities via a one-step reaction from o-chlorobenzaldehyde7. Most of derivatives
described in the literature are substituted at the 2 and 7 positions, whereas functionalization at the
other positions is less documented8,9 despite the fact that the length and position of alkyl side
chains play a crucial role on the resulting structures. It is clear that the 3D structure determines to
a large extent the semiconducting properties5,10 of materials used in organic field-effect
transistors. Methodologies developed to access 2,7-dialkylBTBT include Friedel–Craft acylation
of BTBT followed by Wolff–Kishner reduction,5,8 Sonogashira coupling on 2,7-diiodoBTBT
followed by reduction on Pd/C,5 Kumada coupling on 2,7-dibromoBTBT,11 and acidic
cyclization of 2-[2-(methylsulfinyl)phenyl]-benzo[b]thiophene12. The direct functionalization of
the BTBT core either by lithiation or acylation has been extensively described by Svoboda et al
but only generates 1,6- or 4,9-BTBT in poor yield.8 We have thus opted for a general synthetic
scheme in which functionalization is carried out prior to cyclization. The use of a synthetic
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pathway via a stilbene intermediate, which was inspired by the work of Takimiya et al.13,14
,
allowed us to synthesize 1,6-didodecyl BTBT 1, 2,7-didodecyl BTBT 2, 3,8-didodecyl BTBT 3,
and 4,9-didodecyl BTBT 4 (Figure 1), and to propose a revised cyclization mechanism.
R
S
S
S
R
R
S
S
S
R
2
1
R
R
S
S
R
R
4
3
R = C12H25
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FIGURE 1. Didodecyl[1]benzothieno[3,2-b][1]benzothiophenes
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6
7
8
9
Compounds 1-4 have been synthesized via a McMurry coupling on a 2-
methylthiobenzaldehyde derivative followed by a cyclization with iodine.2,14-16 This synthetic
approach required the preparation of dodecyl-2-methylthiobenzaldehydes by distinct synthetic
pathways detailed below and that rely on the synthesis of 3-bromo-2-(methylthio)benzaldehyde
(7).
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Starting from commercially available 1-bromo-3-iodobenzene (5), the selective
thiomethylation at the 2-position, via a lithiation with lithium diisopropylamide17, followed by a
reaction with dimethyl disulfide, gave 1-bromo-3-iodo-2-methylthiobenzene (6) in 93 % yield.
Subsequent magnesiation of 6 at –78 °C in THF by iodine–magnesium exchange with
iPrMgCl18, followed by trapping with dimethylformamide and hydrolysis with NH4Cl afforded 7
in 77
%
yield. The second pathway entailed the synthesis of 4-bromo-2-
(methylthio)benzaldehyde (9), a known compound that was previously prepared by a different
route starting from 4-bromo-2-fluorobenzoic acid, resulted in a 61 % yield.19 Starting from
commercially available 4-bromo-2-fluorobenzaldehyde (8), a SNAr reaction with freshly
prepared sodium thiomethoxyde20 in DMF21 at
0
°C generated 4-bromo-2-
(methylthio)benzaldehyde (9) in 63 % yield. The third pathway is similar to the second one and
describes the synthesis of 5-bromo-2-(methylthio)benzaldehyde (11) in 87 % yield.22,23 The
fourth pathway deals with the synthesis of 6-bromo-2-(methylthio)benzaldehyde (14). Starting
17
from the commercially available 1-bromo-3-fluorobenzaldehyde (12), selective formylation at
the 2-position via a lithiation with lithium diisopropylamide, followed by a reaction with DMF
gave 2-bromo-6-fluorobenzaldehyde (13) in 82 % yield. A SNAr reaction with freshly prepared
sodium thiomethoxyde in DMF led to 6-bromo-2-(methylthio)benzaldehyde (14) in 60 % yield.
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Treatment of the aldehyde moiety with trimethylorthoformate in methanol with a catalytic
amount of sulphuric acid gave the dimethyl acetal derivative 15 in quantitative yield.24 This
compound was needed later, see Scheme 2. In summary, the four bromo-substituted 2-
(methylthio)benzaldehydes 7, 9, 11, and 14 were synthesized in an overall yield ranging from 49
to 87 %.
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SCHEME 1. Synthesis of dodecyl-2-methylthiobenzaldehydes
McMurry coupling of the four bromo substituted 2-methylthiobenzaldehyde was carried
out under similar conditions used by Takimiya et al. for dinaphto-15,25, alkylated dinaphto-14,26
and dianthra-2 thieno[3,2-b]thiophene. The conditions are quite standard for McMurry coupling,
i.e.TiCl4/Zn in THF at reflux. Thus, reaction of 7, 9, 11, or 14, in these conditions, gave 16, 17,
18, or 19 respectively (Table 1). Yields vary between 61 and 87 % and are similar to those
reported for dinaphtothieno[3,2-b]thiophene14,15,25,26 (26 to 97 %).
