Synthesis of Benzo[b]imidazo[1,5-d][1,5]-thiazepines. Derivatives of a Novel Ring System

Article abstract of DOI:10.1081/SCC-120026866

Derivatives of a novel tricyclic system having a 1,5-benzothiazepine skeleton are described. A method for synthesis of the title compounds 5, consisted of an intramolecular cyclization of 1-(2-carboxymethylthiophenyl)-2H-imidazol-2-ones 4 in PPA, is presented. Compounds 4 were prepared by a reaction of 1-(2-mercaptophenyl)-2H-imidazol-2-ones 3 with chloroacetic acid. 2H-Imidazolones 3 were obtained by a ring transformation of substituted 2(3H)-benzothiazolones 2 in reactions with primary amines. The method is convenient because of its simplicity and good yields.

Full text of DOI:10.1081/SCC-120026866

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Synthesis of Benzo[b]imidazo[1,5-d][1,5]-thiazepines.
Derivatives of a Novel Ring System
K. Petrova a , O. Petrov a , A. Antonova a & V. Kalcheva a
a Sofia University, Faculty of Chemistry, Sofia, Bulgaria
Version of record first published: 21 Aug 2006.
To cite this article: K. Petrova , O. Petrov , A. Antonova & V. Kalcheva (2003): Synthesis of Benzo[b]imidazo[1,5-d]
[1,5]-thiazepines. Derivatives of a Novel Ring System, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:24, 4355-4366
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 24, pp. 4355–4366, 2003
Synthesis of Benzo[b]imidazo[1,5-d ][1,5]-
thiazepines. Derivatives of a Novel Ring System
*
K. Petrova, O. Petrov, A. Antonova, and V. Kalcheva
Sofia University, Faculty of Chemistry,
Sofia, Bulgaria
ABSTRACT
Derivatives of a novel tricyclic system having a 1,5-benzothiazepine
skeleton are described.
A method for synthesis of the title
compounds 5, consisted of an intramolecular cyclization of 1-(2-car-
boxymethylthiophenyl)-2H-imidazol-2-ones 4 in PPA, is presented.
Compounds 4 were prepared by a reaction of 1-(2-mercaptophenyl)-
2H-imidazol-2-ones 3 with chloroacetic acid. 2H-Imidazolones 3
were obtained by a ring transformation of substituted 2(3H )-
benzothiazolones 2 in reactions with primary amines. The method
is convenient because of its simplicity and good yields.
Key Words: Imidazoles; Cyclizations; Polyphosphoric acid; Benzo-
[b]imidazo[1,5-d ][1,5]thiazepine-1,4-diones.
*Correspondence: K. Petrova, Sofia University, Faculty of Chemistry, 1 James
Bourchier, 1164 Sofia, Bulgaria; Fax: 359-2-962-54-38; E-mail: kpetrova@
chem.uni-sofia.bg.
4355
DOI: 10.1081/SCC-120026866
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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4356
Petrova et al.
A number of articles[1] have been published on the chemistry
and biological activity of 1,5-benzothiazepines containing an additional
heterocycle at different positions of the seven-member ring. Especially
interesting are benzothiazepines with demonstrated antihypertensive,
antianginal,[2] and psychotropic activity.[3–5] Based on previous results
with benzodiazepine derivatives the addition of a third ring to bond [d ]
may be expected to enhance the activity or modify the activity profile.
In the course of our previous synthetic work[6] and as a part of a
program intended to produce N,S-containing cyclic systems with poten-
tial pharmacological properties,[7] derivatives of a novel tricyclic system
(1,2,4,5-tetrahydro benzo[b]imidazo[1,5-d ][1,5]thiazepine-1,4-dio-nes 5)
were prepared.
Benzo[b]imidazo[1,5-d ][1,5]thiazepines 5 were obtained as a result of
a three-step procedure shown in Sch. 1.
