Preparation of new nitrogen-bridged heterocycles. 59.1) syntheses and intramolecular interactions of 3-(acylmethylthio)- and 3-[(3-ethoxycarbonyl-2-propenyl)thio]thieno[3,4-b]indolizine derivatives

Article abstract of DOI:10.1248/cpb.55.95

Various thieno[3,4-b]indolizine derivatives having an acylmethylthio or (3-ethoxycarbonyl-2-propenyl)thio group at the 3-position which could not be obtained by a conventional method were prepared by a new procedure using cyanoethyl group as a protecting

Full text of DOI:10.1248/cpb.55.95

January 2007
Chem. Pharm. Bull. 55(1) 95—101 (2007)
95
Preparation of New Nitrogen-Bridged Heterocycles. 59.1) Syntheses and
Intramolecular Interactions of 3-(Acylmethylthio)- and 3-[(3-
Ethoxycarbonyl-2-propenyl)thio]thieno[3,4-b]indolizine Derivatives
Akikazu KAKEHI,* Hiroyuki SUGA, and Hirohide ISOGAI
Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University; Wakasato, Nagano
380–8553, Japan. Received September 15, 2006; accepted October 30, 2006; published online November 6, 2006
Various thieno[3,4-b]indolizine derivatives having an acylmethylthio or (3-ethoxycarbonyl-2-propenyl)thio
group at the 3-position which could not be obtained by a conventional method were prepared by a new procedure
using cyanoethyl group as a protecting group and their intramolecular arene–p interactions were investigated. In
1
the H-NMR spectra of these thieno[3,4-b]indolizines, the low-field shifts (d 0.10—0.33 ppm) for the 5-protons
were observed in comparison with those of 3-(methylthio)thieno[3,4-b]indolizines as a standard. The UV spectra
also exhibited a characteristic absorption band at 425—445 nm attributable to the arene–p interaction but their
intensities were generally lower than those of 3-(arylmethylthio)thieno[3,4-b]indolizines. In their X-ray analyses,
the anti conformation for 3-(acylmethylthio)thieno[3,4-b]indolizines and the gauche one for the 3-(3-ethoxycar-
bonyl-2-propenyl)thio derivatives were exhibited.
Key words thieno[3,4-b]indolizine; arene–p interaction; gauche form; anti form; UV spectra; X-ray analysis
In our previous papers we described the syntheses of vari- gauche and anti forms were low (1—1.5 kcal/mol).8) This
ous 3-(arylmethylthio)- and 3-(allylthio- or propargylthio)- fact means that all of 3-(R-methylthio)thieno[3,4-b]indolizine
thieno[3,4-b]indolizine derivatives and their intramolecular derivatives prefer inherently the gauche forms over the anti
arene–arene or arene–p interactions through a sulfide ones and its G1 form with an intramolecular interaction
1
spacer.2—5) From their H-NMR and UV spectral analyses should be naturally the most favorable. To verify this order
and the molecular calculations (Mopac PM3)6) we deduced (see Fig. 2) in the conformational stability of sulfide deriva-
that a specific conformation (gauche 1 form (G1)) which tives we planned to investigate further the conformation of
makes such intramolecular interaction possible is more pre- other derivatives of this series. In this paper we report the
dominant than the other conformations (gauche 2 (G2), anti syntheses of 3-(acylmethylthio)-, and 3-[(3-ethoxycarbonyl-
1 (A1), anti 2 (A2), and so on) (see Fig. 1).2—5,7) We initially 2-propenyl)thio]thieno[3,4-b]indolizine derivatives, which
thought that the conformational stability of sulfide deriva- were inaccessible from our conventional method,2—5) and
tives have the same order (antiꢀgaucheꢀꢀeclipse) as that of their intramolecular arene–p interactions.
1,2-disubstituted ethanes, but only in the G1 form stabilized
by such interaction its stability exceed that of the anti form Results and Discussion
(gaucheꢀanti). However, the fact that even the crystals of the
Syntheses of 3-[(2-Cyanoethyl)thio]thieno[3,4-b]in-
gauche 2 form (G2), in which the intramolecular interaction dolizine Derivatives We tried first to prepare the title com-
was impossible, were found by X-ray analysis5) allowed us to pounds such as 4 from the procedures described earlier by
suspect the conventional order for these conformations. The us.2—5) However, the S-alkylation of 3-(1-pyridinio)thio-
Mopac PM36) calculations for simple sulfides, which any at- phene-2-thiolates (1a—f) with some acylmethyl halides such
tractive interaction is absent, such as ethyl methyl sulfide, as chloroacetone (2b), phenacyl bromides (2c—e), ethyl bro-
benzyl methyl sulfide, and ethyl phenyl sulfide made clear moacetate (2f), and ethyl 4-bromocrotonate (2g), followed by
our predicted order (gaucheꢀantiꢀꢀeclipse), but the differ- the treatment of the resulting pyridinium salts (3) with a base
ences in the formation energies between the optimized and then dehydrogenating agent gave only complex mixtures
involving small amounts of the expected products (4) (Chart
1). So we next examined the syntheses of thieno[3,4-b]in-
dolizines bearing a protected thiol group at the 3-position.
The S-alkylation of 1a—f with 3-bromopropionitrile (2a) in
acetone in the presence of excess sodium iodide and the
treatment of the resulting pyridinium salts (3a—f) with 1,8-
diazabicyclo[5.4.0]undec-2-ene (DBU) and then chloranil in
chloroform at 0 °C provided the corresponding 3-[(2-cya-
Fig. 1. Principal Conformations of 3-(R-Methylthio)thieno[3,4-b]in-
dolizine
Fig. 2. Conformational Stability of Sulfides, R1SCH2R2
Chart 1
∗ To whom correspondence should be addressed. e-mail: akakehi@gipwc.shinshu-u.ac.jp
© 2007 Pharmaceutical Society of Japan

96
Vol. 55, No. 1
noethyl)thio]thieno[3,4-b]indolizine derivatives (5a—f) in
59—81% yields respectively. These results are summarized
in Chart 2.
