Preparation of new nitrogen-bridged heterocycles. 53. Syntheses of 3-(benzylthio)thieno[3,4-b]indolizine derivatives and their intramolecular arene-arene interactions.

Article abstract of DOI:10.1248/cpb.51.75

Various ethyl 1-arylcarbonyl-3-[(un)substituted methylthio]thieno[3,4-b]indolizine-9-carboxylates were synthesized in good yields by a novel methodology in which the S-alkylation of 5-arylcarbonyl-4-ethoxycarbonylmethyl-3-(1-pyridinio)thiophene-2-thiolates with alkyl or benzyl halides, the 1,5-dipolar cyclization of the resulting pyridinium salts in the presence of a base, and the aromatization were performed. In the X-ray analyses of some 3-(benzylthio)thieno[3,4-b]indolizine-9-carboxylates, a gauche and two anti conformers in relation to the exocyclic sulfide linkage were found. Interestingly, all of the 3-(benzylthio)thieno[3,4-b]indolizine derivatives showed significant high-field shifts (delta up to 0.3 ppm) for the 5- and 6-proton signals compared with those of the 3-methylthio derivatives in the (1)H-NMR spectra and exhibited a definite absorption band near 425 nm in their UV spectra, indicating an intramolecular arene-arene interaction between the thieno[3,4-b]indolizine and the phenyl ring.

Full text of DOI:10.1248/cpb.51.75

January 2003
Chem. Pharm. Bull. 51(1) 75—84 (2003)
75
Preparation of New Nitrogen-Bridged Heterocycles. 53.1) Syntheses of
3-(Benzylthio)thieno[3,4-b]indolizine Derivatives and Their
Intramolecular Arene–Arene Interactions
Akikazu KAKEHI,*,a Suketaka ITO,a Hiroyuki SUGA,a Takeyuki MIWA,a Takashi MORI,a Tsuneo FUJII,b
c
Nobuaki TANAKA,b and Tomoshige KOBAYASHI
a Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University; Wakasato, Nagano
380–8553, Japan: b Department of Environmental Science and Technology, Faculty of Engineering, Shinshu University;
Wakasato, Nagano 380–8553, Japan: and c Faculty of Science, Shinshu University; 3–1–1 Asahi, Matsumoto 390–8621,
Japan. Received September 12, 2002; accepted November 7, 2002
Various ethyl 1-arylcarbonyl-3-[(un)substituted methylthio]thieno[3,4-b]indolizine-9-carboxylates were syn-
thesized in good yields by a novel methodology in which the S-alkylation of 5-arylcarbonyl-4-ethoxycarbonyl-
methyl-3-(1-pyridinio)thiophene-2-thiolates with alkyl or benzyl halides, the 1,5-dipolar cyclization of the result-
ing pyridinium salts in the presence of a base, and the aromatization were performed. In the X-ray analyses of
some 3-(benzylthio)thieno[3,4-b]indolizine-9-carboxylates, a gauche and two anti conformers in relation to the
exocyclic sulfide linkage were found. Interestingly, all of the 3-(benzylthio)thieno[3,4-b]indolizine derivatives
showed significant high-field shifts (d up to 0.3 ppm) for the 5- and 6-proton signals compared with those of the
1
3-methylthio derivatives in the H-NMR spectra and exhibited a definite absorption band near 425 nm in their
UV spectra, indicating an intramolecular arene–arene interaction between the thieno[3,4-b]indolizine and the
phenyl ring.
Key words thieno[3,4-b]indolizine; arene–arene interaction; gauche form; anti form; UV spectra; X-ray analysis
In our preliminary communication1) we reported a new
preparative method for 3-(benzylthio)thieno[3,4-b]indolizine
derivatives having unique stacked structures due to the con-
tribution of intramolecular arene–arene interactions. We also
found that this method using 5-arylcarbonyl-4-ethoxycar-
bonylmethyl-3-(1-pyridinio)thiophene-2-thiolates as key in-
termediates is much more effective than those described ear-
lier by us2—4) and is widely applicable to the preparation of
various 3-alkylthio- and 3-(benzylthio)thieno[3,4-b]indolizine
derivatives. To the best of our knowledge, the intramolecular
arene–arene interaction through a highly flexible spacer such
as the sulfide bond is scarcely reported,5,6) and if its confor-
mational control is possible through such interaction, these
molecules might be used as low energy molecular switches
and chiral auxiliaries.7,8)
For the staggered conformations in relation to the sulfide
spacer in 3-(benzylthio)thieno[3,4-b]indolizine derivatives,
there are two gauche (G1, G2) and one anti form. The latter
is further subdivided into A1, A2, and A3 (see Fig. 1). Only
the G1 form and the eclipse form (E) have the attractive
arene–arene interactions. However, the E form has the great-
est steric hindrance and is not a stable conformer. The title
compounds, 3-(benzylthio)thieno[3,4-b]indolizine deriva-
tives, with intramolecular arene–arene interactions (G1
form) have the following structural features in comparison
with the analogs with a ethylene spacer: 1) the sulfur atom
does not have any substituent and hence the steric repulsion
with the proton(s) and/or group(s) on the adjacent carbon
atom is absent, 2) the long sulfide linkage decreases the en-
ergy difference between the anti (A1, A2, A3) and gauche
conformers (G1, G2), 3) the narrow C–S–C bond angle (near
100°), in contrast with the C–C–C bond angle (109.5°),
makes the through-space interaction between the two remote
aromatic rings possible, 4) the 5- and 6-positions of the
thieno[3,4-b]indolizine and the phenyl ring in the G1 form
are close and therefore an attractive interaction can be ex-
pected, while the other G2 form has no arene–arene interac-
tion and is considerably crowded, 5) the A3 form is consider-
ably hindered than the others (A1, A2). In addition, the elec-
tronic property of the indolizine skeleton in which the pyri-
dine moiety has a cationic character may also assist this at-
tractive interaction in the G1 form. In this paper we report a
novel and effective preparative method of ethyl 1-arylcar-
bonyl-3-[(un)substituted methylthio]thieno[3,4-b]indolizine-
9-carboxylates starting from 1-(ethoxycarbonylacetonyl)pyri-
dinium chlorides and also describe their structures involving
the intramolecular arene–arene interactions.
Results and Discussion
Preparations of 5-Arylcarbonyl-4-ethoxycarbonylmethyl-
3-(1-pyridinio)thiophene-2-thiolates When we found the
unexpected formation of ethyl 3-(R-thio)-1-cynothieno[3,4-
Fig. 1
∗ To whom correspondence should be addressed. e-mail: akakehi@gipwc.shinshu-u.ac.jp
© 2003 Pharmaceutical Society of Japan

76
Vol. 51, No. 1
b]indolizine-9-carboxylates from the alkaline and dehydro- the IR spectra showed characteristic absorption bands near
genative treatment of 1-[1-(R-thio)-1-cyanomethylthio-4- 1730 and 1614—1636 cmꢀ1 due to the saturated ester car-
ethoxycarbonyl-1,3-butadien-2-yl]pyridinium halides,2,3) we bonyl and the largely delocalized carbonyl group, respec-
proposed 1,5-dipolar species, [2-(R-thio)-5-cyano-3-(1-pyri- tively, which were consistent well with the structures of 4a—
dinio)thiophen-4-yl](ethoxycarbonyl)methanides, as the key f.
intermediates in these reaction routes. The retro synthesis of
Preparations of Ethyl 3-(R-thio)-1-(arylcarbonyl)thieno-
the 1,5-dipolar intermediates lead to two potential materials: [3,4-b]indolizine-9-carboxylates To examine the utility of
pyridinium [1-[R-thio(thiocarbonyl)](1-ethoxycarbonylacetyl)] these pyridinium betaines (4a—f) in the synthesis of
methylides and its dehydrated 4-ethoxycarbonylmethyl-3-(1- thieno[3,4-b]indolizine, we first investigated the reactions of
pyridinio)thiophene-2-thiolates (see Chart 1). Recently, we 4a—f with methyl iodide (5a). The S-alkylation of 4a—f
developed a route to 3-(R-thio)thieno[3,4-b]indolizine deriv- with excess 5a in chloroform at room temperature, followed
atives starting from former methylides, but their yields were by treatment of the resulting pyridinium salts (6a—c, 8a—c)
variable and generally low.4) Therefore, we next examined the with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a base at
use of 4-ethoxycarbonylmethyl-3-(1-pyridinio)thiophene-2- 0 °C and then dehydrogenation using chloranil gave the ex-
thiolates for thieno[3,4-b]indolizine synthesis.
pected ethyl 1-arylcarbonyl-3-(methylthio)thieno[3,4-b]in-
The desired compounds, 5-arylcarbonyl-4-ethoxycarbonyl- dolizine-9-carboxylates (7a—c, 9a—c) in good yields (62—
methyl-3-(1-pyridinio)thiophene-2-thiolates (4a—f) were di- 88%). These yields are much higher than those using our
rectly obtained in 30—66% yields from the treatment of a previous methods.2—4) Similar treatment of the corresponding
mixture of 1-(ethoxycarbonylacetonyl)pyridinium chloride pyridinium salts (6d—z, 8d—z), readily obtainable from
(1a, b), carbon disulfide, and phenacyl bromide (2a—c) with pyridinium betaines (4a—f) and a small excess of benzyl
triethylamine in chloroform at room temperature. In these re- bromides (5b—l) or phenethyl bromide (5m), produced 3-
actions pyridinium 1-[(ethoxycarbonylacetyl)[phenacylthio- benzylthio- (7d—x, 9d—x) or 3-phenethylthiothieno[3,4-
(thiocarbonyl)]]methylides (3) which were expected to be b]indolizine derivatives (7y, z, 9y, z) in 62—93% yields.
initially formed could not be detected at all (Chart 2).
