A convenient, rapid microwave-assisted synthesis of 2-substituted phenyl-2,3-dihydrobenzo[B][1,4]thiazepine-3-carboxamide derivatives and its antimicrobial activity

Article abstract of DOI:10.1080/10426507.2011.597800

Using an environmentally benign procedure under microwave irradiation, a variety of 4-methyl-N-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)-2-substituted phenyl-2,3-dihydrobenzo [b][1,4]thiazepine-3-carboxamide compounds were synthesized from 2-arylidene-3-oxo

Full text of DOI:10.1080/10426507.2011.597800

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Phosphorus, Sulfur, and Silicon and the
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A Convenient, Rapid Microwave-Assisted
Synthesis of 2-Substituted Phenyl-2,3-
Dihydrobenzo[B][1,4]Thiazepine-3-
Carboxamide Derivatives and Its
Antimicrobial Activity
Jignesh P. Raval a , Bhanvesh N. Naik b & Kishor R. Desai b
a Department of Pharmaceutical Chemistry, Ashok and Rita Patel
Institute of Integrated Research in Biotechnology and Allied
Sciences, Vallabh Vidyanagar, Gujarat, India
b Department of Chemistry, Veer Narmad South Gujarat University,
Surat, Gujarat, India
Version of record first published: 05 Jan 2012
To cite this article: Jignesh P. Raval, Bhanvesh N. Naik & Kishor R. Desai (2012): A Convenient,
Rapid Microwave-Assisted Synthesis of 2-Substituted Phenyl-2,3-Dihydrobenzo[B][1,4]Thiazepine-3-
Carboxamide Derivatives and Its Antimicrobial Activity, Phosphorus, Sulfur, and Silicon and the Related
Elements, 187:2, 255-267
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Phosphorus, Sulfur, and Silicon, 187:255–267, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.597800
A CONVENIENT, RAPID MICROWAVE-ASSISTED
SYNTHESIS OF 2-SUBSTITUTED PHENYL-2,3-
DIHYDROBENZO[B][1,4]THIAZEPINE-3-CARBOXAMIDE
DERIVATIVES AND ITS ANTIMICROBIAL ACTIVITY
Jignesh P. Raval,1 Bhanvesh N. Naik,2 and Kishor R. Desai2
1Department of Pharmaceutical Chemistry, Ashok and Rita Patel Institute of
Integrated Research in Biotechnology and Allied Sciences, Vallabh Vidyanagar,
Gujarat, India
2Department of Chemistry, Veer Narmad South Gujarat University, Surat,
Gujarat, India
GRAPHICAL ABSTRACT
Abstract Using an environmentally benign procedure under microwave irradiation,
a
variety of 4-methyl-N-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)-2-substituted phenyl-
2,3-dihydrobenzo [b][1,4]thiazepine-3-carboxamide compounds were synthesized from
2-arylidene-3-oxo-N-(4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl)butanamide. Structures of these
compounds were confirmed by IR, NMR (1H & 13C), and mass spectral analyses. Also,
a considerable increase in the reaction rate has been observed with better yield in the
microwave technique. The newly synthesized compounds were evaluated for antimicrobial
activity against a variety of bacterial strains, and some of these compounds have shown
significant antibacterial and antifungal activities.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental
resource: Biological Activity.
Received 1 March 2011; accepted 3 June 2011.
One of the authors (JPR) is thankful to Mr. Priyakant R. Raval, Cyanamid India Ltd., Atul (Gujarat), Charutar
Vidya Mandal’s SICART, Vallabh Vidyanagar, Dist. Anand, Gujarat, India, for providing spectral and analytical
data of the compounds 4a–j and 6a–j. The authors are also thankful to the Head of the Bioscience Department of
VNSGU, Surat, for biological screening.
Address correspondence to Jignesh P. Raval, Department of Pharmaceutical Chemistry, Ashok and Rita Patel
Institute of Integrated Research in Biotechnology and Allied Sciences, Vallabh Vidyanagar – 388120, Gujarat,
India. E-mail: drjpraval@yahoo.co.in
255

256
J. P. RAVAL ET AL.
Keywords 3-(2-Amino-1,3-thiazol-4-yl)-2H-chromen-2-one; antimicrobial activities; 2,3-
dihydro[b][1,4]benzothiazepines; microwave irradiation; 3-oxo-N-[4-(2-oxo-2H-chromen-3-
yl)thiazol-2-yl]butanamide
INTRODUCTION
The advantages of microwave technology over conventional methods in heterocyclic
synthesis have been recently reviewed.1 In a conventional methodology, the yield is some-
times lower than microwave protocols, whereas salient features of the microwave approach
are rapid reaction rates, cleaner reaction conditions, enhancement in chemical yields,2,3
and synthesis on preparative scales.4 Actually, microwave irradiation (MWI) facilitates the
polarization of the molecule under irradiation causing a rapid reaction to occur,5 which ren-
ders the microwave technique superior over conventional methods. Benzothiazepines are
well-known compounds with diverse therapeutic properties such as antimicrobial,6 antihy-
pertensive,7 calcium channel blocker,8 blood platelet aggregation inhibitors,9 and cornary
vasodilators.10 As a result, due to their wide range of biological and synthetic applications,
various methods have been developed for the synthesis of benzothiazepines.11,12 But the de-
velopment of mild and efficient protocols continues to be a challenging endeavor in synthetic
organic chemistry. The most straightforward protocol for the synthesis of benzothiazepine
involves the condensation of chalcones with 2-aminothiophenol in methanol/ethanol under
strong acidic conditions.13 Moreover, this nucleus is also reported to be synthesized using
MWI,14,15 solid-phase synthesis,16,17 etc.
Earlier, we reported microwave-induced Niementowski reaction, that is, the synthesis
of quinazolinones and 3-methyl-1H-5-pyrazolones, using different solid supports,18 and
fluorine-containing pyrozoline derivatives over solid potassium carbonate,19 wherein the
problems associated with prolonged heating were avoided. We have successfully adopted
this technique for the synthesis of various 1,5-benzothiazepine derivatives14,20 too.
Thus, in continuation to our earlier work21 and the application of microwave-induced
organic reaction enhancement (MORE)14,22,23 chemistry to organic synthesis, we report
a simple microwave synthesis of 4-methyl-N-[4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl]-2-
substituted phenyl-2,3-dihydrobenzo [b][1,4]thiazepine-3-carboxamide derivatives 6a–j by
successfully incorporating benzothiazepines with thiazolochromenones and in an attempt
to form novel pharmacologically active compounds. All the compounds were prepared
using both conventional and microwave techniques. A comparative study in terms of yield
and reaction period is discussed. All the compounds synthesized were characterized by
elemental analysis, IR, 1H NMR, 13C NMR, and mass spectrometry.
RESULTS AND DISCUSSION
Compounds 2-arylidene-3-oxo-N-[4-(2-oxo-2H-chromen-3-yl)thiazol-2-yl]butana-
mides 4a–j were prepared using 3-oxo-N-[4-(2-oxo-2H-chromen-3-yl)thiazol-2-
yl]butanamide 2 and various aryl aldehydes 3a–j. Compound 2 was prepared from
3-(2-amino-1,3-thiazol-4-yl◦)-2H-chromen-2-one 1 using ethyl acetoacetate and dimethyl-
formamide (DMF) at 160 C.24 Further, 2-arylidene-3-oxo-N-[4-(2-oxo-2H-chromen-3-
yl)thiazol-2-yl]butanamides 4a–j on treatment with 2-aminothiophenol 5 in the presence of
glacial acetic acid as a catalyst and methanol as a reaction mediator afforded 4-methyl-N-[4-
(2-oxo-2H-chromen-3-yl)thiazol-2-yl]-2-(substituted phenyl)-2,3-dihydrobenzo[b][1,4]
thiazepine-3-carboxamides 6a–j24 (Scheme 1).