The starting compounds 2a, b were obtained by alkylation of 2(3H )-
benzothiazolones 1a, b with chloroacetone in DMF at room temperature
in presence of dry K2CO3 and benzyltriethylammonium chloride
(TEBA-Cl). Under these conditions the alkyl derivatives 2a, b were
prepered for a more short time and in higher yields in comparison with
the literature procedure.[8]
As described in our previous work,[6] imidazolones 3a–k, were
obtained as a result of a ring transformation of 3-(2-oxopropyl)-2(3H )-
benzothiazolones 2a, b upon treatment with primary amines. In this case,
the reaction was carried out in aqueous media, instead of perchloric acid,
using 6–10 fold excess of the amine. To prevent a possible partial
oxidation of the thiol group to disulfide, the products 3a–k were
immediately used in the next step without isolation and further
purification. The reaction of alkylation with chloroacetic acid proceeds
smoothly upon reflux in aqueous NaOH for 30–60 min. The resulting
1-(2-carboxymethylthiophenyl)-2H-imidazol-2-ones 4a–k are stable
compounds and were isolated with good to excellent yields.
In the last step of the synthesis, the building of the thiazepine
cycle and the formation of the tricyclic system was accomplished
through an intramolecular acylation of the compounds 4a–k. The
reaction was carried out at 110–120ꢀC in polyphosphoric acid (PPA)
and the benzo[b]imidazo[1,5-d ][1,5]thizepines 5a–k were isolated in
60–80% yields.
1H NMR spectra show the formation of the seven memberd ring
in the compounds 5a–k. The singlet for the methine proton of the
imidazole ring at 6.10–6.25 ppm disappears and the singlet for the
methylene group moves from 3.75 ppm in the starting acids 4a–k to
3.41–3.55 ppm. The signals in 1H NMR were assigned using COSY

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Benzo[b]imidazo[1,5-d ][1,5]thiazepines
4357
O
H
O
Cl
N
N
O
R1
S
O
R1
S
DMF, K2CO3,
TEBA-Cl
1
1
2a: R =H
1a: R =H
1b: R =Br
1
1
2b: R =Br
R2NH2 / H2O
R2
N
R2
N
O
O
O
N
N
Cl
OH
NaOH
R1
S
R1
SH
OH
O
3a-k
4a-k
1
2
Comp.
R
R
PPA
3, 4, 5
a
b
c
d
e
f
H
H
H
H
H
CH
3
C H
2
5
R2
N
C H
3
7
i-C H
4
9
O
CH C H
2
6
5
N
S
Br
Br
Br
Br
Br
Br
CH
3
g
h
i
C H
2
O
5
R1
C H
3
7
i-C H
4
9
j
CH C H
2 6
5
5a-k
k
C H
6 11
Scheme 1.
experiments. Two carbonyl bands were observed in the IR spectra of
these compounds. One for the carbonyl group in the thiazepine ring
and another for the one in the imidazole ring.
The intramolecular acylation, described in this article, is a convenient
and easily adjustable method for the synthesis of 1,5-benzothiazepines,
containing an annelated imidazole ring substituted at 2-, 3-, or 5-position.
These new compounds are interesting with their potential pharmacological
activity based on the close structural analogy with Diltiazem.
The on-going pharmacological studies of the new tricyclic system will
allow new aspects of the structure-activity relationship in the group of
1,5-benzothiazepines to be revealed.

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4358
Petrova et al.
EXPERIMENTAL
Melting points were determined on a Boetius hot stage microscope
1
and are uncorrected. The H NMR spectra were taken on a Bruker AM
400 (400 MHz) with TMS as internal standard; the values of chemical
shifts (ꢀ) are given in ppm and coupling constants (J) in Hz. The IR
spectra were recorded on a Specord 71 IR spectrometer (Carl Zeiss) in
nujol. The course of the reaction was monitored by TLC on silica gel
plates (Merck, 60 F254) using toluene/chloroform/ethyl acetate (3:1:1)
solvent system for compounds 3 and hexane/ethyl acetate/acetic acid
(20:20:0.1) for compounds 4 and 5. Mass spectra were obtained on
Hewlett Packard-5972 GC-MSD (EI-70 eV).