These results are shown in Charts 3 and 4.
Only one methylene proton singlet appeared at d near 3.8
Elemental analyses of products 7a—z and 9a—z were in
1
in the H-NMR spectra of 4a—f. This fact indicated that the good accord with our proposed structures and their IR spec-
products 4a—f are not pyridinium methylides (3) before the tra showed the characteristic ester carbonyl band (1665—
intramolecular dehydration. The elementary analyses of 4a— 1688 cmꢀ1), and the cyano band (2220—2230 cmꢀ1 for only
f were in good accord with our proposed compositions and 7m—r, 9m—r). Interestingly, the 1H-NMR spectra (see
Table 1 for 7a—z and Table 2 for 9a—z) showed significant
high field shifts (d ꢁ0.3 ppm) for the 5- and 6-protons in the
3-(benzylthio)thieno[3,4-b]indolizines (7d—l, p—w, 9d—
l, p—w) compared with those in the 3-methylthio derivatives
(7a—c, 9a—c). The high field shifts related to the 5-protons
in 3-(2-cyanobenzylthio) (7m—o, 9m—o) and 3-(diphenyl-
methylthio derivatives (7x, 9x) were not observed, but this
does not mean an absence of intramolecular arene–arene in-
teractions in these compounds. This absence must be due to
the anisotropic effect by an additional 2-cyano or phenyl
group because the same effects is present on the adjacent 6-
proton and the characteristic UV absorption band attributable
to arene–arene interactions also appeared as described below.
Similar high field shifts relative to the phenyl protons of the
3-substituent in compounds 7d—x and 9d—x were also ob-
served. On the other hand, shielding effects were not exhib-
Chart 1
Chart 2

January 2003
77
Chart 3
Chart 4
ited in 3-phenethylthio derivatives (7y, z, 9y, z), though the and 515 (shoulder, 7a—c) or 510 nm (shoulder, 9a—c),
phenyl ring can approach much closer to the thieno[3,4-b]in- which were very similar to those for 3-phenethylthio deriva-
dolizine ring than those in 3-benzylthio derivatives (7d—x, tives (7y, z, 9y, z). On the other hand, all spectra9) of 3-(ben-
9d—x). This fact suggests that the type(s) and number of zylthio)thieno[3,4-b]indolizines (7d—x, 9d—x) had a new
atoms involved in the spacer are crucial for this type of band (421—429 nm) together with weak bands (near 480 and
arene–arene interaction. The other isomers of theino[3,4- 515 (shoulder) or 510 nm (shoulder)). The spectra of some
b]indolizines including the conformers could not be detected thieno[3,4-b]indolizines (7a, d, m, x) are shown in Fig. 2. As
1
in these H-NMR spectra of 7a—z and 9a—z at room tem- seen in Fig. 2, 3-(2-cyanobenzylthio)- (7m) and 3-(diphenyl-
perature and also in those of 7d, g even at ꢀ50 °C. However, methylthio)thieno[3,4-b]indolizine (7x) whose 1H-NMR
no nuclear Overhauser effect (NOE) between the 5- and 6- spectra did not show the high field shift for the 5-proton also
protons on the thieno[3,4-b]indolizine ring and the phenyl had the characteristic absorption band due to the arene–arene
protons in these compounds was exhibited at all. The reason interactions near 425 nm, and the 3-(diphenylmethylthio) de-
why the NOE effect could not be detected is not clear.
rivative (7x) provided the largest molar extinction coefficient.
To obtain further structural information we carried out X-
The UV spectra9) of 3-(methylthio)thieno[3,4-b]in-
dolizines (7a—c, 9a—c) which have no arene–arene interac- ray analyses for several thieno[3,4-b]indolizine derivatives
tions exhibited characteristic absorption bands near 330, 480, and found three kinds of crystals (G1, A1, A2). As the repre-

78
Vol. 51, No. 1
Table 1. 1H-NMR Spectral Data for 7-Unsubstituted Thieno[3,4-b]indolizinesa)
No.
C-5
C-6
C-7
C-8
COOEt
COAr
SCHR2R3
d (5-H)b)
d (6-H)b)
d (8-H)b)
c)
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
7q
7r
7s
8.96
8.97
8.96
8.80
8.80
8.81
8.75
8.79
8.79
8.77
8.79
8.78
8.93
8.93
8.93
8.73
8.74
8.73
8.83
8.74
8.71
8.80
8.86
8.95
8.98
8.97
6.72
6.75
6.75
6.49
6.51
6.54
6.50
6.54
6.52
6.49
6.53
6.51
6.59
6.61
6.61
6.52
6.55
6.56
6.51
6.52
6.52
6.54
6.53
6.57
6.64
6.67
8.21
8.21
8.21
8.15
8.13
8.14
8.15
8.15
8.15
8.15
8.17
8.14
8.16
8.15
8.14
8.16
8.16
8.15
8.11
8.16
8.16
8.16
8.15
8.17
8.21
8.22
0.96, 3.61
1.02, 3.72
1.02, 3.72
0.96, 3.66
1.01, 3.75
1.02, 3.76
0.97, 3.67
1.02, 3.76
1.02, 3.75
0.97, 3.67
1.03, 3.77
1.02, 3.76
0.95, 3.67
1.01, 3.76
1.01, 3.76
0.98, 3.69
1.03, 3.79
1.03, 3.78
0.96, 3.67
0.97, 3.68
0.97, 3.68
0.97, 3.68
0.96, 3.67
0.95, 3.66
0.97, 3.65
1.02, 3.74
7.0—8.2
7.2—8.0
7.3—8.0
7.0—8.2
7.2—8.0
7.3—8.0
7.0—8.2
7.2—8.0
7.3—8.0
7.2—8.2
7.2—8.0
7.3—8.0
6.8—8.0
7.0—8.0
7.0—8.0
7.0—8.0
7.0—8.0
7.0—8.0
6.7—8.1
6.8—8.1
6.8—8.1
6.7—8.0
7.0—8.1
7.1—8.2
7.0—8.2
7.0—8.0
2.68
2.70
2.70
4.11, 7.11
4.12, 7.12
0.00
ꢀ0.01
0.00
0.16
0.16
0.15
0.21
0.17
0.17
0.19
0.17
0.18
0.03
0.03
0.03
0.23
0.22
0.23
0.13
0.22
0.25
0.16
0.10
0.01
ꢀ0.02
ꢀ0.01
0.00
ꢀ0.03
ꢀ0.03
0.23
0.21
0.18
0.22
0.18
0.20
0.23
0.19
0.21
0.13
0.11
0.11
0.20
0.17
0.16
0.21
0.20
0.20
0.18
0.19
0.15
0.08
0.05
0.00
0.00
0.00
0.06
0.08
0.07
0.06
0.06
0.06
0.06
0.04
0.07
0.05
0.06
0.07
0.05
0.05
0.06
0.10
0.05
0.05
0.05
0.06
0.04
ꢀ0.01
ꢀ0.02
7.27
7.32
c)
c)
c)
c)
c)
c)
4.13, 7.12
2.40, 4.15, 6.7—7.6
2.41, 4.16, 6.7—7.6
2.40, 4.16, 6.7—7.6
2.20, 4.09, 6.95
2.21, 4.11, 6.97
2.20, 4.10, 6.96
4.26, 6.8—8.0
4.26, 7.0—8.0
4.26, 7.0—8.0
4.11, 7.0—8.0
4.13, 7.0—8.0
4.12, 7.0—8.0
4.19, 6.7—8.1
4.06, 6.8—8.1
4.03, 6.8—8.1
4.09, 6.7—8.0
1.77, 4.36, 7.14
5.53, 7.1—7.7
2.9—3.4, 7.21
2.9—3.4, 7.20
7.26
7.27
7.27
c)
c)
c)
c)
c)
c)
c)
c)
c)
c)
c)
c)
c)
c)
7t
7u
7v
7w
7x
7y
7z
a) The coupling constants are as follows; J5,6ꢂJ6,7ꢂ7.0 Hz, J6,8ꢂ2.0 Hz, J7,8ꢂ9.0 Hz, JEtꢂ7.0 Hz. b) The chemical shifts of compound 7a are selected as the standards.
c) Overlapped with the aromatic proton signals.
Table 2. 1H-NMR Spectral Data for 7-Methylthieno[3,4-b]indolizinesa)
No.
