Magnesium perchlorate as a new and highly efficient catalyst for the synthesis of 2,3-dihydro-1,5-benzothiazepines

Article abstract of DOI:10.1055/s-2007-965892

Commercially available magnesium perchlorate has been found to be a highly efficient catalyst for the reaction of 1,3-diarylprop-2-enones with 2-aminothiophenol leading to the synthesis of 2,3-dihydro-1,5-benzothiazepines in high yields and in short times. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-965892

PAPER
541
Magnesium Perchlorate as a New and Highly Efficient Catalyst for the
Synthesis of 2,3-Dihydro-1,5-benzothiazepines
M
g(ClO
)
-Cataly
o
S
ynthesi
p
of 2,3-Dihy
a
dro-1,5-be
n
l
zothiazepine
L
s
. Khatik, Raj Kumar, Asit K. Chakraborti*
4
2
National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, Punjab 160062, India
Fax +91(172)2214692; E-mail: akchakraborti@niper.ac.in
Received 11 September 2006; revised 23 October 2006
Dedicated to Prof. David E. Nichols
fords the uncyclized thia-Michael adduct as the final prod-
uct and the benzothiazepines are formed only in the case
of activated (methoxy or methyl substituted) bis-2-ami-
nophenyldisulfides. Thus, there is necessity to develop a
more effective synthetic procedure.
Abstract: Commercially available magnesium perchlorate has
been found to be a highly efficient catalyst for the reaction of 1,3-
diarylprop-2-enones with 2-aminothiophenol leading to the synthe-
sis of 2,3-dihydro-1,5-benzothiazepines in high yields and in short
times.
Key words: 1,5-benzothiazepines, 2-aminothiophenol, 1,3-diaryl-
prop-2-enones, magnesium perchlorate, catalyst, chemoselective
We thought that the construction of the 1,5-benzothi-
azepine moiety from 1 and 2 may involve two pathways:
(i) conjugate addition of the sulfhydryl group of 2 to the
a,b-unsaturated carbonyl group of 1 leading to the inter-
mediate formation of the thia-Michael adduct I which, on
subsequent intramolecular nucleophilic attack by the NH2
group on the carbonyl carbon followed by dehydration,
forms the 2,3-dihydro-1,5-benzothiazepine 3 (Path a),16 or
(ii) condensation of the amino group of 2 with the carbo-
nyl group of 1 leading to the intermediate formation of the
aza-diene III, which on subsequent intramolecular conju-
gate addition by the sulfhydryl group forms the isomeric
2,5-dihydro-1,5-benzothiazepine 4 (Path b)17 (Scheme 1).
Thus, the use of an effective ‘electrophilic activation’
agent should make synthesis of benzothiazepines feasible
under milder condition and in shorter times as it would ac-
celerate both the thia-Michael addition and the imine for-
mation steps.
The 1,5-benzothiazepine moiety is a privileged class of
pharmacophore, as compounds bearing this structural unit
possess a broad spectrum of biological activities such as
anti-convulsant,1 Ca+2 channel antagonist,2 anti-anginal,3
anti-HIV,4 squalene synthetase inhibitor,5 V2 arginine va-
sopressin receptor antagonist,6 HIV-1 reverse tran-
scriptase inhibitor,7 etc. These have stimulated interest to
develop new methodologies for the synthesis of 1,5-ben-
zothiazepines.