A CONVENIENT, RAPID MICROWAVE-ASSISTED SYNTHESIS
257
R
O
H
O
O
O
O
3a-j
(i)
(ii)
S
S
N
N
HN
NH2
O
1
2
O
O
O
R
R
O
O
S
N
HS
NH2
O
S
HN
O
N
5
HN
(iii)
S
O
N
4a-j
6a-j
R=
Reagents and reaction conditions :
(i) CH3COCH2COOC2H5/DMF, 160 oC, 8 h.
(ii) Conventional : CH3OH/2%NaOH, Reflux, 4−5 h.
Microwave :
a, 3-OCH3,-4-OH
b, 2-NO2
c, 2-Cl
CH3OH/2%NaOH, MWI,
for p1=300W, t1 2.0−3.0 min. & p2=500W, t2 2.0−2.5 min.
(iii) Conventional : CH3OH/glacial CH3COOH, Reflux, 60 oC−70 oC, 8−9 h.
d, 4-Cl
e, 2,4-(Cl)2
f, 2-OCH3
g, 4-OCH3
h, 3,4,5-(OCH3)3
i, 4-N(CH3)2
J, 2-OH
Microwave :
CH3OH/glacial CH3COOH, MWI, 2.0−3.5 min.
for p1=300W, t1 7.0−8.0 min.& p2=500W, t2 5.0−5.5 min.
Scheme 1
The formation of 4a–j was evidenced by the appearance of a signal at δ 8.41–8.46
ppm due to –C=CH, IR bands at νmax 1689–1682 cm−1 stretching, due to >C=O of α,β-
unsaturated compound, and 13C NMR spectra peaks were observed at δ 167.17–168.19 ppm
for C13, 115.30–116.37 ppm for C14, 130.01–131.11 ppm for C15, and 200.91–201.89 ppm
1
for C16. Similarly, peaks of H NMR spectra of 2,3-dihydrobenzo[b][1,4]thiazepine 6a–j
show a doublet at δ 4.01–4.11 (J = 6.8 Hz) ppm due to –COCH– and a doublet at δ
5.50–5.69 (J = 7.0 Hz) ppm due to CH; the downfield absorption of the CH proton
is explained by its attachment to the electronegative sulfur, a phenyl group, and a car-
bon atom having unsaturation with conjugation. In the 13C NMR spectra, peaks were
observed at δ 122.09–123.18 ppm due to C14 and C16 and δ 76.22–76.79 ppm due to
C15, while IR bands of 1,4-benzothiazepine 6a–j appeared at νmax 1609 cm−1 (stretch-
ing, C=N) and νmax 765–635 cm−1 (stretching, C–S), which confirms the formation of
2,3-dihydrobenzo[b][1,4]thiazepine-3-carboxamide derivatives 6a–j. As examples, the 1H
and 13C NMR spectra of 4b, 4f, 6b, and 6f are presented in the Supplemental Materials
(Figures S1–S8).

258
J. P. RAVAL ET AL.
Table 1 Comparison of conventional and microwave synthesis for 4a–j and 6a–j
Conventional
% yield t (h)
Microwave
Microwave
Compound
% yield
t1 (min)
p1 (W)
% yield
t2 (min)
p2 (W)
4a
4b
4c
4d
4e
4f
4g
4h
4i
72
66
68
71
63
67
68
70
73
64
66
57
55
59
65
58
65
52
60
55
5.0
4.5
5.0
5.0
4.0
4.5
5.0
5.0
4.0
4.0
9.0
8.0
8.0
8.5
8.5
8.0
8.0
8.5
9.0
8.5
83
77
82
81
85
75
77
87
83
74
79
81
71
73
78
80
84
75
79
70
3.0
2.0
3.0
3.0
2.5
3.0
2.5
3.0
2.0
2.5
7.0
8.0
7.5
7.0
7.5
8.0
7.5
7.5
7.0
8.0
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
300
94
87
97
92
91
89
87
92
92
85
81
91
88
85
89
92
91
86
88
83
2.0
2.0
2.5
2.0
2.5
2.0
2.5
2.0
2.0
2.5
5.5
5.5
5.5
5.0
5.0
5.5
5.0
5.0
5.5
5.5
500
500
500
500
500
500
500
500
500
500
500
500
500
500
500
500
500
500
500
500
4j
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
All the reactions under MWI were completed within 7.0–8.0 min, whereas similar
reactions under conventional heating (steam bath) at refluxing temperatures gave poor
yields with comparatively longer reaction time periods (Table 1), demonstrating that the
effect of MWI is not purely thermal. Actually, MWI facilitates the polarization25,26 of the
molecules under irradiation causing a rapid reaction to occur. This is consistent with the
reaction mechanism that involves a polar transition state.5
The impact of MWI and conventional heating for the synthesis of compounds 4a–j
and 6a–j has been compared. Moreover, the effects of irradiation power and time on the
reaction were also studied and the results are summarized in Tables 2 and 3. It was found
the higher yield of compounds 4a–j and 6a–j can be obtained at 300 W in 7.0–8.0 min and
at 500 W in 5.0–5.5 min under MWI conditions. The structures of the above compounds
were in good agreement with spectral and analytical data.
Antimicrobial Activity27,28
The minimum inhibition concentration (MIC) was determined using the streak plate
and cup plate methods according to a standard procedure.27 All the newly synthesized
Table 2 The effect of MWI powera for 6a
Irradiation power (W)
Yield
250
70
300
72
350
74
400
77
450
79
500
81
aIrradiation time is 2 min.

