Formation and ring contraction of benzo[f][1,2]thiazepine-1,1-dioxides from and to benzo[e][1,2]thiazine-1,1-dioxides

Article abstract of DOI:10.1080/00397910802213737

Alkoxide-promoted ring expansion of the novel ethyl 2-(6,7-dimethoxy-3-oxo- 3,4-dihydrobenzo[e][1,2]thiazine-1,1-dioxide-2-yl)acetate 3a and analogous 4,4-diethyl derivative 3b and cyclization of methyl 2-[2- (phenylaminocarbonylmethyl sulfamoyl)-4,5-dimethoxyphenyl] acetate 9 to the corresponding new 3-carboxylates and 3-carboxanilide of 7,8-dimethoxy-4-hydroxy- 2,5-dihydrobenzo[f][1,2]thiazepine-1,1-dioxide (5a,b and 10 respectively) is described. Compound 5a was deacylated upon treatment with sodium hydroxide followed by hydrochloric acid to give 7,8-dimethoxy-2,3-dihydrobenzo[f][1,2] thiazepine-1,1-dioxide-4 (5H)-one 8 and its N-ethyl derivative transferred to 6,7-dimethoxy-2-ethyl-3-oxo-3,4-dihydrobenzo[e][1,2]thiazine-1,1-dioxide 7 by the reaction with ethyl methyl ketone in the presence of pyrrolidine. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802213737

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Formation and Ring
Contraction of Benzo[f]
[1,2]Thiazepine-1,1-Dioxides
from and to Benzo[e]
[1,2]Thiazine-1,1-Dioxides
Ali Khalaj a & Neda Adibpour b
a Department of Medicinal Chemistry, Faculty of
Pharmacy, Tehran University of Medical Sciences,
Tehran, Iran
b Department of Medicinal Chemistry, School of
Pharmacy, Ahwaz Jundishapur University of Medical
Sciences, Ahwaz, Iran
Version of record first published: 14 Oct 2008.
To cite this article: Ali Khalaj & Neda Adibpour (2008): Formation and Ring
Contraction of Benzo[f][1,2]Thiazepine-1,1-Dioxides from and to Benzo[e]
[1,2]Thiazine-1,1-Dioxides, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 38:21, 3662-3671
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Synthetic Communications1, 38: 3662–3671, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802213737
Formation and Ring Contraction
of Benzo[f][1,2]Thiazepine-1,1-Dioxides from and
to Benzo[e][1,2]Thiazine-1,1-Dioxides
Ali Khalaj1 and Neda Adibpour2
1Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran
University of Medical Sciences, Tehran, Iran
2Department of Medicinal Chemistry, School of Pharmacy, Ahwaz
Jundishapur University of Medical Sciences, Ahwaz, Iran
Abstract: Alkoxide-promoted ring expansion of the novel ethyl 2-(6,7-
dimethoxy-3-oxo-3,4-dihydrobenzo[e][1,2]thiazine-1,1-dioxide-2-yl)acetate 3a and
analogous 4,4-diethyl derivative 3b and cyclization of methyl 2-[2-(phenyl-
aminocarbonylmethyl sulfamoyl)-4,5-dimethoxyphenyl] acetate 9 to the corre-
sponding new 3-carboxylates and 3-carboxanilide of 7,8-dimethoxy-4-hydroxy-
2,5-dihydrobenzo[f][1,2]thiazepine-1,1-dioxide (5a,b and 10 respectively) is
described. Compound 5a was deacylated upon treatment with sodium hydroxide
followed by hydrochloric acid to give 7,8-dimethoxy-2,3-dihydrobenzo[f][1,2]thia-
zepine-1,1-dioxide-4 (5H)-one 8 and its N-ethyl derivative transferred to 6,7-
dimethoxy-2-ethyl-3-oxo-3,4-dihydrobenzo[e][1,2]thiazine-1,1-dioxide
reaction with ethyl methyl ketone in the presence of pyrrolidine.
