Synthesis of π-conjugated thiophenes starting from substituted 3-oxopropanenitriles via Gewald reaction

Article abstract of DOI:10.1016/j.tet.2008.09.032

This paper describes the synthesis of β-aryl and β-heteroaryl substituted 2-aminothiophenes as a novel class of building blocks in oligo- and polythiophenes. The synthesis was carried out in two steps, involving synthesis of substituted 3-oxopropanenitrile intermediates, followed by the Gewald reaction.

Full text of DOI:10.1016/j.tet.2008.09.032

Tetrahedron 64 (2008) 11262–11269
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Synthesis of
p
-conjugated thiophenes starting from substituted
3-oxopropanenitriles via Gewald reaction
a,
b
a
a,
*
´
´
´
Zita Puterova , Anita Andicsova , Daniel Vegh
a Institute of Organic Chemistry, Catalysis and Petrochemistry, Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinske´ho 9, 812 37 Bratislava, Slovakia
b
ˇ
Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinciakova 8, 832 32 Bratislava, Slovakia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 June 2008
Received in revised form 25 August 2008
Accepted 11 September 2008
Available online 20 September 2008
This paper describes the synthesis of b-aryl and b-heteroaryl substituted 2-aminothiophenes as a novel
class of building blocks in oligo- and polythiophenes. The synthesis was carried out in two steps, in-
volving synthesis of substituted 3-oxopropanenitrile intermediates, followed by the Gewald reaction.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
variation of substituents and chain extension by a number of
functionalized thiophene units.6 It is well-established that the
Substituted 3-oxopropanenitriles represent a category of ver-
satile synthetic intermediates. They provide miscellaneneous
building blocks in the synthesis of several types of heterocyclic ring
systems. The synthesis of 4-cyano pyrroles, 1,4-dithiafulvenes, 4-
aryl-5-cyano-2-amino pyrimidines, asymmetric reduction of
substitution and chain length critically influence the electronic
properties of oligothiophenes.5b,6b,7
We have explored the synthesis of model derivatives of
-heteroaryl substituted 2-aminothiophenes utilizing the Gewald
reaction.8 The free amino group allows chain elongation and the
b-aryl or
b
b
-ketonitriles followed by enzymatic transformation to optically
growth of p-conjugated systems upon its modification via de-
pure -hydroxy carboxylic acids, one-step fusion of 1,3-thiazine
b
amination reactions,9 followed by the Gewald reaction. The Gewald
reaction represents a simple technique where in one stepdby
choosing suitable substratesdthe functionalization of the final
oligomer is precisely predicted.
and pyrimidine cycles, regio- and stereoselective synthesis 4-cy-
ano-2,3-dihydrofuran-3-carboxamides or biotransformation of nitriles
to amides using nitrile hydratase starting from substituted 3-oxo-
propanenitriles were investigated recently.1 The unique reactivity
of oxonitriles arises from the closeness of two strongly electron-
withdrawing groups. In general, the reactions of saturated oxoni-
triles reflect the high acidity of protons adjacent to carbonyl and
nitrile group. Moreover, the keto and cyano functions are suitably
situated to facilitate reactions with common bidentate reagents.2
Here we present our approach to synthesis of some 3-aryl and
3-heteroaryl 3-oxopropanenitriles as reactants for the conjugated
structures.
Several new oligo- and polythiophene-forming methods were
employed to construct novel types of semiconducting polymers,
which has become one of the most challenging scientific research
areas. Since the initial discovery of organic compounds showing
metallic conductivity, for which 2000 Nobel prize in chemistry was
awarded,3,4 oligo- and polythiophenes have attracted much atten-
tion as advanced molecules with a practical use in electronic de-
vices.5 The main interest has concentrated on sophisticated
syntheses leading to well defined thiophene structures, allowing
2. Results
The group of four 3-oxopropanenitriles Ar–CO–CH2–CN 4a–d (where
Ar¼phenyl, thiophen-2-yl, 1-methyl-1H-pyrrol-2-yl and ((9H-fluoren-
ylidene)methyl)-1-methyl-1H-pyrrol-2-yl) selected for this study
were prepared in three different ways. Aromatic 3-oxopropaneni-
triles can be accessed via the Claisen reaction of carboxylic acid
esters with carboxylic acid nitriles in the presence of strong bases
(Method A).10 By this procedure derivatives 4a and 4b were
obtained starting from the appropriate methyl esters 1a,b in a re-
action with acetonitrile in dry THF in the presence of sodium
hydride (Scheme 1).11 In a parallel experiment, the same 3-oxo-
propanenitriles 4a and 4b were prepared by the Guareshi/Thorpe
type condensation starting from carbonitrilesdbenzonitrile (2a)
and thiophen-2-carbonitrile (2b) (Method B). In the presence of
bulky base tert-butanol and strong base sodium hydride, the re-
action with acetonitrile in diethylether proceeded to form 3-oxo-3-
phenylpropanenitrile 4a and 3-oxo-3-(thiophen-2-yl)propanenitrile
4b (Scheme 1) in higher yields than by the first method (Table 1).
It was noted earlier that there is a danger of self-condensation of
the starting methyl esters producing 3-oxopropanenitriles by the
* Corresponding author. Tel.: þ421 59325 144; fax: þ421 529 68560.
´
E-mail address: daniel.vegh@stuba.sk (D. Vegh).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.09.032

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Z. Puterova et al. / Tetrahedron 64 (2008) 11262–11269
11263
O
N
Method A
Method B
N
X
X
R
R
X
R
O
O
4a-d
1a,b
2a,b
Method C
H
X
R
3a,b
Scheme 1. Synthesis of substituted 3-oxopropanenitriles.
Table 1
Substituted 3-oxopropanenitriles produced via Scheme 1
Substrate
Method
Conditions
Product
R
X
Yield (%)
1a
1b
2a
2b
3a
3b
Method A
Method A
Method B
Method B
Method C
Method C
CH3CN (1.0 equiv), NaH (2.0 equiv), THF, 67 ꢀC, 2.5 h
4a
4b
4a
4b
4c
4d
H
H
H
H
H
CH]CH
S
CH]CH
S
N–CH3
N–CH3
35
60
70
66
87
65
CH3CN (1.0 equiv), NaH (2.0 equiv), THF, 67 ꢀC, 2.5 h
CH3CN (1.0 equiv), tert-BuOH (0.1 equiv) NaH (2.0 equiv), Et2O, rt, 7 h
CH3CN (1.0 equiv), tert-BuOH (0.1 equiv) NaH (2.0 equiv), Et2O, rt, 7 h
CNCH2CO2H (4.0 equiv), Mg(ClO4)2$2H2O (0.01 equiv), Ac2O, 80 ꢀC, 4 h
CNCH2CO2H (4.0 equiv), Mg(ClO4)2$2H2O (0.01 equiv), Ac2O, 80 ꢀC, 4 h
9-Ethylidene-9H-fluorene
Claisen type condensation.10,12 In agreement with this knowledge,
the requisite products 4a and 4b were obtained in only 35–50%
yields using Method A and in 66–70% yields by Method B (Table 1).
