An efficient novel synthesis of β-(azuleno[1,2-b]benzothienyl)-and β-(azuleno[2,1-b]benzothienyl)-α,β-unsaturated ketones by the tropylium ion-mediated intramolecular furan ring-opening reaction and X-ray investigation of methyl ketone derivative

Article abstract of DOI:10.1039/b401579g

Intramolecular reaction of 2-tropylio-3-(5-substituted 2-furyl) benzothiophenes (3), prepared from the corresponding 2-cycloheptatrienyl-3-(5- substituted 2-furyl)benzothiophenes (2), afforded the β-(azuleno[1,2-b] benzothienyl)-α,β-unsaturated ketones (4

Full text of DOI:10.1039/b401579g

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An efficient novel synthesis of ꢀ-(azuleno[1,2-b]benzothienyl)-
and ꢀ-(azuleno[2,1-b]benzothienyl)-ꢁ,ꢀ-unsaturated ketones by
the tropylium ion-mediated intramolecular furan ring-opening
reaction and X-ray investigation of methyl ketone derivative†1
Kimiaki Yamamura,*a Yuuko Houda,a Masao Hashimoto,a Takatomo Kimura,b
Makoto Kamezawab and Takehiko Otanib
a Department of Chemistry, Faculty of Science, Kobe University, Nada, Kobe 657-8501, Japan
b Konan Chemical Industry Co. Ltd., Nakagawa-cho, Takatsuki 569-0066, Japan
Received 3rd February 2004, Accepted 17th March 2004
First published as an Advance Article on the web 7th April 2004
Intramolecular reaction of 2-tropylio-3-(5-substituted 2-furyl)benzothiophenes (3), prepared from the corresponding
2-cycloheptatrienyl-3-(5-substituted 2-furyl)benzothiophenes (2), afforded the β-(azuleno[1,2-b]benzothienyl)-α,β-
unsaturated ketones (4), which are otherwise difficult to obtain, in moderate yields. The reaction involves a ring-
opening process of the furan ring by intramolecular attack of the tropylium ion onto the 2-position of the furan
ring. Similarly, β-(azuleno[2,1-b]benzothienyl)-α,β-unsaturated ketones (8) were obtained from the corresponding
3-tropylio-2-(5-substituted 2-furyl)benzothiophenes (7) albeit in lower yields. The molecular and crystal structures
of the methyl ketone derivative, 8a, are discussed on the basis of X-ray structure analysis.
variety of aromatic fused azulenic enones. Hence, we applied
Introduction
such a type of reaction to see the scope and limitations of the
Azulene and its derivatives, which are typical bicyclic non-
reaction and to construct novel heteroaromatic fused azulene
benzenoid aromatic hydrocarbons, are of interest not only from
rings. Now, this paper will report a new, facile, one-pot syn-
the fundamental viewpoint, but also for pharmaceutical and
physiological activities, and as advanced materials. Hetero-
aromatic fused ring systems containing azulene fragments are
thesis of azuleno[1,2-b]benzothiophenic enones (4) and azu-
leno[2,1-b]benzothiophenic enones (8), which include the novel
tetracyclic π-conjugated azulene nuclei cata-condensed with the
benzothiophene ring, from the corresponding 3-(2-furyl)-2-
tropyliobenzothiophenes (3) and 2-(2-furyl)-3-tropyliobenzo-
thiophenes (7), respectively. Since much attention is currently
also of interest and several kinds of such compounds have been
prepared.2 The synthetic methods were restricted to the hetero-
aromatization of the azulene or the application of Takase and
Yasunami’s azulene-synthesis using 2H-cyclohepta[b]furan-2-
focused on benzo[b]thiophenes due to their biological activ-
one and suitable enamines.3 These methods generally suffered
ities,8 compounds 4 and 8 are expected to display the interesting
from tedious multistage procedures and/or low yields, and the
biological activities. The X-ray structure of methyl ketone
synthetic difficulties have impeded progress in this area. During
derivative (8a) will be also described.
our studies on the intramolecular cyclization reaction by the
tropylium ion,4 we recently found a novel, one-pot synthetic
Results and discussion
method for tricyclic benz[a]azulenes having an α,β-unsaturated
ketone group from the corresponding o-[(2-furyl)cyclohepta-
trienyl]benzenes.5 This reaction seems to involve a furan ring-
opening reaction by intramolecular electrophilic attack of the
initially formed tropylium ion derivatives onto the 2-position of
the furan ring (Scheme 1).