3-(2-Oxopropyl)-2(3H)-benzothiazolone (2a)
To a mixture of 2(3H )-benzothiazolone (7.56 g, 50 mmol), fine
powdered potassium carbonate (4.14 g, 30 mmol) and benzyltriethyl-
ammonium chloride (TEBA-Cl, 200 mg) in DMF (20 mL) was
added chloroacetone (4 mL, 50 mmol). The reaction mixture was stirred
for 30 min at 20–25ꢀC and then poured into 150 mL of water with
stirring. The resulting precipitate was filtered, washed with water, and
recrystallized from isopropanol. Yield: 9.0 g (87%). Colorless needles.
M.p.: 104–106ꢀC (Lit.[8] 104–106ꢀC).
6-Bromo-3-(2-oxopropyl)-2(3H)-benzothiazolone (2b)
Following the above procedure, starting from 1b, leads to the ketone
2b (82%). M.p.: 158–159ꢀC (acetonitrile) (Lit.[8] 157–158ꢀC).
1-(2-Carboxymethylthiophenyl)-1,3-dihydro-3,4-dimethyl-2H-
imidazol-2-one (4a)
A mixture of 3-(2-oxopropyl)-2(3H )-benzothiazolone (2a) (1.04 g,
5 mmol) and 2.9 mL (30 mmol) of 35% aqueous methylamine was
heated at 60–70ꢀC in a pressure tube for 4 h (TLC, toluene/chloroform/
ethyl acetate 3:1:1). The tube was cooled and NaOH (10 mL, 5%) was
added. The excess of methylamine was removed under vacuum and the
reaction mixture was filtered. A solution of chloroacetic acid (0.6 g,
6 mmol) in water (10 mL) was added to the alkaline filtrate, containing

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Benzo[b]imidazo[1,5-d ][1,5]thiazepines
4359
compound 3a. The mixture was refluxed for 30 min and after hot filtration
was acidified with 5% HCl. The precipitation was collected by filtration,
washed with water, and dried. After recrystallization was obtained 1.22 g,
(88%) of compound 4a. M.p.: 178–180ꢀC (from toluene/ethanol 10:1).
1H NMR spectrum (DMSO-d6): 2.05 (d, 3H, J ¼ 1.3 Hz, CH3), 3.11 (s,
3H, NCH3), 3.74 (s, 2H, SCH2), 6.29 (q, 1H, J ¼ 1.3 Hz, CH), 7.21–7.47
(m, 4H, ArH), 12.79 (br s, 1H, COOH, missing after deuteriation). IR
spectrum: 1725 (CO), 1635 (CO). C13H14N2O3S (278.26) Calcd.: C,
56.11; H, 5.07; N, 10.07. Found: C, 56.41; H, 5.31; N, 10.16.
1-(2-Carboxymethylthiophenyl)-1,3-dihydro-3-ethyl-4-methyl-
2H-imidazol-2-one (4b)
This compound was synthesized following the procedure for
compound 4a, using ethylamine and compound 2a as starting materials.
Yield: 1.25 g, (86%). M.p.: 171–174ꢀC (from ethanol). 1H NMR spectrum
(DMSO-d6): 1.17 (t, 3H, CH3), 2.1 (d, 3H, J ¼ 1.3 Hz, CH3), 3.61 (q, 2H,
NCH2), 3.75 (s, 2H, SCH2), 6.31 (d, 1H, J ¼ 1.2 Hz, CH), 7.22–7.48 (m,
4H, ArH), 12.79 (br s, 1H, COOH, missing after deuteriation). IR
spectrum: 1705 (CO), 1645 (CO). C14H16N2O3S (292.29) Calcd.: C,
57.52; H, 5.52; N, 9.58. Found: C, 57.77; H, 5.73; N, 9.19.
1-(2-Carboxymethylthiophenyl)-1,3-dihydro-4-methyl-3-propyl-
2H-imidazol-2-one (4c)
This compound was synthesized following the procedure for
compound 4h, using compound 2a as a starting material. Yield: 1.30 g,
(85%). M.p.: 148–150ꢀC (from toluene/ethanol 10:1). 1H NMR spectrum
(DMSO-d6): 0.89 (t, 3H, CH3), 1.6 (m, 2H, CH2), 2.08 (d, 3H, J ¼ 1.2 Hz,
CH3), 3.54 (t, 2H, NCH2), 3.75 (s, 2H, SCH2), 6.31 (d, 1H, J ¼ 1.4 Hz,
CH), 7.23–7.48 (m, 4H, ArH), 12.78 (br s, 1H, COOH, missing after deu-
teriation). IR spectrum: 1710 (CO), 1645 (CO). C15H18N2O3S (306.31)
Calcd.: C, 58.82; H, 5.92; N, 9.15. Found: C, 59.23; H, 5.78; N, 8.84.
