One-pot two-component [3 + 2] cycloaddition/annulation protocol for the synthesis of highly functionalized thiophene derivatives

Article abstract of DOI:10.1021/jo200685e

An efficient and experimentally rapid protocol for the synthesis of hitherto unreported 2,3-dicarboalkoxy-4-aroyl/heteroaroyl/alkanoyl thiophenes has been developed via 1 - 2 (C - S) and 3 - 4 (C - C) bond connections promoted by 4-dimethylaminopyridine (

Full text of DOI:10.1021/jo200685e

NOTE
pubs.acs.org/joc
One-Pot Two-Component [3 + 2] Cycloaddition/Annulation Protocol
for the Synthesis of Highly Functionalized Thiophene Derivatives
Ganesh Chandra Nandi, Subhasis Samai, and Maya Shankar Singh*
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi-221005, India
S Supporting Information
b
ABSTRACT: An efficient and experimentally rapid protocol for
the synthesis of hitherto unreported 2,3-dicarboalkoxy-4-aroyl/
heteroaroyl/alkanoyl thiophenes has been developed via 1ꢀ2
(CꢀS) and 3ꢀ4 (CꢀC) bond connections promoted by
4-dimethylaminopyridine (DMAP). Optimally, the reaction
takes only 3ꢀ5 min when β-oxodithioester and dialkyl acet-
ylenedicarboxylate are stirred in DCM at room temperature in
the presence of DMAP. This method allows a clean and general
synthesis of previously inaccessible and synthetically demand-
ing thiophenes containing the ferrocenyl group. The speed,
experimental ease, and high yields of this process are improve-
ments over existing methods to access this important
substructure.
hiophenes are widespread in nature and have emerged as a
class of important heterocycles because of their presence in a
regioselective preparation of the thiophene derivatives and thus
represents an attractive but less developed methodology. Alterna-
tively, access to substituted thiophenes from α-oxoketene-S,S-
acetals has been reported.20 Recently, utilizing one-pot multicom-
ponent strategy, numerous highly substituted thiophene derivatives
have been synthesized.21 Ashokan and co-workers22 reported the
synthesis of 2,3,4-trisubstituted thiophenes by the alkylation of
β-ketodithioesters with α-haloketones. Further, regioselective synthe-
sis of polysubstituted thiophenes from BaylisꢀHillman adducts
have been carried out by Kim and co-workers.23 Albeit the
reported approaches are useful tools and represent important
advances toward the objective of a general method for the synthesis
of thiophenes, most of them suffer from significant limitations in
terms of harsh reaction conditions, long reaction time, low yields,
expensive catalyst, and use of strong base or difficult purification.
Therefore, more general, efficient, rapid, and viable routes are very
much desirable in view of their broad array of applications in the
areas of biology, material science, and chemistry and would be of
great relevance to both synthetic and medicinal chemists.
β-Ketodithioesters, which were not commercially sourced,
were prepared according to reported procedures.24 The utility of
β-ketodithioesters as versatile intermediates in organic synthesis
has been well recognized.25 In continuation of our ongoing
research interest for the synthesis of heterocycles via one-pot
reaction from β-ketodithioesters,26 and with the aim to devise a
more general synthetic route for heterocycles, we explored the
highly substituted thiophenes via heteroaromatic annulation of
β-ketodithioesters with dialkyl acetylenedicarboxylates. Thus,
T
broad spectrum of natural and synthetic organic molecules with
diverse biological properties.1,2 Over the years, thiophene deri-
vatives have attracted considerable attention from both medic-
inal and synthetic chemists due to their utility as versatile
intermediates3 in organic synthesis. Additionally, anthelmintic
and insecticidal activities have been ascribed to appropriately