The common strategy for the construction of the 1,5-ben-
zothiazepine moiety is the reaction of 1,3-diarylprop-2-
enones 1 with 2-aminothiophenol 2.8 The various reported
methodologies involve the use of inorganic supports
(2 g/mmol) under heating at 80 °C for 3 hours,9 AcOH
(3 mL/mmol) in DMF under microwave irradiation,10
AcOH or TFA (1 mL/mmol) in EtOH or toluene under re-
flux for 3–6 hours,11 AcOH in DMF or EtOH at 60 °C for
5 hours followed by keeping at room temperature for
overnight,12 EtOH saturated with HCl under reflux for 3
hours,13 piperidine (1 mL/mmol) in toluene under reflux
for 8 hours, and pyridine (15 mL/mmol) under reflux for
3 hours.14 However, these methodologies have one or
more disadvantages such as the use of high boiling solvent
(e.g., DMF) that is difficult to recover, excess amounts of
acid or base, special efforts are required for adsorption of
the reactants on solid support, need to use special appara-
tus, use of corrosive (e.g., HCl gas, TFA) and hazardous
reagents (e.g., pyridine), and long reaction time. The alter-
nate tandem reductive cleavage–condensation protocol
involving the in situ generation of 2 by reduction of the
corresponding disulfide followed by condensation with
115 requires additional reagents such as stoichiometric
amount of triphenylphosphine, and in most of the cases af-
While designing a new catalyst, we thought that the use of
a more effective ‘electrophilic activation’ agent should
accelerate the overall reaction rate and a metal salt derived
from a strong protic acid should be an ideal contender.
The large negative H0 value of –14.1 of TfOH18 makes
TfOH the strongest protic acid and thus metal triflates
drew attention as catalysts.19 However, TfOH is liberated
from metal triflates and may be the actual catalytic
agent.20 The in situ generation of TfOH might be the rea-
son for the potential side reactions (e.g., dehydration, re-
arrangement) with acid-sensitive substrates or
deactivation of the amine substrates due to salt formation.
Thus, metal triflate catalyzed acylation reactions are often
carried out at low temperatures (–8 to –60 °C) and in the
presence of an excess of the acetylating agents,21 and the
metal triflate catalyzed a-aminophosphonate synthesis re-
quires stoichiometric amounts of additional reagents such
as molecular sieves and MgSO4.22 This shifts the attention
to HNTf2 as it is a weaker Brønsted acid than TfOH23 and
ligand exchange does not take place with triflimides.24
However, metal triflimides are costly, many of them are
not available commercially and require additional efforts
and costly reagents for their preparation.25 Hence we fo-
SYNTHESIS 2007, No. 4, pp 0541–0546
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Advanced online publication: 18.01.2007
DOI: 10.1055/s-2007-965892; Art ID: Z18706SS
© Georg Thieme Verlag Stuttgart · New York

542
G. L. Khatik et al.
PAPER
Table 1 Mg(ClO4)2-Catalyzed Reaction of 1a with 2 for the Synthe-
sis of 3a under Various Conditionsa
O
H2N
HS
Yield (%)b,c
30d,e
60e
+
Entry
Solvent
neat
R1
R2
1
2
3
4
5
6
1
2
Path b
Path a
toluene
(CH2Cl)2
CH2Cl2
MeOH
(CH2)4O
89f,g
H2N
S
65e
N
SH
40h
O
62e
a 1a (1 mmol) was treated with 2 (1.1 equiv) in the presence of
Mg(ClO4)2 (5 mol%) in various solvents (5 mL except for entry 1) un-
der reflux.
R2
R1
R1
I
R2
III
b Isolated yield of 3a.
c The product was characterized by IR, NMR and MS data.
d The reaction was carried out at 80 °C.
e The unreacted 1a and 2 remained unchanged (TLC).
f No significant amounts of the thia-Michael adduct or the benzothi-
azepine were formed in carrying out the reaction at r.t. for 4 h and the
starting materials remained unchanged (TLC).
N–
S+H
HN
S
OH
g The starting material remained unchanged with ~5% conversion to
the thia-Michael adduct (TLC) when the reaction was carried out in
the absence of any catalyst.
R2
R1
R2
R1
IV
II
h The thia-Michael adduct was isolated in 45% yield.
The generality of this methodology was established by the
reaction of various 1,3-diarylprop-2-enones with 2 in the
presence of Mg(ClO4)2 (Table 2). The desired 1,5-ben-
zothiazepines 3 were obtained in 80–90% yields after 0.5–
2 hours. The reaction was compatible with various elec-
tron-donating and electron-withdrawing substituents such
as Me, OMe, OCH2Ph, OH, Br, Cl, F, NHSO2Me, OCOPh
and NO2 and heteroaryl rings. Excellent chemoselectivity
was observed. Substrates with halogen atoms27 (entries 2–
6, Table 2) and the NO2 group28 (entries 7–9, Table 2) did
not experience any aromatic nucleophilic substitution.