Although it is well-known that 2-substituted furan deriv-
atives react with protic acid to give the corresponding 1,4-di-
ketones by a ring-opening reaction6 and a few tropylium
ion-mediated azulene syntheses have been reported7, this is the
first case of a tropylium ion-mediated furan-ring-opening reac-
tion to give the benz[a]azulene ring. The successful preparation
of benz[a]azulenic enones opened a route to the synthesis of a
Synthesis of ꢀ-(azuleno[1,2-b]benzothienyl)-ꢁ,ꢀ-unsaturated
ketones (4) and ꢀ-(azuleno[2,1-b]benzothienyl)-ꢁ,ꢀ-unsaturated
ketones (8)
The synthetic sequence leading to 4 from the readily available
3-bromobenzothiophene9 is depicted in Scheme 2.
3-Bromobenzothiophene was treated with LDA in tetra-
hydrofuran at Ϫ78 ЊC, followed by addition of powdered
tropylium tetrafluoroborate to give 3-bromo-2-cyclohepta-
trienylbenzothiophene (1) in 68% yield. The palladium()-cata-
lyzed Stille coupling reaction10 of 1 with 5-substituted 2-tri-
methylstannylfurans, which were readily obtained from the
2-substituted furans according to the previously reported
method,5a gave the corresponding 2-cycloheptatrienyl-3-(2-
furyl)benzothiophenes (2a–f ) as a pale yellow oil. The formyl
derivative (2g) was prepared from 2f and pyridinium p-toluene-
† Electronic supplementary information (ESI) available: physical
properties and the results of elementary analyses of 1, 2a–2h, 5a, 5b, 6a
and 6b. See http://www.rsc.org/suppdata/ob/b4/b401579g/
Scheme 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 1 3 – 1 4 1 8
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Scheme 2
sulfonate.11 The (phenylimino)methyl and styryl derivatives
Table 1
(2h and 2j) were prepared from the formyl derivative (2g). In
order to decrease the steric hindrance at the subsequent
hydride-abstraction process, 2 was then thermally isomerized
by sigmatropic rearrangement to an isomeric mixture of 2
and 2Ј.
Cycloheptatriene (2Ј)
R
Azulenes
Yielda
2aЈ
2bЈ
2cЈ
2dЈ
2eЈ
2fЈ
CH3
CH3CH2
CH3(CH2)3CH2
CH3(CH2)16CH2
C6H5
4a
4b
4c
4d
4e
—
64%
66%
65%
68%
54%
—
With the exception of 2f and 2fЈ, the isomeric mixture 2 and
2Ј was treated with an equimolar amount of triphenylmethyl
tetrafluoroborate at ambient temperature for 10 min., followed
by addition of dry ether, to give the corresponding 3-(2-furyl)-
2-tropyliobenzothiophenes (3) as dark-colored precipitates.
With 2f and 2fЈ, the 1,3-dioxolane ring reacted with triphenyl-
methyl tetrafluoroborate to afford a complex mixture,12 and
no tropylium ion derivatives were obtained. The structure of
3-(5-methyl-2-furyl)-2-tropyliobenzothiophene (3a) was estab-
2gЈ
2hЈ
2iЈ
CHO
C6H5N᎐CH
C6H5CH᎐CH
—
—
4i
—
—
51%
᎐
᎐
a Yields are of isolated and purified products.
1
lished by the H NMR spectrum and elemental analysis.13 The
spectra of other tropylium ion derivatives 3 were not measured
and 3 were used for the next step without further purification.
Conversion of the tropylium ion derivatives 3 to the desired
azuleno[1,2-b]benzothiophenic enones (4) was achieved by
refluxing a dichloromethane solution of 3. The results are
shown in Table 1. The described yields are based on the cyclo-
heptatrienyl derivatives 2. When the substituent on the furan
ring is an alkyl group such as methyl, ethyl, pentyl or octadecyl
group, the corresponding azuleno[1,2-b]benzothiophenic enone
4 was obtained in fairly good yields. When the substituent is
phenyl or styryl group, the azulenoid analogues of chalcone
and dibenzylideneacetone (DBA), 4e and 4i, respectively, were
obtained in slightly lower yield. With 3g and 3h, however, the
starting materials were recovered unchanged after prolonged
reaction time. The non-reactivity of 3g and 3h in this type of
reaction could be attributed to decreased nucleophilicity of the
2-position in the furan ring due to the electron-withdrawing
groups such as the (phenylimino)methyl or formyl groups.
The structures of these β-(azuleno[1,2-b]benzothiophene
1
derivatives (4) were established by their H NMR and mass
spectra as well as elemental analyses. Moreover, the present
single-crystal X-ray analysis showed that the methyl ketone
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 1 3 – 1 4 1 8
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Scheme 3
Scheme 4
Table 2
Cycloheptatriene (6Ј)
Molecular and crystal structures of 8a
Fig. 1 shows the X-ray structure of 8a with atom labeling.
