Synthesis and reactions of lactam sulfonium salts with a sulfonio bridgehead. Part 1. 4,4a,5,6-tetrahydro-5-oxo-1H-thiopyrano[1,2-a]-1,4-benzothiazinium perchlorates

Article abstract of DOI:10.1039/a603348b

Tricyclic benzothiazinium salts 3 are prepared by [2⁺+4] polar cycloaddition of thionium intermediates 2A, generated from the corresponding α-chloro sulfides 2, and dienes in the presence of silver perchlorate. Ring transformation of benzothiaz

Full text of DOI:10.1039/a603348b

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Synthesis and reactions of lactam sulfonium salts with a sulfonio
bridgehead. Part 1. 4,4a,5,6-Tetrahydro-5-oxo-1H-thiopyrano[1,2-a]-
1,4-benzothiazinium perchlorates
Tadashi Kataoka,*,a Yoshihide Nakamura,a Harutoshi Matsumoto,a
Tetsuo Iwama,a Hirohito Kondo,a Hiroshi Shimizu,a Osamu Muraoka a and
Genzoh Tanabeb
a
Gifu Pharmaceutical University, 6-1, Mitahora-higashi 5-chome, Gifu 502, Japan
b Kinki University, Faculty of Pharmaceutical Sciences, 3-4-1, Kowakae, Higashi-osaka,
Osaka 577, Japan
Tricyclic benzothiazinium salts 3 are prepared by [2++4] polar cycloaddition of thionium intermediates
2A, generated from the corresponding á-chloro sulfides 2, and dienes in the presence of silver perchlorate.
R ing transformation of benzothiazinium salts 3 with a reducing agent such as M g, N aBH 4 and Zn–AcOH
or with a base, furnishes spiro-vinylcyclopropane derivatives 4 in moderate to high yields. Electrolysis of
3a at Ϫ1.4 V vs. SCE in acetonitrile also affords vinylcyclopropane 4a (60%). These results indicate that
both ionic and radical mechanisms may account for the vinylcyclopropane formation, although it is
unclear as to the nature of the radical intermediate. The stereochemistry of 4a was determined by X-ray
analysis showing that sulfur and the vinyl group are cis-orientated. Ten-membered lactam sulfides 6 are
obtained as the major product of SmI2 reduction of 3.
Introduction
Me
Me
N
O
Pharmacologically active benzothiazinone derivatives such as
semotiadil, a Ca2+ antagonist,1 or SPR-210, an aldose reductase
inhibitor, have been synthesised.2 Furthermore we earlier
synthesised medium-sized cyclic sulfides both by reduction of
bicyclic sulfonium salts bearing a bridgehead sulfur atom and
by treatment of the salts with a base; we also applied such
methods to bicyclic lactam sulfonium salts with a sulfonio
bridgehead to give medium-sized lactam sulfides by cleavage of
the cross-piece C᎐S bond.3 It has been recently reported that α-
chloro sulfides or thionium ions react with 1,3-dienes to form
the bicyclic sulfonium salts, which undergo rearrangement on
treatment with a base.4,5 We planned to prepare tricyclic lactam
sulfonium salts fused by a 5,6-dihydro-2H-thiopyran skeleton
and to synthesise new lactam sulfides with unusual ring skel-
etons by transformation of the salts with a reducing agent or a
base.6 In this paper we describe the synthesis and ring trans-
formation of benzothiazinium salts with a sulfonio bridgehead.
N
O
R3
i
ii
S
S
R3
Cl
2
1
Me
N
O
Me
N
Me
R3
O
N
O
S
ClO4
R3
S
R3
S
R1
2A
R2
3
3a : R1 = R2 = Me, R3 = H
3b : R1 = R2 = R3 = H
3c : R1 = Me, R2 = R3 = H
3d : R1 = R3 = H , R2 = Me
3e : R1 = R2 = R3 = Me
(82%)
(78%)
(67% : 3c / 3d = 2 / 1)
(11%)
Scheme 1 Reagents and conditions: i, NCS, CH2Cl2, 0 ЊC then room
temp. 5 h; ii, diene, AgClO4, CH3CN, 0 ЊC then room temp. 30 min
Synthesis of lactam sulfonium salts by [2++4] polar cycloaddition
Benzothiazinones 1, prepared according to the literature,7 were
treated with NCS (N-chlorosuccinimide). The resultant crude
α-chloro sulfides 2 reacted with 1,3-dienes such as buta-1,3-
diene, isoprene and 2,3-dimethylbuta-1,3-diene in the presence
of silver perchlorate via an α-thiocarbocation 2A to give benzo-
thiazinium salts 3 in moderate to good yield (Scheme 1). Iso-
prene adducts 3c and 3d were obtained as a mixture of regio-
isomers (3c:3d = 2:1, calculated from the intensities of methyl
Me
N
Me
N
O
O
i
R1
R2
S
S
ClO4
3a,b
R1
a : R1 = R2 = Me
b : R1 = R2 = H
4a,b
R2
1
groups in their H NMR spectrum).
Scheme 2 Reagents and conditions: i, reducing reagent, room temp.,
1 h–11 d, or electrolysis, MeCN, 1 h
Ring transformation of benzothiazinium salts
1
First, we reduced benzothiazinium salts 3 with magnesium, Zn–
AcOH or NaBH4 (Scheme 2, Table 1). Treatment of 3 with
magnesium in tetrahydrofuran (THF) at room temperature
gave spiro vinylcyclopropane derivatives 4 in moderate yield
although the reactions were very slow (over 10 days) (entries 1
and 4). Use of Zn in AcOH or NaBH4 in EtOH gave the spiro
compounds 4 faster and in higher yield (entries 2, 3, 5 and 6).
The structure of 4 was established from its 1H NMR, 13C NMR
and IR spectra. In the H NMR spectrum of 4a (taken as a
representative of vinylcyclopropanes 4) the pair of doublets
at δ 1.25 and 1.90 were assigned to the CH2 protons of the
cyclopropane ring, the small geminal coupling constant (J 6)
of which suggested a similar structure. The 13C NMR signal of
the methylene carbon of the cyclopropane ring was observed
at δ 20.9 and that of the terminal olefinic methylene carbon
appeared at δ 114.2. The IR spectrum showed absorptions for
J. Chem. Soc., Perkin Trans. 1, 1997
309

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Table 1 Reactions of benzothiazinium salts 3 with reducing reagents
NaBH4. We examined the reactions of 3 with a base in order to
confirm that the ionic mechanism is also a reasonable pathway.
Treatment of 3 with a variety of bases furnished vinylcyclopro-
panes 4 as summarised in Table 2. These experiments indicated
that both radical and ionic mechanisms may be possible for the
formation of vinylcyclopropanes.
We recently reported that the SET reduction of sulfonium
salts with SmI2 gave sulfides in high yield.9 Therefore, we
applied this method to the benzothiazinium salts 3 (Scheme 4,
Sulfonium
salt
Reducing
agent
Product
(% yield)
Entry
Solvent
Time
1
2
3
4
5
6
3a
3a
3a
3b
3b
3b
Mg
NaBH4
Zn
Mg
NaBH4
Zn
THF
10 d
1 h
2 h
11 d
2 h
1 h
4a (58)
4a (90)
4a (85)
4b (56)
4b (88)
4b (88)
EtOH
AcOH
THF
EtOH
AcOH
Me
N
Me
N
Me
N
O
O
O
R3
R3
R3
i
4
S
S
S
ClO4
R1
R1
R1
R2
R2
R2
7
3a,b,e
6
a : R1 = R2 = Me, R3 = H b : R1 = R2 = R3 = H
e : R1 = R2 = R3 = Me
Scheme 4 Reagents and conditions: i, SmI2, THF, Ϫ60 ЊC to room
temp., 2–15 h
Table 3). Thus, treatment of 3a with SmI2 (3.0 equiv.) in THF at
room temperature under a nitrogen atmosphere provided the 2-
allylbenzothiazinone derivative 7a (50%) together with the ten-
membered lactam sulfide 6a (22%) (entry 1). At a lower reaction
temperature (Ϫ60 ЊC), the yield of the lactam sulfide 6a
increased (55%) whilst vinylcyclopropane 4a (4%) and 7a (10%)
were also produced (entry 2). SmI2 reduction of 3b at room
temperature gave exclusively medium-sized lactam sulfide 6b
(91%) (entry 3). Reactions of 4a-methylbenzothiazinium salt 3e
lacking a 4a-hydrogen were also examined (entry 4). Treatment
of 3e with SmI2 (3.0 equiv.) in THF at 0 ЊC under a nitrogen
atmosphere provided ten-membered lactam sulfide 6e (49%
isolated yield) although reaction of 3e with MeLi (1.5 equiv.) in
diethyl ether at Ϫ20 ЊC gave a complex mixture.