7 by the
Keywords: 4-Hydroxy-2,5-dihydrobenzo[f][1,2] thiazepine-1,1-dioxides, 3-oxo-3,
4-dihydrobenzo[e][1,2]thiazine-1,1-dioxides, ring contraction, ring expansion
Received March 10, 2008.
Address correspondence to Ali Khalaj, Department of Medicinal Chemistry,
Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
E-mail: khalaj@ams.ac.ir
3662

1,2-Benzothiazepines from and to 1,2-Benzothiazines
INTRODUCTION
3663
In our previous article ring contraction of 3-carboxylate or 3-
carboxamide of 4-hydroxy-2-methyl-3,4-dihydrobenzo[e][1,2]thiazine-
1,1-dioxides and analogous 1(2H)-isoquinoline-3-carboxylates to the
five-membered rings upon the reaction with carbonyl compounds in the
presence of primary or secondary amines was described[1] (Scheme 1).
In continuation of our study on this type of ring transformation, its
application for contraction of the homologous seven-membered ethyl 7,8-
dimethoxy-2-ethyl-4-hydroxy-2,5-dihydrobenzo[f][1,2]thiazepine-1,1-
dioxide-3-carboxylate 6 to six-membered 6,7-dimethoxy-2-ethyl-3-oxo-3,4-
dihydrobenzo[e][1,2]thiazine-1,1-dioxide 7 was investigated (Scheme 2).
Reviewing the literature revealed that preparation of the required
benzothiazepine 6 as starting material has not been reported, and rela-
tively little has been published on the synthesis of 1,2-benzothiazepines.
One possible approach for the preparation of compound 6 seemed to
be alkoxide-promoted ring expansion of the six-membered ethyl 2-(6,7-
dimethoxy-3-oxo-3,4-dihydrobenzo[e][1,2]thiazine-1,1-dioxide-2-yl) acetate
3a to ethyl 7,8-dimethoxy-4-hydroxy-2,5-dihydrobenzo[f][1,2]thiazepinee-
1,1-dioxide-3-carboxylate 5a followed by N-ethylation (Scheme 2).
Although alkoxide-catalyzed rearrangement of five-membered N-
acyl phthalimides to 4-hydroxy-1-oxo-1,2-dihydro-isoquinoline-3-car-
boxylates,[2] known as Gabriel–Colman rearrangement,[3] have been
extensively applied for the preparation of six-membered 3-substituted
2H-1,2-benzothiazine-4-hydroxy-1,1-dioxides from five-membered N-
substituted 1,2-benzisothiazol-3-one-1,1-dioxides[4,5] (acetonyl saccharine)
Scheme 1. Ring contraction of 1,2-benzothiazine-1,1-dioxides Ia,b and analogous
1(2H)-isoquinoline-3-carboxylate Ic to five-membered rings IIa,b.

3664
A. Khalaj and N. Adibpour
Scheme 2. Synthesis of 1,2-benzothiazines and 1,2-benzothiazepines.
(Scheme 1), no example of this kind of ring expansion for transformation
of the analogous six- to seven-membered rings are known. This article is
the first report on the application of this type of reaction for the synthesis
of novel benzothiazepines 5a,b through ring expansion of benzothiazines
3a,b and reverse ring contraction of N-ethyl derivative of 5a, i.e., com-
pound 6 to the six-membered 6,7-dimethoxy-2-ethyl-3-oxo-3,4-dihydro-
benzo[e][1,2]thiazine-1,1-dioxide 7.