A CONVENIENT, RAPID MICROWAVE-ASSISTED SYNTHESIS
259
Table 3 The effect of MWI timea for 6a
Irradiation time (min)
Yield
5.0
70
4.5
72
4.0
74
3.0
77
2.5
79
2.0
81
aIrradiation power is 500 W.
compounds were screened in vitro for their antimicrobial activity against a variety of
bacterial strains such as gram-positive bacteria [Bacills substilis (ATCC-6633) and Staphy-
lococcus aureus (ATCC-6538)], gram-negative bacteria [Escherichia coli (ATCC-6538)
and Pseudomonas aeruginosa (ATCC-1539)], and, in addition, some fungal pathogens
[Candida albicans (ATCC-64550), Candida krusei (ATCC-14243), and Candida parap-
silosis (ATCC-22019)] (Table S1). The sensitivity of the selected microorganisms to some
synthesized compounds 4a–j and 6a–j was determined in vitro at four concentrations 50,
100, 150, and 200 µg/mL in CHCl3.The MIC of the compounds was defined as the lowest
concentration at which there was 80% inhibition of growth compared with the growth for
a drug-free control.28 Standard drugs ampicillin, amoxicillin, penicillin, and fluconazole
were also screened under similar conditions for comparison.
The antimicrobial screening results, presented in Table S1 (Supplemental Materi-
als), revealed that all newly synthesized compounds exhibited potent antibacterial activity.
In general, compounds 6a–j exhibited more pronounced activity than the compounds 4a–j
against both gram-positive and gram-negative bacteria. Among all the compounds tested, 4g
and 6g exhibited remarkable antibacterial activity against the gram-negative Escherichia
coli (ATCC 6538) and Pseudomonas aeruginosa (ATCC 1539) as compared with stan-
dards, which may be due to the presence of a para-substituted methoxy group, while
compound 6i displayed promising activity against gram-positive Bacills substilis (ATCC-
6633) and Staphylococcus aureus (ATCC-6538), which may be due to the presence of a
para-substituted dimethylamino group. On the other hand, compound 6h is more effective
against all fungal strains, which have a trimethoxy group. Thus, by visualizing the antimi-
crobial data, it could be observed that some of the compounds possess significant activity.
However, none of the compounds was superior to standards used against any bacteria or
fungi.
CONCLUSION
In conclusion, a new method for the synthesis of 2,3-dihydrobenzo[b][1,4]thiazepine
derivatives using MWI offers significant improvements over the existing procedures and
thus helps a facile entry into the synthesis of a variety of thiazepines of potentially
high synthetic utility. Also, this simple and reproducible technique affords various 2,3-
dihydrobenzo[b][1,4]thiazepine derivatives with shorter reaction times, excellent yields,
and without the formation of undesirable side products. By visualizing the antimicrobial
data, it could be observed that some of the compounds possess significant activity. How-
ever, the activities of the tested compounds are less than those of standard antibacterial and
antifungal agents used.

260
J. P. RAVAL ET AL.
EXPERIMENTAL
General Procedures
All the melting points were determined on a PMP-DM scientific melting point appa-
ratus and are uncorrected. The purity of compounds was checked by thin layer chromatog-
raphy (TLC; 0.5 mm thickness) using silica gel G-coated Al plates (Merck), and spots
were visualized by exposing the dry plates to iodine vapors. IR spectra (υmax in cm−1
)
were recorded on a Perkin-Elmer spectrum BX series FTIR spectrometer using KBr or
1
Nujol technique. H NMR spectra were recorded on a Bruker WM 400 FT MHz NMR
instrument, using CDCl3 or DMSO-d6 as solvent and TMS as internal reference (chemical
shifts in δ, ppm), and the mass spectra were run on a Varian model MAT MS-311 spec-
trometer at 70 eV. The elemental analysis (C, H, and N) of compounds was performed at
SICART, Vallabh Vidyanagar, Dist. Anand, Gujarat, India, on a Carlo Erba 1108 elemental
analyzer. Their results were found to be in good agreement with the calculated values. The
microwave-assisted reactions are carried out in a “QPro-M Modified Microwave Synthesis
System” manufactured by Questron Technologies Corporation, Ontario, Canada, wherein
microwaves are generated by a magnetron at a frequency of 2450 MHz having an output en-
ergy range of 100–500 W, and an individual sensor for temperature control (optical fiber is
used as a individual sensor for temperature control) along with a reflux condenser attached
to it while constant stirring—thus avoiding the risk of high pressure development—and are
synthesized on preparative scales.
Synthesis of 3-Oxo-N-(4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl)
Butanamide (2). The starting compound was synthesized from the reaction of 3-(2-
amino-1,3-thiazol-4-yl)-2H-chromen-2-one 1 and ethyl acetoacetate.24,29
General Synthesis of 2-Arylidene-3-Oxo-N-(4-(2-Oxo-2H-Chromen-3-yl)
Thiazol-2-yl)Butanamide (4a–j)
Conventional Method. In a 250 mL round bottom flask (RBF), 3-oxo-N-(4-
(2-oxo-2H-chromen-3-yl)thiazol-2-yl)butanamide (0.01 mol) in methanol (30 mL) and
substituted aryl aldehyde (0.01 mol) were taken and to it 2% NaOH (5 mL) solution was
added. The reaction mixture was refluxed for 4.0–5.0 h and then poured into crushed ice.
The solid product thus obtained was filtered and washed with water, dried, and recrystallized
from methanol.
Microwave Method. An equimolar amount of 3-oxo-N-(4-(2-oxo-2H-chromen-
3-yl)thiazol-2-yl)butanamide (0.01 mol) and substituted aryl aldehyde (0.01 mol) in
methanol (30 mL), in the presence of catalytic amount of 2% NaOH (5 mL), was put
in an Erlenmeyer flask and then irradiated under QPro-M Microwave System in two stages
(t1= 2.0–3.0 min and t2 = 2.0–2.5 min) at two different power levels18,26 (p1 = 300 W and
p2 = 500 W) respectively (Table 1). After completion of the reaction (monitored by TLC),
it was poured into crushed ice. The solid product so obtained was filtered, washed with
water, dried, and crystallized from methanol.
Likewise, all compounds 4a–j were prepared by the above method using substituted
aryl aldehydes 3a–j.
2-(4-Hydroxy-3-Methoxybenzylidene)-3-Oxo-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-
◦
◦
2-yl]Butanamide (4a): mp 105 C–107 C; IR [ν (cm−1), KBr]: 3450 (OH), 3267 (C–H,
aliphatic), 3025 (aromatic ring), 2830 (OCH3), 1723 (>C=O, coumarin), 1689 (C=N),