Fig. 1 ORTEP Drawing of spirovinylcyclopropane 4a
the cyclopropyl CH at 3000 and 3080 cmϪ1. The relative con-
figuration of vinylcyclopropane 4a was determined by X-ray
crystallographic analysis (Fig. 1). All of the vinylcyclopropanes
4 gave satisfactory elemental analyses.
Two pathways, path a and path b, may explain the formation
of vinylcyclopropanes 4 (see Scheme 3). The first is by way of
1
The structures of 6 and 7 were determined from H and 13C
NMR spectroscopic results. In the 1H NMR spectrum of 6a, a
pair of doublets at δ 3.05 and 3.94 were assigned to the 10-CH2
protons (J 13). The signals of three methylene carbons were
observed at δ 30.7, 32.5 and 39.6 in the 13C NMR spectrum.
Compound 6a gave an elemental analysis consistent with the
proposed structure. The 1H NMR spectrum of 7a showed that a
doublet of doublets at δ 3.57 (J 6.5 and 9.5, 2-methine proton)
was coupled with a pair of doublet of doublets at δ 2.34 and
2.50 (J 9.5 and 14, 6.5 and 14, respectively, 1Ј-methylene pro-
tons) but showed no signal due to an olefinic proton. In the
13C NMR spectrum two tetrasubstituted olefinic carbons
appeared at δ 121.7 and 122.9, and three methyl carbons were
observed at δ 18.2, 20.3 and 20.8.
path a
Ionic
Mechanism
Me
N
Me
N
Me
N
a
O
O
H
O
Base
R1
R2
S
S
S
ClO4
R1
R1
b
e
4a, b
R2
R2
5
3a, b
Formation of 6 and 7 is also understandable in terms of a
radical mechanism via a sulfuranyl radical 8 (see Scheme 5),
generated by SET reduction of a sulfonium salt with SmI2.
Thus, SET reduction of 9 gives a samarium enolate 10 which is
converted into lactam sulfide 6 by protonation (path a). By path
b, allylic radicals 11 and 12 are formed by homolytic C᎐S
bond cleavage of 8 to furnish 2-allylbenzothiazinone 7 and
cyclopropyl derivative 4, respectively. However, predominant
formation of 6 rather than 4 and 7 may be explained by the
mechanism shown in Scheme 6. A radical cation 13 is formed
by the SET reduction of the carbonyl group which undergoes a
further SET reduction with homolytic cleavage of the cross-
piece C᎐S bond, followed by protonation to give lactam sulfide
6. Both mechanisms would account for the formation of lactam
sulfide 6.
a : R1 = R2 = Me
b : R1 = R2 = H
path b
Radical Mechanism
Scheme 3
an ionic mechanism (path a). Thus, abstraction of a bridgehead
proton by a reducing reagent, which acts as a base, produces an
ylide 5. This then, by attack of the ylide carbanion on the
olefinic carbon, undergoes ionic C᎐S bond cleavage to give 4.4,5
Since we earlier reported that sulfonium salts were reduced by
magnesium or Grignard reagents via the single electron transfer
(SET) process,8 we subjected 3a to electrolysis to confirm the
radical mechanism. In such a way compound 4a was obtained
(60%) by electrolytic reduction of 3a at Ϫ1.4 V vs. saturated
calomel electrode (SCE) in acetonitrile for 1 h. This result sug-
gests that the reactions of 3 with magnesium or Zn–AcOH
probably proceed via path b although it is unclear which radical
intermediates would be generated in the reaction system. How-
ever, the ionic mechanism may predominate in reactions with
Next, we examined the reactions of benzothiazinium salt 3b
with nucleophiles such as PhSNa, PhSH, PhSeNa and KCl
(Scheme 7, Table 4). Treatment of 3b with PhSNa (prepared
from PhSH and NaH) in DMF at 0 ЊC for 2 h provided vinyl-
310
J. Chem. Soc., Perkin Trans. 1, 1997

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Table 2 Reactions of benzothiazinium salts 3 with bases
Sulfonium
Product
Entry
salt
Base
Solvent
T/ЊC
Time
(% yield)
1
2
3
4
5
6
3a
3a
3a
3a
3b
3b
NaH
DMF
THF
EtOH
DMF
DMF
EtOH
0
0.5 h
Overnight
1 h
1 h
0.5 h
1 h
4a (98)
4a (42)
4a (57)
4a (94)
4b (96)
4b (55)
Mg(OH)2
Et3N
Room temp.
0
Room temp.
0
0
PriNH2
NaH
Et3N
Table 3 SmI2 reduction of benzothiazinium salts 3
Me
Me
Me
N
O
N
O
N
O
Products (% yield)
SPh
Sulfonium
salt
i
4b
Entry
t/h
T/ЊC
4
6
7
S
S
S
ClO4
3b
1
2
3
4
3a
3a
3b
3e
2
15
2
Room temp.
Ϫ60
Room temp.
—
4
—
—
22
55
91
49
50
10
—
—
X
15 (X = SPh)
16 (X = SePh)
17 (X = Cl)
14
3
Room temp.
Scheme 7 Reagents: i, nucleophile
Me
Me
N
Me
N
O
O
N
O
Me
N
Me
a
O
N
O
S
S
path a
S
i
b
ClO4
S
S
R1
R1
R1
O
e
9
R2
R2
R2
SmI2
8
PhSe
PhSe
16
3
18
path b
Me
N
Me
N
O
O
Me
N
Me
Me
OSmI2
N
S
O
N
O
S
S
H
S
m-ClC6H4CO2
20 (77%)
diastereoisomeric mixture
OH
S
OH
19 (21%)
SePh
R1
R1
R1
10
R2
11
12
R2
R2
Scheme 8 Reagents and conditions: i, MCPBA, CH2Cl2, Ϫ20 ЊC, 12 h
H
of allyl alcohols 19 was obtained (21%) by [2,3]-sigmatropic
rearrangement of the allyl selenoxide 18 together with selenide
20 (77%) as a diastereoisomeric mixture. The result indicates
that the compound 16 has an allyl selenide moiety.
4
7
6
Scheme 5
We also subjected vinylcyclopropanes 4a and 4b to thermal
rearrangement.10 Spirocyclopentene derivatives 21a (95%) and
21b (97%) were obtained by heating benzene solutions of 4a
and 4b respectively at 230 ЊC in a sealed tube (Scheme 9).
Me
N
Me
N
O
OSmI2
SmI2
6
S
S
ClO4
Me
N
Me
N
R1
R1
e
O
O
R2
R2
3
13
i
Scheme 6
R1
R2
S
R1
S
cyclopropane 4b (82%) together with ring-enlarged product 14
(1%) and ring-opened product 15 (11%) (entry 1). The ratio of
14 and 15 was reversed by use of PhSH as a nucleophile
although yields of the two were much lower (entries 2 and 3).
Reaction of 3b with PhSeNa [prepared from (PhSe)2 and
NaBH4] in EtOH at 0 ЊC afforded 4b (42%) and 16 (31%) (entry
4). When the reaction was carried out at Ϫ20 ЊC and then
warmed to room temperature the yield of 16 increased (94%)
and a trace of 4b was also formed (entry 5). Allyl chloride 17
was exclusively furnished by treatment of 3b with KCl in acet-
one at room temperature for 12 h. All of the compounds 14–17
have cis-J values for vic-olefinic protons in their 1H NMR spec-
tra. In order to determine whether compounds 15–17 are the
ring-opened products, we subjected compound 16 to MCPBA
oxidation in CH2Cl2 (Scheme 8). A diastereoisomeric mixture
a : R1 = R2 = Me
b : R1 = R2 = H
R2
(95%)
21a
21b (97%)
4a, b
Scheme 9 Reagents and conditions: i, sealed tube, benzene, 230 ЊC, 6 h
Conclusions
Lactam sulfonium salts bearing a dihydrothiopyran skeleton
with a sulfonio bridgehead, and benzothiazinium salts, havebeen
synthesised by the reaction of α-chloro sulfides with dienes in
the presence of silver perchlorate by [2++4] polar cycloaddition.
