Synthesis of 5-aryl-5′-formyl-2,2′-bithiophenes as new precursors for nonlinear optical (NLO) materials

Article abstract of DOI:10.1016/j.tet.2008.12.078

A series of formyl-substituted 5-aryl-2,2′-bithiophenes 5 were synthesized using two different methods: Vilsmeier-Haack-Arnold reaction (VHA) or through Suzuki coupling. The synthesis of compounds 5 through the Vilsmeier-Haack-Arnold reaction, starting from inexpensive and easily available precursors such as acetophenones, gave the title compounds in low yields after four reaction steps. On the other hand Suzuki coupling of functionalized arylboronic acids 7 and the 5-bromo-5′-formyl-2,2′-bithiophene 6 gave compounds 5 in good yields in only one step.

Full text of DOI:10.1016/j.tet.2008.12.078

Tetrahedron 65 (2009) 2079–2086
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Synthesis of 5-aryl-50-formyl-2,20-bithiophenes as new precursors for nonlinear
optical (NLO) materials
,
Cyril Herbivo a, Alain Comel a, G. Kirsch a, M. Manuela M. Raposo b
*
a Laboratoire d’Inge´nierie Mole´culaire et Biochimie Pharmacologique, UFR SciFA, Universite´ de Metz, 1, Boulevard Arago, Metz Technopoˆle, 57078 Metz Cedex 3, France
b Centro de Qu´ımica, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal
a r t i c l e i n f o
a b s t r a c t
A series of formyl-substituted 5-aryl-2,20-bithiophenes 5 were synthesized using two different methods:
Vilsmeier–Haack–Arnold reaction (VHA) or through Suzuki coupling. The synthesis of compounds 5
through the Vilsmeier–Haack–Arnold reaction, starting from inexpensive and easily available precursors
such as acetophenones, gave the title compounds in low yields after four reaction steps. On the other
hand Suzuki coupling of functionalized arylboronic acids 7 and the 5-bromo-50-formyl-2,20-bithiophene
6 gave compounds 5 in good yields in only one step.
Article history:
Received 28 November 2008
Received in revised form 17 December 2008
Accepted 26 December 2008
Available online 8 January 2009
Keywords:
Vilsmeier–Haack–Arnold (VHA)
chloroformylation
Ó 2009 Elsevier Ltd. All rights reserved.
Suzuki coupling
Aldehydes
Formyl-substituted aryl-bithiophenes
p-Conjugated systems
UV–vis spectroscopy
Nonlinear optical (NLO) precursors
1. Introduction
we decided to synthesize the new functionalized 5-aryl-50-for-
myl-2,20-bithiophenes, which will be used in the future as
Formyl (oligo)thiophene derivatives are versatile ‘crossroads’
intermediates. Not surprisingly, a large number of methods have
been developed in order to obtain these functionalized heterocy-
cles. Vilsmeier formylation1 and metalation followed by quenching
with DMF constitute the most important routes for the preparation
of formyl-substituted (oligo)thiophenes.1e,2
The obtained formyl- derivatives can further react to yield more
complex molecules, which have made of formyl-(oligo)thiophenes
some of the most important molecules to be used as building blocks
in biological active compounds, supramolecular chemistry, and
molecular electronics.3
Having in mind our recent work in which we have used formyl
heterocyclic systems (oligothiophenes,4 arylthiophenes,5 and
thienylpyrroles6) as precursors for the synthesis of more complex
molecules (dicyanovinyl-derivatives,4a,b,7 organometallic com-
pounds,8 benzothiazoles,5,9 benzimidazoles,10 benzoxazoles,11
imidazo-anthraquinones,12 imidazo-phenanthrolines,13 bis-indolyl-
methanes,14 Schiff-bases, and tertiary amines bearing crown
ether moieties15) for several optical and sensors applications,
versatile synthons in the preparation of a large variety of het-
erocyclic donor–acceptor -conjugated systems.
p
As part of our continuing interest in heterocyclic derivatives for
optical applications, we report in this paper the synthesis and the
UV–vis study of the new 5-formyl-50-aryl-2,20-bithiophenes 5,
which have the conjugated 5-alkoxyaryl- or 5-N,N-di-
alkylaminoaryl-2,20-bithiophene, as strong
moieties.
p-electron donor
2. Results and discussion
2.1. Synthesis
Recently we have reported the synthesis and the characteriza-
tion of 5-alkoxy- and 5-N,N-dialkylamino-50-formyl-2,20-bithio-
phenes 84a (Fig. 1). Formyl derivatives 8 were prepared by
functionalization of 5-alkoxy- or 5-N,N-dialkylamino-2,20-bithio-
phenes16 through the Vilsmeier–Haack reaction or through lith-
iation followed by quenching with DMF. Formyl-terthiophenes 94b
were also reported by us through Stille coupling reaction. The
stannylated derivatives, readily prepared from 5-N,N-dialkylamino-
2,20-bithiophenes were coupled with 2-bromo-5-formylthiophene
to give the expected products. More recently we also reported the
* Corresponding author. Tel.: þ 351 253 604381; fax: þ351 253 604382.
E-mail address: mfox@quimica.uminho.pt (M.M.M. Raposo).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.12.078

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C. Herbivo et al. / Tetrahedron 65 (2009) 2079–2086
R
S
S
S
R
CHO
R
CHO
CHO
8
S
S
S
9
10
b
c
d
e
R = MeO
R = EtO
R = NMe2
R = NEt2
d
R = NMe2
R = piperidino
a
b
c
d
R = H
g
R = MeO
R = EtO
R = NMe2
Figure 1. Structure of compounds 8,4a 9,4b and 10.5
synthesis of 2-formyl-5-arylthiophenes 105 (Fig. 1) through Suzuki
coupling. Formyl derivatives 8 and 10 were used as precursors for
the synthesis of several heterocyclic derivatives with interesting
optical applications (e.g., solvatochromic probes, fluorescent
markers, nonlinear optical materials, and colorimetric and fluori-
metric sensors).4a,5,8,9a,c,12a,13
On the basis of our recent results we decided to synthesize the
new 5-alkoxy- or 5-N,N-dialkylaminoaryl-50-formyl-2,20-bithio-
phenes 5 in order to study the influence of the structure modifi-
previously using the same experimental procedure. Compounds
2a–f were converted to the arylthienyl-ethanones 3a–f in fair to
excellent yields, 23–95%, through condensation with sodium
sulfide Na2S$9H2O, in DMF in the presence of chloroacetone and
base (K2CO3) at 60 ꢀC. Compounds 3a23 and 3b24 have been pre-
viously reported. Although thiophene 3a23 is largely described by
palladium catalyzed coupling reaction in the literature, preparation
of 3b24 is only reported by building of the thiophene ring and
derivatives 3c–f remain surprisingly undescribed. The new com-
pounds 3c–f were prepared by us, in moderate to excellent yields
(50–95%). The second VHA reaction on arylthienyl-ethanones 3
gave compounds 4 in fair to excellent yields (10–99%). Finally, the
second condensation of sodium sulfide, with compounds 4, using
the same experimental conditions described above gave the 5-
cation (i.e., the length and the electronic nature of the p-conjugated
bridge) on the optical properties (UV–vis) of compounds 5 and also
to compare them with our recently reported systems containing
the bithiophene (8), terthiophene (9) or arylthiophene (10)
entities.4a,b,5
In order to choose the most efficient method for the synthesis of
the mentioned formyl derivatives, compounds 5 with aryl and
formyl-50-(4-substituted-phenyl)-2,20-bithiophenes
moderate yields.