RESULTS AND DISCUSSION
Benzothiazine 3a was prepared in 67% yield by the reported method[6] for
the preparation of the analogous compounds through p-toluenesulfonic
acid–catalyzed cyclization of methyl 2-[2-(ethoxycarbonylmethyl sulfa-
moyl)-4,5-dimethoxyphenyl] acetate 2, which in turn was prepared from
the reaction of ethyl 2-aminoacetate with methyl 2-(2-chlorosulfonyl-
4,5-dimethoxyphenyl) acetate 1. The latter was prepared by chlorosul-
fonation of methyl 2-(3,4-dimethoxyphenyl) acetate[7] which by itself
was prepared by esterification of the commercially available 2-(3,4-
dimethoxyphenyl) acetic acid (homoveratric acid) with methanol.[8]
Treatment of the bezothiazine 3a with sodium ethoxide in refluxing
ethanol under conditions described[5] for ring expansion of the analogous
five-membered 1,2-benzisothiazol-3(2H)-one-1,1-dioxides gave ethyl

1,2-Benzothiazepines from and to 1,2-Benzothiazines
3665
7,8-dimethoxy-4-hydroxy-2,5-dihydrobenzo[f][1,2]thiazepine-1,1-dioxide-
3-carboxylate 5a in 25% yield. Hydrolysis and decarboxylation of this com-
pound under conditions reported[5] for the analogous six-membered ring gave
7,8-dimethoxy-2,3-dihydrobenzo[f][1,2]thiazepine-1,1-dioxide-4 (5H)-one 8.
The low yield of formation of 5a may be attributed to the presence
of two enolizable protons in the intermediate 4a, which by analogy to
the mechanism proposed[5] for the ring expansion of five-membered
N-substituted 1,2-benzisothiazol-3-one-1,1-dioxides to the six-membered
N-substituted 3,4-dihydrobenzo[e][1,2]thiazine-1,1-dioxide-3-carboxylates
is formed through nucleophilic attack of sodium ethoxide to the carbonyl
group of the starting ethyl 2-(6,7-dimethoxy-3-oxo-3,4-dihydrobenzo[e]
[1,2]thiazine-1,1-dioxide-2-yl) acetate 3a. In this intermediate, in addition
to isomerizaton of imide anion to carbanion and its intramolecular attack
to the carbonyl group of the acetate group to produce the desired ben-
zothiazepine 5a by displacement of methoxy group, nucleophilic attack
of the carbanion resulting from removal of benzylic hydrogen of the acet-
ate group to the carbonyl group of the amide–ester moiety might result in
the formation of by-products, which lowers the yield of formation of com-
pound 5a. Consistent with this assumption, the yield of the product of the
ring expansion of ethyl 2-(6,7-dimethoxy-4,4-diethyl-3-oxo-3,4-dihydro-
benzo[e][1,2]thiazine-1,1-dioxide-2-yl) acetate 3b, in which formation of
benzylic carbanion is eliminated was higher (48%) than 4,4-unsubstituted
compound 3a under the same reaction condition.
Compound 3b was readily prepared from the reaction of compound
3a with 2 equivalents of ethyl iodide. Further support for this assumption
is that alkoxide-catalyzed ring closure of methyl 2-[2-(phenylaminocarbo-
nylmethyl sulfamoyl)-4,5-dimethoxyphenyl] acetate 9, in which forma-
tion of benzylic carbanion is possible but ꢀ NHAr is not as good of a
leaving group as the methoxy group, gave 7,8-dimethoxy-4-hydroxy-
2,5-dihydrobenzo[f][1,2]thiazepine-1,1-dioxide-3-carboxanilide 10 result-
ing from nucleophilic addition of the imide carbanion to the carbonyl
of the acetate group. The methyl 2-[2-(phenylaminocarbonylmethyl sulfa-
moyl)-4,5-dimethoxyphenyl] acetate 9 was prepared from the reaction of
methyl 2-(2-chlorosulfonyl-4,5-dimethoxyphenyl) acetate 1 with 2-amino-
N-phenyl acetamide 11, which by itself was readily prepared[9] from the
reaction of ethyl 2-aminoacetate with aniline (Scheme 3).