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TABLE 1. Synthesis of bromostibenes and dibromobenzothienobenzothiophenes
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Entry Aldehyde
Stilbene
[%]a BTBT
I [%]a
II [%]a III [%]a
A
B
7
9
61
70
20
21
27
37
53
NDb
NDb
5
4
C
D
11
14
84
87
22
23
40
NDb
20
NDb
28
a Isolated yield. b Not detected
Finally, 16, 17, 18, and 19 was treated with excess iodine in AcOH16 for 2 days to
perform the ring closing reaction, forming the dibromo benzothienothiophenes 20, 21, 22, and 23
in 27, 5, 4, and 20 % yield respectively. It is worth noting that in case of stilbenes 16, 17, and 18
the reaction afforded the partially cyclized benzothiophenes II as a side product. Treatment of
benzothiophenes II with excess iodine formed a mixture of benzothienothiophenes and
benzothiophenes II. In the case of the synthon 19, the reaction gave 4,9-dibromo-4b,9b-
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dihydrobenzothieno[3,2-b]benzothiophene (23III) with the desired compound 23I, but
surprisingly not the partially cyclized benzothiophenes 23II. Use of pyridinium perbromide
instead of iodine gave similar results. Obviously, the presence of the bulky bromine atoms in the
ortho-position of the double bonds is responsible for this unusual reactivity. It is also worth
noting also that compounds 20I to 23I exhibit a moderate solubility in organic solvents.
To explain the presence of compounds 20II, 21II, 22II, and 23III, we propose a
plausible reaction pathway of the cyclization reactions (Scheme 2), that differs from that
suggested by Takimiya et al.13 These authors hypothesized that the last step of the cyclization
mechanism involved a “dehydration – oxidation” reaction. This hypothesis appears to be
incorrect as 23III does not convert to 23I. (vide infra).
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SCHEME 2. Plausible reaction pathway for iodine-promoted cyclization of bromostilbene 16-18
In the initial step of the reaction iodine reacts with the alkene bond giving a three-
membered cyclic halonium cation. Intramolecular nucleophilic substitution by the sulfur atom of
the thiomethyl group follows giving a sulfonium intermediate, with an easily cleavable methyl
group. This leads to the formation of a 2,3-dihydro-3-iodobenzothiophene intermediate by attack
of iodide anion. At this stage, two routes are conceivable. The first route (Route A) starts with an
intramolecular dehydrohalogenation affording partially cyclized benzothiophenes 20II-22II,
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addition of iodine to the alkene to form three-membered cyclic halonium cation, followed by
intramolecular nucleophilic substitution by the sulfur atom of the thiomethyl group, and then
dehydrohalogenation giving 20I23I. The second route (Route B) first involved the elimination of
the iodide anion via a SN mechanism to form the carbocation, followed by intramolecular
nucleophilic substitution by the sulfur atom forming the sulfonium intermediate, liberating the
methyl group by nucleophylic attack by the iodide anion to give 4b,9b-dihydrobenzothieno[3,2-
b]benzothiophene (23III). A crystal structure of 23III was obtained, which showed a racemic
mixture of R,R and S,S (see SI).
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If Route A is favored for 3,4, and 5-bromostilbene, sterical hindranceof bromine atom
promotes Route B for 6-bromostilbene, by preventing iodine addition.
It is worth mentioning that when the isolated intermediates 20II to 22II are subjected to
cyclization conditions they finaly gave the corresponding 20I to 22I compounds. Conversely,
23III does not react under the same reaction conditions, i.e. excess iodine in AcOH for 2 days.
Moreover, the neat compound 23III does not thermaly aromatize, as evidenced by
thermogravimetric analysis, (see SI) before sublimation above 225 °C. It forms a deadend that
significantly reduces the yield of 23I.
A coupling reaction27 could have been used to substitute dibromo compounds 20, 21, 22,
or 23 with didodecyl side chains. However, the poor yield of the ring closing step prompted us to
explore a different synthetic pathway, i.e. the introduction of didodecyl substituents by the
Kumada reaction28 prior to cyclization (Table 2). Dibromostilbenes 16, 17, 18, and 19 were
treated with an excess of dodecylmagnesium bromide, with a catalytic amount of PdCl2(dppf) in
THF giving 24, 25, 26, and 27 respectively in yields ranging from 13 to 82 %.
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TABLE 2. Synthesis of didodecylstilbenes and didodecylbenzothienobenzothiophenes
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Entry
E
Br-stilbene
C12-Stilbene
[%]a
62
BTBT (I)
I [%]a
24
1
67
F
25
26
66
82
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3
G
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H
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33
a Isolated yield.
The poor yield obtained for the synthesis of stilbene 27 was possibly due to steric
hindrance and/or close proximity of the sulphur atoms that could coordinate and deactivate the
palladium catalyst. An alternative route was specifically developed for the synthesis of the
stilbene 27. Starting from 15, Kumada coupling with an excess of dodecylmagnesium bromide
with a catalytic amount of PdCl2(dppf) in THF, follow by treatment with HCl 6M in methanol
afforded 28 in 72 % yield. Subsequent McMurry coupling led to the target stilbene 27 in 40 %
yield. (Scheme 3)
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1) PdCl2(dppf)
C12H25MgBr
THF
2) HCl, MeOH
72%
C12H25
SMe
Zn
TiCl4
THF
SMe H
O
15
40%
MeS
C12H25
C12H25
28
27
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SCHEME 3. Synthesis of stilbene 27
Finally, the stilbene derivatives 24, 25, 26, and 27 were treated with excess iodine16 to
induce a ring closing reaction, forming the desired didodecyl benzothienothiophenes 1, 2, 3, or 4
in 67 %, 3 %, 53 %, and 33 % yield respectively. In sharp contrast to the cyclization of
dibromostilbenes 16, 17, 18, and 19, no uncyclized and/or dihydro derivatives were observed for
these cyclizations. No plausible explanation has been found for the low yield of product 2.
The reported pathways allow the synthesis of 1,6-, 3,8-, and 4,9-didodecyl
benzothiophene 1, 3, and 4 in overall yields of 18 %, 32 %, and 5 % respectively. Importantly for
further physical characterization, the final cyclization step was performed on the half-gram scale.
