Synthesis of benzo[b][1,4]thiazepines by the reaction of 3-aryl-1-(3-coumarinyl)propen-1-ones with 2-aminothiophenol [1]

Article abstract of DOI:10.1002/jhet.5570440633

(Chemical Equation Presented) 3-(2-Aryl-2,3-dihydro-benzo[b][1,4]thiazepin- 4-yl)chromen-2-ones (2a, e, f) and (Z)-3-(2,3-dihydro-2-arylbenzo[b][1,4] thiazepin-4(5H)-ylidene)chroman-2-ones (3a-f) have been synthesized by the reaction of 3-aryl-1-(3-coumarinyl)propen-1-ones (1a-f) with 2-aminothiophenol in a hot mixture of toluene and acetic acid. Structures of all new compounds and their complete ¹H and ¹³C assignments were achieved applying different one- and two-dimensional nmr experiments in combination with various spectroscopic techniques.

Full text of DOI:10.1002/jhet.5570440633

Nov-Dec 2007
1453
Synthesis of Benzo[b][1,4]thiazepines by the Reaction of
3-Aryl-1-(3-coumarinyl)propen-1-ones with
2-Aminothiophenol [1]
Albert Lévai, [a]* József Jekꢀ, [b] Tímea Gondos, [c] András Simon [c]
and Gábor Tóth [c]*
[a] Department of Organic Chemistry, University of Debrecen, P.O.Box 20, H-4010 Debrecen, Hungary
[b] Department of Chemistry, College of Nyíregyháza, Sóstói u. 31/b, H-4400, Nyíregyháza, Hungary
[c] Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Szt.
Gellért tér 4, H-1111 Budapest, Hungary
Received March 17, 2007
Dedicated to Professor Dr. Waldemar Adam on the occasion of his 70th birthday
R
R
R
S
S
O
O
N
H
N
O
O
O
O
O
1a - f
2a, e, f
3a - f
3-(2-Aryl-2,3-dihydro-benzo[b][1,4]thiazepin-4-yl)chromen-2-ones (2a, e, f) and (Z)-3-(2,3-dihydro-2-
arylbenzo[b][1,4]thiazepin-4(5H)-ylidene)chroman-2-ones (3a-f) have been synthesized by the reaction of
3-aryl-1-(3-coumarinyl)propen-1-ones (1a-f) with 2-aminothiophenol in a hot mixture of toluene and acetic
acid. Structures of all new compounds and their complete 1H and 13C assignments were achieved applying
different one- and two-dimensional nmr experiments in combination with various spectroscopic
techniques.
J. Heterocyclic Chem., 44, 1453 (2007).
INTRODUCTION
aryl-1-(3-coumarinyl)propen-1-ones and 2-aminothio-
phenol.
Natural, semisynthetic and synthetic coumarins [2,3]
are important coumarin derivatives in drug research. As a
consequence, numerous coumarin type compounds have
been synthesized, some of them served as versatile
intermediates for the synthesis of various heterocyclic
ring systems. 3-Cinnamoyl coumarins [4-10] obtained by
the reaction of 3-acetylcoumarins with aromatic alde-
hydes proved to be especially convenient starting
materials for this purpose. 3-Cinnamoyl coumarins have
been used for the synthesis of e.g. pyridine, pyrazoline
and isoxazoline derivatives [4-10]. 1,5-Benzodiazepines
and 1,5-benzothiazepines possessing a coumarin moiety
have also been synthesized by the reaction of various
coumarinylchalcones with 1,2-phenylenediamine and 2-
aminothiophenol [11-13].
RESULTS AND DISCUSSION
Chemistry. 3-Aryl-1-(3-coumarinyl)propen-1-ones
(1a-f) were allowed to react with a slight excess of 2-
aminothiophenol (1.2 equivalent) in hot toluene in the
presence of acetic acid and a multicomponent crude
reaction mixture was obtained in each case. Thin-layer
chromatographic (TLC) monitoring of the reaction
showed that quite a large amount of the starting
materials 1a-f remained unchanged under these
reaction conditions. The expected 2,3-dihydro-1,5-
benzothiazepine type compounds could be isolated
only in three cases (2a, e, f, Scheme 1) in low yields
(15-24%). Structures of compounds 2a, e, f have been
elucidated by nmr (vide infra), ir and mass spectro-
scopy (cf. Experimental).
If three equivalents of 2-aminothiophenol was reacted
with 3-aryl-1-(3-coumarinyl)propen-1-ones (1a-f) under
the above-mentioned reaction conditions, a complete
conversion of the starting materials 1a-f has taken place
and, again, a multicomponent reaction mixture was
obtained in each case. One major product and a by-
product were isolated from the crude reaction mixtures
Synthesis of 2,3-dihydro-1,5-benzothiazepines (termed
also as benzo[b][1,4]thiazepine derivatives) by the
reaction of ꢀ,ꢁ-unsaturated ketones with 2-aminothio-
phenol is well known in the literature [14-36]. As a
continuation of our studies on the preparation of 2,4-
disubstituted 2,3-dihydro-1,5-benzothiazepines, in this
paper we report on the synthesis of hitherto unknown
benzo[b][1,4]thiazepine derivatives by the reaction of 3-

1454
A. Lévai, J. Jekꢀ, T. Gondos, A. Simon and G. Tóth
Vol 44
Scheme 1
R
3"
2"
4"
5"
6"
1'
1
S
2
1"
R
SH
9
8'
5'
3"
6"
O
O
2'
2"
1"
7'
6'
3
4
4"
5"
8
7
2
NH2
5'
4'
1
5
4a'
8a'
N
6'
7'
3'
3'
2'
toluene
MeCOOH
6
4'
3
O
1'
O
O
8'
1a - f
2a, e, f
SH
toluene
MeCOOH
NH2
a
b
c
d
e
f
R: H 4-Me 2-MeO 3-MeO 4-MeO 4-Cl
R
4"
3"
2"
5"
6"
1
S
2
1"
9
6
S
S
3
4
8
+
5'
4'
5
4a'
8a'
7
NH2 H2N
N
6'
7'
3'
2'
H
1'
O
O
4
8'
3a - f
by silica gel column chromatography. Electron impact
(70 eV) mass spectra of all isolated major products (3a-f)
revealed molecular ions higher by two Daltons than those
of the expected 3-(2-aryl-2,3-dihydro-benzo[b][1,4]thi-
azepin-4-yl)chromen-2-ones (2a-f). Structures of the
isolated major products were primarily elucidated by
various nmr techniques (vide infra) in combination with
ir, mass spectroscopic data and microanalyses (cf.