A CONVENIENT, RAPID MICROWAVE-ASSISTED SYNTHESIS
261
1685 (stretching band, >C=O, α,β-unsaturated chalcone), 1640 (>C=O), 1545 (NH), 635
(C–S). 1H NMR [400 MHz, δ (ppm), DMSO-d6]: 2.15 (s, 3H, –CH3), 3.80 (s, 3H, –OCH3),
6.43 (s, 1H, –OH), 7.25–7.60 (m, 7H, Ar–H), 7.79 (s, 1H, =CH, thiazole nucleus), 8.23
(s, 1H, =CH, coumarin nucleus), 8.41 (s, 1H, =CH), 8.74 (s, 1H, –NH). 13C NMR (100
MHz, DMSO-d6) δ ppm: 29.24 (C17, CH3), 110.04 (C8), 115.38 (C14), 125.67–129.90
(C3–C6, C19–C23), 129.86 (C18), 130.07 (C15), 133.08 (C9), 133.46 (C11), 136.21 (C10),
151.57 (C12), 154.25 (C1, C2), 158.12 (C7), 168.15 (C13), 201.89 (C16). Anal. calcd. for
C24H18N2O6S (462.476): C, 62.33; H, 3.92; N, 6.06; found: C, 62.21; H, 3.78; N, 6.12.
2-(2-Nitrobenzylidene)-3-Oxo-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl]Butanamide
(4b): mp 131 ◦C– 134 ◦C; IR [ν (cm−1), KBr]: 3270 (C–H, aliphatic), 3027 (aromatic ring),
2928 (–CH3), 1722 (>C=O, coumarin), 1688 (stretching band, >C=O, α,β-unsaturated
chalcone), 1650 (>C=O), 1609 (C=N), 1560 and 1344 (–NO2), 1542 (–NH), 632
(C–S). 1H NMR [400 MHz, δ (ppm), DMSO-d6]: 2.16 (s, 3H, –CH3), 6.71–7.69 (m, 8H,
Ar–H), 7.79 (s, 1H, =CH, thiazole nucleus), 8.25 (s, 1H, =CH, coumarin nucleus), 8.44
(s, 1H, =CH), 8.73 (s, 1H, –NH). 13C NMR (100 MHz, DMSO-d6) δ ppm: 29.14 (C17),
111.04 (C8), 116.37 (C14), 125.57–128.90 (C3–C6, C19–C23), 127.81 (C18), 131.07 (C9),
131.09 (C15), 132.56 (C11), 135.11 (C10), 152.57 (C12), 154.25 (C1, C2), 157.12 (C7),
167.25 (C13), 200.91 (C16). Anal. calcd. for C23H15N3O6S (461.448): C, 59.87; H, 3.28;
N, 9.11; found: C, 59.64; H, 3.14; N, 9.19.
2-(2-Chlorobenzylidene)-3-Oxo-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl]Butana-
mide (4c): mp 152 ◦C– 155 ◦C; IR [ν (cm−1), KBr]: 3256 (C–H, aliphatic), 3023 (aromatic
ring), 1725 (>C=O, coumarin), 1683 (stretching band, >C=O, α,β-unsaturated chalcone),
1
1660 (>C=O), 1612 (C=N), 1542 (–NH), 810 (C–Cl), 638 (C–S). H NMR [400 MHz,
δ (ppm), DMSO-d6]: 2.18 (s, 3H, –CH3), 6.95–7.67 (m, 8H, Ar–H), 7.79 (s, 1H, =CH,
thiazole nucleus), 8.22 (s, 1H, =CH, coumarin nucleus), 8.42 (s, 1H, =CH), 8.75 (s, 1H,
NH). 13C NMR (100 MHz, DMSO-d6) δ ppm: 29.11 (C17), 112.06 (C8), 116.28 (C14),
125.66–128.77 (C3–C6, C19–C23), 129.76 (C18), 131.11 (C15), 132.66 (C11), 134.09 (C9),
135.11 (C10), 152.58 (C12), 154.21 (C1, C2), 157.11 (C7), 167.17 (C13), 200.79 (C16).
Anal. calcd. for C23H15ClN2O4S (450.895): C, 61.27; H, 3.35; N, 6.21; found: C, 61.09;
H, 3.11; N, 6.08.
2-(4-Chlorobenzylidene)-3-Oxo-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl]Butana-
mide (4d): mp 117 ◦C–119 ◦C; IR [ν (cm−1), KBr]: 3265 (C–H, aliphatic), 3028 (aromatic
ring), 1721 (>C=O, coumarin), 1682 (stretching band, >C=O, α,β-unsaturated chalcone),
1
1665 (>C=O), 1613 (C=N), 1548 (–NH), 817 (C–Cl), 634 (C–S). H NMR [400 MHz,
δ (ppm), DMSO-d6]: 2.18 (s, 3H, –CH3), 7.00–7.55 (m, 8H, Ar–H), 7.79 (s, 1H, =CH,
thiazole nucleus), 8.22 (s, 1H, =CH, coumarin nucleus), 8.42 (s, 1H, =CH), 8.77 (s, 1H,
NH). 13C NMR (100 MHz, DMSO-d6) δ ppm: 29.44 (C17), 110.00 (C8), 115.31 (C14),
125.57–128.79 (C3–C6, C19–C23), 129.56 (C18), 130.02 (C15), 133.00 (C9), 133.07 (C11),
136.01 (C10), 151.07 (C12), 154.15 (C1, C2), 159.09 (C7), 168.10 (C13), 201.39 (C16).
Anal. calcd. for C23H15ClN2O4S (450.895): C, 61.27; H, 3.35; N, 6.21; found: C, 61.15;
H, 3.11; N, 6.09.
2-(2,4-Dichlorobenzylidene)-3-Oxo-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl]
◦
◦
Butanamide (4e): mp 120 C–123 C; IR [ν (cm−1), KBr]: 3270 (C–H, aliphatic), 3024
(aromatic ring), 1723 (>C=O, coumarin), 1686 (stretching band, >C=O, α,β-unsaturated
1
chalcone), 1670 (>C=O), 1610 (C=N), 1550 (–NH), 818 (C–Cl), 636 (C–S). H NMR
[400 MHz, δ (ppm), DMSO-d6]: 2.18 (s, 3H, –CH3), 6.74–7.49 (m, 7H, Ar–H), 7.79 (s,
1H, =CH, thiazole nucleus), 8.22 (s, 1H, =CH, coumarin nucleus), 8.40 (s, 1H, =CH),
8.76 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ ppm: 29.20 (C17), 110.14 (C8),

