Synthesis of some prospective bioactive azeto[2,1-d][1,5]benzothiazepinones

Article abstract of DOI:10.1080/10426501003657527

Ten azeto[2,1-d][1,5]benzothiazepinone derivatives 6a-j were synthesized starting from 4-acetyl-2-phenyl-1,2,3-triazole 1. First, condensation of 1 with various aldehydes 2a-e afforded α,β-unsaturated carbonyl compounds 3a-e, which subsequently underwent

Full text of DOI:10.1080/10426501003657527

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Synthesis of Some Prospective Bioactive
Azeto[2,1-d][1,5]benzothiazepinones
Songwei Shen a , Jiawei Ye a & Fangmin Liu a
a College of Materials and Chemical Engineering , Hangzhou Normal
University , Hangzhou , China
Published online: 05 Nov 2010.
To cite this article: Songwei Shen , Jiawei Ye & Fangmin Liu (2010) Synthesis of Some Prospective
Bioactive Azeto[2,1-d][1,5]benzothiazepinones, Phosphorus, Sulfur, and Silicon and the Related
Elements, 185:11, 2366-2374, DOI: 10.1080/10426501003657527
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Phosphorus, Sulfur, and Silicon, 185:2366–2374, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003657527
SYNTHESIS OF SOME PROSPECTIVE BIOACTIVE
AZETO[2,1-d][1,5]BENZOTHIAZEPINONES
Songwei Shen, Jiawei Ye, and Fangmin Liu
College of Materials and Chemical Engineering, Hangzhou Normal University,
Hangzhou, China
Ten azeto[2,1-d][1,5]benzothiazepinone derivatives 6a–j were synthesized starting from
4-acetyl-2-phenyl-1,2,3-triazole 1. First, condensation of 1 with various aldehydes 2a–e
afforded α,β-unsaturated carbonyl compounds 3a–e, which subsequently underwent
cyclization with o-aminothiophenol to yield the corresponding 2,4-disubstituted-1,5-
benzothiazepines 4a–e. Treatment of 4a–e with chloroacetyl chloride 5a or phenoxyacetyl
chloride 5b by [2+2] cycloaddition reaction gave the title compounds 6a–j. The assignment
of the structures of 6a–j was made by 1H NMR, MS, and elemental analyses.
Keywords 4-Acetyl-2-phenyl-1,2,3-triazole; benzothiazepine; [2+2] cycloaddition; β-lactam
INTRODUCTION
1,5-Benzothiazepine is an important seven-membered heterocyclic ring system. In-
tensively used clinically, the drug diltiazem contains this ring system.1 It has been used as a
calcium antagonist,2 anticancer drug,3,4 antibacterial,5 anticonvulsant, tranquilizer,6 nd an-
tidepressant.7 Due to its broad spectrum of biological activity, recent work has demonstrated
the interest to affix an additional heterocycle on 1,5-benzothiazepines. Pharmaceutical prop-
erties of such compounds are magnified when the heterocycle is bound to the hepta-atomic
nucleus.8–10 The diverse pharmacological properties associated with 1,5-benzothiazepine
moiety have been reviewed by Bariwal et al.11
In addition, the 1,2,3-triazole–containing compounds have displayed a wide range
of biological activities. Many 1,2,3-triazole derivatives have been reported to exhibit an-
ticancer,12 insecticidal,13 antibiotic,14 antimycotic,15 and anti-HIV activities.16 Moreover,
the introduction of a 1,2,3-triazole ring into a parent compound may improve its properties
and biological activities, such as in tazobactam sodium.17,18
On the other hand, the β-lactam skeleton is the structural feature of the widely
employed family of antimicrobial agents, which show biological activities that include
inhibition of prostate specific antigen,19 thrombin,20 human cytomegalovirus protein,21 hu-
man leukocyte elastase,22 and cholesterol absorption.23 Most important, antibiotics possess
Received 7 December 2009; accepted 27 January 2010.