The structures of products (5a—f) were determined by
1
their elemental analyses and the IR, UV, and H-NMR spec-
tral analyses. In particular, the IR spectra of 5a—f showed a
saturated cyano absorption band at 2247—2259 cmꢁ1, to-
gether with an ester carbonyl band (1669—1678 cmꢁ1) and a
arylcarbonyl band (1611—1628 cmꢁ1). The absorption bands
near 330, 485, and 505 nm (shoulder) in the UV spectra of
5a—f were almost the same as those of 3-(alkylthio)-
thieno[3,4-b]indolizines which do not have intramolecular
arene–arene or arene–p interactions.9) The chemical shifts
Chart 2
1
and the signal patterns in the H-NMR spectra (Tables 1, 2)
Table 1. 1H-NMR Spectral Data for 7-Unsubstituted Thieno[3,4-b]indolizines
Noa,b)
C-5
C-6
C-7
C-8
R1CH2S
9-CO2Et
d (5-H)
d (6-H)
7sc)
5a
5b
5c
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
8.96
9.19
9.19
9.17
9.28
9.27
9.27
9.15
9.14
9.14
9.07
9.08
9.08
9.07
9.08
9.09
9.26
9.26
9.27
9.14
9.14
9.14
6.73
6.77
6.77
6.77
6.74
6.76
6.76
6.67
6.66
6.68
6.66
6.67
6.66
6.66
6.67
6.67
6.74
6.76
6.76
6.71
6.73
6.72
7.31
8.20
8.23
8.24
8.23
8.21
8.20
8.20
8.18
8.18
8.17
8.18
8.17
8.18
8.19
8.20
8.20
8.22
8.21
8.24
8.22
8.23
8.22
2.68
2.72, 3.22
2.71, 3.20
2.73, 3.21
2.24, 3.90
0.97, 3.61
0.97, 3.68
0.98, 3.75
1.02, 3.76
0.95, 3.64
1.01, 3.74
1.01, 3.74
1.02, 3.75
1.02, 3.75
1.01, 3.75
0.97, 3.67
1.01, 3.73
1.02, 3.74
1.01, 3.63
1.04, 3.76
1.03, 3.76
0.96, 3.65
1.01, 3.76
1.02, 3.77
0.96, 3.67
1.04, 3.78
1.03, 3.77
0.00
ꢁ0.23
ꢁ0.23
ꢁ0.21
ꢁ0.32
ꢁ0.31
ꢁ0.31
ꢁ0.19
ꢁ0.18
ꢁ0.18
ꢁ0.11
ꢁ0.12
ꢁ0.12
ꢁ0.11
ꢁ0.12
ꢁ0.13
ꢁ0.30
ꢁ0.30
ꢁ0.31
ꢁ0.18
ꢁ0.18
ꢁ0.18
0.00
ꢁ0.04
ꢁ0.04
ꢁ0.04
ꢁ0.01
ꢁ0.03
ꢁ0.03
0.06
0.07
0.05
0.07
0.06
0.07
0.07
0.06
0.06
ꢁ0.01
ꢁ0.03
ꢁ0.03
0.02
0.00
0.01
d)
d)
7.39
7.37
7.36
2.25, 3.91
2.25, 3.91
7.36
d)
4.46, 7.1—8.0
4.46, 7.2—8.0
4.44, 7.2—8.0
4.36, 7.3—8.0
4.37, 7.3—8.0
4.37, 7.3—8.0
4.38, 7.3—8.0
4.37, 7.3—8.0
4.37, 7.3—8.0
1.12, 3.69, 4.07
1.12, 3.70, 4.08
1.14, 3.72, 4.07
1.17, 3.67, 4.05, 5.61, 6.93
1.17, 3.67, 4.07, 5.61, 6.95
1.17, 3.66, 4.07, 5.62, 6.95
d)
d)
d)
d)
d)
d)
d)
d)
d)
d)
d)
d)
d)
d)
7m
7n
7o
7p
7q
7r
a) The proton signals for the 1-arylcarbonyl group appeared in the range of d 7.1—8.0 as multiplets. b) The coupling constants are as follows; J5,6ꢂJ6.7ꢂ7.0 Hz,
7,8ꢂ9.0 Hz, J6,8ꢂ2.0 Hz, JEtꢂ7.0 Hz. c) Standard. d) Overlapped with the aromatic proton signals.
J
Table 2. 1H-NMR Spectral Data for 7-Methylthieno[3,4-b]indolizines
Noa,b)
C-5
C-6
C-7
C-8
R1CH2S
9-CO2Et
d (5-H)
d (6-H)
8sc)
5d
5e
5f
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8.84
9.05
9.05
9.04
9.15
9.15
9.16
9.01
9.01
9.02
8.96
8.96
8.97
8.94
8.94
8.94
9.17
9.13
9.15
9.00
9.00
9.00
6.58
6.60
6.63
6.61
6.59
6.61
6.62
6.49
6.51
6.52
6.50
6.51
6.54
6.50
6.50
6.51
6.60
6.59
6.60
6.56
6.59
6.58
2.40
2.41
2.42
2.41
2.40
2.41
2.42
2.39
2.39
2.40
2.40
2.41
2.42
2.40
2.40
2.42
2.42
2.42
2.42
2.39
2.41
2.42
8.00
8.02
8.03
8.02
7.99
7.99
2.67
2.70, 3.19
2.71, 3.20
2.70, 3.20
2.24, 3.89
0.95, 3.56
0.95, 3.64
1.00, 3.73
1.00, 3.72
0.94, 3.62
0.99, 3.70
1.00, 3.72
0.95, 3.61
0.97, 3.65
0.99, 3.71
0.94, 3.60
1.00, 3.72
0.99, 3.70
0.95, 3.61
0.97, 3.69
0.99, 3.71
0.96, 3.66
0.99, 3.74
1.00, 3.74
0.96, 3.66
1.00, 3.73
0.99, 3.70
0.00
ꢁ0.21
ꢁ0.21
ꢁ0.20
ꢁ0.31
ꢁ0.31
ꢁ0.32
ꢁ0.17
ꢁ0.17
ꢁ0.18
ꢁ0.12
ꢁ0.12
ꢁ0.13
ꢁ0.10
ꢁ0.10
ꢁ0.10
ꢁ0.33
ꢁ0.29
ꢁ0.31
ꢁ0.16
ꢁ0.16
ꢁ0.16
0.00
ꢁ0.02
ꢁ0.05
ꢁ0.03
ꢁ0.01
ꢁ0.03
ꢁ0.04
0.09
0.07
0.06
0.08
0.07
0.04
0.08
0.08
0.07
ꢁ0.02
ꢁ0.01
ꢁ0.02
0.02
ꢁ0.01
0.00
2.24, 3.89
2.42, 3.90
8.01
d)
4.42, 7.3—8.0
4.42, 7.3—8.0
4.43, 7.3—8.0
4.34, 7.3—8.0
4.37, 7.3—8.0
4.36, 7.3—8.0
4.35, 7.3—8.0
4.34, 7.3—8.0
4.35, 7.3—8.0
1.14, 3.71, 4.09
1.12, 3.69, 4.07
1.00, 3.69, 4.07
1.16, 3.66, 4.06, 5.61, 6.94
1.18, 3.65, 4.06, 5.63, 6.93
1.18, 3.66, 4.05, 5.64, 6.92
d)
d)
7.97
7.95
7.97
7.97
d)
d)
8m
8n
8o
8p
8q
8r
8.04
8.00
8.02
8.00
8.01
8.00
a) The proton signals for the 1-arylcarbonyl group appeared in the range of d 7.1—8.0 as multiplets. b) The coupling constants are as follows; J5,6ꢂ7.0 Hz, J6,8ꢂ2.0 Hz,
JEtꢂ7.0 Hz. c) Standard. d) Overlapped with the aromatic proton signals.