Direct electrophilic acylation performed with mixed carboxylic
acid anhydrides in the presence of acetic anhydride acting as both
catalyst and a solvent, first published in 200413 seems to be the
most straightforward route of producing substituted 3-oxopropa-
nenitriles. Until then, only acylations of nitriles with acylchlorides
in the presence of suitable catalyst have been known to afford the
3-oxopropanenitriles.14 The reaction takes place only with
substituted or unsubsituted indoles and pyrroles, proceeding in
almost quantitative yields, but completely fails to produce aromatic
3-oxopropanenitriles. In our case, as discussed earlier, the only way
to 3-oxo-3-phenylpropanenitrile 4a and 3-oxo-3-(thiophen-2-
yl)propanenitrile 4b seems to be the base catalyzed condensation.
1-Methyl-1H-pyrrole (3a) and 2-((9H-fluoren-9-ylidene)methyl)-
1-methyl-1H-pyrrole (3b) were chosen as suitable reagents for
direct acylation. The reaction with cyanoacetic acid in acetic
anhydride with magnesium perchloratedMg(ClO4)2$2H2O as
a catalyst (Scheme 1) afforded the 3-(1-methyl-1H-pyrrol-2-yl)-3-
oxopropanenitrile 4c and the 3-[5-((9H-fluoren-2-ylidene)methyl)-
1H-pyrrol-2-yl]-3-oxopropanenitrile 4d smoothly in high yields
(Table 1).
One of the substrates used for the synthesis of substituted
3-oxopropanenitriles, derivative 3bd 2-((9H-fluoren-ylidene)methyl)-
1-methyl-1H-pyrrole belongs to the class of (9H-fluoren-9-ylide-
ne)methyl terminated chromophores. Thiophene and oligothio
phene analogues of 3b show interesting optical properties, and it
was clearly demonstrated that the fluorene moiety present in the
molecule effectively influences optical, photoluminescence and
electrochemical properties.15 The synthesis of the compound was
carried out according to the scheme published for the synthesis of
fluorene–thiophene type of structure.16 A condensation between
1-methyl-1H-pyrrole-2-carbaldehyde and fluorene in a heteroge-
neous water/toluene mixture using tetrabutylammonium bromide
(TBAB) as a phase transfer catalyst afforded product 3b in 98% yield
(Scheme 2).
fluorene,TBAB, NaOH
O
toluene: water (50:50)
N
N
r.t., 3h
98%
3b
Scheme 2. Synthesis of fluorene–pyrrole type structure 3b.
with aryl or heteroaryl substituents at the b-position of 5a–e. The
–COCH2– alignment in 3-oxopropanenitriles is suitable for the
Gewald reaction, which encompasses a Knoevenagel condensation
and cyclization reaction sequence.8 By condensation between the
oxo group of starting 3-oxopropanenitriles 4a–c with the active
methylene group of an activated nitrile (derivative of cyanoacetic
acid), an ylidene (a,b-unsaturated nitrile) is created. The addition of
sulfur to the CH2 group of the formed ylidene is followed by
subsequent intramolecular cyclization resulting in the final
2-aminotiophenes 5a–e (Scheme 3).
O
N
Ar
R1
Ar
sulfur
base
solvent
4a−c
N
S
N
S
Sx
N
R1
ylidene-sulfur adduct
base
solvent
R1
R1
Ar
Ar
N
NH2
NH
S
S
H
N
5a−e
Ar = phenyl, thiophene−2yl, 1-methyl-1H-lpyrrol-2-yl,
(9H-fluoren-ylidene)methyl)-1-methyl-1H-pyrrol-2-yl, R1= CO2CH3, CN
Substituted 3-oxopropanenitriles 4a–c are promising CH-active
substrates for the synthesis of new types of 2-aminothiophenes
Scheme 3. Reaction sequence in a synthesis of 2-aminothiophene.

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Z. Puterova et al. / Tetrahedron 64 (2008) 11262–11269
11264
Classical conditions for the Gewald thiophene synthesis involve
and adding the starting substrates (compound 4a and methyl-
cyanoacetate (1.0 equiv amount each) in methanol) at temperature
not exceeding 45 ꢀC. The increase of the yield is significantdthe
product 5a was obtained in 72% yield after 24 h (Table 2).
the reaction of two starting substrates with sulfur and a base, the
latter being required in each reaction step as shown in Scheme 3. To
find the best reaction conditions, a base screen in methanol as
solvent was performed for the reaction starting from 3-oxo-3-
phenylpropanenitrile 4a leading to methyl 2-amino-5-cyano-4-
phenylthiophene-3-carboxylate 5a (Scheme 4). The reaction was
The structure of MPS and the mechanism of its activity have not
yet been clarified. Authors19 in their study had only described the
formation by recyclization of substituted 2-acetylaminothiophene
in low yield from the appropriate substituted hexa-1,3-diene, as
was later summarized in a Russian review.20 Another study21
contains an account of the discovery that morpholine-polysulfide,
in combination with a substituted triazine, provides excellent
vulcanization of rubbers. Herein the composition of MPS is pre-
sumed to contain from two to five sulfur atoms within two
morpholine molecules.
O
N
O
O
O
sulfur, base
methanol
NH2
N
O
S
N
4a
5a
In our opinion, the morpholine shows the best solubility of
sulfur from all the organic bases used in the Gewald reaction (i.e.,
diethylamine, piperidine, pyridine). MPS acts then in two waysdas
a base needed in each reaction step, and also as a sulfurization
agent in the addition step of the reaction (Scheme 3). Indeed, while
applying the MPS, the reaction is not only directed towards
substituted 2-aminothiophenes, but at the same time the recycli-
zation of dimerized six-membered hexa-1,3-diene to the appro-
priate thiophene ring 5a is favoured. During the stepwise Gewald
reaction process, dimerization of the ylidene occurs spontaneously
as a side reaction (Scheme 5). The yields of dimer are highly de-
pendent on the reaction conditions.
Scheme 4. Synthesis of 2-aminothiophene 5a from 3-oxo-3-phenylpropanenitrile 4a
by variation of the Gewald reaction conditions.