R
Azulenes
Yielda
6aЈ
6bЈ
CH3
CH3CH2
8a
8b
31%
30%
a Yields are of isolated and purified products.
derivative 4a had an (E)-4-(11-azuleno[1,2-b]benzothiophenyl)-
3-buten-2-one skeleton, although the α,β-unsaturated carbonyl
group suffered some disorder to result in a somewhat ambigu-
ous structure of the moiety.14
The coupling constants between the olefinic protons on 4
were ca. 16 Hz. This shows that the trans configuration is
between the azuleno[1,2-b]benzothiophene ring and the carb-
onyl group. X-ray crystallographic analysis of 4a also supports
the trans configuration. If the above-mentioned mechanism for
the formation of 4 is correct, the azuleno[1,2-b]benzothiophene
ring and the carbonyl group should be cis to each other. This
can be explained by the assumption that the initially formed cis
isomer changes into the more stable trans isomer by the acid
generated in the course of the reaction and/or by the post-
treatment for the isolation and purification of the products.
In a similar manner as described above, other isomers, β-azu-
leno[2,1-b]benzothienyl-α,β-unsaturated ketones (8), could be
obtained from the corresponding tropylium ion derivatives (7)
(Scheme 3). The results are shown in Table 2.
However, the yields of 8 are lower than those of 4. Although
the reason for the lower yield is not yet clear at present, a likely
explanation is that, for 7, the heptafulvene-type structures (7B
and 7C) contribute appreciably to the structure (Scheme 4) and,
therefore, the electrophilicity of the tropylium ion is decreased.
The coupling constants between the olefinic protons on 8a
and 8b show that the azuleno[2,1-b]thiophene ring and the
carbonyl group are also trans to each other. A single-crystal
X-ray analysis of 8a also supports trans configuration between
the azuleno[2,1-b]thiophene ring and the carbonyl group (vide
infra).
Fig. 1 X-ray structure of 8a with atom labeling.
The result of the X-ray analysis confirmed the molecular
structure of 8a. The molecule has Cs symmetry. The C8–C9,
C9–C10, C10–C11, C11–C12, C12–C13, and C13–C14 bond
lengths in the seven-membered ring of 8a are 1.387(3), 1.389(4),
1.382(4), 1.376(4), 1.385(4), and 1.387(3) Å, respectively. Thus,
these bond lengths do not exhibit such clear bond-length
alternation as those found for azuleno[1,2-b]thiophene,15
9-phenylbenz[a]azulene16, and 4-(10-benz[a]azulenyl)-1,1,1-
triphenyl-2-butanone.17 Similar to the case of 4-(10-benz[a]azu-
lenyl)-1,1,1-triphenyl-3,4-buten-2-one,18 conjugation between
the enone moiety and the seven-membered ring seems to result
in the absence of a distinct bond-length alternation (Scheme 5).
Molecular stacking of two 8a molecules is shown in Fig. 2.
The inter-plane distance of the stacking is b/2 (ca. 3.38 Å). The
close contact suggests a certain π–π interaction between the
stacked molecules resulting in the dark greenish-brown colour
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 1 3 – 1 4 1 8
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General procedure for the synthesis of 2-cycloheptatrienyl-3-
(2-furyl)benzothiophenes (2a–2f)
All of these reactions were carried out under a nitrogen atmos-
phere. The mixture of 1 (4.5 g, 14.8 mmol), 2-substituted
5-trimethylstannylfuran5
(21
mmol),
bis(triphenyl-
phosphine)palladium() chloride (5.0 g, 7.1 mmol) and dry
tetrahydrofuran (200 cm3) was refluxed for 8 h. The solvent was
evaporated, and the residue was purified by column chromato-
graphy (silica gel, hexane–benzene (1 : 1)) to give the corre-
sponding 2-cycloheptatrienyl-3-(2-furyl)benzothiophenes (2);
The yields of 2a, 2b, 2c, 2d, 2e, and 2f were 77, 80, 62, 79, 78,
and 52%, respectively.
Scheme 5
2-Cycloheptatrienyl-3-(5-formyl-2-furyl)benzothiophene (2g)
A solution of 2f (3.00 g, 8.29 mmol) and pyridinium p-toluene-
sulfonate (0.63 g, 2.49 mmol) in acetone (50 cm3) and H2O
(5 cm3) was heated at reflux for 3 h. The solvent was evaporated
and the residue was dissolved in 100 cm3 of ether. The ether
solution was washed with 10% aqueous sodium carbonate solu-
tion, dried over anhydrous sodium sulfate, and concentrated in
vacuo. The residue was purified by short column chromato-
graphy over silica gel using benzene as eluent to give 2g (2.06 g,
78%).
Fig. 2 Stacking of 8a molecules viewed along the b axis. Symmetry
codes: a: x, y, z; b: Ϫx, y ϩ 0.5, Ϫz.