Experimental). All these investigations unequivocally
prove the formation of (Z)-3-(2,3-dihydro-2-arylbenzo-
[b][1,4]thiazepin-4(5H)-ylidene)chroman-2-ones (3a-f,
Scheme 1). Structures of compounds 3a-f is corroborated
by their mass spectroscopic fragmentation (Scheme 2),
base peak is m/z = 280.
Together with the isolation of compounds 3a-f as major
products we have also isolated bis(2-aminophenyl)
disulfide (4) as by-product from each crude reaction
mixture. On this basis, previously we have suggested a
plausible reaction mechanism for the formation of
compounds 3a-f [1]. Now, we managed to convert the 3-(2-
phenyl-2,3-dihydrobenzo[b][1,4]thiazepin-4-yl)chromen-2-
one (2a) into (Z)-3-(2,3-dihydro-2-phenylbenzo[b][1,4]-
thiazepin-4(5H)-ylidene)chroman-2-one (3a) on treatment
with 2-aminothiophenol in hot toluene in the presence of
acetic acid. In this case bis(2-aminophenyl) disulfide (4)
has also been isolated as by-product. This experimental
result helps us to suggest another possible mechanism for
the formation of compounds 3a-f (cf. Scheme 3).
Scheme 2
+
R
S
+
N
C
S
O
O
N
H
R
m/z = 280
O
O
3a - f

Nov-Dec 2007
Synthesis of Benzo[b][1,4]thiazepines
1455
Scheme 3
H2N
HS
H2N
HS
H2N
Ar
Ar
S
S
S
N
N
H
O
O
O
O
2
Ar
S
S
S
+
N
H
NH2 H2N
4
O
O
3
We suppose that first 3-(2-aryl-2,3-dihydrobenzo[b]-
[1,4]thiazepin-4-yl)chromen-2-ones (2) are formed by the
reaction of 3-aryl-1-(3-coumarinyl)propen-1-ones (1) with
2-aminothiophenol (Scheme 1). Compounds 2 react with
2-aminothiophenol to afford Mannich-adducts (Scheme
3). These intermediates react with another 2-amino-
thiphenol molecule in the presence of proton catalyst to
provide (Z)-3-(2,3-dihydro-2-arylbenzo[b][1,4]thiazepin-
4(5H)-ylidene)chroman-2-ones (3) together with bis(2-
aminophenyl) disulfide (4).
benzothiazepine moiety. A further support for this
arrangement resulted from the 3-Htrans/C-3' (2.94/125.3)
response. The value of J(3-Htrans,2-H) = 12.5 Hz proved
3
the antiperiplanar position of this two hydrogen atoms
which resulted from the preference of the chair
conformation of the seven-membered ring with equatorial
Ph at C-2 position. In addition, the 3-Htrans/C-1"
correlation provided the assignment of the C-1" ipso
carbon atom. Considering the signal intensities, the
identification of the other signals (C-2",6", C-3",5" and C-
4") of the monosubstituted phenyl ring is straightforward.
The structure determination of compounds 3a-f was
achieved as described for compound 2a. The electron
impact mass spectrum of 3a revealed a molecular ion
Nuclear Magnetic Resonance Spectroscopy. The
structures of compounds (2a, e, f and 3a-f) were
1
elucidated by nmr spectroscopy using H, 13C, DEPT-135,
one-dimensional selective TOCSY, one-dimensional
selective NOESY, two-dimensional 1H-13C HSQC, 1H-13C
HMBC, 1H-1H COSY and 1H-1H NOESY techniques,
applying widely accepted strategies [37,38]. The route of
the signal and structure assignments of 2a is discussed as
a representative example. Utilizing the 1H and 1H-1H
COSY spectra we identified five separated spin systems,
one 1,2-disubstituted aromatic ring with S– and N–, one
another 1,2-disubstituted aromatic ring with O– and C–
substituents, one –C6H5 phenyl group. Furthermore, one
=CH and one –CH–CH2– moiety (see DEPT results) have
also been detected. The long-range JC,H HMBC
correlations of the isolated =CH signal at 8.80 (4'-H)
resulted cross-peaks to C-4, C-2', C-8a', C-5' and C-4a'
atoms (ꢀ: 168.4, 159.8, 154.8, 129.6 and 119.0 ppm,
respectively). The 4'-H/ C-5' correlation assigned ꢀC-5' to
129.6 ppm, whereas the HSQC spectrum gave 5'-H ꢀ:
7.71 chemical shift, serving as starting point to the 1H-1H
COSY of 5'-H, 6'-H, 7'-H, 8'-H spin system. The 4'-H/C-4
(8.80/168.4) cross-peak revealed that the 3-coumarinyl
group is attached to C-4 atom of the 2,3-dihydro-1,5-
1
higher by two Daltons than that of compound 2a. The H
and 13C nmr spectra, beside the high similarity, exhibited
some characteristic differences.