C-5
C-6
C-7
C-8
COOEt
COAr
SCHR2R3
d (5-H)b)
d (6-H)b)
d (8-H)b)
9a
9b
9c
9d
9e
9f
9g
9h
9i
9j
9k
9l
9m
9n
9o
9p
9q
9r
9s
8.86
8.86
8.83
8.70
8.67
8.67
8.68
8.67
8.65
8.65
8.64
8.66
8.86
8.84
8.81
8.57
8.58
8.57
8.74
8.58
8.54
8.66
8.76
8.82
8.86
8.84
6.58
6.60
6.59
6.36
6.39
6.37
6.38
6.39
6.38
6.35
6.37
6.38
6.49
6.49
6.47
6.37
6.41
6.37
6.38
6.36
6.35
6.38
6.39
6.40
6.50
6.51
2.40
2.42
2.42
2.36
2.37
2.35
2.38
2.38
2.37
2.37
2.36
2.38
2.40
2.39
2.38
2.38
2.40
2.38
2.35
2.37
2.38
2.35
2.37
2.37
2.40
2.40
8.01
8.01
7.99
7.95
7.93
7.93
7.95
7.93
7.93
7.96
7.94
0.95, 3.59
0.99, 3.68
1.00, 3.69
0.95, 3.62
0.99, 3.71
0.99, 3.71
0.95, 3.62
0.99, 3.71
0.99, 3.70
0.95, 3.64
1.00, 3.72
1.00, 3.74
0.95, 3.66
0.99, 3.72
0.99, 3.72
0.95, 3.66
1.01, 3.75
1.01, 3.75
0.94, 3.64
0.95, 3.64
0.96, 3.66
0.95, 3.65
0.95, 3.64
0.93, 3.61
0.95, 3.61
1.00, 3.70
7.3—8.2
7.3—8.1
7.3—8.0
7.3—8.2
7.3—8.1
7.3—8.0
7.3—8.2
7.3—8.1
7.3—8.0
7.3—8.2
7.3—8.1
7.3—8.0
7.0—8.1
7.0—8.0
7.0—8.0
7.0—8.1
7.0—8.1
7.0—8.1
6.7—8.1
6.8—8.1
6.7—8.1
6.7—8.1
7.1—8.1
7.1—8.1
7.0—8.1
7.3—8.0
2.66
2.68
2.67
4.11, 7.14
4.12, 7.13
0.00
0.00
0.03
0.16
0.19
0.19
0.18
0.19
0.21
0.21
0.22
0.20
0.00
0.02
0.05
0.29
0.28
0.29
0.12
0.28
0.32
0.20
0.10
0.04
0.00
0.02
0.00
ꢀ0.02
ꢀ0.01
0.22
0.19
0.21
0.20
0.19
0.20
0.23
0.21
0.20
0.09
0.09
0.11
0.21
0.17
0.21
0.20
0.22
0.23
0.20
0.19
0.18
0.08
0.07
0.00
0.00
0.02
0.06
0.08
0.08
0.06
0.08
0.08
0.05
0.07
0.06
—
0.07
0.07
0.06
0.06
0.08
—
4.11, 7.12
2.38, 4.16, 6.7—7.7
2.38, 4.15, 6.7—7.7
2.37, 4.13, 6.7—7.5
2.21, 4.09, 6.97
2.21, 4.08, 6.96
2.21, 4.11, 6.99
4.28, 7.0—8.1
4.26, 7.0—8.0
4.25, 7.0—8.0
4.09, 7.0—8.1
4.11, 7.0—8.1
4.10, 7.0—8.1
4.18, 6.7—8.1
4.04, 6.8—8.1
4.02, 6.7—8.1
4.07, 6.7—8.1
1.77, 4.36, 7.13
5.51, 7.1—7.7
2.8—3.5, 7.20
2.8—3.5, 7.20
7.95
c)
7.94
7.94
7.95
7.95
7.93
c)
9t
7.97
0.04
0.04
—
0.04
0.05
0.00
0.01
9u
9v
9w
9x
9y
9z
7.97
c)
7.97
7.96
8.01
8.00
a) The coupling constants are as follows; J5,6ꢂ7.0 Hz, J6,8ꢂ2.0 Hz, JEtꢂ7.0 Hz. b) The chemical shifts of compound 9a are selected as the standards. c) Overlapped with
the aromatic proton signals.

January 2003
79
Fig. 2. UV Spectra of Some Thieno[3,4-b]indolizines 7a, d, m, x in CHCl3
Fig. 5. ORTEP Drawing of Ethyl 1-Benzoyl-3-(4-bromobenzylthio)-
thieno[3,4-b]indolizine-9-carboxylate (7u)
Fig. 3. ORTEP Drawing of Ethyl 1-(4-Chlorobenzoyl)-3-(2-cyanoben-
zylthio)thieno[3,4-b]indolizine-9-carboxylate (7n)
Fig. 6. ORTEP Drawing of Ethyl 1-(4-Chlorobenzoyl)-7-methyl-3-
(phenethylthio)thieno[3,4-b]indolizine-9-carboxylate (9z)
sentatives for G1, A1, and A2 conformers thus confirmed,
the ORTEP drawings10) for 7n, 9p, and 7u are shown in Figs.
3—5, and that for the 3-phenethylthio derivative 9z is shown
in Fig. 6. In general, the G1 crystals were mainly obtained in
the cases of 7-unsubstituted 3-(benzylthio)thieno[3,4-b]in-
dolizines,11) and the A1 ones in those of the 7-methyl deriva-
tives.12) The A2 form was only observed in 7u. In the G1
crystals found in thienoindolizines 7g, n and 9n, which have
an unsymmetrically substituted 3-benzyl group such as a 2-
methylbenzyl or 2-cyanobenzyl, the overlapping of the 2-
substituent on the thienoindolizne ring was not observed.
The distances (C4–C19) (see ORTEP drawings for its num-
bering) and the dihedral angles (C2–S2–C18–C19) for
7g, j, n and 9n (G1 form) are 3.671—3.983 Å and 50.5—
67.1° respectively, while those for 9p, z (A1 form) and 7u
(A2 form) are over 5 Å and 168.3—176.2° respectively. As
might be expected, the dihedral angles of the least-square
planes of the thienoindolizine and the interacting phenyl ring
Fig. 4. ORTEP Drawing of Ethyl 1-Benzoyl-3-(4-cyanobenzylthio)-7-
methylthieno[3,4-b]indolizine-9-carboxylate (9p)

80
Vol. 51, No. 1
Table 3. Some Structural Data for Thieno[3,4-b]indolizines
No. Form C2–S2a) S2–C18a) N1–C19a) C2–S2–C18b) DA1b,c) DA2b,d)
7g G1 1.746(4) 1.844(5) 3.983
7j G1 1.761(9) 1.85 (1) 3.671
7n G1 1.756(5) 1.848(7) 3.686
7u A2 1.75 (1) 1.83 (1) 5.993
9n G1 1.747(4) 1.838(7) 3.762
9p A1 1.746(5) 1.824(5) 5.044
100.3(2)
99.8(4)
97.7(3)
103.4(5)
100.8(3)
100.4(2)
102.8(4)
53.3(4) 39.77
53.3(8) 24.75
67.1(6) 26.07
172.9(9) 103.18
50.5(5) 25.22
176.2(4)
8.93
9z
—
1.750(1) 1.793(8) 5.772
168.3(7) 103.71
Fig. 7. Atomic Charges (Ground State) of Ethyl 1-Benzoyl-3-
(benzylthio)thieno[3,4-b]indolizine-9-carboxylate (7a) and Its Initially Ex-
pected Ionic Structure
a) Å. b) °C. c) Dihedral angle for C2–S2–C18–C19. d) Dihedral angle of the
least-square planes of thieno[3,4-b]indolizine and the interacting phenyl ring.
Chart 5
filtered. The filtrate was concentrated at reduced pressure and the residue
was separated by column chromatography on alumina using chloroform as
an eluent. The chloroform layers of pyridinium betaines were combined and
concentrated at reduced pressure. Recrystallization of the crude products
from chloroform–ether afforded the corresponding 3-(1-pyridinio)thio-
were fairly wide (24.75—39.44°). Some structural data for
7g, j,1) n, u and 9p, z are listed in Table 3.
The atomic charges in the AM1 calculation13) of com-
pound 7d showed the high electronic densities at the C-5, C-
6, C-7, and C-8 carbons on the pyridine ring, indicating the phene-2-thiolates as yellow needles. In these reactions no pyridinium 1-
[(ethoxycarbonylacetyl)[(phenacylthio)thiocarbonyl]]methylides (3) could
be obtained.
Selected data for new products 4b, c, e, f are as follows:
5-(4-Chlorobenzoyl)-4-ethoxycarbonylmethyl-3-(1-pyridinio)thiophene-3-
low possibility of a cation-p like interaction in this ring sys-
tem (see Fig. 7). Similarly, the HOMO–LUMO interaction of
the same molecule did not exhibited any favorable effect be-
tween the pyridine and the phenyl rings.
thiolate (4b): 40% (from 1a, carbon disulfide, and p-chlorophenacyl bro-
mide (2b)), mp 221—223 °C. IR (KBr) cmꢀ1: 1728, 1635. 1H-NMR (60
MHz, CDCl3) d: 1.23 (3H, t, Jꢂ7.0 Hz), 3.78 (2H, s), 4.18 (2H, q, Jꢂ7.0
Hz), 7.2—8.9 (9H, m). Anal. Calcd for C20H16ClNO3S2: C, 57.48; H, 3.86;
N, 3.35. Found: C, 57.70; H, 3.75; N, 3.24.
5-(4-Bromobenzoyl)-4-ethoxycarbonylmethyl-3-(1-pyridinio)thiophene-3-
thiolate (4c): 66% (from 1a, carbon disulfide, and p-bromophenacyl bromide
(2c)), mp 236—238 °C. IR (KBr) cmꢀ1: 1728, 1620. 1H-NMR (60 MHz,
CDCl3) d: 1.24 (3H, t, Jꢂ7.0 Hz), 3.77 (2H, s), 4.15 (2H, q, Jꢂ7.0 Hz),
7.2—9.0 (9H, m). Anal. Calcd for C20H16BrNO3S2: C, 51.95; H, 3.49; N,
3.03. Found: C, 51.89; H, 3.35; N, 2.89.
Reaction Mechanisms The possible reaction mecha-
nisms are shown in Chart 5. Except for the smooth dehydra-
tion of pyridinium (thiocarbonyl)methylides 3 to the corre-
sponding pyridinium betaines (4a—f), these reactions pro-
ceeded well according to our initially proposed routes.