Table 2
Base and reaction screen for the Gewald reaction outlined in Scheme 4
Reaction conditions: amount of used base and sulfur,
reaction temperature (ꢀC), reaction
time (h)
Yield of 5a (%)
Et3N (2.0 equiv),a S8 (1.2 equiv),a 60 ꢀC, 72 h
30
50
72
Morpholine (2.2 equiv),b S8 (1.0 equiv),b 45 ꢀC, 5 h
Morpholine (3.0 equiv),c S8 (2.0 equiv),c (20–45) ꢀC, 24 h
a
In our case, its concentration was not significant enough for
further identification. Our declarations on the formation of dimer
as a product of the parallel side reaction are based on the latest
study22 in which the structure of an analogous dimer was claimed.
However, it is clear that by the one-pot and one-step technique
utilizing MPS, the reaction is directed towards the target 2-amino
thiophenes. Employing the same reaction conditions as in our
Base was added to sulfur, compound 4a and methylcyanoacetate suspended in
methanol in one portion.
b
Base was added to sulfur, compound 4a and methylcyanoacetate suspended in
methanol dropwise.
c
Morpholine-polysulfide (MPS) prepared at 150 ꢀC first and then methanolic
solution of starting substrates was added dropwise.
previous work23 we have used MPS in a synthesis of
b-heteroaryl
substituted 2-aminothiophenes 5b–e from the appropriate 3-oxo-
propanenitriles 4b–d in yields ranging from 50 to 62% (Table 3).
carried out in the presence of triethylamine (2.0 equiv),17 and
formed the corresponding product in only 30% after 3 days (Table
2). Using morpholine (2.2 equiv)18 as a base caused an increase in
the yield of 5a to 50% after 5 h reaction time (Table 2). Even if the
yield and the time of the reaction were in that case satisfactory, we
turned to a procedure published by Gudriniece and co-workers in
1983.19 Morpholine-polysulfide (MPS) is formed first in situ by
mixing the sulfur (2.0 equiv) with morpholine (3.0 equiv) at 150 ꢀC
Structures 5a–e represent such novel types of
thiophenes where the elongation of the conjugated system is well-
established with the heteroaromatic substituent in the -position.
p-conjugated
b
Their synthesis by the Gewald reaction using MPS represents
a convenient and easy route to substituted oligothiophenes, and
Addition of sulfur
Condensation
O
O
O
MPS
methanol
20-45 °C
MPS
methanol
20-45 °C
O
N
O
4a
N
N
S
Sx
N
N
S
O
ylidene
ylidene-sulfur adduct
Cyclization
N
O
Dimerization
Re-cyclization
NH2
O
O
NC
CO2CH3
CN
CN
MPS
methanol
20-45 °C
NH2
S
N
5a
dimer
Scheme 5. The study of the Gewald reaction mechanism involving the dimerization and recyclization step using MPS.

´
Z. Puterova et al. / Tetrahedron 64 (2008) 11262–11269
11265
Table 3
underwent substitution by Friedel–Crafts acylation. The acylated
product 7 was formed only in 39% yield. In general, it is a fact
that substituted thiophenes are rather unreactive towards acyl-
chlorides. The reaction succeeded only when propionylchloride
(1.5 equiv) was used as acylating agent and tin tetrachloride
Products of the Gewald reaction 5b–e starting from 3-oxopropanenitriles 4b–d
Substituted
3-oxopropanenitrile
Reaction
time (h)
Product
Yield (%)
(3.0 equiv) as
a
Lewis agent24 in boiling 1,2-dichlorethane
S
O
(Scheme 6). The propan-1-one side chain allows formation of the
2-aminothiophene ring in the final step. Performing the Gewald
type cyclization of compound 7 with cyanoacetic acid in the
presence of MPS under the same conditions as in case of
compounds 5a–e resulted to final structure 8 in which three
thiophene rings are combined. The product was achieved in an
acceptable 56% yield (Scheme 6).
The target derivatives 5a–e, 6–8 are highly stable, soluble in
common solvents such as methanol, ethanol, dichloromethane,
ethylacetate, and particularly in chloroform, hexane, toluene. Our
proposal of their preparation by the Gewald reaction represents
a comfortable route with the possibility of the connection of an-
other thiophene ring by repeating the three-step process as shown
on Scheme 6. By this procedure, the conjugated system can be
easily prolonged to oligothiophene type structure (in general the
oligothiophene is a structure with six thiophene rings fused to-
gether). The free amino group allows its change to halogend bro-
mine or iodine. Such halogenated derivatives undergo coupling
reactions. With the right choice of starting substrates the func-
tionalization of final structures can be achieved (i.e., aryl or
heteroaryl substitution, prediction of hydrophilic or hydrophobic
character of final structures)dFigure 1.
S
N
O
24
18
62a
O
N
N
N
S
4b
NH2
5b
S
N
N
S
58b
N
O
4b
S
NH2
5c
O
N
N
O
18
52a
O
S
NH2
4c
5d
20
50a
O
N
N
N
O
O
4d
N
S
NH2
5e
3. Conclusion
a
With methylcyanoacetate using MPS.
With malonodinitrile using MPS.
b
In summary, we have disclosed the convenient synthesis of
b-aryl and b-heteroaryl substituted 2-aminothiophenes as useful
other oligomers in which the basic properties of different compo-
nents are fused together (i.e., stability of thiophenedderivatives
5b,c, optical and electrochemical properties of thiophene and
pyrroled5d, fluorescent properties of fluorened5e) providing
good candidates for applications.
The creation of longer systems containing more than two
thiophene units is exemplified by the derivative 5b. The first
stepddeaminationdwas performed under classical conditions
with sodium nitrite and sulfuric acid.9a After the evolution of
nitrogen from the intermediate diazonium salt, the deaminated
tools in development of thiophene oligomers and polymers for
molecular devices in optoelectronics (i.e., organic switchers,
Langmuir/Blodgett films, light emitting diodes, photovoltaic cells,
etc.). Our main interest was concerned with the utilization and
development of the Gewald reaction and its synthetic potential in
material chemistry and synthesis. The mechanism of the Gewald
type cyclization involving a parallel side reaction is discussed.
Starting from substituted 3-oxopropanenitriles, novel variously
substituted 2-aminothiophenes have been prepared showing
interesting optical and electrochemical properties. Work to that
end is in progress.
product
6
was obtained in 67% yield. The free
a
-position
O
O
O
O
1) NaNO2, H2SO4
O
SnCl4
0-5 °C, methanol
S
S
NH2
5b
Cl
2) -N2, 40 °C, 1h
1,2-dichloroethane,
83 °C, 24 h
S
S
N
N
39%
6
67%
O
O
O
O
O
O
MPS
methanol,
20-45 °C, 24h
O
N
S
NH2
S
O
S
S
O
S
56%
N
N
7
8
Scheme 6. Elongation of conjugated thiophene system in a three-step procedure: deamination reaction/Friedel–Crafts acylation/Gewald reaction.