functionalized thiophene derivatives.4 Moreover, thiophene de-
rivatives have been identified as potent antiplatelet agent
(Plavix)5 a blockbuster drug used in the treatment of coronary
artery disease. Articaine6 is the most commonly used dental
anesthetic in Europe, and PaTrin-27 is an inhibitor of the DNA
repair enzyme O6-methylguanine-DNA methyl transferase with
potential to increase the effectiveness of alkylating agents as
cancer therapeutics. Recently, a number of thiophenes have been
reported to show excellent and marked potent activity toward
CB1 receptors with good CB1/CB2 selectivity.8 Furthermore,
thiophene derivatives also find broad applications as functional
materials in electrically conducting organic materials,9 semi-
conductors,10 organic light-emitting diodes (OLEDs),11 organic
field effect transistors (OFETs),12 organic solar cells,13 lasers,14
dyes, liquid crystals, and molecular wires.15
Numerous synthetic routes to thiophene derivatives have been
reported16 performing variations and improvements on the origin-
ally published Gewald and PaalꢀKnorr synthesis of polysubstituted
thiophenes.17 The general synthetic approaches to thiophene
derivatives involve either modification of the preconstructed thio-
phene ring (usually α-metalation or β-halogenation)18 or the
construction of thiophene ring via the annulation reactions of
suitably substituted open chain precursors.19 The latter allows
Received: April 5, 2011
Published: August 18, 2011
r
2011 American Chemical Society
8009
dx.doi.org/10.1021/jo200685e J. Org. Chem. 2011, 76, 8009–8014
|

The Journal of Organic Chemistry
NOTE
Scheme 1. Synthesis of 2,3,4-Trisubstituted Thiophenes
Scheme 2. Thiophene Formation via α-Oxoketene Dithio-
acetal I
Table 1. Base and Solvent Screen for Thiophene Synthesis
α-oxoketene dithioacetal I with the help of analytical and spectral
studies. However, when α-oxoketene dithioacetal I was further
stirred with DMAP (1 equiv) at room temperature for 4 h gave
the desired thiophene 3j in 94% yield. Interestingly, in case of
DABCO also first the adduct α-oxoketene dithioacetal I was
formed, which upon further stirring for 4 h converted to the
desired thiophene in 82% yield (Table 1, entry 3). Notably, DBU
(1 equiv) facilitated the formation of desired thiophene in 78%
yield in 5 min at room temperature (Table 1, entry 4). To our
delight, the desired thiophene 3j was formed exclusively in 90%
yield within 3 min, when 1e was treated with 2a in the presence of
DMAP (1 equiv) at room temperature (Table 1, entry 5). The
higher reactivity of the base DMAP may be attributed to the
presence of electron-donating dimethylamino group at para-
position of the pyridine ring.
With DMAP base as good promoter in hand, next we intended
to optimize its loading, and it was found that the use of 1 equiv of
DMAP provided the best result. Reducing the equivalents of
DMAP in the reaction increased the reaction time and lowered
the yield drastically (Table 1, entry 6). However, no better yield
was obtained when the DMAP was increased to 1.2 equiv
(Table 1, entry 7). We immediately undertook a study to
examine the effects of different solvents on this transformation.
The results demonstrated that DCM appeared to be the best
choice for this transformation (Table 1). Thus, the best yield,
cleanest reaction, and most facile workup were achieved employ-
ing 1 equiv of DMAP in DCM at room temperature.
entry
base (equiv)
solvent
time
24 h
yielda (%)
1
2
none
DCM
DCM
DCM
DCM
DCM
DCM
DCM
EtOH
CH3CN
water
NRb
APc
82
TEA (1)
10 min
4 h
3
DABCO (1)
DBU (1)
4
5 min
3 min
30 min
3 min
10 min
7 min
24 h
78
5
DMAP (1)
DMAP (0.5)
DMAP (1.2)
DMAP (1)
DMAP (1)
DMAP (1)
90
6
40
7
88
8
72
9
82
NRb
10
a Isolated pure yields. b No reaction. c No thiophene; only addition
product (AP) α-oxoketene dithioacetal I was obtained in 88% yield.