Although reaction of the benzothiazepine 5a with ethyl methyl ketone
in the presence of pyrrolidine gave a mixture of unresolved products, its
N-ethyl derivative (i.e., compound 6), similar to our reported method
1
for the ring contraction of the related benzothiazines[ ] (Scheme 1), gave
6,7-dimethoxy-2-ethyl-3-oxo-3,4-dihydrobenzo[e][1,2]thiazine-1,1-dioxide
7, which is another example in support of this kind of novel ring
contraction. In conclusion, by extrapolation of the Gabriel–Colman ring

3666
A. Khalaj and N. Adibpour
Scheme 3. Synthesis of 1,2-benzothiazepine-3-carboxanilide 10.
expansion, two novel benzothiazepines 5a,b were synthesized in one step
from readily prepared benzothiazines 3a,b, which otherwise cannot be
prepared by convenient methods.
EXPERIMENTAL
Melting points were determined on a Reichert hot plate and are uncor-
rected. 1H NMR spectra were recorded on a Bruker 80 NMR instrument
using CDCl3 as solvent. Chemical shifts (d) are reported in parts per mil-
lion (ppm) relative to TMS as internal standard. Mass spectra were
obtained on a Finningan TSQ-70 instrument. Infrared spectra were
recorded on a Nicolet Magna IR 550 spectrometer. Elemental analyses
for C, H, and N were performed using a Heracus CHN–O rapid elemen-
tal analyzer, and the results are within ꢁ0.4% of the theoretical values.
The spectroscopic and analytical data of the known compounds
methyl 2-(3,4-dimethoxyphenyl) acetate,[8] 1[7] and 11[9] matched those
described in the literature.
N-Substituted Sulfonamides 2 and 9
Preparation of Methyl 2-[2-(ethoxycarbonylmethyl Sulfamoyl)-
4,5-dimethoxyphenyl] Acetate (2)
A mixture of 2 g (0.0065 mol) of methyl 2-(2-chlorosulfonyl-4,5-
dimethoxyphenyl) acetate 1, 0.7 g (0.0067 mol) of ethyl 2-aminoacetate,

1,2-Benzothiazepines from and to 1,2-Benzothiazines
3667
and 0.5 g (0.005 mol, 0.7 mL) of triethylamine in anhydrous chloroform
was refluxed for 7 h. The mixture was then cooled to room temperature,
and the chloroform solution was washed with water, dried over
anhydrous MgSO4, and rotary evaporated to give 1.87 g of compound
2; yield: 77%; mp 127–130ꢂC. IR (KBr, cmꢀ1): 3340, 1730, 1320, 1155.
1H NMR (80 MHz, CDCl3): d 1.2 (t, 3H, J ¼ 7.2 Hz, CH2CH3), 3.72–
3.8 (m, 5H, CH3, CH2CH3), 3.92 (s, 6H, OCH3), 4.1–4.3 (m, 4H,
2CH2), 6.8 (s, 1H, H6), 7.4 (s, 1H, H3). EI-MS m=z: 375.6 (Mþ), 297.3,
272.3, 245.2. Anal. calcd. for C15H21NO8S: C, 47.99; H, 5.64; N,3.73;
S, 8.54. Found: C, 48.01; H, 5.63; N, 3.73; S, 8.53.
Preparation of Methyl 2-[2-(Phenylaminocarbonylmethyl Sulfamoyl)-
4,5-dimethoxyphenyl] Acetate (9)
To a solution of 0.5 g (0.0016 mol) of methyl 2-(2-chlorosulfonyl-4,5-
dimethoxyphenyl) acetate 1 in 10 mL of anhydrous benzene, 0.3 g
(0.002 mol) of the 2-amino-N-phenyl acetamide 11 in 5 mL of
anhydrous pyridine was added, and the resulting solution was heated
under reflux for 6 h. The residue after evaporation of the solvent was
dissolved in chloroform (30 mL), and the chloroform solution was
washed with water, dehydrated over anhydrous Na2SO4, and then eva-
porated under reduced pressure to give 0.48 g of the compound 9; yield:
1
70%; mp 157–160ꢂC. IR (KBr, cmꢀ1): 3490, 3340, 1700, 1670, 1325. H
NMR (80 MHz, CDCl3): d 3.5(s, 3H, OCH3), 3.7 (s, 2H, CH2), 3.8 (s,
2H, NCH2), 3.9 (s, 6H, OCH3), 6.8 (s, 1H, H6), 7.2–7.5 (m, 6H, phenyl
and H3), 10.5 (s, 1H, CONH). EI-MS m=z: 422.1 (Mþ), 391.2, 363.