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Z. Puterova et al. / Tetrahedron 64 (2008) 11262–11269
11266
C19H15N (257.33): C, 88.68; H, 5.88; N, 5.44. Found: C, 88.80; H,
6.11; N, 5.37. Mass (ESI) m/z (%) 258.12 (MþH), 280.12 (MþNa).
1. NH2 group - allows elongation of the system
upon various types of deaminations
O
O
4.3. General procedures for the synthesis of substituted
3-oxopropanenitriles
2. Functionalization -prediction of the hydrophilic or
hydorphobic character by right choice of substrates
S
NH2
S
3. Aryl or heteroaryl substitution - variable by
chosing the substrates
N
Method A. The appropriate methyl ester (methyl benzoate 1a:
7.0 mmol, 0.95 g; methyl thiophene-2-carboxylate 1b: 7.0 mmol,
1.0 g) and NaH (14.0 mmol, 0.35 g) in boiling tetrahydrofuran
(5.0 mL) were treated with solution of acetonitrile (7.0 mmol,
0.29 g, 0.4 mL) in tetrahydrofuran (1.0 mL) dropwise. The mixture
was heated to reflux for 2.5 h and after cooling down to room
temperature, it was diluted with diethylether (15.0 mL) and left to
stand at room temperature for 48 h. The precipitated sodium salt
was filtered and washed with diethylether. The dry compound was
dissolved in water (5.0 mL) and acidified with HCl (1:1) to pH 2. The
product was extracted with a 3:1 mixture of diethylether/benzene
(3ꢂ10 mL). The collected extracts were washed with a saturated
solution of NaHCO3, dried with Na2SO4 and evaporated. The prod-
uct was crystallized from toluene.
Figure 1. Possible variations on 5a–e type structures prepared by the Gewald reaction.
4. Experimental
4.1. General
All chemicals were purchased from Sigma–Aldrich or Merck
and used without further purification. All solvents were of HPLC
grade and used as supplied. The melting points were measured
on a Griffin Melting Point apparatus. Elemental analyses were
determined using a Carlo Erba 1108-Elemental Analyser. The IR
spectra of compounds 3b, 4c and 4d were recorded on a Perkin–
Elmer System 1600 FTIR instrument using KBr pellets. IR spectra
of the compounds 5a–e, 6–8 were measured using diamond
smart orbit ATR on Nicolet 5700 FTIR instrument. All mass
spectra were recorded on a Buker Esquire LC-00050 electrospray
ionisation mass spectrometer using CH3CN or CH3OH as a ma-
trix. Routine 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra
were recorded on a VARIAN VXR 300 instrument at 25 ꢀC. The
measurements were done using protiated solventsdCDCl3 and
DMSO-d6, with TMS as an internal standard reference. Two
dimensional spectra gs-H,H-COSY, 1D-gs-NOESY, gs-HSQC and
gs-HMBC were measured using standard software programs
provided by VARIAN. Coupling constans (J) are quoted to the
Method B. To a stirred suspension of NaH (20.0 mmol, 0.5 g) in
diethylether (10.0 mL) at reflux
a solution of tert-butanol
(1.0 mmol, 80 mg, 0.1 mL) in diethylether (0.5 mL) was added first,
then the appropriate nitrile (benzonitrile 2a: 10.0 mmol, 1.0 g;
thiophene-2-carbonitrile 2b: 10.0 mmol, 1.1 g) and finally acetoni-
trile (10.0 mmol, 0.4 g, 0.5 mL). Reflux was continued for 7 h. After
cooling down to room temperature it was allowed to stand at 4 ꢀC
overnight. The precipitated sodium salt was filtered off and washed
with diethylether. The dry sodium salt was dissolved in ethanol
(10.0 mL) and treated with hydrochloric acid (3.2 mL) and kept at
room temperature for 30 min while stirring. After diluting with
water (5.0 mL), the solution was extracted with diethylether
(3ꢂ10 mL). Extracts were dried with Na2SO4 and evaporated. The
crude product was crystallized from diethylether.
nearest 0.1 Hz and chemical shifts (d-scale) are quoted in parts
per million (ppm) and following abbreviations are used:
s¼singlet, d¼doublet, t¼triplet, q¼quartet, m¼multiplet,
br¼broad. Column chromatography was performed using Silica
4.3.1. 3-Oxo-3-phenylpropanenitrile (4a)
Yield: 35% (355 mg)dMethod A, 70% (711 mg)dMethod B, white
crystals; mp 80–81 ꢀC. Analytical data corresponds to those pub-
lished for 3-oxo-3-phenylpropanenitrile, C9H7NO (145.16), see Refs.
10 and 11.
gel Kiesegel 60 with particle size 40–63 mm (230–400 mesh,
Merck) by preparing the slurry with the eluent mixture and
packing into chromatography column. The collected fraction
samples were analyzed by TLC. Compounds are numbered
according to Schemes 1–6.
4.3.2. 3-Oxo-3-(thiophen-2-yl)propanenitrile (4b)
Yield: 60% (635 mg)dMethod A, 66% (700 mg)dMethod B, yello-
wish crystals; mp 112–115 ꢀC. Analytical data corresponds to those
published for 3-oxo-3-(thiophen-2-yl)propanenitrile, C7H5NOS
(151.19), see Ref. 25.
4.2. General procedure for the synthesis of fluorene–pyrrole
type structure
Method C. To a solution of cyanoacetic acid (16.0 mmol, 1.4 g,
1.3 mL) in acetic anhydride (3.0 mL), the appropriate pyrrole was
added (1-methyl-1H-pyrrole 3a: 4.0 mmol, 0.32 g; 2-((9H-fluoren-
9-ylidene)methyl)-1-methyl-1H-pyrrole 3b: 4.0 mmol, 1.0 g) at
80 ꢀC under an inert argon atmosphere. The solution was heated at
80 ꢀC for a further 4 h. After cooling down to room temperature, the
reaction mixture was poured onto ice water (5.0 mL) and extracted
into dichloromethane (3ꢂ10 mL). The collected extracts were dried
with Na2SO4 and evaporated to dryness. Crude products were
crystallized from dichloromethane.
4.2.1. 2-((9H-Fluoren-9-ylidene)methyl)-1-methyl-1H-pyrrole (3b)
Fluorene (6.0 mmol, 1.0 g) and 1-methyl-1H-pyrrole-2-carbal-
dehyde (6.0 mmol, 0.66 g) were dissolved in toluene (8.5 mL).
Then, TBAB (1.0 mmol, 0.35 g) in 10.0 mL of NaOH solution (6.0 g
of NaOH in water) was added. The mixture was stirred vigor-
ously at room temperature for 3 h. After the reaction was
complete, the water and toluene layers were separated. The
organic phase was washed with diluted HCl (1:1, 5.0 mL), water
(5.0 mL) and saturated brine (5.0 mL), then dried with Na2SO4.
