Synthesis of 4H-indeno[1,2-b]thiophenes, 8H-indeno[2,1-b]-thiophenes and 8H-indeno[2,1-b]furans having acrylic acid unit

Article abstract of DOI:10.1002/jhet.5570450252

(Chemical Equation Presented) Treatment of methyl propiolate and 2-(thiophen-2-yl)benzaldehyde, 2-(thiophen-3-yl)benzaldehyde or 2-(furan-3-yl)benzaldehyde with tetrabutylammonium iodide/zirconium (IV) chloride or treatment of methyl acrylate and the same

Full text of DOI:10.1002/jhet.5570450252

Mar-Apr 2008
615
Synthesis of 4H-Indeno[1,2-b]thiophenes, 8H-Indeno[2,1-b]-
thiophenes and 8H-Indeno[2,1-b]furans Having Acrylic Acid Unit
Ki Joon Jeon and Kee-Jung Lee*
Organic Synthesis Laboratory, Department of Chemical Engineering
Hanyang University, Seoul 133-791, Korea
Fax +82(2)22984101; E-mail: leekj@hanyang.ac.kr
Received August 14, 2007
HC CCO2Me
Bu4NI, ZrCl4
CH2Cl2
or
H2C CHCO2Me
DABCO
Het
Het
Het
CO2Me
X
OH
H2SO4, CCl4
CO2Me
X
CHO
Het = 2-thienyl, 3- thienyl and 3-furyl
X = I and H
Treatment of methyl propiolate and 2-(thiophen-2-yl)benzaldehyde, 2-(thiophen-3-yl)benzaldehyde or 2-
(furan-3-yl)benzaldehyde with tetrabutylammonium iodide/zirconium (IV) chloride or treatment of methyl
acrylate and the same aldehydes with 1,4-diazabicyclo[2,2,2]octane and triethanolamine induce an aldol-
type reaction to furnish Baylis-Hillman adducts β-iodo-α-(hydroxymethyl)acrylates or α-(hydroxy-
methyl)acrylates, respectively. These can be used for the preparation of indenothiophenes and
indenofurans having acrylic acid unit by intramolecular Friedel-Crafts reaction with sulfuric acid in
tetrachloromethane.
J. Heterocyclic Chem., 45, 615 (2008).
The Baylis-Hillman (BH) reaction has become a
powerful tool for construction of carbon-carbon bonds in
organic chemistry because it is completely atom
economical and provides densely functionalized structural
units, which have been successfully employed in a variety
of interesting organic transformations [1]. The Friedel-
Crafts reaction is one of the most fundamental carbon-
carbon bond forming reaction in organic synthesis [2].
Recently, we reported the synthesis of 2-(9-fluorenyl)-
acrylic acid derivatives from BH adducts of 2-
biphenylcarboxaldehydes by an intramolecular Friedel-
Crafts reaction as shown in Scheme 1 [3]. During
continued efforts to develop BH chemistry [4], we
subsequently envisioned that application of this protocol
to BH adducts of several thiophene- or furan-substituted
benzaldehydes might lead to indenothiophenes or
indenofurans having acrylic acid unit.
Indenothiophene is the core structure of potent molecules
such as inhibitors of 1kk-β phosphorylation of 1kB [8]
and neurotransmitter release enhancers useful in the
treatment of cognitive disorders [9]. A general method for
the synthesis of indenothiophenes is reduction of
corresponding indenothiophenones. The most useful
syntheses of indenothiophenones include Friedel-Crafts
ring closures of 2-thienylbenzoic acids and derivatives
[10], cycloaromatization of non-conjugated thienyl
tetraynes [11], palladium-catalyzed cyclocarbonylation of
o-haloheteroaryls [12], and direct double metalation of the
appropriate 3-phenylhetarene with butyllithium followed
by treatment of the resulting dilithium compound with
ethyl N,N-dimethylcarbamate [13]. However, far less
attention has been devoted to indenofurans synthesis in
the literature to date [12-14].