Address correspondence to Fangming Liu, College of Materials and Chemical Engineering, Hangzhou
Normal University, Hangzhou, 310036, China. E-mail: fmliu859@sohu.com
2366

BIOACTIVE AZETO[2,1-d][1,5]BENZOTHIAZEPINONES
2367
a representative structure of a β-lactam fused, five- or six-membered heterocyclic ring
containing nitrogen and sulfur atoms.24–28
However, to date there have been no reports on the syntheses of derivatives with
a 1,2,3-triazole nucleus attached to a 1,5-benzothiazepine ring, which may show in-
teresting biological activities. In view of these facts and in order to search for new
1,5-benzothiazepine compounds with higher bioactivity, this article deals with synthe-
ses of compounds having a tricyclic ring system containing 1,5-benzothiazepine, 1,2,3-
triazole, and β-lactam. This search is possibly correlated with the biological activity of
1,5-benzothiazepines and the fusion of the heterocyclic nucleus to the thiazepine system,
which could induce an increase of the ring inversion barrier and consequently modify the
activity profile.
RESULTS AND DISCUSSION
The α,β-unsaturated carbonyl compounds 3a–c were prepared by a condensation
reaction of 4-acetyl-2-phenyl-1,2,3-triazole 1 with substituted aldehydes 2a–c accord-
ing to the method described for benzalacetophenone,29,30 but an attempt to prepare α,β-
unsaturated carbonyl compounds 3d,e by the same method failed and instead gave Michael-
type addition products 7d,e as major products. Therefore the procedure was altered by
dropping the 4-acetyl-2-phenyl-1,2,3-triazole 1 into the solution of the aldehydes 2d,e in
ethanol slowly, so the expected α,β-unsaturated carbonyl compounds 3d,e were obtained
(Scheme 1).
CHO
O
N
N Ph
O
H3CC
R
N
2a-e
N Ph
N
N
2%NaOH/
%
1
EtOH
R
3a-e
2
N
a
O
H
N
O
C
/
E
t
O
N Ph
H
H2C
CH
H2C
N
R
N
O
N
N Ph
C
O
HOC
N Ph
N
N
7d,e
2,3,7 R
a: R= H
b: R= CH3
d: R= Cl
e: R= NO2
c: R= OCH3
Scheme 1
The α,β-unsaturated carbonyl compounds 3a–e were treated with o-
1
aminobenzenethiol in ethanol to afford the 1,5-benzothiazepines 4a–e. The H NMR
spectra of the products are characteristic of the imino structure. The imino structure,
formed instantaneously, would have given three distinct double doublets in the ABX
pattern at δ 5.2∼3.0 ppm, which are the characteristic peaks of dihydrobenzothiazepine
moiety.31,32
The generally applied routes for the construction of a β-lactam ring include the
Staudinger cycloaddition of imines to ketenes, the enolate-imine condensations and

2368
S. SHEN ET AL.
subsequent ring-closure of β-amino esters, and the ketene-imine cycloaddition using
metallo-carbene intermediates.33,34 The Staudinger cycloaddition of imines to ketenes
is probably the most important one. The 1,5-benzothiazepines 4a–e were reacted with
chloroacetyl chloride 5a and phenoxyacetyl chloride 5b, in the presence of triethylamine
in anhydrous benzene, to give 2-chloro- or 2-phenoxy-2a-(2-phenyl-1,2,3-triazole-4-yl)-4-
aryl-2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]benzothiazepin-1-ones 6a–j through parallel
1
solution-phase synthesis. Their structures were confirmed by H NMR, IR, MS, and ele-
mental analyses. The IR spectra of the compound 6a–j exhibit characteristic C O bands
1
in the region of 1780–1760 cm−1. It is noted that in the H NMR spectra of β-lactam
derivatives, a characteristic singlet of the azetidinone ring proton is recorded at δ 5.47–5.18
(s, 1H). Three distinct double doublets in the ABX pattern at δ 4.1∼3.0 ppm were recorded
in compounds 6a–j, the S-C-2-Hx proton singlet is recorded at δ 4.11–4.04 (dd, 1H) for
its attachment with an electronegative sulfur atom and electronegative phenyl group and
C-3-Ha, and C-3-Hb proton singlets are recorded at δ 3.80–3.69 (dd, 1H) and δ 3.19–3.01
(dd, 1H). Absorption peaks as multiplets of compound 6a–j aromatic protons were found
at δ 8.08–6.94 (m, Ar H), and the proton of the triazole-ring is also recorded at this region.