262
J. P. RAVAL ET AL.
115.37 (C14), 125.87–129.89 (C3–C6, C19–C23), 129.81 (C18), 130.08 (C15), 133.28 (C9),
133.44 (C11), 136.23 (C10), 151.55 (C12), 154.75 (C1, C2), 158.10 (C7), 168.16 (C13),
201.90 (C16). Anal. calcd. for C23H14Cl2N2O4S (485.340): C, 56.92; H, 2.91; N, 5.77;
found: C, 56.79; H, 2.69; N, 5.65.
2-(2-Methoxybenzylidene)-3-Oxo-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl]Buta-
namide (4f): mp 112 ◦C–115 ◦C; IR [ν (cm−1), KBr]: 3267 (C–H, aliphatic), 3029
(aromatic ring), 2830 (OCH3), 1722 (>C=O, coumarin), 1685 (stretching band, >C=O,
α,β-unsaturated chalcone), 1677 (>C=O), 1611 (C=N), 1545 (NH), 637 (C–S). 1H NMR
[400 MHz, δ (ppm), DMSO-d6]: 2.22 (s, 3H, CH3), 3.63 (s, 3H, OCH3), 6.76–7.29 (m,
8H, Ar–H), 7.79 (s, 1H, =CH, thiazole nucleus), 8.20 (s, 1H, =CH, coumarin nucleus),
8.46 (s, 1H, =CH), 8.71 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ ppm: 29.27
(C17), 110.08 (C8), 115.34 (C14), 125.65–129.60 (C3–C6, C19–C23), 129.88 (C18), 130.05
(C15), 133.09 (C9), 133.41 (C11), 136.20 (C10), 151.52 (C12), 154.24 (C1, C2), 158.17 (C7),
168.13 (C13), 201.86 (C16). Anal. calcd. for C24H18N2O5S (446.476): C, 64.56; H, 4.06;
N, 6.27; found: C, 64.42; H, 4.22; N, 6.14.
2-(4-Methoxybenzylidene)-3-Oxo-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl]Buta-
namide (4g): mp 158 ◦C–160 ◦C; IR [ν (cm−1), KBr]: 3261 (C–H, aliphatic), 3027
(aromatic ring), 2837 (OCH3), 1727 (>C=O, coumarin), 1680 (stretching band, >C=O,
α,β-unsaturated chalcone), 1672 (>C=O), 1607 (C=N), 1540 (NH), 633 (C–S). 1H NMR
[400 MHz, δ (ppm), DMSO-d6]: 2.22 (s, 3H, CH3), 3.66 (d, 3H, OCH3), 6.74–7.29 (m,
8H, Ar–H), 7.79 (s, 1H, =CH, thiazole nucleus), 8.20 (s, 1H, =CH, coumarin nucleus),
8.46 (s, 1H, =CH), 8.73 (s, 1H, –NH). 13C NMR (100 MHz, DMSO-d6) δ ppm: 29.23
(C17), 110.04 (C8), 115.30 (C14), 125.61–129.92 (C3–C6, C19–C23), 129.84 (C18), 130.01
(C15), 133.05 (C9), 133.47 (C11), 136.26 (C10), 151.58 (C12), 154.20 (C1, C2), 158.13 (C7),
168.19 (C13), 201.82 (C16). Anal. calcd. for C24H18N2O5S (446.476): C, 64.56; H, 4.06;
N, 6.27; found: C, 64.44; H, 4.14; N, 6.05.
2-(3,4,5-Trimethoxybenzylidene)-3-Oxo-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-
yl]Butanamide (4h): mp 135 ◦C–138 ◦C; IR [ν (cm−1), KBr]: 3265 (C–H, aliphatic), 3028
(aromatic ring), 2838 (OCH3), 1723 (>C=O, coumarin), 1683 (stretching band, >C=O,
α,β-unsaturated chalcone), 1679 (>C=O), 1612 (C=N), 1542 (NH), 637 (C–S). 1H NMR
[400 MHz, δ (ppm), DMSO-d6]: 2.19 (s, 3H, CH3), 3.66 (s, 3H × 3, –OCH3), 4.12 (s, 1H,
–OH), 6.76–7.22 (m, 8H, Ar–H), 7.79 (s, 1H, =CH, thiazole nucleus), 8.25 (s, 1H, =CH,
coumarin nucleus), 8.47 (s, 1H, =CH), 8.77 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6)
δ ppm: 29.21 (C17), 110.01 (C8), 115.37 (C14), 125.68–129.90 (C3–C6, C19–C23), 129.81
(C18), 130.17 (C15), 133.02 (C9), 133.44 (C11), 136.23 (C10), 151.55 (C12), 154.27 (C1,
C2), 158.10 (C7), 168.16 (C13), 201.80 (C16). Anal. calcd. for C26H22N2O7S (506.528): C,
61.65; H, 4.38; N, 5.53; found: C, 61.51; H, 4.25; N, 5.39.
2-[4-(Dimethylamino)Benzylidene]-3-Oxo-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-
2-yl]Butanamide (4i): mp 147 ◦C–149 ◦C; IR [ν (cm−1), KBr]: 3271 (C–H, aliphatic), 3024
(aromatic ring), 1727 (>C=O, coumarin), 1689 (stretching band, >C=O, α,β-unsaturated
1
chalcone), 1640 (>C=O), 1612 (C=N), 1544 (NH), 1319 (–N(CH3)2), 635 (C–S). H
NMR [400 MHz, δ (ppm), DMSO-d6]: 2.15 (s, 3H, CH3), 2.92 (d, 6H, N(CH3)2), 6.76–7.87
(m, 8H, Ar–H), 7.79 (s, 1H, =CH, thiazole nucleus), 8.21 (s, 1H, =CH, coumarin nucleus),
8.41 (s, 1H, =CH), 8.79 (s, 1H, –NH). 13C NMR (100 MHz, DMSO-d6) δ ppm: 29.27
(C17), 110.14 (C8), 115.34 (C14), 125.65–129.97 (C3–C6, C19–C23), 129.88 (C18), 130.05
(C15), 133.11 (C9), 133.41 (C11), 136.20 (C10), 151.52 (C12), 154.21 (C1, C2), 158.11 (C7),
168.13 (C13), 201.86 (C16). Anal. calcd. for C25H21N3O4S (459.518): C, 65.34; H, 4.61;
N, 9.14; found: C, 65.21; H, 4.51; N, 9.10.