1-(2-Carboxymethylthiophenyl)-1,3-dihydro-3-isobutyl-
4-methyl-2H-imidazol-2-one (4d)
This compound was synthesized following the procedure for
compound 4h, using isobutylamine and compound 2a as starting
materials. Yield: 1.13 g, (71%). M.p.: 153–155ꢀC (from toluene). 1H NMR

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4360
Petrova et al.
spectrum (DMSO-d6): 0.89 (d, 6H, 2CH3), 2.0 (m, 1H, CH(CH3)2), 2.12
(d, 3H, J ¼ 1.2 Hz, CH3), 3.38 (d, 2H, NCH2), 3.75 (s, 2H, SCH2), 6.31 (d,
1H, J ¼ 1.3 Hz, CH), 7.24–7.48 (m, 4H, ArH), 12.79 (br s, 1H, COOH,
missing after deuteriation). IR spectrum: 1725 (CO), 1650 (CO).
C16H20N2O3S (320.34) Calcd.: C, 59.99; H, 6.29; N, 8.75. Found: C,
60.30; H, 6.59; N, 8.83.
3-Benzyl-1-(2-carboxymethylthiophenyl)-1,3-dihydro-4-methyl-
2H-imidazol-2-one (4e)
This compound was synthesized following the procedure for
compound 4j, using compound 2a as a starting material. Yield: 1.23 g,
(69%). M.p.: 155–157ꢀC (from ethanol). 1H NMR spectrum (DMSO-d6):
1.95 (d, 3H, J ¼ 1.4 Hz, CH3), 3.79 (s, 2H, SCH2), 4.71 (s, 2H, NCH2),
6.38 (d, 1H, J ¼ 1.4 Hz, CH), 7.28–7.50 (m, 9H, ArH), 12.82 (br s, 1H,
COOH, missing after deuteriation). IR spectrum: 1730 (CO), 1650 (CO).
C19H18N2O3S (354.35) Calcd.: C, 64.40; H, 5.12; N, 7.91. Found: C,
64.06; H, 5.31; N, 8.14.
1-(4-Bromo-2-carboxymethylthiophenyl)-1,3-dihydro-
3,4-dimethyl-2H-imidazol-2-one (4f )
This compound was synthesized following the procedure for
compound 4a, using compound 2b as a starting material. Yield: 1.43 g,
(80%). M.p.: 187–190ꢀC (from ethanol). 1H NMR spectrum (DMSO-d6):
2.06 (d, 3H, J ¼ 1.3 Hz, CH3), 3.12 (s, 3H, NCH3), 3.85 (s, 2H, SCH2),
6.31 (d, 1H, J ¼ 1.4 Hz, CH), 7.16–7.62 (m, 3H, ArH), 12.89 (br s, 1H,
COOH, missing after deuteriation). IR spectrum: 1735 (CO), 1675 (CO).
C13H13BrN2O3S (357.16) Calcd.: C, 43.72; H, 3.67; N, 7.84. Found: C,
44.09; H, 4.01; N, 8.19.
1-(4-Bromo-2-carboxymethylthiophenyl)-1,3-dihydro-3-ethyl-
4-methyl-2H-imidazol-2-one (4g)
This compound was synthesized following the procedure for
compound 4a, using ethylamine and compound 2b as starting materials.