Treatment of benzothiazinium salts with Mg, NaBH4, Zn–
AcOH or a base furnished benzothiazinone derivatives with
a spirovinylcyclopropane ring. SmI2 reduction of the salts
afforded ten-membered lactam sulfides as the major products.
J. Chem. Soc., Perkin Trans. 1, 1997
311

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Table 4 Reactions of benzothiazinium salt 3b with nucleophiles
Entry
Nucleophile
Conditions
Products (% yield)
1
2
3
4
5
6
PhSNa
PhSH
PhSH
PhSeNa
PhSeNa
KCl
DMF, 0 ЊC, 2 h
DMF, room temp., 12 h
THF, reflux, 12 h
EtOH, 0 ЊC, 2 h
EtOH, Ϫ20 ЊC to room temp., 5 h
Acetone, room temp., 12 h
4b (82), 14 (1), 15 (11)
14 (9), 15 (2)
14 (11), 15 (6)
4b (42), 16 (31)
4b (2), 16 (94)
17 (100)
Thermal rearrangement of vinylcyclopropanes furnished spiro-
cyclopentene derivatives. Since some benzothiazinones1,2 pos-
sess potent pharmacological activity, all of the new compounds
with unusual skeletons synthesised in this paper are of
pharmacological interest.
ddd, J 2, 4 and 11, 2-H), 7.42 (1 H, t, J 8, ArH), 7.59 (1 H, d, J
8, ArH), 7.88 (1 H, t, J 8, ArH) and 7.92 (1 H, d, J 8, ArH);
δC(CD3CN) 24.5 (t), 33.6 (q), 34.6 (t), 42.9 (d), 105.3 (s), 116.8
(d), 120.8 (d), 126.0 (d), 130.0 (d), 134.4 (d), 137.7 (d), 142.9 (s)
and 161.1 (s).
3,6-Dimethyl-4,4a,5,6-tetrahydro-5-oxo-1H-thiopyrano[1,2-
a]-1,4-benzothiazinium perchlorate 3c and 2,6-dimethyl-4,4a,
5,6-tetrahydro-5-oxo-1H-thiopyrano[1,2-a]-1,4-benzothiazinium
perchlorate 3d. Yield 67% as a mixture of 3c and 3d, colourless
prisms (CH3CN–ether) (Found: C, 48.4; H, 4.7; N, 4.0.
C14H16ClNO5S requires C, 48.63; H, 4.66; N, 4.05%); νmax(KBr)/
cmϪ1 1670 (C=O) and 1080 (ClO4Ϫ); 3c δH (CD3CN) 1.88 (3 H, s,
Me), 2.83 (1 H, dd, J 5 and 19, 4-H), 3.31 (1 H, dd, J 2 and 19,
4-H), 3.50 (3 H, s, NMe), 4.13 (1 H, br d, J 16, 1-H), 4.17 (1 H,
dd, J 6 and 16, 1-H), 4.75 (1 H, dd, J 2 and 5, 4a-H), 5.58 (1 H,
br d, J 6, 2-H), 7.38–7.50 (2 H, m, ArH) and 7.84–7.94 (2 H, m,
ArH); δC(CD3CN) 23.7 (q), 28.1 (t), 32.9 (q), 34.0 (t), 42.6 (d),
104.7 (s), 110.5 (d), 120.2 (d), 125.4 (d), 134.0 (d), 137.0 (d),
138.3 (s), 142.2 (s) and 160.6 (s); 3d δH (CD3CN) 1.84 (3 H, s, Me),
2.72–2.92 (1 H, m, 4-H), 3.25–3.35 (1 H, m, 4-H), 3.50 (3 H, s,
NMe), 3.99 and 4.10 (each 1 H, br d, J 16, 1-H), 4.79 (1 H, dd, J
2 and 5, 4a-H), 5.82 (1 H, br s, 3-H), 7.38–7.50 (2 H, m, ArH)
and 7.84–7.94 (2 H, m, ArH); δC(CD3CN) 23.4 (q), 23.8 (t), 32.9
(q), 36.6 (t), 41.4 (d), 104.7 (s), 110.5 (d), 122.9 (d), 124.7 (s),
125.4 (d), 133.7 (d), 137.1 (d), 142.2 (s) and 160.5 (s).
2,3,4a,6-Tetramethyl-4,4a,5,6-tetrahydro-5-oxo-1H-thio-
pyrano[1,2-a]-1,4-benzothiazinium perchlorate 3e. This com-
pound was synthesised from 2,4-dimethyl-2H-1,4-benzo-
thiazin-3(4H)-one. Yield 11%, colourless prisms (acetone–
ether), mp 179–180 ЊC (Found: C, 51.15; H, 5.4; N, 3.8.
C16H20ClNO5S requires C, 51.40; H, 5.39; N, 3.74%); νmax(KBr)/
cmϪ1 1690 (C=O) and 1070 (ClO4Ϫ); δH (CD3CN) 1.57 (3 H, s,
Me), 1.76 (3 H, s, Me), 1.78 (3 H, s, Me), 2.67 (1 H, d, J 18.6, 4-
H), 3.38 (1 H, d, J 18.6, 4-H), 3.48 (3 H, s, NMe), 4.11 (2 H, br
s, 1-H), 7.45 (1 H, t, J 8, ArH), 7.51 (1 H, d, J 8, ArH), 7.90 (1
H, t, J 8, ArH) and 7.94 (1 H, d, J 8, ArH); δC(CD3CN) 19.4 (q),
19.9 (q), 21.4 (q), 33.7 (q), 38.6 (t), 40.5 (t), 50.6 (s), 103.7 (s),
117.6 (s), 120.8 (d), 126.4 (d), 130.1 (d), 135.2 (d), 137.8 (s),
142.0 (s) and 163.8 (s); m/z 289 (M+, 83%) and 241 (100).
Experimental
Melting points were obtained with a Yanagimoto micro melting
point apparatus and are uncorrected. IR Spectra of solids
(KBr) and liquids (NaCl) were recorded on a JASCO IRA-100
spectrophotometer. 1H NMR Spectra were recorded on a
Hitachi R-20B (60 MHz), a JEOL GX-270 (270 MHz) or a
JEOL EX-400 (400 MHz) spectrometer with tetramethylsilane
as an internal standard. 13C NMR Spectra and NOE spectra
were run on a JEOL EX-400 spectrometer. J Values are given in
Hz. Mass spectra were recorded on a JEOL JMS-D 300 spec-
trometer with a direct-insertion probe at 70 eV. Elemental
analyses of new compounds were performed by a YANACO
CHN CORDER MT-5. All chromatographic isolations were
achieved either with Kieselgel 60 (70–230 mesh) for column
chromatography or Kieselgel 60 PF254 containing gypsum for
preparative TLC. Ether refers to diethyl ether.
Synthesis of 6-methyl-4,4a,5,6-tetrahydro-5-oxo-1H-thiopyrano-
[1,2-a]-1,4-benzothiazinium perchlorates 3
General procedure. To a stirred solution of benzothiazinone
1 (5 mmol) in dry CH2Cl2 (25 cm3) was added NCS (5 mmol) at
0 ЊC. After 5 h at room temperature, the mixture was evapor-
ated and benzene was added to the residue. The precipitated
succinimide was filtered off and rinsed with benzene. The fil-
trate was concentrated under reduced pressure to give the crude
α-chloro sulfide 2. A solution of the crude product 2 and a
diene (10 mmol) in dry CH3CN (25 cm3) was treated with
AgClO4 (5 mmol) at 0 ЊC, and then stirred for 30 min at room
temperature. The precipitate of AgCl was filtered off and
washed with CH3CN. The filtrate was evaporated and the
resultant benzothiazinium salt
recrystallisation.