The NO229 and the a,b-unsaturated carbonyl30 groups did
not experience any competitive reduction although thiols
possess single electron transfer property.31 For substrates
having aryl alkyl ether (entries 10–14 and 17, Table 2)
and O-benzoyl (entry 18, Table 2) groups, no O-
dealkylation32/debenzoylation32c,d,33 took place. No com-
petitive O-dimethylamino was observed for substrate with
NHSO2Me group (entry 16, Table 2) although thiolates
are known to be effective reagents for O-demethylation of
methylcarboxylates.32c,d,34
N
S
HN
S
R2
R2
R1
R1
3
4
Scheme 1 Synthetic strategy for the construction of the 1,5-benzo-
thiazepine moiety.
cused our attention to catalysts derived from HClO4 as it
is weaker than TfOH, metal perchlorates do not undergo
ligand exchange reaction and have been reported as effi-
cient ‘electrophilic activation’ catalysts.26 Herein we de-
scribe the use of commercially available Mg(ClO4)2 as a
highly efficient catalyst for synthesis of 1,5-benzothiaz-
epines from 1,3-diarylprop-2-enones and 2-ami-
nothiophenol.
To find the best reaction condition, 1,3-diphenylprop-2-
enone (1a) was treated with 2 in the presence of
Mg(ClO4)2 under various conditions (Table 1). The best
result was obtained by carrying out the reaction under re-
flux in 1,2-dichloroethane (DCE) for 45 minutes affording
the desired 1,5-benzothiazepine (3a) in 89% yield. Inferi-
or results were obtained by carrying out the reaction either
under neat condition at 80 °C or in toluene, CH2Cl2,
MeOH and THF under reflux. It is interesting to note that
although the use of MeOH as solvent facilitates the conju-
gate addition of thiols to 1,3-diphenylprop-2-enone,26a,b
the desired benzothiazepine 3a was obtained only in 40%
yield (entry 5, Table 1).
The following representative examples demonstrate the
superiority of the present method over the recently report-
ed procedure for synthesis of 1,5-benzothiazepines. The
reaction of 3-phenyl-1-(4-methoxyphenyl)prop-2-enone
on SiO2 (2 g/mmol) with 1.5 equivalents of 2 at 80 °C for
3 hours afforded 44% yield following the reported
procedure9 as compared to a 89% yield obtained after 1
hour under the present study (entry 10, Table 2). A 68%
yield was obtained during the reaction of 3-(4-nitrophe-
nyl)-1-phenylprop-2-enone adsorbed on SiO2 (2 g/mmol)
with 1.5 equivalents of 2 at 80 °C for 3 hours following
Synthesis 2007, No. 4, 541–546 © Thieme Stuttgart · New York

PAPER
Mg(ClO4)2-Catalyzed Synthesis of 2,3-Dihydro-1,5-benzothiazepines
543
the reported procedure9 in comparison to an 87% yield ob- Ba(ClO4)2. The use of Mg(ClO4)2·6H2O afforded 50%
tained after 45 minutes (entry 8, Table 2) for the yield. We were surprised to observe that Zn(ClO4)2·6H2O
Mg(ClO4)2-catalyzed reaction.
was inferior to Mg(ClO4)2 although the former is a better
‘electrophilic activation’ agent for thia-Michael addition
reaction.26b To clarify this aspect, we planned to compare
the catalytic efficiency of Zn(ClO4)2·6H2O and
Mg(ClO4)2 under various conditions. The treatment of 1a
with 2 in DCE at room temperature for 45 minutes afford-
ed the thia-Michael adduct in 40% and 85% yields in the
presence of Zn(ClO4)2·6H2O and Mg(ClO4)2, respective-
ly. This demonstrated that the benzothiazepine formation
(Tables 1 and 2) proceeded via the intermediate formation
of the thia-Michael adducts. However, when the reaction
of 1a with 2 was carried out in MeOH at room temperature
for 45 minutes the thia-Michael adduct was formed in
80% and 45% yields in the presence of Zn(ClO4)2·6H2O
and Mg(ClO4)2, respectively. The treatment of 1a with 2
in MeOH under reflux for 45 min in the presence of
Zn(ClO4)2·6H2O resulted in the formation of the thia-
Michael adduct and the benzothiazepine in 55% and 45%
yields, respectively. This highlighted the role of the cata-
lyst in imine formation from the thia-Michael adduct I.