Yield: 1.45 g, (78%). M.p.: 156–158ꢀC (from ethanol). 1H NMR
spectrum (DMSO-d6): 1.16 (t, 3H, CH3), 2.09 (d, 3H, J ¼ 1.3 Hz, CH3),
3.62 (q, 2H, NCH2), 3.86 (s, 2H, SCH2), 6.31 (d, 1H, J ¼ 1.4 Hz, CH),

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Benzo[b]imidazo[1,5-d ][1,5]thiazepines
4361
7.21–7.71 (m, 3H, ArH), 12.88 (br s, 1H, COOH, missing after
deuteriation). IR spectrum: 1720 (CO), 1650 (CO). C14H15BrN2O3S
(371.19) Calcd.: C, 45.30; H, 4.07; N, 7.55. Found: C, 45.77; H, 4.43;
N, 7.81.
1-(4-Bromo-2-carboxymethylthiophenyl)-1,3-dihydro-4-methyl-
3-propyl-2H-imidazol-2-one (4h)
Propylamine (4 mL, 50 mmol) in water (5 mL) was added to
6-bromo-3-(2-oxopropyl)-2(3H )-benzothiazolone (2b) (1.43 g, 5 mmol).
The mixture was refluxed for 5 h (TLC, toluene/chloroform/ethyl acetate
3:1:1) and then worked up as described for compound 4a to yield 1.55 g
(80%) of the title compound 4h. M.p.: 140–142ꢀC (from toluene).
1H NMR spectrum (DMSO-d6): 0.8 (t, 3H, CH3), 1.47–1.56 (m, 2H,
CH2), 1.99 (d, 3H, J ¼ 1.3 Hz, CH3), 3.47 (t, 2H, NCH2), 3.77 (s, 2H,
SCH2), 6.23 (d, 1H, J ¼ 1.3 Hz, CH), 7.09–7.6 (m, 3H, ArH), 12.82 (br s,
1H, COOH, missing after deuteriation). IR spectrum: 1710 (CO), 1650
(CO). C15H17BrN2O3S (385.22) Calcd.: C, 46.76; H, 4.45; N, 7.27.
Found: C, 47.06; H, 4.61; N, 7.04.
1-(4-Bromo-2-carboxymethylthiophenyl)-1,3-dihydro-
3-isobutyl-4-methyl-2H-imidazol-2-one (4i)
This compound was synthesized following the procedure for
compound 4h, using isobutylamine and compound 2b as starting
materials. Yield: 1.50 g, (75%). M.p.: 160–162ꢀC (from toluene).
1H NMR spectrum (DMSO-d6): 0.88 (d, 6H, 2CH3), 1.90–1.99 (m, 1H,
CH(CH3)2), 2.06 (d, 3H, J ¼ 1.3 Hz, CH3), 3.37 (d, 2H, NCH2), 3.85 (s,
2H, SCH2), 6.32 (d, 1H, J ¼ 1.3 Hz, CH), 7.12–7.83 (m, 3H, ArH), 12.88
(br s, 1H, COOH, missing after deuteriation). IR spectrum: 1720 (CO),
1660 (CO). C16H19BrN2O3S (399.24) Calcd.: C, 48.12; H, 4.76; N, 7.02.
Found: C, 48.37; H, 4.95; N, 6.80.
3-Benzyl-1-(4-bromo-2-carboxymethylthiophenyl)-1,3-dihydro-
4-methyl-2H-imidazol-2-one (4j)
A mixture of 6-bromo-3-(2oxopropyl)-2(3H )-benzothiazolone (2b)
(1.43 g, 5 mmol), benzylamine (3.3 mL, 30 mmol) and water (5 mL) was

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4362
Petrova et al.
refluxed for 8 h (TLC, toluene/chloroform/ethyl acetate 3:1:1). After
cooling to room temperature and acidifying with 5% HCl, the product
3j separates as thick, heavy oil. After decanting, the oil was dissolved in
5% NaOH (10 mL) and a solution of chloroacetic acid (0.6 g, 6 mmol) in
water (10 mL) was added to it. The mixture was refluxed for 60 min,
filtered while hot and after cooling to room temperature acidified
with 5% HCl. The precipitation (compound 4j) was collected, washed
with water, and dried to give 1.62 g (75%). M.p.: 170–172ꢀC (from
ethanol). 1H NMR spectrum (DMSO-d6): 1.94 (d, 3H, J ¼ 1.3 Hz,
CH3), 3.89 (s, 2H, SCH2), 4.85 (s, 2H, NCH2), 6.38 (d, 1H, J ¼ 1.4 Hz,
CH), 7.25–7.66 (m, 8H, ArH), 12.92 (br s, 1H, COOH, missing after
deuteriation). IR spectrum: 1715 (CO), 1660 (CO). C19H17BrN2O3S
(433.26) Calcd.: C, 52.70; H, 3.96; N, 6.46. Found: C, 52.96; H,
4.11; N, 6.84.