A CONVENIENT, RAPID MICROWAVE-ASSISTED SYNTHESIS
263
2-(2-Hydroxybenzylidene)-3-Oxo-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl]Buta-
namide (4j): mp 162 ◦C–165 ◦C; IR [ν (cm−1), KBr]: 3456 (OH), 3272 (C–H, aliphatic),
3027 (aromatic ring), 1725 (>C=O, coumarin), 1610 (C=N), 1682 (stretching band,
>C=O, α,β-unsaturated chalcone), 1611 (>C=O), 1548 (NH), 638 (C–S). 1H NMR [400
MHz, δ (ppm), DMSO-d6]: 2.11 (s, 3H, CH3), 4.17 (s, 1H, OH), 6.89–7.23 (m, 8H, Ar–H),
7.79 (s, 1H, =CH, thiazole nucleus), 8.27 (s, 1H, =CH, coumarin nucleus), 8.44 (s, 1H,
=CH), 8.75 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ ppm: 29.22 (C17), 110.04
(C8), 115.39 (C14), 125.61–129.92 (C3–C6, C19–C23), 129.83 (C18), 130.00 (C15), 133.04
(C9), 133.46 (C11), 136.25 (C10), 151.57 (C12), 154.20 (C1, C2), 158.13 (C7), 168.18 (C13),
201.81 (C16). Anal. calcd. for C23H16N2O5S (432.450): C, 63.88; H, 3.73; N, 6.48; found:
C, 63.74; H, 3.61; N, 6.36.
General Synthesis of 4-Methyl-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-
yl]-2-Substituted Phenyl-2,3-Dihydrobenzo[b][1,4]Thiazepine-3-Carboxamides
(6a–j)
Conventional Method.24 In a 250 mL RBF, 2-arylidene-3-oxo-N-[4-(2-oxo-2H-
chromen-3-yl)thiazol-2-yl]butanamide (0.01 mol), 2-aminothiophenol, and glacial acetic
acid (5 mL) in methanol (20 mL) were taken. The reaction mixture was refluxed on a water
bath at 65 ◦C–70 ◦C for 8.0–9.0 h and the solvent was distilled off. Then, it was poured into
crushed ice. The product obtained was filtered, washed with water, dried, and crystallized
from ethanol.
Similarly, all compounds 6a–j were prepared by the above method.
Microwave Method. An equimolar amount of 2-arylidene-3-oxo-N-[4-(2-oxo-
2H-chromen-3-yl)thiazol-2-yl]butanamide (0.01 mol), 2-aminothiophenol (0.01 mol) in
the presence of catalytic amount glacial acetic acid (5 mL) in methanol (20 mL) were put in
an Erlenmeyer flask and then irradiated under a QPro-M Microwave System in two stages
(t1= 7.0–8.0 min and t2 = 5.0–5.5 min) at two different power levels18,26 (p1 = 300 W
and p2 = 500 W) respectively (Table 1). After completion of the reaction (monitored by
TLC), the reaction mass was poured into crushed ice. The product so obtained was filtered,
washed with water, dried, and crystallized from ethanol.
Likewise, all compounds 6a–j were prepared by the above method using various
4a–j. Spectral and analytical data of compounds 6a–j are given in the following sections
(for numbering pattern see Figure 1).
2-(4-Hydroxy-3-Methoxyphenyl)-4-Methyl-N-(4-(2-Oxo-2H-Chromen-3-yl)Thiazol-
◦
◦
2-yl)-2,3-Dihydrobenzo[b][1,4]Thiazepine-3-Carboxamide (6a): mp 116 C–118 C; IR
[ν (cm−1), KBr]: 3450 (OH), 3261 (C–H, aliphatic), 3025 (Ar–H, aromatic ring), 2832
(OCH3), 2920 (CH3), 1725 (>C=O, coumarin), 1640 (>C=O), 1612 (C=N), 1553 (NH),
1
662 (C–S). H NMR [400 MHz, δ (ppm), DMSO-d6]: 2.04 (s, 3H, –CH3), 4.03 (d, 1H,
–CH, J = 6.8 Hz), 5.56 (d, 1H, –CH, J = 7.0 Hz), 3.83 (d, 3H, OCH3), 4.11 (s, 1H, OH),
7.09–7.69 (m, 11H, Ar–H), 8.19 (s, 1H, C–H of thiazole), 8.28 (s, 1H, –CH of coumarin),
9.80 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ ppm: 23.46 (C17), 76.25 (C15), 35.77
(OCH3), 110.08 (C8), 116.25–129.90 (C3–C6, C20–C23, C25–C29), 123.07 (C14, C16),
133.08 (C9), 135.22 (C11), 152.33 (C18, C19), 153.60 (C10), 154.25 (C1, C2), 158.11 (C7),
159.47 (C12), 159.93 (C24), 166.15 (C13). MS: m/z [570]+. Anal. calcd. for C30H23N3O5S
(569.653): C, 63.25; H, 4.07; N, 7.38; found: C, 63.11; H, 4.15; N, 7.26.
2-(2-Nitrophenyl)-4-Methyl-N-(4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl)-2,3-Dihy-
drobenzo[b][1,4]Thiazepine-3-Carboxamide (6b): mp 102 ◦C–104 ◦C; IR [ν (cm−1),

