Investigation of the reaction of chloroacetyl chloride with 1,5-benzothiazepines: Selective synthesis of azeto[2,1-d][1,5]benzothiazepines by green chemical methods and their biological activity

Article abstract of DOI:10.1080/10426500802062236

An efficient and exclusive synthesis of the tricyclic azeto[2,1-d][1,5] benzothiazepine ring system has been developed. By use of microwave irradiation in the presence of basic alumina, the reaction time has been brought down from hours to minutes with im

Full text of DOI:10.1080/10426500802062236

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Phosphorus, Sulfur, and Silicon
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Investigation of the Reaction of
Chloroacetyl Chloride with 1,5-
Benzothiazepines: Selective
Synthesis of Azeto[2,1-d]
[1,5]benzothiazepines by
Green Chemical Methods and
Their Biological Activity
Anshu Dandia a , Ruby Singh a , Rekha Sharma a &
Dharmendra Singh a
a Department of Chemistry , University of
Rajasthan , Jaipur, India
Published online: 03 Nov 2008.
To cite this article: Anshu Dandia , Ruby Singh , Rekha Sharma & Dharmendra
Singh (2008) Investigation of the Reaction of Chloroacetyl Chloride with 1,5-
Benzothiazepines: Selective Synthesis of Azeto[2,1-d][1,5]benzothiazepines by Green
Chemical Methods and Their Biological Activity, Phosphorus, Sulfur, and Silicon and
the Related Elements, 183:12, 3116-3126, DOI: 10.1080/10426500802062236
To link to this article: http://dx.doi.org/10.1080/10426500802062236
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Phosphorus, Sulfur, and Silicon, 183:3116–3126, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802062236
Investigation of the Reaction of Chloroacetyl Chloride
with 1,5-Benzothiazepines: Selective Synthesis of
Azeto[2,1-d][1,5]benzothiazepines by Green Chemical
Methods and Their Biological Activity
Anshu Dandia, Ruby Singh, Rekha Sharma,
and Dharmendra Singh
Department of Chemistry, University of Rajasthan, Jaipur, India
An efficient and exclusive synthesis of the tricyclic azeto[2,1-d][1,5]benzothiazepine
ring system has been developed. By use of microwave irradiation in the presence of
basic alumina, the reaction time has been brought down from hours to minutes with
improved yields in comparison to conventional heating. Antimicrobial screening of
the synthesized compounds has shown promising activity.
Keywords 1,5-Benzothiazepines; β-lactams; microwaves; antifungal activity
INTRODUCTION
1,5-Benzothiazepines are well-known seven-membered heterocyclic
compounds and owing to their diverse bioactivities1 they are impor-
tant substances in the drug research. Thiazesim,2 a well known an-
tidepressant, and Diltiazem,3 used as coronary vasodilator and for
the treatment of angina pectoris, possess 1,5-benzothiazepine skele-
tons. The synthesis of compounds containing a β-lactam moiety has
been the subject of intense studies by a number of research groups.4
Though there are some effective antimicrobial agents now, it seems
necessary to synthesize some novel compounds with a fused β-lactam
Received 15 November 2007; accepted 4 March 2008.
Financial assistance from CSIR and UGC New Delhi is gratefully acknowledged. One
of us (R. S.) is thankful to CSIR for the award of a Research Associateship. We are also
thankful to Department of Pathology, Agricultural Research Station, Durgapura, and
Jaipur, for antifungal screening and RSIC, CDRI, Lucknow, and NIPER Chandighar for
the elemental and spectral analyses.
Address correspondence to Anshu Dandia, Department of Chemistry, University of
Rajasthan, Jaipur 302004, India. E-mail: dranshudandia@yahoo.com
3116