In compound 3a there are 24 carbon atoms of 22
different types and 22 signals were assigned in its 13C nmr
spectrum. As a basic difference between the 13C nmr
spectra of substances 2a and 3a is the presence of an
additional CH2 group in the latter instead of a =CH
moiety. In the sp3 CH range of the 1H nmr spectrum of 3a,
two AB type doublets were detected at 3.61 and 3.45 ppm
assigned to the protons attached to the C-4' carbon atom.
In addition, a sharp NH signal appeared at 11.47 ppm. Its
high chemical shift indicates strong hydrogen bonding.
The long-range JC,H HMBC correlations of the NH, SCH
and the isolated –CH2– hydrogen atoms (cf. Figure 1)
provided an unambiguous assignment of the benzo-
thiazepine and coumarin units. The NH/C-3' correlation
proved the C-4 position of the coumarinyl moiety,
whereas the NH/C-3 cross-peak revealed the presence of
the thiazepine ring.

1456
A. Lévai, J. Jekꢀ, T. Gondos, A. Simon and G. Tóth
Vol 44
arrangement the ꢁ-gauche effect of the 2"-OCH3
4.65
substituent results in a characteristic 6 ppm upfield shift
H
1
on ꢂC-2, moreover other small changes in the H and 13C
S
chemical shifts of the spatial neighbouring nuclei (cf.
Experimental).
3.61/3.45
CH2
In conclusion, an unprecedented formation of new type
of 2,3-dihydro-1,5-benzothiazepines with an exocyclic
double bond at position 4 has been achieved in our
present study. Although the yields of compounds 3a-f are
only medium (39-59%), these results seem to be valuable
contribution to the chemistry of the 2,3-dihydro-1,5-
benzothiazepines. 1,5-Benzothiazepines with an exocyclic
double bond has been mentioned as a possible tautomeric
form in the case of such compounds obtained by the
reaction of ꢃ,ꢄ-unsaturated ketones derived from
dehydroacetic acid and 2-aminothiophenol [35].
N
H
O
O
11.47
Figure 1. Characteristic HMBC correlations of the NH, 2-H and 4'-H2
hydrogen atoms in compound 3a.
In the NOESY spectrum a cross-peak (4.65/3.45) was
detected between 2-Hax and one of the doublet signal of
the separated –CH2– group. This steric proximity (ca. 3 Å,
see the double arrows) is possible only in the chair
conformation of the seven-membered thiazepine ring,
where the configuration of the exo ꢀ4,3' double bond is Z.
EXPERIMENTAL
Melting points were measured with a Kofler hot-stage
apparatus and are uncorrected. The nmr spectra were recorded
on BRUKER Avance DRX-500 and Bruker Avance 500 MHz
spectrometers. Chemical shifts were determined on ꢂ-scale. For
structure elucidation and 1H/13C nmr signal assignment one-
dimensional 1H, 13C, APT, DEPT-135, selective 1D-NOESY,
selective 1D-ROESY and two-dimensional gradient selected
1H,1H-COSY, 1H,13C-HSQC, 1H,13C-HSQC, 1H,13C-HMBC,
1H,1H-NOESY and 1H,1H-ROESY spectra were run. Pulse
programs were taken from the Bruker software library. Ir (KBr)
spectra were recorded with Perkin-Elmer 16 PC spectrometer.
Mass spectra were obtained with a VG Trio-2 instrument.
Elemental analyses were obtained with a Carlo-Erbo 1106
apparatus. Thin layer chromatography (TLC) was performed
with Merck silica gel (60 F254) foils with toluene: ethyl acetate
(4:1 v/v) as eluent. Starting materials 1a-f were synthesized by
known procedures [4-10].
General Procedure for the Synthesis of 3-(2-Aryl-2,3-
dihydro-benzo[b][1,4]thiazepin-4-yl)chromen-2-ones 2a, e, f.
A mixture of the appropriate 3-aryl-1-(3-coumarinyl)propen-1-
one (1a, e, f, 5.0 mmoles), 2-aminothiophenol (6.0 mmoles),
toluene (50 ml) and acetic acid (5.0 ml) was heated at reflux for
6 h, and then the solvent was evaporated under reduced pressure.
Compounds 2a, e, f (Scheme 1) were isolated from the residue
by silica gel column chromatography with toluene: ethyl acetate
(4:1 v/v) as eluent and recrystallized from methanol.
3-(2-Phenyl-2,3-dihydro-benzo[b][1,4]thiazepin-4-yl)chro-
men-2-one (2a) [29]. This compound was isolated as white
needles in 22% yield, mp 202-203° (recrystallized from
Figure 2. Stereo structures of compounds 3a and 3c.