1-(4-Bromo-2-carboxymethylthiophenyl)-3-cyclohexyl-
1,3-dihydro-4-methyl-2H-imidazol-2-one (4k)
This compound was synthesized following the procedure for
compound 4j using cyclohexylamine and compound 2b as starting
materials. Yield: 1.33 g, (63%). M.p.: 155–157ꢀC (from ethanol).
1H NMR spectrum (DMSO-d6): 1.09–2.05 (m, 10H, cyclohexyl), 2.08
(s, 3H, CH3), 3.71–3.81 (m, 1H, NCH), 3.81 (s, 2H, SCH2), 6.26 (s,
1H, CH), 7.16–7.6 (m, 3H, ArH), 12.76 (br s, 1H, COOH, missing
after deuteriation). IR spectrum: 1725 (CO), 1650 (CO).
2-Alkyl-3-methyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d ]-
[1,5]thiazepine-1,4-dione (5a–k)
General Procedure
The corresponding compound 4 (5 mmol) was added in small
portions to 20 mL of hot (110–120ꢀC) polyphosphoric acid. The reaction
mixture was stirred at this temperature for additional 1–3 h, until the
TLC analysis (hexane/ethyl acetate/acetic acid 20:20:0.1) shows that the
reaction is complete. The reaction mixture was then cooled and poured
onto 100 g of ice. The precipitation was filtered, washed with water to
neutral, dried, and recrystallized.
2,3-Dimethyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d ][1,5]thiazepine-
1,4-dione (5a). Yield (75%). M.p.: 166–168ꢀC (from isopropanol).
1H NMR spectrum (CDCl3): 2.53 (s, 3H, CH3), 3.38 (s, 3H, NCH3),

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Benzo[b]imidazo[1,5-d ][1,5]thiazepines
4363
3.53 (s, 2H, SCH2), 7.3–7.78 (m, 4H, ArH). IR spectrum: 1690 (CO),
1640 (CO). C13H12N2O2S (260.25) Calcd.: C, 59.99; H, 4.65; N, 10.77.
Found: C, 60.02; H, 4.85; N, 10.63. MS m/z (intensity): Mþ 260 (100),
231 (24), 217 (49), 189 (15), 159 (16), 109 (14), 56 (79).
2-Ethyl-3-methyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d][1,5]thiazepine-1,4-
dione (5b). Yield (82%). M.p.: 161–163ꢀC (from ethanol). H NMR spectrum
1
(CDCl3): 1.35 (t, 3H, CH3), 2.54 (s, 3H, CH3), 3.52 (s, 2H, SCH2), 3.88 (q, 2H,
NCH2), 7.25–7.79 (m, 4H, ArH). IR spectrum: 1690 (CO), 1640 (CO).
C14H14N2O2S (274.27) Calcd.: C, 61.30; H, 5.14; N, 10.22. Found: C, 61.55;
H, 5.34; N, 10.06. MS m/z (intensity): Mþ 274 (100), 245 (14), 231 (37), 217 (10),
203 (17), 189 (10), 159 (14), 115 (7), 70 (12).
3-Methyl-2-propyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d][1,5]thiazepine-
1,4-dione (5c). Yield (73%). M.p.: 123–125ꢀC (from ethanol). 1H NMR spec-
trum (CDCl3): 1.01 (t, 3H, CH3), 1.76 (m, 2H, CH2), 2.52 (s, 3H, CH3), 3.53
(s, 2H, SCH2), 3.77 (t, 2H, NCH2), 7.25–7.78 (m, 4H, ArH). IR spectrum:
1700 (CO), 1650 (CO). C15H16N2O2S (288.31) Calcd.: C, 62.48; H, 5.59; N
9.72. Found: C, 62.84; H, 6.02; N, 10.10. MS m/z (intensity): Mþ 288 (100),
245 (21), 217 (11), 203 (33), 189 (10), 159 (10).