Reaction of Chloroacetyl Chloride with 1,5-Benzothiazepines
3117
heterocyclic ring for the bioassay of antibacterial activity because of the
growing resistance of bacteria against penicillin and cephalosporin like
compounds.5
Since most of the important antibiotics possess the representative
structure of a β-lactam fused to thiazaheterocycles,6 we thought it
would be interesting to construct a system that may combine these
two bioactive rings in a single molecular framework to see the addi-
tive effect towards their biological activity. This fact prompted us to
build up structurally diverse fused azeto[2,1-b] benzothiazepines from
1,5-benzothiazepines exhibiting an azomethine functionality. How-
ever, scanty reports on the conventional synthesis7 of this fused
ring system mention the long reaction times, if basic catalyst and
volatile organic solvents are used, and the formation of product
mixture.
Thus, a simple, general and efficient procedure for the exclusive
synthesis of this important tricyclic ring system is required that is
more eco-friendly than the traditional one, in view of the increas-
ing concern about the impact of chemicals on the environment. The
use of microwave irradiation in synthetic chemistry offers a promis-
ing alternative.8 Microwave heating is more efficient in terms of
the energy used and enhances the reactivity and selectivity in some
cases.9
In continuation of our interest on the facile, economical and eco-
friendly synthesis of biodynamic heterocycles under microwaves,10 we
carried out the cycloaddition reaction of 1 with 2 and 4 under microwave
irradiation over the basic alumina as inorganic solid support. In this
case, the reaction occurred in 5−6 min, and only the desired product
5 was formed exclusively with excellent yield in the absence of any
solvent and external base,since the basicity of alumina is sufficient to
cause this cycloaddition reaction. Intermediate 1,5-benzothiazepines
(3) were formed in-situ by the reaction of β-benzoyl arylic acid (1) and
5-substituted 2-aminobenzenethiols (2) under microwave irradiation.
Thus, the whole procedure was rendered into a facile one pot synthe-
sis. Earlier reports mentioned the variable formation of cis and trans
isomers of β-lactams depending on the order of addition of the reac-
tants in conventional syntheses.11 Encouraged by this, we also studied
the title cycloaddition reaction conventionally by changing the order
of reactants in basic medium (triethylamine in dry benzene), and the
results showed that under all conditions only one isomer of 5a was
obtained along with other products 6a and 7a. The formation of un-
desirable side products decreases the yields of the target adduct and
render their purification difficult. The results are given in Table I.

3118
A. Dandia et al.
TABLE I Reaction of 2,3-Dihydro-8-methoxy-4-phenyl-1,5-
benzothiazepine-2-carboxylic acid (3) with Chloroacetyl
Chloride (4)
5a
6a
7a
Yield
Mode of
heating
Yield
(%)
M.p.
(◦C )
Yield
(%)
M.p.
(◦C )
M.p.
(◦C )
Procedure*
(%)
A
B
C
D
E
Conventional
Conventional
Conventional
Conventional
Microwave
30
22
—
—
90
240
240
—
—
240
15
—
—
—
—
158
—
—
—
—
—
10
20
25
—
—
176
176
176
—
*Procedure A-D as described in the experimental section.
RESULTS AND DISCUSSION
When a solution of triethylamine in benzene was added drop-wise
into a solution of chloroacetyl chloride and 1,5-benzothiazepine (3)
in benzene (Table I, Procedure A), a mixture of azeto[2,1-d][1,5]-
benzothiazepines (5) and the ring contracted product 2-substituted
2,3-dihydro-3-phenyl-N-acetyl-2-styrylbenzothiazole (6) was obtained.
The low yield of azeto[2,1-d][1,5]benzothiazepine (5) is due to the com-
petitive ring contraction with ‘Staudinger reaction’ under the reaction
conditions. N-Acetylated phenyl 1,5-benzothiazepine intermediates are
formed in the reaction mixture and the ring contraction could oc-
cur before triethylamine was added.2 On the basis of the literature
mechanism,12 the yield of the fused system 5 could be improved if a so-
lution of chloroacetyl chloride (4) in benzene was added drop-wise into
a solution of benzothiazepine and triethylamine in benzene (Table I,
TABLE II Physical and analytical data of compounds 5a-f.
Compd.
X
Timea (min)
M.p. (oC)
Yield (%)
Rfb
5a
5b
5c
5d
5e
5f
OCH3
CH3
Cl
Br
CF3
F
12+3
10+5
12+6
10+5
9+4
240
203
199
215
232
226
90
87
83
86
88
87
0.80
0.74
0.79
0.81
0.77
0.82
10+5
aTime (12+3) indicates first irradiation for 12 min. gives compound 3 (detected by
TLC) and then further irradiation after adding chloroacetyl chloride for 3 min yields 5a;
and bUsing solvent system benzene: ethyl acetate (8 : 2).