The use of MeOH, a hydroxylic solvent, perhaps does not
permit the dehydration to take place from the intermediate
aminal II (Scheme1). These led to interesting conclu-
sions: (i) benzothiazepine formation takes place via the in-
termediate formation of the thia-Michael adduct, (ii)
catalytic assistance is required in the final cyclodehydra-
tion step leading to intra-molecular imine formation, (iii)
the efficiency of a catalyst for thia-Michael addition and
imine formation is dependent on the nature of the solvent,
and (iv) Mg(ClO4)2 is a unique ‘electrophilic activation’
agent that has the dual catalytic property for thia-Michael
addition and imine formation.
We next compared the catalytic efficiency of Mg(ClO4)2
with other metal perchlorates (Table 3) for the reaction of
1a with 2 and found that Mg(ClO4)2 was superior to
Mn(ClO4)2,
BiOClO4·xH2O,
Zn(ClO4)2·6H2O,
ZrO(ClO4)2·8H2O, Cu(ClO4)2·6H2O, LiClO4 and
Table 2 Mg(ClO4)2-Catalyzed Synthesis of 1,5-Benzothiazepinesa
Entry 1,3-Diarylprop-2-enones
Time (min) Yield (%)b,c
O
R1
R2
1
2
R1 = R2 = H
45
30
30
40
40
40
45
45
45
60
60
120
60
60
60
60
60
60
89
88
80
88
90
82
89
87
90
89
85
81
85
88
87
85
84
83
R1 = 4-Cl, R2 = H
R1 = H, R2 = 4-Cl
R1 = 4-F, R2 = H
3
4
5
R1 = H, R2 = 4-F
6
R1 = 4-Br, R2 = H
R1 = 4-NO2, R2 = H
R1 = H, R2 = 4-NO2
R1 = H, R2 = 3-NO2
R1 = 4-OMe, R2 = H
R1 = H, R2 = 4-OMe
R1 = R2 = 4-OMe
7
8
9
10
11
12
13
14
15
16
17
18
Table 3 Reaction of 1a with 2 for the Synthesis of 3a in the Pres-
R1 = 4-Me, R2 = 4-OMe
R1 = 4-Cl, R2 = 4-OMe
R1 = 4-OH, R2 = H
ence of Various Metal Perchloratesa
Entry
Catalyst
Yield (%)b,c
1
2
3
4
5
6
7
8
9
Mg(ClO4)2
89
50
60
50
50
30
10
40
40
R1 = 4-NHSO2Me, R2 = H
R1 = 4-OCH2Ph, R2 = H
R1 = 4-OCOPh, R2 = H
O
Mg(ClO4)2·6H2O
Mn(ClO4)2
BiOClO4·xH2O
Zn(ClO4)·6H2O
LiClO4
X
Ba(ClO4)2
19
20
X = S
X = O
60
60
87
85
ZrO(ClO4)2·8H2O
Cu(ClO4)2·6H2O
a The 1,3-diphenylprop-2-enone (1 mmol) was treated with 2 (1.1
equiv) in the presence of Mg(ClO4)2 (5 mol%) in DCE (5 mL) under
reflux.
a Compound 1a (1 mmol) was treated with 2 (1.1 equiv) in the pres-
ence of the catalyst (5 mol%) in DCE (5 mL) under reflux (~85 °C)
for 45 min.
b Yield of the corresponding 1,5-benzothiazepines obtained after pu-
rification.
b Isolated yield of 3a.
c The products were characterized by IR, MS and NMR spectroscopy.
c The product was characterized by IR and NMR spectroscopy.