January 2007
97
Chart 3
Fig. 3. ORTEP Drawings (the Over-View (a) and the Side-View (b)) of 8b
Chart 4
of 5a—f are also very similar to those of thieno[3,4-b]in-
dolizines prepared previously by us2—5) except the signals of
the 3-substituent, which appeared near d 2.20 (2H, t,
Jꢂ7.0 Hz, CH2CN) and 3.20 (2H, t, Jꢂ7.0 Hz, SCH2). Inter-
estingly, a weak low field shift (d 0.20—0.23 ppm) for the 5- Fig. 4. ORTEP Drawings (the Over-View (a) and the Side-View (b)) of 8e
proton in these molecules (5a—f) was observed, suggesting
some participation of the G1 conformation.
1584—1638 cmꢁ1, together with a characteristic carbonyl
Syntheses of 3-(Acylmethylthio)-, and 3-[(3-Ethoxycar- band derived from the alkylating agents (2b—g) employed
bonyl-2-propenyl)thio]thieno[3,4-b]indolizine Derivatives here. The UV spectra of 7a—r and 8a—r exhibited an ab-
As might be expected, the deprotection of 3-[(2-cyanoethyl)- sorption band near 440 nm attributable to the arene–p inter-
thio]thieno[3,4-b]indolizine derivatives (5a—c) by treatment action, but their molar extinction coefficients were generally
with potassium tert-butoxide in dimethylformamide (DMF) weaker than those observed for 3-(arylmethylthio)thieno[3,4-
and the reactions of the resulting potassium thieno[3,4-b]in- b]indolizines.2—4) The characteristic bands of 3-acetonylthio
dolizine-3-thiolate (6a—c) with chloroacetone (2b) afforded (7a, b, m—o) and 3-ethoxycarbonylthio derivatives (8m, n)
3-(acetonylthio)thieno[3,4-b]indolizine derivatives (7a—c) in were particularly weak and only a shoulder was observed.
good yields. Similar reactions of 6a—c with phenacyl The chemical shifts for the pyridine ring protons of 7a—r
bromide (2c), 4-chlorophenacyl bromide (2d), 4-bromo- and 8a—r in the 1H-NMR spectra were compared with those
phenacyl bromide (2e), ethyl bromoacetate (2f), and ethyl of ethyl 1-benzoyl-3-(methylthio)thieno[3,4-b]indolizine-9-
4-bromocrotonate (2g) provided the corresponding 3- carboxylate (7s (ArꢂPh, R1ꢂH)) and its 7-methyl deriva-
phenacylthio- (7d—f), 3-(4-chlorophenacylthio)- (7g—i), 3- tives 8s (ArꢂPh, R1ꢂH)2,3,9) which do not have any intramol-
(4-bromophenacylthio)- (7j—l), 3-(ethoxycarbonylmethyl- ecular interactions (see Tables 1, 2). As seen in these tables,
thio)- (7m—o), 3-[(3-ethoxycarbonyl-2-propenyl)thio]- the 5-protons in 7a—r and 8a—r appeared at lower mag-
thieno[3,4-b]indolizine derivatives (7p—r) in moderate to netic fields than those of 7s and 8s respectively; the low field
good yields respectively (Chart 3). Similarly, the deprotec- shifts for the 5-proton were in the range of d 0.10—0.33 ppm
tion of the 7-methyl compounds (5e—f), followed by the S- and these values were comparable to those (d 0.10—0.34) in
alkylations of the resulting potassium 7-methylthieno[3,4- 3-(allylthio)- and 3-(propargylthio)thieno[3,4-b]indolizines.5)
b]indolizine-3-thiolates (6d—f) with 2b—g gave the corre- The X-ray analyses of 3-(acetonylthio)- (8b) and 3-
sponding products (8a—r) in 61—99% yields (Chart 4).
(phenacylthio)thieno[3,4-b]indolizine (8e) showed only the
The elemental analyses for these products (7a—r, 8a—r) A1 form, while that of 3-[(3-ethoxycarbonyl-2-propenyl)-
were in good accord with our proposed structures. The IR thio]thieno[3,4-b]indolizine (7p) exhibited the G1 form. The
spectra of 7a—r and 8a—r showed an ester carbonyl band ORTEP drawings10) of compounds 8b, e and 7p are shown in
near 1680 cmꢁ1 and a shifted ketone carbonyl band at Figs. 3—5. From the above results we could deduced the

98
Vol. 55, No. 1
small differences in the conformational stability of their
gauche and anti forms.
Conformational Analyses by Mopac PM3 Calcula-
tions6) Since molecular calculations for some 3-(2-
propenylthio)thieno[3,4-b]indolizine derivatives were already
described,5) we performed the Mopac PM3 (precise) calcula-
tions for the optimized geometry of 3-(acylmethylthio)-
thieno[3,4-b]indolizines (7a—o, 8a—o) to obtain further
conformational information. From theoretical consideration
and the NMR spectral and X-ray analyses, we classified their
possible conformers for compounds (7a, d, m) as seen in Fig.
6. As shown in this figure, there are 3 principal conforma-
tions for each Forms A and B. Furthermore, each principal
form is subdivided into 4 conformations for a total of 12 con-
formations for both Forms, but only the subdivided ones for
Form A were shown. In the Mopac calculations (Table 3) for
these conformers the preferences of Form A over Form B
and of the gauche form over the anti one were exhibited, but
Fig. 5. ORTEP Drawings (the Over-View (a) and the Side-View (b)) of 7p
Fig. 6. Principal Conformations of 7a, d, m and the Subdivided Comformations for Form A
Table 3. Mopac PM3 (Pricise) Calculation for 3-(Acylmethylthio)thieno[3,4-b]indolizines
No
7a
Form
d (G1CF-SVa))
d (G1CB-SVa))
d (G1TF-SVa))
d (G1TB-SVa))
d (G2CF-SVa))
d (G2CB-SVa))
A
B
A
B
A
B
0
ꢁ0.31616
0.10654
ꢁ0.22287
0.32223
ꢁ0.23457
0.13561
0.61173
0.94197
0.61755
1.18061
0.62409
0.97686
0.72023
0.83383
ꢁ0.32735
1.06583
0.51114
0.86542
0.57730
0.49503
0.83979
0.79369
0.73079
0.09266
0.33898
0.25959
0.84461
0.57246
0.46743
0.29681
0.30446
0
0.56361
0
7d
7m
0.32556
No
7a
Form
d (G2TF-SVa))
d (G2TB-SVa))
d (A1CF-SVa))
d (A1CB-SVa))
d (A1TF-SVa))
d (A1TB-SVa))
A
B
A
B
A
B
1.24103
0.77756
1.28817
1.58782
1.20574
0.69800
1.11019
0.72946
1.65032
1.03189
1.26289
0.76257
to G1b)
1.33927
to G1b)
0.08601
to G1b)
1.36884
to G1b)
1.06926
to G1b)
1.16516
to G1b)
1.09807
to G1b)
1.96084
to G1b)
0.67672
to G1b)
1.99289
to G1b)
1.85232
to G1b)
0.59165
to G1b)
1.88510
7d
7m
a) Optimized formation energy for G1CF conformation of form A: ꢁ44.17875 kcal/mol for 7a; ꢁ8.71871 kcal/mol for 7d; ꢁ89.20690 kcal/mol for 7m. b) Conversion to
G1 conformer.