5 in fair to
bithiophene units acting as linking
p
-conjugated bridges between
Although the very low global yields for the synthesis of alde-
hydes 5 using the VHA reaction this synthetic route seems to have
some interest due to its originality, which lies on the double use of
the classical combination of VHA reaction and condensation with
sodium sulfide to obtain functionalized aryl-bithiophenes. Even in
our case the Vilsmeier–Haack–Arnold reaction were not very suc-
cessful due to the lower yields, there are several reported examples
in which the VHA formylation works very well demonstrating the
synthetic potential of this reaction.17
the donor groups (alkoxy, N,N-dialkylamino) and the formyl func-
tionality were synthesized using two different methods: a simple
multi-step procedure: Vilsmeier–Haack–Arnold reaction (VHA)17
or through Suzuki coupling.5
2.1.1. Synthesis of compounds 5 through Vilsmeier–Haack–Arnold
(VHA) reaction
Compounds 5 were first synthesized through a sequence in
which the first step was VHA17 reaction starting from inexpensive
and easily available precursors (Scheme 1). The starting acetophe-
nones 1a,b were commercially available while compounds 1c–f
were prepared according previously published procedures18–21
Therefore, compounds 2 were prepared from acetophenones 1a–f
2.1.2. Synthesis of compounds 5 through Suzuki coupling
Secondly, formyl compounds 5 were synthesized through
a Suzuki cross-coupling reaction of commercially available aryl-
boronic acids 6a–d with 50-bromo-5-formyl-2,20-bithiophene 7.
Precursor 7 was obtained from commercial 5-formyl-2,20-bithio-
phene by bromination with NBS in DMF in 98% yield.11c The Suzuki
coupling reactions were performed in 1,2-dimethoxyethane (DME)
through Vilsmeier–Haack–Arnold (VHA) reaction to give b-chloro-
b
-arylacroleins 2a–f in moderate to excellent yields (40–99%)
(Table 1). Compounds 2a,b,17c 2c,22 and 2d17c were described
O
H
O
O
R
Na2S.9 H2O / DMF
Cl
POCl3 / DMF / 60 °C
CH3
S
ClCH2COCH3 / K2CO3
R
R
2a-f
1a-f
3a-f
a
R = H
b
c
d
e
f
R = MeO
R = EtO
R = NMe2
R = NEt2
R = pyrrolidino
POCl3 / DMF / 60 °C
O
Na2S.9 H2O / DMF
ClCH2CHO / K2CO3
R
R
H
S
S
CHO
S
Cl
5a-b, d-f
4a-f
Scheme 1. Synthesis of compounds 2–5 through Vilsmeier–Haack–Arnold reactions.

C. Herbivo et al. / Tetrahedron 65 (2009) 2079–2086
2081
Table 1
Yields of compounds 2–5
Entry
R
Compound 2
Yield (%)
Compound 3
Yield (%)
Compound 4
Yield (%)
Compound 5
Yield (%)
Global
Yield (%)
1
2
3
4
5
6
H
MeO
EtO
NMe2
NEt2
a
b
c
d
e
f
40
82
85
95
52
99
a
b
c
d
e
f
23
77
95
59
64
50
a
b
c
d
e
f
10
25
50
99
70
99
a
b
c
d
e
f
22
44
d
0.2
6.9
d
44
13
10
24
3.0
4.9
Pyrrolidino
and aqueous 2 M Na2CO3 (2 equiv) under an argon atmosphere and
Pd(PPh3)4 (6 mol %) was used as palladium catalyst at 80 ꢀC5 for 2–
24 h (Scheme 2). Formyl derivatives 5 were obtained in good yields
53–80% (Table 2).
compound 5c, which was not possible to obtain using the VHA
reaction was prepared through Suzuki coupling in a good yield
(80%).
The structures of compounds 5 were unambiguously confirmed
by their analytical and spectral data.
Bithiophenes 5 are rarely described in the literature. The prep-
aration of compound 5a by building of the thiophene ring using
a three steps synthetic way is reported in a patent25a but only
elemental analyses are given. More recently the synthesis of the
same compound has been described through Suzuki coupling of
phenyl boronic acid and 5-formyl-50-iodo-2,20-bithiophene using
different coupling conditions and again no experimental data are
reported.25b The synthesis of 5-formyl-50-(4-N,N-dimethylamino-
phenyl)-2,20-bithiophene 5d has been reported by Mignani et al.2a
(overall yield 20% yield) through Negishi coupling between 2,20-
bithiophen-5-yl zinc chloride with 1-bromo-4-N,N-dimethylami-
nobenzene followed by lithiation and reaction with DMF in THF. No
experimental details or analytical data about the derivative were
given. More recently the same formyl derivative 5d was prepared
by Clays et al.26 in 97% yield, through Suzuki coupling using the
same coupling components described by us but slightly different
reaction conditions (1 equiv of aldehyde 7, 1.2 equiv of boronic acid
6d, (10 mol %) of Pd(PPh3)4 and 10 equiv of K2CO3, toluene, reflux).
In comparison to the method described earlier, compound 5d, was
obtained by us, through our experimental conditions, in a similar
yield (64%). Attempts to synthesize compound 5d using the same
experimental procedure described by Clays et al., gave, in our
hands, the expected compound but only in 65% yield after 24 h of
reflux (Table 2). More recently the synthesis of compound 5e has
been described in a Japanese patent27 through Suzuki coupling
using 5-formyl-50-bromo-2,20-bithiophene and 4-(N,N-dieth-
ylamino)phenyl boronic acid as coupling components. Un-
fortunately, the details concerning the practical procedure are
given in Japanese. The formyl derivative 5e was used as precursor in
the preparation of organic electroluminescent materials.
2.2. UV–vis study of formyl-aryl-2,20-bithiophenes 5
The electronic spectra of formyl-aryl-2,20-bithiophenes 5,
recorded in ethanol solutions (10ꢁ4 M) showed an intense lowest
energy charge-transfer absorption band in the UV–vis region. The
position of this band depended on the electronic nature of the
substituent (H, alkoxy, or N,N-dialkylamino) at position 4 of the aryl
moiety (Table 3). The reason for the substantial red shift in the
investigated compounds 5b–f, functionalized with donor groups,
lmax¼397.0–442.0 nm, relative to that of unsubstituted formyl-
aryl-2,20-bithiophene 5a (lmax¼382.5 nm) was the strong inductive
and conjugative effect of the alkoxy and N,N-dialkylamino sub-
stituents at the para position of the phenyl ring.