when β-ketodithioesters 1 were treated with dialkyl acetylene-
dicarboxylates 2 in dichloromethane in the presence of base
4-dimethylaminopyridine at room temperature, the correspond-
ing 2,3,4-trisubstituted thiophenes 3 were obtained within 3ꢀ5
min in good yields (Scheme 1). The Lewis base DMAP is the
prototypical synthetic nucleophilic catalyst, which has become
not only a useful tool in synthesis but also a contextual testing
ground for applying new design principles to asymmetric
catalysis.27
On the basis of above optimized reaction conditions, we
commenced exploration of our substrate scope. To assess the
generality and applicability of this methodology, attempts to
expand the scope of the reaction proved successful and a wide
range of R groups (aromatic, heteroaromatic, and aliphatic) were
incorporated, which provided a functional handle for further
manipulation. Results are summarized in Table 2. Even extre-
mely electron-rich aromatic β-ketodithioesters such as 1d and 1e
proceeded smoothly (Table 2, entries 7ꢀ10). In addition to
incorporation of aryl, heteroaryl, and aliphatic substituents at the
4-position, ferrocenyl group is also viable for this protocol
(Table 2, entry 19). However, when some unsymmetric elec-
tron-deficient alkynes such as 3-phenylpropiolate and acetyl
phenylacetylene were used under the optimized reaction condi-
tions, the starting materials were completely consumed after 6 h
of stirring, but it led to a mixture of very close spots on the TLC
plate that could not be isolated, thus limiting the scope of this
reaction to some extent. To overcome the above problem, the
model reaction was performed under various varying conditions,
Using 3-oxo-3-thiophen-2-yldithiopropionic acid methyl ester
1e and the dimethyl acetylenedicarboxylate 2a as test substrates
for the synthesis of 2,3,4-trisubstituted thiophenes, optimization
of the reaction conditions was investigated through screening of
various bases using different solvents at room temperature.
Initially, a test reaction using the above model reaction was
performed without any base in DCM at room temperature to
establish the real effectiveness of the base. It was found that no
trace amount of the desired product was obtained even after 24 h
of stirring (Table 1, entry 1), and the starting materials were
totally unreacted (monitored by TLC). With this failure, we next
performed the reaction of 1e and 2a in the presence of different
bases like TEA, DABCO, DBU, and DMAP separately, at room
temperature. Thus, when above model reaction was carried out
in the presence of TEA, to our surprise the reaction ended to give
adduct of 1e and 2a within 10 min (Scheme 2, Table 1, entry 2),
the reaction was further stirred but no change was observed even
after 24 h. The adduct was isolated in 88% yield and identified as
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NOTE
Table 2. Substrate Scope for the Synthesis of Thiophenes
Scheme 3. Plausible Mechanism for the Synthesis of
Thiophene
entry
R
R0
product time (min) yielda (%)
1
C6H5
C6H5
Et
3a
3b
3c
3d
3e
3f
3
3
3
3
4
5
4
4
5
5
5
5
5
5
3
3
3
3
5
92
94
93
94
92
92
94
95
88
90
85
88
83
85
80
84
84
87
76
2
Me
Et
3
4-OMeC6H4
4-OMeC6H4
4-ClC6H4
4-ClC6H4
2-furyl
4
Me
Et
5
6
Me
Et
7
3g
3h
3i
8
2-furyl
Me
Et
9
2-thienyl
2-thienyl
10
11
12
13
14
15
16
17
18
19
Me
3j
3-(N-methylpyrrole) Et
3-(N-methylpyrrole) Me
3k
3l
first step in the mechanism is believed to be the abstractions of
acidic proton of β-ketodithioester 1 by DMAP followed by
nucleophilic attack on the sp-hybridized carbon of the 2,3-
dimethyl acetylenedicarboxylate 2 to generate open-chain adduct
α-oxoketene dithioacetal A. The intermediate A, which is the key
rate-determining step, undergoes intramolecular cyclization with
the extrusion of MeSH to give the thiophene derivative 3. The
intermediacy of α-oxoketene dithioacetal A has been confirmed
by its isolation and characterization when TEA was utilized as
base. This operationally simple and two-component domino
process concomitantly created two new CꢀS and CꢀC bond
leading to thiophene ring.
3-pyridyl
3-pyridyl
isopropyl
isopropyl
methyl
Et
3m
3n
3o
3p
3q
3r
3s
Me
Et
Me
Et
methyl
Me
Me
ferrocenyl
a Isolated pure yields.
’ CONCLUSION
In summary, a rapid and experimentally convenient synthesis
of 2,3-dicarboalkoxy-4-aroyl/heteroaroyl/alkanoyl thiophenes
has been developed for the first time via [3 + 2] heteroannulation
of β-ketodithioesters and dialkyl acetylenedicarboxylates by 1ꢀ2
(CꢀS) and 3ꢀ4 (CꢀC) bond formation. In addition, the
carboalkoxy and aroyl substituents in the 2-, 3-, and 4-positions
to the thiophene ring are quite reactive; this makes these
compounds good candidates as precursors for further synthetic
transformations to meet the need for various useful purposes.
