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in hexane) to give the thionocarbonate intermediate as
an oil (5.1 g, 46%) [MS CI m/z 448 (M+1)]. This oil
was heated under vacuum (200 ꢁC/0.5 mmHg) for
5 min. The flask was cooled and the residue was purified
by chromatography (hexane to 25% EtOAc in hexane) to
give the elimination product 2 as an oil (2.33 g, 70%): 1H
NMR (CDCl3) d 6.85 (s, 1H), 6.62 (d, J = 7.7 Hz, 1 H),
6.13 (d, J = 7.7 Hz, 1H), 3.87 (t, J = 6.8 Hz, 2H), 3.42
(t, J = 5.7 Hz, 2H), 3.33 (s, 3H), 2.02 (m, 2H); 13C
NMR (CDCl3) d 141.1, 133.3, 129.6, 123.9, 120.8,
101.9, 68.3, 58.5, 45.8, 30.3.
To a solution of 4 (0.40 g, 1.0 mmol) in THF (5 ml) at
ꢀ30 ꢁC in a glass pressure tube was added an excess of
trimethylamine (1 ml). The sealed tube was allowed to
warm to room temperature (1 h) and then heated at
50 ꢁC for 3 h. After cooling, the solid was collected by
filtration and dried to give 5 (0.40 g, 89%): mp
>255 ꢁC dec; 1H NMR (DMSO-d6) d 8.13 (s, 2H),
7.69 (s, 1H), 7.19 (d, J = 7.6 Hz, 1H), 6.55 (d,
J = 7.6 Hz, 1H), 3.88 (t, J = 6.0 Hz, 2H), 3.35 (t,
J = 6.0 Hz, 2H), 3.05 (s, 9H). Anal. (C12H20BrN3O4S3)
C, H, N.
To a solution of 2 in THF (35 ml) at ꢀ78 ꢁC was added n-
BuLi (4.1 ml of a 2.1 M solution in hexane, 8.7 mmol) and
the mixture was stirred for 45 min. Sulfur dioxide gas was
passed over the reaction mixture for 5 min followed by
evaporation to a residue, which was dissolved in water
(40 ml). Sodium acetate trihydrate (5.35 g, 39.3 mmol)
and hydroxylamine-O-sulfonic acid (2.67 g, 23.6 mmol)
were added and the mixture was stirred at room tempera-
ture for 4 h and extracted with EtOAc (5 · 8 ml). The ex-
tract was washed with brine, dried, and evaporated to a
residue, which was purified by chromatography (gradient,
25% EtOAc in hexane to 30% MeOH in CH2Cl2) to give
the sulfamoyl product as an oil (0.91 g, 34%). To a solu-
tion of this oil in ethanol (1.5 ml) was added 2 N NaOH
(1.3 ml). Ethyl ether was added to form a precipitate,
which was isolated and dried to give 3 as a colorless solid
(0.81 g, 90%): mp 90–92 ꢁC; 1H NMR (DMSO-d6) d 7.16
(s, 1H), 6.93 (d, J = 7.7 Hz, 1H), 6.32 (d, J = 7.7 Hz, 1H),
3.76 (t, J = 7.0 Hz, 2H), 3.30 (t, J = 6 Hz, 2H), 3.20 (s,
3H), 1.86 (m, 2H); 13C NMR (DMSO-d6) d 161.2, 141.5,
133.2, 122.9, 122.1, 102.3, 68.4, 57.9, 44.5, 29.9; MS
CI m/z 339 (M+1). Anal. (C10H13N2O5S3Na Æ 2H2O) C,
H, N.
5.1.4. 6-(Aminosulfonyl)-N,N,N-trimethyl-1,1-dioxo-2H-
thieno[3,2-e]-1,2-thiazine-2-propanaminium chloride (6).
A solution of 5 (3 g, 0.67 mmol) in water (20 ml) was
passed through a column of Amberlyst-A27 resin
(20 g). Evaporation of the water provided a syrup
which, when scratched under ethanol, provided 6 as a
white solid (0.25 g, 92%): mp 255 ꢁC dec; 1H NMR
(DMSO-d6) d 8.23 (s, 2H), 7.71 (s, 1H), 7.24 (d,
J = 7.6 Hz, 1H), 6.55 (d, J = 7.6 Hz, 1H), 3.86 (t,
J = 7.2 Hz, 2H), 3.35 (t, 2H), 3.05 (s, 9H), 2.12 (m,
2H). Anal. (C12H20ClN3O4S3) C, H, N.