264
J. P. RAVAL ET AL.
3
O
O
1
7
5
6
R
8
11
R
19
10
3
4
2
20
O
O
1
2
7
9
4
S
25
26
5
6
21
18
22
N
12
28
29
8
11
27
O
10
23
HN
9
S
24
15
13
15
O
14
N
12
16
17
16
H C
17
14
3
S
HN
13
19
N
O
18
21
20
23
6a-j
4a-j
22
Figure 1 The numbering system of the compounds for 13C NMR spectra.
KBr]: 3270 (C–H, aliphatic), 3026 (Ar–H, aromatic ring), 2930 (CH3), 1728 (>C=O,
coumarin), 1646 (>C=O), 1619 (C=N), 1570 and 1377 (NO2), 1529 (NH), 652 (C–S). 1H
NMR [400 MHz, δ (ppm), DMSO-d6]: 2.02 (s, 3H, CH3), 4.02 (d, 1H, CH, J = 6.8 Hz),
5.54 (d, 1H, –CH, J = 7.0 Hz), 7.10–7.70 (m, 12H, Ar–H), 8.16 (s, 1H, –CH of thiazole),
8.26 (s, 1H, –CH of coumarin), 9.40 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ ppm:
22.46 (C17), 76.24 (C15), 110.07 (C8), 114.24–128.81 (C3–C6, C20–C23, C25–C29), 122.09
(C14, C16), 132.10 (C9), 134.37 (C11), 151.37 (C18, C19), 152.57 (C10), 153.24 (C1, C2),
157.10 (C7), 158.36 (C12), 159.91 (C24), 165.14 (C13). MS: m/z [568]+. Anal. calcd. for
C29H20N4O5S2 (568.625): C, 61.25; H, 3.55; N, 9.85; found: C, 61.12; H, 3.41; N, 9.71.
2-(2-Chlorophenyl)-4-Methyl-N-(4-(2-Oxo-2H-chro◦men-3-yl)thiazol-2-yl)-2,3-dihy-
◦
drobenzo[b][1,4]thiazepine-3-carboxamide (6c): mp 97 C–99 C; IR [ν (cm−1), KBr]:
3270 (C–H, aliphatic), 3024 (Ar–H, aromatic ring), 2925 (CH3), 1724 (>C=O, coumarin),
1660 (>C=O), 1619 (C=N), 1542 (NH), 811 (C–Cl), 632 (C–S). 1H NMR [400 MHz, δ
(ppm), DMSO-d6]: 2.06 (s, 3H, –CH3), 4.01 (d, 1H, –CH, J = 6.8 Hz), 5.50 (d, 1H, –CH,
J = 7.0 Hz), 7.09–7.79 (m, 12H, Ar–H), 8.18 (s, 1H, –CH of thiazole), 8.26 (s, 1H, –CH of
coumarin), 9.60 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ ppm: 23.44 (C17), 76.22
(C15), 110.11 (C8), 116.20–129.77 (C3–C6, C20–C23, C25–C29), 123.09 (C14, C16), 133.14
(C9), 135.25 (C11), 153.67 (C10), 159.67 (C12), 152.21 (C18, C19), 154.18 (C1, C2), 158.18
(C7), 159.78 (C24), 166.18 (C13). MS: m/z [559]+. Anal. calcd. for C29H20ClN3O3S2
(558.072): C, 62.41; H, 3.61; N, 7.53; found: C, 62.29; H, 3.79; N, 7.39.
2-(4-Chlorophenyl)-4-Methyl-N-(4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl)-2,3-Dihy-
drobenzo[b][1,4]Thiazepine-3-Carboxamide (6d): mp 105 ◦C–107 ◦C; IR [ν (cm−1),
KBr]: 3270 (C–H, aliphatic), 3023 (Ar–H, aromatic ring), 2925 (CH3), 1724 (>C=O,
1
coumarin), 1666 (>C=O), 1619 (C=N), 1542 (NH), 814 (C–Cl), 632 (C–S). H NMR
[400 MHz, δ (ppm), DMSO-d6]: 2.06 (s, 3H, –CH3), 4.01 (d, 1H, –CH, J= 6.8 Hz), 5.52
(d, 1H, –CH, J = 7.0 Hz), 7.09–7.79 (m, 12H, Ar–H), 8.17 (s, 1H, –CH of thiazole), 8.25
(s, 1H, –CH of coumarin), 9.59 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ ppm:
22.89 (C17), 75.89 (C15), 114.09 (C8), 114.27–127.90 (C3–C6, C20–C23, C25–C29), 122.79
(C14, C16), 131.11 (C9), 134.78 (C11), 151.67 (C18, C19), 152.77 (C10), 153.11 (C1, C2),
158.89 (C12), 159.14 (C7), 159.91 (C24), 165.18 (C13). MS: m/z [558]+. Anal. calcd. for
C29H20ClN3O3S2 (558.072): C, 62.41; H, 3.61; N, 7.53; found: C, 62.28; H, 3.49; N, 7.40.

A CONVENIENT, RAPID MICROWAVE-ASSISTED SYNTHESIS
265
2-(2,4-Dichlorophenyl)-4-Methyl-N-(4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl)-2,3-
Dihydrobenzo[b][1,4]Thiazepine-3-Carboxamide (6e): mp 127 ◦C–130 ◦C; IR [ν (cm−1),
KBr]: 3270 (C–H, aliphatic), 3022 (Ar–H, aromatic ring), 2927 (CH3), 1724 (>C=O,
1
coumarin), 1677 (>C=O), 1619 (C=N), 1542 (NH), 820 (C–Cl), 632 (C–S). H NMR
[400 MHz, δ (ppm), DMSO-d6]: 2.10 (s, 3H, CH3), 4.06 (d, 1H, –CH, J = 6.8 Hz), 5.58
(d, 1H, –CH, J = 7.0 Hz), 7.10–7.90 (m, 11H, Ar–H), 8.18 (s, 1H, –CH of thiazole), 8.28
(s, 1H, –CH of coumarin), 9.62 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δ ppm:
23.47 (C17), 76.52 (C15), 112.18 (C8), 116.15–129.10 (C3–C6, C20–C23, C25–C29), 123.09
(C14, C16), 131.28 (C9), 135.77 (C11), 152.83 (C18, C19), 153.79 (C10), 154.15 (C1, C2),
158.14 (C7), 159.74 (C12), 159.92 (C24), 166.18 (C13). MS: m/z [593]+. Anal. calcd. for
C29H19Cl2N3O3S2 (592.517): C, 58.78; H, 3.23; N, 7.09; found: C, 58.66; H, 3.09; N,
7.00.
2-(2-Methoxyphenyl)-4-Methyl-N-(4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl)-2,3-
Dihydrobenzo[b][1,4]Thiazepine-3-Carboxamide (6f): mp 109 ◦C–111 ◦C; IR [ν (cm−1),
KBr]: 3270 (C–H, aliphatic), 3024 (Ar–H, aromatic ring), 2935 (CH3), 2828 (OCH3),
1722 (>C=O, coumarin), 1652 (>C=O), 1619 (C=N), 1542 (NH), 632 (C–S). 1H NMR
[400 MHz, δ (ppm), DMSO-d6]: 2.06 (s, 3H, CH3), 3.80 (s, 3H, OCH3), 4.04 (d, 1H, –CH,
J = 6.8 Hz), 5.60 (d, 1H, –CH, J = 7.0 Hz), 6.89–7.69 (m, 12H, Ar–H), 8.16 (s, 1H,
–CH of thiazole), 8.24 (s, 1H, –CH of coumarin), 9.82 (s, 1H, NH). 13C NMR (100 MHz,
DMSO-d6) δ ppm: 23.74 (C17), 76.52 (C15), 34.09 (OCH3), 110.09 (C8), 116.52–129.09
(C3–C6, C20–C23, C25–C29), 123.18 (C14, C16), 133.11 (C9), 135.27 (C11), 152.89 (C18,
C19), 153.65 (C10), 154.52 (C1, C2), 158.11 (C7), 159.74 (C12), 161.11 (C24), 166.18 (C13).
MS: m/z [552]+; Anal. calcd. for C30H23N3O4S2 (553.653): C, 65.08; H, 4.19; N, 7.59;
found: C, 65.14; H, 4.07; N, 7.46.
2-(4-Methoxyphenyl)-4-Methyl-N-(4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl)-2,3-
Dihydrobenzo[b][1,4]Thiazepine-3-Carboxamide (6g): mp 121 ◦C–124 ◦C; IR [ν (cm−1),
KBr]: 3270 (C–H, aliphatic), 3024 (Ar–H, aromatic ring), 2935 (CH3), 2830 (OCH3),
1720 (>C=O, coumarin), 1659 (>C=O), 1614 (C=N), 1542 (NH), 632 (C–S). 1H NMR
[400 MHz, δ (ppm), DMSO-d6]: 2.16 (s, 3H, CH3), 3.89 (s, 3H, OCH3), 4.04 (d, 1H, –CH,
J = 6.8 Hz), 5.67 (d, 1H, –CH, J = 7.0 Hz), 6.85–7.77 (m, 12H, Ar–H), 8.14 (s, 1H,
–CH of thiazole), 8.24 (s, 1H, –CH of coumarin), 9.77 (s, 1H, NH). 13C NMR (100 MHz,
DMSO-d6) δ ppm: 24.77 (C17), 35.11 (OCH3), 75.72 (C15), 110.11 (C8), 116.62–129.18
(C3–C6, C20–C23, C25–C29), 122.77 (C14, C16), 132.78 (C9), 134.99 (C11), 152.78 (C10),
153.18 (C18, C19), 158.14 (C7), 154.51 (C1, C2), 158.88 (C12), 160.09 (C24), 165.18 (C13).
MS: m/z [552]+. Anal. calcd. for C30H23N3O4S2 (553.653): C, 65.08; H, 4.19; N, 5.59;
found: C, 65.26; H, 4.27; N, 5.45.
2-(3,4,5-Trimethoxyphenyl)-4-Methyl-N-(4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl)-
2,3-Dihydrobenzo[b][1,4]Thiazepine-3-Carboxamide (6h): mp 141 ◦C–146 ◦C; IR [ν
(cm−1), KBr]: 3270 (C–H, aliphatic), 3027 (Ar–H, aromatic ring), 2935 (CH3), 2835
(OCH3), 1720 (>C=O, coumarin), 1652 (>C=O), 1614 (C=N), 1542 (NH), 632 (C–S).
1H NMR [400 MHz, δ (ppm), DMSO-d6]: 2.18 (s, 3H, CH3), 3.89 (s, 9H, OCH3), 4.11
(d, 1H, –CH, J = 6.8 Hz), 5.69 (d, 1H, –CH, J = 7.0 Hz), 6.80–7.77 (m, 10H, Ar–H),
8.18 (s, 1H, –CH of thiazole), 8.26 (s, 1H, –CH of coumarin), 9.79 (s, 1H, NH). 13C
NMR (100 MHz, DMSO-d6) δ ppm: 24.97 (C17), 35.18 (OCH3), 75.79 (C15), 110.10 (C8),
116.65–129.99 (C3–C6, C20–C23, C25–C29), 122.87 (C14, C16), 133.78 (C9), 153.87 (C10),
134.99 (C11), 154.11 (C18, C19), 154.77 (C1, C2), 158.77 (C12), 164.11 (C13), 160.18 (C24),
168.11 (C7). MS: m/z [612]+. Anal. calcd. for C32H27N3O6S2 (613.705): C, 62.63; H,
4.43; N, 6.85; found: C, 62.49; H, 4.32; N, 6.71.