Experimental
Melting points were measured with a Yanagimoto micromelting point ap-
paratus and are not corrected. Microanalyses were carried out on a Perkin-
Elmer 2400 elemental analyzer. The 1H-NMR spectra were determined with
a Hitachi R-600 spectrometer (60 MHz) or JEOL JNM-LA400 (1H and 13C:
400 MHz) spectrometer in deuteriochloroform with tetramethylsilane used
as the internal standard; the chemical shifts are expressed in d values. The
IR and UV spectra were taken with a JASCO FT/IR-5300 IR and a SHI-
MADZU UV-2500PC spectrophotometers, respectively.
Preparation of 3-(1-Pyridinio)thiophene-2-thiolates. General Method
A chloroform solution (100 ml) of 1-(ethoxycarbonylacetonyl)pyridinium
chloride (1, 10 mmol) and carbon disulfide (1.520 g, 20 mmol) was treated
with triethylamine (3.0 g, 30 mmol) under stirring at rt for 1 h, and then
phenacyl bromide (2, 10 mmol) was added to the reaction mixture and the
resulting solution was allowed to react at rt for another 12 h. The solution
was poured into water (300 ml) and extracted twice with 200 ml portions of
chloroform. The combined extracts were dried over sodium sulfate and then
5-(4-Chlorobenzoyl)-4-ethoxycarbonylmethyl-3-(4-methyl-1-pyridinio)-
thiophene-3-thiolate (4e): 30% (from 1a, carbon disulfide, and p-
chlorophenacyl bromide (2b)), mp 223—226 °C. IR (KBr) cmꢀ1: 1726,
1
1614. H-NMR (60 MHz, CDCl3) d: 1.25 (3H, t, Jꢂ7.0 Hz), 2.75 (3H, s),
3.76 (2H, s), 4.15 (2H, q, Jꢂ7.0 Hz), 7.2—8.8 (8H, m). Anal. Calcd for
C21H18ClNO3S2: C, 58.39; H, 4.20; N, 3.24. Found: C, 58.37; H, 4.12; N,
3.08.
5-(4-Bromobenzoyl)-4-ethoxycarbonylmethyl-3-(4-methyl-1-pyridinio)-
thiophene-3-thiolate (4f): 44% (from 1a, carbon disulfide, and p-bro-
mophenacyl bromide (2c)), mp 239—242 °C. IR (KBr) cmꢀ1: 1728, 1636.
1H-NMR (60 MHz, CDCl3) d: 1.25 (3H, t, Jꢂ7.0 Hz), 2.75 (3H, s), 3.76
(2H, s), 4.16 (2H, q, Jꢂ7.0 Hz), 7.2—8.8 (8H, m). Anal. Calcd for
C21H18BrNO3S2: C, 52.94; H, 3.81; N, 2.94. Found: C, 53.13; H, 3.73; N,
2.79.

January 2003
81
Preparation of Ethyl 1-Arylcarbonyl-3-[(un)substituted methylthio]-
thieno[3,4-b]indolizine-9-carboxylates. General Method A chloroform
solution (30 ml) of 1-(pyridinio)thiophene-2-thiolate (4, 1 mmol) and methyl
iodide (5a, 0.71 g, 5 mmol) or benzyl or phenethyl bromide (2b—m, 1.2
mmol) was kept at room temperature until the spot of the pyridinium betaine
(4) disappeared by TLC monitoring (from 30 min to 12 h). After S-alkylation
was completed, the resulting solution was concentrated at reduced pressure
and the residue was washed three times with 20 ml portions of ether to re-
move any excess alkylating agent. Without further purification, pyridinium
salt (6 or 8) was dissolved in chloroform (30 ml) and the solution was treated
with DBU (0.20 g, 1.3 mmol) under stirring in an ice bath for 15 min and
then with chloranil (0.499 g, 1 mmol) under the same conditions for another
12 h. The reaction mixture was concentrated at reduced pressure and the
residue was separated by column chromatography on alumina using chloro-
form as an eluent. The reddish chloroform layers of product (7 or 9) were
combined and concentrated at reduced pressure. Recrystallization of the
crude products from chloroform–hexane afforded the corresponding ethyl
1-arylcarbonyl-3-[(un)substituted methylthio]thieno[3,4-b]indolizine-9-car-
boxylates.
lmax (CHCl3) nm (log e) ca. 328 (shoulder), 422 (3.96), 476 (3.70), ca. 515
(shoulder). Anal. Calcd for C28H23NO3S2: C, 69.25; H, 4.77; N, 2.88. Found:
C, 69.15; H, 4.69; N, 3.06.
Ethyl 1-(4-Chlorobenzoyl)-3-(2-methylbenzylthio)thieno[3,4-b]indolizine-
9-carboxylate (7h): 80% (from 4b and 2-methylbenzyl bromide (5c)), red
needles, mp 150—152 °C. IR (KBr) cmꢀ1: 1671, 1588. UV lmax (CHCl3)
nm (log e) ca. 322 (shoulder), 423 (3.90), 474 (3.77), ca. 515 (shoulder).
Anal. Calcd for C28H22ClNO3S2: C, 64.67; H, 4.26; N, 2.69. Found: C,
64.81; H, 4.42; N, 2.57.
Ethyl 1-(4-Bromobenzoyl)-3-(2-methylbenzylthio)thieno[3,4-b]indolizine-
9-carboxylate (7i): 71% (from 4c and 2-methylbenzyl bromide (5c)), red
needles, mp 150—151 °C. IR (KBr) cmꢀ1: 1671, 1584. UV lmax (CHCl3)
nm (log e) ca. 324 (shoulder), 423 (3.93), 482 (3.79), ca. 515 (shoulder).
Anal. Calcd for C28H22BrNO3S2: C, 59.57; H, 3.93; N, 2.48. Found: C,
59.59; H, 3.94; N, 2.38.
Ethyl 1-Benzoyl-3-(4-methylbenzylthio)thieno[3,4-b]indolizine-9-carboxy-
late (7j): 83% (from 4a and 4-methylbenzyl bromide (5d)), red prisms, mp
149—151 °C. IR (KBr) cmꢀ1: 1674, 1597. UV lmax (CHCl3) nm (log e) 328
(4.09), 423 (3.90), 480 (3.84), ca. 515 (shoulder). Anal. Calcd for
C28H23NO3S2: C, 69.25; H, 4.77; N, 2.88. Found: C, 69.39; H, 4.68; N, 2.82.
Ethyl 1-(4-Chlorobenzoyl)-3-(4-methylbenzylthio)thieno[3,4-b]indolizine-
9-carboxylate (7k): 90% (from 4b and 4-methylbenzyl bromide (5d)), red
needles, mp 148—149 °C. IR (KBr) cmꢀ1: 1682, 1589. UV lmax (CHCl3)
nm (log e) 325 (4.09), 423 (3.90), 482 (3.81), ca. 515 (shoulder). Anal.
Calcd for C28H22ClNO3S2: C, 64.67; H, 4.26; N, 2.69. Found: C, 64.41; H,
3.27; N, 2.50.
Ethyl 1-(4-Bromobenzoyl)-3-(4-methylbenzylthio)thieno[3,4-b]indolizine-
9-carboxylate (7l): 71% (from 4c and 4-methylbenzyl bromide (5d)), red
needles, mp 147—149 °C. IR (KBr) cmꢀ1: 1682, 1588. UV lmax (CHCl3)
nm (log e) 325 (4.09), 423 (3.94), 485 (3.81), ca. 515 (shoulder). Anal.
Calcd for C28H22BrNO3S2: C, 59.57; H, 3.93; N, 2.48. Found: C, 59.78; H,
3.83; N, 2.37.
Ethyl 1-Benzoyl-3-(2-cyanobenzylthio)thieno[3,4-b]indolizine-9-carboxy-
late (7m): 76% (from 4a and 2-cyanobenzyl bromide (5e)), brown prisms,
mp 119—120 °C. IR (KBr) cmꢀ1: 2226, 1688, 1630. UV lmax (CHCl3) nm
(log e) 322 (4.13), 422 (4.00), 480 (3.83), ca. 515 (shoulder). Anal. Calcd
for C28H20N2O3S2: C, 67.72; H, 4.06; N, 5.64. Found: C, 67.77; H, 4.01; N,
5.54.
Ethyl 1-(4-Chlorobenzoyl)-3-(2-cyanobenzylthio)thieno[3,4-b]indolizine-
9-carboxylate (7n): 87% (from 4b and 2-cyanobenzyl bromide (5e)), brown
prisms, mp 121—122 °C. IR (KBr) cmꢀ1: 2220, 1684, 1614. UV lmax
(CHCl3) nm (log e) 323 (4.12), 422 (4.00), 484 (3.82), ca. 515 (shoulder).
Anal. Calcd for C28H19ClN2O3S2: C, 63.33; H, 3.61; N, 5.28. Found: C,
63.51; H, 3.55; N, 5.16.
Ethyl 1-(4-Bromobenzoyl)-3-(2-cyanobenzylthio)thieno[3,4-b]indolizine-
9-carboxylate (7o): 75% (from 4c and 2-cyanobenzyl bromide (5e)), brown
prisms, mp 128—130 °C. IR (KBr) cmꢀ1: 2220, 1682, 1611. UV lmax
(CHCl3) nm (log e) 323 (4.14), 422 (4.03), 485 (3.84), ca. 515 (shoulder).
Anal. Calcd for C28H19BrN2O3S2: C, 58.44; H, 3.33; N, 4.87. Found: C,
58.47; H, 3.24; N, 4.67.