5.1.5. 6-(Aminosulfonyl)-N,N,N-2-tetramethyl-1,1-dioxo-
2H-thieno[3,2-e]-1,2-thiazine-3-methanaminium chloride
(9a). A solution of 7a24 (1.00 g, 3.22 mmol) in THF
(20 ml) was cooled (0 ꢁC) and DMAP (0.78 g, 6.5 mmol)
was added followed by p-toluenesulfonyl chloride (1.2 g,
6.5 mmol). This mixture was stirred for 2 h at 0 ꢁC and
then at room temperature for an additional 2 h. Ethyl
acetate (50 ml) was added and the mixture was washed
with water (30 ml). The organic layer was dried and
the solvent was evaporated to give a residue, which
was purified by chromatography (20% acetone in hex-
ane) to give 8a as an oil (0.50 g, 50%): 1H NMR
(DMSO-d6) d 8.12 (s, 2H), 7.72 (s, 1H), 6.89 (s, 1H),
4.81 (s, 2H), 3.55 (s, 3H).
5.1.3. 6-(Aminosulfonyl)-N,N,N-trimethyl-1,1-dioxo-2H-
thieno[3,2-e]-1,2-thiazine-2-propanaminium bromide (5).
A solution of 3 (1.85 g, 5.47 mmol) in dichloromethane
(80 ml) was cooled (0 ꢁC) and boron tribromide
(10.30 g, 60.45 mmol) was added; this mixture was stir-
red for 1 h at 0 ꢁC and then allowed to warm to room
temperature and stirred for an additional hour. Water
(50 ml) was added and the organic layer was washed
with brine (40 ml), dried, and evaporated to a residue,
which was purified by chromatography (hexane/acetone,
1:1) to give the hydroxypropyl intermediate as an oil
(1.0 g, 56%) [1H NMR (CDCl3) d 7.52 (s, 1H), 6.75 (d,
J = 7.6 Hz, 1H), 6.30 (d, J = 7.6 Hz, 1H), 5.15 (br s,
2H), 3.96 (s, 2H), 3.70 (m, 2H), 1.90 (m, 2H)]. A solution
of this oil (1.0 g, 3.1 mmol) in dichloromethane (20 ml)
was cooled (0 ꢁC) and phosphorus tribromide (30 ml
of a 1.0 M dichloromethane solution, 30 mmol) was
added; this mixture was allowed to warm to room tem-
perature and stirred for 4 h. After evaporating the sol-
vent, the residue was dissolved in EtOAc (50 ml) and
the solution was washed with water (50 ml) and brine
(50 ml), dried, and evaporated to a residue, which was
purified by chromatography (acetone/hexane, 1:1) to
give 4 as an oil (0.40 g, 32%): 1H NMR (CDCl3) d
7.52 (s, 1H), 6.88 (d, J = 7.6 Hz, 1H), 6.30 (d,
J = 7.7 Hz, 1H), 5.65 (br s, 2H), 3.90 (t, J = 5.9 Hz,
2H), 3.55 (t, J = 6.1 Hz, 2H), 2.33 (m, 2H).
A solution of 8a (0.40 g, 1.2 mmol) in THF (5.0 ml) was
added to a saturated solution of trimethylamine in
THF (10 ml) at ꢀ78 ꢁC and this mixture was heated
at 60 ꢁC for 12 h in a sealed tube. After cooling to
room temperature, the solid that formed was collected,
washed with ether, and dried to give 9a as a white pow-
1
der (0.25 g, 53%): mp >190 ꢁC dec; H NMR (DMSO-
d6) d 8.45 (br s, 2H), 7.95 (s, 1H), 7.40 (s, 1H), 4.81 (s,
2H), 3.55 (m, 12H). Anal. (C11H18ClN3O4S3 Æ 0.25-
C4H8O) C, H, N.
5.1.6. 6-(Aminosulfonyl)-N,N,N-trimethyl-2-(3-methoxy-
phenyl)-1,1-dioxo-2H-thieno[3,2-e]-1,2-thiazine-3-methan-
aminium chloride (9b). A solution of 7b24 (1.00 g,
2.48 mmol) in THF (20 ml) was treated as described
for the preparation of 8a to give, following chromato-
graphy (20% acetone in hexane), 8b as an oil (0.60 g,
60%): 1H NMR (DMSO-d6) d 8.13 (s, 2H), 7.81 (s,
1H), 7.35 (t, J = 8 Hz, 1H), 7.15 (s, 1H), 7.10 (dd,
J = 6 Hz, 1H), 6.77 (m, 2H), 4.32 (s, 2H), 3.75 (s, 3H).
A solution of 8b (0.30 g, 0.70 mmol) in THF (5.0 ml)
was treated as described for the preparation of 9a to give
1
9b as a white solid (0.20 g, 50%): mp > 208 ꢁC dec.; H