Reaction of Chloroacetyl Chloride with 1,5-Benzothiazepines
3119
Procedure B). Although the ring contraction could be inhibited under
this addition mode, the yield of the desired product 5a was still low
when 1.5 equivalents of 4 were used and a new byproduct 7 was ob-
tained. When 3.0 equivalents of 4 were applied to improve the yield of
the desired product 5, the desired azeto[]2,1-d][1,5]benzothiazepines 5
were not obtained but the yield of the new byproduct 7 was improved
slightly (Table I, Procedure C).
Procedure D (Table I) involves first the formation of diketenes
through addition of triethylamine to a solution of 4 in benzene and
subsequently the addition of the 1,5-benzothiazepine 5a into the re-
sulting reaction mixture. In this case, only the 1,3-oxazine derivative 7
was obtained.
Under microwave irradiation, on the other hand, the desired
azeto[2,1-d][1,5]-benzothiazepine (5a) was formed with good yield and
as the only product. This rapid, economic, simple-to-handle, selective,
and environmentally benign protocol proceeds under mild conditions.
The structures of all azeto[2,1-d][1,5]benzothiazepines (5a-f), and
the other products 6 and 7, have been elucidated by elemental analy-
ses and spectroscopic studies. Theoretically, compound 5a-f exhibiting
1
two chiral centers could exist in two diastereomeric forms, but the H
NMR spectra and chromatographic studies of the isolated compounds
indicated the formation of only one diastereomer. In the mass spec-
trum of 5a the appearance of molecular ion peaks m/z (M+) at 389 and
(M++2) at 391 due to the chlorine-37 isotope showed the formation of
the fused ring system azeto-1,5-benzothiazepine.
Evaluation of the Antifungal Activity
The synthesized compounds were screened for antifungal activity
against three pathogenic fungi, namely Rhizoctonia solani causing root
rot of okra; Fusarium oxysporum causing wilt of mustard; and Col-
letotrichum capsici causing leaf spot and fruit rot of chile.
Poison Plate Technique13
The compounds synthesized were dissolved in acetone (1000 and 500
ppm). Potato-dextrose-agar (PDA) medium was prepared in flasks and
sterilized. To this medium, a requisite quantity of solution was added
and then the medium was poured into Petri-plates in three replications.
A culture of the test fungus was grown on PDA for 6−7 days. Small
discs (4 mm) of the fungus culture were cut with a sterile cork-drill
and transferred aseptically, upside-down in the center of Petri-dishes

3120
A. Dandia et al.
TABLE III Effect of Concentrations of Different Chemicals on the
Mean Radial Growth (cm) of Different Fungus in vitro
Rhizoctonia solani
Fusarium oxysporum
Colletotrichum capsici
Compd.
1000 ppm
500 ppm
1000 ppm
500 ppm
1000 ppm
500 ppm
5a
5b
5c
5d
5e
5f
Check
CD%
1.25a
2.18
3.63
5.42
1.32b
1.28b
9.00
0.74
1.72b
2.22b
4.20
2.08b
2.62
3.90
3.92
1.78a
2.23b
8.17
0.77
2.52
3.98a
4.05
4.89
1.02a
2.18
8.17
1.14
1.78a
3.52
2.51b
3.95
2.08a
3.45
2.90b
4.88
6.83
1.98b
1.69a
9.00
2.16b
2.42b
7.33
2.50a
3.00b
7.33
1.22
1.08
1.25
Check = Growth only in PDA without any treatment; CD% = Critical difference of
all values; amin. value- best and significantly superior compound; b-at par with min.
values- when difference of a; and other significant value is under the CD%.
containing the medium and the fungicides. The plates were incubated
at 25◦C 1◦C for 6 days. The colony diameters were measured and the
data were statistically analyzed (Table III).
Pot Trial Method14
White seeded sorghum grains were soaked in water for about 12 h,
160 g of the soaked kernels were placed in 500-ml flasks, and 20 ml of
water were added to each. The material was autoclaved twice on suc-
cessive days before inoculation. After sterilization, fungus bits were in-
oculated in each flask, and the flasks were kept for 10 days at 25−27◦C.
One-hundred seeds of okra were taken for one treatment of each com-
pound. Inoculum The inoculant was added at 2g/kg of soil 3 days prior
to sowing. Sowing was performed after 3 days, and germination data
were recorded after 7, 15, and 25 days of sowing. Suitable checks were
maintained and the data were statistically analyzed (Table IV). It was
found that 5a and 5e, exhibiting OCH3 or CF3 substituents, showed
maximum germination (72−76%), indicating that these are the most
effective compounds in controlling the growth of pathogens. “Baynate”
and “Thiram” are recommended as standard fungicide as seed dressers
to control this disease are having N and S elements, similar to the syn-
thesized compounds, which is responsible for their antifungal activity.
Antibacterial Activity
All the compounds were screened for their antibacterial activity
against Staphylococcus aureus, Escherichia coli, and Bacillus subtilis.