Ethyl 1-Benzoyl-3-(4-cyanobenzylthio)thieno[3,4-b]indolizine-9-carboxy-
late (7p): 66% (from 4a and 4-cyanobenzyl bromide (5f)), red needles, mp
172—173 °C. IR (KBr) cmꢀ1: 2222, 1674, 1593. UV lmax (CHCl3) nm
(log e) 327 (4.10), 421 (4.06), 477 (3.70), ca. 515 (shoulder). Anal. Calcd
for C28H20N2O3S2: C, 67.72; H, 4.06; N, 5.64. Found: C, 67.89; H, 4.02; N,
5.50.
Ethyl 1-(4-Chlorobenzoyl)-3-(4-cyanobenzylthio)thieno[3,4-b]indolizine-
9-carboxylate (7q): 62% (from 4b and 4-cyanobenzyl bromide (5f)), brown
prisms, mp 152—153 °C. IR (KBr) cmꢀ1: 2226, 1674, 1587. UV lmax
(CHCl3) nm (log e) 328 (4.01), 422 (4.03), 483 (3.73), ca. 515 (shoulder).
Anal. Calcd for C28H19ClN2O3S2: C, 63.33; H, 3.61; N, 5.28. Found: C,
63.37; H, 3.85; N, 5.00.
Ethyl 1-(4-Bromobenzoyl)-3-(4-cyanobenzylthio)thieno[3,4-b]indolizine-
9-carboxylate (7r): 75% (from 4c and 4-cyanobenzyl bromide (5f)), brown
prisms, mp 125—127 °C. IR (KBr) cmꢀ1: 2230, 1670, 1583. UV lmax
(CHCl3) nm (log e) 326 (4.09), 421 (3.82), 485 (3.82), ca. 515 (shoulder).
Anal. Calcd for C28H19BrN2O3S2: C, 58.44; H, 3.33; N, 4.87. Found: C,
58.47; H, 3.54; N, 4.60.
Ethyl 1-Benzoyl-3-(2-chlorobenzylthio)thieno[3,4-b]indolizine-9-carboxy-
late (7s): 67% (from 4a and 2-chlorobenzyl bromide (5g)), orange needles,
mp 127—129 °C. IR (KBr) cmꢀ1: 1678, 1630. UV lmax (CHCl3) nm (log e)
328 (4.07), 423 (3.83), 478 (3.72), ca. 515 (shoulder). Anal. Calcd for
C27H20ClNO3S2: C, 64.08; H, 3.98; N, 2.77. Found: C, 64.20; H, 3.95; N,
2.69.
1
The H-NMR (60 MHz) spectral data for products 7a—z, and 9a—z are
listed in Table 1, and the other data for them are as follows:
Ethyl 1-Benzoyl-3-(methylthio)thieno[3,4-b]indolizine-9-carboxylate (7a):
80% (from 4a and methyl iodide (5a)), red needles, mp 128—129 °C (Lit.2)
1
127—129 °C). H-NMR (CDCl3, 400 MHz) d: 0.97 (3H, t, Jꢂ7.1 Hz), 2.68
(3H, s), 3.60 (2H, q, Jꢂ7.1 Hz), 6.73 (1H, dt, Jꢂ6.8, 1.2 Hz), 7.31 (1H, ddd,
Jꢂ9.2, 6.8, 1.0 Hz), 7.41 (2H, br t, Jꢂ7.3 Hz), 7.51 (1H, br t, Jꢂ7.3 Hz),
7.93 (2H, br d, Jꢂ7.3 Hz), 8.20 (1H, br d, Jꢂ9.2 Hz), 8.96 (1H, br d,
Jꢂ6.8 Hz). 13C-NMR (CDCl3, 400 MHz) d: 14.3, 21.8, 9.0, 93.8, 111.0,
120.1, 122.0, 122.8, 127.4, 128.2, 129.3, 130.1, 132.3, 135.0, 135.2, 139.3,
150.0, 164.1, 187.6. UV lmax (CHCl3) nm (log e) 331 (4.05), 481 (4.02), ca.
515 (shoulder).
Ethyl 1-(4-Chlorobenzoyl)-3-(methylthio)thieno[3,4-b]indolizine-9-car-
boxylate (7b): 84% (from 4b and methyl iodide (5a)), red needles, mp
154—155 °C (Lit.2) 153—155 °C). UV lmax (CHCl3) nm (log e) 331 (4.08),
483 (4.07), ca. 515 (shoulder).
Ethyl 1-(4-Bromobenzoyl)-3-(methylthio)thieno[3,4-b]indolizine-9-car-
boxylate (7c): 88% (from 4c and methyl iodide (5a)), red needles, mp 140—
142 °C (Lit.2) 137—139 °C). UV lmax (CHCl3) nm (log e) 331 (4.09), 484
(4.09), ca. 515 (shoulder).
Ethyl 1-Benzoyl-3-(benzylthio)thieno[3,4-b]indolizine-9-carboxylate (7d):
74% (from 4a and benzyl bromide (5b)), red needles, mp 135—137 °C. IR
(KBr) cmꢀ1: 1688, 1589. 1H-NMR (CDCl3, 400 MHz) d: 0.96 (3H, t, Jꢂ7.1
Hz), 3.64 (2H, q, Jꢂ7.1 Hz), 4.11 (2H, s), 6.50 (1H, dt, Jꢂ6.8, 1.2 Hz),
7.0—7.2 (5H, m), 7.22 (1H, ddd, Jꢂ9.2, 6.8, 1.0 Hz), 7.42 (2H, br t,
Jꢂ7.3 Hz), 7.52 (1H, br t, Jꢂ7.3 Hz), 7.91 (2H, br d, Jꢂ7.3 Hz), 8.12 (1H,
br d, Jꢂ9.2 Hz), 8.77 (1H, br d, Jꢂ6.8 Hz). 13C-NMR (CDCl3, 400 MHz) d:
14.3, 44.7, 59.0, 93.3, 110.4, 116.1, 119.8, 125.1, 126.8, 127.9, 128.3, 128.6,
128.8, 129.4, 130.1, 132.5, 134.7, 136.3, 137.2, 139.0, 149.8, 164.0, 188.1.
UV lmax (CHCl3) nm (log e) 328 (4.08), 422 (3.91), 480 (3.80), ca. 515
(shoulder). Anal. Calcd for C27H21NO3S2: C, 68.77; H, 4.99; N, 2.97. Found:
C, 68.63; H, 4.37; N, 2.84.
Ethyl 3-Benzylthio-1-(4-chlorobenzoyl)thieno[3,4-b]indolizine-9-carboxy-
late (7e): 83% (from 4b and benzyl bromide (5b)), red needles, mp 142—
144 °C. IR (KBr) cmꢀ1: 1667, 1588. UV lmax (CHCl3) nm (log e) 328
(4.09), 423 (3.93), 481 (3.78), ca. 515 (shoulder). Anal. Calcd for
C27H20ClNO3S2: C, 64.08; H, 3.98; N, 2.77. Found: C, 64.02; H, 4.02; N,
2.80.
Ethyl 3-Benzylthio-1-(4-bromobenzoyl)thieno[3,4-b]indolizine-9-carboxy-
late (7f): 91% (from 4c and benzyl bromide (5b)), red needles, mp 141—
143 °C. IR (KBr) cmꢀ1: 1682, 1586. UV lmax (CHCl3) nm (log e) 328
(3.89), 422 (3.72), 481 (3.61), ca. 515 (shoulder). Anal. Calcd for
C27H20BrNO3S2: C, 58.91; H, 3.66; N, 2.54. Found: C, 58.77; H, 3.71; N,
2.62.
Ethyl 1-Benzoyl-3-(2-methylbenzylthio)thieno[3,4-b]indolizine-9-carboxy-
late (7g): 86% (from 4a and 2-methylbenzyl bromide (5c)), red prisms, mp
1
120—122 °C. IR (KBr) cmꢀ1: 1678, 1595. H-NMR (CDCl3, 400 MHz) d:
0.96 (3H, t, Jꢂ7.1 Hz), 2.40 (3H, s), 3.64 (2H, q, Jꢂ7.1 Hz), 4.14 (2H, s),
6.51 (1H, dt, Jꢂ6.8, 1.2 Hz), 6.77 (1H, d, Jꢂ7.1 Hz), 6.88 (1H, t, Jꢂ7.5 Hz),
7.03 (1H, dt, Jꢂ7.6, 7.6, 1.2 Hz), 7.09 (1H, d, Jꢂ7.3 Hz), 7.22 (1H, ddd,
Jꢂ9.3, 6.8, 1.0 Hz), 7.42 (2H, br t, Jꢂ7.3 Hz), 7.53 (1H, br t, Jꢂ7.6 Hz),
7.92 (2H, br d, Jꢂ7.1 Hz), 8.13 (1H, br d, Jꢂ9.3 Hz), 8.76 (1H, br d,
Jꢂ7.1 Hz). 13C-NMR (CDCl3, 400 MHz) d: 14.3, 19.2, 42.8, 59.0, 93.3,
110.4, 116.4, 119.8, 125.1, 125.9, 126.7, 128.2, 128.3, 129.4, 129.6, 130.1,
130.7, 132.5, 134.0, 134.7, 136.3, 137.2, 139.0, 149.8, 164.0, 188.1. UV

82
Vol. 51, No. 1
Ethyl 1-Benzoyl-3-(4-chlorobenzylthio)thieno[3,4-b]indolizine-9-carboxy-
Ethyl 1-Benzoyl-7-methyl-3-(2-methylbenzylthio)thieno[3,4-b]indolizine-
late (7t): 76% (from 4a and 4-chlorobenzyl bromide (5h)), orange flakes, mp 9-carboxylate (9g): 65% (from 4d and 2-methylbenzyl bromide (5c)), or-
150—152 °C. IR (KBr) cmꢀ1: 1674, 1595. UV lmax (CHCl3 nm (log e) 328
ange flakes, mp 180—183 °C. IR (KBr) cmꢀ1: 1671, 1595. UV lmax (CHCl3)
(4.09), 422 (3.96), 481 (3.81), ca. 515 (shoulder). Anal. Calcd for nm (log e) ca. 326 (shoulder), 427 (3.97), 473 (3.73), ca. 510 (shoulder).