After evaporation of the solvent, the crude product was dried
and crystallized from n-heptane. Yield: 98% (3.0 g) of yellowish
4.3.3. 3-(1-Methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile (4c)
Yield: 87% (516 mg)dMethod C, white solid; mp 109–110 ꢀC. IR
crystals; mp 80–82 ꢀC. IR (KBr)
Hethylidene), 3024, 3001, 2942, 1650 (C]Cethylidene), 1611, 1592,
1586, 1510, 1479, 1405, 1376, 830, 770, 688 cmꢁ1 1H NMR
(300 MHz, CDCl3) 3.71 (s, 3H), 6.32–6.30 (m, 1H), 6.79–6.83
n 3137 (N–CH3), 3059 (]C–
(KBr)
1396, 1384, 1294, 1250, 1212, 1105, 1074, 923, 907, 880, 762 cmꢁ1. 1H
NMR (300 MHz, CDCl3) 3.85 (s, 3H), 4.42 (s, 2H), 6.16–6.17 (m, 1H),
7.12–7.13 (m,1H), 7.24–7.25 (m,1H); 13C NMR (75 MHz, CDCl3)
29.3,
n 3141 (N–CH3), 2259 (CN),1639 (C]O),1530,1467,1438,1410,
.
d
d
(m, 2H), 7.18–7.24 (m, 1H), 7.30–7.39 (m, 4H), 7.73–7.79 (m, 3H),
d
8.23 (d, J¼7.8 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d
4.4, 108.4,
37.0, 108.5, 116.1, 121.3, 128.0, 133.3, 178.2. Anal. Calcd for C8H8N2O
(148.16): C, 64.85; H, 5.44; N,18.91. Found: C, 65.10; H, 5.70; N,19.03.
Mass (ESI) m/z (%) 149.0 (MþH), 171.0 (MþNa).
112.8, 115.7, 119.5, 119.6, 119.8, 123.7, 123.8, 124.4, 126.7, 127.6,
128.2, 129.0, 134.4, 136.6, 138.6, 139.7, 140.6. Anal. Calcd for

´
Z. Puterova et al. / Tetrahedron 64 (2008) 11262–11269
11267
4.3.4. 2-((9H-Fluoren-9-ylidene)methyl)-1-methyl-1H-pyrrole (4d)
Yield: 65% (843 mg)dMethod C, yellow solid; mp 133–135 ꢀC. IR
(C]Oester), 1618, 1526, 1430, 1232 (C–Oester), 1020, 970, 888, 750,
540 cmꢁ1. 1H NMR (300 MHz, DMSO-d6)
3.77 (s, 3H, CO2CH3), 5.24
d
(KBr)
1688 (C]O), 1654 (C]Cethylidene), 1605, 1560, 1512, 1455, 1400,
1372, 810, 714. 1H NMR (300 MHz, CDCl3)
3.94 (s, 3H), 3.52 (s, 2H),
n
3119 (N–CH3), 3061 (]C–Hethylidene), 3040, 3012, 2246 (CN),
(br s, 2H, NH2), 7.34 (d, J¼7.2 Hz, 1H), 7.43 (t, J¼7.8 Hz, 1H), 7.87 (t,
J¼7.8 Hz, 2H), 7.99 (d, J¼7.2 Hz, 1H); 13C NMR (75 MHz, DMSO-d6)
d
d 25.4 (CO2CH3), 128.5, 129.7, 140.1, 141.8 (C-3), 152.2 (C-4), 159.2
6.58 (d, J¼4.4 Hz, 1H), 7.07 (d, J¼4.4 Hz, 1H), 7.12 (t, J¼7.7 Hz, 1H),
7.19 (s, 1H), 7.29–7.42 (m, 4H), 7.56 (d, J¼7.8 Hz, 1H), 7.68 (d,
J¼7.2 Hz, 1H), 7.74 (d, J¼7.2 Hz, 1H); 13C NMR (75 MHz, CDCl3)
(CO2CH3), 168.6 (C-2). Anal. Calcd for C13H10N2O2S (258.30): C,
60.45; H, 3.90; N, 10.85; S, 12.41. Found: C, 60.80; H, 4.00; N, 11.03;
S, 12.54. Mass (ESI) m/z (%) 259.1 (MþH), 281.0 (MþNa).
d
29.5, 34.4, 112.2, 112.7, 114.5, 119.8, 120.0, 120.5, 120.6, 124.2, 127.2,
127.3, 128.7, 129.3, 129.6, 135.8, 138.4, 139.5, 139.6, 141.1, 141.5, 176.1.
Anal. Calcd for C22H16N2O (324.38): C, 81.46; H, 4.97; N, 8.64.
Found: C, 81.70; H, 5.02; N, 8.43. Mass (ESI) m/z (%) 325.13 (MþH),
347.13 (MþNa).
4.4.2. Methyl 2-amino-5-cyano-4-(thiophene-2-yl)thiophene-
3-carboxylate (5b)
Yield: 62% (660 mg)dMethod C, light orange solid; mp 128–
132 ꢀC. IR (diamond smart orbit ATR)
n
3270 (NH2), 2972, 2928,
2264 (CN), 1693 (C]Oester), 1541, 1450, 1429, 1217 (C–Oester),
1105, 1031, 975, 840, 719, 587 cmꢁ1 1H NMR (300 MHz, DMSO-
4.4. Gewald reaction: synthesis of
substituted 2-aminothiophenes
b-aryl and
b
-heteroaryl
.
d6)
d
3.87 (s, 3H, CO2CH3), 4.41 (br s, 2H, NH2), 7.10 (d, J¼5.8 Hz,
1H, H-30), 7.37 (dd, J¼5.8 Hz, 1H, H-40), 7.64 (d, J¼5.8 Hz, 1H, H-
General procedure A. To
a
mixture of 3-oxo-3-phenyl-
50); 13C NMR (75 MHz, DMSO-d6)
d 16.8 (CO2CH3), 111.0 (C-5),
propanenitrile 4a (4.0 mmol, 581 mg), sulfur (4.8 mmol, 154 mg)
and methylcyanoacetate (4.0 mmol, 396 mg, 350 mL) in methanol
(15.0 mL), triethylamine (14.0 mmol, 1.42 g, 2.0 mL) was added.
After stirring at 60 ꢀC for 3 days, the reaction mixture was evapo-
rated and water was added (10 mL). The formed crystals were fil-
tered off and filtrate extracted with dichloromethane (2ꢂ20 mL).