1
methanol); H nmr (500 MHz, CDCl3): ꢂ 5.37 (dd, J = 12.5, 4.9
3
The J(3-Htrans,2-H) = 10.9 Hz value is in accordance
Hz, 1H, 2-H), 2.94 (t, J = 12.5 Hz, 1H, 3-Htrans), 3.62 (dd, J =
12.5, 4.9 Hz, 1H, 3-Hcis), 7.36 (d, 1H, 6-H), 7.51 (t, 1H, 7-H),
7.23 (t, 1H, 8-H), 7.69 (d, 1H, 9-H), 8.80 (s, 1H 4'-H), 7.71 (d,
1H, 5'-H), 7.37 (t, 1H, 6'-H), 7.65 (t, 1H, 7'-H), 7.42 (d, 1H, 8'-
H), 7.36 (dm, 2H, 2",6"-H), 7.30 (t, 2H, 3",5"-H), 7.25 (t, 1H,
4"-H); 13C nmr (125 MHz, CDCl3): ꢂ 60.5 (d, C-2), 39.7 (t, C-
3), 168.4 (s, C-4), 150.3 (s, C-5a), 125.5 (d, C-6), 129.8 (d, C-7),
126.3 (d, C-8), 135.3 (d, C-9), 124.3 (s, C-9a), 159.8 (s, C-2'),
125.3 (s, C-3'), 145.3 (d, C-4'), 119.0 (s, C-4a'), 129.6 (d, C-5'),
125.0 (d, C-6'), 133.4 (d, C-7'), 116.6 (d, C-8'), 154.8 (s, C-8a'),
with the antiperiplanar arrangement of these hydrogen
atoms. The results of the semiempirical PM3 calculations
(HyperChem 7.0) also supported this stereo structure
(Figure 2). In the case of the boat conformation of the
thiazepine ring the 2-H/4'-H distance is higher by 4.5 Å.
According to the NOESY results in compound 3c in the
preferred conformation the 2"-OCH3 group is interestingly
coplanar with 2–H bond (cf. Figure 2). Due to this spatial

Nov-Dec 2007
Synthesis of Benzo[b][1,4]thiazepines
1457
144.1 (s, C-1"), 126.2 (2xd, C-2",6"), 128.7 (2xd, C-3",5"),
127.7 (d, C-4"); ir (KBr): cm-1 1724, 1610, 1565, 1453, 1217,
1165, 986, 763, 698; ms: m/z 383 (M+, 5), 350 (5), 279 (100),
251 (28). Anal. Cald. for C24H17NO2S: C, 75.18; H, 4.47; N,
3.65. Found: C, 75.27; H, 4.51; N, 3.59.
11.47 (s, 1H, NH); 13C nmr (125 MHz, CDCl3): ꢀ 53.2 (d, C-2),
35.9 (t, C-3), 159.3 (s, C-4), 141.6 (s, C-5a), 123.5 (d, C-6),
130.1 (d, C-7), 125.9 (d, C-8), 135.3 (d, C-9), 125.7 (s, C-9a),
166.4 (s, C-2'), 84.6 (s, C-3'), 26.8 (t, C-4'), 120.3 (s, C-4a'),
127.9 (d, C-5'), 123.6 (d, C-6'), 127.5 (d, C-7'), 116.1 (d, C-8'),
150.5 (s, C-8a'), 142.8 (s, C-1"), 126.2 (2xd, C-2",6"), 128.6
(2xd, C-3",5"), 127.8 (d, C-4"); ir (KBr): cm-1 3412, 1665, 1582,
1491, 1456, 1332, 1229, 1186, 1164, 1118, 987, 760, 698; ms:
m/z 385 (M+, 22), 352 (7), 280 (100), 236 (27). Anal. Calcd. for
C24H19NO2S: C, 74.79; H, 4.97; N, 3.63. Found: C, 74.92; H,
5.03; N, 3.54.
3-[2-(4-Methoxyphenyl)-2,3-dihydro-benzo[b][1,4]thiaze-
pin-4-yl]chromen-2-one (2e). This substance was obtained as
white plates in 15% yield, mp 140-141° (recrystallized from
methanol); 1H nmr (500 MHz, CDCl3): ꢀ 5.34 (dd, J = 12.5, 4.9
Hz, 1H, 2-H), 2.91 (t, J = 12.5 Hz, 1H, 3-Htrans), 3.57 (dd, J =
12.5, 4.9 Hz, 1H, 3-Hcis), 7.35 (d, 1H, 6-H), 7.50 (t, 1H, 7-H),
7.21 (t, 1H, 8-H), 7.67 (d, 1H, 9-H), 8.75 (s, 1H, 4'-H), 7.70 (d,
1H, 5'-H), 7.36 (t, 1H, 6'-H), 7.64 (t, 1H, 7'-H), 7.41 (d, 1H, 8'-
H), 7.26 (dm, 2H, 2",6"-H), 6.82 (dm, 2H, 3",5"-H), 3.78 (s, 3H,
4"-OCH3); 13C nmr (125 MHz, CDCl3): ꢀ 60.1 (d, C-2), 39.8 (t,
C-3), 168.2 (s, C-4), 150.4 (s, C-5a), 125.4 (d, C-6), 129.7 (d, C-
7), 126.2 (d, C-8), 135.3 (d, C-9), 124.2 (s, C-9a), 159.8 (s, C-
2'), 125.6 (s, C-3'), 145.1 (d, C-4'), 119.0 (s, C-4a'), 129.5 (d, C-
5'), 124.9 (d, C-6'), 133.3 (d, C-7'), 116.6 (d, C-8'), 154.7 (s, C-
8a'), 136.5 (s, C-1"), 127.3 (2xd, C-2",6"), 113.9 (2xd, C-3",5"),
159.0 (s, C-4"), 55.3 (q, 4"-OCH3); ir (KBr): cm-1 1724, 1608,
1558, 1510, 1453, 1256, 1176, 1033, 983, 8.32, 759; ms: m/z
413 (M+, 2), 279 (17), 251 (10), 134 (100). Anal. Calcd. for
C25H19NO3S: C, 72.63; H, 4.63; N 3.39. Found: C, 72.69; H,
4.68; N 3.32.