The reaction conditions and work-up used here indicate that the production of these compounds
could easily be scaled up. Our synthetic pathway to 2,7-didodecyl benzothiophene 2 is inefficient
with an overall yield of 0.8 % in comparison to prior work. Better results are obtained by
acylation of benzothiophene, followed by Wolff-Kishner reduction,5,8 or by Sonogashira
coupling on 2,7-diiodobenzothiophene, followed by reduction5.
There are several noteworthy observations. Firstly, the yields are globally superior
(entries E,G,H) to those found for the cyclization of dibromostilbenes (entries A,B,C). This is
likely due to the electron donating character of the alkyl side chains. Secondly, the comparison
of entries B and F is instructive. The yield of the cyclization step of dibromostilbene 17 and
didodecyl stilbene 25 remains very poor when performed under the same reaction conditions.
This lack of reactivity is puzzling since neither steric, nor electronic factors could be invoked, i.
e. the substituents are in the meta position and their electronic effects are opposite. Thirdly, a
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comparison of entries C and G lead to the suprising conclusion that the didodecyl stilbene 26 is
dramatically more reactive that its counterpart 18, under same experimental conditions. Again no
direct explanation could be proposed but we must stress that the reactions were repeated at least
one time and that the yields are reproducible. Lastly, the unknown didodecyl
benzothienothiophenes 1, 3, and 4 were synthesized in contrasting yields. Interestingly, the 3,8
isomer 3 is the easiest to prepare in large amount.
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Experimental Section
13
General Methods. 1H NMR (300 MHz) and C NMR (75 MHz) spectra were collected
at room temperature in CDCl3 unless otherwise noted. High resolution mass spectra (HRMS)
under electron impact ionization (+ mode) were obtained on an instrument combining six sectors
of cE1B1cE2qcE3B2cE4 geometry (Ei stands for electric sector, Bi for magnetic sector, q for a
quadrupole collision cell and c for conventional collision cells). Melting points are uncorrected.
A silica gel (40 µm average particle size) was used for column chromatography. Anhydrous,
reagent grade CH3CN, DMF, MeOH, and absolute EtOH were used as received. 2,4-
Dinitrophenylhydrazine was used as visualization reagent for the detection of aldehydes. Sodium
thiomethoxide20 was prepared following the literature procedure.
1-Bromo-3-iodo-2-(methylthio)benzene (6). Following a reported procedure,17 a solution
of 1-bromo-3-iodobenzene (5) (2.56 mL, 20.0 mmol) in anhydrous THF (40 mL) at –100 °C was
treated with LDA (15 mL, 2 M in THF/n-heptane/ethylbenzene, 30.0 mmol) over 1 h. After
stirring for 30 min at –100 °C, dimethyldisulfide (2.88 mL, 32.0 mmol) was added dropwise, and
the mixture was stirred for 1 h at – 100 °C. A saturated solution of NH4Cl was added, and the
mixture was stirred for 10 min. Ethyl acetate was added, and the organic layer was separated,
dried over MgSO4, and concentrated under vacuum. The resulting residue was subjected to
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column chromatography [silica, n-hexane] to afford an off-white solid (5.25 g, 93 %): m.p.: 47–
5
6
7
1
48 °C; H NMR δ 2.46 (s, 3H), 6.79 (t, J = 7.9 Hz, 1H, H5), 7.65 (dd, J = 7.9 and 1.2 Hz, 1H),
7.88 (dd, J = 7.9 and 1.2 Hz, 1H); 13C NMR δ 19.2, 109.6, 129.7, 131.1, 133.7, 139.3, 141.2; EI-
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HRMS obsd 327.8407, calc 327.8418 (C7H6BrIS).
3-Bromo-2-(methylthio)benzaldehyde (7). Following a reported procedure,18 a solution
of 6 (2.82 g, 0.01 mol) in anhydrous THF (30 mL) at – 78 °C was treated with iPrMgCl (5.5 mL,
2 M in Et2O, 0.011 mol). After stirring for 3 h at – 78 °C, DMF (1.26 mL, 0.015 mol) was added
dropwise, and the mixture was stirred for 1 h at – 78 °C, and then allowed to warm overnight to
room temperature. A saturated solution of NH4Cl was added, and the mixture was stirred for 10
min. Ethyl acetate was added, and the organic layer was separated, dried over MgSO4, and
concentrated under vacuum. The resulting residue was subjected to column chromatography
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[silica, n-hexane/ethyl acetate (95:5)] to afford a pale yellow oil (1.78 g, 77%): H NMR δ 2.46
(s, 3H), 7.35 (m, 1H), 7.89 (m, 2H), 10.76 (s, 1H); 13C NMR δ 20.4, 127.6, 130.1, 132.6, 138.4,
139.9, 140.6, 192.6; EI-HRMS obsd 229.9411, calc 229.9400 (C8H7BrOS).