The combined organic layers were washed with brine, dried with
Na2SO4 and evaporated. The residue combined with the filtered
crystal product was purified by column chromatography on silica
gel (absorbed with 1% triethylamine) eluting with a mixture of
dichloromethane/methanol (98:2) followed by crystallization from
a mixture of methanol/1,4-dioxane (50:50).
114.1 (CN), 126.1 (C-50), 127.3 (C-30), 129.1 (C-40), 136.2 (C-20),
140.3 (C-3), 151.8 (C-4), 163.4 (CO2CH3), 172.3 (C-2). Anal. Calcd
for C11H8N2O2S (264.32): C, 49.98; H, 3.05; N, 10.60; S, 24.26.
Found: C, 49.70; H, 3.18; N, 10.75; S, 24.42. Mass (ESI) m/z (%)
265.0 (MþH), 287.0 (MþNa).
4.4.3. 5-Amino-3-(thiophen-2-yl)thiophene-2,4-dicarbonitrile (5c)
Yield: 58% (613 mg)dMethod C, orange solid; mp 138–142 ꢀC. IR
(diamond smart orbit ATR)
n 3319 (NH2), 2972, 2257 (CN), 2230
(CN), 1520, 1448, 1046, 962, 792, 565 cmꢁ1 1H NMR (300 MHz,
.
DMSO-d6)
d
4.21 (br s, 2H, NH2), 7.08 (d, J¼6.2 Hz, 1H, H-50), 7.44
(dd, 1H, J¼6.2 Hz, H-40), 7.62 (d, 1H, J¼6.2 Hz, H-30); 13C NMR
General procedure B. A mixture of 3-oxo-3-phenylpropanenitrile
4a (4.0 mmol, 581 mg), sulfur (4.8 mmol, 154 mg) and methyl-
cyanoacetate (4.0 mmol, 396 mg, 350 mL) in methanol (15.0 mL)
was treated dropwise with morpholine (8.8 mmol, 766 mg, 0.8 mL)
at 45 ꢀC. After being stirred for 5 h at 45 ꢀC, the mixture was diluted
with water (20 mL) and extracted with dichloromethane
(3ꢂ20 mL). Collected extracts were washed with water (20 mL) and
with brine (20 mL) and dried with Na2SO4. The solvent was re-
moved in vacuo. The crude product was purified by column chro-
matography on silica gel (absorbed with 1% triethylamine) eluting
with a mixture of dichloromethane/methanol (98:2) followed by
crystallization from mixture methanol/1,4-dioxane (50:50).
General procedure C. A mixture of morpholine (12.0 mmol, 1.0 g,
1.0 mL) and sulfur (8.0 mmol, 256 mg) was stirred at 110 ꢀC for 3 h
under an inert argon atmosphere. The formed morpholine-poly-
sulfide (dark reddish mass) was cooled down to room temperature
and solution of starting compounds (4.0 mmol of starting 3-oxo-
propanenitriles 4a–d, 4.0 mmol of cyanoacetic acid deriva-
tivedmethylcyanoacetate or malononitrile) in methanol (40 mL)
were added dropwise over 30 min at a temperature not exceeding
45 ꢀC. After addition was complete, the reaction mixture was stir-
red for a further 24 h at room temperature. The reaction mixture
was diluted with water (40 mL). The formed crystals were filtered
off and the filtrate extracted with dichloromethane (2ꢂ20 mL). The
combined organic layers were washed with brine and dried with
Na2SO4 and evaporated. The residue combined with the filtered
crystalline product was purified by column chromatography on
silica gel (absorbed with 1% triethylamine) eluting with a mixture
of dichloromethane/methanol (98:2) followed by crystallization
from a mixture of methanol/1,4-dioxane (50:50).
(75 MHz, DMSO-d6) d 110.9 (C-2), 111.4 (C-4), 113.6 (CN), 115.1 (CN),
126.1 (C-50), 127.2 (C-30), 127.8 (C-40), 140.9 (C-20), 157.1 (C-3), 165.3
(C-5). Anal. Calcd for C10H5N3S2 (231.30): C, 51.93; H, 2.18; N, 18.17;
S, 27.73. Found: C, 52.10; H, 2.24; N, 18.22; S, 27.83. Mass (ESI) m/z
(%) 232.0 (MþH), 254.0 (MþNa).
4.4.4. Methyl 2-amino-5-cyano-4-(1-methyl-1H-pyrrol-2-yl)-
thiophene-3-carboxylate (5d)
Yield: 52% (543 mg)dMethod C, orange solid; mp 138–142 ꢀC. IR
(diamond smart orbit ATR)
(CN), 1651 (C]Oester), 1515, 1435, 1291, 1239 (C–Oester), 1108, 1024,
843, 747, 549 cmꢁ1. 1H NMR (300 MHz, DMSO-d6)
3.10 (s, 3H, N-
n 3291 (NH2), 3122 (N–CH3), 2952, 2237
d
CH3), 3.86 (s, 3H, CO2CH3), 4.35 (br s, 2H, NH2), 6.16 (d, J¼6.6 Hz, 1H,
H-50), 7.12 (d, J¼6.6 Hz, 1H, H-30), 7.2 (dd, J¼6.6 Hz, 1H, H-40); 13C
NMR (75 MHz, DMSO-d6)
d
22.4 (CO2CH3), 30.1 (N–CH3),107.4 (C-5),
0
0
0
´
113.6 (CN), 115.5 (C-4 ), 116.6 (C-3 ), 118.9 (C-5), 130.5 (C-2 ), 144.6
(C-3), 158.2 (C-4), 160.0 (CO2CH3), 174.4 (C-2). Anal. Calcd for
C12H11N3O2S (261.30): C, 55.16; H, 4.24; N, 16.08; S, 12.27. Found: C,
55.28; H, 4.36; N, 16.19; S, 12.19. Mass (ESI) m/z (%) 262.1 (MþH),
284.0 (MþNa).