The influence of the strength of the donor group was demon-
strated by comparison of the absorption maxima of compounds 5b
and 5e as the longest wavelength transition was shifted from
397.0 nm in 5-formyl-50-(4-methoxyphenyl)-2,20-bithiophene 5b
to 442.0 nm in 5-formyl-50-(4-N,N-diethylaminopheny)-2,20-
bithiophene 5e (Table 3, entries 2 and 5, respectively).
The shifts of the absorption maxima were proportional to the
intramolecular charge-transfer (ICT) between the electron-releasing
and withdrawing group. In general, the stronger the donor and/or
acceptor group, the smaller theenergy difference between ground and
excited states, and the longer the wavelength of absorption.28
At this stage, a comparison could also be made between the UV–
vis study of the new 5-formyl-50-aryl-2,20-bithiophenes 5 with 5-
formyl-50-alkoxy- and 5-N,N-dialkylamino-2,20-bithiophenes 8,4a
formyl-N,N-dialkylamino-terthiophenes 9,4b and 5-formyl-2-
arylthiophenes 10,5 recently reported by us (Fig. 1). The nature of
the thiophenic bridge had a clear influence on the absorption bands
of compounds 5, 8, 9, and 10. The obtained results showed that, the
The synthesis of compounds 5 through Vilsmeier–Haack–
Arnold reactions gave the title compounds in low yields after four
reaction steps. In comparison to the first method described earlier,
compounds 5a–d were prepared by Suzuki coupling in higher
yields using only one step, from commercially available reagents,
using simple work-up procedures, resulting in good yielding
preparation and ease of isolation of these derivatives. Moreover,
substitution of a benzene ring by a thiophene on the p-conjugated
bridge, while maintaining the same donor group produced a bath-
ochromic shift on the absorption wavelength maxima (see, for
example, the comparison between 10d, R¼NMe2, lmax¼410.0 nm,
B(OH)2
S
S
CHO
DME / Pd(PPH3)4
Na2CO3(2M) / 80 °C / Ar
Br
CHO
+
S
S
R
R
6a-d
7
5a-d
a
b
c
d
R = H
R = MeO
R = EtO
R = NMe2
Scheme 2. Synthesis of formyl-arylbithiophenes 5 through Suzuki coupling.

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C. Herbivo et al. / Tetrahedron 65 (2009) 2079–2086
Table 2
Yields of compounds 5 through Suzuki coupling and 1H NMR, IR, and UV–vis absorption data
b
Entry
R
Compound 5
Yield (%)
dH (ppm)a
Reaction
time (h)
IR
n
(cmꢁ1
)
lmax (3
) (nm)c
1
2
3
4
H
a
b
c
78
53
80
64
65d
d
9.88
9.87
9.86
9.85
2
12
3
24
3d
d
d
1654
1665
1672
1657
382.5 (26,775)
394.5 (27,936)
395.5 (18,965)
424.0 (24,538)
MeO
EtO
NMe2
d
5
6
NEt2
Pyrrolidino
e
f
9.85
9.85
1652
1645
435.5 (26,966)
433.0 (32,976)
d
a
For the CHO proton for formyl-arylbithiophenes 5 (300 MHz, DMSO-d6).
For the C]O stretching band (recorded in Nujol).
b
c
All the UV–vis spectra were recorded in dioxane.
d
Using the experimental procedure reported by Clays et al.26
Table 3
UV–vis absorption data for formyl derivatives 5, 8,4a and 105 in ethanol
Entry
R
Compound 5
lmax (nm)
Compound 8
lmax (nm)
Compound 10
lmax (nm)
1
2
3
4
5
6
H
MeO
EtO
NMe2
NEt2
a
b
c
d
e
f
382.5
397.0
398.0
430.5
442.0
435.0
a
b
c
d
e
f
d
a
b
c
d
e
f
287.0
345.0
345.0
410.0
d
385.0
383.0
451.0
463.0
d
Pyrrolidino
d
with 8d, R¼NMe2, lmax¼451.0) (Table 3, entry 4) or comparison
between 8d with 9d, R¼NMe2, lmax¼465.5.4b This observation
clearly indicates that the incorporation of thiophene units in push–
pull compounds enhances their charge-transfer properties. The
optical data obtained are not surprising and could be explained
having in mind the bathochromic effect of sulfur, the partial de-
crease of aromatic character of the thiophene heterocycle com-
Suzuki coupling. As far as we know this is the first time that the
double use of the classical combination between VHA reaction and
condensation with sodium sulfide was used to synthesize func-
tionalized aryl-bithiophenes. Commercial reagents and simple and
convenient procedures were used in the preparation of the men-
tioned compounds in both synthetic routes.
The formyl- derivatives 5 studied exhibit an absorption band in
the UV–vis range influenced by electronic nature of the substituent
pared to benzene and also the increase of the
p-overlap between
the thiophene units.4b,29
on the 4-position of the aryl-bithienyl
p-conjugated bridge. Com-
The wavelength of maximum absorption for compounds 5
compared to compounds 10 was shifted to longer wavelengths
(20.5–95.5 nm) as the number of thiophene units increased, as
expected from the increase in conjugation. The same trend was
observed also for the formyl-terthiophene derivative 9d
pounds 5 revealed also good optical properties compared to similar
formyl derivatives 8–10.
In agreement with previous findings4a,b,5,7,9 the new compounds
have potential importance in the manufacture of new materials for
several optical applications. Therefore, the conjugated formyl de-
rivatives of 5-arylbithiophenes 5 will be used in the future, as pre-
cursors in the preparation of compounds with stronger electron
withdrawinggroups,whichshould exhibitstrongNLO properties.4a,b,7
(
(
lmax¼465.5 nm) compared to the formyl-bithiophene 8d
lmax¼451.0 nm). In the case of alkoxyphenyl-2,20-bithiophene
derivatives 5a,b a bathochromic shift of 12–15 nm was also ob-
served in comparison to the alkoxy-2,20-bithiophenes 8a,b due to
the introduction of a benzene ring on the bithienyl conjugated
bridge. On the contrary, comparison of the wavelength of maxi-
mum absorption of the N,N-dialkylaminophenyl-2,20-bithiophenes
5d and 5e with N,N-dialkylamino-2,20-bithiophenes 8d and 8e
functionalized with the same donor groups, showed that although
4. Experimental
4.1. General
All melting points were measured on a Gallenkamp melting
point apparatus and are uncorrected. TLC analyses were carried out
on 0.25 mm thick precoated silica plates (Merck Fertigplatten Kie-
selgel 60F254) and spots were visualized under UV light. Chroma-
tography on silica gel was carried out on Merck Kieselgel (230–240
mesh). IR spectra were determined on a BOMEM MB 104 spectro-
photometer using KBr discs or Nujol. UV–vis absorption spectra
(200–800 nm) were obtained using a Shimadzu UV/2501PC spec-
trophotometer. 1H NMR spectra were recorded on a Varian 300
spectrometer in CDCl3 at 300 MHz at 25 ꢀC. All chemical shifts are
given in parts per million using dH Me4Si¼0 ppm as reference and
J values are given in hertz. 13C NMR spectra were run in the same
instrument at 75.4 MHz using the solvent peak as internal refer-
ence (Braga, Portugal). 1H NMR spectra were also recorded on a AC
Bruker 250 MHz spectrometer. 13C NMR spectra were run in the
same instrument at 62.9 MHz using the solvent peak as internal
compounds 8d,e contain a smaller
p-conjugating system consti-
tuted by the bithienyl moiety, the wavelength of their maximum
absorption exhibits bathochromic shifts of 21 nm. This experi-
mental result could perhaps be explained by evoking the auxiliary
donor effect of the electron-rich thiophene heterocycle7,9b,10,30 di-
rectly linked to the stronger N,N-dialkylamino donor groups, in
compounds 8d,e, and also some lost of planarity of molecules 5d,e
in which the N,N-dialkylamino donor groups are linked on
4-position on the benzene ring.