The required β-iodo-BH adducts 2a, 2c, 2e were
prepared by the reaction of methyl propiolate with
tetrabutylammonium iodide, followed by an aldol process
with aldehydes 1a-c in the presence of zirconium (IV)
chloride in 62-68% yields, originally reported by
Taniguchi [15] and Lu [16]. The typical BH reaction of
1a-c with methyl acrylate, 1,4-diazabicyclo[2,2,2]octane
(DABCO), and triethanolamine without solvent gave BH
adducts 2b, 2d, 2f in 61-75% yields. On Friedel-Crafts
cyclization of 2a-2f with 95% sulfuric acid in tetrachloro-
methane at room temperature for 2-5 hours, 4H-indeno-
[1,2-b]thiophenes 3a, 3b, 8H-Indeno[2,1-b]thiophenes 3c,
3d or 8H-Indeno[2,1-b]furans 3e, 3f were produced in 38-
71% yields, respectively, presumably through the
Scheme 1
CO2Me
X
H2SO4
CCl4, r.t.
OH
CO2Me
X
Indenothiophene derivatives have received considerable
attention in the field of organometallic chemistry because
their transition metal complexes have been found to be
promising catalysts for olefin polymerization [5-7].

616
K. J. Jeon and K.-J. Lee
Vol 45
Scheme 2
HC CCO2CH3
Bu4NI, ZrCl4
CH2Cl2, 0°C, 4 h
S
95% H2SO4
CCl4, r.t., 3~5 h
S
S
CO2Me
X
OH
or
CO2Me
X
CHO
H2C CHCO2CH3
DABCO, (HOCH2CH2)3N
r.t., 12 d
1a
3a, X = I (71%)
3b, X = H (61%)
2a, X = I (68%)
2b, X = H (75%)
HC CCO2CH3
Bu4NI, ZrCl4
CH2Cl2, 0°C, 2 h
S
S
S
95% H2SO4
CCl4, r.t., 2 h
CO2Me
OH
or
CO2Me
CHO
X
H2C CHCO2CH3
DABCO, (HOCH2CH2)3N
r.t., 15 d
X
1b
2c, X = I (62%)
2d, X = H (73%)
3c, X = I (65%)
3d, X = H (64%)
O
HC CCO2CH3
Bu4NI, ZrCl4
CH2Cl2, 0°C, 5 h
O
O
95% H2SO4
CCl4, r.t., 2~4 h
CO2Me
OH
or
CHO
CO2Me
X
H2C CHCO2CH3
DABCO, (HOCH2CH2)3N
r.t., 14 d
X
3e, X = I (40%)
3f, X = H (38%)
1c
2e, X = I (66%)
2f, X = H (61%)
resonance-stabilized, more stable benzylic carbocation
(Scheme 2).
an aldehyde in this study. The corresponding β-iodo-BH
adduct was not produced by the reaction of methyl
propiolate with tetrabutylammonium iodide and
zirconium (IV) chloride, presumably due to basic nature
of the pyridine. When using excess zirconium (IV)
chloride and tetrabutylammonium iodide the reaction was
unsuccessful. On the other hand, the typical BH reaction
of 1d with methyl acrylate, DABCO, and triethanolamine
without solvent gave BH adduct 2g in 78% yield.
However, on Friedel-Crafts cyclization of 2g with sulfuric
1
The structures of 3a, 3c, 3e were elucidated by H and
13C NMR and elemental analyses. In the 1H NMR spectra,
the characteristic chemical shift of the methine protons of
indene were found at δ = 4.85-5.04 as a singlet and the
alkenic protons were observed at δ = 6.91-7.06 as a
doublet (J = 0.9 Hz) for indenothiophenes 3a, 3c, and at δ
= 6.98 as a singlet for indenofuran 3e. The two vinyl
protons of 3b, 3d, 3f were found at δ = 5.44-5.53 and
6.16-6.21, and the indene methine protons were observed
at δ =4.87-5.03 as singlets. The two thiophene protons of
indenothiophenes 3a-3d resonated at δ =7.02-7.25 and δ =
7.30-7.38 as two doublet (J = 4.9 Hz) and one of the two
furan protons of indenofurans 3e, 3f was found at δ =
6.63-6.65 as a doublet (J = 1.8 Hz) and another one was
observed at aromatic region. The Z-stereoselectivity of
3a-f was determined from 1H NMR analysis by
comparison with the chemical shift of the olefinic protons
of the known methyl (Z)-2-(9H-fluoren-9-yl)-3-iodopro-
penoate [3]. In the 13C NMR spectra, the characteristic sp3
carbon atom of hetarenoindenes were observed at δ =
44.3-51.1.