(Z)-3-[2,3-Dihydro-2-(4-methylphenyl)benzo[b][1,4]thiaze-
pin-4(5H)-ylidene]chroman-2-one (3b). This substance was
prepared as white plates in 51% yield, mp 180-181°
1
(recrystallized from methanol); H nmr (500 MHz, CDCl3): ꢀ
4.74 (dd, J = 10.5, 4.6 Hz, 1H, 2-H), 2.84 (dd, J = 13.7, 10.5 Hz,
1H, 3-Htrans), 3.00 (dd, J = 13.7, 4.6 Hz, 1H, 3-Hcis), 7.22 (d, 1H,
6-H), 7.42 (t, 1H, 7-H), 7.19 (t, 1H, 8-H), 7.59 (d, 1H, 9-H), 3.56
(d, J = 18.3 Hz, 1H, 4'-Ha), 3.71 (d, J = 18.3 Hz, 1H, 4'-Hb),
7.04 (d, 1H, 5'-H), 7.04 (t, 1H, 6'-H), 7.21 (t, 1H, 7'-H), 7.05 (d,
1H, 8'-H), 7.24 (dm, 2H, 2",6"-H), 7.13 (dm, 2H, 3",5"-H), 2.35
(s, 3H, 4"-CH3), 11.62 (s, 1H, NH); 13C nmr (125 MHz, CDCl3):
ꢀ 53.2 (d, C-2), 36.1 (t, C-3), 159.1 (s, C-4), 142.2 (s, C-5a),
123.9 (d, C-6), 130.2 (d, C-7), 125.9 (d, C-8), 135.6 (d, C-9),
126.1 (s, C-9a), 166.3 (s, C-2'), 84.9 (s, C-3'), 27.3 (t, C-4'),
120.7 (s, C-4a'), 128.1 (d, C-5'), 123.7 (d, C-6'), 127.7 (d, C-7'),
116.6 (d, C-8'), 151.0 (s, C-8a'), 140.1 (s, C-1"), 126.4 (2xd, C-
2",6"), 129.5 (2xd, C-3",5"), 137.9 (s, C-4"), 21.1 (q, 4"-CH3); ir
(KBr): cm-1 3408, 1667, 1583, 1559, 1492, 1455, 1333, 1230,
1186, 1166, 1104, 990, 755, 633; ms: m/z 399 (M+, 17), 366 (8),
280 (100), 236 (17). Anal. Calcd. for C25H21NO2S: C, 75.17; H,
5.30; N, 3.50. Found: C, 75.26; H, 5.26; N, 3.57.
3-[2-(4-Chlorophenyl)-2,3-dihydro-benzo[b][1,4]thiazepin-
4-yl]chromen-2-one (2f). This compound was prepared as white
needles in 24% yield, mp 182-183° (recrystallized from
1
methanol); H nmr (500 MHz, CDCl3): ꢀ 5.37(dd, J = 12.5, 4.9
Hz, 1H, 2-H), 2.85 (t, J = 12.5 Hz, 1H, 3-Htrans), 3.57 (dd, J =
12.5, 4.9 Hz, 1H, 3-Hcis), 7.37 (d, 1H, 6-H), 7.51 (t, 1H, 7-H),
7.23 (t, 1H, 8-H), 7.67 (d, 1H, 9-H), 8.82 (s, 1H, 4'-H), 7.72 (d,
1H, 5'-H), 7.37 (t, 1H, 6'-H), 7.65 (t, 1H, 7'-H), 7.41 (d, 1H, 8'-
H), 7.29 (dm, 2H, 2",6"-H), 7.26 (dm, 2H, 3",5"-H); 13C nmr
(125 MHz, CDCl3): ꢀ 59.6 (d, C-2), 39.7 (t, C-3), 168.0 (s, C-4),
150.1 (s, C-5a), 125.5 (d, C-6), 130.0 (d, C-7), 126.4 (d, C-8),
135.3 (d, C-9), 123.9 (s, C-9a), 159.9 (s, C-2'), 125.0 (s, C-3'),
145.4 (d, C-4'), 118.9 (s, C-4a'), 129.7 (d, C-5'), 125.0 (d, C-6'),
133.0 (d, C-7'), 116.6 (d, C-8'), 154.8 (s, C-8a'), 142.6 (s, C-1"),
127.6 (2xd, C-2",6"), 128.8 (2xd, C-3",5"), 133.3 (s, C-4"); ir
(KBr): cm-1 1720, 1607, 1558, 1489, 1453, 1273, 1206, 1090,
983, 761; ms: m/z 417 (M+, 2), 384 (2), 279 (100), 251 (24).
Anal. Calcd. for C24H16ClNO2S: C, 68.98; H, 3.86; N 3.35.
Found: C, 68.89; H, 3.90, N, 3.30.
General Method for the Preparation of (Z)-3-(2,3-
Dihydro-2-arylbenzo[b][1,4]thiazepin-4(5H)ylidene)chroman-
2-ones 3a-f. A mixture of the respective 3-aryl-1-(3-
coumarinyl)propen-1-one (1a-f, 5.0 mmoles), 2-aminothio-
phenol (15.0 mmoles), toluene (50 ml) and acetic acid (5.0 ml)
were treated as described for the synthesis of compounds 2a,e,f
to afford benzothiazepines 3a-f on column chromatography
(Scheme 1).