266
J. P. RAVAL ET AL.
2-[4-(Dimethylamino)Phenyl]-4-Methyl-N-[4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-
yl]-2,3-Dihydrobenzo[b][1,4]Thiazepine-3-Carboxamide (6i): mp 132 ◦C–134 ◦C;
IR [ν (cm−1), KBr]: 3270 (C–H, aliphatic), 3029 (Ar–H, aromatic ring), 2937
(CH3), 1725 (>C=O, coumarin), 1636 (>C=O), 1617 (C=N), 1542 (NH), 1315
(N(–CH3)2), 632 (C–S). 1H NMR [400 MHz, δ (ppm), DMSO-d6]: 2.18 (s, 3H,
CH3), 2.90 (m, 6H, –N(CH3)2), 3.79 (s, 3H, OCH3), 4.06 (d, 1H, –CH, J =
6.8 Hz), 5.67 (d, 1H, –CH, J = 7.0 Hz), 6.71–7.83 (m, 12H, Ar–H), 8.14 (s, 1H,
–CH of thiazole), 8.22 (s, 1H, –CH of coumarin), 9.75 (s, 1H, NH). 13C NMR (100 MHz,
DMSO-d6) δ ppm: 24.79 (C17), 75.74 (C15), 110.18 (C8), 116.65–129.81 (C3–C6, C20–C23,
C25–C29), 122.79 (C14, C16), 132.87 (C9), 133.11 (C11), 152.79 (C10), 153.19 (C18, C19),
154.52 (C1, C2), 158.09 (C12), 158.18 (C7), 165.11 (C13), 160.14 (C24). MS: m/z [566]+.
Anal. calcd. for C31H26N4O3S2 (566.695): C, 65.70; H, 4.62; N, 9.89; found: C, 65.56; H,
4.48; N, 9.78.
2-(2-Hydroxyphenyl)-4-Methyl-N-(4-(2-Oxo-2H-Chromen-3-yl)Thiazol-2-yl)-2,3-
Dihydrobenzo[b][1,4]Thiazepine-3-Carboxamide (6j): mp 118 ◦C–119 ◦C; IR [ν (cm−1),
KBr]: 3460 (OH), 3270 (C–H, aliphatic), 3020 (Ar–H, aromatic ring), 2920 (CH3), 1727
(>C=O, coumarin), 1678 (>C=O), 1617 (C=N), 1542 (NH), 632 (C–S). 1H NMR [400
MHz, δ (ppm), DMSO-d6]: 2.18 (s, 3H, CH3), 4.02 (d, 1H, –CH, J = 6.8 Hz), 4.14 (s,
1H, OH), 5.65 (d, 1H, –CH, J = 7.0 Hz), 6.87–7.79 (m, 12H, Ar–H), 8.16 (s, 1H, –CH
of thiazole), 8.25 (s, 1H, –CH of coumarin), 9.79 (s, 1H, NH). 13C NMR (100 MHz,
DMSO-d6) δ ppm: 24.74 (C17), 75.74 (C15), 110.00 (C8), 116.63–129.16 (C3–C6, C20–C23,
C25–C29), 122.72 (C14, C16), 132.72 (C9), 134.11 (C11), 152.74 (C10), 153.11 (C18, C19),
154.52 (C1, C2), 158.89 (C12), 165.11 (C13), 160.10 (C7), 160.11 (C24). MS: m/z [540]+.
Anal. calcd. for C29H21N3O4S2 (539.627): C, 64.55; H, 3.92; N, 7.79; found: C, 64.41; H,
3.78; N, 7.67.
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