Scheme 3
N
N
H2C CHCO2CH3
DABCO, (HOCH2CH2)3N
r.t., 11 d
OH
CO2Me
CHO
78%
2g
1d
N
CO2Me
H2SO4
In order to extend the scope of this methodology we
have also examined 2-(pyridin-4-yl)benzaldehyde (1d) as
3g

Mar-Apr 2008
Synthesis of 4H-Indeno[1,2-b]thiophenes, 8H-Indeno[2,1-b]- thiophenes and …
617
was diluted with water (20 mL) and extracted with
dichloromethane (3 × 40 mL). The combined organic layers
were dried over anhydrous magnesium sulfate and the solvent
was evaporated in vacuo. The resulting mixture was
chromatographed on silica gel eluting with hexane/ethyl acetate
(6:1) to produce 2.06 g (75%) of 2b as an oil; ir (potassium
acid or p-toluenesulfonic acid in tetrachloromethane or
tetrahydrofuran at room or reflux temperature the desired
methyl 2-(9H-indeno[2,1-c]pyridin-9-yl)propenoate (3g)
was not produced, instead only decomposition was
observed (Scheme 3).
1
bromide): 3469, 1727, 1630, 1600, 1531, 1483, 1440 cm-1; H
In conclusion, we have demonstrated a new synthetic
method for the preparation of indenothiophenes and
indenofurans having acrylic acid unit by Friedel-Crafts
cyclization of Baylis-Hillman adducts of hetarenobenz-
aldehydes. There is some limitation as regards the
reactivity of Baylis-Hillman adduct having pyridine ring
with sulfuric acid.
nmr (deuteriochloroform): δ 2.84 (br s, 1 H), 3.71 (s, 3 H), 5.67
(s, 1 H), 5.89 (s, 1 H), 6.37 (s, 1 H), 7.05-7.08 (m, 2 H), 7.31-
7.43 (m, 4 H), 7.53-7.56 (m, 1 H); 13C nmr (deuterio-
chloroform): δ 52.0, 69.2, 125.8, 126.7, 127.0, 127.1 (two),
127.9, 128.4, 131.2, 133.8, 138.9, 141.3, 142.2, 166.8. Anal.
Calcd. for C15H14O3S: C, 65.67; H, 5.14; S, 11.69. Found: C,
65.49; H, 5.03; S, 11.51.
Methyl (Z)-2-[1-Hydroxy-1-{2-(thiophen-3-yl)phenyl}
methyl]-3-iodopropenoate (2c). To a mixture 1b (1.88 g, 10
mmoles), methyl propiolate (0.98 mL, 11 mmoles) and Bu4NI
(4.43 g, 12 mmoles) in anhydrous dichloromethane (40 mL) was
added ZrCl4 (2.80 g, 12 mmoles) at 0 °C. The mixture was
stirred at 0 °C under nitrogen atmosphere for 2 hours. Then,
water (20 mL) was added and the mixture was extracted with
dichloromethane (3 × 40 mL). The combined organic layers
were dried over anhydrous magnesium sulfate and the solvent
was evaporated in vacuo. The resulting mixture was chromato-
graphed on silica gel eluting with hexane/ethyl acetate (6:1) to
produce 2.48 g (62%) of 2c as an oil; ir (potassium bromide):
3500, 1731, 1598, 1484, 1434 cm-1; 1H nmr (deuterio-
chloroform): δ 2.64 (d, J = 5.2 Hz, 1 H), 3.68 (s, 3 H), 5.71 (d, J
= 3.6 Hz, 1 H), 7.05 (d, J = 1.6 Hz, 1 H), 7.10-7.12 (m, 1 H),
7.22-7.24 (m, 1 H), 7.31-7.41 (m, 4 H), 7.46-7.50 (m, 1H); 13C
nmr (deuteriochloroform): δ 51.9, 72.5, 87.1, 123.2, 125.6,
126.8, 128.1, 128.3, 128.8, 130.4, 136.2, 137.4, 140.3, 145.3,
166.3. Anal. Calcd. for C15H13IO3S: C, 45.01; H, 3.27; S, 8.01.
Found: C, 45.25; H, 3.03; S, 7.75.
EXPERIMENTAL
Silica gel 60 (70-230 mesh ASTM) used for column
chromatography was supplied by E. Merck. Analytical thin layer
chromatography (TLC) was performed on Merck silica gel 60
F254 TLC plates. Melting points were measured by an
Electrothermal melting point apparatus and were uncorrected.