January 2007
99
an equimolar amount of alkylating agent (2) was added and allowed to react
for a further 5 h at room temperature. The reaction mixture was acidified
with diluted hydrochloric acid and the precipitated substances were collected
by suction. The crude product was purified by column chromatography on
alumina using chloroform as an eluent. The solvent was evaporated and the
the energy differences were expectedly small.
In conclusion, we synthesized some 3-(acylmethylthio)-
and 3-[(3-ethoxycarbonyl-2-propenyl)thio]thieno[3,4-b]in-
dolizines by using a new procedure via the S-protected 3-
thiol derivatives, and could observe their arene–p interac- recrystallization from chloroform–ethanol gave the corresponding products
1
(7a—r, 8a—r). The H-NMR spectral data for compounds (7a—r, 8a—r)
tions.
listed in Tables 1 and 2, and other data are as follows:
Experimental
Ethyl 3-Acetonylthio-1-benzoylthieno[3,4-b]indolizine-9-carboxylate (7a):
Melting points were measured with a Yanagimoto micromelting point ap- 97% (from 5a and chloroacetone (2b)), red flakes, mp 153—154 °C. IR
paratus and were not corrected. Microanalyses were carried out on a Perkin- (KBr) cmꢁ1: 1715, 1684, 1608. UV lmax (CHCl3) nm (log e): 327 (shoul-
Elmer 2400 elemental analyzer. The 1H-NMR spectra were determined with der), 443 (shoulder), 479 (3.84), ca. 500 (shoulder). Anal. Calcd for
a Hitachi R-600 spectrometer (60 MHz) in deuteriochloroform with tetra-
methylsilane used as the internal standard; the chemical shifts are expressed
C23H19NO4S2: C, 63.14; H, 4.38; N, 3.20. Found: C, 63.22; H, 4.27; N, 3.22.
Ethyl 3-Acetonylthio-1-(4-chlorobenzoyl)thieno[3,4-b]indolizine-9-car-
in d values. The IR and UV spectra were taken with JASCO FT/IR-5300 IR boxylate (7b): 88% (from 5b, 2b), red needles, mp 145—146 °C. IR (KBr)
and SHIMADZU UV-2450 spectrophotometers, respectively.
cmꢁ1: 1717, 1686, 1611. UV lmax (CHCl3) nm (log e): 327 (shoulder), 445
Preparation of Ethyl 1-Arylcarbonyl-3-(2-cyanoethylthio)thieno[3,4- (shoulder), 483 (3.90), ca. 500 (shoulder). Anal. Calcd for C23H18ClNO4S2:
b]indolizine-9-carboxylates. General Method A mixture of 1-(pyri- C, 58.53; H, 3.84; N, 2.97. Found: C, 58.60; H, 3.78; N, 2.96.
dinio)thiophene-2-thiolate (1, 2 mmol), 3-bromopropanenitrile (2, 2.2
mmol), and sodium iodide (2 g) in acetone (30 ml) was kept at 40 °C in a
Ethyl 3-Acetonylthio-1-(4-bromobenzoyl)thieno[3,4-b]indolizine-9-car-
boxylate (7c): 85% (from 5c, 2b), red needles, mp 166—167 °C. IR (KBr)
water bath under occasional stirring until the spot of the material (1) disap- cmꢁ1: 1727, 1676, 1620. UV lmax (CHCl3) nm (log e): 328 (shoulder), 443
peared by TLC monitoring (0.5—1 d). After S-alkylation was completed, the (3.73), 483 (3.81), ca. 500 (shoulder). Anal. Calcd for C23H18BrNO4S2: C,
resulting solution was concentrated at reduced pressure and the residue was 53.49; H, 3.51; N, 2.71. Found: C, 53.55; H, 3.30; N, 2.86.
washed three times with 10 ml portions of ether to remove any unaltered
Ethyl 1-Benzoyl-3-(phenacylthio)thieno[3,4-b]indolizine-9-carboxylate
alkylating agent. Without further purification the resulting mixture involving (7d): 78% (from 5a and phenacyl bromide (2c)), red needles, mp 162—
pyridinium salt (3) was dissolved in chloroform (30 ml) and the solution was 163 °C. IR (KBr) cmꢁ1: 1690, 1665, 1607. UV lmax (CHCl3) nm (log e): 328
treated with DBU (0.40 g, 2.6 mmol) under stirring in an ice bath for 10 min
and then with chloranil (0.492 g, 2 mmol) under the same conditions for an-
other 5 h. The reaction mixture was concentrated at reduced pressure and the
(shoulder), 425 (3.74), 470 (3.63), ca. 500 (shoulder). Anal. Calcd for
C28H21NO4S2: C, 67.31; H, 4.24; N, 2.80. Found: C, 67.37; H, 4.21; N, 2.77.
Ethyl 1-(4-Chlorobenzoyl)-3-(phenacylthio)thieno[3,4-b]indolizine-9-car-
residue was separated by column chromatography on alumina using chloro- boxylate (7e): 84% (from 5b, 2c), red needles, mp 148—149 °C. IR (KBr)
form as an eluent. The reddish chloroform layers of product (5) were com- cmꢁ1: 1684, 1624. UV lmax (CHCl3) nm (log e): 328 (shoulder), 431 (3.73),
bined and concentrated at reduced pressure. Recrystallization of the crude
472 (3.63), ca. 500 (shoulder). Anal. Calcd for C28H20ClNO4S2: C, 62.97; H,
product from ethanol afforded the corresponding ethyl 1-arylcarbonyl-3-(2- 3.77; N, 2.62. Found: C, 63.04; H, 3.74; N, 2.58.
cyanoethylthio)thieno[3,4-b]indolizine-9-carboxylate. The 1H-NMR spectral
Ethyl 1-(4-Bromobenzoyl)-3-(phenacylthio)thieno[3,4-b]indolizine-9-car-
data for these compounds (5a—f) are shown in Tables 1 and 2, and some boxylate (7f): 78% (from 5c, 2c), red needles, mp 163—165 °C. IR (KBr)
other results and properties are as follows:
Ethyl 1-Benzoyl-3-(2-cyanoethylthio)thieno[3,4-b]indolizine-9-carboxy- 472 (3.67), ca. 500 (shoulder). Anal. Calcd for C28H20BrNO4S2: C, 58.13; H,
cmꢁ1: 1676, 1612. UV lmax (CHCl3) nm (log e): 327 (shoulder), 431 (3.77),
late (5a): 65% (from 1a and 3-bromopropanenitrile (2a)), orange needles,
3.48; N, 2.42. Found: C, 58.23; H, 3.47; N, 2.33.