Synthesis 2007, No. 4, 541–546 © Thieme Stuttgart · New York

544
G. L. Khatik et al.
PAPER
2-(4-Methoxyphenyl)-4-(4-methoxyphenyl)-2,3-dihydro-1,5-
benzothiazepine (Entry 12, Table 2)
Yellow solid; mp 107–108 °C.
In conclusion, we have described herein Mg(ClO4)2 as a
novel and highly efficient catalyst for 1,5-benzothiaz-
epine formation by the reaction of 1,3-diarylprop-2-
enones with 2-aminothiophenol. The advantages include,
(i) the use of a cheap, easy to handle and commercially
available catalyst, (ii) short reaction times, and (iii) high
yields.
IR (KBr): 1603, 2922 cm–1.
1H NMR (CDCl3, 300 MHz): d = 3.01 (t, J = 12.8 Hz, 1 H), 3.24
(dd, J = 4.5, 13.0 Hz, 1 H), 3.79 (s, 3 H), 4.01 (s, 3 H), 4.94 (dd,
J = 4.3, 12.1 Hz, 1 H), 6.82 (d, J = 8.3 Hz, 2 H), 6.95 (d, J = 8.4 Hz,
2 H), 7.11 (t, J = 7.5 Hz, 1 H), 7.20–7.29 (m, 3 H), 7.44 (t, J = 7.5
Hz, 1 H), 7.58 (d, J = 8.4 Hz, 1 H), 8.01 (d, J = 7.6 Hz, 2 H).
13C NMR (CDCl3, 75 MHz): d = 23.3, 30.3, 32.5, 38.1, 60.5, 114.6,
123.4, 125.5, 125.8, 127.7, 129.7, 130.2, 130.9, 135.6, 137.2, 153.2,
159.6, 162.6, 168.7.
1,5-Benzothiazepines; 2,4-Diphenyl-2,3-dihydro-1,5-benzothi-
azepine (3a); Typical Procedure (Entry 1, Table 2)
To a mixture of 1,3-diphenylprop-2-enone (1a; 0.209 g, 1 mmol), 2-
aminothiophenol (2; 0.137 g, 1.1 mmol, 1.1 equiv) in anhyd DCE (5
mL) in a round-bottomed flask (10 mL) was added anhyd
Mg(ClO4)2 (0.011 g, 0.05 mmol, 5 mol%) and the mixture was re-
fluxed for 45 min under N2. The mixture was cooled to r.t., evapo-
rated under vacuum on a rotary evaporator and was purified by
passing through a column of silica gel, eluting with 2% EtOAc in
hexane to afford 3a (0.28 g, 89%) as yellow solid; mp 114–116 °C.
MS (APCI): m/z = 375.8 (MH)+.
Anal. Calcd for C23H21NO2S: C, 73.57; H, 5.64; N, 3.73; S, 8.54.
Found: C, 73.59; H, 5.66; N, 3.75; S, 8.55.
2-(4-Methoxyphenyl)-4-(4-methylphenyl)-2,3-dihydro-1,5-ben-
zothiazepine (Entry 13, Table 2)
Yellow solid; mp 108–110 °C.
1H NMR (300 MHz, CDCl3): d = 3.07 (t, J = 12.6 Hz, 1 H), 3.32
(dd, J = 4.7, 13.1 Hz, 1 H), 4.99 (dd, J = 4.5, 12.0 Hz, 1 H), 7.12–
7.17 (m, 1 H), 7.25–7.30 (m, 5 H), 7.44–7.51 (m, 4 H), 7.62 (d,
J = 6.1 Hz, 2 H), 8.06 (d, J = 7.5 Hz, 1 H).
The 1 H NMR spectrum of 3a was identical with an authentic sam-
ple.9 The remaining reactions were carried out following this typical
procedure. The spectral data (IR, 1H and 13C NMR and MS) of all
known compounds were in full agreement with those of authentic
compounds. The physical data of new compounds are provided be-
low.