2-Cycloheptatrienyl-3-[5-(phenylimino)methyl-2-furyl]-
benzothiophene (2h)
of the crystal that is clearly different from the yellow colour of
the solution.
A mixture of 2g (1.00 g, 3.14 mmol), aniline (0.35 g, 3.77
mmol), and benzene (10 cm3) was heated at reflux for 1 h under
a nitrogen atmosphere. The reaction mixture was purified by
column chromatography over silica gel using benzene as eluent
to give 2h (2.06 g, 96%) as yellow needles.
Conclusion
We have developed an efficient synthetic method for β-(azuleno-
[1,2-b]benzothienyl-α,β-unsaturated ketones (4) and β-(azu-
leno[2,1-b]benzothienyl-α,β-unsaturated ketones (8) which are
difficult to synthesize by other methods because of the inaccess-
ibility of suitable precursors. The X-ray structure of 8a was
determined. Compound 8a shows a short intermolecular
face-to-face packing in the crystal.
2-Cycloheptatrienyl-3-(5-styryl-2-furyl)benzothiophene (2i)
To an ice-cooled mixture of 2g (0.64 g, 2.02 mmol), benzyl-
triphenylphosphonium bromide (0.88 g, 2.02 mmol), 18-crown-
6 (0.052 g, 0.20 mmol), and dichloromethane (20 cm3),
powdered potassium hydroxide (0.22 g, 4.00 mmol) was added
and then the mixture was stirred for 3 h at ambient temperature.
After the filtration of insoluble materials, the filtrate was
washed with water, and dried over anhydrous sodium sulfate.
The solvent was evaporated and the residue was purified by
column chromatography over silica gel using hexane as eluent
to give 2i as the mixture of geometrical isomers (0.49 g, 62%),
which was used for the next step without separation; m/z: 392
(Mϩ); Found: C, 82.81; H, 5.26. C27H20OS requires C, 82.62; H,
5.14%.
Experimental
All melting points were determined with a Yanaco MO JP-3
apparatus and are uncorrected. 1H NMR spectra were obtained
on a Brucker DPX-250 spectrometer (250 MHz) using tetra-
methylsilane as an internal reference. For all NMR spectra,
δ values are given in ppm and J values in Hz. The mass spectra
were determined with a Shimazdu GC-MS QP200A spectro-
meter. All dry solvents were freshly distilled over an appropriate
drying agent before use. Column chromatography was per-
formed on silica gel (Wako-gel, C-200). The elemental analyses
were performed by Miss Masuko Nishinaka, Department of
Chemistry, Faculty of Science, Kobe University.
3-Bromo-2-(5-methyl-2-furyl)benzothiophene (5a)
A mixture of 2,3-dibromobenzothiophene19(5.0 g, 17 mmol),
2-methyl-5-trimethylstannylfuran (5.15 g, 21 mmol), bis(tri-
phenylphosphine)palladium() (1.5 g, 2.14 mmol), and dry
tetrahydrofuran (50 cm3) was refluxed for 8 h under a nitrogen
atmosphere. The solvent was evaporated and the residue was
purified by column chromatography over silica gel using hexane
as eluent to give 5a (2.58 g, 52%).
The physical properties and the results of elementary analy-
ses of 1, 2a–2h, 5a, 5b, 6a, and 6b have been deposited as ESI.†
Preparation of 3-bromo-2-cycloheptatrienylbenzothiophene (1)
To a stirred solution of 3-bromobenzothiophene (7.0 g, 33
mmol) in dry tetrahydrofuran (200 cm3) was added slowly 19.8
ml of lithium diisopropylamide (2.0 M solution in heptane/
tetrahydrofuran/ethylbenzene, 39 mmol) under a nitrogen
atmosphere at Ϫ78 ЊC. After the addition was complete, the
reaction mixture was stirred at Ϫ78 ЊC for 2 h. Then powdered
tropylium tetrafluoroborate (6.2 g, 35 mmol) was added in
limited amounts. The mixture was allowed to warm to room
temperature and stirred overnight. After addition of 300 ml of
ether, the solution was then neutralized with 10% aqueous
ammonium chloride solution. The ether layer was separated,
dried over anhydrous sodium sulfate, and the solvent was evap-
orated. The residue was purified by column chromatography
(silica gel, hexane) to give 1 (6.8 g, 68%) as colourless crystals.
3-Bromo-2-(5-ethyl-2-furyl)benzothiophene (5b)
The procedure described above was used yielding 5b (42%).