2-Isobutyl-3-methyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d][1,5]thiazepine-
1,4-dione (5d). Yield (47%). M.p.: 110–112ꢀC (from cyclohexane). HNMR
1
spectrum (CDCl3): 1.04 (d, 6H, 2CH3), 2.18 (m, 1H, CH(CH3)2), 2.55 (s, 3H,
CH3), 3.56 (s, 2H, SCH2), 3.65 (d, 2H, NCH2), 7.28–7.81 (m, 4H, ArH). IR
spectrum: 1705 (CO), 1650 (CO). C16H18N2O2S (302.34) Calcd.: C, 63.56; H,
6.00; N, 9.27. Found: C, 63.98; H, 6.33; N, 9.23. MS m/z (intensity): Mþ 302
(99), 259 (11), 246 (21), 217 (15), 204 (18), 202 (71), 148 (12), 134 (10), 57 (10).
2-Benzyl-3-methyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d][1,5]thiazepine-
1,4-dione (5e). Yield (78%). M.p.: 165–166ꢀC (from ethanol). 1H NMR spec-
trum (CDCl3): 2.44 (s, 3H, CH3), 3.52 (s, 2H, SCH2), 5.03 (s, 2H, NCH2),
7.25–7.81 (m, 9H, ArH). IR spectrum: 1695 (CO), 1655 (CO). C19H16N2O2S
(336.34) Calcd.: C, 67.85; H, 4.79; N, 8.33. Found: C, 67.63; H, 5.07; N, 8.07.
MS m/z (intensity): Mþ 336 (85), 245 (29), 202 (23), 159 (11), 116 (8), 91 (100),
65 (14).
8-Bromo-2,3-dimethyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d ][1,5]thia-
zepine-1,4-dione (5f). Yield (83%). M.p.: 215–217ꢀC (from ethanol).
1H NMR spectrum (CDCl3): 2.53 (s, 3H, CH3), 3.38 (s, 3H, NCH3), 3.53
(s, 2H, SCH2), 7.56–7.83 (m, 3H, ArH). IR spectrum: 1705 (CO),
1635(CO). C13H11BrN2O2S (339.16) Calcd.: C, 46.04; H, 3.27; N, 8.26.
Found: C, 46.35; H, 3.33; N, 7.97. MS m/z (intensity): 340 (12), Mþ 339
(80), 338 (13), 337 (83), 310 (16), 308 (16), 296 (33), 294 (32), 268 (12), 266
(12), 239 (12), 237 (11), 56 (100).
8-Bromo-2-ethyl-3-methyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d ][1,5]
thiazepine-1,4-dione (5g). Yield (81%). M.p.: 159–161ꢀC (from ethanol).

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Petrova et al.
1H NMR spectrum (CDCl3): 1.39 (t, 3H, CH3), 2.57 (s, 3H, CH3), 3.57
(s, 2H, SCH2), 3.91 (q, 2H, NCH2), 7.58–7.87 (m, 3H, ArH). IR
spectrum: 1705 (CO), 1655 (CO). C14H13BrN2O2S (353.18) Calcd.: C,
47.61; H, 3.71; N, 7.93. Found: C, 47.92; H, 3.90; N, 8.03. MS m/z (inten-
sity): 354 (16), Mþ 353 (99), 352 (17), 351 (95), 324 (13), 322 (12), 310
(32), 308 (31), 282 (19), 280 (19), 268 (12), 266 (12), 239 (17), 237 (14),
158 (16), 70 (21).
8-Bromo-3-methyl-2-propyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d][1,5]
thiazepine-1,4-dione (5h). Yield (77%). M.p.: 144–146ꢀC (from ethanol).
1H NMR spectrum (CDCl3): 1.0 (t, 3H, CH3), 1.75 (m, 2H, CH2), 2.52 (s,
3H, CH3), 3.53 (s, 2H, SCH2), 3.76 (t, 2H, NCH2), 7.54–7.83 (m, 3H, ArH).