Ethyl 1-Benzoyl-3-(4-chlorophenacylthio)thieno[3,4-b]indolizine-9-car-
mp 156—157 °C. IR (KBr) cmꢁ1: 2253, 1672, 1628. UV lmax (CHCl3) nm
(log e): 329 (4.03), 485 (3.94), ca. 510 (shoulder). Anal. Calcd for boxylate (7g): 77% (from 5a and 4-chlorophenacyl bromide (2d)), red nee-
C23H18N2O3S2: C, 63.57; H, 4.18; N, 6.45. Found: C, 63.87; H, 3.92; N, dles, mp 144—145 °C. IR (KBr) cmꢁ1: 1688, 1667, 1624. UV lmax (CHCl3)
6.38.
nm (log e): 327 (shoulder), 427 (3.74), 471 (3.63), ca. 500 (shoulder). Anal.
Ethyl 1-(4-Chlorobenzoyl)-3-(2-cyanoethylthio)thieno[3,4-b]indolizine-9- Calcd for C28H20ClNO4S2: C, 62.97; H, 3.77; N, 2.62. Found: C, 62.94; H,
carboxylate (5b): 69% (from 1b, 2a), orange needles, mp 153—154 °C. IR
3.78; N, 2.65.
(KBr) cmꢁ1: 2251, 1678, 1622. UV lmax (CHCl3) nm (log e): 328 (3.97),
Ethyl 1-(4-Chlorobenzoyl)-3-(4-chlorophenacylthio)thieno[3,4-b]in-
484 (3.89), ca. 509 (shoulder). Anal. Calcd for C23H17ClN2O3S2: C, 58.90; dolizine-9-carboxylate (7h): 68% (from 5b, 2d), red needles, mp 205—
H, 3.65; N, 5.97. Found: C, 59.04; H, 3.76; N, 5.72.
Ethyl 1-(4-Bromobenzoyl)-3-(2-cyanoethylthio)thieno[3,4-b]indolizine-9- (shoulder), 431 (3.76), 471 (3.64), ca. 500 (shoulder). Anal. Calcd for
207 °C. IR (KBr) cmꢁ1: 1680, 1613. UV lmax (CHCl3) nm (log e): 327
carboxylate (5c): 66% (from 1c, 2a), red needles, mp 153—154 °C. IR
(KBr) cmꢁ1: 2259, 1672, 1626. UV lmax (CHCl3) nm (log e): 329 (4.07),
485 (3.99), ca. 508 (shoulder). Anal. Calcd for C23H17BrN2O3S2: C, 53.81;
H, 3.34; N, 5.46. Found: C, 53.90; H, 3.34; N, 5.36.
C28H19Cl2NO4S2: C, 59.16; H, 3.37; N, 2.46. Found: C, 59.26; H, 3.30; N,
2.43.
Ethyl 1-(4-Bromobenzoyl)-3-(4-chlorophenacylthio)thieno[3,4-b]in-
dolizine-9-carboxylate (7i): 72% (from 5c, 2d), red needles, mp 202—
Ethyl 1-Benzoyl-3-(2-cyanoethylthio)-7-methylthieno[3,4-b]indolizine-9- 203 °C. IR (KBr) cmꢁ1: 1682, 1611. UV lmax (CHCl3) nm (log e): 327
carboxylate (5d): 60% (from 1d, 2a), red prisms, mp 150—151 °C. IR (KBr)
(shoulder), 432 (3.75), 473 (3.65), ca. 500 (shoulder). Anal. Calcd for
C28H19BrClNO4S2: C, 54.87; H, 3.12; N, 2.29. Found: C, 54.64; H, 2.98; N,
cmꢁ1: 2251, 1669, 1613. UV lmax (CHCl3) nm (log e): 329 (4.13), 482
(4.01), ca. 504 (shoulder). Anal. Calcd for C24H20N2O3S2: C, 64.26; H, 4.49; 2.29.
N, 6.25. Found: C, 64.45; H, 4.45; N, 6.10.
Ethyl 1-Benzoyl-3-(4-bromophenacylthio)thieno[3,4-b]indolizine-9-car-
Ethyl 1-(4-Chlorobenzoyl)-3-(2-cyanoethylthio)-7-methylthieno[3,4-b]in- boxylate (7j): 78% (from 5a and 4-bromophenacyl bromide (2e)), red flakes,
dolizine-9-carboxylate (5e): 59% (from 1e, 2a), red prisms, mp 164—
mp 140—141 °C. IR (KBr) cmꢁ1: 1689, 1667, 1624. UV lmax (CHCl3) nm
(log e): 327 (shoulder), 434 (3.72), 477 (3.66), ca. 500 (shoulder). Anal.
165 °C. IR (KBr) cmꢁ1: 2247, 1671, 1611. UV lmax (CHCl3) nm (log e): 319
(4.13), 329 (4.13), 484 (4.03), ca. 506 (shoulder). Anal. Calcd for Calcd for C28H20BrNO4S2: C, 58.13; H, 3.48; N, 2.42. Found: C, 58.16; H,
C24H19ClN2O3S2: C, 59.68; H, 3.97; N, 5.80. Found: C, 59.86; H, 3.99; N, 3.40; N, 2.47.
5.59.
Ethyl 3-(4-Bromophenacylthio)-1-(4-chlorobenzoyl)thieno[3,4-b]in-
Ethyl 1-(4-Bromobenzoyl)-3-(2-cyanoethylthio)-7-methylthieno[3,4-b]in- dolizine-9-carboxylate (7k): 79% (from 5b, 2e), red needles, mp 214—
dolizine-9-carboxylate (5f): 81% (from 1f, 2a), red flakes, mp 160—163 °C. 215 °C. IR (KBr) cmꢁ1: 1680, 1613. UV lmax (CHCl3) nm (log e): 328
IR (KBr) cmꢁ1: 2247, 1671, 1611. UV lmax (CHCl3) nm (log e): 329 (4.03),
(shoulder), 434 (3.74), 478 (3.67), ca. 500 (shoulder). Anal. Calcd for
485 (4.05), ca. 507 (shoulder). Anal. Calcd for C24H19BrN2O3S2: C, 54.65; C28H19BrClNO4S2: C, 54.87; H, 3.12; N, 2.29. Found: C, 54.97; H, 3.02; N,
H, 3.63; N, 5.31. Found: C, 54.79; H, 3.70; N, 5.10.
Preparation of Ethyl 1-Arylcarbonyl-3-(R-thio)thieno[3,4-b]indoli-
2.29.
Ethyl 1-(4-Bromobenzoyl)-3-(4-bromophenacylthio)thieno[3,4-b]in-
zine-9-carboxylates. General Method A mixture of 3-[(2-cyanoethyl)- dolizine-9-carboxylate (7l): 80% (from 5c, 2e), red needles, mp 212—
thio]thieno[3,4-b]indolizine (5, 1 mmol), potassium tert-butoxide (168 mg,
1.5 mmol), and DMF (3 ml) was heated at 80 °C in a water bath for 15 min,
214 °C. IR (KBr) cmꢁ1: 1680, 1613. UV lmax (CHCl3) nm (log e): 328
(shoulder), 434 (3.79), 477 (3.72), ca. 500 (shoulder). Anal. Calcd for
and then the generated acrylonitrile was completely evaporated at reduced C28H19Br2NO4S2: C, 51.16; H, 2.91; N, 2.13. Found: C, 51.14; H, 2.83; N,
pressure. To the solution of potassium thieno[2,3-b]indolizine-3-thiolate (6) 2.22.