3-Cycloheptatrienyl-2-(5-methyl-2-furyl)benzothiophene (6a)
To a solution of 5a (2.00 g, 6.83 mmol) in 150 cm3 of dry ether,
5.10 ml of butyllithium (1.6 M solution in hexane, 8.16 mmol)
was added slowly under a nitrogen atmosphere. After the addi-
tion was complete, the reaction mixture was stirred at Ϫ78 ЊC
for 2 h. Then powdered tropylium tetrafluoroborate (1.80 g,
10.0 mmol) was added in limited amounts. The mixture was
allowed to warm to room temperature and stirred overnight.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 1 3 – 1 4 1 8
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After addition of 100 cm3 of ether, the solution was then neu-
tralized with 10% aqueous ammonium chloride solution. The
ether layer was separated, dried over anhydrous sodium sulfate,
and the solvent was evaporated. The residue was purified by
column chromatography (silica gel, hexane) to give 6a (1.20 g,
58%) as colourless crystals.
6.95 (1H, d, J 15.9, olefin), 2.98–2.72 (2H, m, methylene), 1.86–
1.78 (2H, m, methylene), 1.48–1.38 (4H, m, methylene), 0.98
(3H, t, J 6.4); m/z: 358 (Mϩ).
(E )-1-(11-Azuleno[1,2-b]benzothiophenyl)-1-henicosen-3-one
(4d)
This compound was obtained as dark brown needles in 68%
yield; mp 82–84 ЊC (Found: C, 82.36; H, 9.05. C37H48OS
requires C, 82.17; H, 8.95%); δH(CDCl3) 8.67 (1H, d, J 10.0,
seven-membered ring), 8.56 (1H, d, J 16.0, olefin), 8.50–8.43
(1H, m, six-membered ring), 8.35 (1H, d, J 9.3, seven-mem-
bered ring), 7.98–7.89 (1H, m, six-membered ring), 7.63 (1H,
dd, J 9.8, 9.7, seven-membered ring), 7.56–7.48 (2H, m, six-
membered ring), 7.38–7.25 (2H, m, seven-membered ring), 6.99
(1H, d, J 16.0, olefin), 2.78 (2H, t, J 7.5, methylene), 1.80 (2H,
m, methylene), 1.40–1.18 (30H, m, methylene), 0.88 (3H, t,
J 7.2); m/z: 540 (Mϩ).
3-Cycloheptatrienyl-2-(5-ethyl-2-furyl)benzothiophenes (6b)
The procedure described above was used yielding 6b (82%) as
colourless crystals.
Thermal isomerization of 2 and 6 to 2Ј and 6Ј, respectively
The xylene solution of 2 was refluxed for 5 h. The solvent was
evaporated in vacuo and the residue was short-chromato-
graphed over silica gel to give the isomeric mixture 2Ј in almost
quantitative yield. In a similar manner, 6 was thermally isomer-
ized to the isomeric mixture 6Ј.
(E )-3-(11-Azuleno[1,2-b]benzothiophenyl)-1-phenyl-2-propen-
1-one (4e)
General procedure for the synthesis of azuleno[1,2-b]benzothio-
phenic enones (4) and azuleno[2,1-b]benzothiophenic enones (8)
A solution of 2Ј (0.526 mmol) in 5 cm3 of dry dichloromethane
was added to a solution of triphenylmethyl tetrafluoroborate
(180 mg, 0.545 mmol) in dry dichloromethane (10 cm3) at 0 ЊC
and was stirred for 10 min. Then, 200 cm3 of dry ether was
added and stirred for 10 min. 3-(2-Furyl)2-tropyliobenzothio-
phene (3), which separated out as dark-colored precipitates,
was collected by filtration and washed with dry ether. This
product was dissolved in 80 cm3 of dichloromethane and the
solution was refluxed for 1 h. The solvent was removed under
reduced pressure and the residue was purified by column chro-
matography (silica gel, hexane-ethyl acetate (3 : 1)) and re-
crystallization from toluene to afford 4. In a similar manner, 8
was obtained from the corresponding 3-cycloheptatrienyl-2-
(2-furyl)benzothiophenes 6Ј.
This compound was obtained as dark green needles in 54%
yield; mp 140–142 ЊC (Found: C, 82.51; H, 4.30. C25H16OS
requires C, 82.39; H, 4.42%); δH (CDCl3) 8.85 (1H, d, J 16.0,
olefin), 8.76 (1H, d, J 10.2, seven-membered ring), 8.60–8.57
(1H, m, six-membered ring), 8.39 (1H, d, J 9.5, seven-
membered ring), 8.10 (2H, dd, J 8.3, 7.8, phenyl), 7.98–7.94
(1H, m, six-membered ring), 7.78 (1H, d, J 16.0, olefin), 7.68
(1H, dd, J 9.9, 9.8, seven-membered ring), 7.59–7.48 (5H,
m, six-membered ring & phenyl), 7.36–7.22 (2H, m, seven-
membered ring); m/z: 364 (Mϩ).