Reaction of Chloroacetyl Chloride with 1,5-Benzothiazepines
3121
TABLE IV Evaluation of Azeto[2,1-d][1,5]benzothiazepine (5a-f)
as Seed Dressers Against Rhizoctonia solani Causing Root Rot of
Okra ( in Pot Trial)
Compd.
Percent germination
Plant stand 25 DAS
5a
5b
5c
5d
5e
5f
72.00
49.00
47.00
68.00
76.00
69.00
98.00
79.00
10.00
90.00
64.00
62.00
69.00
57.00
61.00
57.00
64.00
68.00
6.00
Baynate (0.2%)
Thiram (0.3%)
Check with inoculum
Check without inoculum
81.00
DAS = days after sowing.
Nutrient agar was used as culture medium. Test solutions and
standard drug Norfloxacin solution (100µg/mL) were prepared in DMF
and used for testing the growth inhibition by the cup-plate method.15
The results are shown in Table V. Compound 5a, 5d, and 5f showed a
good activity against S. aureus. The activity of all compounds against
E. coli and B. subtilis was moderate.
EXPERIMENTAL
Melting points were determined in open glass capillaries and were un-
corrected. IR spectra were recorded on a Shimadzu FTIR-8400S spec-
trometer on KBr Pellets. 1H NMR and 13C NMR spectra were recorded
on a Bruker DRX-300 spectrometer using CDCl3 at 300.15 and 75.47
MHz, respectively. TMS was used as internal reference. Mass spectra
TABLE V Antibacterial Activity of Compounds 5a–f (% Inhibition)
Compd.
Escherichia coli
Staphylococcus aureus
Bacillus subtilis
5a
5b
5c
5d
5e
5f
24.6
39.3
40.4
35.7
57.8
49.8
100
68.2
52.9
38.4
50.2
48.3
57.6
100
35.8
20.5
18.5
31.7
15.3
51.5
100
Norfloxacin

3122
A. Dandia et al.
of representative compounds were recorded on a Kratos 50 mass spec-
trometer at 70 eV. The purity of all compounds was checked by TLC
using silica Gel-G coated glass plates and benzene:ethyl acetate (8 :
2) as eluent. The microwave induced reactions were carried out in a
BMO-700T modified multimode oven fitted with a condenser and a
magnetic stirrer. 5-Substituted 2-aminobenzenethiols16 and 3-benzoyl-
2-propionic acids17 were prepared by literature methods.
2-Chloro-7-methoxy-1-oxo-2a-phenyl-2,2a,3,4-
tetrahydroazeto[2,1-d][1,5]-benzothiazepine-4-carboxylic
acid (5a)
Conventional Synthesis
2,3-Dihydro-8-methoxy-4-phenyl-1,5-benzothiazepine-2-
carboxylic Acid (3a)
An equimolar mixture (0.01 mol) of β-benzoylacryclic acid (1) and
2-amino-5-methoxy-benzenethiol (2) was refluxed for 7 h with dry
ethanol (20ml) saturated with hydrogen chloride gas, whereupon the
reaction mixture changed from yellow to dark green. Excess of solvent
was removed by distillation under reduced pressure. The product so
obtained was recrystallized from methanol to give 3a.
Reaction of 3a with Chloroacetyl Chloride (4)
Procedure A
A solution of triethylamine (1.5 mmol) in anhydrous benzene (5 ml)
was added drop wise into a solution of 3 (2 mmol) and chloroacetyl
chloride (4) (2 mmol) in benzene (8 ml) for a period of 10−15 min. The
resulting mixture was refluxed for 10−11 h. The precipitated triethy-
lamine hydrochloride was removed by filtration, and the filtrate was
washed with saturated aqueous sodium bicarbonate solution (30 ml),
water and saturated brine, respectively, and dried over MgSO4. After
removal of the solvent, the residue was separated by chromatography
on silica gel with a mixture of ethyl acetate and benzene (1:15; V:V)
as the eluent to afford colorless crystals of dihydrobenzothiazole (6)
and azeto [2,1-d][1,5]-benzothiazepine (5a) after crystallization from
ethanol.
Procedure B
A solution of 4 (2 mmol) in anhydrous benzene (5 ml) was added
drop wise into a solution of 3 (2 mmol) and triethylamine (1.5 mmol)