The simplicity of execution, mild conditions, high yields, flexible
substituted patterns, broad range of potential utility of the
products, and more importantly the metal-catalyst-free proce-
dure make the protocol attractive for academic research and
practical applications.
’ EXPERIMENTAL SECTION
General. The starting materials were commercially available and
used as received without further purification. β-Oxodithioesters 1aꢀj
were prepared following the known procedure.24 Thin-layer chroma-
tography (TLC) was performed using silica gel 60 F254 precoated
plates. Infrared (IR) spectra are measured in KBr, and wavelengths (ν)
are reported in cmꢀ1. 1H and 13C NMR spectra were recorded on NMR
spectrometer operating at 300 and 75.5 MHz, respectively. Chemical
shifts (δ) are given in parts per million (ppm) using the residue solvent
peaks as reference relative to TMS. J values are given in hertz. Mass
spectra were recorded using electrospray ionization (ESI) mass spectro-
metry. The C, H, and N analyses were performed from microanalytical
laboratory. The melting points are uncorrected.
Figure 1. ORTEP diagram of 3b.
but unfortunately our all efforts were found to be ineffective. The
low electron-withdrawing ability of phenyl group may be re-
sponsible for this outcome.
The structures of all the thiophene derivatives 3aꢀs were
1
deduced from their satisfactory elemental and spectral (IR, H,
13C NMR, and mass) studies and unequivocally established by
the X-ray single crystal diffraction analysis (see the Supporting
Information) of one representative compound 4-benzoyl-2,3-
dicarbomethoxythiophene 3b (Figure 1).28
General Procedure for the Synthesis of the Trisubstituted Thio-
phenes (3aꢀs). To a mixture of β-ketodithioester (1.0 mmol) and
dialkyl acetylenedicarboxylate (1.0 mmol) in dichloromethane (3 mL)
was added 4-dimethylaminopyridine (1.0 mmol), and the reaction
On the basis of the above experimental results together with
the related reports, a plausible reaction scenario for this one-pot
two-component heteroannulation is outlined in Scheme 3. The
8011
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The Journal of Organic Chemistry
NOTE
mixture was stirred for the stipulated period of time at room tempera-
ture. After completion of the reaction (monitored by TLC), water
(20 mL) was added to the reaction mixture followed by extraction
with dichloromethane (2 ꢁ 10 mL). The combined organic layer was
dried over anhyd Na2SO4 and then evaporated in vacuo. The crude
residue was purified by column chromatography over silica gel using
ethyl acetate/hexane (1:10) as eluent to afford pure thiophenes.
Characterization Data of the Isolated Compounds. 4-Benzoyl-2,
3-dicarboethoxythiophene (3a). White solid; mp 53ꢀ54 °C. IR
(KBr, cmꢀ1): 3031, 1729, 1632, 1220. 1H NMR (300 MHz, CDCl3):
δ 7.90 (s, 1H), 7.81 (d, J = 7.2 Hz, 2H), 7.60 (t, J = 7.2 Hz, 1H), 7.48 (t, J =
7.5 Hz, 2H), 4.43ꢀ4.34 (m, 4H), 1.40ꢀ1.35 (m, 6H). 13C NMR
(75 MHz, CDCl3): δ 188.5, 164.6, 160.3, 139.9, 137.2, 132.9, 132.7,
129.6, 129.1, 128.8, 128.3, 62.2, 62.1, 14.3, 13.6. MS: m/z = 332 (M+).
Anal. Calcd for C17H16O5S: C, 61.43; H, 4.85. Found: C, 61.69; H, 4.62.
4-Benzoyl-2,3-dicarbomethoxythiophene (3b). White solid; mp 92ꢀ
4-(2-Thienoyl)-2,3-dicarboethoxythiophene (3i). White solid; mp
65ꢀ67 °C. IR (KBr, cmꢀ1): 3091, 2984, 1737, 1712, 1619, 1258. 1H NMR
(300 MHz, CDCl3): δ 8.07 (s, 1H), 7.73 (d, J = 4.2 Hz, 2H), 7.18
(t, J = 4.5 Hz, 1H), 4.45ꢀ4.33 (m, 4H), 1.40ꢀ1.35 (m, 6H). 13C NMR
(75 MHz, CDCl3): δ 179.8, 164.4, 160.2, 142.8, 139.9, 139.5, 135.7,
134.6, 134.1, 133.1, 128.1, 62.2, 62.1, 14.1, 13.9. MS: m/z = 338 (M+).