3
was purified by
2,3,6-Trimethyl-4,4a,5,6-tetrahydro-5-oxo-1H-thiopyrano-
[1,2-a]-1,4-benzothiazinium perchlorate 3a. Yield 82%, colour-
less prisms (CH3CN–ether), mp 164–165 ЊC (Found: C, 49.9; H,
5.1; N, 4.0. C15H18ClNO5S requires C, 50.07; H, 5.04; N,
3.89%); νmax(KBr)/cmϪ1 1675 (C=O) and 1080 (ClO4Ϫ);
δH (CD3CN) 1.77 (3 H, s, Me), 1.80 (3 H, s, Me), 2.82 (1 H, br d,
J 16, 4-H), 3.29 (1 H, br d, J 16, 4-H), 3.48 (3 H, s, NMe), 3.95
(1 H, d, J 15.6, 1-H), 4.12 (1 H, d, J 15.6, 1-H), 4.70 (1 H, dd, J
2 and 5, 4a-H), 7.41 (1 H, t, J 8, ArH), 7.49 (1 H, d, J 8, ArH),
7.87 (1 H, t, J 8, ArH) and 7.90 (1 H, d, J 8, ArH); δC(CD3CN)
19.0 (q), 19.1 (q), 29.0 (t), 32.5 (q), 36.9 (t), 41.7 (d), 104.4 (s),
116.8 (s), 119.7 (d), 125.0 (d), 129.0 (s), 133.4 (d), 136.6 (d),
141.8 (s) and 160.2 (s).
6-Methyl-4,4a,5,6-tetrahydro-5-oxo-1H-thiopyrano[1,2-a]-
1,4-benzothiazinium perchlorate 3b. Yield 78%, colourless
prisms (CH3CN–ether), mp 168–169 ЊC (Found: C, 46.8;
H, 4.2; N, 4.2. C13H14ClNO5S requires C, 47.06; H, 4.25;
N, 4.22%); νmax(KBr)/cmϪ1 1670 (C=O) and 1070 (ClO4Ϫ);
δH (CD3CN) 2.79 –2.92 (1 H, m, 4-H), 3.41 (1 H, ddd, J 2, 5 and
7, 4-H), 3.48 (3 H, s, NMe), 4.05–4.23 (2 H, m, 1-H), 4.75 (1 H,
br d, J 5, 4a-H), 5.84 (1 H, ddd, J 2, 6 and 11, 3-H), 6.12 (1 H,
Reduction of benzothiazinium salts 3 with magnesium
General procedure. A mixture of benzothiazinium salt (1
mmol) and magnesium (73 mg, 3 mmol) in dry THF (20 cm3)
was stirred at room temperature for several days. Saturated
aqueous NH4Cl was added to the reaction mixture which was
then stirred until the excess of magnesium had dissolved. The
organic layer was separated and the water layer was extracted
with ether. The organic layer and the extracts were combined,
washed successively with water and saturated brine, dried
(MgSO4) and evaporated under reduced pressure. The residue
was purified by preparative TLC eluting with ethyl acetate–
hexane (1:10). Reaction conditions and the results are summar-
ised in Table 1.
2Ј-Isopropenyl-2Ј,4-dimethyl-2H-benzothiazine-2-
spirocyclopropan-3(4H)-one 4a. Colourless prisms (CH2Cl2), mp
87–89 ЊC (Found: C, 69.7; H, 6.7; N, 5.4. C15H17NOS requires
C, 69.46; H, 6.61; N, 5.37%); νmax(KBr)/cmϪ1 3080 and 3000
(cyclopropane) and 1660 (C=O); δH (CDCl3) 1.14 (3 H, s, Me),
1.27 (3 H, s, Me), 1.25 (1 H, d, J 6, 3Ј-H), 1.90 (1 H, d, J 6,
3Ј-H), 3.49 (3 H, s, NMe), 4.71 (1 H, br s, olefinic H), 4.94 (1 H,
312
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br s, olefinic H), 6.98 (1 H, t, J 8, ArH), 7.06 (1 H, d, J 8 ArH)
and 7.20–7.27 (2 H, m, ArH); δC(CDCl3) 18.1 (q), 20.8 (q), 20.9
(t), 32.4 (s), 33.0 (q), 38.6 (s), 114.2 (t), 117.3 (d), 123.0 (d),
125.0 (s), 126.8 (d), 127.8 (d), 139.6 (s), 144.1 (s) and 167.0 (s);
m/z 259 (M+, 18%) and 121 (100).
ium salt 3 (0.5 mmol) in EtOH (5 cm3) was added triethylamine
(5 cm3) at room temperature. After 1 h, 3  hydrochloric acid
was added to the reaction mixture which was then extracted
with CH2Cl2. The extracts were dried (MgSO4) and evaporated
under reduced pressure. The residue was purified by preparative
TLC eluting with ethyl acetate–hexane (1:10). Reaction condi-
tions and the results are summarised in Table 2.
4-Methyl-2Ј-vinyl-2H-benzothiazine-2-spirocyclopropane-
3(4H)-one 4b. Colourless prisms (CH2Cl2), mp 81–82 ЊC
(Found: C, 73.35; H, 6.1; N, 6.6. C13H13NOS requires C, 73.20;
H, 6.14; N, 6.57%); νmax(KBr)/cmϪ1 3090 and 3000 (cyclo-
propane) and 1660 (C=O); δH (CDCl3) 1.04 (1 H, dd, J 5.5 and 7,
3Ј-H), 1.98 (1 H, dd, J 5.5 and 9, 3Ј-H), 2.22 (1 H, ddd, J 7, 8.5
and 9, 2Ј-H), 3.41 (3 H, s, NMe), 5.11 (1 H, dd, J 1.5 and 10,
CH=CH2), 5.15 (1 H, dd, J 1.5 and 17, CH=CH2), 5.56 (1 H,
ddd, J 8.5, 10 and 17, 4Ј-H), 6.98–7.03 (2 H, m, ArH) and 7.21–
7.29 (2 H, m, ArH); δC(CDCl3) 19.5 (t), 29.4 (s), 29.8 (d), 32.7
(q), 116.8 (d), 118.1 (t), 122.3 (s), 123.3 (d), 127.2 (d), 128.1 (d),
133.8 (d), 139.9 (s) and 169.3 (s); m/z 231 (M+, 20%) and 121
(100).
Reaction of benzothiazinium salt 3a with magnesium hydroxide
A suspension of 3a (180 mg, 0.5 mmol) and Mg(OH)2 (1
mmol) in dry THF (2 cm3) was stirred at room temperature
overnight after which it was diluted with water and extracted
with ethyl acetate. The extracts were washed with water, dried
(MgSO4) and evaporated under reduced pressure. The residue
was purified by preparative TLC eluting with ethyl acetate–
hexane (1:5) to give 4a (55 mg, 42%).
Reaction of benzothiazinium salt 3a with isopropylamine
To a stirred solution of 3a (180 mg, 0.5 mmol) in dry DMF was
added isopropylamine (0.55 mmol) at room temperature. After
1 h the reaction mixture was diluted with water and extracted
with ethyl acetate. The extracts were washed with water, dried
(MgSO4) and evaporated under reduced pressure. The residue
was purified by preparative TLC eluting with ethyl acetate–
hexane (1:5) to give 4a (122 mg, 94%).
Reactions of benzothiazinium salts 3 with sodium borohydride
General procedure. To a suspension of benzothiazinium salt 3
(1 mmol) in EtOH (5 cm3) was added NaBH4 (1.0–1.1 mmol)
at 0 ЊC. After the reaction mixture had been stirred at room
temperature for several hours, it was diluted with water and
extracted with CH2Cl2. The extracts were washed successively
with water and saturated brine, dried (MgSO4) and evaporated
under reduced pressure. The residue was purified by preparative
TLC eluting with ethyl acetate–hexane (1:10). Reaction condi-
tions and the results are summarised in Table 1.
Reduction of benzothiazinium salts 3 with samarium diiodide
General procedure. To a suspension of benzothiazinium salt 3
(1 mmol) in THF (5 cm3) containing MeOH (0.6 cm3) was
added 0.1  SmI2 solution in THF 11 (30 cm3, 3 mmol) at 0 ЊC
under a nitrogen atmosphere. After 2 h at room temperature the
reaction mixture was treated with conc. hydrochloric acid and
extracted with ether. The extracts were washed successively with
saturated aqueous NaHCO3, 10% aqueous Na2S2O3 and water,
dried (MgSO4) and evaporated under reduced pressure. The
residue was purified by preparative TLC eluting with ethyl
acetate–hexane (1:10). Reaction conditions and the results are
summarised in Table 3.