Microanalysis was obtained using
a
Thermo Electron
Corporation Flash EA 1112 element analyzer. Infrared spectra
were recorded with a Nicolet Magna 550 FTIR spectrometer.
The H and 13C NMR spectra were measured on a Gemini 300
spectrometer using deuteriochloroform. All chemical shifts are
reported in parts per million relative to tetramethylsilane. The
coupling constants (J) are expressed in Hertz.
1
The known 2-(thiophen-2-yl)benzaldehyde (1a) [17], 2-(thio-
phen-3-yl)benzaldehyde (1b) [18], 2-(furan-3-yl)benz-aldehyde
(1c) [19] and 2-(pyridin-4-yl)benzaldehyde (1d) [20] were
prepared from commercially available 2-formylphenyl-boronic
acid with 2-bromo-, 3-bromothiophene, 3-bromofuran and 4-
bromopyridine by Suzuki reaction according to the literature
procedure.
Methyl 2-[1-Hydroxy-1-{2-(thiophen-3-yl)phenyl}methyl]
propenoate (2d). A mixture of 1b (1.88 g, 10 mmoles), methyl
acrylate (2.70 mL, 30 mmoles), DABCO (1.12 g, 10 mmoles)
and triethanolamine (0.93 mL, 8 mmoles) without solvent was
stirred at room temperature for 15 days. The reaction mixture
was diluted with water (20 mL) and extracted with
dichloromethane (3 × 40 mL). The combined organic layers
were dried over anhydrous magnesium sulfate and the solvent
was evaporated in vacuo. The resulting mixture was chromato-
graphed on silica gel eluting with hexane/ethyl acetate (6:1) to
produce 2.00 g (73%) of 2d as an oil; ir (potassium bromide):
Methyl (Z)-2-[1-Hydroxy-1-{2-(thiophen-2-yl)phenyl}-
methyl]-3-iodopropenoate (2a). To a mixture of 1a (1.88 g, 10
mmoles), methyl propiolate (0.98 mL, 11 mmoles) and
tetrabutylammonium iodide (Bu4NI) (4.43 g, 12 mmoles) in
anhydrous dichloromethane (40 mL) was added zirconium
chloride (ZrCl4) (2.80 g, 12 mmoles) at 0 °C. The mixture was
stirred at 0 °C under nitrogen atmosphere for 4 hours. Then,
water (20 mL) was added and the mixture was extracted with
dichloromethane (3 × 40 mL). The combined organic layers
were dried over anhydrous magnesium sulfate and the solvent
was evaporated in vacuo. The resulting mixture was chromato-
graphed on silica gel eluting with hexane/ethyl acetate (6:1) to
produce 2.72 g (68%) of 2a as a solid; mp 62-63 °C; ir
(potassium bromide): 3485, 1724, 1597, 1482, 1447, 1432 cm-1;
1H nmr (deuteriochloroform): δ 2.65 (d, J = 4.9 Hz, 1 H), 3.70
(s, 3 H), 5.84 (d, J = 4.0 Hz, 1 H), 7.03-7.11 (m, 3 H), 7.33-7.44
(m, 4 H), 7.50-7.53 (m, 1 H); 13C nmr (deuteriochloroform): δ
52.0, 72.2, 87.7, 126.1, 127.0, 127.1, 127.3, 128.3, 128.7, 131.4,
133.7, 138.0, 140.9, 145.0, 166.2. Anal. Calcd. for C15H13IO3S:
C, 45.01; H, 3.27; S, 8.01. Found: C, 44.87; H, 3.15; S, 7.79.
1
3444, 1724, 1630, 1601, 1484, 1440 cm-1; H nmr (deuterio-
chloroform): δ 2.76 (br s, 1 H), 3.70 (s, 3 H), 5.69 (s, 1 H), 5.77
(s, 1 H), 6.36 (s, 1 H), 7.16-7.18 (m, 1 H), 7.27-7.28 (m, 1 H),
7.32-7.40 (m, 4 H), 7.49-7.52 (m, 1 H); 13C nmr (deuterio-
chloroform): δ 52.0, 69.3, 123.1, 125.3, 126.5, 126.8, 127.8,
127.9, 129.0, 130.2, 136.3, 138.4, 140.7, 142.2, 166.7. Anal.
Calcd. for C15H14O3S: C, 65.67; H, 5.14; S, 11.69. Found: C,
65.83; H, 4.89; S, 11.47.