Anal. Calcd for C15H14O5S2: C, 53.24; H, 4.17. Found: C, 53.36;
H, 4.07.
4-(2-Thienoyl)-2,3-dicarbomethoxythiophene (3j). White solid; mp
110ꢀ112 °C. IR (KBr, cmꢀ1): 3087, 2976, 1737, 1723, 1260. 1H NMR
(300 MHz, CDCl3): δ 8.11 (s, 1H), 7.75ꢀ7.73 (m, 2H), 7.17 (t, J = 4.2
Hz, 1H), 3.95 (s, 3H), 3.91 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
179.6, 164.9, 160.5, 142.5, 139.8, 139.5, 135.9, 134.7, 134.1, 132.4, 128.1,
53.1, 52.9. MS: m/z = 310 (M+). Anal. Calcd for C13H10O5S2: C, 50.31;
H, 3.25. Found: C, 50.52; H, 3.13.
2,3-Dicarboethoxy-4-[3-(N-methylpyrroloyl)]thiophene (3k). White
solid; mp 112ꢀ113 °C. IR (KBr, cmꢀ1): 3095, 2956, 1725, 1630, 1284.
1H NMR (300 MHz, CDCl3): δ 7.96 (s, 1H), 7.22 (s, 1H), 6.63 (s, 2H),
4.44ꢀ4.32 (m, 4H), 3.71 (s, 3H), 1.38 (t, J = 3.6 Hz, 3H), 1.35 (t, J = 3.6
Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 181.9, 164.9, 160.5, 141.9,
139.6, 134.5, 132.3, 128.3, 124.3, 123.6, 110.6, 62.0, 61.9, 36.6, 14.0, 13.9.
MS: m/z = 335 (M+). Anal. Calcd for C16H17NO5S: C, 57.30; H, 5.11; N,
4.18. Found: C, 57.46; H, 5.36; N, 4.02.
2,3-Dicarbomethoxy-4-[3-(N-methylpyrroloyl)]thiophene (3l). White
solid; mp 109ꢀ110 °C. IR (KBr, cmꢀ1): 3087, 2935, 1733, 1624, 1285. 1H
NMR (300 MHz, CDCl3): δ 7.99 (s, 1H), 7.23 (s, 1H), 6.62 (s, 2H), 3.94
(s, 3H), 3.89 (s, 3H), 3.70 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 181.7,
165.4, 160.7, 141.8, 139.6, 134.7, 131.6, 128.3, 124.1, 123.6, 110.5, 52.9,
52.7, 36.6. MS: m/z= 307 (M+). Anal. Calcd for C14H13NO5S: C, 54.71; H,
4.26; N, 4.56. Found: C, 54.53; H, 4.38; N, 4.64.
1
93 °C. IR (KBr, cmꢀ1): 3025, 1721, 1609, 1212. H NMR (300 MHz,
CDCl3): δ 7.92 (s, 1H), 7.81 (d, J = 7.5 Hz, 2H), 7.61 (t, J = 7.2 Hz, 1H),
7.49 (t, J = 7.5 Hz, 2H), 3.94 (s, 3H), 3.92 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 188.4, 165.0, 160.6, 139.8, 137.7, 137.0, 133.0, 129.3, 128.5,
128.2, 127.6, 53.0, 52.8. MS: m/z = 304 (M+). Anal. Calcd for C15H12O5S:
C, 59.20; H, 3.97. Found: C, 59.46; H, 4.25.
2,3-Dicarboethoxy-4-(4-methoxybenzoyl)thiophene (3c). White solid;
mp 75ꢀ76 °C. IR (KBr, cmꢀ1): 3020, 1721, 1600, 1526, 1215. 1H NMR
(300 MHz, CDCl3): δ 7.84ꢀ7.81 (m, 3H), 6.95 (d, J = 8.7 Hz, 2H),
4.40ꢀ4.34 (m, 4H), 3.88 (s, 3H), 1.39ꢀ1.33 (m, 6H). 13CNMR(75MHz,
CDCl3): δ 187.2, 164.6, 163.6, 160.3, 140.5, 139.7, 136.2, 132.9, 131.9,
129.9, 113.8, 62.1, 62.0, 55.5, 14.1, 13.9. MS: m/z = 362 (M+). Anal. Calcd
for C18H18O6S: C, 59.66; H, 5.01. Found: C, 59.82; H, 4.91.