IR spectrum: 1700 (CO), 1650 (CO). C15H15BrN2O2S (367.29) Calcd.: C,
49.05; H, 4.12; N, 7.63. Found: C, 49.38; H, 4.37; N, 7.48. MS m/z (inten-
sity): 369 (18), 368 (99), Mþ 367 (18), 366 (100), 324 (20), 322 (19), 296 (14),
294 (13), 282 (40), 280 (41), 239 (15), 237 (12), 214 (8), 212 (8), 172 (8), 158
(18), 132 (7), 75 (9), 63 (11).
8-Bromo-2-isobutyl-3-methyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d][1,5]
thiazepine-1,4-dione (5i). Yield (74%). M.p.: 139–141ꢀC (from ethanol
1H NMR spectrum (CDCl3): 0.99 (d, 6H, 2CH3), 2.13 (m, 1H, CH(CH3)2),
2.51 (s, 3H, CH3), 3.54 (s, 2H, SCH2), 3.61 (d, 2H, NCH2), 7.56–7.83 (m, 3H,
ArH). IR spectrum: 1700 (CO), 1650 (CO). C16H17BrN2O2S (381.23) Calcd.:
C, 50.40; H, 4.46; N, 7.35. Found: C, 50.51; H, 4.79; N, 7.39. MS m/z
(intensity): 383 (19), 382 (99), Mþ 381 (19), 380 (97), 325 (36), 323 (35),
296 (17), 294 (15), 282 (79), 280 (76), 239 (16), 237 (12), 228 (14), 226 (14),
214 (14), 212 (3), 187 (33), 158 (18), 75 (83), 57 (27).
2-Benzyl-8-bromo-3-methyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d ][1,5]
thiazepine-1,4-dione (5j). Yield (68%). M.p.: 156–158ꢀC (from ethanol).
1H NMR spectrum (CDCl3): 2.44 (s, 3H, CH3), 3.51 (s, 2H, SCH2), 5.02
(s, 2H, NCH2), 7.31–7.39 (m, 5H, ArH), 7.59–7.85 (m, 3H, ArH). IR
spectrum: 1695 (CO), 1650 (CO). C19H15BrN2O2S (415.24) Calcd.: C,
54.95; H, 3.64; N, 6.75. Found: C, 54.85; H, 4.19; N, 6.28. MS m/z
(intensity): 417 (6), 416 (26), Mþ 415 (6), 414 (25), 324 (7), 322 (7), 282
(5), 280 (6), 239 (3), 237 (3), 172 (3), 158 (6), 91 (99), 65 (12).
8-Bromo-2-cyclohexyl-3-methyl-1,2,4,5-tetrahydrobenzo[b]imidazo[1,5-d][1,5]
thiazepine-1,4-dione (5k). Yield (58%). M.p.: 211–213ꢀC (from ethanol).
1H NMR spectrum (CDCl3): 1.23–2.35 (m, 10H, cyclohexyl), 2.54 (s, 3H,
CH3), 3.53 (s, 2H, SCH2), 3.94–4.0 (m, 1H, NH), 7.53–7.82 (m, 3H, ArH).
IR spectrum: 1700 (CO), 1645 (CO). C18H19BrN2O2S (407.26) Calcd.: C, 53.08;
H, 4.77; N, 6.88. Found: C, 53.42; H, 4.94; N, 6.79. MS m/z (intensity): 409 (13),
408 (63), Mþ 407 (13), 406 (63), 325 (99), 323 (96), 297 (16), 295 (15), 282 (80),
280 (77), 239 (13), 237 (12), 214 (13), 212 (12), 158 (17), 147 (7), 132 (6), 83 (12),
75 (9), 63 (9), 55 (84).

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Benzo[b]imidazo[1,5-d ][1,5]thiazepines
ACKNOWLEDGMENTS
4365
We wish to thank our colleagues Dr. I. Kozekov and Dr. L. Nechev
from Vanderbilt University (Nashville, Tennessee) for the NMR spectra.
We also gratefully acknowledge the assistance of Dr. L. Nechev in
preparing the manuscript.
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MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
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Received in the UK June 19, 2003