IR (KBr): 1599, 2928 cm–1.
1H NMR (CDCl3, 300 MHz): d = 2.42 (s, 3 H), 3.01 (t, J = 12.9 Hz,
1 H), 3.25 (dd, J = 4.9, 12.6 Hz, 1 H), 3.77 (s, 3 H), 4.94 (dd,
J = 4.9, 12.8 Hz, 1 H), 6.82 (d, J = 8.4 Hz, 2 H), 7.11 (t, J = 7.4 Hz,
1 H), 7.16–7.34 (m, 5 H), 7.44 (t, J = 7.3 Hz, 1 H), 7.58 (d, J = 7.7
Hz, 1 H), 7.93 (d, J = 8.4 Hz, 2 H).
13C NMR (CDCl3, 75 MHz): d = 21.4, 37.6, 55.3, 60.03, 114.0,
122.9, 125.0, 125.2, 127.1, 127.4, 129.4, 129.6, 135.0, 136.6, 141.5,
152.5, 159.1, 168.7.
MS (APCI): m/z = 360.1 (MH)+.
2-(4-Fluorophenyl)-4-phenyl-2,3-dihydro-1,5-benzothiazepine
(Entry 5, Table 2)
Yellow solid; mp 101–103 °C.
Anal. Calcd for C23H21NOS: C, 76.84; H, 5.89; N, 3.90; S, 8.92.
Found: C, 76.86; H, 5.91; N, 3.93; S, 8.95.
IR (KBr): 1597, 2947 cm–1.
4-(4-Chlorophenyl)-2-(4-methoxyphenyl)-2,3-dihydro-1,5-ben-
zothiazepine (Entry 14, Table 2)
Yellow solid; mp 133–135 °C.
IR (KBr): 1599, 2928 cm–1.
1H NMR (CDCl3, 300 MHz): d = 3.02 (t, J = 12.5 Hz, 1 H), 3.21
(dd, J = 5.1, 12.9 Hz, 1 H), 3.75 (s, 3 H), 4.95 (dd, J = 4.5, 11.9 Hz,
1 H), 6.82 (d, J = 8.0 Hz, 2 H), 7.11–7.30 (m, 4 H), 7.38–7.48 (m,
3 H), 7.79 (d, J = 7.6 Hz, 1 H), 7.97 (d, J = 8.5 Hz, 2 H).
1H NMR (CDCl3, 300 MHz): d = 3.01 (t, J = 12.1 Hz, 1 H), 3.28
(dd, J = 4.7, 12.7 Hz, 1 H), 4.97 (dd, J = 4.9, 12.4 Hz, 1 H), 6.98 (t,
J = 8.6 Hz, 2 H), 7.09–7.16 (m, 1 H), 7.25–7.32 (m, 3 H), 7.44–7.61
(m, 5 H), 8.04 (d, J = 6.0 Hz, 2 H).
13C NMR (CDCl3, 75 MHz): d = 38.3, 60.3, 115.9, 116.3, 125.9,
126.0, 128.0, 128.2, 129.3, 130.4, 131.4, 131.7, 135.6, 138.2, 140.6,
164.3, 169.3.
MS (EI): m/z = 332 (M)+.
13C NMR (CDCl3, 75 MHz): d = 38.2, 55.9, 60.7, 114.6, 123.5,
125.8, 125.9, 127.7, 129.3, 129.5, 130.3, 135.6, 136.8, 137.8, 152.7,
159.8, 168.2.
Anal. Calcd for C21H16FNS: C, 75.65; H, 4.84; N, 4.20; S, 9.62.
Found: C, 75.66; H, 4.85; N, 4.22; S, 9.63.
MS (APCI): m/z = 379.9 (MH)+.
4-(4-Nitrophenyl)-2-phenyl-2,3-dihydro-1,5-benzothiazepine
(Entry 7, Table 2)
Yellow solid; mp 116–118 °C.
Anal. Calcd for C22H18ClNOS: C, 69.55; H, 4.78; N, 3.69; S, 8.44.
Found: C, 69.57; H, 4.79; N, 3.72; S, 8.46.