2,3-Dicarbomethoxy-4-(4-methoxybenzoyl)thiophene (3d). White
solid; mp 128ꢀ129 °C. IR (KBr, cmꢀ1): 3028, 1723, 1598, 1258. 1H NMR
(300 MHz, CDCl3): δ 7.87 (s, 1H), 7.82 (d, J = 8.7 Hz, 2H), 6.96 (d, J =
8.7 Hz, 2H), 3.93 (s, 3H), 3.91 (s, 3H), 3.89 (s, 3H). 13C NMR
(75 MHz, CDCl3): δ 187.1, 165.1, 163.6, 160.7, 140.4, 139.8, 136.4,
131.9, 129.7, 113.8, 55.5, 53.0, 52.9. MS: m/z = 334 (M+). Anal. Calcd
for C16H14O6S: C, 57.48; H, 4.22. Found: C, 57.32; H, 4.35.
4-(4-Chlorobenzoyl)-2,3-dicarboethoxythiophene (3e). White solid;
mp 73ꢀ74 °C. IR (KBr, cmꢀ1): 3091, 2954, 1734, 1653, 1256. 1H NMR
(300 MHz, CDCl3):δ7.87 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.46 (d, J= 8.1
Hz, 2H), 4.43ꢀ4.34 (m, 4H), 1.40ꢀ1.34 (m, 6H). 13C NMR (75 MHz,
CDCl3): δ 187.2, 164.4, 160.1, 139.5, 139.5, 137.3, 135.4, 133.2, 130.7,
128.9, 62.2, 62.1, 14.0, 13.8. MS: m/z = 366 (M+). Anal. Calcd for
C17H15ClO5S: C, 55.66; H, 4.12. Found: C, 55.45; H, 4.35.
4-(4-Chlorobenzoyl)-2,3-dicarbomethoxythiophene (3f). White solid;
mp 123ꢀ124 °C. IR (KBr, cmꢀ1): 3098, 2958, 1733, 1653, 1261. 1H NMR
(300 MHz, CDCl3): δ 7.88 (s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 8.4
Hz, 2H), 3.93 (s, 3H), 3.92 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 187.2,
164.9, 160.5, 139.6, 137.4, 135.3, 130.8, 128.9, 53.1, 52.9. MS: m/z= 338 (M+).
Anal. Calcd for C15H11ClO5S: C, 53.18; H, 3.27. Found: C, 52.85; H, 3.46.
2,3-Dicarboethoxy-4-(2-furoyl)thiophene (3g). White solid; mp 72ꢀ
73 °C. IR (KBr, cmꢀ1): 3085, 2959, 1723, 1635, 1463, 1270. 1H NMR
(300 MHz, CDCl3): δ 8.54 (s, 1H), 7.67 (s, 1H), 7.35 (d, J = 3.6 Hz, 1H),
6.61 (s, 1H), 4.46 (q, J = 6.9 Hz, 2H), 4.36 (q, J = 6.9 Hz, 2H), 1.43ꢀ1.34
(m, 6H). 13C NMR (75 MHz, CDCl3): δ 173.6, 164.8, 160.2, 152.2,
146.8, 140.0, 138.3, 137.6, 132.0, 119.9, 112.6, 62.1, 62.0, 14.0, 13.9. MS:
m/z = 322(M+). Anal. CalcdforC15H14O6S:C, 55.89;H, 4.38. Found: C,
55.61; H 4.52.
2,3-Dicarbomethoxy-4-(2-furoyl)thiophene (3h). White solid; mp
110ꢀ111 °C. IR (KBr, cmꢀ1): 3071, 2954, 1720, 1633, 1279. 1H NMR
(300 MHz, CDCl3): δ 8.58 (s, 1H), 7.68 (s, 1H), 7.37 (d, J = 3.3 Hz,
1H), 6.61 (d, J = 1.8 Hz, 1H), 4.00 (s, 3H), 3.91 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 173.5, 165.3, 160.6, 152.3, 146.8, 140.1, 138.3, 137.8,
131.5, 119.9, 112.7, 53.1, 52.8. MS: m/z = 294 (M+). Anal. Calcd for
C13H10O6S: C, 53.06; H, 3.43. Found: C, 53.33; H, 3.22.