4.4.5. Methyl 2-amino-5-cyano-4-(5-(9H-fluoren-9-ylidene)-
methylpyrrol-2-yl)thiophen-3-carboxylate (5e)
Yield: 52% (875 mg)dMethod C, red solid; mp 194–198 ꢀC. IR
(diamond smart orbit ATR) n 3332 (NH2), 3233 (N–CH3), 2183 (CN),
2960 (]C–Hethylidene), 1724 (C]Oester), 1614 (C]Cethylidene), 1541,
1427, 1261, 1231 (C–Oester), 1108, 1022, 887, 775, 729, 619 cmꢁ1. 1H
NMR (300 MHz, DMSO-d6)
d 3.11 (s, 3H, N–CH3), 3.91 (s, 3H,
CO2CH3), 4.12 (br s, 2H, NH2), 5.90 (d, J¼6.8 Hz, 1H, H-30), 6.20 (d,
J¼6.8 Hz, 1H, H-40), 6.92 (s, 1H), 7.65 (d, J¼8.0 Hz, 2H, ArH fluorene),
7.50 (t, J¼8.2 Hz, 2H, ArH fluorene), 7.35 (t, J¼8.2 Hz, 2H, ArH flu-
orene), 7.20 (d, J¼8.0 Hz, 2H, ArH fluorene); 13C NMR (75 MHz,
4.4.1. Methyl 2-amino-5-cyano-4-phenylthiophene-
3-carboxylate (5a)
Yield: 30% (310 mg)dMethod A, 50% (520 mg)dMethod B, 72%
(744 mg)dMethod C, yellow solid; mp 109–111 ꢀC. IR (diamond
DMSO-d6)
d 20.6 (CO2CH3), 28.4 (N–CH3),109.9 (C-5),111.9,112.4 (C-
40, C-30), 114.8 (CN), 116.6 (C- ), 131.4 (C-50), 141.8 (C-3), 126.3, 127.0,
a
128.8, 138.0, 140.3, 142.2 (13ꢂC fluorene), 144.6 (C-20), 156.7 (C-4),
162.4 (CO2CH3),172.6 (C-2). Anal. Calcd for C26H19N3O2S (437.5): C,
smart orbit ATR)
n 3276 (NH2), 2988, 2860, 2234 (CN), 1676

´
Z. Puterova et al. / Tetrahedron 64 (2008) 11262–11269
11268
71.38; H, 4.38; N, 9.60; S, 7.33. Found: C, 71.54; H, 4.46; N, 9.47; S,
7.25. Mass (ESI) m/z (%) 437.2 (MþH), 460.0 (MþNa).
4.5.3. Gewald reaction: synthesis of methyl 2-amino-5-methyl-4-
[30-methoxycarbonyl-50-cyano-40-(thiophen-200-yl)thiophen]-3-
carboxylate (8)
4.5. Synthesis of trithiophene system utilizing a three-step
procedure: deamination reaction/Friedel–Crafts acylation/
Gewald cyclization
Morpholine-polysulfide was prepared in situ by mixing sulfur
(4.5 mmol,150 mg) with morpholine (6.0 mmol, 300 mg, 0.3 mL) at
110 ꢀC for 3 h. A solution of methyl-5-cyano-2-propionyl-4-(thio-
phen-2-yl)thiophen-3-carboxylate (7, 1.5 mmol, 450 mg) and
methylcyanoacetate (3.0 mmol, 300 mg, 0.1 mL) in methanol
(6.0 mL) was added dropwise to the in situ prepared MPS at room
temperature with stirring. The reaction mixture was stirred at room
temperature for 24 h, and then poured into water (15 mL). The
aqueous solution was extracted with ethylacetate (3ꢂ15 mL), then
the combined organic layers washed with water and dried with
Na2SO4. The crude product was purified by column chromatogra-
phy on silica gel (absorbed with 1% triethylamine) eluting with
a mixture of dichloromethane/methanol (90:10) followed by crys-
tallization from mixture methanol/1,4-dioxane (50:50) to yield
a red powder. Yield: 56% (351 mg)dMethod C, orange solid; mp
4.5.1. Deamination reaction: synthesis of methyl 5-cyano-4-
(thiophen-2-yl)thiophene-3-carboxylate (6)
To an ice cold solution of methyl 2-amino-5-cyano-4-(thio-
phene-2-yl)thiophene-3-carboxylate (4b, 10.0 mmol, 2.6 g) in
methanol (40 mL), concentrated sulfuric acid (2.0 mL) was added
with vigorous stirring. The mixture was cooled down to ꢁ5 ꢀC and
solution of sodium nitrite (12.0 mmol, 1.2 g) in 6 mL of water was
added dropwise via a syringe whose tip is kept below of the re-
action solution, with vigorous stirring keeping the temperature
below ꢁ2 ꢀC. The dark red solution was stirred at ꢁ2 ꢀC for
30 min, then gently warmed to 40 ꢀC and heated at 40–50 ꢀC 1 h.
After the evolution of nitrogen had ceased, the reaction mixture
was cooled to room temperature, neutralized with saturated
NaHCO3 (intensively foaming!) and then extracted with chloroform
(3ꢂ30 mL). The combined chloroform extracts were washed with
5% aqueous NaHCO3, saturated NaCl, water and dried with Na2SO4
and evaporated to yield dark red-brown solid. The crude product
was chromatographed over SiGel using mixture of dichloro-
methane/methanol (97:3) to give deaminated bithiophene as
shiny yellow solid. Yield: 67% (1.7 g); mp 128–132 ꢀC. IR (diamond
138–142 ꢀC. IR (diamond smart orbit ATR)
n 3312 (NH2), 2927, 2227
(CN), 1650 (C]Oester), 1502, 1466, 1434, 1271 (C–Oester), 1234
(C–Oester), 1190, 1105, 1065, 1024, 976, 841, 780, 588 cmꢁ1. 1H NMR
(300 MHz, DMSO-d6)
d 2.12 (s, 3H, CH3), 3.68 (s, 3H, CO2CH3), 3.74
(s, 3H, CO2CH3), 7.16 (d, J¼6.0 Hz, 1H, H-300), 7.69 (dd, J¼6.0 Hz, 1H,
H-400), 7.76 (d, J¼6.0 Hz, 1H,H-500), 7.88 (br s, 2H, NH2); 13C NMR
(75 MHz, DMSO-d6)
d
26.9 (CH3), 44.2 (2ꢂCO2CH3), 110.1 (C-50),
113.6 (CN), 126.1 (C-500), 127.7 (C-300), 129.3 (C-400), 136.2 (C-5), 138.8
(C-200),140.6 (C-30),142.1 (C-3),144.1 (C-4),154.2 (C-40), 156.7 (C-20),
162.1 (2ꢂCO2CH3), 165.5 (C-2). Anal. Calcd for C18H14N2O4S3
(418.51): C, 51.66; H, 3.37; N, 6.69; S, 22.99. Found: C, 51.85; H, 3.64;
N, 6.90; S, 23.12. Mass (ESI) m/z (%) 419.01 (MþH), 441.02 (MþNa).
smart orbit ATR)
n 2221 (CN), 1650 (C]Oester), 1525, 1277, 1215
(C–Oester), 1006, 927, 860, 756, 623 cmꢁ1 1H NMR (300 MHz,
.