100
Vol. 55, No. 1
Ethyl 1-Benzoyl-3-(ethoxycarbonylmethylthio)thieno[3,4-b]indolizine-9- C29H22ClNO4S2: C, 63.55; H, 4.05; N, 2.56. Found: C, 63.65; H, 3.88; N,
carboxylate (7m): 99% (from 5a and ethyl bromoacetate (2f)), red prisms, 2.43.
mp 102—103 °C. IR (KBr) cmꢁ1: 1730, 1676, 1622. UV lmax (CHCl3) nm
(log e): 318 (4.06), 328 (4.05), 440 (shoulder), 480 (3.92), ca. 500 (shoul-
Ethyl 1-(4-Chlorobenzoyl)-3-(4-chlorophenacylthio)-7-methylthieno[3,4-
b]indolizine-9-carboxylate (8h): 78% (from 5e, 2d), red needles, mp 201—
der). Anal. Calcd for C24H21NO5S2: C, 61.65; H, 4.53; N, 3.00. Found: C, 202 °C. IR (KBr) cmꢁ1: 1676, 1638. UV lmax (CHCl3) nm (log e): 329
61.68; H, 4.49; N, 3.01.
(shoulder), 437 (3.80), 479 (shoulder), ca. 500 (shoulder). Anal. Calcd for
Ethyl 1-(4-Chlorobenzoyl)-3-(ethoxycarbonylmethylthio)thieno[3,4-b]in- C29H21Cl2NO4S2: C, 59.79; H, 3.63; N, 2.40. Found: C, 59.93; H, 3.52; N,
dolizine-9-carboxylate (7n): 88% (from 5b, 2f), red needles, mp 122—
124 °C. IR (KBr) cmꢁ1: 1723, 1665, 1630. UV lmax (CHCl3) nm (log e): 328
2.37.
Ethyl 1-(4-Bromobenzoyl)-3-(4-chlorophenacylthio)-7-methylthieno[3,4-
(shoulder), 438 (shoulder), 482 (3.94), ca. 500 (shoulder). Anal. Calcd for b]indolizine-9-carboxylate (8i): 61% (from 5f, 2d), red needles, mp 196—
C24H20ClNO5S2: C, 57.42; H, 4.02; N, 2.79. Found: C, 57.71; H, 3.93; N, 197 °C. IR (KBr) cmꢁ1: 1676, 1638. UV lmax (CHCl3) nm (log e): 329
2.50.
(shoulder), 437 (3.81), 479 (shoulder), ca. 500 (shoulder). Anal. Calcd for
Ethyl 1-(4-Bromobenzoyl)-3-(ethoxycarbonylmethylthio)thieno[3,4-b]in- C29H21BrClNO4S2: C, 55.56; H, 3.38; N, 2.23. Found: C, 55.66; H, 3.28; N,
dolizine-9-carboxylate (7o): 82% (from 5c, 2f), red flakes, mp 84—85 °C. 2.23.
IR (KBr) cmꢁ1: 1713, 1688, 1626. UV lmax (CHCl3) nm (log e): 327 (shoul-
Ethyl 1-Benzoyl-3-(4-bromophenacylthio)-7-methylthieno[3,4-b]in-
der), 440 (shoulder), 483 (3.94), ca. 500 (shoulder). Anal. Calcd for dolizine-9-carboxylate (8j): 78% (from 5d, 2e), red prisms, mp 148—
C24H20BrNO5S2: C, 52.75; H, 3.69; N, 2.56. Found: C, 52.86; H, 3.65; N, 150 °C. IR (KBr) cmꢁ1: 1671, 1637. UV lmax (CHCl3) nm (log e): 328
2.49.
(shoulder), 433 (3.90), 476 (shoulder), ca. 500 (shoulder). Anal. Calcd for
Ethyl 1-Benzoyl-3-[(3-ethoxycarbonyl-2-propenyl)thio]thieno[3,4-b]in- C29H22BrNO4S2: C, 58.79; H, 3.74; N, 2.36. Found: C, 58.78; H, 3.73; N,
dolizine-9-carboxylate (7p): 63% (from 5a and ethyl 4-bromocrotonate 2.38.
(2g)), red prisms, mp 96—97 °C. IR (KBr) cmꢁ1: 1715, 1678, 1622. UV
Ethyl 3-(4-Bromophenacylthio)-1-(4-chlorobenzoyl)-7-methylthieno[3,4-
lmax (CHCl3) nm (log e): 326 (shoulder), 437 (3.80), 477 (3.82), ca. 500 b]indolizine-9-carboxylate (8k): 61% (from 5e, 2e), red needles, mp 212—
(shoulder). Anal. Calcd for C26H23NO5S2: C, 63.27; H, 4.70; N, 2.84. Found: 213 °C. IR (KBr) cmꢁ1: 1676, 1638. UV lmax (CHCl3) nm (log e): 329
C, 63.17; H, 4.70; N, 2.94.
(shoulder), 438 (3.81), 479 (shoulder), ca. 500 (shoulder). Anal. Calcd for
Ethyl 1-(4-Chlorobenzoyl)-3-[(3-ethoxycarbonyl-2-propenyl)thio]thieno- C29H21BrClNO4S2: C, 55.56; H, 3.38; N, 2.23. Found: C, 55.61; H, 3.29; N,
[3,4-b]indolizine-9-carboxylate (7q): 65% (from 5b, 2g), red needles, mp
127—128 °C. IR (KBr) cmꢁ1: 1715, 1672, 1622. UV lmax (CHCl3) nm
(log e): 326 (shoulder), 435 (3.84), 477 (3.78), ca. 500 (shoulder). Anal.
2.26.
Ethyl 1-(4-Bromobenzoyl)-3-(4-bromophenacylthio)-7-methylthieno[3,4-
b]indolizine-9-carboxylate (8l): 72% (from 5f, 2e), red needles, mp 210—
Calcd for C26H22ClNO5S2: C, 59.14; H, 4.20; N, 2.65. Found: C, 58.98; H, 211 °C. IR (KBr) cmꢁ1: 1676, 1638. UV lmax (CHCl3) nm (log e): 329
4.12; N, 2.56.
(shoulder), 437 (3.80), 480 (shoulder), ca. 500 (shoulder). Anal. Calcd for
Ethyl 1-(4-Bromobenzoyl)-3-[(3-ethoxycarbonyl-2-propenyl)thio]thieno- C29H21Br2NO4S2: C, 51.88; H, 3.15; N, 2.09. Found: C, 51.90; H, 3.11; N,
[3,4-b]indolizine-9-carboxylate (7r): 60% (from 5c, 2f), red needles, mp
117—118 °C. IR (KBr) cmꢁ1: 1717, 1674, 1622. UV lmax (CHCl3) nm
(log e): 326 (shoulder), 434 (3.83), 476 (3.78), ca. 500 (shoulder). Anal.