1-(11-Azuleno[1,2-b]benzothiophenyl)-5-phenyl-1,4-pentadien-
3-one (4i)
This compound was obtained as dark reddish-brown needles in
51% yield; mp 52–54 ЊC (Found: C, 82.88; H, 4.43. C27H18OS
requires C, 83.05; H, 4.65%); δH (CDCl3) 8.78 (1H, d, J 15.3,
olefin), 8.77 (1H, d, J 11.2, seven-membered ring), 8.62–8.56
(1H, m, six-membered ring), 8.41 (1H, d, J 9.2, seven-
membered ring), 8.01–7.96 (1H, m, six-membered ring), 7.82
(1H, d, J 15.9, olefin), 7.75–7.63 (3H, m, seven-membered ring
& phenyl), 7.57–7.53 (2H, m, six-membered ring), 7.47–7.31
(5H, m, seven-membered ring & phenyl), 7.35 (1H, d, J 15.9,
olefin), 7.17 (1H, d, J 15.9, olefin); m/z: 390 (Mϩ).
(E )-4-(11-Azuleno[1,2-b]benzothiophenyl)-3-buten-2-one (4a)
This compound was obtained as black prisms in 64% yield; mp
166–169 ЊC (Found: C, 79.29; H, 4.77. C20H14OS requires C,
79.44; H, 4.67%); δH(CDCl3) 8.63 (1H, d, J 9.8, seven-mem-
bered ring), 8.43 (1H, d, J 16.0, olefin), 8.45–8.39 (1H, m, six-
membered ring), 8.27 (1H, d, J 9.2, seven-membered ring),
7.94–7.87 (1H, m, six-membered ring), 7.60 (1H, dd, J 10.2, 9.8,
seven-membered ring), 7.53–7.46 (2H, m, six-membered ring),
7.29 (2H, dd, J 10.2, 9.8, seven-membered ring), 6.91 (1H, d,
J 16.0, olefin), 2.49 (3H, s, methyl); m/z: 302 (Mϩ).
(E )-4-(11-Azuleno[2,1-b]benzothiophenyl)-3-buten-2-one (8a)
This compound was obtained as dark greenish-brown prisms in
31% yield; mp 119–121 ЊC (Found: C, 79.26; H, 4.43. C20H14OS
requires C, 79.44; H, 4.67%); δH (CDCl3) 8.82 (1H, d, J 9.5,
seven-membered ring), 8.59 (1H, d, J 10.1, seven-membered
ring), 8.35 (1H, d, J 7.7, six-membered ring), 8.32 (1H,
d, J 15.6, olefin), 7.96 (1H, d, six-membered ring), 7.73
(1H, dd, J 9.8, 9.8, seven-membered ring), 7.55 (dd, 1H,
J = 10.0, 7.3 Hz, seven-membered ring), 7.44 (dd, 1H, J = 9.8,
9.6 Hz, seven-membered ring), 7.57–7.40 (2H, m, six-membered
ring), 6.70 (1H, d, J 15.6, olefin), 2.47 (3H, s, methyl); m/z: 302
(Mϩ).
(E )-5-(11-Azuleno[1,2-b]benzothiophenyl)-4-penten-3-one (4b)
This compound was obtained as dark green prisms in 66%
yield; mp 138–141 ЊC (Found: C, 79.58; H, 5.22. C21H16OS
requires C, 79.71; H, 5.10%); δH (CDCl3) 8.67 (1H, d, J 10.0,
seven-membered ring), 8.56 (1H, d, J 16.0, olefin), 8.50–8.43
(1H, m, six-membered ring), 8.37 (1H, d, J 9.2, seven-mem-
bered ring), 8.02–7.92 (1H, m, six-membered ring), 7.66 (1H,
dd, J 10.0, 9.7, seven-membered ring), 7.59–7.49 (2H, m, six-
membered ring), 7.38–7.22 (2H, m, seven-membered ring), 7.00
(1H, d, J 16.0, olefin), 2.82 (2H, q, J 7.3, methylene), 1.28 (3H,
t, J 7.3, methyl); m/z: 316 (Mϩ).
(E )-5-(11-Azuleno[2,1-b]benzothiophenyl)-4-penten-3-one (8b)
(E )-1-(11-Azuleno[1,2-b]benzothiophenyl)-1-octen-3-one (4c)
This compound was obtained as dark green prisms in 30%
yield; mp 91–93 ЊC (Found: C, 79.88; H, 5.08. C21H16OS
requires C, 79.71; H, 5.10%); δH (CDCl3) 8.78 (1H, d, J 8.6,
seven-membered ring), 8.58 (1H, d, J 10.2, seven-membered
ring), 8.37 (1H, d, J 15.3, olefin), 8.33 (1H, d, J 7.3, six-
membered ring), 7.94 (1H, d, J 7.9, six-membered ring), 7.70–
7.39 (5H, m, six- & seven-membered rings), 6.71 (1H, d, J 15.5,
olefin), 2.77 (2H, q, J 7.4, methylene), 1.27 (3H, t, J 7.4,
methyl); m/z: 316 (Mϩ).