IR (KBr): 1597, 2925 cm–1.
4-(4-Methanesulfonylaminophenyl)-2-phenyl-2,3-dihydro-1,5-
benzothiazepine (Entry 16, Table 2)
Yellow solid; mp 187–189 °C.
IR (KBr): 1603, 2924 cm–1.
1H NMR (CDCl3, 300 MHz): d = 3.01–3.09 (m, 3 H + 1 H), 3.27
(dd, J = 5.1, 12.9 Hz, 1 H), 4.96 (dd, J = 4.3, 11.9 Hz, 1 H), 7.13–
7.35 (m, 9 H), 7.47 (t, J = 7.3 Hz, 1 H), 7.62 (d, J = 7.4 Hz, 1 H),
8.01 (d, J = 8.4 Hz, 2 H).
1H NMR (CDCl3, 300 MHz): d = 3.12 (t, J = 12.6 Hz, 1 H), 3.29
(dd, J = 5.3, 13.2 Hz, 1 H), 5.03 (dd, J = 5.2, 12.0 Hz, 1 H), 7.17–
7.22 (m, 1 H), 7.25–7.35 (m, 6 H), 7.51 (t, J = 7.7 Hz, 1 H), 7.64 (d,
J = 7.6 Hz, 1 H), 8.19 (d, J = 8.7 Hz, 2 H), 8.32 (d, J = 8.7 Hz, 2 H).
13C NMR (CDCl3, 75 MHz): d = 37.8, 60.8, 122.9, 123.8, 125.6,
126.1, 128.1, 128.3, 128.9, 129.9, 135.2, 143.3, 143.4, 149.2, 151.8,
166.9.
MS (APCI): m/z = 361 (MH)+.
13C NMR (CDCl3, 75 MHz): d = 38.1, 39.9, 60.9, 119.7, 123.4,
125.8, 125.9, 126.5, 128.4, 129.3, 129.5, 130.4, 135.6, 144.4, 169.3.
Anal. Calcd for C21H16N2O2S: C, 69.98; H, 4.47; N, 7.77; S, 8.90.
Found: C, 69.99; H, 4.48; N, 7.79; S, 8.93.
MS (APCI): m/z = 409 (MH)+.
Anal. Calcd for C22H20N2O2S2: C, 64.68; H, 4.93; N, 6.86; S, 15.70.
Found: C, 64.69; H, 4.94; N, 6.88; S, 15.72.
Synthesis 2007, No. 4, 541–546 © Thieme Stuttgart · New York

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Mg(ClO4)2-Catalyzed Synthesis of 2,3-Dihydro-1,5-benzothiazepines
545
4-(4-Benzyloxyphenyl)-2-phenyl-2,3-dihydro-1,5-benzothiaz-
epine (Entry 17, Table 2)
Anal. Calcd for C19H15NOS: C, 74.72; H, 4.95; N, 4.59; S, 10.50.
Found:. C, 74.74; H, 4.96; N, 4.61; S, 10.53.
Yellow solid; mp 115–117 °C.
IR (KBr): 1601, 2897 cm–1.
Acknowledgment
1H NMR (CDCl3, 300 MHz): d = 3.01 (t, J = 12.9 Hz, 1 H), 3.23
(dd, J = 5.0, 12.9 Hz, 1 H), 4.92 (dd, J = 4.4, 12.0 Hz, 1 H), 5.11 (s,
2 H), 7.02–7.11 (m, 3 H), 7.22–7.44 (m, 11 H), 7.58 (d, J = 7.5 Hz,
2 H), 7.85–7.93 (m, 1 H), 7.99 (d, J = 8.6 Hz, 2 H).
The authors thank the Department of Science of Technology, New
Delhi, India for financial support (Grant No. 93143).
13C NMR (CDCl3, 75 MHz): d = 37.9, 61.0, 70.7, 115.6, 123.5,
125.6, 125.9, 126.7, 128.1, 128.4, 128.7, 129.3, 129.4, 129.8, 130.3,
131.1, 135.6, 137.1, 144.8, 153.3, 161.8, 168.7.
