Preparation of new nitrogen-bridged heterocycles. 68. One-pot synthsis of 4-substituted 5-acylthieno[3,2-d]-thiazole derivatives

Article abstract of DOI:10.3987/COM-09-11852

The reactions of 5-acyl-3-(1-pyridinio)thiophene-2-thiolates with dimethyl acetylenedicarboxylate in xylene at the reflux temperature afforded the corresponding 2-unsubstituted 5-acylthieno[3,2-d]thiazoles in 25-69% yields together with dimethyl phthalate as another fragmentation product. In a few reactions, the unexpected products, dimethyl 2-[2-acylthieno[2′,3′:2,3]-1,4-thiazino[4,5-a]pyrrol-8-ylidene]succinate derivatives, were also isolated, though their yields were very low.

Full text of DOI:10.3987/COM-09-11852

HETEROCYCLES, Vol. 81, No. 1, 2010
175
HETEROCYCLES, Vol. 81, No. 1, 2010, pp. 175 - 184. © The Japan Institute of Heterocyclic Chemistry
Received, 8th October, 2009, Accepted, 5th November, 2009, Published online, 6th November, 2009
DOI: 10.3987/COM-09-11852
PREPARATION OF NEW NITROGEN-BRIDGED HETEROCYCLES. 68.
ONE-POT SYNTHSIS OF 4-SUBSTITUTED 5-ACYLTHIENO[3,2-d]-
THIAZOLE DERIVATIVES1
Akikazu Kakehi,* Hiroyuki Suga, Yukihisa Okumura, and Takashi Nishi
Department of Chemistry and Material Engineering, Faculty of Engineering,
Shinshu University, Wakasato, Nagano 380-8553, Japan
E-Mail: xkakehi@shinshu-u.ac.jp
Abstract – The reactions of 5-acyl-3-(1-pyridinio)thiophene-2-thiolates with
dimethyl acetylenedicarboxylate in xylene at the reflux temperature afforded the
corresponding 2-unsubstituted 5-acylthieno[3,2-d]thiazoles in 25―69% yields
together with dimethyl phthalate as another fragmentation product. In a few
reactions, the unexpected products, dimethyl 2-[2-acylthieno[2’,3’:2,3]-1,4-
thiazino[4,5-a]pyrrol-8-ylidene]succinate derivatives, were also isolated, though
their yields were very low.
Thieno[3,2-d]thiazole derivatives have been prepared by the cyclizations of suitably substituted
thiophenes2,3 and thiazoles4,5 or the thermolyses of thieno[3,2-e][1,2,4]triazines.6 However, these
methods are less useful from the preparative point of view, because the access to the substrates was not
easy in the former methods and the yields of the products were low in the latter. In the continuation of
our work in heterocyclic syntheses, we are interested in the development of a new construction method
for this thieno[3,2-d]thiazole skeleton, since we previously observed a smooth thermolysis of dimethyl
3-alkylthio-4-thia-1-azatetracyclo[5.4.0.05,11.06,8]undeca-2,9-diene-5,6-dicarboxylates
to
the
corresponding 5-(alkylthio)thiazoles and dimethyl phthalate,7 and we thought that an extension of this
type of reaction to the thiophene-fused substrates may lead to the corresponding thieno[3,2-d]thiazoles.
Furthermore, the ready availabilities of the substrates and the reagent (dimethyl acetylenedicarboxylate,
DMAD) and the simplicity of the operation also may be the main advantages of this reaction. Here we
report a one-pot synthesis of the title compounds, 2-unsubstituted 5-acylthieno[3,2-d]thiazole derivatives,
from the reactions of 5-acyl-3-(1-pyridinio)thiophene-2-thiolates with DMAD in xylene under the reflux
temperature.

176
HETEROCYCLES, Vol. 81, No. 1, 2010
RESULTS AND DISCUSSION
When the reactions of 5-acyl-3-(1-pyridinio)thiophene-2-thiolates (1a—l), which were prepared from the
alkaline treatment of 1-(acylmethyl)pyridinium chloride, carbon disulfide, and some acylmethyl halides
such as chloroacetone, phenacyl bromide, p-chlorophenacyl bromide, and p-bromophenacyl bromide
according to the procedure reported by us,8,9 with DMAD (2) were carried out in xylene at the reflux
temperature for 36 h and, by the column chromatographic separation of the resulting mixtures, the
expected 5-acylthieno[3,2-d]thiazole (3a—l) were obtained as colorless crystals in 25—69% yields,
together with dimethyl phthalate (4). In addition, the unexpected products, dimethyl
2-[2-acylthieno[2’,3’:2,3]-1,4-thiazino[4,5-a]pyrrol-8-ylidene]succinates 5a,b,e, were also obtained as
pale yellow products in the reactions of 3-(1-pyridinio)thiophene-2-thiolate (1a,b,e) with 2, but their
yields were in trace or very low.