This compound was obtained as dark green needles in 65%
yield; mp 65–70 ЊC (Found: C, 80.28; H, 6.38. C24H22OS
requires C, 80.41; H, 6.19%); δH(CDCl3) 8.60 (1H, d, J 10.2,
seven-membered ring), 8.51 (1H, d, J 15.9, olefin), 8.46–8.41
(1H, m, six-membered ring), 8.36 (1H, d, J 9.2, seven-
membered ring), 7.96–7.90 (1H, m, six-membered ring), 7.62
(1H, dd, J 9.9, 9.8, seven-membered ring), 7.53–7.46 (2H, m,
six-membered ring), 7.30–7.18 (2H, m, seven-membered ring),
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 1 3 – 1 4 1 8
1417

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X-ray analysis of 8a
References and notes
Dark greenish-brown prismatic crystals of 8a (C20H14OS,
FW = 302.4) were grown from a toluene solution of the com-
pound and a single crystal having dimensions of 0.06 × 0.18 ×
0.26 mm3 was used for the single crystal X-ray diffraction
experiment. A SMART 1000 diffractometer and Mo-Kα
radiation (λ = 0.71073 Å, 2θmin = 4.2Њ and 2θmax = 54.2Њ) were
used for the experiment. Crystal structure analysis was carried
out by using a program package SHELXL-97.20 At first, we
1 Preliminary communication, Y. Houda, M. Sasabe, X. Bo,
H. Takagi and K. Yamamura, J. Heterocycl. Chem., 2000, 37, 1363.
2 (a) T. Okujima, T. Terazono, S. Ito, N. Morita and T. Asao,
Heterocycles, 2001, 54, 667; (b) T. D. Lash and S. T. Chaney, Angew.
Chem., Int. Ed. Engl., 1997, 36, 839; (c) K. Fujimori, T. Fujita,
K. Yamane, M. Yasunami and K. Takase, Chem. Lett., 1983, 1721;
(d ) K. Yamane, K. Fujimori and S. Ichikawa, Chem. Lett., 1982,
707; (e) T. Morita, T. Nakadate and K. Takase, Heterocycles, 1981,
15, 835 and references therein.
3 (a) M. Yasunami, S. Miyoshi, N. Kanegae and K. Takase, Bull.
Chem. Soc. Jpn., 1993, 66, 892; (b) M. Yasunami, A. Chen, P. W.
Yang and K. Takase, Chem. Lett., 1980, 579; (c) P. W. Yang,
M. Yasunami and K. Takase, Tetrahedron Lett., 1971, 4725.
4 (a) K. Yamamura, T. Yamane, H. Takagi and H. Miyake,
Heterocycles, 1997, 45, 467; (b) K. Yamamura, H. Miyake,
S. Nakatsuji and I. Murata, Chem. Lett., 1992, 1213;
(c) K. Yamamura, H. Miyake, K. Azumi and I. Murata, Chem.
Lett., 1989, 1511.
5 (a) M. Sasabe, Y. Houda, H. Takagi, T. Sugane, X. Bo and
K. Yamamura, J. Chem. Soc., Perkin Trans. 1, 2000, 3786;
(b) K. Yamamura, T. Yamane, M. Hashimoto, H. Miyake and
S. Nakatsuji, Tetrahedron Lett., 1996, 37, 4965.
6 (a) M. V. Sargent and T. M. Cresp, “Comprehensive Organic
Chemistry”, Pergamon Press, London, 1979, vol. 4, p. 693; (b) E. J.
Stamhuis, W. Drenth and H. Van Den Berg, Recl. Trav. Chim.
Pays-Bas, 1964, 83, 167.
7 (a) D. A. Becker and R. L. Danheiser, J. Am. Chem. Soc., 1989,
111, 389; (b) N. Ott and D. Rewicki, Angew. Chem., Int. Ed. Engl.,
1982, 21, 68; (c) K. Hafner, H. W. Riedel and D. J. M. Danielisz,
Angew. Chem., Int. Ed. Engl., 1963, 2, 214.