4-Bromo-2-(methylthio)benzaldehyde (9). A solution of 4-bromo-2-fluorobenzaldehyde
(8) (5 g, 24.6 mmol) in anhydrous DMF (15 mL) at 0 °C was treated with freshly prepared
NaSMe (1.9 g, 27.1 mmol). After stirring 1 h at 0 °C, the mixture was allowed to warm to room
temperature overnight, and then cooled to 0 °C. Crushed ice was added, and the precipitate was
filtered, washed with water, and dried. Crystallization in hexane afforded a yellow solid (3.61g,
63 %): m.p.: 88–89 °C; 1H NMR δ 2.51 (s, 3H), 7.40–7.44 (m, 2H), 7.65 (d, J = 8 Hz, 1H), 10.18
(s, 1H); 13C NMR δ 15.4, 127.5, 127.8, 129.7, 131.3, 134.4, 145.5, 190.2; EI-HRMS obsd
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229.9393, calc 229.9401 (C8H7BrOS). H NMR data are identical to those reported in
literature.19
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5-Bromo-2-(methylthio)benzaldehyde (11). Following a reported procedure,23 a solution
of 5-bromo-2-fluorobenzaldehyde (10) (5 g, 24.6 mmol) in anhydrous DMF (15 mL) was treated
with freshly prepared NaSMe (1.9 g, 27.1 mmol). After stirring 1 h, crushed ice was added, and
the precipitate was filtered, washed with water, and dried. Crystallization in hexane afforded a
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yellow solid (4.94 g, 87%): mp.: 90–91 °C; H NMR δ 2.50 (s, 3H), 7.21 (d, J = 8.5 Hz, 1H),
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7.64 (dd, J = 8.5 and 2.3 Hz, 1H), 7.92 (d, J = 2.3 Hz, 1H), 10.21 (s, 1H); C NMR δ 15.7,
118.2, 127.4, 134.1, 135.2, 136.6, 142.4, 189.8; EI-HRMS obsd 229.9400, calc 229.9401
(C8H7BrOS). 1H NMR data are identical to those reported in literature.23
2-Bromo-6-fluorobenzaldehyde (13). Following a reported procedure,17 a solution of 1-
bromo-3-fluorobenzene (12) (6.00 mL, 54.6 mmol) in anhydrous THF (100 mL) at –100 °C was
treated with LDA (30 mL, 2 M in THF/n-heptane/ethylbenzene, 60.0 mmol) over 1 h. After
stirring for 30 min at –100 °C, dimethyldisulfide (6.43 mL, 89 mmol) was added dropwise, and
the mixture was stirred for 1 h at – 100 °C. A saturated solution of NH4Cl was added, and the
mixture was stirred for 10 min. Ethyl acetate was added, and the organic layer was separated,
dried over MgSO4, and concentrated under vacuum. The resulting residue was subjected to
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column chromatography [silica, n-hexane] to afford an colorless oil (9.06 g, 82%): H NMR δ
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7.16 (m, 1H), 7.41 (td, J = 8.0 and 5.0 Hz, 1H), 7.50 (dt, J = 8.0 and 0.9 Hz, 1H); C NMR δ
116.3 (d, 2J = 22 Hz), 122.8 (d, J = 9 Hz), 125.3 (d, J = 3 Hz), 130.1 (d, J = 4 Hz), 135.3 (d, J =
1
10 Hz), 163.1 (d, J = 266 Hz), 188.5 (d, J = 2 Hz); EI-HRMS obsd 201.9429, calc 201.9429
(C7H4OFBr).
6-Bromo-2-(methylthio)benzaldehyde (14). Following a reported procedure,23 a solution
of 2-bromo-6-fluorobenzaldehyde (13) (5 g, 24.6 mmol) in anhydrous DMF (15 mL) was treated
with freshly prepared NaSMe (1.9 g, 27.1 mmol). After stirring 1 h, crushed ice was added, and
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the precipitate was filtered, washed with water, and dried. Crystallization in hexane afforded a
yellow solid (3.43 g, 60%): mp.: 90–93 °C; 1H NMR δ 2.45 (s, 3H, SMe), 7.26 (m, 1H), 7.33 (m,
1H), 7.42 (m, 1H), 10.53 (s, J = 0.7 Hz, 1H, CHO); 13C NMR δ 15.5, 13.7, 128.9, 129.0, 129.6,
133.6, 147.0, 192.7; EI-HRMS obsd 229.9395, calc 229.9401 (C8H7BrOS).
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1-Bromo-2-dimethoxymethyl-3-(methylthio)benzene (15). A solution of 6-bromo-2-
(methylthio)benzaldehyde (14) (3.82 g, 16.0 mmol) and trimethyl orthoformate (3.62 mL, 33.0
mmol) in methanol (80 mL) was treated with 1 drop of concentrated H2SO4, and the mixture was
refluxed for 1 h. A saturated solution of K2CO3 was added to pH = 9. Ethyl acetate was added
and the organic layer was separated, dried over MgSO4, and concentrated under vacuum to
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afford a colorless oil (4.25 g, 96 %): H NMR δ 2.42 (s, 3H), 3.48 (s, 6H), 5.85 (s, 1H), 7.05–
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7.20 (m, 2H), 7.33 (dd, J = 7.7 and 1.2 Hz 1H); C NMR δ 16.1, 55.6, 106.8, 124.3, 124.6,
129.3, 129.6, 132.9, 141.1; EI-HRMS obsd 275.9811, calc 275.9819 (C10H13BrO2S).