Es
S9
Es
2
Es
R
3
N
7
4
Es
Es
Es
8
N
5 COR1
6
2
+
+
N
S1
2
COR1
S
S
reflux in xylene
4
R
5
6
1
S
3
4
R
R1OC
3a
l
Es=CO2Me
5a,b,e
1a
l
Yield (%)
R1
3
Entry
5
R
51
53
65
63
25
29
33
41
43
62
69
a
b
c
d
e
f
g
h
i
trace
trace
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Me
Ph
C6H4Cl-p
C6H4Br-p
Me
Ph
C6H4Cl-p
C6H4Br-p
0
0
9
0
0
0
0
0
0
0
CH2CO2Et Me
j
CH2CO2Et Ph
k
l
CH2CO2Et C6H4Cl-p
CH2CO2Et C6H4Br-p 66
Scheme 1
The structures of these thieno[3,2-d]thiazoles 3a—l were assigned by their spectral inspection and
elemental analyses. The IR spectra of 3a—l showed a largely shifted absorption band (1611—1649
cm-1) characteristics of carbonyl group at the 2-position of five-membered heteroaromatics such as furan
and thiophene. The 1H-NMR spectra exhibited the 2-proton on the thieno[3,2-d]thiazole ring as a sharp
singlet at low magnetic fields ( 8.89—8.98).
The chemical shifts for the 2-proton in

HETEROCYCLES, Vol. 81, No. 1, 2010
177
thieno[3,2-d]thiazole derivatives 3a—l are almost parallel to
those ( 8.63—8.81) for the 2-proton in 5-(alkylthio)thiazole
derivatives reported earlier by us.7 The elementary analyses
for these products 3a—l were in good accord with our proposed
compositions and the X-ray analysis for one compound,
5-(p-bromobenzoyl)-4-(ethoxycarbonylmethyl)thieno[3,2-d]-
thiazole (3l), confirmed its structure. The ORTEP drawing10 of
3l is shown in Figure 1. On the other hand, the structures of
O2
N1
O1
O3
S1
S2
1
by-products 5a,b,e were presumed from the H-NMR spectral
Br1
inspection and finally determined by the X-ray analysis of one
Figure 1. ORTEP drawing of 3l
compound 5a because of their low yields. In particular, the
numbers of the hydrogen atoms in 5a,b,e were indicated to be 17, 19, and 19 respectively and their
numbers coincided with those in the molecular formulas (C18H17NO5S2, C23H19NO5S2, and C23H19NO5S2)
expected for the 1:1 adducts between 1a,b,e and reagent 2. For example, the 1H-NMR spectrum showed
four methyl proton singlet signals ( 2.51, 2.79, 3.78, and 3.85) due to a methyl and an acetyl group on
the thiophene ring and to two methoxycarbonyl groups, a methylene singlet ( 3.88), and three vicinal
unsaturated protons ( 6.50 (1H, dd, J=3.9 and 2.9 Hz), 6.53 (1H, dd, J=2.9 and 1.4 Hz), and 7.44 (1H, dd,
J=3.9 and 1.4 Hz)). The disappearance of the vicinal five-proton configuration on the pyridine ring in
starting materials 1a,b,e and the new appearance of a vicinal three-proton one which has small vicinal
couplings (J=3.9 and 2.9 Hz) in comparison with those in 6-menbered aza-heterocycles made us suspect
the presence of an aromatic pyrrole ring in the structures of products 5a,b,e. Since we had previously
observed
the
formation
of
dimethyl
4-aryl-5-thia-2,3-
diazatricyclo[4.3.2.02,7]undeca-3,8,10-triene-6,11-dicarboxylates
(2,5-dihydropyrrole ring is involved) via the intervention of
O3
O2
O5
intermediates
dimethyl
5aH-2-arylpyrido[1,2-d][1,3,4]-
thiadiazepine-4,5-dicarboxylates (1,2-dihydropyridine ring is
involved) in the reactions of pyridinium 1-(arylthiocarbonyl)-
aminides with 2,11,12 it is not unimaginable such successive ring
changes are possible: 1,2-dihydropyridine → 2,5-dihydropyrrole →
aromatic pyrrole. However, we could not determine their structures
with certainty only by these data. Fortunately, one (5a) of these
products was obtained as single crystals, so X-ray analysis was
performed and the structure was finally confirmed to be dimethyl
O4
S2
N1
S1
O1
Figure 2. ORTEP drawing of 5a

178
HETEROCYCLES, Vol. 81, No. 1, 2010
2-[2-acetyl-3-methylthieno[2’,3’:2,3]-1,4-thiazino[4,5-a]pyrrol-8-ylidene]succinate (see Figure 2).