Reaction of Chloroacetyl Chloride with 1,5-Benzothiazepines
3123
in benzene (8 ml) for 10−15 min. The resulting mixture was refluxed
for 10−11 h. After the same workup as described in Procedure A, the
residue was separated by chromatography in silica gel with a mixture
of ethyl acetate and petroleum ether as the eluent to afford colorless
crystals of azeto [2,1-d][1,5]-benzothiazepine 5a and [1,3]oxazino [2,3-
d][1,5]benzothiazepinone (7).
Procedure C
A solution of 4 (3 mmol) in anhydrous benzene (5 ml) was added drop
wise into a solution of 3 (2 mmol) and triethylamine (1.5 mmol) in ben-
zene (8 ml) during 10−15 min. The resulting mixture was refluxed for
10−11 h. After the same workup as described in the procedure B. Crys-
tals of [1,3]oxazino [2,3-d][1,5]benzothiazepinone (7) were obtained.
Procedure D
A solution of 3 (2 mmol) in benzene (l ml) was added drop wise
into the solution of 4 (3 mmol) and triethylamine (2mmol) in benzene
(4 ml) for a period of 10−15 min. The resulting mixture was refluxed
for 10−11 h. After the same workup as described in for Procedure B,
colorless crystals of 7 were obtained.
Microwave Assisted Synthesis (One-Pot Synthesis)
An equimolar mixture (2 mmol) of 1 and 2a was adsorbed on basic
alumina (2 g) via a solution of ethanol and swirled for a while followed
by removal of the solvent under gentle vacuum. It was irradiated inside
a microwave oven at 90% power, i.e., 645 W for 12 min (monitored by
TLC). The intermediate 3a so obtained in reasonable purity (TLC, 100%
conversion), was used as such for the next step. 4 (2.5 mmol) was added
to the reaction mixture, mixed thoroughly and irradiated again inside
a microwave oven at 640 W for an appropriate time. The product 5a
was obtained by desorption with ethanol and found to be pure by TLC.
Compounds 5b-f were similarly prepared under solvent-free condi-
tions, using basic alumina as solid support. For analytical and spectro-
scopic studies the products were recrystallized from ethanol.
Compound 5a
1H NMR (CDCl3)δ 3.75 (s, 3H, OCH3), 3.08 (dd, 1H, HA, JA−B = 15.28,
JA−X = 9.15 Hz), 3.62 (dd, 1H, HB, JA−B = 15.28, JB−X = 8.12 Hz), 4.02
(dd, 1H, HX, JA−X = 9.15 Hz, JB−X = 8.12 Hz), 5.12 (s, 1H, Cl-CH),
6.58−7.79 (m, 8H, Ar-H), 8.47 (bs, 1H, COOH). IR (cm−1) 1680, 1725
(two C=O), 3288 (b, OH), 748 (C-Cl). Anal. calcd. for C19H16ClNO4S:

3124
A. Dandia et al.
C, 58.54; H, 4.14; N, 3.59; S, 8.23; Cl, 9.09. Found C, 58.70; H, 4.16; N,
3.58; S, 8.20; Cl, 9.05.
Compound 5b
1H NMR (CDCl3)δ 2.61 (s, 3H, CH3), 3.14 (dd, 1H, HA, JA−B = 15.17,
JA−X = 9.69 Hz), 3.71 (dd, 1H, HB, JA−B = 15.17, JB−X = 8.52 Hz),
4.31 (dd, 1H,HX, JA−X = 9.29, JB−X = 8.52 Hz), 4.95 (s, 1H, Cl-CH),
6.62−7.81 (m, 8H, Ar-H), 8.21 (bs, 1H, COOH). IR (cm−1) 1678, 1722
(two C=O), 3270 (b, OH), 748 (C-Cl). Anal. calcd. for C19H16ClNO3S:
C,61.04;H, 4.31; N, 3.75. Found C, 61.21; H, 4.28; N, 3.76.
Compound 5c
1H NMR (CDCl3), 3.27 (dd, 1H, HA, JA−B = 16.18, JA−X = 9.22 Hz),
3.76 (dd, 1H,HB, JA−B = 16.18, JB−X = 8.42 Hz), 4.74 (dd, 1H,HX, JA−X
=
9.22 Hz, JB−X = 8.42 Hz), 5.10 (s, 1H, Cl-CH), 6.60−7.69 (m, 8H, Ar-H),
8.58 (bs, 1H, COOH). IR (cm−1) 1680, 1728 (two C=O), 3278 (b, OH),
748 (C-Cl). Anal. calcd. for C18H13Cl2NO3S: C, 54.83; H, 3.32; N, 3.55.
Found C, 54.67; H, 3.34; N, 3.54.
Compound 5d
1H NMR (CDCl3), 3.29 (dd, 1H, HA, JA−B = 16.17, JA−X = 9.20 Hz),
3.73 (dd, 1H,HB, JA−B = 16.18, JB−X = 8.40 Hz), 4.76 (dd, 1H,HX,
JA−X = 9.18 Hz, JB−X = 8.40 Hz), 5.13 (s, 1H, Cl-CH), 6.61−7.70(m,