Reduction of benzothiazinium salts 3 with zinc in acetic acid
General procedure. To a solution of benzothiazinium salt 3 (1
mmol) in acetic acid was added activated Zn (washed succes-
sively with alcohol and ether, and dried under reduced pres-
sure). After several hours, the inorganic materials were filtered
off and ether was added to the filtrate. This was then washed
successively with 5% aqueous NaOH and water. The alkaline
and aqueous layers were combined and back-extracted with
ether. The organic layer and extracts were combined, dried
(MgSO4) and evaporated under reduced pressure. The residue
was purified by preparative TLC eluting with ethyl acetate–
hexane (1:10). Reaction conditions and the results are summar-
ised in Table 1.
3,4,8-Trimethyl-5,6,7,8-tetrahydro-2H-benzo[b][1,4]-
thiazecin-7-one 6a. Colourless prisms (CH2Cl2), mp 82 ЊC
(Found: C, 68.8; H, 7.3; N, 5.4. C15H19NOS requires C, 68.93;
H, 7.33; N, 5.36%); νmax(KBr)/cmϪ1 1680 (C=O); δH (CDCl3)
1.39 (3 H, s, Me), 1.64 (3 H, s, Me), 1.96 (1 H, ddd, J 3, 7 and
14, 5-H), 2.27 (1 H, ddd, J 3, 8 and 14, 6-H), 2.31 (1 H, ddd, J 3,
7 and 14, 6-H), 2.47 (1 H, ddd, J 3, 8 and 14, 5-H), 3.03 (1 H, d,
J 13, 2-H), 3.31 (3 H, s, NMe), 3.94 (1 H, d, J 13, 2-H), 7.17 (1
H, dd, J 1.5 and 7, ArH), 7.25 (1 H, dt, J 1.5 and 7, ArH), 7.36
(1 H, dt, J 1.5 and 7, ArH) and 7.59 (1 H, dd, J 1.5 and 7, ArH);
δC(CDCl3) 17.9 (q), 19.6 (q), 30.7 (t), 32.5 (t), 36.3 (q), 39.6 (t),
125.6 (s), 128.3 (d), 129.1 (d), 130.0 (d), 132.8 (s), 133.3 (s),
138.3 (d), 147.9 (s) and 174.7 (s); m/z 261 (M+, 30%) and 166
(100).
2-(2,3-Dimethylbut-2-enyl)-4-methyl-2H-1,4-benzothiazin-3-
one 7a. Yellow oil (Found: C, 69.0; H, 7.3; N, 5.4. C15H19NOS
requires C, 68.93; H, 7.33; N, 5.36%); νmax(NaCl)/cmϪ1 1680
(C=O); δH (CDCl3) 1.47 (3 H, s, Me), 1.65 (6 H, s, Me × 2), 2.34
(1 H, dd, J 9.5 and 14, 1Ј-H), 2.50 (1 H, dd, J 6.5 and 14, 1Ј-H),
3.44 (3 H, s, NMe), 3.57 (1 H, dd, J 6.5 and 9.5, 2-H), 6.99–7.07
(2 H, m, ArH) and 7.22–7.36 (2 H, m, ArH); δC(CDCl3) 18.2
(q), 20.3 (q), 20.8 (q), 32.2 (q), 34.3 (t), 42.4 (d), 117.0 (d), 121.7
(s), 122.9 (s), 123.3 (d), 127.0 (d), 128.6 (s), 129.0 (d), 140.0 (s)
and 167.3 (s); m/z 261 (M+, 24%) and 179 (100).
Electrolysis of 3a
Electrolysis was performed under potentiostatic conditions
with a three-electrode system consisting of a carbon working
electrode, a saturated calomel reference electrode (SCE) and a
Pt counter electrode. Benzothiazinium salt 3a was dissolved in
acetonitrile containing tetraethylammonium perchlorate (0.15
mol dmϪ3) as a supporting electrolyte. The reduction was carried
out at Ϫ1.4 V vs. SCE for 1 h after which the reaction mixture
was diluted with water and extracted with CH2Cl2. The extracts
were washed with water, dried (MgSO4) and evaporated under
reduced pressure. The residue was purified by preparative TLC
eluting with ethyl acetate–hexane (1:5) to give 4a (60%).
Reactions of benzothiazinium salts 3 with sodium hydride
General procedure. To a stirred suspension of NaH (60% in
paraffin oil; 1.1 mmol) in dry DMF (2 cm3) was added benzo-
thiazinium salt 3 (1 mmol) at 0 ЊC. After 30 min at room tem-
perature, the reaction mixture was diluted with water and
extracted with ethyl acetate. The extracts were washed with
water, dried (MgSO4) and evaporated under reduced pressure.
The residue was purified by preparative TLC eluting with ethyl
acetate–hexane (1:5). Reaction conditions and the results are
summarised in Table 2.
8-Methyl-5,6,7,8-tetrahydro-2H-benzo[b][1,4]thiazecin-7-one
6b. Colourless prisms (CH2Cl2), mp 79–80 ЊC (Found: C, 66.7;
H, 6.4; N, 6.0. C13H15NOS requires C, 66.92; H, 6.48; N,
6.01%); νmax(KBr)/cmϪ1 1690 (C=O); δH (CDCl3) 2.02–2.11 (1 H,
m, 5-H), 2.21–2.41 [3 H, m, 6-H (2 H) and 5-H (1 H)], 3.10 (1 H,
dd, J 5 and 13, 2-H), 3.32 (3 H, s, NMe), 3.77 (1 H, dd, J 10.5
and 13, 2-H), 5.41–5.51 (2 H, m, 4-H and 3-H), 7.18 (1 H, dd,
J 1.5 and 7, ArH), 7.28 (1 H, dt, J 1.5 and 7, ArH), 7.36 (1 H,
Reactions of benzothiazinium salts 3 with triethylamine
General procedure. To a stirred suspension of benzothiazin-
J. Chem. Soc., Perkin Trans. 1, 1997
313

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dt, J 1.5 and 7, ArH) and 7.60 (1 H, dd, J 1.5 and 7, ArH);
δC(CDCl3) 23.1 (t), 31.9 (t), 36.2 (q), 53.6 (t), 128.2 (d), 128.5
(d), 129.1 (d), 129.8 (d), 131.1 (d), 132.6 (s), 137.7 (d), 146.8 (s)
and 174.9 (s); m/z 233 (M+, 23%) and 139 (100).
Reaction of benzothiazinium salt 3b with PhSeNa
Method A. To a stirred solution of PhSeNa [prepared from
(PhSe)2 (312 mg, 1 mmol) and NaBH4 (10 mg, 0.26 mmol)] in
EtOH (5 cm3) was added 3b (166 mg, 0.5 mmol) at 0 ЊC. After
2 h, the reaction mixture was diluted with water (10 cm3) and
extracted with ethyl acetate. The extracts were washed with
water, dried (MgSO4) and evaporated under reduced pressure.
The residue was purified by preparative TLC eluting with ethyl
acetate–hexane (1:5) to give 4b (48 mg, 42%) and (Z)-4-methyl-
2-(4-phenylselenobut-2-enyl)-2H-benzothiazin-3(4H)-one 16
(61 mg, 31%).
Compound 16. Yellow oil (Found: C, 58.8; H, 5.0; N, 3.6.