It is well-known that 2,4-disubstituted 2,3-dihydro-1,5-benzothiazepine 1 adopts a
boat-like conformation.35 Based on literature results,36–38 the nitrogen atom of the C N
bond in each benzothiazepine 1 attacks the carbonyl group of the ketene, generated from
acyl chloride and triethylamine, to yield a zwitterionic intermediate 3 (Scheme 2), then
undergoes a conrotatory ring closure in the downward direction, in which the whole azepine
ring rotates downwards, to yield a boat-like product 4 through forming a β-lactam ring
from the outside of the thiazepine ring. It then undergoes conformational transfer to produce
finally the predominant chair-like product 2. The structure of the products, however, shows
that its dominant conformation favors an arrangement where the 2a-triazole group and the
2-halogen atom (or phenoxy) are on the same side.
R
SH
O
S
NH2
N
N
N Ph
N
N
N
R
CF3COOH
N Ph
3a-e
4a-e
3,4 R
a: R= H
b: R= CH3
c: R= OCH3
d: R= Cl
e: R= NO2
Scheme 2
The structures of all compounds are also confirmed by mass spectral analysis. The
mass spectra show M+ peaks at corresponding masses of respective moleculars.
In conclusion, we have described a convenient method for the synthesis of 2-chloro-
or 2-phenoxy-2a-(2-phenyl-1,2,3-triazole-4-yl)-4-aryl-2,2a,3,4-tetrahydro-1H-azeto[2,1-
d][1,5]benzothiazepin-1-ones 6a–j from the corresponding aldehydes. Our search has been
successful in synthesizing novel derivatives of 1,5-benzothiazepines 6a–j with potential
biological activity. Compounds 6a–j reported are new and have been characterized by
spectral and analytical data (Scheme 3).

BIOACTIVE AZETO[2,1-d][1,5]BENZOTHIAZEPINONES
2369
R
R
5a:X=Cl
XCH2COCl
S
S
5b:X=OPh
Et3N
N
N
N
N
N
N
N Ph
N Ph
O
H
6a-j
X
4a-e
6
f: R= H
X= OPh
a: R= H
X= Cl
g: R= CH3 X= OPh
h: R= OCH3 X= OPh
b: R= CH3 X= Cl
c: R= OCH3 X= Cl
i: R= Cl
j: R= NO2 X= OPh
X= OPh
d: R= Cl
X= Cl
e: R= NO2 X= Cl
Scheme 3
EXPERIMENTAL
All purchased solvents and chemicals were of analytical grade and were used without
further purification. Melting points were obtained on an X-5 micro melting point apparatus,
and temperatures were uncorrected. 1H NMR spectra were recorded with a Varian Mercury
400 MHz using CDCl3 as the deuterated solvent and TMS as the internal standard at room
temperature. The solid-state IR spectra were recorded from KBr on a Bruker Tensor 27
spectrophotometer. MS were recorded on an Agilent 5975 mass selective detector. Element
analyses were performed on a Perkin-Elmer 240 CHN analyzer. The starting compound 2-
phenyl-4-acetyl-1,2,3-triazole 1 was obtained from 4-carboxy-2-phenyl-1,2,3-triazole acid
according to the literature.39
Preparation of 2-Phenyl-1,2,3-triazole-4-yl-α,β-unsaturated Ketones
(3a–3c)
2-Phenyl-4-acetyl-1,2,3–triazole 1 (2.5 mmol) and aldehydes 2a–2c (2.5 mmol) were
dissolved in ethanol (20 mL), and a solution of aqueous (2%) sodium hydroxide (2.5 mL)
was added dropwise slowly. The reaction mixture was kept under magnetic stirring at room
temperature for 2–3 h. The precipitate was then separated by filtration, washed with water
until the product was neutralized to pH = 7, washed with cold aq. Ethanol (2–3 mL), and
then dried in air. The crude product was recrystallized from ethanol.