Anal. calcd. for C19H22N2O7S: C, 54.02; H, 5.25; N, 6.63; S, 7.59.
Found: C, 53.97; H, 5.27; N, 6.62; S, 7.57.
Cyclization of the N-Substituted Sulfonamides 2 and 9
Preparation of Ethyl 2-(6,7-Dimethoxy-3-oxo-3,4-dihydrobenzo[e]
[1,2]thiazine-1,1-dioxide-2-yl) Acetate (3a)
A mixture of 1 g (0.0026 mol) of compound 2 and 0.5 g (0.0029 mol) of
p-toluenesulfonic acid in 30 mL of xylene was stirred and heated under
reflux for 12 h. The mixture was then cooled to room temperature, and
the solution was washed with water, dried over anhydrous MgSO4, and
evaporated under vacuum. Crystallization of the residue from methanol
gave 0.6 g of the compound 3a; yield: 67% mp 140–143ꢂC. IR (KBr,
cmꢀ1): 1760, 1705, 1345, 1190. 1H NMR (80 MHz, CDCl3): d 1.2
(t, 3H, CH3), 3.9 (s, 6H, OCH3), 4.1–4.2 (m, 4H, H4 and OCH2), 4.6

3668
A. Khalaj and N. Adibpour
(s, 2H, NCH2), 6.8 (s, 1H, H5), 7.3 (s, 1H, H8). EI-MS m=z: 343.1 (Mþ),
329.4, 297.4, 269.7. Anal. calcd. for C14H17NO7S: C, 48.97; H, 4.99; N,
4.08; S, 9.34. Found: C, 48.89; H, 5.00; N, 4.07; S, 9.36.
Preparation of 7,8-Dimethoxy-4-hydroxy-2,5-dihydrobenzo[f][1,2]
thiazepine-1,1-dioxide-3-carboxanilide (10)
To a solution of 0.13 g (0.002 mol) sodium methoxide in 15 mL of the abso-
lute methanol, 1 g (0.0023 mol) of compound 9, was added and the mixture
was stirred and heated under reflux for 8 h. The residue after evaporation
of the solvent was treated with water (5 mL) and concentrated hydrochlo-
ric acid. The resulting precipitate was filtered to give 0.2 g of compound 10;
1
yield 21.6%; mp 197–202ꢂC. IR (KBr, cmꢀ1): 3335, 3240, 1720, 1665. H
NMR (80 MHz, CDCl3): d 3.7 (s, 2H, H5), 3.9 (s, 6H, OCH3), 6.0 (bs,
1H, NH), 6.9–7.3 (m, 7H, phenyl, H6 and H9), 13.1 (s, 1H, OH). EI-MS
m=z: 390.1 (Mþ), 272, 208, 193. Anal. calcd. for C18H18N2O6S: C, 55.38;
H, 4.65; N, 7.18; S, 8.21. Found: C, 55.36; H, 4.64; N, 7.17; S, 8.19.