C19H19NOSSe requires C, 58.76; H, 4.93; N, 3.61%);
νmax(NaCl)/cmϪ1 1670 (C=O); δH (CDCl3) 2.12 (1 H, ddd, J 7.3,
8.8 and 15, 1Ј-H), 2.40 (1 H, ddd, J 6.4, 7.3 and 15, 1Ј-H), 3.13
(1 H, dd, J 6.4 and 8.8, 2-H), 3.40 (2 H, d, J 7.3, 4Ј-H), 3.42 (3
H, s, NMe), 5.46 (1 H, dt, Jcis 11 and 7.3, olefinic H), 5.74 (1 H,
dt, Jcis 11 and 7.3, olefinic H), 7.00–7.05 (2 H, m, ArH), 7.16–
7.20 (3 H, m, ArH), 7.25 (1 H, t, J 7, ArH), 7.32 (1 H, d, J 6,
ArH) and 7.41–7.44 (2 H, m, ArH); δC(CDCl3) 24.6 (t), 26.5 (t),
32.3 (q), 42.9 (d), 117.2 (d), 121.6 (s), 123.4 (d), 127.1 (d), 127.3
(d), 128.5 (d), 128.7 (d), 128.8 (d), 129.6 (s), 134.0 (d), 139.7 (s)
and 166.8 (s); m/z 389 (M+), 232 (M+ Ϫ SePh, 100%) and 157
(SePh, 5).
3,4,6,8-Tetramethyl-5,6,7,8-tetrahydro-2H-benzo[b][1,4]-
thiazecin-7-one 6e. White powder, mp 93–96 ЊC (Found:
275.1362. C16H21NOS requires 275.1344); νmax(KBr)/cmϪ1 1650
(C=O); δH (CDCl3) 1.18 (3 H, d, J 6.8, 6-Me), 1.35 (3 H, s, Me),
1.50 (1 H, d, J 14.2, 5-H), 1.62 (3 H, s, Me), 2.38 (1 H, quintet,
J 6.8, 6-H), 2.76 (1 H, dd, J 6.8 and 14.2, 5-H), 2.87 (1 H, d,
J 12.7, 2-H), 3.33 (3 H, s, NMe), 4.11 (1 H, d, J 12.7, 2-H), 7.08
(1 H, d, J 7, ArH), 7.22 (1 H, t, J 7, ArH), 7.34 (1 H, t, J 7, ArH)
and 7.54 (1 H, d, J 7, ArH); δC(CDCl3) 17.4 (q), 20.2 (q), 20.9
(q), 35.7 (q), 36.0 (d), 38.7 (t), 40.2 (t), 124.1 (s), 128.0 (d), 129.1
(d), 129.7 (d), 131.8 (s), 133.5 (s), 137.9 (d), 147.6 (s) and 178.1
(s); m/z 275 (M+, 14%) and 166 (100).
Reaction of benzothiazinium salt 3b with PhSNa
To a stirred solution of PhSNa [0.5 mmol; prepared from PhSH
(55 mg) and NaH in paraffin oil (60%; 20 mg)] in DMF (1.5
cm3) was added 3b (166 mg, 0.5 mmol) at 0 ЊC. After 2 h, the
reaction mixture was diluted with water (5 cm3) and extracted
with ethyl acetate. The extracts were washed with water, dried
(MgSO4) and evaporated under reduced pressure. The residue
was purified by preparative TLC eluting with ethyl acetate–
hexane (1:5) to give 4b (96 mg, 82%), (Z)-8-methyl-6-phenyl-
thio-5,6,7,8-tetrahydro-2H-benzo[b][1,4]thiazecin-7-one 14 (2
mg, 1%) and (Z)-4-methyl-2-(4-phenylthiobut-2-enyl)-2H-
benzothiazin-3(4H)-one 15 (18 mg, 11%).
Compound 14. Yellow oil (Found: 341.0890. C19H19NOS2
requires 341.0908); νmax(NaCl)/cmϪ1 1665 (C=O); δH (CDCl3)
2.25 (1 H, ddd, J 5, 9 and 15, 5-H), 2.52–2.58 (1 H, m, 5-H), 3.28
(1 H, dd, J 6 and 9, 6-H), 3.42 (3 H, s, NMe), 3.43 and 3.50
(each 1 H, dd, J 5 and 12, 2-H), 5.52 (1 H, dt, Jcis 10 and J 5, 3-
H), 5.51–5.56 (1 H, m, 4-H), 7.00–7.07 (2 H, m, ArH), 7.13 (1
H, t, J 8, ArH), 7.20–7.27 (3 H, m, ArH) and 7.30–7.35 (3 H, m,
ArH); δC(CDCl3) 31.9 (t), 32.4 (q), 36.2 (t), 43.1 (d), 117.2 (d),
121.7 (s), 123.4 (d), 126.2 (d), 127.1 (d), 128.7 (d), 128.8 (d),
129.0 (d), 130.1 (d), 135.8 (s), 139.7 (s) and 137.0 (s); m/z 341
(M+, 2%) and 232 (100).
Compound 15. Yellow oil (Found: 341.0932. C19H19NOS2
requires 341.0908) νmax(NaCl)/cmϪ1 1660 (C=O); δH (CDCl3)
2.22 (1 H, ddd, J 7.3, 8.8 and 15, 1Ј-H), 2.51 (1 H, ddd, J 6.3, 7.3
and 15, 1Ј-H), 3.22 (1 H, dd, J 6.3 and 8.8, 2-H), 3.42 (2 H, d,
J 7.8, 4Ј-H), 3.43 (3 H, s, NMe), 5.55 (1 H, dt, Jcis 10 and 7.3,
2Ј-H), 5.67 (1 H, dt, Jcis 10 and 7.8, 3Ј-H), 7.01–7.07 (2 H,
m, ArH), 7.13 (1 H, t, J 7, ArH) and 7.20–7.36 (6 H, m, ArH);
δC(CDCl3) 26.9 (t), 31.5 (t), 32.4 (q), 43.1 (d), 117.3 (d), 121.6 (s)
123.5 (d), 126.5 (d), 127.2 (d), 128.0 (d), 128.8 (d), 128.9 (d),
130.6 (d), 135.7 (s), 139.7 (s) and 166.9 (s); m/z 341 (M+, 2%),
232 (M+ Ϫ SPh, 100) and 109 (SPh, 52).
Method B. To a stirred solution of PhSeNa [prepared from
(PhSe)2 (312 mg, 1 mmol) and NaBH4 (10 mg, 0.26 mmol)] in
EtOH (5 cm3) was added 3b (166 mg, 0.5 mmol) at Ϫ20 ЊC.
After 5 h at Ϫ20 ЊC, warming to room temperature, the reaction
mixture was diluted with water (10 cm3) and extracted with
ethyl acetate. The extracts were washed with water, dried
(MgSO4) and evaporated under reduced pressure. The residue
was purified by preparative TLC eluting with ethyl acetate–
hexane (1:5) to give 4b (2 mg, 2%) and 16 (183 mg, 94%).
Reaction of benzothiazinium salt 3b and KCl
To a stirred suspension of KCl (8 mg, 0.1 mmol) in acetone (3
cm3) was added 3b (33 mg, 0.1 mmol) at room temperature.
After 12 h, the reaction mixture was diluted with water (10 cm3)
and extracted with ethyl acetate. The extracts were washed with
water, dried (MgSO4) and evaporated under reduced pressure.
The residue was purified by preparative TLC eluting with ethyl
acetate–hexane (1:10) to give (Z)-2-(4-chloro-but-2-enyl)-4-
methyl-2H-benzothiazin-3(4H)-one 17 (27 mg, 100%) as a col-
ourless oil (Found: C, 58.8; H, 5.0; N, 3.6. C13H14CINOS
requires C, 58.76; H, 4.93; N, 3.61%); νmax(NaCl)/cmϪ1 1660
(C=O); δH (CDCl3) 2.42 (1 H, ddd, J 7, 8 and 15, 1Ј-H), 2.68 (1
H, dt, J 15 and 7, 1Ј-H), 3.45 (1 H, dd, J 7 and 8, 2-H), 3.45 (3
H, s, NMe), 3.94 (2 H, d, J 7, 4Ј-H), 5.66 and 5.79 (each 1 H, dt,
Jcis 11 and 7, olefinic H), 7.02–7.10 (2 H, m, ArH) and 7.25–7.37
(2 H, m, ArH); δC(CDCl3) 27.0 (t), 32.4 (q), 38.9 (t), 42.7 (d),
117.3 (d), 121.2 (s), 123.5 (d), 127.3 (d), 128.4 (d), 128.8 (d),
129.5 (d), 139.6 (s) and 166.6 (s); m/z 267 (M+, 17%), 232 (M+ Ϫ
Cl, 98) and 150 (100).