Compound (3a). Yield 80%, mp: 167–168◦C. Pale yellow crystals. IR: 3126
(Ar H), 1683 (C O), 1594, 1493, 1454 (C C). MS, m/z (%): 276 (M++1), 172 (100%),
145, 117, 103, 91, 77. Anal.Calcd. (%) for C17H13N3O: C, 74.17; H, 4.76; N, 15.26. Found
(%): C, 74.06; H, 4.83; N, 15.29.
Compound (3b). Yield 83%, mp: 132–133◦C. Pale yellow crystals. IR: 3125
(Ar H), 2919 (CH3), 1663 (C O), 1595, 1491, 1451 (C C). MS, m/z (%): 289 (M+), 274
(100%), 145, 115, 91, 77. Anal.Calcd. (%) for C18H15N3O: C, 74.72; H, 5.23; N, 14.52.
Found (%): C, 74.64; H, 5.34; N, 14.58.
Compound (3c). Yield 86%, mp: 145–146◦C. Yellow and green needle-like crys-
tals. IR: 3130 (Ar H), 2972 (CH3), 1664 (C O), 1594, 1513, 1449 (C C), 1258
(C O C). MS, m/z (%): 305 (M+), 290, 274, 172, 145, 134, 117, 102, 91, 77 (100%).
Anal.Calcd. (%) for C18H15N3O2: C, 70.81; H, 4.95; N, 13.76. Found (%): C, 70.68; H,
5.10; N, 13.74.

2370
S. SHEN ET AL.
2-Phenyl-1,2,3-triazole-4-yl-α,β-unsaturated Ketones (3d, 3e)
To an aldehyde 2d,2e (5 mmol) and a solution of aqueous (2%), sodium hydroxide
(2.5 mL) mixed in ethanol (15 mL) and 4-acetyl-2-phenyl-1,2,3–triazole 1 (2.5 mmol) in
ethanol (30 mL) was added dropwise slowly. The reaction mixture was kept under magnetic
stirring at room temperature for 2∼3 h. The precipitate was then separated by filtration,
washed with water until the product was neutralized to pH = 7, washed with cold aq.
Ethanol (2–3 mL), and then dried naturally in air. The crude product was recrystallized
from ethanol.
Compound (3d). Yield 82%, mp: 133–134◦C. Pale yellow needle-like crystals.
IR: 3103 (Ar H), 1667 (C O), 1606, 1491, 1462 (C C). MS, m/z (%): 311 (M++2), 309
(M+), 274, 172, 165, 145, 137, 117, 102, 91, 77 (100%). Anal.Calcd. (%) for C17H12ClN3O:
C, 65.92; H, 3.90; N, 13.57. Found (%): C, 65.86; H, 3.86; N, 13.62.
Compound (3e). Yield 79%, mp: 171–173◦C. Yellow needle-like crystals. IR:
3126 (Ar H), 1673 (C O), 1613 ( NO2), 1596 1494, 1426 (C C), 1516, 1299 ( NO2).
MS, m/z (%): 321 (M++1), 176, 172 (100%), 145, 117, 102, 91, 77. Anal.Calcd. (%) for
C17H12N4O3: C, 63.75; H, 3.78; N, 17.49. Found (%): C, 63.66; H, 3.91; N, 17.41.
2-Aryl-4-(2-phenyl-1,2,3-triazole-4-yl)-2,3-dihydro-[1,5] benzothiazepine
(4a–4e)
To a solution of α,β-unsaturated ketone 3 (4.0mmol) in ethanol, 60 mL o-
aminothiophenol (4.0 mmol) was added. The mixture was heated under reflux for
20–30 min, and then CF3COOH (1.2 mL) was added. Refluxing was continued for 5–6 h.
The solvent volume was reduced by half using a rotovap, and the resulting mixture was
allowed to stand at room temperature. The crystalline solid product was filtered, washed
with cold aq. ethanol (2–3 mL), and dried in air. The crude compound was recrystallized
from ethanol.