Methyl (Z)-2-[1-{2-(Furan-3-yl)phenyl}-1-hydroxymethyl]-
3-iodopropenoate (2e). To a mixture of 1c (1.72 g, 10 mmoles),
methyl propiolate (0.98 mL, 11 mmoles) and Bu4NI (4.43 g, 12
mmoles) in anhydrous dichloromethane (40 mL) was added
ZrCl4 (2.80 g, 12 mmoles) at 0 °C. The mixture was stirred at 0
°C under nitrogen atmosphere for 5 hours. Then, water (20 mL)
was added and the mixture was extracted with dichloromethane
(3 × 40 mL). The combined organic layers were dried over
anhydrous magnesium sulfate and the solvent was evaporated in
Methyl 2-[1-Hydroxy-1-{2-(thiophen-2-yl)phenyl}methyl]
propenoate (2b). A mixture of 1a (1.88 g, 10 mmoles), methyl
acrylate (2.70 mL, 30 mmoles), DABCO (1.12 g, 10 mmoles)
and triethanolamine (0.93 mL, 8 mmoles) without solvent was
stirred at room temperature for 12 days. The reaction mixture

618
K. J. Jeon and K.-J. Lee
Vol 45
vacuo. The resulting mixture was chromatographed on silica gel
eluting with hexane/ethyl acetate (6:1) to produce 2.53 g (66%)
of 2e as an oil; ir (potassium bromide): 3500, 1731, 1601, 1505,
1434 cm-1; 1H nmr (deuteriochloroform): δ 2.55 (d, J = 5.2 Hz, 1
H), 3.72 (s, 3 H), 5.79 (d, J = 3.7 Hz, 1 H), 6.52-6.53 (m, 1 H),
7.07 (d, J = 1.8 Hz, 1 H), 7.31-7.40 (m, 3 H), 7.46-7.51 (m, 3
H); 13C nmr (deuteriochloroform): δ 52.0, 72.4, 87.1, 111.7,
124.0, 127.0, 128.0, 128.5, 130.3, 132.1, 137.4, 140.1, 143.0,
145.5, 166.4. Anal. Calcd. for C15H13IO4: C, 46.90; H, 3.41.
Found: C, 46.67; H, 3.37.
122.4, 125.0, 125.6, 127.9 (two), 137.9, 141.5, 143.1, 146.8,
148.0, 166.8. Anal. Calcd. for C15H11IO2S: C, 47.14; H, 2.90; S,
8.39. Found: C, 47.30; H, 2.78; S, 8.12.
Methyl 2-(4H-Indeno[1,2-b]thiophen-4-yl)propenoate (3b).
To a stirred solution of 2b (0.55 g, 2 mmoles) in carbon
tetrachloride (5 mL) was added 95% sulfuric acid (0.11 mL, 2
mmoles) at room temperature. After 5 hours, the mixture was
neutralized with saturated sodium bicarbonate solution and
extracted with dichloromethane (5 × 10 mL). The combined
organic layers were dried over anhydrous magnesium sulfate
and the solvent was evaporated in vacuo. The resulting mixture
was chromatographed on silica gel eluting with hexane/ethyl
acetate (6:1) to produce 0.31 g (61%) of 3b as a solid; mp 42-43
℃; ir (potassium bromide): 1723, 1626, 1605, 1455, 1438 cm-1;
1H nmr (deuteriochloroform): δ 3.86 (s, 3 H), 4.93 (s, 1 H), 5.44
(s, 1 H), 6.16 (s, 1 H), 7.02 (d, J = 4.9 Hz, 1 H), 7.16-7.21 (m, 1
H), 7.30 (d, J = 4.9 Hz, 1 H), 7.32-7.48 (m, 3 H); 13C nmr
(deuteriochloroform): δ 47.1, 52.2, 119.0, 122.7, 125.0, 125.2,
125.3, 127.5 (two), 138.1, 139.0, 142.7, 148.3, 149.7, 167.4.
Anal. Calcd. for C15H12O2S: C, 70.29; H, 4.72; S, 12.51. Found:
C, 69.98; H, 4.50; S, 12.29.