C27H20ClNO3S2: C, 64.08; H, 3.98; N, 2.77. Found: C, 64.25; H, 4.01; N, Anal. Calcd for C29H25NO3S2: C, 69.71; H, 5.04; N, 2.80. Found: C, 69.87;
2.58.
Ethyl 1-Benzoyl-3-(4-bromobenzylthio)thieno[3,4-b]indolizine-9-carboxy-
H, 5.01; N, 2.67.
Ethyl 1-(4-Chlorobenzoyl)-7-methyl-3-(2-methylbenzylthio)thieno[3,4-b]-
late (7u): 75% (from 4a and 4-bromobenzyl bromide (5i)), red prisms, mp indolizine-9-carboxylate (9h): 77% (from 4e and 2-methylbenzyl bromide
123—125 °C. IR (KBr) cmꢀ1: 1672, 1608. UV lmax (CHCl3) nm (log e) 327
(5c)), orange needles, mp 180—181 °C. UV lmax (CHCl3) nm (log e) ca. 326
(4.07), 421 (3.98), 479 (3.75), ca. 515 (shoulder). Anal. Calcd for (shoulder), 427 (3.97), 477 (3.77), ca. 510 (shoulder). IR (KBr) cmꢀ1: 1674,
C27H20BrNO3S2: C, 58.91; H, 3.66; N, 2.54. Found: C, 59.14; H, 3.56; N, 1588. UV lmax (CHCl3) nm (log e) ca. 326 (shoulder), 427 (3.97), 477
2.41.
(3.77), ca. 510 (shoulder). Anal. Calcd for C29H24ClNO3S2: C, 65.22; H,
Ethyl 1-Benzoyl-3-(4-fluorobenzylthio)thieno[3,4-b]indolizine-9-carboxy- 4.53; N, 2.62. Found: C, 65.33; H, 4.51; N, 2.52.
late (7v): 91% (from 4a and 4-fluorobenzyl bromide (5j)), red prisms, mp
Ethyl 1-(4-Bromobenzoyl)-7-methyl-3-(2-methylbenzylthio)thieno[3,4-b]-
indolizine-9-carboxylate (9i): 70% (from 4f and 2-methylbenzyl bromide
148—150 °C. IR (KBr) cmꢀ1: 1682, 1603. UV lmax (CHCl3) nm (log e) 328
(4.08), 423 (3.83), 481 (3.89), ca. 515 (shoulder). Anal. Calcd for (5c)), brown prisms, mp 133—135 °C. IR (KBr) cmꢀ1: 1674, 1586. UV lmax
C27H20FNO3S2: C, 66.78; H, 4.40; N, 2.78. Found: C, 66.73; H, 4.30; N, (CHCl3) nm (log e) ca. 325 (shoulder), 428 (4.05), 473 (3.78), ca. 510
2.65.
(shoulder). Anal. Calcd for C29H24BrNO3S2: C, 60.21; H, 4.18; N, 2.42.
Ethyl 1-Benzoyl-3-(1-phenylethylthio)thieno[3,4-b]indolizine-9-carboxy- Found: C, 60.31; H, 4.15; N, 2.35.
late (7w): 75% (from 4a and 1-phenylethyl bromide (5k)), red prisms, mp
Ethyl 1-Benzoyl-7-methyl-3-(4-methylbenzylthio)thieno[3,4-b]indolizine-
9-carboxylate (9j): 65% (from 4d and 4-methylbenzyl bromide (5d)), red
110—111 °C. IR (KBr) cmꢀ1: 1669, 1620. UV lmax (CHCl3) nm (log e) 319
(4.05), 422 (3.91), 478 (3.74), ca. 515 (shoulder). Anal. Calcd for needles, mp 110—111 °C. IR (KBr) cmꢀ1: 1674, 1591. UV lmax (CHCl3)
C28H23NO3S2: C, 69.25; H, 4.77; N, 2.88. Found: C, 69.39; H, 4.70; N, 2.81.
Ethyl 1-Benzoyl-3-(diphenylmethylthio)thieno[3,4-b]indolizine-9-carboxy-
late (7x): 79% (from 4a and diphenylmethyl bromide (5l)), orange needles,
mp 177—179 °C. IR (KBr) cmꢀ1: 1667, 1633. UV lmax (CHCl3) nm (log e)
nm (log e) 327 (4.09), 428 (3.98), 474 (3.78), ca. 510 (shoulder). Anal.
Calcd for C29H25NO3S2: C, 69.71; H, 5.04; N, 2.80. Found: C, 69.81; H,
5.04; N, 2.67.
Ethyl 1-(4-Chlorobenzoyl)-7-methyl-3-(4-methylbenzylthio)thieno[3,4-b]-
330 (4.07), 422 (4.05), 475 (3.56), ca. 515 (shoulder). Anal. Calcd for indolizine-9-carboxylate (9k): 89% (from 4e and 4-methylbenzyl bromide
C33H25NO3S2: C, 72.37; H, 4.60; N, 2.56. Found: C, 72.08; H, 4.69; N, 2.76.
Ethyl 1-Benzoyl-3-(2-phenylethylthio)thieno[3,4-b]indolizine-9-carboxy- (CHCl3) nm (log e) 325 (4.12), 428 (4.02), 478 (3.80), ca. 510 (shoulder).
(5d)), brown prisms, mp 179—182 °C. IR (KBr) cmꢀ1: 1667, 1586. UV lmax
late (7y): 79% (from 4a and 2-phenethyl bromide (5m)), red needles, mp
147—149 °C. IR (KBr) cmꢀ1: 1672, 1624. UV lmax (CHCl3) nm (log e) 330
(4.08), 483 (4.01), ca. 515 (shoulder). Anal. Calcd for C28H23NO3S2: C,
69.25; H, 4.77; N, 2.88. Found: C, 69.39; H, 4.74; N, 2.78.
Anal. Calcd for C29H24ClNO3S2: C, 65.22; H, 4.53; N, 2.62. Found: C,
65.09; H, 4.50; N, 2.54..
Ethyl 1-(4-Bromobenzoyl)-7-methyl-3-(4-methylbenzylthio)thieno[3,4-b]-
indolizine-9-carboxylate (9l): 71% (from 4f and 4-methylbenzyl bromide
Ethyl 1-(4-chlorobenzoyl-3-(2-phenylethylthio)thieno[3,4-b]indolizine-9- (5d)), brown prisms, mp 177—180 °C. IR (KBr) cmꢀ1: 1667, 1584. UV lmax
carboxylate (7z): 93% (from 4b and 2-phenethyl bromide (5m)), red nee-
(CHCl3) nm (log e) ca. 326 (shoulder), 427 (3.96), 482 (3.89), ca. 510
(shoulder). Anal. Calcd for C29H24BrNO3S2: C, 60.21; H, 4.18; N, 2.42.
dles, mp 111—112 °C. IR (KBr) cmꢀ1: 1672, 1620. UV lmax (CHCl3) nm
(log e) 331 (4.03), 485 (3.99), ca. 515 (shoulder). Anal. Calcd for Found: C, 60.35; H, 4.16; N, 2.32.
C28H22ClNO3S2: C, 64.67; H, 4.26; N, 2.69. Found: C, 64.68; H, 4.27 N,
2.53.
Ethyl 1-Benzoyl-3-(2-cyanobenzylthio)-7-methylthieno[3,4-b]indolizine-
9-carboxylate (9m): 62% (from 4d and 2-cyanobenzyl bromide (5e)), orange
needles, mp 186—188 °C. IR (KBr) cmꢀ1: 2224, 1662, 1624. UV lmax
(CHCl3) nm (log e) 322 (4.07), 426 (4.03), 471 (3.70), ca. 510 (shoulder).
Anal. Calcd for C29H22N2O3S2: C, 68.21; H, 4.34; N, 5.49. Found: C, 68.31;
Ethyl 1-Benzoyl-7-methyl-3-(methylthio)thieno[3,4-b]indolizine-9-carboxy-
late (9a): 62% (from 4d and methyl iodide (5a)), red needles, mp 116—
118 °C (Lit.2) 113—115 °C). 1H-NMR (CDCl3, 400 MHz) d: 0.95 (3H, t,
Jꢂ7.1 Hz), 2.40 (3H, s), 2.67 (3H, s), 3.56 (2H, q, Jꢂ7.1 Hz), 6.68 (1H, dd, H, 4.18; N, 5.55.
Jꢂ7.1, 1.7 Hz), 7.40 (2H, br t, Jꢂ7.3 Hz), 7.50 (1H, br t, Jꢂ7.3 Hz), 7.94
Ethyl 1-(4-Chlorobenzoyl)-3-(2-cyanobenzylthio)-7-methylthieno[3,4-b]-
(2H, br d, Jꢂ7.1 Hz), 8.00 (1H, br s), 8.84 (1H, d, Jꢂ7.1 Hz). 13C-NMR indolizine-9-carboxylate (9n): 90% (from 4e and 2-cyanobenzyl bromide
(CDCl3, 400 MHz) d: 14.3, 21.7, 22.1, 58.9, 92.7, 113.8, 118.2, 121.5, (5e)), red prisms, mp 167—169 °C. IR (KBr) cmꢀ1: 2226, 1676, 1633. UV
122.4, 126.7, 128.2, 129.2, 132.2, 135.1, 135.4, 139.3, 142.3, 150.6, 164.3,
187.7. UV lmax (CHCl3) nm (log e) 331 (4.18), 478 (4.11), ca. 510 (shoul- der). Anal. Calcd for C29H21ClN2O3S2: C, 63.90; H, 3.88; N, 5.14. Found: C,
lmax (CHCl3) nm (log e) 321 (4.13), 426 (4.06), 479 (3.79), ca. 510 (shoul-
der).