Reaction of Chloroacetyl Chloride with 1,5-Benzothiazepines
3125
8H, Ar-H), 8.60 ( bs, 1H, COOH). IR (cm−1) 1680, 1730 (two C=O),
3275 (b, OH), 748 (C-Cl). Anal. calcd. for C18H13ClBrNO3S: C, 49.28;
H, 2.99; N, 3.19. Found C, 49.13; H, 2.97; N, 3.20.
Compound 5e
1H NMR (CDCl3), 3.23 (dd, 1H, HA, JA−B = 16.28, JA−X = 9.20 Hz),
3.72 (dd, 1H,HB, JA−B = 16.28, JB−X = 8.39 Hz), 4.74 (dd, 1H,HX, JA−X
=
9.20 Hz, JB−X = 8.39 Hz), 5.10 (s, 1H, Cl-CH), 6.63−7.65 (m, 8H, Ar-H),
8.59 ( bs, 1H, COOH). IR (cm−1) 1684, 1725 (two C=O), 3278 (b, OH),
748 (C-Cl). Anal. calcd. for C19H13ClF3NO3S: C, 53.54; H; 3.06; N, 3.27.
Found C, 53.71; H, 3.04; N, 3.28.
Compound 5f
1H NMR (CDCl3), 3.19 (dd, 1H,HA, JA−B = 16.12, JA−X = 9.21Hz),
3.76 (dd, 1H, HB, JA−B = 16.12, JB−X = 8.47 Hz), 4.69 (dd, HX, 1H,
JA−X = 9.21 Hz, JB−X = 8.47 Hz), 5.10 (s, 1H, Cl-CH), 6.57−7.67 (m,
8H, Ar-H), 8.63 ( bs, 1H, COOH). IR (cm−1) 1680, 1730 (two C=O),
3278 (b, OH), 748 (C-Cl). Anal. calcd. for C18H13ClFNO3S: C, 57.22; H,
3.47; N, 3.17. Found C, 57.04; H, 3.50; N, 3.18.
Compound 6a
1H NMR (CDCl3)δ 3.45 (d, 1H, CHH, J = 14.8 Hz), 3.60 (d, 1H, CHH,
J = 14.8 Hz), 3.82 (s, 3H, OCH3), 6.17 (d, 1H, CH= 15.4 Hz), 6.42 (d, 1H,
CH=, J = 15.4 Hz), 6.98−7.32 (m, 8H, Ar-H), 8.42 (bs, 1H, COOH). IR
(cm−1) 1680, 1710 (two C=O). Anal. calcd. for C19H16ClNO4S: C, 58.54;
H, 1.14; S, 8.23; Cl, 9.09; N, 3.59; Found C, 58.35; H, 4.17; S, 8.23; Cl,
9.06; N, 3.57. MS (EI) m/z (%) (M+2, 391), 389 (M+),
Compound 7a
1H NMR (CDCl3)δ 2.67 (dd, 1H, HA, JA−B = 14.98 Hz, JA−X = 8.89
Hz), 3.25 (dd, 1H,HB, JA−B = 14.98 Hz, JB−X = 8.12 Hz), 3.58 (s, 2H,
CH2Cl, ), 3.86 (s, 3H, OCH3), 4.06 (dd, HX, JA−X = 8.89 Hz, JB−X
=
8.12Hz), 6.98−7.32 (m, 8H, Ar-H), IR (cm−1) 1680, 1710 (two C=O).
Anal. calcd. for C21H17Cl2NO5S: C, 54.09;H, 3.67; S, 6.88; Cl, 15.20 ; N,
3.00. Found C, 54.26; H, 3.65; S, 6.86; Cl, 15.24; N, 2.98. MS (EI) m/z
(%) (M+2, 468), 466 (M+),
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