3. Conclusions
In summary, we have achieved the first synthesis of a series of 5-
formyl-50-aryl-2,20-bithiophenes 5 through two different synthetic
strategies: a sequence using Vilsmeier–Haack–Arnold reaction and

C. Herbivo et al. / Tetrahedron 65 (2009) 2079–2086
2083
reference (Metz, France). Assignments were made by comparison of
chemical shifts, peak multiplicities and J values and were supported
by spin decoupling-double resonance and bidimensional hetero-
nuclear HMBC and HMQC correlation techniques. Mass spectrom-
etry analyses were performed at the ‘C.A.C.T.I.dUnidad de
Espectrometria de Masas’ at the University of Vigo, Spain. Ele-
mental analyses were carried out on a Leco CHNS 932 instrument.
Acetophenone 1a and 4-methoxyacetophenone 1b used as
precursors for the synthesis of compounds 5 were purchased from
Aldrich and Acros and used as received.
After this time a solution of acetophenones 1 (148 mmol) in DMF
(150 ml) was added dropwise with stirring. The reaction mixture
was then heated 3 h at 60 ꢀC. The solution cooled at room tem-
perature was then poured slowly into a sodium acetate aqueous
solution (10%). The pH was adjusted at 4 with sodium acetate. The
solid obtained was filtered and washed with water to afford com-
pounds 2a–f, which were used in the next reaction step without
further purification.
4.3.1.
Orange solid (85%). Mp 40–41 ꢀC (lit.22 44 ꢀC). 1H NMR
(250 MHz, CDCl3)
1.44 (t, 3H, J¼7.0 Hz), 4.1 (q, 2H, J¼7.0 Hz), 6.65
b-Chloro-b-(4-ethoxyphenyl)-propenal (2c)
The synthesis of arylacrylaldehydes 2a,b,17c 2d,17c and 5-bromo-
50-formyl-2,20-bithiophene 711c was described elsewhere.
d
(d, 1H, J¼7.0 Hz), 6.8 (d, 2H, J¼9.0 Hz), 7.3 (d, 2H, J¼9.0 Hz), 10.1 (d,
4.2. Synthesis of acetophenones 1c–f
1H, J¼7.0 Hz). 13C NMR (62.9 MHz, CDCl3)
d 14.6, 63.7, 114.4, 122.3,
130.5, 152.2, 162.1, 191.5.
4.2.1. 4-Ethoxyacetophenone (1c)
To a solution of 4-hydroxyacetophenone (68 g, 0.5 mol) in
250 ml of DMF were added bromoethane (65.4 g, 0.6 mol) and
K2CO3 (83 g, 0.6 mol). The mixture was stirred at 60 ꢀC during 1 day,
cooled at room temperature and quenched in a mixture of ice and
water. The product was filtered and washed with water to afford
the 4-ethoxyacetophenone 77 g (94%) as a pale brown solid. Mp
4.3.2. b-Chloro-b-(4-N,N-diethylaminophenyl)-propenal (2e)
Orange solid (52%). Mp 80–81 ꢀC. 1H NMR (250 MHz, CDCl3)
d
1.16 (t, 6H, J¼7.1 Hz), 3.43 (q, 4H, J¼7.1 Hz), 6.54 (d, 1H, J¼7.5 Hz),
6.63 (d, 2H, J¼9.0 Hz), 7.65 (d, 2H, J¼9.0 Hz), 10.12 (d, 1H, J¼7.5 Hz).
13C NMR (62.9 MHz, CDCl3)
149.7, 152.7, 191.6.
d 12.2, 45.3, 111.6, 119.7, 129.2, 132.0,
38–39 ꢀC (lit.18 34–38 ꢀC). 1H NMR (250 MHz, CDCl3)
d 1.42 (t, 3H,
J¼5.1 Hz), 2.52 (s, 3H), 4.07 (q, 2H, J¼5.1 Hz), 6.95 (d, 2H, 7.5 Hz),
4.3.3. b-Chloro-b-(4-pyrrolidinophenyl)-propenal (2f)
7.90 (d, 2H, J¼7.5 Hz).
Green solid (99%). Mp 120–121 ꢀC. 1H NMR (250 MHz, CDCl3)
d
2.03 (q, 4H, J¼3.4 Hz), 3.36 (t, 4H, J¼3.4 Hz), 6.55 (d, 2H, J¼8.9 Hz),
4.2.2. 4-N,N-Dimethylaminoacetophenone (1d)
6. 60 (d, 1H, J¼7.0 Hz), 7.66 (d, 2H, J¼8.9 Hz), 10.13 (d, 1H, J¼7.0 Hz).
To a solution of 4-aminoacetophenone (27 g, 0.2 mol) in 200 ml
of DMF were added iodomethane (62 g, 0.44 mol) and K2CO3 (61 g,
0.44 mol). The mixture was stirred at 60 ꢀC during 1 day, cooled at
room temperature and quenched with a mixture of ice and water.
The product was filtered and washed with water to afford the 4-
N,N-dimethylaminoacetophenone (31 g, 95%) as a white solid. Mp
13C NMR (62.9 MHz, CDCl3)
150.3, 153.4, 191.6.
d 25.4, 47.6, 111.9, 119.0, 121.0, 113.9,
4.4. General procedure for the synthesis of arylthenyl-
ethanones 3a–f
108–109 ꢀC (lit.19 105 ꢀC). 1H NMR (250 MHz, CDCl3)
d
2.50 (s, 3H),
To a solution of Na2S$9H2O (30.5 g, 127 mmol) and DMF
3.05 (s, 6H), 6.64 (d, 2H, J¼7.5 Hz), 7.86 (d, 2H, J¼7.5 Hz).
(200 ml) was added b-chloroacroleine (127 mmol). The mixture
was stirred at 60 ꢀC during 2 h. Chloroacetone (11.7 g, 127 mmol)
was added rapidly and the reaction was stirred during 3 h at 60 ꢀC.