3,3'-dibromo-2,2'-dimethylthio-trans-stilbene (16). Following a procedure for McMurry
coupling,15 a suspension of Zn (1.97 g, 30.0 mmol) in anhydrous THF (40 mL) at 0 °C was
treated dropwise with TiCl4 (3.30 mL, 30.0 mmol), and the resulting mixture was heated at
reflux for 1 h. After cooling to 0 °C, a solution of 7 (2.32 g, 10.0 mmol) in anhydrous THF (20
mL) was added, and the resulting mixture was heated at reflux overnight. After cooling to room
temperature, the mixture was poured in saturated solution of NaHCO3 (100 mL) and
dichloromethane (100 mL) and stirred for 3 h. The mixture was filtered through a Celite pad,
washed with hot chloroform, and the layers of the filtrate were separated. The aqueous layer was
extracted with dichloromethane, and the combined organic layer was dried over MgSO4 and
concentrated under vacuum. Recrystallization from n-hexane affords a white solid (1.34 g, 61
%): m.p.: 131–137 °C; 1H NMR δ 2.36 (s, 6H), 7.22 (t, J = 7.9 Hz, 2H), 7.65 (d, J = 7.9 Hz, 2H),
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7.70 (d, J = 7.8 Hz, 2H), 7.83 (s, 2H); 13C NMR δ 19.4, 125.8, 129.8, 131.0, 132.0, 132.7, 136.1,
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143.5; EI-HRMS obsd 427.8905, calc 427.8904 (C16H14Br2S2).
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4,4'-dibromo-2,2'-dimethylthio-trans-stilbene (17). The coupling was performed with
3.00 g (13 mmol) of 9 following the above procedure for 16. Recrystallization from n-hexane
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affords a white solid (2.00 g, 70 %): mp.: 178–186 °C (184–186 °C, xylene)29; H NMR δ 2.48
(s, 6H), 7.30 (dd, J = 8.3 and 1.9 Hz, 2H), 7.33 (s, 2H), 7.36 (d, J = 1.9 Hz, 2H), 7.45 (d, J = 8.3
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Hz, 2H, H6+H6’); C NMR δ 16.3, 122.2, 127.1, 127.5, 128.5, 128.9, 135.0, 139.5; EI-HRMS
obsd 427.8892, calc 427.8904 (C16H14Br2S2).
5,5'-dibromo-2,2'-dimethylthio-trans-stilbene (18). The coupling was performed with
3.00 g (13 mmol) of 11 following the above procedure for 16. Recrystallization from n-hexane
affords a white solid (2.31 g, 84 %): m.p.: 216–224 °C; 1H NMR δ 2.46 (s, 6H), 7.15 (d, J = 8.4
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Hz, 2H), 7.36 (s, 2H), 7.38 (dd, J = 8.4 and 2.1 Hz, 2H), 7.70 (d, J = 2.1 Hz, 2H); C NMR δ
19.7, 119.6, 127.7, 128.8, 129.0, 131.1, 136.6, 138.1; EI-HRMS obsd 427.8892, calc 427.8904
(C16H14Br2S2).
6,6'-dibromo-2,2'-dimethylthio-trans-stilbene (19). The coupling was performed with
3.00 g (13 mmol) of 14 following the above procedure for 16. Recrystallization from n-hexane
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affords a white solid (2.49 g, 87 %): m.p.: 127–135 °C; H NMR δ 2.46 (s, 6H), 6.99 (s, 2H),
7.09 (t, J = 7.8 Hz, 2H), 7.16 (dd, J = 7.8 and 0.7 Hz, 2H), 7.43 (dd, J = 7.7 and 1.1 Hz, 2H); 13C
NMR δ 16.5, 123.9, 124.1, 128.5, 129.3, 133.4, 135.4, 140.5; EI-HRMS obsd 427.8918, calc
427.8904 (C16H14Br2S2).
1,6-Dibromo[1]benzothieno[3,2-b][1]benzothiophene (20I). A solution of 16 (500 mg,
1.19 mmol) in AcOH (80 mL) at reflux was treated with powdered iodine (9.64 g, 38.0 mmol).
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The resulting mixture was heated at reflux for 2 days. After cooling to room temperature, the
mixture was poured in sodium dithionite solution (100 mL), and the solid collected by filtration.
The filtered material was subjected overnight to high vacuum. The resulting residue was
subjected to column chromatography [silica, hot n-hexane] to afford 20I as an off-white solid
(128 mg, 27%) followed by 7-bromo-2-(3-bromo-2-(methylthio)phenyl)benzo[b]thiophene (20-
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II) as an off-white solid (182 mg, 37 %). 20I : m.p.: 280–282 °C; H NMR (1,1,2,2-
tetrachloroethane-d2, 400 MHz, 100 °C) δ 7.43 (t, J = 7.8 Hz, 2H), 7.65 (dd, J = 7.7 and 0.9 Hz,
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2H), 7.93 (dd, J = 7.9 and 0.9 Hz, 2H); C NMR (1,1,2,2-tetrachloroethane-d2, 100 MHz, 100
°C) δ 116.9, 120.3, 126.3, 128.1, 133.9, 134.3, 143.6; EI-HRMS obsd 395.8261, calc 395.8277
(C14H6Br2S2). 20-II : mp.: 92–94 °C; 1H NMR δ 2.29 (s, 3H), 7.19 (t, J = 7.9 Hz, 1H), 7.24 (t, J
= 7.8 Hz, 1H), 7.47 (dd, J = 7.7 and 1.4 Hz, 1H), 7.48 (dd, J = 7.7 and 0.9 Hz, 2H), 7.50 (s, 1H),
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7.68 (dd, J = 8.0 and 1.4 Hz, 1H), 7.73 (dd, J = 7.9 and 0.9 Hz, 1H); C NMR δ 19.7, 115.3,
122.7, 125.0, 125.7, 127.3, 129.3, 130.7, 132.2, 133.7, 136.5, 140.3, 140.5, 142.0, 143.6; EI-
HRMS obsd 411.8581, calc 411.8591 (C15H10Br2S2).
2,7-Dibromo[1]benzothieno[3,2-b][1]benzothiophene (21I). The cyclization was
performed with a solution of 17 (495 mg, 1.17 mmol) following the above procedure for 20I.