Reaction of benzothiazinium salt 3b with PhSH
Method A. To a stirred solution of PhSH (110 mg, 1 mmol) in
DMF (1.5 cm3) was added 3b (166 mg, 0.5 mmol) at room
temperature. After 12 h, the reaction mixture was diluted with
water (5 cm3) and extracted with ethyl acetate. The extracts were
washed with water, dried (MgSO4) and evaporated under
reduced pressure. The residue was purified by preparative TLC
eluting with ethyl acetate–hexane (1:5) to give 14 (15 mg, 9%)
and 15 (4 mg, 2%).
Method B. To a stirred solution of PhSH (110 mg, 1 mmol) in
THF (2 cm3) was added 3b (166 mg, 0.5 mmol) at room tem-
perature under a nitrogen atmosphere. The mixture was
refluxed for 12 h after which it was cooled, diluted with water (5
cm3) and extracted with ethyl acetate. The extracts were washed
with water, dried (MgSO4) and evaporated under reduced pres-
sure. The residue was purified by preparative TLC eluting with
ethyl acetate–hexane (1:5) to give 14 (19 mg, 11%) and 15 (10
mg, 6%).
MCPBA oxidation of allyl selenide 16
To a stirred solution of allyl selenide 16 (183 mg, 0.47 mmol) in
CH2Cl2 (5 cm3) with ice–NaCl cooling was added MCPBA
(85% purity; 95 mg, 0.47 mmol) in several portions. After 12 h,
saturated aqueous NaHCO3 was added to the reaction mixture
and the organic layer was separated, dried (MgSO4) and con-
centrated under reduced pressure. The residue was purified by
preparative TLC eluting with ethyl acetate–hexane (1:2) to give
as the third fraction 2-(2-hydroxybut-3-enyl)-4-methyl-2H-
benzothiazin-3(4H)-one 19 (25 mg, 21%), a light yellow oil as a
mixture of diastereoisomers (Found: 249.0812. C13H15NO2S
requires 249.0824); νmax(NaCl)/cmϪ1 3420 (OH) and 1655
(C=O); δH (CDCl3) of major isomer 1.85 (1 H, ddd, J 5.9, 8 and
14, 1Ј-H), 2.13 (1 H, ddd, J 5, 8.8 and 14, 1Ј-H), 2.92 (1 H, br s,
OH), 3.46 (3 H, s, NMe), 3.61 (1 H, dd, J 5.9 and 8.8, 2-H), 4.33
(1 H, br s, 2Ј-H), 5.12 (1 H, d, Jcis 10, 4Ј-H), 5.29 (1 H, d, Jtrans
314
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17, 4Ј-H), 5.81 (1 H, ddd, J 6, 10 and 17, 3Ј-H), 7.02–7.09 (2 H,
m, ArH), 7.27 (1 H, t, J 8, ArH) and 7.36 (1 H, d, J 8, ArH); of
minor isomer 1.70–1.80 (1 H, m, 1Ј-H), 2.06–2.15 (1 H, m, 1Ј-
H), 2.67 (1 H, br s, OH), 3.44 (3 H, s, NMe), 3.67 (1 H, dd, J 7
and 8, 2-H), 4.32 (1 H, br s, 2Ј-H), 5.09 (1 H, d, Jcis 9, 4Ј-H), 5.25
(1 H, d, Jtrans 17, 4Ј-H), 5.76–5.84 (1 H, m, 3Ј-H), 6.97–7.08 (2
H, m, ArH), 7.25 (1 H, t, J 7, ArH) and 7.52 (1 H, d, J 7, ArH);
δC(CDCl3) of major isomer 32.6 (q), 36.7 (t), 39.4 (d), 70.3 (d),
115.6 (t), 117.4 (d), 122.2 (s), 123.6 (d), 127.2 (d), 128.6 (d),
139.5 (s) and 168.0 (s); of minor isomer 32.6 (q), 36.4 (t), 40.3
(d), 70.0 (d), 114.9 (t), 117.4 (d), 123.4 (d), 123.5 (d), 127.2 (d),
128.6 (d), 140.2 (s) and 168.2 (s); m/z 249 (M+, 100%). [3-(3-
Chlorobenzoyloxy)-2-hydroxy-4-phenylselenobutyl]-4-methyl-
2H-benzothiazin-3(4H)-one 20 was isolated as a mixture of
diastereoisomers composing the first (129 mg, 49%) and the
second (74 mg, 28%) fractions, respectively; the first fraction
was a yellow oil (Found: 561.0266. C26H24ClNO4SSe requires
561.0280); νmax(NaCl)/cmϪ1 3450 (OH), 1730 (C=O) and 1665
(C=O); δH (CDCl3) 2.11–2.16 (1 H, m, 1Ј-H), 2.18 (1 H, br s,
OH), 2.32–2.39 (1 H, m, 1Ј-H), 3.39 (3 H, s, NMe), 3.61 (1 H, br
m, 3Ј-H), 3.71 (1 H, dd, J 5 and 9, 2-H), 4.15 (1 H, br m, 2Ј-H),
4.60 (1 H, dd, J 5 and 11, 4Ј-H), 4.70 (1 H, d, J 9 and 11, 4Ј-H),
7.01–7.03 (2 H, m, ArH), 7.23 (4 H, br m, ArH), 7.30–7.36 (2 H,
m, ArH), 7.50 (1 H, d, J 7, ArH), 7.52–7.57 (2 H, m, ArH), 7.82
(1 H, d, J 8, ArH), and 7.91 (1 H, s, ArH); δC(CDCl3) 32.4 (q),
36.1 (t), 40.0 (d), 51.1 (d), 65.6 (t), 68.2 (d), 117.3 (d), 121.9 (s),
123.6 (d), 127.2 (d), 127.7 (d), 128.4 (s), 128.6 (d), 129.2 (d),
129.5 (d), 129.6 (d), 131.5 (s), 133.0 (d), 134.2 (d), 134.4 (s),
139.3 (s), 165.0 (s) and 167.5 (s); m/z 561 (M+, 3%) and 139
(100); the second fraction was also a yellow oil (Found:
561.0273. C26H24ClNO4SSe requires 561.0279); νmax(NaCl)/
cmϪ1 3430 (OH), 1720 (C=O) and 1660 (C=O); δH (CDCl3) 1.85
(1 H, ddd, J 7, 8 and 12, 1Ј-H), 1.94 (1 H, br s, OH), 2.57 (1 H,
ddd, J 7, 10 and 12, 1Ј-H), 3.44 (3 H, s, NMe), 3.67 (1 H, t, J 7,
2-H), 3.79 (1 H, br m, 3Ј-H), 4.21 (1 H, br m, 2Ј-H), 4.61 (1 H,
dd, J 5 and 12, 4Ј-H), 4.71 (1 H, dd, J 9 and 12, 4Ј-H), 6.98 (1 H,
t, J 7, ArH), 7.06 (1 H, d, J 8, ArH), 7.23–7.28 (5 H, m, ArH),
7.36 (1 H, t, J 8, ArH), 7.52 (1 H, d, J 8, ArH), 7.57–7.59 (2 H,
m, ArH), 7.85 (1 H, d, J 7, ArH) and 7.93 (1 H, s, ArH);
δC(CDCl3) 32.9 (q), 35.5 (t), 41.2 (d), 51.9 (d), 65.9 (t), 68.5 (d),
117.7 (d), 122.1 (s), 123.9 (d), 127.6 (d), 128.1 (d), 128.7 (s),
128.8 (d), 129.5 (d), 129.9 (d), 130.0 (d), 131.8 (s), 133.4 (d),
134.6 (d), 134.8 (s), 139.8 (s), 165.4 (s) and 168.5 (s); m/z 561
(M+, 6%) and 139 (100).
X-Ray study of 2Ј-isopropenyl-2Ј,4-dimethyl-2H-benzothiazine-
2-spirocyclopropan-3(4H)-one 4a
A colourless prism was mounted on a glass fibre and trans-
ferred to the diffractometer.
Crystal data. C15H17NOS, M = 259.37. Monoclinic, a =
11.825(3), b = 9.659(3), c = 12.386(3) Å, β = 103.79(2)Њ, V =
1373.9(5) Å3 (from setting angles of 20 centred reflections
with 20.1 ≤ 2θ ≤ 26.4Њ, λ = 0.710 73 Å, T = 298 K), space group
P21/a (alt P21/c, No. 14), Z = 4, Dx = 1.254 cm3, colourless
prism 0.2 × 0.2 × 0.1 mm, µ(Mo-Kα) = 0.213 mmϪ1
.