(Z)-3-[2,3-Dihydro-2-(2-Methoxyphenyl)benzo[b][1,4]thia-
zepin-4(5H)-ylidene]chroman-2-one (3c). This compound was
obtained as white plates in 52% yield, mp 176-177°
1
(recrystallized from methanol); H nmr (500 MHz, CDCl3): ꢀ
5.23 (dd, J = 12.0, 4.6 Hz, 1H, 2-H), 2.67 (dd, J = 13.6, 12.0 Hz,
1H, 3-Htrans), 3.06 (dd, J = 13.6, 4.6 Hz, 1H, 3-Hcis), 7.22 (d, 1H,
6-H), 7.41 (t, 1H, 7-H), 7.20 (t, 1H, 8-H), 7.67 (d, 1H, 9-H), 3.76
(d, J = 18.4 Hz, 1H, 4'-Ha), 3.92 (d, J = 18.4 Hz, 1H, 4'-Hb), 7.12
(d, 1H, 5'-H), 7.08 (t, 1H, 6'-H), 7.23 (t, 1H, 7'-H), 7.07 (d, 1H,
8'-H), 6.93 (d, 1H, 3"-H), 7.28 (t, 1H, 4"-H), 6.94 (t, 1H, 5"-H),
7.50 (d, 1H, 6"-H), 3.95 (s, 3H, 2"-OCH3), 11.58 (s, 1H, NH);
13C nmr (125 MHz, CDCl3): ꢀ 46.7 (d, C-2), 34.9 (t, C-3), 159.9
(s, C-4), 142.3 (s, C-5a), 123.7 (d, C-6), 130.0 (d, C-7), 125.9 (d,
C-8), 135.8 (d, C-9), 126.1 (s, C-9a), 166.3 (s, C-2'), 84.6 (s, C-
3'), 27.0 (t, C-4'), 121.0 (s, C-4a'), 128.0 (d, C-5'), 123.7 (d, C-
6'), 127.7 (d, C-7'), 116.7 (d, C-8'), 151.1 (s, C-8a'), 134.1 (s, C-
1"), 155.4 (d, C-2"), 110.4 (d, C-3"), 128.8 (d, C-4"), 120.9 (d,
C-5"), 127.1 (d, C-6"), 55.5 (q, 2"-OCH3); ir (KBr): cm-1 3442,
1665, 1583, 1558, 1457, 1335, 1238, 1187, 1168, 1105, 986,
752, 692; ms: m/z 415 (M+, 15), 382 (6), 280 (100), 236 (31).
Anal. Calcd. for C25H21NO3S: C, 72.27; H, 5.10; N, 3.37. Found:
C, 72.36; H, 5.04; N, 3.44.
(Z)-3-(2,3-Dihydro-2-phenylbenzo[b][1,4]thiazepin-4(5H)-
ylidene)chroman-2-one (3a). This compound was isolated as
white needles in 46% yield, mp 185-186° (recrystallized from
(Z)-3-[2,3-Dihydro-2-(3-methoxyphenyl)benzo[b][1,4]thia-
zepin-4(5H)-ylidene]chroman-2-one (3d). This material was
obtained as white plates in 39% yield, mp 166-167°
1
methanol); H nmr (500 MHz, CDCl3): ꢀ 4.65 (dd, J = 10.9, 5.0
Hz, 1H, 2-H), 2.74 (dd, J = 13.7, 10.9 Hz, 1H, 3-Htrans), 2.91 (dd,
J = 13.7, 5.0 Hz, 1H, 3-Hcis), 7.12 (d, 1H, 6-H), 7.33 (t, 1H, 7-
H), 7.10 (t, 1H, 8-H), 7.48 (d, 1H, 9-H), 3.45 (d, J = 18.6 Hz,
1H, 4'-Ha), 3.61 (d, J = 18.6 Hz, 1H, 4'-Hb), 6.96 (d, 1H, 5'-H),
6.95 (t, 1H, 6'-H), 7.09 (t, 1H, 7'-H), 6.91 (d, 1H, 8'-H), 7.23
(dm, 2H, 2",6"-H), 7.22 (t, 2H, 3",5"-H), 7.19 (t, 1H, 4"-H),
1
(recrystallized from methanol); H nmr (500 MHz, CDCl3): ꢀ
4.72 (dd, J = 10.7, 5.0 Hz, 1H, 2-H), 2.84 (dd, J = 13.8, 10.7 Hz,
1H, 3-Htrans), 3.02 (dd, J = 13.8, 5.0 Hz, 1H, 3-Hcis), 7.23 (d, 1H,
6-H), 7.43 (t, 1H, 7-H), 7.20 (t, 1H, 8-H), 7.60 (d, 1H, 9-H), 3.59
(d, J = 18.1 Hz, 1H, 4'-Ha), 3.73 (d, J = 18.1 Hz, 1H, 4'-Hb), 7.06

1458
A. Lévai, J. Jekꢀ, T. Gondos, A. Simon and G. Tóth
Vol 44
(d, 1H, 5'-H), 7.07 (t, 1H, 6'-H), 7.22 (t, 1H, 7'-H), 7.05 (d, 1H,
8'-H), 6.92 (s, 1H, 2"-H), 6.84 (d, 1H, 4"-H), 7.26 (t, 1H, 5"-H),
6.91 (d, 1H, 6"-H), 3.75 (s, 3H, 3"-OCH3), 11.61 (s, 1H, NH);
13C nmr (125 MHz, CDCl3): ꢀ 53.4 (d, C-2), 36.1 (t, C-3), 159.0
(s, C-4), 142.2 (s, C-5a), 123.8 (d, C-6), 130.3 (d, C-7), 126.0 (d,
C-8), 135.6 (d, C-9), 126.1 (s, C-9a), 166.3 (s, C-2'), 85.0 (s, C-
3'), 27.3 (t, C-4'), 120.6 (s, C-4a'), 128.1 (d, C-5'), 123.7 (d, C-
6'), 127.8 (d, C-7'), 116.6 (d, C-8'), 151.0 (s, C-8a'), 144.6 (s, C-
1"), 112.4 (d, C-2"), 159.9 (d, C-3"), 113.3 (d, C-4"), 129.9 (d,
C-5"), 118.7 (d, C-6"), 55.2 (q, 3"-OCH3); ir (KBr): cm-1 3426,
1655, 1597, 1560, 1465, 1332, 1268, 1228, 1184, 1117, 985,
759, 698; ms: m/z 415 (M+, 11), 382 (6), 280 (100), 236 (11).