The resulting residue was subjected to column chromatography [silica, hot n-hexane] to afford
21I as an off-white solid (23 mg, 5 %) followed by 6-bromo-2-(4-bromo-2-
(methylthio)phenyl)benzo[b]thiophene (21-II) (256 mg, 53 %): 21I : m.p.: 280 °C (299–300 °C,
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AcOH)29; H NMR (1,1,2,2-tetrachloroethane-d2, 400 MHz, 100 °C) δ 7.63 (dd, J = 8.4 and 1.7
Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H), 8.11 (d, J = 1.5 Hz, 2H); 13C NMR (1,1,2,2-tetrachloroethane-
d2, 100 MHz, 100 °C) δ 119.2, 122.6, 126.7, 128.7, 131.8, 133.6, 144.0; EI-HRMS obsd
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395.8274, calc 395.8277 (C14H6Br2S2). 21-II : mp.: 149–151 °C; H NMR δ 2.45 (s, 3H), 7.28
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(d, J = 8.0 Hz, 1H), 7.32 (dd, J = 8.0 and 1.8 Hz, 1H), 7.38 (d, J = 1.8 Hz, 1H), 7.41 (d, J = 0.5
Hz, 1H), 7.46 (dd, J = 8.5 and 1.7 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.98 (d, J = 1.7 Hz, 1H); 13C
NMR δ 16.0, 118.4, 123.3, 124.1, 124.6, 124.9, 127.7, 127.8, 127.9, 131.2, 132.1, 138.5, 140.7,
140.9, 141.6; EI-HRMS obsd 411.8602, calc 411.8590 (C15H10Br2S2).
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3,8-Dibromo[1]benzothieno[3,2-b][1]benzothiophene (22I). The cyclization was
performed with a solution of 18 (282 mg, 0.67 mmol) following the above procedure for 20I.
The resulting residue was subjected to column chromatography [silica, hot cyclohexane] to
afford 22 as an off-white solid (10 mg, 4 %) followed by 5-bromo-2-(5-bromo-2-
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(methylthio)phenyl)benzo[b]thiophene (22-II) (256 mg, 40 %): 22I : m.p.: 239–241 °C; H
NMR (1,1,2,2-tetrachloroethane-d2, 400 MHz, 100 °C) δ 7.59 (dd, J = 8.6 and 1.7 Hz, 2H), 7.84
(d, J = 8.6 Hz, 2H), 8.08 (d, J = 1.7 Hz, 2H); 13C NMR (1,1,2,2-tetrachloroethane-d2, 100 MHz,
100 °C) δ 119.6, 124.6, 125.4, 128.6, 134.5, 136.1, 141.2; EI-HRMS obsd 395.8272, calc
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395.8277 (C14H6Br2S2). 22II : m.p.: 116–118 °C; H NMR δ 2.41 (s, 3H), 7.15 (d, J = 8.5 Hz,
1H), 7.38 (d, J = 0.5 Hz, 1H), 7.44 (dd, J = 8.6 and 2.0 Hz, 1H), 7.47 (dd, J = 8.5 and 2.2 Hz,
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1H), 7.57 (d, J = 2.2 Hz, 1H), 7.69 (d, J = 8.6 Hz, 1H), 7.94 (d, J = 1.8 Hz, 1H); C NMR δ
16.2, 118.3, 118.5, 123.4, 123.9, 126.4, 127.2, 127.7, 131.9, 133.5, 134.3, 137.6, 138.8, 141.2,
141.7; EI-HRMS obsd 411.8590, calc 411.8590 (C15H10Br2S2).
4,9-Dibromo[1]benzothieno[3,2-b][1]benzothiophene (23I). The cyclization was
performed with 242 mg (0.576 mmol) of 19 following the above procedure for 20I. The resulting
residue was subjected to column chromatography [silica, hot cyclohexane] to afford an off-white
solid (46 mg, 20 %) followed by 4,9-dibromo-4b,9b-dihydrobenzothieno[3,2-b]benzothiophene
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(23III) (64 mg, 28 %). 23I : m.p.: 252–260 °C; H NMR (1,1,2,2-tetrachloroethane-d2, 400
MHz, 100 °C) δ 7.34 (t, J = 7.6 Hz, 2H), 7.71 (d, J = 7.6 Hz, 2H), 7.95 (d, J = 7.9 Hz, 2H); 13C
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NMR (1,1,2,2-tetrachloroethane-d2, 100 MHz, 100 °C) δ 116.4, 122.8, 126.2, 128.5, 129.7,
132.6, 143.6; EI-HRMS obsd 395.8278, calc 395.8277 (C14H6Br2S2). 23III : mp.: 226–228 °C;
1H NMR δ 5.96 (s, 2H), 7.04 (t, J = 7.7 Hz, 2H), 7.12 (d, J = 7.6 Hz, 2H), 7.21 (d, J = 7.7 Hz,
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1H); C NMR δ 60.9, 120.5, 120.8, 127.9, 130.5, 138.1, 143.2; EI-HRMS obsd 397.8447, calc
397.8434 (C14H8Br2S2).
3,3'-Didocecyl-2,2'-dimethylthio-trans-stilbene (24). Following a general procedure for
Kumada coupling,28 a solution of 16 (438 mg, 1 mmol) and PdCl2(dppf) (146 mg, 0.2 mmol) in
anhydrous THF (20 mL) at 0 °C was treated dropwise with 1-dodecylmagnesium bromide (10
mL, 0.5 M in THF, 5 mmol), and the mixture was heated at reflux for 12 h. After cooling to
room temperature, a saturated solution of NH4Cl was added, and the mixture was stirred for 10
min. The mixture was filtered through a Celite pad, and the layers of the filtrate were separated.