Alkylation of Benzothiazine 3a and Benzothiazepine 5a with Ethyl Iodide
Preparation of Ethyl 2-(6,7-Dimethoxy-4,4-diethyl-3-oxo-3,4-
dihydrobenzo[e][1,2]thiazine-1,1-dioxide-2-yl) Acetate (3b)
A mixture of 0.5 g (0.0014 mol) of benzothiazine 3a, 0.45 g (0.0029 mol,
0.16 mL) of ethyl iodide, and 1 g of anhydrous potassium carbonate in
10 mL of anhydrous acetone was heated under reflux for 5 h. After filtra-
tion of the mixture and evaporation of the solvent, the residue was dis-
solved in chloroform (30 mL), and the solution was washed with water
(2 ꢃ 15 mL) and dried over anhydrous sodium sulfate. Evaporation of
the solvent gave 0.2 g of the compound 3b; yield: 35%; mp 153ꢂC. IR
(KBr, cmꢀ1): 1760, 1720, 1345, 1190. 1H NMR (80 MHz, CDCl3): d
0.8(t, 6H, J ¼ 7.2 Hz, CH2CH3), 1.3 (t, 3H, J ¼ 7.2 Hz, OCH2CH3),
1.9–2.3 (m, 4H, CH2CH3), 3.9 (s, 6H, OCH3), 4.2 (q, 2H, J ¼ 7.2 Hz,
OCH2CH3), 4.6 (s, 2H, NCH2), 6.8 (s, 1H, H5), 7.4 (s, 1H, H8). EI-MS
m=z: 399.1 (Mþ), 354, 326. Anal. calcd. for C18H25NO7S: C, 54.12; H,
6.31; N, 3.51; S, 8.03. Found: C, 54.14; H, 6.32; N, 3.52; S, 8.02.
Preparation of Ethyl 7,8-Dimethoxy-2-ethyl-4-hydroxy-2,5-
dihydrobenzo[f][1,2]thiazepine-1,1-dioxide-3-carboxylate (6)
Alkylation of 0.4 g (0.0011 mol) of benzothiazepine 5a, with 0.2 g
(0.0013 mol, 0.2 mL) of ethyl iodide under the same experimental

1,2-Benzothiazepines from and to 1,2-Benzothiazines
3669
conditions gave 0.23 g of the compound 6; yield: 54%; mp 40–42ꢂC. IR
1
(KBr, cmꢀ1): 1700, 1610, 1340, 1150. H NMR (80 MHz, CDCl3): d 1.3
(t, 6H, 2CH2CH3), 3.5 (s, 2H, H5), 3.9 (s, 6H, OCH3), 4.0–4.3 (m, 4H,
NCH2 and OCH2CH3), 6.8 (s, 1H, H6), 7.5 (s, 1H, H9), 12.4 (s, 1H,
OH). EI-MS m=z: 371 (Mþ), 326, 297. Anal. calcd. for C16H21NO7S: C,
51.74; H, 5.70; N, 3.77; S, 8.63. Found: C, 51.74; H, 5.71; N, 3.76; S, 8.62.
Ring Expansion of Benzothiazines
Preparation of Ethyl 7,8-Dimethoxy-4-hydroxy-2,5-dihydrobenzo[f]
[1,2]thiazepine-1,1-dioxide-3-carboxylate (5a)
To a solution of 0.2 g (0.0028 mol) of sodium ethoxide in 10 mL of absolute
ethanol 0.4 g (0.001 mol) of benzothiazine 3a was added, and the solution
while protected from moisture was stirred at reflux for 6 h. The solution
was then cooled in an ice bath and acidified with 3 N hydrochloric acid and
the precipitate was filtered to give 0.1 g of the compound 5a; yield: 25%;
mp 83–85ꢂC. IR (KBr, cmꢀ1): 3240, 1700, 1350. 1H NMR (80 MHz, CDCl3):
d 1.3 (t, 3H, J ¼ 7.2 Hz, CH3), 3.7 (s, 2H, H5), 3.9 (s, 6H, OCH3), 4.2 (q, 2H,
J¼ 7.2 Hz, OCH2CH3), 6.5 (bs, 1H, NH), 6.8 (s, 1H, H6), 7.4 (s, 1H, H9), 13.0
(s, 1H, OH). EI-MS m=z: 343 (Mþ), 270. Anal. calcd. for C14H17NO7S: C,
48.97; H, 4.99; N, 4.08; S, 9.34. Found: C, 49.01; H, 4.98; N, 4.06; S, 9.37.