The possible reaction mechanisms (Scheme 2) for the formation of products 3a—l and 5a,b,e are shown
in Scheme 2. The formation mechanism of thieno[3,2-d]thiazoles 3a—l is fundamentally the same as
that proposed earlier by us for the formation of 5-(alkylthio)thiazoles.7 On the other hand, that for
by-products 5a,b,e was unclear, but it must involve a key intermediate such as 10.
Es
Es
Es
H
Es
a
Es
Es
Es
Es
10
Path b
2
5,10-Cycliz.
S
S
S
b
S
N
N
N
N
1,2-Shift
S
S
5
S
R1
R1
6
R1
S
l
R1
10
R2
R2
R2
R2
7
1a
IDA
Es=CO2Me
Path a
Es
R
Es
S
R
N
N
S
FRAG
Es
RDA
R
COR1
N
COR1
S
l
COR1
S
S
S
N
Es
Es
S
Es
S
3a
9
8
Es
Es
R1
5a,b,e
R2
IDA = intramolecular Diels-Alder reaction
RDA = retro-Diels-Alder reaction
FRAG= fragmentation
4
Scheme 2
EXPERIMENTAL
Melting points were measured with a Yanagimoto micromelting point apparatus and were not corrected.
13
Microanalyses were carried out on a Perkin-Elmer 2400 elemental analyzer.
1H-NMR and C-NMR
13
spectra were determined with a JEOL JNM-LA400 (1H: 400 MHz and C: 100.4 MHz) spectrometer in
deuteriochloroform with tetramethylsilane used as the internal standard; the chemical shifts were
expressed in  values.
The IR spectra were taken with a JASCO FT/IR-5300 IR spectrophotometer.
Preparations of 3-(1-pyridinio)thiophene-2-thiolates (1a―l).
Of these compounds
4-ethoxycarbonylmethyl-3-(1-pyridinio)thiophene-2-thiolates (1i―l) were prepared according to our
previous paper,8,9 and other 4-methyl- and 4-phenyl derivatives 1a―h according to the following
general procedure. An ethanolic solution (50 mL) of 1-acetonyl- or 1-phenacylpyridinium chloride (10
mmol) and carbon disulfide (1.140 g, 15 mmol) was treated with an aqueous solution (10 mL) of sodium
hydroxide (1.000 g, 25 mmol) under stirring at room temperature for 0.5 h, and then an alkylating agent
(10 mmol) such as chloroacetone, phenacyl chloride, p-chlorophenacyl bromide, and p-bromophenacyl
bromide was added to the reaction mixture and the resulting solution was allowed to react at that

HETEROCYCLES, Vol. 81, No. 1, 2010
179
temperature for another 12 h. The solution was poured into ice-water (300 mL) and the precipitates
which separated were collected by suction. Recrystallization of the crude products from acetone afforded
the corresponding 3-(1-pyridinio)thiophene-2-thiolates.
Some data for the new products 1a―i are as follows:
5-Acetyl-4-methyl-3-(1-pyridinio)thiophene-2-thiolate (1a): From 1-acetonylpyridinium chloride,
carbon disulfide, and chloroacetone, 69%, brown needles (from CHCl3), mp 269—272 °C. IR (KBr):
1628 cm-1. 1H-NMR: 2.33 (3H, s, COMe), 2.39 (3H, s, 4-Me), 8.06 (2H, br dd, J=7.8, 5.6 Hz, Py-H),
8.45 (1H, br t, J=7.8 Hz, Py-H), 8.74 (2H, br d, J=5.6 Hz, Py-H). Anal. Calcd for C12H11NOS2: C,
57.80; H, 4.45; N, 5.62. Found: C, 57.96; H, 4.32; N, 5.59.
5-Benzoyl-4-methyl-3-(1-pyridinio)thiophene-2-thiolate (1b): From 1-acetonylpyridinium chloride,
carbon disulfide, and phenacyl chloride, 95%, brown needles (from CHCl3), mp 279—281 °C. IR
(KBr): 1615 cm-1. 1H-NMR: 2.39 (3H, s, 4-Me), 7.43 (2H, br dd, J=7.6, 7.1 Hz, Ph-H), 7.51 (1H, br t,
J=7.6 Hz, Ph-H), 7.80 (2H, br d, J=7.1 Hz, Ph-H), 8.08 (2H, br dd, J=7.8, 5.6 Hz, Py-H), 8.47 (1H, br t,
J=7.8 Hz, Py-H), 8.76 (2H, br d, J=5.6 Hz, Py-H). Anal. Calcd for C17H13NOS2: C, 65.57; H, 4.21; N,
4.50. Found: C, 65.79; H, 4.09; N, 4.39.
5-(p-Chlorobenzoyl)-4-methyl-3-(1-pyridinio)thiophene-2-thiolate (1c): From 1-acetonylpyridinium
chloride, carbon disulfide, and p-chlorophenacyl bromide, 94%, brown needles (from CHCl3), mp
260—263 °C. IR (KBr): 1620 cm-1. 1H-NMR: 2.38 (3H, s, 4-Me), 7.41 (2H, br d, J=8.3 Hz, Ph-H),
7.76 (2H, br d, J=8.3 Hz, Ph-H), 8.09 (2H, br dd, J=7.8, 5.6 Hz, Py-H), 8.47 (1H, br t, J=7.8 Hz, Py-H),
8.76 (2H, br d, J=5.6 Hz, Py-H). Anal. Calcd for C17H12ClNOS2: C, 59.04; H, 3.50; N, 4.05. Found: C,
58.99; H, 3.56; N, 4.03.