K2CO3 (17.6 g, 127 mmol) was dissolved in water (1 ml) and added
to the reaction. The mixture was stirred during 10 min at 60 ꢀC,
cooled at room temperature and quenched in water. The solid
obtained was filtered and the crude product was washed with
water and recrystallized from ethanol.
4.2.3. 4-N,N-Diethylaminoacetophenone (1e)
To a solution of 4-aminoacetophenone (20 g, 148 mmol) in
150 ml of DMF were added bromoethane (35.5 g, 326 mmol), K2CO3
(50 g, 355 mmol), and KI (27 g, 326 mmol). The mixture was stirred
at 60 ꢀC during 1 day, cooled at room temperature and quenched
with a mixture of ice and water. The product was filtered and
washed with water to afford (32 g, 99%) of 4-N,N-dieth-
ylaminoacetophenone as a pale yellow solid. Mp 44–45 ꢀC (lit.20
4.4.1. 1-(5-Phenylthiophen-2-yl)ethanone (3a)
47–48 ꢀC). 1H NMR (250 MHz, CDCl3)
3H), 3.39 (q, 4H, J¼7.0 Hz), 6.60 (d, 2H, 7.2 Hz), 7.82 (d, 2H,
J¼7.2 Hz).
d
1.18 (t, 6H, J¼7.0 Hz), 2.49 (s,
Dark brown solid (23%). Mp 101–102 ꢀC (lit.23 109–110 ꢀC). IR
(Nujol)
n 1650 (C]O), 1531, 1274, 1087, 1074, 999, 966, 926, 909,
843, 808, 757, 720, 688, 661, 641, 611, 590 cmꢁ1. 1H NMR (250 MHz,
CDCl3)
d
2.54 (s, 3H), 7.32 (d, 1H, J¼4.0 Hz), 7.41 (m, 3H), 7.64 (m,
4.2.4. 4-Pyrrolidinoacetophenone (1f)
2H), 7.66 (d, 1H, J¼4.0 Hz). 13C NMR (62.9 MHz, CDCl3)
d 26.0, 123.3,
To a solution of 4-aminoacetophenone (20 g, 148 mmol) in
300 ml of DMF were added 1,4-dichlorobutane (20.7 g, 163 mmol),
K2CO3 (52 g, 370 mmol), and KI (55 g, 326 mmol). The mixture was
stirred at 60 ꢀC during 2 days, cooled at room temperature and
quenched with a mixture of ice and water. The product was filtered
and washed with water to afford (24 g, 84%) of 4-pyrrolinoaceto-
phenone as a pale orange solid. Mp. 127–128 ꢀC (lit.21 134–135 ꢀC).
125.7, 128.5, 128.6, 132.8, 132.9, 142.5, 152.3, 190.1.
4.4.2. 1-(5-(4-Methoxyphenyl)thiophen-2-yl)ethanone (3b)
Dark brown solid (77%). Mp 156–157 ꢀC (lit.24 150–152 ꢀC). 1H
NMR (250 MHz, CDCl3)
d 2.55 (s, 3H), 3.85 (s, 3H), 6.95 (d, 2H,
J¼8.8 Hz), 7.21 (d, 1H, J¼3.9 Hz), 7.59 (d, 2H, J¼8.8 Hz), 7.63 (d, 1H,
J¼3.9 Hz). 13C NMR (62.9 MHz, CDCl3)
d 44.2, 56.5, 111.2, 120.2,
121.0, 127.3, 133.8, 140.6, 147.3, 155.7, 190.2.
1H NMR (250 MHz, CDCl3)
d
1.18 (q, 4H, J¼6.7 Hz), 2.49 (s, 3H), 3.33
(q, 4H, J¼6.7 Hz), 6.48 (d, 2H, 7.0 Hz), 7.84 (d, 2H, J¼7.0 Hz). 13C NMR
(62.9 MHz, CDCl3)
d
25.4, 25.7, 47.8, 111.8, 126.6, 130.2, 151.0, 196.2.
4.4.3. 1-(5-(4-Ethoxyphenyl)thiophen-2-yl)ethanone (3c)
Dark brown solid (95%). Mp 117–118 ꢀC. IR (Nujol)
1651 (C]O),
n
4.3. General procedure for the Vilsmeier–Haack–Arnold
1603, 1571, 1533, 1509, 1311, 1083, 1034, 962, 921, 893, 838, 797, 748,
reaction of acetophenones 1 to give
propenal 2
b-chloro b-aryl
723, 695, 642, 628, 610, 591, 535 cmꢁ1. 1H NMR (250 MHz, CDCl3)
d
1.42 (t, 3H, J¼3.1 Hz), 2.59 (s, 3H), 4.07 (q, 2H, J¼3.1 Hz), 6.91 (d,
2H, J¼8.85 Hz), 7.20 (d, 1H, J¼3.95 Hz), 7.56 (d, 2H, J¼8.85 Hz), 7.62
POCl3 (17 ml, 182 mmol) was slowly added to DMF (20 ml,
255 mmol) at 0 ꢀC and the mixture was stirred for 10 min at 0 ꢀC.
(d, 1H, J¼3.95 Hz). 13C NMR (62.9 MHz, CDCl3)
d 12.5, 26.3, 44.4,
111.4, 120.2, 121.0, 127.5, 133.9, 140.3, 148.3, 154.6, 190.3. MS (EI) m/z

2084
C. Herbivo et al. / Tetrahedron 65 (2009) 2079–2086
(%): 246 (Mþ, 75), 231 (30), 218 (20), 203.0 (100), 189 (10), 175 (11),
147 (11), 131 (12), 121 (5), 102 (7). HRMS: m/z (EI) for C14H14O2S
calcd 246.0715; found: 246.0712.
7.20 (d, 1H, J¼4.0 Hz), 7.52 (d, 2H, J¼8.8 Hz), 7.61 (d, 1H, J¼4.0 Hz),
10.12 (d, 1H, J¼6.9 Hz). 13C NMR (62.9 MHz, CDCl3)
d 57.5, 115.6,
121.2, 123.1, 126.2, 127.5, 132.5, 137.5, 145.0, 151.2, 160.0, 191.2.
4.4.4. 1-(5-(4-N,N-Dimethylaminophenyl)thiophen-2-yl)
4.5.3.
propenal (4c)
Dark brown solid (50%). Mp 120–121 ꢀC. 1H NMR (250 MHz,
CDCl3)
b-Chloro-b-(5-(4-ethoxyphenyl)thiophen-2-yl)-
ethanone (3d)
Dark brown solid (59%). Mp 124–125 ꢀC. IR (Nujol)
n 1699
(C]O), 1650, 1601, 1515, 1354, 1270, 1194, 1155, 1093, 1077, 1033,
d
1.27 (t, 3H, J¼2.4 Hz), 3.84 (q, 2H, J¼2.4 Hz), 6.36 (d, 1H,
1014, 961, 922, 899, 813, 769, 747, 735, 724, 685, 633, 609 cmꢁ1. 1H
J¼6.9 Hz), 6.73 (d, 2H, J¼8.8 Hz), 7.01 (d, 1H, J¼4.0 Hz), 7.34 (d, 2H,
NMR (250 MHz, CDCl3)
d 2.53 (s, 3H), 3.02 (s, 6H), 6.70 (d, 2H,
J¼8.8 Hz), 7.42 (d, 1H, J¼4.0 Hz), 9.93 (d, 1H, J¼6.9 Hz). 13C NMR
J¼8.8 Hz), 7.15 (d, 1H, J¼4.0 Hz), 7.53 (d, 2H, J¼8.8 Hz), 7.60 (d, 1H,
(62.9 MHz, CDCl3) d 14.6, 63.3, 115.3, 121.0, 123.8, 126.4, 127.2, 132.3,
J¼4.0 Hz). 13C NMR (62.9 MHz, CDCl3)
d
47.6, 55.2, 112.0, 120.5,
137.8, 145.0, 151.2, 160.0, 191.3.