Compound (4a). Yield 76%; Pale yellow crystals, mp: 159–161◦C. IR: 3127
(Ar H), 1647 (C N), 1597, 1497, 1465 (C C); 1H NMR (CDCl3, 400 MHz) δ: 8.17–6.80
(m, 15H, Ar H and N C H), 5.17–5.11 (dd,1H, H2x, Jax = 4.72Hz, Jbx = 12.21 Hz),
3.14–3.08 (dd, 1H, H3a, Jax = 4.72Hz, Jab = 12.42 Hz), 3.08–3.01 (dd, 1H, H3b, Jbx
=
12.21 Hz, Jab = 12.42 Hz); 70ev MS, m/z (%): 382 (M+), 349, 278, 210, 108, 104, 91,
77 (100%); Anal.Calcd. (%) for C23H18N4S: C, 72.22; H, 4.74; N, 14.65. Found (%): C,
72.04; H, 4.81; N, 14.58.
Compound (4b). Yield 83%; Yellow and green crystals, mp: 170–171◦C. IR: 3130
(Ar H), 2960 (CH3), 1635 (C N), 1558, 1487, 1459 (C C); 1H NMR (CDCl3, 400 MHz)
δ: 8.14–6.81 (m, 14H, Ar H and N C H), 5.16–5.11 (dd, 1H, H2x, Jax = 4.77 Hz, Jbx
= 11.97 Hz), 3.66–3.47 (dd, 1H, H3a, Jax = 4.77 Hz, Jab = 12.43 Hz), 3.09–3.01 (dd, 1H,
H3b, Jbx = 11.97 Hz, Jab = 12.43 Hz), 2.48 (s, 3H, -CH3); 70ev MS, m/z (%): 396 (M+),
363, 278 (100%), 250, 118, 91, 77, 64; Anal.Calcd. (%) for C24H20N4S: C, 72.70; H, 5.08;
N, 14.13. Found (%): C, 72.52; H, 5.06; N, 14.19.
Compound (4c). Yield 81%; Yellow and green crystals, mp: 150–151◦C. IR: 3131
(Ar H), 2952 (CH3), 1620 (C N), 1598, 1509, 1454 (C C), 1242 (C O C); 1H NMR
(CDCl3, 400 MHz) δ: 8.15–6.80 (m, 14H, Ar H and N C H), 5.18–5.13 (dd, 1H, H2x,
Jax = 4.80 Hz, Jbx = 12.01 Hz), 3.79 (s, 3H, -OCH3), 3.70–3.65 (dd, 1H, H3a, Jax = 4.80
Hz, Jab = 12.40 Hz), 3.08–3.01 (dd, 1H, H3b, Jbx = 12.01 Hz, Jab = 12.40 Hz); 70ev

BIOACTIVE AZETO[2,1-d][1,5]BENZOTHIAZEPINONES
2371
MS, m/z (%): 412(M+), 379, 278, 210, 134 (100%), 119, 108, 91, 77; Anal.Calcd. (%) for
C24H20N4OS: C, 69.88; H, 4.89; N, 13.58. Found (%): C, 69.60; H, 4.94; N, 13.52.
Compound (4d). Yield 80%; Pale yellow crystals, mp: 167–168◦C. IR: 3124
(Ar H), 1646 (C N), 1596, 1491, 1467 (C C); 1H NMR (CDCl3, 400 MHz) δ: 8.18–6.80
(m, 14H, Ar H and N C H), 5.18–5.10 (dd, 1H, H2x, Jax = 4.74 Hz, Jbx = 12.24 Hz),
3.74–3.71 (dd, 1H, H3a, Jax = 4.74 Hz, Jab = 12.44 Hz), 3.10–3.06 (dd, 1H, H3b, Jbx
=
12.24 Hz, Jab = 12.44 Hz); 70ev MS, m/z (%): 418(M++2), 416 (M+), 383, 278, 108, 102,
91 (100%), 77; Anal.Calcd. (%) for C23H17ClN4S: C, 66.26; H, 4.11; N, 13.44. Found (%):
C, 66.09; H, 4.17; N, 13.38.