Ethyl 1-(4-Chlorobenzoyl)-7-methyl-3-(methylthio)thieno[3,4-b]indolizine-
9-carboxylate (9b): 74% (from 4e and methyl iodide (5a)), red needles, mp
64.12; H, 3.79; N, 5.01.
Ethyl 1-(4-Bromobenzoyl)-3-(2-cyanobenzylthio)-7-methylthieno[3,4-b]-
indolizine-9-carboxylate (9o): 82% (from 4c and 2-cyanobenzyl bromide
167—169 °C (Lit.2) 163—165 °C). UV lmax (CHCl3) nm (log e) 332 (4.13), (5e)), brown prisms, mp 169—170 °C. IR (KBr) cmꢀ1: 2226, 1676, 1635.
480 (4.10), ca. 510 (shoulder).
UV lmax (CHCl3) nm (log e) 323 (3.99), 426 (3.93), 478 (3.65), ca. 510
(shoulder). Anal. Calcd for C29H21BrN2O3S2: C, 59.08; H, 3.59; N, 4.75.
Found: C, 59.32; H, 3.54; N, 4.57.
Ethyl 1-Benzoyl-3-(4-cyanobenzylthio)-7-methylthieno[3,4-b]indolizine-
9-carboxylate (9p): 70% (from 4d and 4-cyanobenzyl bromide (5f)), brown
prisms, mp 202—204 °C. IR (KBr) cmꢀ1: 2226, 1666, 1595. UV lmax
(CHCl3) nm (log e) 322 (4.20), 426 (4.20), 472 (3.79), ca. 510 (shoulder).
Anal. Calcd for C29H22N2O3S2: C, 68.21; H, 4.34; N, 5.49. Found: C, 68.23;
Ethyl 1-(4-Bromobenzoyl)-7-methyl-3-(methylthio)thieno[3,4-b]indolizine-
9-carboxylate (9c): 73% (from 4f and methyl iodide (5a)), red needles, mp
173—175 °C (Lit.2) 169—171 °C). UV lmax (CHCl3) nm (log e) 332 (4.12),
481 (4.09), ca. 510 (shoulder).
Ethyl 1-Benzoyl-3-benzylthio-7-methylthieno[3,4-b]indolizine-9-carboxy-
late (9d): 67% (from 4d and benzyl bromide (5b)), red needles, mp 144—
147 °C. IR (KBr) cmꢀ1: 1669, 1595. UV lmax (CHCl3) nm (log e) 329
(4.12), 425 (4.18), 479 (3.58), ca. 510 (shoulder). Anal. Calcd for H, 4.34; N, 5.26.
C28H23NO3S2: C, 69.25; H, 4.77; N, 2.88. Found: C, 69.37; H, 4.77; N, 2.77.
Ethyl 1-(4-Chlorobenzoyl)-3-(4-cyanobenzylthio)-7-methylthieno[3,4-b]-
Ethyl 3-Benzylthio-1-(4-chlorobenzoyl)-7-methylthieno[3,4-b]indolizine- indolizine-9-carboxylate (9q): 80% (from 4e and 4-cyanobenzyl bromide
9-carboxylate (9e): 75% (from 4e and benzyl bromide (5b)), red needles, mp
(5f)), orange needles, mp 171—173 °C. IR (KBr) cmꢀ1: 2228, 1670, 1601.
UV lmax (CHCl3) nm (log e) ca. 325 (shoulder), 426 (4.07), 478 (3.73), ca.
153—155 °C. IR (KBr) cmꢀ1: 1671, 1586. UV lmax (CHCl3) nm (log e) 326
(4.09), 428 (3.99), 476 (3.74), ca. 510 (shoulder). Anal. Calcd for 510 (shoulder). Anal. Calcd for C29H21ClN2O3S2: C, 63.90; H, 3.88; N, 5.14.
C28H22ClNO3S2: C, 64.67; H, 4.26; N, 2.69. Found: C, 64.77; H, 4.23; N, Found: C, 63.93; H, 4.15; N, 4.84.
2.62.
Ethyl 1-(4-Bromobenzoyl)-3-(4-cyanobenzylthio)-7-methylthieno[3,4-b]-
Ethyl 3-Benzylthio-1-(4-bromobenzoyl)-7-methylthieno[3,4-b]indolizine- indolizine-9-carboxylate (9r): 74% (from 4f and 4-cyanobenzyl bromide
9-carboxylate (9f): 80% (from 4f and benzyl bromide (5b)), orange needles,
(5f)), brown prisms, mp 173—174 °C. IR (KBr) cmꢀ1: 2228, 1670, 1585.
mp 163—165 °C. IR (KBr) cmꢀ1: 1667, 1584. UV lmax (CHCl3) nm (log e) UV lmax (CHCl3) nm (log e) ca. 326 (shoulder), 427 (3.99), 484 (3.87), ca.
326 (4.11), 429 (3.96), 477 (3.76), ca. 510 (shoulder). Anal. Calcd for 510 (shoulder). Anal. Calcd for C29H21BrN2O3S2: C, 59.08; H, 3.59; N, 4.75.
C28H22BrNO3S2: C, 59.57; H, 3.93; N, 2.48. Found: C, 59.49; H, 4.21; N, Found: C, 59.20; H, 3.78; N, 4.47.
2.28.
Ethyl 1-Benzoyl-3-(2-chlorobenzylthio)-7-methylthieno[3,4-b]indolizine-

January 2003
83
9-carboxylate (9s): 66% (from 4d and 2-chlorobenzyl bromide (5g)), red
flakes, mp 194—195 °C. IR (KBr) cmꢀ1: 1667, 1620. UV lmax (CHCl3) nm
(log e) 325 (4.09), 425 (4.07), 476 (3.71), ca. 510 (shoulder). Anal. Calcd
for C28H22ClNO3S2: C, 64.67; H, 4.26; N, 2.69. Found: C, 64.69; H, 4.29; N,
2.65.
Ethyl 1-Benzoyl-3-(4-chlorobenzylthio)-7-methylthieno[3,4-b]indolizine-
9-carboxylate (9t): 83% (from 4d and 4-chlorobenzyl bromide (5h)), red
needles, mp 156—157 °C. IR (KBr) cmꢀ1: 1667, 1630. UV lmax (CHCl3)
nm (log e) 327 (4.10), 426 (4.06), 473 (3.76), ca. 510 (shoulder). Anal.
Calcd for C28H22ClNO3S2: C, 64.67; H, 4.26; N, 2.69. Found: C, 64.78; H,
4.25; N, 2.59.
Ethyl 1-Benzoyl-3-(4-bromobenzylthio)-7-methylthieno[3,4-b]indolizine-
9-carboxylate (9u): 74% (from 4d and 4-bromobenzyl bromide (5i)), orange
flakes, mp 138—139 °C. IR (KBr) cmꢀ1: 1669, 1622. UV lmax (CHCl3) nm
(log e) 323 (4.09), 426 (4.05), 474 (3.73), ca. 510 (shoulder). Anal. Calcd
for C28H22BrNO3S2: C, 59.57; H, 3.93; N, 2.48. Found: C, 59.68; H, 3.96; N,
2.35.
Ethyl 1-Benzoyl-3-(4-fluorobenzylthio)-7-methylthieno[3,4-b]indolizine-
9-carboxylate (9v): 65% (from 4d and 4-fluorobenzyl bromide (5j)), orange
flakes, mp 145—147 °C. IR (KBr) cmꢀ1: 1669, 1597. UV lmax (CHCl3) nm
(log e) 327 (4.10), 426 (4.00), 476 (3.81), ca. 510 (shoulder). Anal. Calcd
for C28H22FNO3S2: C, 66.78; H, 4.40; N, 2.78. Found: C, 66.73; H, 4.30; N,
2.65.
Ethyl 1-Benzoyl-7-methyl-3-(1-phenylethylthio)thieno[3,4-b]indolizine-9-
carboxylate (9w): 91% (from 4d and 1-phenylethyl bromide (5k)), red
prisms, mp 151—153 °C. IR (KBr) cmꢀ1: 1672, 1620. UV lmax (CHCl3) nm
(log e) 325 (4.08), 426 (3.99), 472 (3.74), ca. 510 (shoulder). Anal. Calcd
for C29H25NO3S2: C, 69.71; H, 5.04; N, 2.80. Found: C, 69.82; H, 4.99; N,
2.75.
Ethyl 1-Benzoyl-3-(diphenylmethylthio)-7-methylthieno[3,4-b]indolizine-
9-carboxylate (9x): 61% (from 4d and diphenylmethyl bromide (5l)), orange
needles, mp 205—207 °C. IR (KBr) cmꢀ1: 1665, 1631. UV lmax (CHCl3)
nm (log e) 330 (4.10), 427 (4.14), 473 (3.65), ca. 510 (shoulder). Anal.
Calcd for C34H27NO3S2: C, 72.70; H, 4.85; N, 2.49. Found: C, 72.82; H,
4.83; N, 2.39.