121.0, 127.6, 134.2, 140.0, 148.3, 154.8, 190.2. MS (EI) m/z (%): 245
(Mþ, 100), 230 (60), 202 (40), 158 (55). HRMS: m/z (EI) for
C14H15NOS calcd 245.0874; found: 245.0871.
4.5.4.
b-Chloro-b-(5-(4-N,N-dimethylaminophenyl)thiophen-2-yl)-
propenal (4d)
Dark brown solid (99%). Mp 74–75 ꢀC. 1H NMR (250 MHz, CDCl3)
4.4.5. 1-(5-(4-N,N-Diethylaminophenyl)thiophen-2-yl)
d
3.00 (s, 6H), 6.04 (d, 1H, J¼7.5 Hz), 6.65 (d, 2H, J¼8.8 Hz), 7.03 (d,
ethanone (3e)
1H, J¼4.0 Hz), 7.49 (d, 2H, J¼8.8 Hz), 7.62 (d, 1H, J¼4.0 Hz), 10.12 (d,
Dark brown solid (64%). Mp 90–91 ꢀC. IR (Nujol)
n
1651 (C]O),
1H, J¼7.5 Hz). 13C NMR (62.9 MHz, CDCl3)
d 55.4, 114.6, 120.6, 122.7,
1608, 1517, 1290, 1231, 1193, 1168, 1090, 1064, 1035, 1008, 963, 945,
125.6, 127.0, 132.1, 137.0, 144.5, 150.6, 160.4, 190.7.
922, 869, 813, 798, 722, 614, 514 cmꢁ1. 1H NMR (250 MHz, CDCl3)
d
1.20 (t, 6H, J¼5.47 Hz), 2.52 (s, 3H), 3.38 (q, 4H, J¼5.47 Hz), 6.65 (d,
4.5.5.
propenal (4e)
b-Chloro-b-(5-(4-N,N-diethylaminophenyl)thiophen-2-yl)-
2H, J¼9 Hz), 7.12 (d, 1H, J¼4 Hz), 7.50 (d, 2H, J¼9 Hz), 7.59 (d, 1H,
J¼4 Hz). 13C NMR (62.9 MHz, CDCl3)
d
25.4, 26.3, 47.5, 112.0, 120.4,
Dark brown solid (70%). Mp 74–75 ꢀC. 1H NMR (250 MHz, CDCl3)
120.9, 127.5, 133.5, 140.3, 149.4, 153.8, 190.4. MS (EI) m/z (%): 273
(Mþ, 39), 258 (100), 230 (30). HRMS: m/z (EI) for C16H19NOS2 calcd
273.1187; found: 273.1192.
d
1.21 (t, 6H, J¼6.75 Hz), 3.83 (q, 4H, J¼6.75 Hz), 6.32 (d, 1H,
J¼6.92 Hz), 6.69 (d, 2H, J¼8.82 Hz), 6.98 (d, 1H, J¼4.05 Hz), 7.29 (d,
2H, J¼8.82 Hz), 7.38 (d, 1H, J¼4.05 Hz), 9.88 (d, 1H, J¼6.92 Hz). 13C
NMR (62.9 MHz, CDCl3) d 25.5, 43.6, 111.5, 119.3, 120.4, 127.2, 132.6,
4.4.6. 1-(5-(4-Pyrrolidinophenyl)thiophen-2-yl)ethanone (3f)
134.9, 144.7, 148.4, 152.5, 160.3, 190.7.
Dark brown solid (50%). Mp 198–199 ꢀC. IR (Nujol)
n 1643
(C]O), 1605, 1536, 1519, 1483, 1316, 1288, 1249, 1229, 1214, 1183,
4.5.6.
propenal (4f)
Dark brown solid (99%). Mp 115–116 ꢀC. 1H NMR (250 MHz,
CDCl3)
b-Chloro-b-(5-(4-(pyrrolidino)phenyl)thiophen-2-yl)-
1119, 1087, 1030, 1006, 969, 955, 921, 894, 862, 815, 809, 862, 697,
666, 609, 596, 521 cmꢁ1. 1H NMR (250 MHz, CDCl3)
d 2.03 (qu, 4H,
J¼2.5 Hz), 2.53 (s, 3H), 3.33 (t, 4H, J¼2.5 Hz), 6.55 (d, 2H, J¼7.5 Hz),
d
2.00 (q, 4H, J¼3.6 Hz), 3.30 (t, 4H, J¼3.6 Hz), 6.51 (d, 1H,
7.14 (d, 1H, J¼5 Hz), 7.52 (d, 2H, J¼7.5 Hz), 7.61 (d, 1H, J¼5 Hz). 13C
J¼7.0 Hz), 6.55 (d, 2H, J¼8.8 Hz), 7.14 (d, 1H, J¼4.1 Hz), 7.48 (d, 2H,
NMR (62.9 MHz, CDCl3)
d 25.4, 26.3, 47.5, 111.7, 120.4, 120.9, 127.3,
J¼8.8 Hz), 7.60 (d, 1H, J¼4.1 Hz), 10.10 (d, 1H, J¼7.0 Hz). 13C NMR
133.9, 140.3, 148.4, 154.8, 190.2. MS (EI) m/z (%): 271 (Mþ, 100), 270
(80), 228 (25), 215 (25), 184 (11). HRMS: m/z (EI) for C16H17NOS
calcd 271.1031; found: 271.1032.
(62.9 MHz, CDCl3) d 25.3, 44.3, 111.6, 120.5, 122.6, 127.0, 127.5, 128.1,
133.8, 136.9, 146.8, 147.6, 191.5.
4.5. General procedure for the Vilsmeier–Haach–Arnold
4.6. General procedure for the synthesis of 5-formyl-50-aryl-
2,20-bithiophenes 5a–f
reaction of ethanones 3a–f to give
propenal 4a–f
b-chloro-b-arylthienyl-
To a solution of Na2S$9H2O (30.5 g, 127 mmol) and DMF
POCl3 (17 ml, 182 mmol) was slowly added to DMF (20 ml,
255 mmol) at 0 ꢀC and the mixture was stirred for 10 min at 0 ꢀC.