4-(p-Bromobenzoyl)-4-methyl-3-(1-pyridinio)thiophene-2-thiolate (1d): From 1-acetonylpyridinium
chloride, carbon disulfide, and p-bromophenacyl chloride, 89%, brown needles (from CHCl3), mp
243—245 °C. IR (KBr): 1618 cm-1. 1H-NMR: 2.37 (3H, s, 4-Me), 7.57 (2H, br d, J=8.3 Hz, Ph-H),
7.68 (2H, br d, J=8.3 Hz, Ph-H), 8.09 (2H, br dd, J=7.8, 5.6 Hz, Py-H), 8.48 (1H, br t, J=7.8 Hz, Py-H),
8.76 (2H, br d, J=5.6 Hz, Py-H). Anal. Calcd for C17H12BrNOS2: C, 52.31; H, 3.10; N, 3.59. Found: C,
52.55; H, 3.09; N, 3.36.
5-Acetyl-4-phenyl-3-(1-pyridinio)thiophene-2-thiolate (1e): From 1-phenacylpyridinium chloride,
carbon disulfide, and chloroacetone, 71%, brown needles (from CHCl3), mp 279—281 °C. IR (KBr):
1603 cm-1. 1H-NMR: 1.96 (3H, s, COMe), 7.15—7.21 (2H, m, Ph-H), 7.29—7.35 (3H, m, Ph-H), 7.77
(2H, br dd, J=7.8, 5.6 Hz, Py-H), 8.20 (1H, br t, J=7.8 Hz, Py-H), 8.60 (2H, br d, J=5.6 Hz, Py-H).
Anal. Calcd for C17H13NOS2: C, 65.57; H, 4.21; N, 4.50. Found: C, 65.61; H, 4.19; N, 4.47.
5-Benzoyl-4-phenyl-3-(1-pyridinio)thiophene-2-thiolate (1f): From 1-phenacylpyridinium chloride,
carbon disulfide, and phenacyl chloride, 84%, orange needles (from CHCl3), mp 272—274 °C. IR

180
HETEROCYCLES, Vol. 81, No. 1, 2010
(KBr): 1620 cm-1. 1H-NMR: 6.93 (2H, br d, J=6.8 Hz, Ph-H), 7.04—7.14 (3H, m, Ph-H), 7.17 (2H, br
dd, J=7.8, 7.3 Hz, Ph-H), 7.30 (1H, br t, J=7.3 Hz, Ph-H), 7.58 (2H, br d, J=7.8 Hz, Ph-H), 7.78 (2H, br
dd, J=7.8, 5.6 Hz, Py-H), 8.22 (1H, br t, J=7.8 Hz, Py-H), 8.61 (2H, br d, J=5.6 Hz, Py-H).
Anal.
Calcd for C22H15NOS2: C, 70.75; H, 4.05; N, 3.75. Found: C, 70.70; H, 3.86; N, 3.98.
5-(p-Chlorobenzoyl)-4-phenyl-3-(1-pyridinio)thiophene-2-thiolate (1g): From 1-phenacylpyridinium
chloride, carbon disulfide, and p-chlorophenacyl bromide, 83%, brown needles (from CHCl3), mp
262—264 °C. IR (KBr): 1620 cm-1. 1H-NMR: 6.91 (2H, br d, J=7.3 Hz, Ph-H), 7.04—7.20 (5H, m,
Ph-H), 7.48 (2H, br d, J=8.3 Hz, Ph-H), 7.79 (2H, br dd, J=7.8, 5.6 Hz, Py-H), 8.24 (1H, br t, J=7.8 Hz,
Py-H), 8.60 (2H, br d, J=5.6 Hz, Py-H).
Anal. Calcd for C22H14ClNOS2: C, 64.78; H, 3.46; N, 3.43.
Found: C, 64.98; H, 3.48; N, 3.21.
5-(p-Bromobenzoyl)-4-phenyl-3-(1-pyridinio)thiophene-2-thiolate (1h): From 1-phenacylpyridinium
chloride, carbon disulfide, and p-bromophenacyl bromide, 85%, orange needles (from CHCl3), mp
247—250 °C. IR (KBr): 1620 cm-1.