2.11.
Ethyl 1-Benzoyl-3-(ethoxycarbonylmethylthio)-7-methylthieno[3,4-b]in-
dolizine-9-carboxylate (8m): 96% (from 5d, 2f), red needles, mp 101—
Calcd for C26H22BrNO5S2: C, 54.55; H, 3.87; N, 2.45. Found: C, 54.71; H, 102 °C. IR (KBr) cmꢁ1: 1734, 1674, 1613. UV lmax (CHCl3) nm (log e): 328
3.73; N, 2.43.
(shoulder), 445 (shoulder), 482 (3.90), ca. 500 (shoulder). Anal. Calcd for
Ethyl 3-Acetonylthio-1-benzoyl-7-methylthieno[3,4-b]indolizine-9-car- C25H23NO5S2: C, 62.35; H, 4.81; N, 2.91. Found: C, 62.58; H, 4.80; N, 2.68.
boxylate (8a): 96% (from 5d, 2b), red prisms, mp 144—145 °C. IR (KBr)
cmꢁ1: 1719, 1678, 1638. UV lmax (CHCl3) nm (log e): 328 (shoulder), 438
(3.75), 474 (shoulder), ca. 500 (shoulder). Anal. Calcd for C24H21NO4S2: C,
63.84; H, 4.69; N, 3.10. Found: C, 63.84; H, 4.66; N, 3.13.
Ethyl 1-(4-Chlorobenzoyl)-3-(ethoxycarbonylmethylthio)-7-methylthi-
eno[3,4-b]indolizine-9-carboxylate (8n): 80% (from 5e, 2f), red needles, mp
135—136 °C. IR (KBr) cmꢁ1: 1721, 1676, 1632. UV lmax (CHCl3) nm
(log e): 328 (shoulder), 448 (shoulder), 482 (3.90), ca. 500 (shoulder). Anal.
Ethyl 3-Acetonylthio-1-(4-chlorobenzoyl)-7-methylthieno[3,4-b]in- Calcd for C25H22ClNO5S2: C, 58.19; H, 4.30; N, 2.71. Found: C, 58.13; H,
dolizine-9-carboxylate (8b): 80% (from 5e, 2b), red prisms, mp 160—
4.41; N, 2.75.
161 °C. IR (KBr) cmꢁ1: 1719, 1680, 1637. UV lmax (CHCl3) nm (log e): 329
Ethyl 1-(4-Bromobenzoyl)-3-(ethoxycarbonylmethylthio)-7-methylthieno-
(shoulder), 439 (3.81), 474 (shoulder), ca. 500 (shoulder). Anal. Calcd for [3,4-b]indolizine-9-carboxylate (8o): 99% (from 5f, 2f), red needles, mp
C24H20ClNO4S2: C, 59.31; H, 4.15; N, 2.88. Found: C, 59.30; H, 4.00; N, 134—135 °C. IR (KBr) cmꢁ1: 1719, 1674, 1632. UV lmax (CHCl3) nm
3.04.
(log e): 329 (shoulder), 445 (3.83), 481 (3.86), ca. 500 (shoulder). Anal.
Ethyl 3-Acetonylthio-1-(4-bromobenzoyl)-7-methylthieno[3,4-b]in- Calcd for C25H22BrNO5S2: C, 53.57; H, 3.96; N, 2.50. Found: C, 53.84; H,
dolizine-9-carboxylate (8c): 99% (from 5f, 2b), red prisms, mp 148—
3.94; N, 2.43.
149 °C. IR (KBr) cmꢁ1: 1719, 1678, 1637. UV lmax (CHCl3) nm (log e): 330
Ethyl 1-Benzoyl-3-[(3-ethoxycarbonyl-2-propenyl)thio]-7-methylthieno-
(shoulder), 439 (3.82), 473 (shoulder), ca. 500 (shoulder). Anal. Calcd for [3,4-b]indolizine-9-carboxylate (8p): 73% (from 5d, 2g), red prisms, mp
C24H20BrNO4S2: C, 54.34; H, 3.80; N, 2.64. Found: C, 54.41; H, 3.72; N, 141—142 °C. IR (KBr) cmꢁ1: 1715, 1676, 1622. UV lmax (CHCl3) nm
2.65.
(log e): 327 (shoulder), 435 (3.89), 474 (shoulder), ca. 500 (shoulder). Anal.
Ethyl 1-Benzoyl-7-methyl-3-(phenacylthio)thieno[3,4-b]indolizine-9-car- Calcd for C27H25NO5S2: C, 63.88; H, 4.96; N, 2.76. Found: C, 64.07; H,
boxylate (8d): 93% (from 5d, 2c), red needles, mp 141—142 °C. IR (KBr)
cmꢁ1: 1694, 1674, 1612. UV lmax (CHCl3) nm (log e): 329 (shoulder), 432
(3.80), 477 (shoulder), ca. 500 (shoulder). Anal. Calcd for C29H23NO4S2: C,
67.81; H, 4.51; N, 2.73. Found: C, 67.87; H, 4.53; N, 2.64.
4.92; N, 2.61.
Ethyl 1-(4-Chlorobenzoyl)-3-[(3-ethoxycarbonyl-2-propenyl)thio]-7-
methylthieno[3,4-b]indolizine-9-carboxylate (8q): 60% (from 5e, 2g), red
prisms, mp 138—139 °C. IR (KBr) cmꢁ1: 1715, 1672, 1622. UV lmax
Ethyl 1-(4-Chlorobenzoyl)-7-methyl-3-(phenacylthio)thieno[3,4-b]in- (CHCl3) nm (log e): 328 (shoulder), 439 (3.91), 474 (shoulder), ca. 500
dolizine-9-carboxylate (8e): 83% (from 5e, 2c), red prisms, mp 165—
167 °C. IR (KBr) cmꢁ1: 1680, 1671, 1638. UV lmax (CHCl3) nm (log e): 328
(shoulder), 432 (3.84), 478 (shoulder), ca. 500 (shoulder). Anal. Calcd for
(shoulder). Anal. Calcd for C27H24ClNO5S2: C, 59.83; H, 4.46; N, 2.52.
Found: C, 59.91; H, 4.45; N, 2.51.
Ethyl 1-(4-Bromobenzoyl)-3-[(3-ethoxycarbonyl-2-propenyl)thio]-7-
C29H22ClNO4S2: C, 63.55; H, 4.05; N, 2.56. Found: C, 63.52; H, 4.24; N, methylthieno[3,4-b]indolizine-9-carboxylate (8r): 74% (from 5f, 2f), red
2.39.
prisms, mp 104—106 °C. IR (KBr) cmꢁ1: 1715, 1674, 1622. UV lmax
Ethyl 1-(4-Bromobenzoyl)-7-methyl-3-(phenacylthio)thieno[3,4-b]in- (CHCl3) nm (log e): 327 (shoulder), 440 (3.88), 474 (shoulder), ca. 500
dolizine-9-carboxylate (8f): 78% (from 5f, 2c), red needles, mp 170—
171 °C. IR (KBr) cmꢁ1: 1694, 1674, 1618. UV lmax (CHCl3) nm (log e): 328
(shoulder), 437 (3.81), 479 (shoulder), ca. 500 (shoulder). Anal. Calcd for
(shoulder). Anal. Calcd for C27H24BrNO5S2: C, 55.29; H, 4.12; N, 2.39.