Compound (4e). Yield 79%; Yellow crystals, mp: 193–194◦C. IR: 3121 (Ar H),
1642 (C N), 1596, 1518, 1468 (C C), 1516, 1299 ( NO2); 1H NMR (CDCl3, 400 MHz)
δ: 8.19–6.79 (m, 14H, Ar H and N C H), 5.19–5.12 (dd, 1H, H2x, Jax = 4.73 Hz, Jbx
=
12.23 Hz), 3.74–3.71 (dd, 1H, H3a, Jax = 4.73 Hz, Jab = 12.46 Hz), 3.10–3.06 (dd, 1H,
H3b, Jbx = 12.23 Hz, Jab = 12.46 Hz); 70ev MS, m/z (%): 427 (M+), 278, 149, 119, 108,
103, 91 (100%), 77; Anal.Calcd. (%) for C23H17N5O2S: C, 64.62; H, 4.01; N, 16.38. Found
(%): C, 64.32; H, 4.23; N, 16.43.
2-Chloro- or 2-Phenoxy-2a-(2-phenyl-1,2,3-triazole-4-yl)-4-aryl-2,2a,3,4-
tetrahydro-1H-azeto[2,1-d][1,5]benzothiazepin-1-ones (6a–j)
1,5-Benzothiazepine 4 (1mmol) and acyl chloride 5 (2mmol) were dissolved in
anhydrous benzene (15 mL), and dried triethylamine (0.28 mL, 2mmol) in anhydrous
benzene (10 mL) was added dropwise into the solution over a period of 15 min. After
having been stirred and refluxed for 5 h, the crystalline triethylamine hydrochloride that
had formed was removed by filtration. After removal of the solvent, the residue was purified
by silica gel column chromatography with light petroleum (60–90◦C)/ethyl acetate (V:V =
8:1). A colorless crystal was cultured from light petroleum and ethyl acetate (V:V = 8:1).
Compound (6a). Yield 52%; White floccules, mp: 201–202◦C. IR: 3097 (Ar H),
1
1781 (C O), 1612 (C N, C C), 1497 (C C), 1367 (C N), 762 (C Cl); H NMR
(CDCl3, 400 MHz) δ: 8.02–7.24 (m, 15H, Ar H and N C H), 5.17 (s,1H, Cl CH),
4.01–3.97 (dd, 1H, H2x, Jax = 1.12 Hz, Jbx = 10.84 Hz), 3.75–3.70 (dd, 1H, H3a, Jax = 1.12
Hz, Jab = 14.56 Hz), 3.10–3.05 (dd, 1H, H3b, Jbx = 10.84 Hz, Jab = 14.56 Hz); 70ev MS,
m/z (%): 460(M++2), 458(M+), 382, 349, 272, 211 (100%), 171, 108, 91, 77; Anal.Calcd.
(%) for C25H19ClN4OS: C, 65.42; H, 4.17; N, 12.21. Found (%): C, 65.34; H, 4.22; N,
12.16.
Compound (6b). Yield 56%; White floccules, mp: 192–193◦C. IR: 3110 (Ar H),
2920 (CH3), 1767 (C O), 1590 (C N,C C), 1479 (C C), 1366 (C N), 751 (C Cl);
1H NMR (CDCl3, 400 MHz) δ: 8.01–7.24 (m, 14H, Ar H and N C H), 5.18 (s, 1H,
Cl CH), 4.01–3.98 (dd, 1H, H2x, Jax = 1.09 Hz, Jbx = 10.31 Hz), 3.74–3.69 (dd, 1H, H3a,
Jax = 1.09 Hz, Jab = 14.56 Hz), 3.11–3.04 (dd, 1H, H3b, Jbx = 10.31 Hz, Jab = 14.56 Hz),
2.40 (s, 3H, CH3); 70ev MS, m/z (%): 474 (M++2), 472 (M+), 437, 279, 226, 168, 117, 91
(100%), 77; Anal.Calcd. (%) for C26H21ClN4OS: C, 66.02; H, 4.48; N, 11.85. Found (%):
C, 66.11; H, 4.46; N, 11.91.