1H-NMR: 6.90 (2H, br d, J=7.1 Hz, Ph-H), 7.08 (2H, br dd,
J=7.2, 7.1 Hz, Ph-H), 7.16 (1H, br t, J=7.2 Hz, Ph-H), 7.28 (2H, br d, J=8.3 Hz, Ph-H), 7.41 (2H, br d,
J=8.3 Hz, Ph-H), 7.78 (2H, br dd, J=7.8, 5.6 Hz, Py-H), 8.23 (1H, br t, J=7.8 Hz, Py-H), 8.60 (2H, br d,
J=5.6 Hz, Py-H).
Anal. Calcd for C22H14BrNOS2: C, 58.41; H, 3.12; N, 3.10. Found: C, 58.30; H,
3.19; N, 3.14.
5-Acetyl-4-ethoxycarbonylmethyl-3-(1-pyridinio)thiophene-2-thiolate
(1i):
From
1-(3-ethoxycarbonylacetonyl)pyridinium chloride, carbon disulfide, and chloroacetone, 54%, brown
needles (from CHCl3), mp 205—210 °C. IR (KBr): 1618, 1711 cm-1. 1H-NMR: 1.25 (3H, t, J=7.1 Hz,
OCH2CH3), 2.38 (3H, s, COMe), 3.73 (2H, s, CH2CO), 4.13 (2H, q, J=7.1 Hz, OCH2CH3), 8.04 (2H, br
dd, J=7.8, 5.6 Hz, Py-H), 8.44 (1H, br t, J=7.8 Hz, Py-H), 8.88 (2H, br d, J=5.6 Hz, Py-H).
Anal.
Calcd for C15H15NO3S2: C, 56.05; H, 4.70; N, 4.36. Found: C, 56.04; H, 4.78; N, 4.30.
Reactions of 3-(1-pyridinio)thiophene-2-thiolates (1) with dimethyl acetylenedicarboxylate (2) at the
xylene reflux temperature. General Method. xylene solution (30 mL) of
A
3-(1-pyridinio)thiophene-2-thiolate (1, 1 mmol) and dimethyl acetylenedicarboxylate (2, 0.156g, 1.1
mmol) was heated at the reflux temperature for 36 h. The resulting solution was concentrated under
reduced pressure to remove the solvent. The residue was separated by column chromatography on
alumina using hexane and then ether as an eluent. The combined ether fraction was concentrated under
reduced pressure, and recrystallization of the residue from chloroform-hexane afforded the corresponding
thieno[3,2-d]thiazole derivative (3).
1
In these reactions the formation of dimethyl phthalate (4) was always confirmed by H-NMR spectra of
the crude products. Some data for these products 3a―i are as follows:

HETEROCYCLES, Vol. 81, No. 1, 2010
181
5-Acetyl-4-methylthieno[3,2-c]thiazole (3a): From 1a and 2, 51%, colorless needles, mp 68—71 °C
(from CHCl3-hexane). IR (KBr): 1634 cm-1. 1H-NMR: 2.62 (3H, s, 4-Me), 2.87 (3H, s, COMe), 8.92
(1H, s, 2-H). 13C-NMR: 15.00, 29.34, 134.48, 135.08, 141.48, 155.82 (2-C), 162.61, 191.26. Anal.
Calcd for C8H7NOS2: C, 48.71; H, 3.58; N, 7.10. Found: C, 48.64; H, 3.61; N, 7.14.
5-Benzoyl-4-methylthieno[3,2-c]thiazole (3b): From 1b and 2, 53%, colorless needles, mp 69—70 °C
(from CHCl3-hexane). IR (KBr): 1616 cm-1. 1H-NMR: 2.65 (3H, s, 4-Me), 7.50 (2H, br dd, J=8.0, 7.4
Hz, Ph-H), 7.60 (1H, br t, J=7.4 Hz, Ph-H), 7.82 (2H, br d, J=8.0 Hz, Ph-H), 8.93 (1H, s, 2-H). Anal.
Calcd for C13H9NOS2: C, 60.21; H, 3.50; N, 5.40. Found: C, 60.08; H, 3.52; N, 5.28.
5-(p-Chlorobenzoyl)-4-methylthieno[3,2-c]thiazole (3c): From 1c and 2, 65%, colorless needles, mp
140—143 °C (from CHCl3-hexane). IR (KBr): 1640 cm-1. 1H-NMR: 2.66 (3H, s, 4-Me), 7.48 (2H, br
d, J=8.4 Hz, Ph-H), 7.78 (2H, br d, J=8.4 Hz, Ph-H), 8.94 (1H, s, 2-H). 13C-NMR: 15.23, 128.64, 130.35,
135.13, 136.12, 137.16, 138.75, 138.95, 155.97 (2-C), 162.14, 188.34. Anal. Calcd for C13H8ClNOS2: C,
53.15; H, 2.74; N, 4.77. Found: C, 53.11; H, 2.75; N, 4.80.