Data collection and processing. Rigaku AFC-5R four-circle
diffractometer with 12 kW rotating anode generator, ω/2θ
scans with
ω scan width (1.52 + 0.30 tan θ)Њ, graphite-
monochromated Mo-Kα X-radiation; 3508 reflections meas-
ured to 2θmax = 55Њ, 3354 unique (merging R = 0.046), giving
1443 with F ≥ 6σ(F) which were retained in all calculations. No
crystal decay was observed and no corrections were applied for
absorption.
Structure solution and refinement. Automatic direct
methods12 (all non-H atoms). Full-matrix least-squares refine-
ment 13 with all non-H atoms anisotropic.
2
2
The weighting scheme w = 4Fo /σ2(Fo ) gave satisfactory
agreement analyses. Final R = 0.047, Rw = 0.051, S = 1.45 for
163 refined parameters. The final ∆F synthesis showed no peaks
above ± 0.20 e ÅϪ3
.
Detailed crystallographic results for this study have been
deposited with the Cambridge Crystallographic Data Centre.
Any requests for this material should be accompanied by a full
bibliographic citation together with the reference number
CCDC 207/64. For details of this scheme, see Instructions for
Authors (1997), J. Chem. Soc., Perkin Trans. 1, 1997, Issue 1.
Acknowledgements
We are grateful to Dr Kenji Kano for the electroreduction
studies. This work was supported in part by a grant from the
Ministry of Education, Science and Culture.
References
1 M. Fujita, S. Ito, A. Ota, N. Kato, K. Yamamoto, Y. Kawashima,
H. Yamauchi and J. Iwao, J. Med. Chem., 1990, 33, 1898; A. Ota,
H. Suhara and Y. Kawashima, Chem. Pharm. Bull., 1992, 40, 833.
2 T. Aotsuka, H. Hosono, T. Kurihara, Y. Nakamura, T. Matsui and
F. Kobayashi, Chem. Pharm. Bull., 1994, 42, 1264.
3 T. Kataoka, K. Tsutsumi, T. Iwama, H. Shimizu and M. Hori,
Tetrahedron Lett., 1990, 31, 3027; T. Kataoka, T. Iwama, K. Tsut-
sumi, Y. Nakamura, H. Matsumoto, H. Shimizu and M. Hori,
J. Chem. Res., 1992 (S), 393; (M), 3153.
4 E. J. Corey and S. W. Walinsky, J. Am. Chem. Soc., 1972, 94, 8932;
H. Ishibashi, Y. Kitano, H. Nakatani, M. Okada, M. Ikeda,
M. Okura and Y. Tamura, Tetrahedron Lett., 1984, 25, 423; H. Ishi-
bashi, Y. Kitano, H. Nakatani, M. Ikeda and Y. Tamura, J. Chem.
Soc., Perkin Trans. 1, 1986, 1763.
Thermal rearrangement of vinylcyclopropane derivatives 4
General procedure. A solution of vinylcyclopropane 4 (0.5
mmol) in benzene (5 cm3) was heated at 230 ЊC in a sealed tube
for 6 h. After cooling, the reaction mixture was evaporated and
the residue was purified by preparative TLC eluting with ethyl
acetate–hexane
(1:10)
to
give
3Ј,4,4Ј-trimethyl-2H-
benzothiazine-2-spirocyclopent-3Ј-en-3(4H)-one 21a as colour-
less prisms, mp 84.5–86.0 ЊC (Found: C, 69.2; H, 6.6; N, 5.4.
C15H17NOS requires C, 69.46; H, 6.61; N, 5.40%); νmax(KBr)/
cmϪ1 1660 (C=O); δH (CDCl3) 1.57 (6 H, s, Me × 2), 2.30 (2 H,
d, J 16, CH2), 3.11 (2 H, d, J 16, CH2), 3.46 (3 H, s, NMe), 6.99
(1 H, t, J 7, ArH), 7.04 (1 H, d, J 7, ArH), 7.20 (1 H, t, J 7, ArH)
and 7.30 (1 H, d, J 7, ArH); δC(CDCl3) 13.2 (q), 32.8 (q), 47.9
(t), 48.6 (s), 116.9 (d), 122.9 (d), 126.9 (d), 127.5 (s × 2), 128.8
(d), 140.2 (s) and 169.8 (s); m/z 259 (M+, 38%) and 121 (100).
4-Methyl-2H-benzothiazine-2-spirocyclopent-3Ј-en-3(4H)-
one 21b, colourless prisms, mp 47–49 ЊC (Found: C, 67.4; H,
5.6; N, 6.1. C13H13NOS requires C, 67.50; H, 5.67; N, 6.06%);
νmax(KBr)/cmϪ1 1670 (C=O); δH (CDCl3) 2.40 (2 H, d, J 16,
CH2), 3.15 (2 H, d, J 16, CH2), 3.47 (3 H, s, NMe), 5.61 (2 H, br
s, olefinic H), 7.00 (1 H, t, J 7, ArH), 7.06 (1 H, d, J 7, ArH),
7.25 (1 H, t, J 7, ArH) and 7.31 (1 H, d, J 7, ArH); δC(CDCl3)
32.9 (q), 42.8 (t), 50.7 (s), 117.0 (d), 122.6 (s), 123.0 (d), 127.0
(d), 127.2 (d), 128.9 (d), 140.2 (s) and 169.4 (s); m/z 231 (M+,
52%) and 139 (100).
5 H. Shimizu, S. Miyazaki, T. Kataoka and M. Hori, Tetrahedron
Lett., 1991, 32, 5571; H. Shimizu, S. Miyazaki, T. Kataoka and
M. Hori, J. Chem. Soc., Chem. Commun., 1992, 1586; H. Shimizu,
S. Miyazaki, T. Kataoka and M. Hori, J. Chem. Soc., Perkin Trans.
1, 1995, 1583.
6 T. Kataoka, Y. Nakamura, H. Matsumoto, T. Iwama and H. Shimi-
zu, Heterocycles, 1994, 38, 1733.
7 H. Tawada, Y. Sugiyama, H. Ikeda, Y. Yamamoto and K. Meguro,
Chem. Pharm. Bull., 1990, 38, 1238.
8 M. Hori, T. Kataoka, H. Shimizu and K. Tsutsumi, Tetrahedron
Lett., 1989, 30, 981; T. Kataoka, K. Tsutsumi, K. Kano, K. Mori,
M. Miyake, M. Yokota, H. Shimizu and M. Hori, J. Chem. Soc.,
Perkin Trans. 1, 1990, 3017.
9 T. Kataoka, T. Iwama, H. Shimizu and M. Hori, Phosphorus Sulfur
Silicon Relat. Elem., 1992, 67, 169.
10 T. Hudlicky, T. M. Kutchan and S. M. Naqvi, Org. React. (N.Y.),
1985, 33, 247; T. Hudlicky and J. W. Reed, in Comprehensive Organic
Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford,
1991, vol. 5, p. 899.
11 P. Girard, J. L. Namy and H. B. Kagan, J. Am. Chem. Soc., 1980,
102, 2693.
J. Chem. Soc., Perkin Trans. 1, 1997
315

View Article Online
12 Structure Solution Methods: MITHRIL; C. J. Gilmore, MITHRIL
—an integrated direct methods computer program, University of
Glasgow, Scotland, J. Appl. Crystallogr., 1984, 17, 42. DIRDIF:
P. T. Beurskens, DIRDIF: Direct Methods for Difference Struc-
tures—an automatic procedure for phase extension and refine-
ment of difference structure factors. Technical Report 1984/1
Crystallography Laboratory, Toernooiveld, 6525 Ed. Nijmegen,
Netherlands.
13 D. T. Cromer and J. T. Waber, Table 2.2A in International Tables for
X-Ray Crystallography, Kynoch Press, Birmingham, England, 1974,
vol. 4.
Paper 6/03348B
Received 13th May 1996
Accepted 9th September 1996
316
J. Chem. Soc., Perkin Trans. 1, 1997