Anal. Calcd. for C25H21NO3S: C, 72.27; H, 5.10; N, 3.37. Found:
C, 72.19; H, 5.15; N 3.31.
REFERENCES
[1] Oxazepines and Thiazepines, 45. For Part 44, see Lévai, A.; Tóth,
G.; Gondos, T.; Jekꢀ J.; Brahmbhatt, D. I. Heterocycles 2006, 68, 1319.
[2] Geisman, T. A.; The Chemistry of Flavonoid Compounds,
Pergamon Press, Oxford, 1962.
[3] Brahmbhatt, D. I.; Raolgi, G. B.; Pandya, U. R.; Pandya, S.
U., Indian J. Chem. 1999, 38B, 212.
[4] Miky, J. A. A.; Farrag, A. A., Indian J. Chem. 1997, 36B, 357.
[5] Essawy, A. I.; Elkady M.; Mohamed, A. Y., Indian J. Chem.
1980, 19B, 567.
[6] van den Goorbergh, J. A. M.; van der Steeg, M.; van der Gen,
A. Synthesis 1984, 859.
[7] Dimitrova, E.; Anghelova, Y. Synth. Commun. 1986, 16,
1195.
(Z)-3-[2,3-Dihydro-2-(4-methoxyphenyl)benzo[b][1,4]thia-
zepin-4-(5H)-ylidene]chroman-2-one (3e). This compound was
isolated as white plates in 59% yield, mp 161-162°
[8] van den Goorbergh, J. A. M.; van der Steeg, M.; van der Gen,
A. Synthesis 1987, 314.
[9] Yagodinets, P. I.; Skripskaya, O. V.; Chernyuk, I. N.;
Shevchuk, M. I. Zh. Obschch. Khim. 1991, 61, 1856.
[10] Mulwad, V. V.; Bhagat, R. D. Indian J. Heterocycl. Chem.,
1990, 9, 13.
[11] Djudjic, R.; Trkovnik, M. Croat. Chem. Acta 1999, 63, 13.
[12] Prashant, A.; Rao, S. S.; Chowdary, K. S.; Krishnan, V. S. H.
Heterocycl. Commun. 2001, 7, 61.
[13] Mulwad, V. V.; Pawar, R. B. Indian J. Chem., 2003, 42B,
2091.
[14] Ried, W.; Marx, W. Chem. Ber. 1957, 90, 2683.
[15] Stephen, W. D.; Field, L. J. Org. Chem. 1959, 24, 1576.
[16] Hideg-Hankovszky, O.; Hideg, K. Acta Chim. Acad. Sci.
Hung. 1971, 68, 403.
[17] Lévai, A.; Bognár, R. Acta Chim. Acad. Sci. Hung. 1976, 88, 293.
[18] Lévai, A.; Bognár, R. Acta Chim. Acad. Sci. Hung. 1977, 92,
415.
[19] Lévai, A. Pharmazie 1979, 34, 439.
[20] Lévai, A.; Bognár, R.; Kajtár, J. Acta Chim. Acad. Sci. Hung.
1980, 103, 27.
1
(recrystallized from methanol); H nmr (500 MHz, CDCl3): ꢀ
4.76 (dd, J = 10.1, 5.0 Hz, 1H, 2-H), 2.82 (dd, J = 13.6, 10.1 Hz,
1H, 3-Htrans), 2.99 (dd, J = 13.6, 5.0 Hz, 1H, 3-Hcis), 7.21 (d, 1H,
6-H), 7.42 (t, 1H, 7-H), 7.19 (t, 1H, 8-H), 7.58 (d, 1H, 9-H), 3.50
(d, J = 18.1 Hz, 1H, 4'-Ha), 3.69 (d, J = 18.1 Hz, 1H, 4'-Hb), 7.03
(d, 1H, 5'-H), 7.04 (t, 1H, 6'-H), 7.21 (t, 1H, 7'-H), 7.04 (d, 1H,
8'-H), 7.27 (dm, 2H, 2",6"-H), 6.83 (dm, 2H, 3",5"-H), 3.78 (s,
3H, 4"-OCH3), 11.62 (s, 1H, NH); 13C nmr (125 MHz, CDCl3): ꢀ
53.0 (d, C-2), 36.2 (t, C-3), 159.0 (s, C-4), 142.1 (s, C-5a), 123.7
(d, C-6), 130.1 (d, C-7), 125.9 (d, C-8), 135.5 (d, C-9), 126.1 (s,
C-9a), 166.3 (s, C-2'), 84.9 (s, C-3'), 27.2 (t, C-4'), 120.7 (s, C-
4a'), 128.0 (d, C-5'), 123.6 (d, C-6'), 127.7 (d, C-7'), 116.5 (d, C-
8'), 151.0 (s, C-8a'), 135.0 (s, C-1"), 127.7 (2xd, C-2",6"), 114.1
(2xd, C-3",5"), 159.3 (s, C-4"), 55.3 (q, 4"-OCH3); ir (KBr): cm-
1
3432, 1669, 1583, 1559, 1511, 1469, 1332, 1231, 1185, 1161,
1033, 981, 756, 640; ms: m/z 415 (M+, 36), 382 (8), 280 (100),
236 (12). Anal. Cald. for C25H21NO3S: C, 72.27; H, 5.10; N,
3.37. Found: C, 72.33; H, 5.16; N, 3.42.
[21] Lévai, A. Pharmazie 1981, 36, 449.