5-(p-Bromobenzoyl)-4-methylthieno[3,2-c]thiazole (3d): From 1d and 2, 63%, colorless needles, mp
152—153 °C (from CHCl3-hexane). IR (KBr): 1640 cm-1. 1H-NMR: 2.66 (3H, s, 4-Me), 7.64 (2H, br
d, J=8.5 Hz, Ph-H), 7.70 (2H, br d, J=8.5 Hz, Ph-H), 8.94 (1H, s, 2-H). 13C-NMR: 15.25, 127.35,
130.45, 131.64, 135.19, 136.22, 137.63, 138.94, 155.96 (2-C), 162.19, 188.48. Anal. Calcd for
C13H8BrNOS2: C, 46.16; H, 2.38; N, 4.14. Found: C, 46.39; H, 2.25; N, 4.05.
5-Acetyl-4-phenylthieno[3,2-c]thiazole (3e): From 1e and 2, 25%, colorless needles, mp 137—139 °C
(from CHCl3-hexane). IR (KBr): 1636 cm-1. 1H-NMR: 2.15 (3H, s, COMe), 7.48—7.57 (5H, m,
Ph-H), 8.89 (1H, s, 2-H). Anal. Calcd for C13H9NOS2: C, 60.21; H, 3.50; N, 5.40. Found: C, 60.20; H,
3.53; N, 5.39.
5-Benzoyl-4-phenylthieno[3,2-c]thiazole (3f): From 1f and 2, 29%, colorless needles, mp 151—153 °C
(from CHCl3-hexane). IR (KBr): 1611 cm-1. 1H-NMR: 7.13 (2H, br dd, J=8.1, 7.5 Hz, Ph-H),
7.13—7.19 (3H, m, Ph-H), 7.30 (1H, br t, J=7.5 Hz, Ph-H), 7.38—7.44 (2H, m, Ph-H), 7.59 (2H, br d,
J=8.1 Hz, Ph-H), 8.97 (1H, s, 2-H). 13C-NMR: 127.66, 127.92, 128.20, 129.52, 130.14, 132.16, 133.11,
134.90, 136.79, 137.30, 141.61, 156.26 (2-C), 160.28, 190.09. Anal. Calcd for C18H11NOS2: C, 67.27;
H, 3.45; N, 4.36. Found: C, 67.40; H, 3.36; N, 4.32.
5-(p-Chlorobenzoyl)-4-phenylthieno[3,2-c]thiazole (3g): From 1g and 2, 33%, colorless needles, mp
162—164 °C (from CHCl3-hexane). IR (KBr): 1622 cm-1. 1H-NMR: 7.09 (2H, br d, J=8.4 Hz, Ph-H),
7.17—7.25 (3H, m, Ph-H), 7.37—7.43 (2H, m, Ph-H), 7.51 (2H, br d, J=8.4 Hz, Ph-H), 8.98 (1H, s, 2-H).
13C-NMR: Anal. Calcd for C18H10ClNOS2: C, 60.75; H, 2.83; N, 3.94. Found: C, 60.92; H, 2.71; N, 3.88.
5-(p-Bromobenzoyl)-4-phenylthieno[3,2-c]thiazole (3h): From 1h and 2, 41%, colorless needles, mp
174—176 °C (from CHCl3-hexane). IR (KBr): 1622 cm-1. 1H-NMR: 7.16—7.25 (3H, m, Ph-H), 7.26

182
HETEROCYCLES, Vol. 81, No. 1, 2010
(2H, br d, J=8.5 Hz, Ph-H), 7.36—7.41 (2H, m, Ph-H), 7.43 (2H, br d, J=8.5 Hz, Ph-H), 8.98 (1H, s, 2-H).
Anal. Calcd for C18H10BrNOS2: C, 54.01; H, 2.52; N, 3.50. Found: C, 54.02; H, 2.45; N, 3.56.
5-Acetyl-4-(ethoxycarbonylmethyl)thieno[3,2-c]thiazole (3i): From 1i and 2, 43%, colorless needles,
mp 126—129 °C (from CHCl3-hexane). IR (KBr): 1649, 1732 cm-1. 1H-NMR: 1.28 (3H, t, J=7.2 Hz,
OCH2CH3), 2.59 (3H, s, COMe), 4.20 (2H, q, J=7.2 Hz, OCH2CH3), 4.39 (2H, s, CH2CO), 8.94 (1H, s,