2,3-Dicarboethoxy-4-(3-pyridoyl)thiophene (3m). White solid; mp
72ꢀ73 °C. IR (KBr, cmꢀ1): 3075, 2967, 1737, 1714, 1632, 1278. 1H NMR
(300 MHz, CDCl3): δ 9.03 (s, 1H), 8.82 (s, 1H), 8.11 (d, J = 8.1 Hz,
1H), 7.92 (s, 1H), 7.46 (q, J = 5.1 Hz, 1H), 4.46ꢀ4.35 (m, 4H),
1.41ꢀ1.36 (m, 6H). 13C NMR (75 MHz, CDCl3): δ 186.6, 164.4, 160.0,
153.3, 150.1, 139.5, 139.1, 138.0, 136.7, 133.4, 132.9, 123.6, 62.3, 62.2,
14.0, 13.8. MS: m/z = 333 (M+). Anal. Calcd for C16H15NO5S: C, 57.65;
H, 4.54; N, 4.20. Found: C, 57.89; H, 4.35; N, 4.46.
2,3-Dicarbomethoxy-4-(3-pyridoyl)thiophene (3n). White solid; mp
1
94ꢀ95 °C. IR (KBr, cmꢀ1): 3081, 2957, 1731, 1727, 1622, 1276. H
NMR (300 MHz, CDCl3): δ 9.03 (s, 1H), 8.83 (s, 1H), 8.12 (d, J = 6.6
Hz, 1H), 7.95 (s, 1H), 7.47 (t, J = 5.1 Hz, 1H), 3.96 (s, 3H), 3.93 (s, 3H).
13C NMR (75 MHz, CDCl3): δ 186.6, 164.8, 160.4, 153.4, 150.1, 139.5,
139.1, 138.1, 136.7, 132.9, 132.8, 123.6, 53.2, 53.0. MS: m/z = 305 (M+).
Anal. Calcd for C14H11NO5S: C, 55.08; H, 3.63; N, 4.59. Found: C,
55.25; H, 3.48; N, 4.78.
2,3-Dicarboethoxy-4-isobutanoylthiophene (3o). White solid; mp
71ꢀ72 °C. IR (KBr, cmꢀ1): 3085, 2986, 1732, 1712, 1693, 1259. 1H NMR
(300 MHz, CDCl3): δ 8.08 (s, 1H), 4.46 (q, J = 7.2 Hz, 2H), 4.33
(q, J = 7.2 Hz, 2H), 3.31ꢀ3.26 (m, 1H), 1.43ꢀ1.36 (m, 6H), 1.22 (s,
3H), 1.20 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 185.0, 160.8, 157.3,
129.2, 129.1, 128.5, 127.6, 55.3, 54.3, 34.5, 21.0, 15.0, 14.8. MS: m/z =
298 (M+). Anal. Calcd for C14H18O5S: C, 56.36; H, 6.08. Found: C,
56.52; H, 5.95.
2,3-Dicarbomethoxy-4-isobutanoylthiophene (3p). White solid; mp
108ꢀ110 °C. IR (KBr, cmꢀ1): 3094, 2981, 1735, 1720, 1690, 1262. 1H NMR
(300 MHz, CDCl3): δ 8.09 (s, 1H), 4.00 (s, 3H), 3.89 (s, 3H), 3.31ꢀ3.26
(m, 1H), 1.22 (s, 3H), 1.20 (s, 3H). 13C NMR (75 MHz, CDCl3):
δ 197.3, 165.7, 160.6, 139.4, 136.1, 131.7, 129.2, 53.1, 52.8, 36.9, 18.9. MS:
m/z= 270(M+). Anal. CalcdforC12H14O5S:C, 53.32;H, 5.22. Found:C,
53.46; H, 5.03.