Compound (6c). Yield 59%; White floccules, mp: 193–194◦C. IR: 3115 (Ar H),
2916 (CH3), 1777 (C O), 1602 (C N,C C), 1479 (C C), 1350 (C N), 1245 (C O C),
1
755 (C Cl); H NMR (CDCl3, 400 MHz) δ: 8.05–6.94 (m, 14H, Ar H and N C H),
5.18 (s, 1H, Cl CH), 4.02–3.99 (dd, 1H, H2x, Jax = 1.12 Hz, Jbx = 10.38 Hz), 3.73–3.70

2372
S. SHEN ET AL.
(dd, 1H, H3a, Jax = 1.12 Hz, Jab = 14.55 Hz), 3.68 (s, 3H, OCH3), 3.10–3.04 (dd, 1H, H3b,
Jbx = 10.38 Hz, Jab = 14.55 Hz); 70ev MS, m/z (%): 490 (M++2), 488 (M+), 453, 412,
379, 241 (100%), 171,108, 91; Anal.Calcd. (%) for C26H21ClN4O2S: C, 63.86; H, 4.33; N,
11.46. Found (%): C, 63.79; H, 4.38; N, 11.51.
Compound (6d). Yield 45%; White floccules, mp: 231–232◦C. IR: 3138 (Ar H),
1
1770 (C O), 1601 (C N, C C), 1483 (C C), 1366 (C N), 755 (C Cl); H NMR
(CDCl3, 400 MHz) δ: 8.06–7.09 (m, 14H, Ar H and N C H), 5.18 (s, 1H, Cl CH),
4.01–3.98 (dd, 1H, H2x, Jax = 1.07Hz, Jbx = 10.33Hz), 3.74–3.70 (dd, 1H, H3a, Jax
=
1.07Hz, Jab = 14.54Hz), 3.08–3.01 (dd, 1H, H3b, Jbx = 10.33 Hz, Jab = 14.54 Hz); 70ev
MS, m/z (%): 496 (M++4), 494 (M++2), 492 (M+), 457, 383, 279, 246, 138, 91 (100%),
71; Anal.Calcd. (%) for C25H18Cl2N4OS: C, 60.86; H, 3.68; N, 11.36. Found (%): C, 60.77;
H, 3.75; N, 11.41.
Compound (6e). Yield 39%; White floccules, mp: 264–265◦C. IR: 3130 (Ar H),
1771 (C O), 1600 (C N, C C), 1523 (C C), 1345 (C N), 1315 ( NO2), 755 (C Cl);
1H NMR (CDCl3, 400 MHz) δ: 8.08–7.10 (m, 14H, Ar H and N C H), 5.19 (s, 1H,
Cl CH), 4.11–4.08 (dd, 1H, H2x, Jax = 1.10 Hz, Jbx = 10.36 Hz), 3.79–3.75 (dd, 1H, H3a,
Jax = 1.10 Hz, Jab = 14.56 Hz), 3.11–3.04 (dd, 1H, H3b, Jbx = 10.36 Hz, Jab = 14.56
Hz); 70ev MS, m/z (%): 505 (M++2), 503 (M+), 468, 347, 279, 211, 146, 91 (100%), 77;
Anal.Calcd. (%) for C25H18ClN5O3S: C, 59.58; H, 3.60; N, 13.90. Found (%): C, 59.50;
H, 3.53; N, 13.98.
Compound (6f). Yield 51%; White floccules, mp: 198–199◦C. IR: 3117 (Ar H),
1769 (C O), 1601 (C N, C C), 1482 (C C), 1361 (C N), 1240 (C O C); 1H NMR
(CDCl3, 400 MHz) δ: 7.98–7.11 (m, 20H, Ar H and N C H), 5.47 (s, 1H, PhOCH),
4.07–4.04 (dd, 1H, H2x, Jax = 1.15 Hz, Jbx = 10.74 Hz), 3.77–3.74 (dd, 1H, H3a, Jax
=
1.15 Hz, Jab = 14.52 Hz), 3.18–3.11 (dd, 1H, H3b, Jbx = 10.74 Hz, Jab = 14.52 Hz); 70ev
MS, m/z (%): 516 (M+), 423, 272, 211 (100%), 171, 108, 91, 77; Anal.Calcd. (%) for
C31H24N4O2S: C, 72.07; H, 4.68; N, 10.85. Found (%): C, 72.12; H, 4.65; N 10.90.