Found: C, 55.42; H, 3.98; N, 2.40.
Crystallography of Ethyl 1-Benzoyl-3-[(3-ethoxycarbonyl-2-pro-
C29H22BrNO4S2: C, 58.79; H, 3.74; N, 2.36. Found: C, 59.00; H, 3.55; N, penyl)thio]thieno[3,4-b]indolizine-9-carboxylate (7p) A red prismatic
2.34. single crystal (0.12ꢃ0.36ꢃ0.42 mm) grown from CHCl3–ethanol was used
Ethyl 1-Benzoyl-3-(4-chlorophenacylthio)-7-methylthieno[3,4-b]in- for the unit-cell determinations and data collection by a Rigaku AFC5S
dolizine-9-carboxylate (8g): 73% (from 5d, 2d), red needles, mp 144—
four-circle diffractometer with graphite-monochromated MoKa radiation
(lꢂ0.71069 Å). The crystal data of these compounds are as follows:
145 °C. IR (KBr) cmꢁ1: 1674, 1636. UV lmax (CHCl3) nm (log e): 328
(shoulder), 437 (3.80), 478 (shoulder), ca. 500 (shoulder). Anal. Calcd for 7p: C26H23NO5S2; Mꢂ493.59; monoclinic, space group P21/n (#14), Zꢂ4

January 2007
101
tached at the idealized position and not refined. The final R- and Rw-factors
after full-matrix least-squares refinements were 0.074 and 0.066 for 2058
(Iꢀ2.00s(I)) observed reflections, respectively.
with aꢂ14.455(4) Å, bꢂ11.811(5) Å, cꢂ15.705(3) Å, bꢂ115.00(1)°; Vꢂ
2430(1) Å3 and Dcalc.ꢂ1.349 g/cm3. All calculations were performed using
the teXsan package.11) The structure was solved by a direct method (SIR).12)
The non-hydrogen atoms were refined anisotropically, and the hydrogen
atoms were attached at the idealized position and not refined. The final R-
and Rw-factors after full-matrix least-squares refinements were 0.082 and
0.075 for 1808 (Iꢀ2.00s(I)) observed reflections, respectively.
Crystallography of Ethyl 3-Acetonylthio-1-(4-chlorobenzoyl)-7-
methylthieno[3,4-b]indolizine-9-carboxylate (8b) A red prismatic single
crystal (0.06ꢃ0.42ꢃ0.84 mm) grown from CHCl3–ethanol was used for
the unit-cell determinations and data collection by a Rigaku AFC5S four-
circle diffractometer with graphite-monochromated MoKa radiation
(lꢂ0.71069 Å). Crystal data of these compounds are as follows: 8b:
C24H20ClNO4S2; Mꢂ486.00; monoclinic, space group P21/a (#14), Zꢂ4
with aꢂ14.31(1) Å, bꢂ11.13(1) Å, cꢂ15.06(1) Å, bꢂ100.80(6)°; Vꢂ
2355(3) Å3 and Dcalc.ꢂ1.371 g/cm3. All calculations were performed using
the teXsan package.11) The structure was solved by a direct method (SIR).12)
The non-hydrogen atoms were refined anisotropically, and the hydrogen
atoms were attached at the idealized position and not refined. The final R-
and Rw-factors after full-matrix least-squares refinements were 0.071 and
0.071 for 2192 (Iꢀ2.00s(I)) observed reflections, respectively.
References and Notes
1) For part 58 of this series, see Kakehi A., Suga H., Kaneko Y., Fujii T.,
Tanaka N., Chem. Pharm. Bull., 53, 1430—1438 (2005).
2) Kakehi A., Ito S., Suga H., Miwa T., Mori T., Kobayashi T., Heterocy-
cles, 57, 17—20 (2002).
3) Kakehi A., Ito S., Suga H., Miwa T., Mori T., Fujii T., Tanaka N.,
Kobayashi T., Chem. Pharm. Bull., 51, 75—84 (2003).
4) Kakehi A., Suga H., Kako T., Fujii T., Tanaka N., Kobayashi T., Chem.
Pharm. Bull., 51, 1246—1252 (2003).
5) Kakehi A., Suga H., Kaneko Y., Fujii T., Tanaka N., Chem. Pharm.
Bull., 53, 1430—1438 (2005).
6) “WinMOPAC (Version 3.0),” Fujitsu Corporation.
7) The presentation of each conformation is for the sulfide bond in these
molecules.
8) The formation energies (FEg and FEa) for the opitimized gauche and
anti conformations are as follows: ethyl methyl sulfide (FEgꢂ
ꢁ15.1451 kcal/mol and FEaꢂꢁ14.1033 kcal/mol); benzyl methyl sul-
fide (FEgꢂ17.9939 kcal/mol and FEaꢂ19.4272 kcal/mol); ethyl
phenyl sulfide (FEgꢂ18.8116 kcal/mol and FEaꢂ20.2082).
9) Kakehi A., Ito S., Suga H., Yasuraoka K., Heterocycles, 54, 185—200
(2001).
10) Johnson C. K., “ORTEP II, Report ORNL-5138,” Oak Ridge National
Laboratory, Oak Ridge, Tennessee, 1976.
11) teXsan for Windows version 1.06: Crystal Structure Analysis Package,
Molecular Structure Corporation (1997-9).
Crystallography of Ethyl 1-(4-Chlorobenzoyl)-7-methyl-3-(phen-
acylthio)thieno[3,4-b]indolizine-9-carboxylate (8e) A red dark prismatic
single crystal (0.20ꢃ0.62ꢃ0.62 mm) grown from CHCl3–ethanol was used
for the unit-cell determinations and data collection by a Rigaku AFC5S
four-circle diffractometer with graphite-monochromated MoKa radiation
(lꢂ0.71069 Å). The crystal data of these compounds are as follows: 8e:
C29H22ClNO4S2; Mꢂ548.07; orthorohmbic, space group Pbca (#61), Zꢂ8
with aꢂ14.11(1) Å, bꢂ31.64(1) Å, cꢂ11.34(1) Å; Vꢂ5066(6) Å3 and
D
calc.ꢂ1.437 g/cm3. All calculations were performed using the teXsan pack-
12) SIR92: Altomare A., Cascarano G., Giacovazzo C., Guagliardi A., J.
Appl. Cryst., 26, 343—350 (1993).
age.11) The structure was solved by a direct method (SIR).12) The non-hydro-
gen atoms were refined anisotropically, and the hydrogen atoms were at-