2-H). 13C-NMR: 14.15, 28.77, 34.02, 61.10, 131.08, 133.92, 141.10, 156.50 (2-C), 161.94, 169.61,
190.73. Anal. Calcd for C11H11NO3S2: C, 49.05; H, 4.12; N, 5.20. Found: C, 49.10; H, 4.08; N, 5.19.
5-Benzoyl-4-(ethocycarbonylmethyl)thieno[3,2-c]thiazole (3j): From 1j and 2, 62%, colorless needles,
mp 130—131 °C (from CHCl3-hexane). IR (KBr): 1632, 1730 cm-1. 1H-NMR: 1.25 (3H, t, J=7.2 Hz,
OCH2CH3), 4.17 (2H, q, J=7.2 Hz, OCH2CH3), 4.27 (2H, s, CH2CO), 7.49 (2H, br dd, J=7.7, 7.4 Hz,
Ph-H), 7.60 (1H, br t, J=7.4 Hz, Ph-H), 7.86 (2H, br d, J=7.7 Hz, Ph-H), 8.94 (1H, s, 2-H). 13C-NMR:
14.23, 34.12, 61.12, 128.37, 129.05, 131.86, 132.53, 135.09, 138.68, 140.48, 156.37 (2-C), 161.77,
169.67, 189.06. Anal. Calcd for C16H13NO3S2: C, 57.99; H, 3.95; N, 4.23. Found: C, 58.17; H, 4.07; N,
3.93.
5-(p-Chlorobenzoyl)-4-(ethoxycarbonylmethyl)thieno[3,2-c]thiazole (3k): From 1k and 2, 69%,
colorless needles, mp 122—124 °C (from CHCl3-hexane). IR (KBr): 1632, 1738 cm-1. 1H-NMR: 1.25
(3H, t, J=7.2 Hz, OCH2CH3), 4.17 (2H, q, J=7.2 Hz, OCH2CH3), 4.28 (2H, s, CH2CO), 7.47 (2H, br d,
J=8.5 Hz, Ph-H), 7.82 (2H, br d, J=8.5 Hz, Ph-H), 8.95 (1H, s, 2-H). Anal. Calcd for C16H12ClNO3S2: C,
52.53; H, 3.31; N, 3.83. Found: C, 52.64; H, 3.24; N, 3.78.
5-(p-Bromobenzoyl)-4-(ethoxycarbonylmethyl)thieno[3,2-c]thiazole (3l): From 1l and 2, 66%,
colorless needles, mp 147—149 °C (from CHCl3-hexane). IR (KBr): 1630, 1738 cm-1. 1H-NMR: 1.25
(3H, t, J=7.2 Hz, OCH2CH3), 4.17 (2H, q, J=7.2 Hz, OCH2CH3), 4.28 (2H, s, CH2CO), 7.64 (2H, br d,
J=8.5 Hz, Ph-H), 7.74 (2H, br d, J=8.5 Hz, Ph-H), 8.95 (1H, s, 2-H). Anal. Calcd for C16H12BrNO3S2: C,
46.84; H, 2.95; N, 3.41. Found: C, 46.86; H, 2.92; N, 3.42.
Dimethyl 2-[2-acetyl-3-methylthieno[2’,3’:2,3]-1,4-thiazino[4,5-a]pyrrol-8-ylidene]succinate (5a):
1
From 1a and 2, trace, pale yellow prisms. H-NMR: 2.51 (3H, s, 3-Me), 2.79 (3H, s, COMe), 3.78 and
3.85 (each 3H, s, OMe), 3.88 (2H, s, CH2CO), 6.50 (1H, dd, J=3.9, 2.9 Hz, 6-H), 6.53 (1H, dd, J=3.9, 1.4
Hz, 7-H), 7.44 (1H, dd, J=2.9, 1.4 Hz, 5-H).
Dimethyl 2-[2-benzoyl-3-methylthieno[2’,3’:2,3]-1,4-thiazino[4,5-a]pyrrol-8-ylidene]succinate (5b):
From 1b and 2, trace, pale yellow powder. 1H-NMR: 2.70 (3H, s, 3-Me), 3.78 and 3.85 (each 3H, s, OMe),
3.89 (2H, s, CH2CO), 6.51 (1H, dd, J=3.9, 2.9 Hz, 6-H), 6.54 (1H, dd, J=3.9, 1.4 Hz, 7-H), 7.48 (2H, br
dd, J=7.6, 7.5 Hz, Ph-H), 7.49 (1H, dd, J=1.9, 1.4 Hz, 5-H), 7.60 (1H, br t, J=7.5 Hz, Ph-H), 7.80(2H, br
d, J=7.6 Hz, Ph-H).

HETEROCYCLES, Vol. 81, No. 1, 2010
183
Dimethyl 2-[2-acetyl-3-phenylthieno[2’,3’:2,3]-1,4-thiazino[4,5-a]pyrrol-8-ylidene]succinate (5e):
From 1e and 2, 9%, pale yellow prisms (from CHCl3-hexane), mp 189—191 °C (from CHCl3-hexane).