Methyl (Z)-2-(8H-Indeno[2,1-b]thiophen-8-yl)-3-iodoprop-
enoate (3c). To a stirred solution of 2c (0.80 g, 2 mmoles) in
carbon tetrachloride (5 mL) was added 95% sulfuric acid (0.11
mL, 2 mmoles) at room temperature. After 2 hours, the mixture
was neutralized with saturated sodium bicarbonate solution and
extracted with dichloromethane (5 × 10 mL). The combined
organic layers were dried over anhydrous magnesium sulfate
and the solvent was evaporated in vacuo. The resulting mixture
was chromatographed on silica gel eluting with hexane/ethyl
acetate (6:1) to produce 0.49 g (65%) of 3c as an oil; ir
(potassium bromide): 1728, 1606, 1588, 1487, 1453, 1436 cm-1;
1H nmr (deuteriochloroform): δ 3.90 (s, 3 H), 5.04 (s, 1 H), 7.06
(d, J = 0.9 Hz, 1 H), 7.18-7.23 (m, 1 H), 7.24 (d, J = 4.9 Hz, 1
H), 7.32-7.36 (m, 2 H), 7.38 (d, J = 4.9 Hz, 1 H), 7.50-7.53 (m,
1 H); 13C nmr (deuteriochloroform): δ 51.1, 52.2, 87.1, 118.6,
119.7, 125.1, 125.2, 127.9, 129.8, 138.7, 140.9, 145.6, 146.4,
147.1, 166.3. Anal. Calcd. for C15H11IO2S: C, 47.14; H, 2.90; S,
8.39. Found: C, 47.05; H, 2.78; S, 8.17.
Methyl 2-[1-{2-(Furan-3-yl)phenyl}-1-hydroxymethyl]
propenoate (2f). A mixture of 1c (1.72 g, 10 mmoles), methyl
acrylate (2.70 mL, 30 mmoles), DABCO (1.12 g, 10 mmoles)
and triethanolamine (0.93 mL, 8 mmoles) without solvent was
stirred at room temperature for 14 days. The reaction mixture
was diluted with water (20 mL) and extracted with dichloro-
methane (3 × 40 mL). The combined organic layers were dried
over anhydrous magnesium sulfate and the solvent was
evaporated in vacuo. The resulting mixture was chromato-
graphed on silica gel eluting with hexane/ethyl acetate (6:1) to
produce 1.57 g (61%) of 2f as an oil; ir (potassium bromide):
3437, 1722, 1631, 1506, 1439 cm-1; 1H nmr (deuterio-
chloroform): δ 2.77 (d, J = 4.3 Hz, 1 H), 3.72 (s, 3 H), 5.70 (s, 1
H), 5.83 (s, 1 H), 6.38 (s, 1 H), 6.56-6.57 (m, 1 H), 7.33-7.38
(m, 3 H), 7.47-7.52 (m, 3 H); 13C nmr (deuteriochloroform): δ
52.0, 69.3, 111.8, 124.3, 126.5, 126.9, 127.8, 128.0, 130.1,
132.2, 138.4, 140.1, 142.3, 142.8, 166.8. Anal. Calcd. for
C15H14O4: C, 69.76; H, 5.46. Found: C, 69.55; H, 5.24.
Methyl 2-[1-Hydroxy-1-{2-(pyridin-4-yl)phenyl}methyl]
propenoate (2g). A mixture of 1d (1.85 g, 10 mmoles), methyl
acrylate (2.70 mL, 30 mmoles), DABCO (1.12 g, 10 mmoles)
and triethanolamine (0.93 mL, 8 mmoles) without solvent was
stirred at room temperature for 11 days. The reaction mixture
was diluted with water (20 mL) and extracted with
dichloromethane (3 × 40 mL). The combined organic layers
were dried over anhydrous magnesium sulfate and the solvent
was evaporated in vacuo. The resulting mixture was chromato-
graphed on silica gel eluting with hexane/ethyl acetate (6:1) to
produce 2.10 g (78%) of 2g as a white solid; mp 116-117 ℃; ir
(potassium bromide): 3190, 1712, 1628, 1598, 1541, 1478,
Methyl 2-(8H-Indeno[2,1-b]thiophen-8-yl)propenoate (3d).