4-Acetyl-2,3-dicarboethoxythiophene (3q). White solid. mp 63ꢀ
65 °C IR (KBr, cmꢀ1): 3064, 2979, 1725, 1720, 1682, 1270. 1H NMR
(300 MHz, CDCl3): δ 8.10 (s, 1H), 4.45 (q, J = 6.9 Hz, 2H), 4.34
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NOTE
(q, J = 6.9 Hz, 2H), 2.51 (s, 3H), 1.44ꢀ1.33 (m, 6H). 13C NMR (75
MHz, CDCl3): δ 190.5, 165.1, 160.2, 140.5, 138.7, 136.9, 132.3, 62.2,
62.0, 27.0, 14.0, 13.8. MS: m/z = 270 (M+). Anal. Calcd for C12H14O5S:
C, 53.32; H, 5.22. Found: C, 53.18; H, 5.47.
4-Acetyl-2,3-dicarbomethoxythiophene (3r). White solid; mp 99ꢀ
100 °C. IR (KBr, cmꢀ1): 3056, 2977, 1729, 1714, 1687, 1265. 1H NMR
(300 MHz, CDCl3): δ 8.10 (s, 1H), 4.00 (s, 3H), 3.89 (s, 3H), 2.52 (s,
3H). 13C NMR (75 MHz, CDCl3): δ 190.5, 165.6, 160.6, 140.6, 138.7,
136.9, 131.9, 53.1, 52.9, 27.0. MS: m/z = 242 (M+). Anal. Calcd for
C10H10O5S: C, 49.58; H, 4.16. Found: C, 49.76; H, 4.07.
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2,3-Dicarbomethoxy-4-η5-ferrocenylthiophene (3s). Reddish solid;
mp 135ꢀ137 °C. IR (KBr, cmꢀ1): 3103, 2926, 1727, 1630, 1262. 1H NMR
(300 MHz, CDCl3): δ 8.12 (s, 1H), 4.91 (s, 2H), 4.62 (s, 2H), 4.27
(s, 5H), 4.00 (s, 3H), 3.91 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
190.5, 165.4, 160.8, 141.4, 139.6, 134.1, 131.7, 72.9, 70.9, 70.3, 70.0, 53.0,
52.8. MS: m/z = 412 (M+). Anal. Calcd for C19H16FeO5S: C, 55.36; H,
3.91. Found: C, 55.27; H, 4.03.
2-(1-Methylsulfanyl-3-(2-thienoyl)propenylsulfanyl)but-2-enedioic
Acid Dimethyl Ester (I). Colorless sticky liquid. IR (KBr, cmꢀ1): 2931,
1723, 1626, 1243. 1H NMR (300 MHz, CDCl3): δ 7.63ꢀ7.59 (m, 2H),
7.11 (t, J = 4.2 Hz, 1H), 7.00 (s, 1H), 6.80 (s, 1H), 3.84 (s, 3H), 3.73 (s,
3H), 2.57 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 179.0, 164.8, 158.5,
145.5, 144.7, 133.3, 130.7, 128.2, 128.1, 125.7, 121.1, 53.6, 52.4, 17.3.
MS: m/z = 358 (M+). Anal. Calcd for C14H14O5S3: C, 46.91; H, 3.94.
Found: C, 47.12; H, 3.76.
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’ ASSOCIATED CONTENT
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S
Supporting Information. Full experimental details, ana-
b
lytical and spectroscopic data (copies of H and 13C NMR for
compounds 3 and I). X-ray structures and crystallographic
information files (CIF) for compound 3b. This material is
available free of charge via the Internet at http://pubs.acs.org.
1
’ AUTHOR INFORMATION
Corresponding Author
*Tel.: +91-542-6702502; fax: +91-542-2368127; e-mail: mssinghbhu@
yahoo.co.in.
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’ ACKNOWLEDGMENT
We gratefully acknowledge the generous financial support from
Council of Scientific and Industrial Research (Grant 01(2260)/
08/EMR-II) and Department of Science and Technology (Grant
SR/S1/OC-66/2009), New Delhi. The authors (G.C.N. and S.S)
thank CSIR, New Delhi, for a senior research fellowship.
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the Cambridge Crystallographic Data Centre; deposition no. CCDC
818986 (3b). These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre, 12 Union Rd., Cambridge
CB2 1EZ, UK or via www.ccdc.cam.ac.uk/conts/retrieving.html.
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