[22] Mane, R. A.; Ingle, D. B. Indian J. Chem. 1982, 21B, 973.
[23] Orlov, V. D.; Kolos N. N.; Ruzhinckaya, N. N. Khim.
Geterotsikl. Soedin. 1983, 1638.
[24] Gupta, A. K.; Singh, V. K.; Pant, U. C. Indian J. Chem.
1983, 22B, 1057.
[25] Jadhav, K. P.; Ingle, D. B. Indian J. Chem. 1983, 22B, 180.
[26] Pant, U. C.; Gaur, B. S.; Chugh, M. Indian J. Chem. 1988,
27B, 752.
(Z)-3-[2,3-Dihydro-2-(4-chlorophenyl)benzo[b][1,4]thiaze-
pin-4-(5H)-ylidene]chroman-2-one (3f). This compound was
obtained as pale yellow needles in 57% yield, mp 170-171°
1
(recrystallized from methanol); H nmr (500 MHz, CDCl3): ꢀ
4.73 (dd, J = 10.6, 5.1 Hz, 1H, 2-H), 2.80 (dd, J = 13.9, 10.6 Hz,
1H, 3-Htrans), 3.00 (dd, J = 13.9, 5.1 Hz, 1H, 3-Hcis), 7.24 (d, 1H,
6-H), 7.44 (t, 1H, 7-H), 7.21 (t, 1H, 8-H), 7.57 (d, 1H, 9-H), 3.56
(d, J = 18.0 Hz, 1H, 4'-Ha), 3.70 (d, J = 18.0 Hz, 1H, 4'-Hb), 7.05
(d, 1H, 5'-H), 7.06 (t, 1H, 6'-H), 7.23 (t, 1H, 7'-H), 7.06 (d, 1H,
8'-H), 7.29 (s, 2H, 2",6"-H), 7.29 (s, 2H, 3",5"-H), 11.60 (s, 1H,
NH); 13C nmr (125 MHz, CDCl3): ꢀ 52.7 (d, C-2), 36.0 (t, C-3),
159.5 (s, C-4), 142.2 (s, C-5a), 123.9 (d, C-6), 130.5 (d, C-7),
126.1 (d, C-8), 135.6 (d, C-9), 125.6 (s, C-9a), 166.4 (s, C-2'),
85.2 (s, C-3'), 27.3 (t, C-4'), 120.6 (s, C-4a'), 128.1 (d, C-5'),
123.9 (d, C-6'), 127.9 (d, C-7'), 116.6 (d, C-8'), 151.0 (s, C-8a'),
141.5 (s, C-1"), 127.9 (2xd, C-2",6"), 129.1 (2xd, C-3",5"),
133.9 (s, C-4"); ir (KBr): cm-1 3423, 1668, 1584, 1491, 1456,
1331, 1265, 1231, 1185, 1164, 1103, 985, 758, 630; ms: m/z 419
(M+, 13), 384 (8), 280 (100), 251 (23). Anal. Calcd. for
C24H18ClNO2S: C, 68.65; H, 4.32; N, 3.33. Found: C, 68.74; H,
4.28; N 3.38.
[27] Lévai, A. Pharmazie 1999, 44, 317.
[28] Lévai, A. Heterocycl. Commun. 1999, 5, 359.
[29] Swellen, R. H.; Allam, Y. A.; Nawwar, G. A. M. Z.
Naturforsch., 1999, 54b, 1197.
[30] Katritzky, A. R.; Rogovoy, B. V.; Chassing, C.; Vvedensky,
V.; Forood, B.; Flatt B.; Nakai, H. J. Heterocycl. Chem. 2000, 37, 1655.
[31] Lévai, A. J. Heterocycl. Chem. 2000, 37, 199.
[32] Nagarapu, L.; Narendar, R.; Sucheta, K.
Commun., 2003, 9, 35.
Heterocycl.
[33] Kodomari, M.; Noguchi T.; Aoyama, T. Synth. Commun.,
2004, 34, 1783.
[34] Lévai, A. J. Heterocycl. Chem., 2004, 41, 399.
[35] Prakash, O.; Kumar, A.; Sadana, A.; Prakash, R.; Singh, A.
P.; Claramunt, R. M.; Sanz, D.; Alkorta, I.; Elguero, J. Tetrahedron,
2005, 61, 6642.
[36] Rao, V.; Reddy, M. Phosphorus, Sulfur and Silicon and
Relat. Elem., 2006, 181, 461.
Acknowledgments. The present study was sponsored by the
Hungarian Scientific Research Fund (Grant Nos. OTKA
T046127 and T049468) for which our gratitude is expressed.
Technical assistance of Mrs. M. Nagy is highly appreciated. A.
S. is grateful for the Varga/Rohr fellowship.
[37] Pretsch, E.; Tóth, G.; Munk, M. E.; Badertscher, M.
Computer-aided Structure Elucidation and Structure Generation, Wiley-
VCH, Weinheim, 2002.
[38] Duddeck, H.; Dietrich, W.; Tóth, G.; Structure Elucidation by
Modern NMR, Springer-Steinkopff, Darmstadt, 1998.