IR (KBr): 1642, 1672, 1738 cm-1. 1H-NMR: 1.92 (3H, s, COMe), 3.75 and 3.86 (each 3H, s, OMe), 3.87
(2H, s, CH2CO), 6.11 (1H, dd, J=3.9, 2.9 Hz, 6-H), 6.23 (1H, dd, J=3.9, 1.4 Hz, 7-H), 6.43 (1H, dd, J=2.9,
1.4 Hz, 5-H), 7.37—7.42 (2H, m, Ph-H), 7.52—7.57 (3H, m, Ph-H). Anal. Calcd for C23H19NO5S2: C,
60.91; H, 4.22; N, 3.09. Found: C, 60.98; H, 4.18; N, 3.01.
Crystallography of 5-(p-bromobenzoyl)-4-ethoxycarbonylmethylthieno[3,2-d]thiazole (3l)
A
single crystal (0.68×0.54×0.22 mm) grown from CHCl3–hexane was used for the unit-cell determinations
and the data collection by a Rigaku AFC5S four-circle diffractometer with graphite-monochromated
MoKradiation (=0.71069 Å). Crystal data of these compounds are as follows: 3a: C18H17NO5S2;
M=391.46; monoclinic, space group P-1 (#2), Z=4 with a=17.967 (18) Å, b=11.708 (10) Å, c=10.334
(11) Å, =90.00(9)o; =102.33 (6)o; =88.74(9)o; V=1777.5 (29) Å3, and Dcalc.=1.463 g/cm3. All
calculations were performed using CrystalStructure.13
The structure was solved by a direct method
(SIR).14 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 0.064 and 0.053 respectively for 5382 (I>2.00 observed reflections.
Crystallography of dimethyl 2-[2-acetyl-3-methylthieno[2’,3’:2,3]-1,4-thiazino[4,5-a]pyrrol-8-
ylidene]succinate (5a).
A single crystal (0.68×0.54×0.22 mm) grown from CHCl3–hexane was used
for the unit-cell determinations and the data collection by a Rigaku AFC5S four-circle diffractometer with
graphite-monochromated MoKradiation (=0.71069 Å). Crystal data of these compounds are as
follows: 3a: C18H17NO5S2; M=391.46; monoclinic, space group P-1 (#2), Z=4 with a=17.967 (18) Å,
b=11.708 (10) Å, c=10.334 (11) Å, =90.00(9)o; =102.33 (6)o; =88.74(9)o; V=1777.5 (29) Å3, and
Dcalc.=1.463 g/cm3. All calculations were performed using CrystalStructure.13
The structure was
solved by a direct method (SIR).14 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 0.064 and 0.053 respectively for 5382 (I>2.00 observed
reflections.
REFERENCES AND NOTES
1. For part 67 of this series, see A. Kakehi, H. Suga, Y. Okumura, M. Shinohara, T. Kako, T. Sekiguchi,
and M. Shiro, Chem. Pharm. Bull., 2009, 57, 1385.
2. L. Grehn, J. Heterocycl. Chem., 1978, 15, 81.

184
HETEROCYCLES, Vol. 81, No. 1, 2010
3. C. Paulmier, Bull. Soc. Chim. Fr., 1980, 151.
4. T. Y. Kvitko, R. V. Khozeeva, N. S. Fedorova, V. A. Sminova, and A. V. El’tsov, Chim. Getro.
Soedin., 1979, 474.
5. M. Augustin, W. Dölling, and P. Kindt, Zeit. Fuer Chem., 1990, 30, 18.
6. Y. A. Ibrahim, N. A. Al-Awadi, and M. R. Ibrahim, Tetrahedron, 2004, 60, 9121.
7. A. Kakehi, S. Ito, M. Mitani, and M. Kanaoka, Bull. Chem. Soc. Jpn., 1994, 67, 1646.
8. A. Kakehi, H. Suga, T. Miwa, T. Mori, and T. Kobayashi, Heterocycles, 2002, 57, 17.
9. A. Kakehi, H. Suga, T. Miwa, T. Mori, T. Fujii, N. Tanaka, and T. Kobayashi, Chem. Pharm Bull.,
2003, 51, 75.
10. C. K. Johnson, "ORTEO II, Report ORNL-5138," Oak Ridge National Laboratory, Oak Ridge,
Tennessee, 1976.
11. A. Kakehi, S. Ito, F. Ishida, and Y. Tominaga, Heterocycles, 1995, 42, 2657.
12. A. Kakehi, S. Ito, F. Ishida, and Y. Tominaga, J. Org. Chem., 1997, 62, 7788.
13. CrystalStructure 3.8: Crystal Structure Analysis Package, Rigaku and Rigaku/MSC (2000—2006).
9009 New Trails Dr. The Woodlands TX 77381 USA.
14. SIR92: A. Altomore, M. Cascarano, C. Giacovazzo, and A. Guagliardi, J. Appl. Cryst., 1994, 26,
343.