The aqueous layer was extracted with dichloromethane, and the combined organic layer was
dried over MgSO4 and concentrated under vacuum. The resulting residue was subjected to
column chromatography [silica, n-hexane/CH2Cl2 (85/15)] to afford an off-white solid (380 mg,
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62 %): m.p.: 77–79 °C; H NMR δ 0.88 (t, J = 6.2 Hz, 6H), 1.25–1.34 (m, 36H), 1.59 (m, 4H),
2.23 (s, 6H), 2.93 (t, J = 7.6 Hz, 4H), 7.18 (dd, J = 7.4 and 0.9 Hz, 2H), 7.29 (t, J = 7.59 Hz, 2H),
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7.63 (dd, J = 7.8 and 0.9 Hz, 2H), 7.85 (s, 2H); C NMR δ 14.2, 20.2, 22.8, 29.5, 29.7, 29.8
(5X), 32.0, 32.1, 35.5, 124.7, 128.5, 129.0, 130.3, 134.8, 142.1, 147.4; EI-HRMS obsd 608.4464,
calc 608.4449 (C40H64S2).
4,4'-Didocecyl-2,2'-dimethylthio-trans-stilbene (25). The Kumada coupling was
performed with 438 mg (1 mmol) of 17 following the above procedure for 24. The resulting
residue was subjected to column chromatography [silica, n-hexane/CH2Cl2 (85/15)] to afford an
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(m, 36H), 1.62 (m, 4H), 2.46 (s, 6H), 2.59 (t, J = 7.7 Hz, 4H), 7.02 (dd, J = 7.9 and 1.4 Hz, 2H),
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7.11 (d, J = 1.4 Hz, 2H), 7.44 (s, 2H), 7.56 (d, J = 7.9 Hz, 2H); C NMR δ 14.1, 16.9, 22.7,
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29.3, 29.4, 29.5, 29.6 (2X), 29.7, 31.4, 31.9, 35.8, 126.1, 126.2, 126.9, 127.7, 135.6, 136.5,
143.0; EI-HRMS obsd 608.4427, calc 608.4449 (C40H64S2).
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5,5'-Didocecyl-2,2'-dimethylthio-trans-stilbene (26). The Kumada coupling was
performed with 438 mg (1 mmol) of 18 following the above procedure for 24. The resulting
residue was subjected to column chromatography [silica, petroleum ether/CH2Cl2 (90/10)] to
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afford an off-white solid (500 mg, 82 %): m.p.: 73–75 °C; H NMR δ 0.88 (t, J = 6.9 Hz, 6H),
1.25–1.34 (m, 36H), 1.63 (m, 4H), 2.45 (s, 6H), 2.61 (t, J = 7.6 Hz, 4H), 7.08 (dd, J = 8.0 and 1.7
Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 1.7 Hz, 2H), 7.49 (s, 2H); 13C NMR δ 14.1, 17.2,
22.7, 29.4 (2X), 29.5, 29.6 (2X), 29.7, 31.5, 31.9, 35.6, 126.4, 127.8, 128.2, 128.3, 133.8, 137.1,
140.9; EI-HRMS obsd 608.4457, calc 608.4449 (C40H64S2).
6,6'-Didocecyl-2,2'-dimethylthio-trans-stilbene (27). Route A: The Kumada coupling
was performed with 438 mg (1 mmol) of 19 following the above procedure for 24. The resulting
residue was subjected to column chromatography [silica, n-hexane/CH2Cl2 (85/15)] to afford an
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off-white solid (80 mg, 13 %): m.p.: 78–82 °C; H NMR δ 0.88 (t, J = 6.5 Hz, 6H), 1.22–1.38
(m, 36H), 1.61 (m, 4H), 2.44 (s, 6H), 2.83 (t, J = 7.8 Hz, 4H), 6.74 (s, 2H), 7.03-7.09 (m, 4H),
13
7.20 (t, J = 7.7 Hz, 2H); C NMR δ 14.1, 16.1, 22.7, 29.4, 29.7 (5X), 29.8, 31.6, 31.9, 33.8,
122.0, 125.8, 127.3, 131.9, 135.6, 138.3, 141.8; EI-HRMS obsd 608.4459, calc 608.4449
(C40H64S2). Route B: The McMurry coupling was performed with 1.45 g (5 mmol) of 28
following the above procedure for 24. Column chromatography [silica, petroleum ether/CH2Cl2
(80/20)] affords an off-white solid (609 mg, 40 %).
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2-Dodecyl-6-(methylthio)benzaldehyde (28). Following a general procedure for Kumada
coupling,28 a solution of 15 (1.83g, 6.6 mmol) and PdCl2(dppf) (483 mg, 0.66 mmol) in
anhydrous THF (30 mL) at 0 °C was treated dropwise with 1-dodecylmagnesium bromide (33
mL, 0.5 M in THF, 16.5 mmol), and the mixture was heated at reflux for 12 h. After cooling to
room temperature, 6 M aqueous HCl (20 mL) was added and the mixture was stirred for 10 min.