Ethyl 1-Benzoyl-7-methyl-3-(2-phenylethylthio)thieno[3,4-b]indolizine-9-
carboxylate (9y): 83% (from 4d and 2-phenethyl bromide (5m)), orange
needles, mp 178—179 °C. IR (KBr) cmꢀ1: 1672, 1589. UV lmax (CHCl3)
nm (log e) 332 (4.13), 481 (4.05), ca. 510 (shoulder). Anal. Calcd for
C29H25NO3S2: C, 69.71; H, 5.04; N, 2.80. Found: C, 69.71; H, 4.96; N, 2.88.
Ethyl 1-Benzoyl-7-methyl-3-(2-phenylethylthio)thieno[3,4-b]indolizine-9-
carboxylate (9z): 77% (from 4e and 2-phenethyl bromide (5m)), red prisms,
mp 127—128 °C. IR (KBr) cmꢀ1: 1672, 1635. UV lmax (CHCl3) nm (log e)
332 (4.13), 485 (4.07), ca. 510 (shoulder). Anal. Calcd for C29H24ClNO3S2:
C, 65.22; H, 4.53; N, 2.62. Found: C, 65.32; H, 4.48; N, 2.52.
b]indolizine-9-carboxylate (7u) A single crystal (0.18ꢃ0.18ꢃ0.64 mm)
grown from CHCl3–hexane was used for the unit-cell determinations and
data collection by a Rigaku AFC5S four-circle diffractometer with graphite-
monochromated MoKa radiation (lꢂ0.71069Å). Crystal data of these com-
pounds are as follows: 7u: C27H20BrNO3S2; Mꢂ550.48; monoclinic, space
group P21/a (#14), Zꢂ4 with aꢂ8.700 (3)Å, bꢂ16.442 (2)Å, cꢂ
16.865 (3)Å, bꢂ99.68° (2); Vꢂ2378.1 (8)Å3 and Dcalc.ꢂ1.537 g/cm3. All
calculations were performed using the teXsan program.14) The structure was
solved by a direct method (SIR).15) The non-hydrogen atoms were refined
anisotropically, and the hydrogen atoms were attached at the idealized posi-
tion and not refined. The final R- and Rw-factors after full-matrix least-
squares refinements were 0.064 and 0.055 for 1850 (Iꢄ2.00s(I)) observed
reflections, respectively.
Crystallography of Ethyl 1-(4-Chlorobenzoyl-3-(2-cyanobenzylthio)-
7-methylthieno[3,4-b]indolizine-9-carboxylate (9n)
A single crystal
(0.42ꢃ0.54ꢃ0.68 mm) grown from CHCl3–hexane was used for the unit-
cell determinations and data collection by a Rigaku AFC5S four-circle dif-
fractometer with graphite-monochromated MoKa radiation (lꢂ0.71069Å).
The crystal data of these compounds are as follows: 9n: C29H21N2O3S2Cl;
¯
Mꢂ531.06; triclinic, space group P1 (#2), Zꢂ2 with aꢂ11.224 (2)Å,
bꢂ12.752 (3)Å, cꢂ10.709 (3)Å, aꢂ109.93 (2)°, bꢂ108.20° (3), gꢂ
101.93° (2); Vꢂ1281.9 (7)Å3 and Dcalc.ꢂ1.376 g/cm3. All calculations were
performed using the teXsan program.14) The structure was solved by a direct
method (SIR).15) 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
0.056 and 0.045 for 2873 (Iꢄ2.00s(I)) observed reflections, respectively.
Crystallography of Ethyl 1-Benzoyl-3-(4-cyanobenzylthio)-7-methylth-
ieno[3,4-b]indolizine-9-carboxylate (9p) A single crystal (0.08ꢃ0.42ꢃ
1.00 mm) grown from CHCl3–hexane was used for the unit-cell determina-
tions and data collection by a Rigaku AFC5S four-circle diffractometer with
graphite-monochromated MoKa radiation (lꢂ0.71069Å). The crystal data
of these compounds are as follows: 9p: C29H22N2O3S2; Mꢂ510.62; triclinic,
¯
space group P1 (#2), Zꢂ2 with aꢂ11.824 (2)Å, bꢂ13.586 (2)Å, cꢂ
8.902 (2)Å, aꢂ108.89 (1)°, bꢂ103.38° (1), gꢂ100.29° (1); Vꢂ1265.3 (5)Å3
and Dcalc.ꢂ1.340 g/cm3. All calculations were performed using the teXsan
program.14) The structure was solved by a direct method (SIR).15) 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 0.063 and 0.051 for 2598
(Iꢄ2.00s(I)) observed reflections, respectively.
Crystallography
of
Ethyl
1-(4-Cyanobenzoyl)-7-methyl-3-
(phenethylthio)thieno[3,4-b]indolizine-9-carboxylate (9z) A single crys-
tal (0.24ꢃ0.64ꢃ0.86 mm) grown from CHCl3–hexane was used for the unit-
cell determinations and data collections by a Rigaku AFC5S four-circle dif-
fractometer with graphite-monochromated MoKa radiation (lꢂ0.71069Å).
The crystal data of 9z are as follows: C29H24ClNO3S2; Mꢂ534.09; mono-
clinic, space group P21/a (#14), Zꢂ4 with aꢂ14.650 (3)Å, bꢂ11.055 (3)Å,
cꢂ15.963 (2)Å, bꢂ96.23° (1); Vꢂ2570.1 (9)Å3 and Dcalc.ꢂ1.380 g/cm3. All
calculations were performed using the teXsan program.14) The structure was
solved by a direct method (MITHRIL).15) The non-hydrogen atoms were re-
fined 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 0.073 and 0.078 for 2705 (Iꢄ2.00sI)) observed
reflections, respectively.
Crystallography of Ethyl 1-Benzoyl-3-(2-methylbenzylthio)thieno[3,4-
b]indolizine-9-carboxylate (7g) A single crystal (0.12ꢃ0.46ꢃ0.68 mm)
grown from CHCl3–hexane 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: 7g: C28H23NO3S2; Mꢂ485.61; triclinic, space
¯
group P1 (#2), Zꢂ2 with aꢂ11.736 (3)Å, bꢂ12.268 (4)Å, cꢂ9.437 (3)Å,
aꢂ109.31 (2)°, bꢂ105.68° (3), gꢂ73.98° (3); Vꢂ1208.2 (8)Å3 and
D
calc.ꢂ1.335 g/cm3. All calculations were performed using the teXsan pro-
gram.14) The structure was solved by a direct method (SIR).15) The non-hy-
drogen atoms were refined anisotropically, and the hydrogen atoms were at-
tached at the idealized position and not refined. The final R- and Rw-factors
after full-matrix least-squares refinements were 0.062 and 0.053 for 2857
(Iꢄ2.00s(I)) observed reflections, respectively.
References and Notes
1) For part 52 of this series, see Kakehi A., Ito S., Suga H., Miwa T.,
Mori T., Kobayashi T., Heterocycles, 57, 17—20 (2002).
2) Kakehi A., Ito S., Sa H., Chem. Pharm. Bull., 47, 1607—1613 (2000).
3) Kakehi A., Ito S., Hirata K., Zuo P., Chem. Pharm. Bull., 48, 865—
869 (2000).
4) Kakehi A., Ito S., Suga H., Yasuraoka K., Heterocycles, 54, 185—200
(2001).
5) Martin H.-D., Mayer B., Angew. Chem. Int. Ed. Engl., 22, 283—314
(1983).
6) Gleiter R., Schafer W., Acc. Chem. Res., 23, 369—375 (1990).
7) Kawabata T., Nagato M., Takasu K., Fuji K., J. Am. Chem. Soc., 119,
3169—3170 (1997).
8) Yamada S., Ichikawa M., Tetrahedron Lett., 40, 4231—4234 (1999).
9) These UV spectra were measured in chloroform with a drop of triethy-
lamine in order to avoid the influence of the hydrogen chloride gener-
ated.
Crystallography of Ethyl 1-(4-Chlorobenzoyl)-3-(2-cyanobenzylthio)-
thieno[3,4-b]indolizine-9-carboxylate (7n)
A single crystal (0.42ꢃ
0.48ꢃ0.82 mm) grown from CHCl3–hexane was used for the unit-cell deter-
minations and data collection by a Rigaku AFC5S four-circle diffractometer
with graphite-monochromated MoKa radiation (lꢂ0.71069Å). The crystal
data of these compounds are as follows: 7n: C28H19ClN2O3S2; Mꢂ517.04;
monoclinic, space group C2/c (#15), Zꢂ8 with aꢂ15.497 (3)Å,
bꢂ15.378 (4)Å, cꢂ22.152 (4)Å, bꢂ102.94° (2); Vꢂ5145 (2)Å3 and Dcalc.ꢂ
1.335 g/cm3. All calculations were performed using the teXsan program.14)
The structure was solved by a direct method (SIR).15) 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 0.068 and 0.055 for 2422
(Iꢄ2.00s(I)) observed reflections, respectively.
Crystallography of Ethyl 1-Benzoyl-3-(4-bromobenzylthio)thieno[3,4-
10) Johnson C. K., “ORTEP II, Report ORNL-5138,” Oak Ridge National

84
Vol. 51, No. 1
Laboratory, Oak Ridge, Tennessee, 1976.
11) The single crystals of compounds 7i, o, s and 9i, n were shown to have 14) teXsan for Windows version 1.06: Crystal Structure Analysis Package,
the corresponding G1 form by the X-ray analyses. Molecular Structure Corporation (1997-9).
12) The single crystals of compounds 7k and 9k, l, t were shown to have 15) SIR92: Altomare A., Cascarano G., Giacovazzo C., Guagliardi A., J.
the corresponding A1 form by the X-ray analyses. Appl. Cryst., 26, 343—350 (1993).
13) “WinMOPAC (Version 3.0)”, Fujitsu Corporation.