To a stirred solution of 2d (0.55 g, 2 mmoles) in carbon
tetrachloride (5 mL) was added 95% sulfuric acid (0.11 mL, 2
mmoles) at room temperature. After 2 hours, the mixture was
neutralized with saturated sodium bicarbonate solution and
extracted with dichloromethane (5 × 10 mL). The combined
organic layers were dried anhydrous magnesium sulfate and the
solvent was evaporated in vacuo. The resulting mixture was
chromatographed on silica gel eluting with hexane/ethyl acetate
(6:1) to produce 0.32 g (64%) of 3d as an oil; ir (potassium
1
1437, 1152, 1045 cm-1; H nmr (deuteriochloroform): δ 3.65 (s,
3 H), 3.68 (br s, 1 H), 5.61 (s, 1 H), 5.89 (s, 1 H), 6.40 (s, 1 H),
7.21-7.24 (m, 1 H), 7.35-7.52 (m, 5 H), 8.52-8.54 (m, 2 H); 13C
nmr (deuteriochloroform): δ 51.9, 68.7, 124.4, 126.1, 127.1,
128.1, 128.9, 129.6, 138.1, 138.9, 142.3, 149.0, 149.3, 166.4.
Anal. Calcd. for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found:
C, 71.12; H, 5.39; N, 5.07.
Methyl (Z)-2-(4H-Indeno[1,2-b]thiophen-4-yl)-3-iodoprop-
enoate (3a). To a stirred solution of 2a (0.80 g, 2 mmoles) in
carbon tetrachloride (5 mL) was added 95% sulfuric acid (0.11
mL, 2 mmoles) at room temperature. After 3 hour, the mixture
was neutralized with saturated sodium bicarbonate solution and
extracted with dichloromethane (5 × 10 mL). The combined
organic layers were dried over anhydrous magnesium sulfate
and the solvent was evaporated in vacuo. The resulting mixture
was chromatographed on silica gel eluting with hexane/ethyl
acetate (6:1) to produce 0.54 g (71%) of 3a as a solid; mp: 83-84
°C; ir (potassium bromide): 1731, 1605, 1581, 1455, 1433 cm-1;
1H nmr (deuteriochloroform): δ 3.85 (s, 3 H), 4.91 (s, 1 H), 6.91
(d, J = 0.9 Hz, 1 H), 7.02 (d, J = 4.9 Hz, 1 H), 7.18-7.24 (m, 1
H), 7.32 (d, J = 4.9 Hz, 1 H), 7.34-7.39 (m, 2 H), 7.45-7.48 (m,
1 H); 13C nmr (deuteriochloroform): δ 50.7, 52.1, 85.4, 119.2,
1
bromide): 1716, 1629, 1607, 1488, 1454, 1437 cm-1; H nmr
(deuteriochloroform): δ 3.90 (s, 3 H), 5.03 (s, 1 H), 5.53 (s, 1
H), 6.19 (s, 1 H), 7.16-7.22 (m, 1 H), 7.25 (d, J = 4.9 Hz, 1 H),
7.30-7.33 (m, 1 H), 7.35 (d, J = 4.9 Hz, 1 H), 7.38-7.41 (m, 1
H), 7.51-7.54 (m, 1 H); 13C nmr (deuteriochloroform): δ 47.8,
52.3, 118.5, 119.5, 124.8, 125.2, 125.3, 127.4, 129.3, 138.9,
139.2, 146.0, 147.0, 148.3, 167.2. Anal. Calcd. for C15H12O2S: C,
70.29; H, 4.72; S, 12.51. Found: C, 70.11; H, 4.50; S, 12.39.
Methyl (Z)-2-(8H-Indeno[1,2-c]furan-8-yl)-3-iodopropen-
oate (3e). To a stirred solution of 2e (0.77 g, 2 mmoles) in
carbon tetrachloride (5 mL) was added 95% sulfuric acid (0.11
mL, 2 mmoles) at room temperature. After 4 hours, the mixture
was neutralized with saturated sodium bicarbonate solution and

Mar-Apr 2008
Synthesis of 4H-Indeno[1,2-b]thiophenes, 8H-Indeno[2,1-b]- thiophenes and …
619
Fleming, I. Eds, Pergamon Press, Oxford, 1991, p 733. [d] Smith, M. B.
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W. P.; Lee, K. -J. Synthesis 2006, 963. [g] Yi, H. -W.; Park, H. W.;
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[6] Ryabov, A. N.; Gribkov, D. V.; Izmer, V. V.;
Voskoboynikov, A. Z. Organometallics 2002, 21, 2842.