References
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1997, 53, 2421.
MS (APCI): m/z = 421.9 (MH)+.
Anal. Calcd for C28H23NOS: C, 79.78; H, 5.50; N, 3.32; S, 7.61.
Found: C, 79.79; H, 5.52; N, 3.34; S, 7.63.
4-(4-Benzoyloxyphenyl)-2-phenyl-2,3-dihydro-1,5-benzothiaz-
epine (Entry 18, Table 2)
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(5) Yang, X.; Buzon, L.; Hamanaka, E.; Liu, K. K.-C.
Yellow solid; mp 187–190 °C.
IR (KBr): 1612, 1743, 2921 cm–1.
1H NMR (CDCl3, 300 MHz): d = 3.06 (t, J = 6.5 Hz, 1 H), 3.31 (dd,
J = 4.6, 12.7 Hz, 1 H), 5.01 (dd, J = 4.4, 12.1 Hz, 1 H), 7.10–7.18
(m, 1 H), 7.25–7.37 (m, 8 H), 7.45–7.56 (m, 3 H), 7.61–7.69 (m, 2
H), 8.13 (d, J = 8.3 Hz, 2 H), 8.23 (d, J = 7.7 Hz, 2 H).
13C NMR (CDCl3, 75 MHz): d = 37.0, 59.9, 121.5, 122.3, 124.8,
125.5, 127.3, 128.1, 128.3, 128.7, 129.2, 129.7, 133.3, 134.5, 134.8,
143.5, 151.8, 152.7, 167.4.
Tetrahedron: Asymmetry 2000, 11, 4447.
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Look, R.; Ericson, E.; Murray, W. V.; Rybczynski, P. J.;
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2004, 34, 1783.
MS (EI): m/z = 435 (M)+.
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Anal. Calcd for C28H21NO2S: C, 77.21; H, 4.86; N, 3.22; S, 7.36.
Found: C, 77.23; H, 4.87; N, 3.23; S, 7.38.
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2-Phenyl-4-(2-thienyl)-2,3-dihydro-1,5-benzothiazepine (Entry
19, Table 2)
Yellow solid; mp 123–125 °C.
IR (KBr): 1592, 2929 cm–1.
1H NMR (CDCl3, 300 MHz): d = 3.06 (t, J = 12.6 Hz, 1 H), 3.23
(dd, J = 4.7, 12.8 Hz, 1 H), 5.03 (dd, J = 4.7, 12.0 Hz, 1 H), 7.08–
7.14 (m, 2 H), 7.26–7.31 (m, 6 H), 7.41–7.46 (m, 2 H), 7.52 (d,
J = 4.9 Hz, 1 H), 7.60 (d, J = 7.6 Hz, 1 H).
13C NMR (CDCl3, 75 MHz): d = 37.5, 59.3, 122.3, 124.3, 124.6,
125.1, 126.8, 127.8, 128.7, 130.2, 133.9, 142.9, 143.9, 150.8, 162.7.
MS (MALDI-TOF/TOF): m/z = 322.506 (MH)+.
Anal. Calcd for C19H15NS2: C, 70.99; H, 4.70; N, 4.36; S, 19.95.
Found: C, 71.01; H, 4.72; N, 4.37; S, 19.97.
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4-(2-Furyl)-2-phenyl-2,3-dihydro-1,5-benzothiazepine (Entry
20, Table 2)
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Yellow solid; mp115–117 °C.
IR (KBr): 1609, 3051 cm–1.
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6.55 (m, 1 H), 7.02 (d, J = 3.1 Hz, 1 H), 7.11 (t, J = 7.1 Hz, 1 H),
7.21–7.23 (m, 6 H), 7.43 (t, J = 7.3 Hz, 1 H), 7.60 (d J = 6.9 Hz, 2
H).
13C NMR (CDCl3, 75 MHz): d = 38.2, 61.2, 112.9, 114.5, 123.9,
125.9, 126.4, 126.7, 128.2, 128.4, 128.9, 129.3, 130.4, 135.7, 144.5,
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