The mixture was filtered through a Celite pad, and the layers of the filtrate were separated. The
aqueous layer was extracted with dichloromethane, and the combined organic layer was dried
over MgSO4 and concentrated under vacuum. The resulting residue was subjected to column
chromatography [silica, petroleum ether/CH2Cl2 (60/40)] to afford an off-white solid (1.53 g, 72
%). m.p.: 60–64 °C; 1H NMR δ 0.88 (t, J = 6.5 Hz, 3H), 1.22–1.38 (m, 18H), 1.61 (m, 2H), 2.46
(s, 3H), 2.95 (t, J = 7.6 Hz, 1H), 7.02 (dd, J = 7.6 and 0.7 Hz, 1H), 7.19 (d, J = 8.0 Hz, 1H), 7.40
(d, J = 7.8 Hz, 1H), 10.58 (s, 1H); 13C NMR δ 14.1, 16.1, 22.7, 29.3, 29.4, 29.5 (2X), 29.6 (3X),
31.9, 32.9, 33.2, 123.3, 126.9, 130.3, 133.0, 144.2, 147.8, 191.2; EI-HRMS obsd 320.2176, calc
320.2174 (C20H32OS).
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1,6-Didodecyl[1]benzothieno[3,2-b][1]benzothiophene (1). The cyclization was
performed with 263 mg (0.43 mmol) of 24 following the above procedure for 20. The resulting
residue was subjected to column chromatography [silica, hot n-hexane] to afford an off-white
1
solid (166 mg, 67 %): m.p.: 86.3 °C; H NMR δ 0.87 (t, J = 6.9 Hz, 6H), 1.19–1.45 (m, 36H),
1.85 (m, 4H), 2.92 (t, J = 7.6 Hz, 4H), 7.22 (dd, J = 7.5 and 0.8 Hz, 2H), 7.41 (t, J = 7.5 Hz, 2H),
7.74 (dd, J = 7.8 and 0.8 Hz, 2H); 13C NMR δ 14.1, 22.7, 29.3 (2X), 29.5, 29.6 (2X), 29.7 (3X),
31.9, 34.8, 119.2, 124.3, 125.2, 133.2, 133.5, 138.2, 141.9; EI-HRMS obsd 576.3806, calc
576.3823 (C38H56S2).
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2,7-Didodecyl[1]benzothieno[3,2-b][1]benzothiophene (2). The cyclization was
performed with 312 mg (0.51 mmol) of 25 following the above procedure for 20. The resulting
residue was subjected to column chromatography [silica, hot n-hexane] to afford an off-white
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solid (10 mg, 3 %): m.p.: 117.4 °C (121–123 °C, hexane)5; H NMR δ 0.87 (t, J = 6.9 Hz, 6H),
1.25–1.38 (m, 36H), 1.69 (m, 4H), 2.75 (t, J = 7.8 Hz, 4H), 7.26 (dd, J = 8.1 and 1.3 Hz, 2H),
13
7.70 (d, J = 1.3 Hz, 2H), 7.75 (d, J = 8.1 Hz, 2H); C NMR δ 14.1, 22.7, 29.3 (2X), 29.5, 29.6
(3X), 29.7 (2X), 31.7, 31.9, 121.0, 123.3, 125.8, 131.2, 132.5, 140.0, 142.4; EI-HRMS obsd
576.3816, calc 576.3823 (C38H56S2). These data are identical to those reported in the literature.5
3,8-Didodecyl[1]benzothieno[3,2-b][1]benzothiophene (3). The cyclization was
performed with 414 mg (0.94 mmol) of 26 following the above procedure for 20. The resulting
residue was subjected to column chromatography [silica, hot n-hexane] to afford an off-white
1
solid (287 mg, 53 %): m.p.: 106.5 °C; H NMR δ 0.88 (t, J = 6.9 Hz, 6H), 1.25–1.38 (m, 36H),
1.71 (m, 4H), 2.76 (t, J = 7.6 Hz, 4H), 7.23 (dd, J = 8.3 and 1.5 Hz, 2H), 7.66 (d, J = 1.5 Hz,
2H), 7.81 (d, J = 8.3 Hz, 2H); 13C NMR δ 14.1, 22.7, 29.4 (2X), 29.5, 29.6 (2X), 29.7 (2X), 31.8,
36.0, 121.0, 123.6 (2X), 126.0, 133.4, 139.4, 140.0; EI-HRMS obsd 576.3828, calc 576.3823
(C38H56S2).
4,9-Didodecyl[1]benzothieno[3,2-b][1]benzothiophene (4). The cyclization was
performed with 480 mg (0.79 mmol) of 27 following the above procedure for 20. The resulting
residue was subjected to column chromatography [silica, hot n-hexane] to afford an off-white
solid (151 mg, 33 %): m.p.: 89 °C; 1H NMR δ 0.87 (t, J = 6.9 Hz, 6H), 1.20–1.60 (m, 36H), 1.80
(m, 4H), 3.13 (t, J = 7.9 Hz, 4H), 7.25 (d, J = 7.6 Hz, 2H), 7.33 (t, J = 7.5 Hz, 2H), 7.78 (d, J =
13
7.8 Hz, 2H); C NMR δ 14.1, 22.7, 29.6 (2X), 29.7 (4X), 31.2, 31.9, 34.7, 121.1, 124.9 (2X),
131.7, 131.9, 137.4, 143.1; EI-HRMS obsd 576.3812, calc 576.3823 (C38H56S2).
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Crystallographic information and copies of H NMR and C NMR spectra for all products.
This material is available free of charge via the Internet at http://pubs.acs.org. CCDC 936655
contains supplementary crystallographic data for this paper. These data can be obtained free of
charge
from
The
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgments
This work has been financially supported by a concerted research action of the French
Community of Belgian (ARC project N°20061), and by the Walloon Region (WCS project
N°1117306).
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