[7] Grandini, C.; Camurati, I.; Guidotti, S.; Mascellani, N.;
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extracted with dichloromethane (5 × 10 mL). The combined
organic layers were dried over anhydrous magnesium sulfate
and the solvent was evaporated in vacuo. The resulting mixture
was chromatographed on silica gel eluting with hexane/ethyl
acetate (6:1) to produce 0.29 g (40%) of 3e as an oil; ir
(potassium bromide): 1728, 1613, 1548, 1482, 1451, 1433 cm-1;
1H nmr (deuteriochloroform): δ 3.84 (s, 3 H), 4.85 (s, 1 H), 6.63
(d, J = 1.8 Hz, 1 H), 6.98 (s, 1 H), 7.12-7.17 (m, 1 H), 7.28-7.40
(m, 3 H), 7.49-7.50 (m, 1 H); 13C nmr (deuteriochloroform): δ
47.7, 52.2, 86.3, 105.2, 119.7, 124.8, 124.9, 127.9, 128.6, 136.4,
139.6, 144.3, 147.6, 161.5, 166.2. Anal. Calcd. for C15H11IO3: C,
49.20; H, 3.03. Found: C, 48.87; H, 2.80.
Methyl 2-(8H-Indeno[1,2-c]furan-8-yl)propenoate (3f). To
a stirred solution of 2f (0.52 g, mmoles) in carbon tetrachloride
(5 mL) was added 95% sulfuric acid (0.11 mL, 2 mmoles) at
room temperature. After 2 hours, the mixture was neutralized
with saturated sodium bicarbonate solution and extracted with
dichloromethane (5 × 10 mL). The combined organic layers
were dried over anhydrous magnesium sulfate and the solvent
was evaporated in vacuo. The resulting mixture was chromato-
graphed on silica gel eluting with hexane/ethyl acetate (6:1) to
produce 0.18 g (38%) of 3f as an oil; ir (potassium bromide):
[9] Christopher, C. A.; Wilkerson, W. W.; Earl, R. A; US Patent
5594001; Chem. Abstr. 1997, 126, 171622.
[10a] MacDowell, D. W. H.; Patrick, T. B. J. Org. Chem. 1967, 32,
2441. [b] MacDowell, D. W. H.; Jeffries, A. T. J. Org. Chem. 1970, 35,
871. [c] MacDowell, D. W. H.; Jeffries, A. T. J. Org. Chem. 1971, 36,
1053. [d] Jeffries, A. T.; Moore, K. C.; Ondeyka, D. M.; Springsteen, A.
W.; MacDowell, D. W. H. J. Org. Chem. 1981, 46, 2885. [e]
Guillaumel, J.; Boccara, N.; Demerseman, P. J. Heterocycl. Chem. 1990,
27, 1047. [f] Sauter, F.; Dzerovicz, A. Monatsh. Chem. 1969, 100, 913.
[g] Sauter, F.; Deinhammer, W. Monatsh. Chem. 1970, 101, 544.
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1
1723, 1626, 1614, 1483, 1453, 1438 cm-1; H nmr (deuterio-
chloroform): δ 3.85 (s, 3 H), 4.87 (s, 1 H), 5.45 (s, 1 H), 6.21 (s,
1 H), 6.65 (d, J = 1.8 Hz, 1 H), 7.10-7.15 (m, 1 H), 7.28-7.40
(m, 3 H), 7.49-7.50 (m, 1 H); 13C nmr (deuteriochloroform): δ
44.3, 52.2, 105.1, 119.4, 124.6, 124.9, 125.9, 127.4, 128.2,
136.5, 137.4, 146.0, 147.1, 163.0, 166.9. Anal. Calcd. for
C15H12O3: C, 74.99; H, 5.03. Found: C, 74.82; H, 4.78.
[12] Campo, M. A.; Larock, R. C. J. Org. Chem. 2002, 67, 5616.
[13] Kashulin, I. A.; Nifant’ev, I. E. J. Org. Chem. 2004, 69,
5476.
Acknowledgement. This work was supported by the
Research Fund of Hanyang University (HY-2007-I).
[14a] Kinder, F. R.; Padwa, A. Tetrahedron Lett. 1990, 31, 6835.
[b] Padwa, A.; Kinder, F. R. J. Org. Chem. 1993, 58, 21. [c] Harrison, P.
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Hoornaert, G. J. Eur. J. Org. Chem. 2004, 2707. [e] Zhang, S. -W.;
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REFERENCES AND NOTES
*
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