8 G. W. Gribble and T. L. Gilchrist, Heterocycl. Chem., 2002, 14, 102;
G. W. Gribble and T. L. Gilchrist, Heterocycl. Chem., 2001, 13, 98.
9 J. Szmuszkovicz and F. J. Modest, J. Am. Chem. Soc., 1950, 72, 571.
10 (a) J. K. Stille, Angew. Chem., Int. Ed. Engl., 1986, 25, 508;
(b) A. Dondoni, A. R. Mastellari, A. Medici, E. Negrini and
P. Pedrini, Synthesis, 1986, 757; (c) V. N. Kalinin, Synthesis, 1992,
413; (d ) T. N. Mitchell, Synthesis, 1992, 803.
¯
assumed four space groups, P21/m, P21, Pm and P1 to solve
the structure. In the cases of the last three space groups, the
structures could be solved by direct methods and subse-
quent refinements of them by methods similar to that described
below gave the following results: R(F) for data with I > 2σ(I ),
wR2 for all reflections and S were 0.0412, 0.1152, and
1.041 for P21-model; 0.0437, 0.1216, and 1.035 for Pm-model;
¯
0.0477, 0.1255, and 1.041 for P1-model. In the case of the
first space group (P21/m), the direct method failed to solve
the structure. Then, an initial structure for this space group
was derived by the following method; the y coordinates of
the non-hydrogen atom in the P21-model were replaced by
1/4, since the model showed pseudo mirror symmetry. In this
trial, subsequent refinements by full matrix least-squares
method gave reasonable positions of the non-hydrogen
atoms. Then, all of the hydrogen positions were determined
from different Fourier maps. Non-hydrogen and hydrogen
atoms were included in the refinement by applying anisotropic
and isotropic displacement parameters, respectively, to give
the final results given below. Monoclinic space group of P21/m
with a = 10.287(2) Å, b = 6.764(1) Å, c = 11.472(2) Å,
β = 111.162(3)Њ, V = 744.3(2) Å3, Z = 2, Dcalc = 1.349 g cmϪ3
,
µ = 0.216 mmϪ1. Out of 3962 total data (R(int) = 0.0322)
with absorption correction by SADABS, unique 1608 reflec-
tions were used, parameters being 173. R(F) = 0.0413 for
1315 data with I > 2σ(I ), wR2 = 0.1173 and S = 1.027 for all
reflections. Although the R factors of the P21-model were
comparable with those of the P21/m-model, the benzene moiety
and the positions of the H atoms in the former model exhibited
significant deformations. Therefore, the P21/m-mode was
adopted.‡
11 R. Sterzycki, Synthesis, 1979, 724.
12 D. H. Barton, P. D. Magnus, G. Smith, G. Streckert and D. Zurr,
J. Chem. Soc., Perkin Trans. 1, 1992, 542.
13 Mp > 200 ЊC (Found: C, 61.28; H, 4.08. C20H15BF4OS requires C,
61.56; H, 3.87%); δH (CD2Cl2) 8.94–8.82 (6H, m, tropylium ring),
8.22–8.19 (1H, m, six-membered ring), 8.08–8.02 (1H, m, six-
membered ring), 7.67–7.55 (2H, m, six-membered ring), 6.85 (1H, d,
J 3.3, furan ring), 6.33 (1H, d, J 3.3, furan ring), 2.20 (3H, s, methyl).
14 Crystal data for 4a. Orthorhombic, space group Pca21, a =
18.905(3), b = 4.772(1), c = 33.799(5) Å, V = 3049.0(8) Å3, Z = 8.
Final R(F) = 0.0829 for 2635 data >2σ(I ) and R(F2) = 0.2371 for all
5720 reflections.
15 S. Kashino, M. Haisa, K. Fujimori and K. Yamane,
Acta Crystallogr., Sect. B, 1982, 38, 2729.
16 M. Buhl, W. Kozminski, A. Linden, D. Nanz, D. Sperandio and
H.-J. Hansen, Helv. Chim. Acta, 1996, 79, 837.
Acknowledgements
This work was supported in part by a Grant-in-Aid for
Scientific Research (No. 13640579) from the Ministry of
Education and Technology, Japan. The authors thank Miss
Masuko Nishinaka, Faculty of Science, Kobe University, for
elemental analyses.
17 K. Yamamura, Y. Kitagawa and M. Hashimoto, Anal. Sci., 2002, 18,
499.
18 K. Yamamura, Y. Kitagawa and M. Hashimoto, Anal. Sci., 2002, 18,
373.
‡ CCDC reference numbers 226170 (8a) and 232411 (4a). See http://
www.rsc.org/suppdata/ob/b4/b401579g/ for crystallographic data in.cif
or other electronic format.
19 W. Reid, Chem. Ber., 1995, 88, 38.
20 G. M. Sheldrick, SHELXL-97, Program for the Refinement of
Crystal Structures, Univ. Goettingen, Germany, 1997.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 4 1 3 – 1 4 1 8
1418