Preparation of Ethyl 7,8-Dimethoxy-5,5-diethyl-4-hydroxy-2,5-dihydro-
benzo[f][1,2]thiazepine-1,1-dioxide-3-carboxylate (5b)
Rearrangement of 0.2 g (0.0005 mol) of benzothiazine 3b in the presence
of 0.1 g (0.0014 mol) of sodium ethoxide in 10 mL of ethanol under simi-
lar conditions gave 0.1 g of the compound 5b; yield: 48%; mp 140ꢂC. IR
1
(KBr, cmꢀ1): 3250, 1750, 1380, 1160. H NMR (80 MHz, CDCl3): d 0.7
(t, 6H, J ¼ 7.2 Hz, CH2CH3), 1.3 (t, 3H, J ¼ 7.2 Hz, OCH2CH3), 2.1 (q,
4H, J ¼ 7.2 Hz, CH2CH3), 3.9 (s, 6H, OCH3), 4.2 (q, 2H, J ¼ 7.2 Hz,
OCH2), 6.1 (bs, 1H, NH), 6.8 (s, 1H, H6), 7.5 (s, 1H, H9), 11.5 (s, 1H,
OH). EI-MS m=z: 399.1 (Mþ), 370, 354, 326. Anal. calcd. for
C18H25NO7S: C, 54.12; H, 6.31; N, 3.51; S, 8.03. Found: C, 53.95; H,
6.29; N, 3.50; S, 8.02.
Preparation of 7,8-Dimethoxy-2,3-dihydrobenzo[f][1,2]thiazepine-1,1-
dioxide-4 (5H)-one (8)
Hydrolysis and decarboxylation of the compound 5a according to the
method described for the analogous six-membered compounds[5] gave

3670
A. Khalaj and N. Adibpour
1
compound 8; yield: 14%; oil. H NMR (80 MHz, CDCl3): d 3.68 (s, 2H,
H5), 3.92 (s, 6H, OCH3), 4.18 (s, 2H, H3), 6.7 (s, 1H, H6), 7.4 (s, 1H, H9).
EI-MS m=z: 271.1 (Mþ). Anal. calcd. for C11H13NO5S: C, 48.70; H, 4.83;
N, 5.16; S, 11.82. Found: C, 48.68; H, 4.82; N, 5.14; S, 11.79.
Ring Contraction of Benzothiazepine 6
Preparation of 6,7-Dimethoxy-2-ethyl-3-oxo-3,4-dihydrobenzo[e][1,2]
thiazine-1,1-dioxide (7)
To a stirred solution of 0.36 g (0.001 mol) of benzothiazepine 6 in 20 mL
of anhydrous benzene, 0.05 mL (0.00063 mol) of pyrrolidine was added,
and after heating under reflux for 15 min, the solution was treated with
0.6 mL of ethyl methyl ketone. The resulting suspension was heated again
under reflux for 24 h. After cooling to room temperature, and evapora-
tion of the solvent, the residue was dissolved in chloroform, and the solu-
tion was washed successively with 5% HCl (5 mL), 5% sodium hydroxide
solution (5 mL), and water (2 ꢃ 25 mL) and dried over anhydrous
MgSO4. After evaporation of the organic solvent, the residue gave
0.16 g of benzothiazine 7; yield: 60%; mp 53ꢂC. IR (KBr, cmꢀ1): 1720,
1345, 1190. 1H NMR (80 MHz, CDCl3): d 1.3 (t, 3H, J ¼ 7.2 Hz,
CH2CH3), 3.7 (s, 2H, H4), 3.9 (s, 6H, OCH3), 4.2 (q, 4H, J ¼ 7.2 Hz,
CH2CH3), 6.7 (s, 1H, H5), 7.5 (s, 1H, H8). EI-MS m=z: 285 (Mþ), 256.
Anal. calcd. for C12H15NO5S: C, 50.52; H, 5.30; N,4.91; S, 8.03. Found:
C, 50.53; H, 5.29; N, 4.90; S, 8.02.
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