Compound (6g). Yield 55%; White floccules, mp: 240–241◦C. IR: 3121 (Ar H),
2856 (CH3), 1770 (C O), 1601 (C N, C C), 1485 (C C), 1372 (C N), 1233 (C O C);
1H NMR (CDCl3, 400 MHz) δ: 7.99–7.14 (m, 19H, Ar H and N C H), 5.47 (s, 1H,
PhOCH), 4.09–4.06 (dd, 1H, H2x, Jax = 1.17 Hz, Jbx = 10.57 Hz), 3.79–3.75 (dd, 1H, H3a,
Jax = 1.17 Hz, Jab = 14.59 Hz), 3.19–3.13 (dd, 1H, H3b, Jbx = 10.57 Hz, Jab = 14.59 Hz),
2.36 (s, 3H, CH3); 70ev MS, m/z (%): 530 (M+), 437, 319, 278 (100%), 118, 105, 91, 77;
Anal.Calcd. (%) for C32H26N4O2S: C, 72.43; H, 4.94; N, 10.56. Found (%): C, 72.51; H,
4.89; N, 10.58.
Compound (6h). Yield 58%; White floccules, mp: 254–255◦C. IR: 3122 (Ar H),
2922 (CH3), 1768 (C O), 1601 (C N, C C), 1479 (C C), 1376 (C N), 1232 (C O C);
1H NMR (CDCl3, 400 MHz) δ: 7.99–7.11 (m, 19H, Ar H and N C H), 5.47 (s, 1H,
PhOCH), 4.10–4.07 (dd, 1H, H2x, Jax = 1.16 Hz, Jbx = 10.31 Hz), 3.80–3.76 (dd, 1H, H3a,
Jax = 1.16 Hz, Jab = 14.39 Hz), 3.74 (s, 3H, OCH3), 3.18–3.12 (dd, 1H, H3b, Jbx = 10.31
Hz, Jab = 14.39 Hz); 70ev MS, m/z (%): 546 (M+), 453, 319, 302, 279, 134 (100%), 105,
77; Anal.Calcd. (%) for C32H26N4O3S: C, 70.31; H, 4.79; N, 10.25. Found (%): C, 70.23;
H, 4.76; N, 10.29.
Compound (6i). Yield 43%; White floccules, mp: 264–265◦C. IR: 3127 (Ar H),
1773 (C O), 1611 (C N, C C), 1483 (C C), 1370 (C N), 1235 (C O C), 754 (C Cl);
1H NMR (CDCl3, 400 MHz) δ: 7.99–7.15 (m, 19H, Ar H and N C H), 5.47 (s, 1H,
PhOCH), 4.10–4.07 (dd, 1H, H2x, Jax = 1.15 Hz, Jbx = 10.81 Hz), 3.76–3.73 (dd, 1H, H3a,
Jax = 1.15 Hz, Jab = 14.51 Hz), 3.15–3.08 (dd, 1H, H3b, Jbx = 10. 81 Hz, Jab = 14.51

BIOACTIVE AZETO[2,1-d][1,5]BENZOTHIAZEPINONES
2373
Hz); 70ev MS, m/z (%):552 (M++2), 550 (M+), 457, 319, 278 (100%), 138, 105, 91, 77;
Anal.Calcd. (%) for C31H23ClN4O2S: C, 67.75; H, 4.21; N, 10.17. Found (%): C, 67.65;
H, 4.17; N, 10.23.
Compound (6j). Yield 36%; White floccules, mp: 287–288◦C. IR: 3126 (Ar H),
1777 (C O), 1608 (C N, C C), 1481 (C C), 1370 (C N), 1233 (C O C), 1297
( NO2); 1H NMR (CDCl3, 400 MHz) δ: 8.00–7.17 (m, 19H, Ar H and N C H), 5.47
(s, 1H, PhOCH), 4.09–4.06 (dd, 1H, H2x, Jax = 1.13 Hz, Jbx = 10.83 Hz), 3.77–3.73 (dd,
1H, H3a, Jax = 1.13 Hz, Jab = 14.50 Hz), 3.15–3.09 (dd, 1H, H3b, Jbx = 10.83 Hz, Jab
=
14.50 Hz); 70ev MS, m/z (%): 561 (M+), 468, 278 (100%), 248, 105, 91, 77; Anal.Calcd.
(%) for C31H23N5O4S: C, 66.30; H, 4.13; N, 12.47. Found (%): C, 66.23; H, 4.05; N, 12.53.
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