After this time a solution of acetophenones 1 (148 mmol) in DMF
(150 ml) was added dropwise with stirring. The reaction mixture
was then heated 3 h at 60 ꢀC. The solution cooled at room tem-
perature was then poured slowly into a sodium acetate aqueous
solution (10%). The pH was adjusted at 4 with sodium acetate. The
solid obtained was filtered and washed with water to afford com-
pounds 4, which were used in the next reaction step without fur-
ther purification.
(200 ml) was added b-chloroacroleine (127 mmol). The mixture
was stirred at 60 ꢀC during 2 h. Chloroacetaldehyde (11.7 g,
127 mmol) was added rapidly and the reaction was stirred during
3 h at 60 ꢀC. K2CO3 (17.6 g, 127 mmol) was dissolved in water (1 l)
and added to the reaction. The mixture was stirred during 10 min at
60 ꢀC, cooled at room temperature and quenched in water. The
mixture was filtered and the crude was washed with water. The
solid was recrystallized from ethanol and purified through column
chromatography on silica with increasing amounts of dichloro-
methane in light petroleum as eluent.
4.5.1.
b
-Chloro-
b
-(5-phenylthiophen-2-yl)-propenal (4a)
4.6.1. 5-Formyl-50-phenyl-2,20-bithiophene (5a)25
Dark brown solid (10%). Mp 105–106 ꢀC. 1H NMR (250 MHz,
Brown solid (22%). Mp 119–120 ꢀC. UV (dioxane): lmax nm
CDCl3)
d
6.59 (d, 1H, J¼6.9 Hz), 7.33 (d, 1H, J¼4.0 Hz), 7.41 (m, 3H),
(3 n 1654 (C]O), 1546, 1516,
, Mꢁ1 cmꢁ1) 382.5 (26,609). IR (Nujol)
7.64 (m, 3H), 10.16 (d, 1H, J¼6.9 Hz). 13C NMR (62.9 MHz, CDCl3)
1300, 1229, 1152, 1100, 1077, 1052, 1027, 998, 955, 906, 813, 798,
d
115.5, 122.2, 123.1, 126.4, 127.5, 132.6, 137.4, 145.2, 151.3, 161.3,
755, 723, 699, 687, 668, 627, 598, 580, 546 cmꢁ1. 1H NMR (300 MHz,
190.3.
DMSO-d6) d
7.38 (m, 1H, 400-H), 7.44 (m, 2H, 300-H and 500-H), 7.55 (d,
1H, J¼3.9 Hz, 4-H), 7.59 (d, 1H, J¼3.9 Hz, 30-H), 7.62 (d, 1H, J¼3.9 Hz,
4.5.2.
b-Chloro-b-(5-(4-methoxyphenyl)thiophen-2-yl)-
3-H), 7.72 (m, 2H, 200-H and 600-H), 8.00 (d, 1H, J¼3.9 Hz, 40-H), 9.88
propenal (4b)
Dark brown solid (25%). Mp 126–127 ꢀC. 1H NMR (250 MHz,
CDCl3)
3.83 (s, 3H), 6.55 (d, 1H, J¼6.9 Hz), 6.96 (d, 2H, J¼8.8 Hz),
(s, 1H, CHO). 13C NMR (75.4 MHz, DMSO-d6)
d 125.2, 125.3, 125.4,
128.2, 128.4, 129.2, 132.7, 134.2, 139.2, 141.2, 145.0, 145.3, 183.8. MS
d
(EI) m/z (%): 270 (Mþ, 45), 241 (6), 213 (12), 197 (16), 185 (16), 129

C. Herbivo et al. / Tetrahedron 65 (2009) 2079–2086
2085
(26), 97 (35), 95 (29), 83 (38), 81 (64), 69 (100). HRMS: m/z (EI) for
C15H10OS2 calcd 270.0173; found: 270.0170.
(7), 257 (17), 236 (26), 155 (26), 137 (23), 127 (34), 111 (48), 98 (42),
97 (91), 83 (100), 69 (91). HRMS: m/z (EI) for C19H17NOS2 calcd
339.0752; found: 339.0752.
4.6.2. 5-Formyl-50-(4-methoxyphenyl)-2,20-bithiophene (5b)
Orange solid (44%). Mp 134–135 ꢀC. UV (dioxane): lmax nm (
3,
4.7. General procedure for the synthesis of aldehydes 5
through Suzuki coupling
M
ꢁ1 cmꢁ1) 394.5 (27,936), inf. 323.5 (4816). IR (Nujol)
n 1665
(C]O), 1606, 1571, 1548, 1522, 1504, 1417, 1309, 1287, 1255, 1226,
1213, 1179, 1113, 1051, 1027, 958, 830, 795, 753, 722, 697, 669, 629,
5-Bromo-50-formyl-2,20-bithiophene 7 (0.25 mmol, 67 mg) was
coupled to boronic acids 6a–d (0.33 mmol) in a mixture of DME
(4 ml), aqueous 2 M Na2CO3 (0.2 ml) and Pd(PPh3)4 (6 mol %) at
80 ꢀC under nitrogen. The reactions were monitored by TLC, which
determined the different reaction times (2–24 h). After cooling, the
mixture was filtered. Ethyl acetate and a saturated solution of NaCl
were added and the phases were separated. The organic phase was
washed with water (3ꢂ10 ml) and with a solution of NaOH (10%)
(1ꢂ10 ml). The organic phase obtained was dried (MgSO4), filtered,
and solvent removed to give a crude mixture, which was submitted
to column chromatography on silica with increasing amounts of
ether in light petroleum as eluent to afford the coupled products 5.
594 cmꢁ1. 1H NMR (300 MHz, DMSO-d6)
d 3.79 (s, 3H, OCH3), 7.00
(d, 2H, J¼9.0 Hz, 300-H and 500-H), 7.45 (d, 1H, J¼3.9 Hz, 4-H), 7.51 (d,
1H, J¼3.9 Hz, 30-H), 7.57 (d, 1H, J¼3.9 Hz, 3-H), 7.63 (d, 2H, J¼9.0 Hz,
200-H and 600-H), 7.98 (d, 1H, J¼3.9 Hz, 40-H), 9.87 (s, 1H, CHO). 13C
NMR (75.4 MHz, DMSO-d6)
d 55.3, 79.2, 114.7, 124.1, 124.8, 125.5,
126.9, 128.3, 133.1, 139.3, 145.2, 145.6, 159.5, 183.8. MS (EI) m/z (%):
301 (Mþ, 100), 288 (33), 239 (30), 197 (60). HRMS: m/z (EI) for
C16H12O2S2 calcd 301.03515; found: 301.03501. Anal. Calcd for
C16H12O2S2: C, 63.97; H, 4.03; S, 21.35. Found: C, 63.64; H, 3.99; N,
11.47; S, 20.57.
4.6.3. 5-Formyl-50-(4-N,N-dimethylaminophenyl)-2,20-
bithiophene (5d)2a,26
4.7.1. 5-Formyl-50-phenyl-2,20-bithiophene (5a)
Yellow solid (78%). Mp 116–117 ꢀC. Other analytical data were
identical to those described above for the same compound.