CDCl3)
d
3.82 (s, 3H, CO2CH3), 6.96 (d, J¼6.0 Hz, 1H, H-30), 7.17 (dd,
J¼6.0 Hz, 1H, H-40), 7.41 (d, J¼6.0 Hz, 1H, H-50), 8.2 (s, 1H, H-2); 13C
NMR (75 MHz, CDCl3)
d 49.8 (CO2CH3), 108.2 (C-5), 112.0 (CN),
Acknowledgements
125.3 (C-50), 127.6 (C-30), 128.0 (C-40), 130.1 (C-3), 139.3 (C-20),
142.9 (C-2), 153.4 (C-4), 162.1 (CO2CH3). Anal. Calcd for
C11H7NO2S2 (249.3): C, 52.99; H, 2.83; N, 5.62; S, 25.72. Found: C,
53.10; H, 2.92; N, 5.73; S, 25.88. Mass (ESI) m/z (%) 250.0 (MþH),
270.0 (MþNa).
This work was supported by the Ministry of Education of the
Slovak RepublicdVEGA Grant No. 1/4453/07. Z.P. is indebted to Dr.
´
´
Peter Zalupsky for correcting the language of the manuscript. The
´
authors are grateful to Mrs. Silvia Markusova for IR spectra
measurements.
4.5.2. Friedel–Crafts acylation: synthesis of methyl-5-cyano-2-
propionyl-4-(thiophen-2-yl)thiophen-3-carboxylate (7)
References and notes
To methyl 5-cyano-4-(thiophen-2-yl)thiophene-3-carboxylate
(6, 4.5 mmol, 1.1 g) dissolved in dry 1,2-dichloroethane (15 mL),
propionylchloride (6.75 mmol, 600 mg, 0.6 mL) was added and the
mixture was stirred for 30 min under an inert argon atmosphere.
Tin tetrachloride (13.5 mmol, 3.3 g, 1.5 mL) was added dropwise via
a syringe with vigorous stirring at room temperature. After addition
had completed, the reaction mixture was stirred at 83 ꢀC for 24 h
and then cooled down to room temperature. The mixture was
carefully poured into water (45 mL) and neutralized with a satu-
rated solution of Na2CO3 (consumption of solution 15–20 mL, in-
tensively foams during neutralization!). The mixture was stirred at
room temperature for 1 h and then extracted into chloroform
(3ꢂ30 mL), and washed with water. The combined organic layers
were dried with Na2SO4 and evaporated to yield a yellow powder.
Yield: 39% (536 mg); mp 112–114 ꢀC. IR (diamond smart orbit ATR)
1. For recent syntheses of various derivatives from substituted 3-oxopropaneni-
triles, see: (a) Magnus, N. A.; Staszak, M. A.; Udodong, U. E.; Wepsiec, J. P. Org.
Process Res. Dev. 2006, 10, 899; (b) Alias, S.; Andreu, R.; Blesa, M. J.; Franco, S.;
Garin, J.; Gragera, A.; Orduna, J.; Romero, P.; Villacampa, B.; Allain, J. J. Org.
Chem. 2007, 72, 6440; (c) Hughes, T. V.; Emanuel, S. L.; Beck, A. K.; Wetter, S. K.;
Connolly, P. J.; Karnachi, P.; Reuman, M.; Seraj, S.; Fuentes-Pesquera, A. R.;
Gruninger, R. H.; Middleton, S. A.; Lin, R.; Davis, J. M.; Moffat, D. F. C. Bioorg.
Med. Chem. 2007, 17, 3266; (d) Zhu, D.; Ankati, H.; Mukherjee, Ch.; Yang, Y.;
Biehl, E. R.; Hua, L. Org. Lett. 2007, 9, 2561; (e) Ryabukhin, S. V.; Plaskon, A. S.;
Ostapchuk, E. N.; Volochnyuk, D. M.; Shishkin, O. V.; Shivanyuk, A. N.; Tol-
machev, A. A. Org. Lett. 2007, 9, 4215; (f) Burgaz, E. V.; Yilmaz, M.; Pekel, A. T.;
¨
ˇ
ˇ ´
´
Oktemer, A. Tetrahedron 2007, 63, 7229; (g) Kubac, D.; Kaplan, O.; Elisakova, V.;
Pa´tek, M.; Vojtech, V.; Sla´mova´, K.; To´thova´, A.; Lemaire, M.; Gallienne, E.; Lutz-
´
ˇ
Wahl, S.; Fischer, L.; Kuzma, M.; Pelantova, H.; van Pelt, S.; Bolte, J.; Kren, V.;
Martinkova´, L. J. Mol. Catal. B: Enzym. 2008, 50, 107.
2. Fleming, F. F.; Iyer, P. S. Synthesis 2006, 893.
3. Shirakawa, H.; Louis, E. J.; MacDiarnid, A. G.; Chiang, C. K.; Heeger, A. J. J. Chem.
Soc., Chem. Commun. 1977, 578.
4. (a) Shirakawa, H. Synth. Met. 2002, 125, 3; (b) MacDiarmid, A. G. Synth. Met.
2002, 125, 11; (c) Heeger, A. J. Synth. Met. 2002, 125, 23.
n
2260, 1707 (C]Oketone), 1670 (C]Oester), 1518, 1446, 1212 (C–
Oester), 974, 922, 796, 740, 632 cmꢁ1 1H NMR (300 MHz, CDCl3)
.
5. Application of oligothiophenes and other
p-conjugated organic oligomers is
d
1.22 (t, 3H, COCH2CH3), 3.82 (s, 3H, CO2CH3), 4.11 (q, 2H,
outlined in: (a) Hoeben, F. J. M.; Jonkheijm, P.; Meijer, E. W.; Schenning, A. P. H.
J. Chem. Rev. 2005, 105, 1491; (b) Constanzo, F.; Tonelli, D.; Scalmani, G.; Cornil,
J. Polymer 2006, 47, 6692; (c) Sonar, P.; Benmansour, H.; Geiger, T.; Schlu¨ter,
A. D. Polymer 2007, 48, 4996; (d) Schueppel, R.; Schmidt, K.; Ulrich, C.; Schulze,
COCH2CH3), 7.06 (d, J¼6.2 Hz, 1H, H-30), 7.27 (dd, J¼6.2 Hz, 1H, H-
40), 7.31 (d, J¼6.2 Hz, 1H, H-50); 13C NMR (75 MHz, CDCl3)
d 19.4
(COCH2CH3), 38.0 (COCH2CH3), 48.6 (CO2CH3), 112.4 (CN), 115.2 (C-
5), 126.6 (C-50), 127.0 (C-30), 127.5 (C-40), 137.1 (C-20), 138.4 (C-3),
155.8 (C-4), 160.0 (CO2CH3), 165.1 (C-2), 179.6 (COCH2CH3). Anal.
Calcd for C14H11NO3S2 (305.37): C, 55.06; H, 3.63; S, 21.00; N, 4.59.
Found: C, 55.15; H, 3.80; N, 4.75; S, 21.16. Mass (ESI) m/z (%) 306.0
(MþH), 328.0 (MþNa).
´
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