Orange solid (44%). Mp 228–230 ꢀC (lit26 228–230 ꢀC). UV (di-
oxane): lmax nm (
352.0 (6375). IR (Nujol)
1507, 1326, 1293, 1230, 1171, 1139, 1071, 1051, 1005 cmꢁ1
(300 MHz, DMSO-d6)
3
, Mꢁ1 cmꢁ1) 424.0 (24,538), 322.0 (10,448), inf.
n
1657 (C]O), 1644, 1606, 1553, 1546, 1526,
.
1H NMR
4.7.2. 5-Formyl-50-(4-methoxyphenyl)-2,20-bithiophene (5b)
Yellow solid (53%). Mp 156–157 ꢀC. Other analytical data were
identical to those described above for the same compound.
d
2.94 (s, 6H, (CH3)2N), 6.74 (d, 2H, J¼9.0 Hz,
300-H and 500-H), 7.34 (d, 1H, J¼3.9 Hz, 4-H), 7.47 (d, 1H, J¼3.9 Hz, 30-
H), 7.51 (d, 2H, J¼9.0 Hz, 200-H and 600-H), 7.54 (d, 1H, J¼3.9 Hz, 3-H),
7.97(d, 1H, J¼3.9 Hz, 40-H), 9.84 (s, 1H, CHO). 13C NMR (75.4 MHz,
4.7.3. 5-Formyl-50-(4-ethoxyphenyl)-2,20-bithiophene (5c)
DMSO-d6) d 39.8, 112.3, 120.4, 122.3, 124.2, 126.4, 128.2, 131.5, 139.3,
Yellow solid (80%). Mp 140–141 ꢀC. UV (dioxane): lmax nm (
3,
140.4, 146.0, 146.6, 150.3, 183.5. MS (EI) m/z (%): 313 (Mþ, 39), 236
(29), 155 (22), 129 (22), 127 (35), 111 (60), 98 (47), 97 (99), 95 (78),
83 (100), 81 (84), 71 (80). HRMS: m/z (EI) for C19H19NOS2 calcd
313.0595; found: 313.0582. Anal. Calcd for C17H15NOS2: C, 65.14; H,
4.82; N, 4.47; S, 20.46. Found: C, 65.32; H, 4.72; N, 4.54; S, 20.14.
M
ꢁ1 cmꢁ1) 395.5 (18,965), 323.5 (6220). IR (Nujol)
1604, 1570, 1549, 1522, 1504, 1400, 1310, 1284, 1254, 1224, 1212,
1181, 1118, 1048, 958, 921, 881, 835, 830, 795, 753, 670 cmꢁ1 1H
NMR (250 MHz, DMSO-d6)
n 1672 (C]O),
.
d
1.32 (t, 3H, J¼7.0 Hz), 4.06 (q, 2H,
J¼7.0 Hz), 7.00 (d, 2H, J¼8.8 Hz), 7.45 (d, 1H, J¼3.9 Hz), 7.52 (d, 1H,
J¼3.9 Hz), 7.58 (d, 1H, J¼3.9 Hz), 7.62 (d, 2H, J¼8.8 Hz), 7.99 (d, 1H,
4.6.4. 5-Formyl-50-(4-N,N-diethylaminophenyl)-2,20-
J¼3.9 Hz), 9.86 (s, 1H, CHO). 13C NMR (62.9 MHz, CDCl3)
d 14.5, 63.2,
bithiophene (5e)27
115.1, 123.9, 124.7, 125.3, 126.9, 128.1, 133.0, 139.2, 140.8, 145.3,
145.6, 158.8, 183.7. HRMS: m/z (EI) for C17H14O2S2 calcd 314.0435;
found: 314.0440.
Red solid (13%). Mp 158–160 ꢀC. UV (dioxane): lmax nm (
3,
M
ꢁ1 cmꢁ1) 435.5 (26,966), 325.5 (11,803), inf. 357.5 (6391). IR
(Nujol) 1652 (C]O), 1601, 1555, 1524, 1505, 1269, 1227, 1196, 1156,
1096, 1072, 1049, 1003, 877, 815, 796, 750, 738, 733, 693, 661,
631 cmꢁ1. 1H NMR (300 MHz, DMSO-d6)
n
4.7.4. 5-Formyl-50-(4-N,N-dimethylaminophenyl)-2,20-
bithiophene (5d)
Orange solid (64%). Mp 226–227. Other analytical data were
identical to those described above for the same compound.
d
1.1 (t, 6H, J¼6.9 Hz, CH3–
CH2–N), 3.35 (q, 2H, J¼6.9 Hz, CH3–CH2–N), 6.68 (d, 2H, J¼8.7 Hz,
300-H and 500-H), 7.30 (d, 1H, J¼3.9 Hz, 4-H), 7.47 (m, 3H, 200-H, 600-H
and 30-H), 7.53 (d, 1H, J¼3.9 Hz, 3-H), 7.97 (d, 1H, J¼3.9 Hz, 40-H),
9.85 (s, 1H, CHO). 13C NMR (75.4 MHz, DMSO-d6)
d 12.4, 43.6, 111.5,
Acknowledgements
119.4, 121.9, 124.1, 126.7, 128.3, 131.1, 139.3, 140.3, 146.1, 146.8, 147.5,
183.5. MS (EI) m/z (%): 341 (Mþ, 60), 326 (100), 312 (4), 297 (54),
224.0 (13), 155.1 (12), 127.1 (34). HRMS: m/z (EI) for C19H19NOS2
calcd 341.0908; found: 341.0907. Anal. Calcd for C19H19NOS2: C,
66.83; H, 5.61; N, 4.10; S, 18.78. Found: C, 66.92; H, 5.45; N, 4.19; S,
18.72.
˜
ˆ
Thanks are due to the Fundaçao para a Ciencia e Tecnologia
´
(Portugal) for financial support through Centro de QuımicadUni-
versidade do Minho and through project PTDC/QUI/66251/2006.
The authors are also indebted to bilateral program Acço˜es
Integradas Luso-Francesas/CRUP-CPU, for the bilateral agreements
4.6.5. 5-Formyl-50-(4-pyrrolidinophenyl)-2,20-bithiophene (5f)
Dark brown solid (10%). Mp 228–229 ꢀC. UV (dioxane): lmax nm
´
numbers F-36/06 and F-37/08. C.H. acknowledges the l’Universite
Paul Verlaine–Metz for a travel grant.
(3
, Mꢁ1 cmꢁ1) 433.0 (32,976), 326.5 (12,716), inf. 355.0 (8647). IR
(Nujol)
1184, 1163, 969, 951, 925, 877, 809, 792, 750, 723, 699, 682, 663, 637,
629 cmꢁ1. 1H NMR (300 MHz, DMSO-d6)
1.96 (m, 4H, CH2–CH2–
n 1645 (C]O),1605,1553,1541,1525,1318,1280,1248,1225,
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