April 1998
SYNTHESIS
425
Anal. C7H7NO2S2 (201.3): Calcd C 41.78, H 3.51, N 6.96. Found C
41.76, H 3.46, N 7.03.
MS (EI): m/z (%) = 201 (M+, 29), 149 (9), 137 (9), 136 (100), 109
(12), 86 (9), 84 (14), 69 (7), 49 (18), 44 (11).
IR (KBr): n = 3250 (N-H), 1310, 1150 cm–1 (SO2).
1H NMR (acetone-d6): d = 4.40 (s, 2 H, CH2), 6.96 (d, 1 H, J = 7.8 Hz,
ArH), 7.04 (t, 1 H, J = 7.8 Hz, ArH), 7.18 (t, 1 H, J = 7.8 Hz, ArH),
7.24 (d, 1 H, J = 7.8 Hz, ArH), 9.10 (br s, 1 H, NH).
13C NMR (acetone-d6): d = 46.1 (t), 118.4 (s), 122.1 (d), 124.8 (d),
128.0 (d), 128.3 (d), 138.4 (s).
Scheme 4
Scheme 5
2-Cyclohexyl-3-phenyl-1,2-thiazetidine 1,1-Dioxide (11):
To a suspension of Ph3P·Cl2 (2) (323 mg, 1 mmol) in MeCN (2 mL)
sodium aminosulfonate 10 (305 mg, 1 mmol) was added in portions
at r.t. The mixture was stirred overnight at r.t. and Et3N (0.14 mL,
1 mmol) was added dropwise at 0°C. After 1 h at r.t., water (10 mL)
was added to the mixture and it was extracted with EtOAc
(3 ´ 10 mL). The extracts were combined, washed with sat. brine
(2 ´ 10 mL), dried (MgSO4) and evaporated under reduced pressure.
The residue was purified by preparative TLC (silica gel, hexane/
EtOAc, 5:1) to give b-sultam 11 as colorless prisms (EtOAc/hexane);
yield: 202 mg (76%); mp 128–129 °C.
1
were recorded on a JASCO IRA-100 spectrophotometer. H NMR
spectra were recorded on a JEOL GX-270 (270 MHz) or a JEOL EX-
400 (400 MHz) or JEOL EX-90 (90 MHz) spectrometer with TMS as
an internal standard. The J values are given in Hz. Mass spectra were
recorded on a JEOL JMS-D 300 spectrometer with a direct-insertion
probe at 70 eV. Elemental analyses of new compounds were per-
formed by a Yanaco CHN Corder MT-5. All chromatographic isola-
tions were accomplished with either Kieselgel 60 (70–230 mesh) for
column chromatography or Kieselgel 60 PF254 containing gypsum for
preparative TLC.
Anal. C14H19NO2S (265.4): Calcd C 63.37, H 7.22, N 5.28. Found C
63.34, H 7.15, N 5.34.
MS (EI): m/z (%) = 265 (M+, 5), 232 (24), 158 (9), 110 (16), 105 (12),
104 (100), 91 (12), 55 (11), 41 (19).
N-Benzylbenzenesulfonamide (5a); Typical Procedure with Sodi-
um Sulfonates and Ph3P·Br2 (1):
1H NMR (CDCl3) d = 1.08–1.27 (m, 4 H), 1.42–1.74 (m, 5 H), 2.04
(br d, 1 H, J = 13 Hz), 3.20–3.28 (m, 1 H, 1¢-H), 3.86 (dd, 1 H, J = 8.8
and 15.1 Hz, 4-H), 4.34 (dd, 1 H, J = 7.8 and 15.1 Hz, 4-H), 4.35 (dd,
1 H, J = 7.8 and 8.8 Hz, 3-H), 7.27–7.43 (m, 3 H, ArH), 7.50–7.53 (m,
2 H, ArH).
To a suspension of Ph3P (2.62 g, 10 mmol) in MeCN (10 mL) was
carefully added dropwise at 0°C Br2 (ca. 0.52 mL, 10 mmol) until the
color of Br2 did not disappear. A trace amount of Ph3P was added to
the suspension to consume slightly excess Br2. Sodium benzene-
sulfonate (1.80 g, 10 mmol) was added in portions to the mixture at
r.t. After 1 h, benzylamine (1.07 g, 10 mmol) and Et3N (1.4 mL, 10
mmol) were added dropwise successively at 0°C. After 30 min, water
(40 mL) was added to the mixture and the whole was extracted with
EtOAc (3 ´ 40 mL). The extracts were combined, washed with sat.
brine (2 ´ 40 mL), dried (MgSO4) and evaporated under reduced
pressure. The residue was purified by column chromatography (silica
gel, hexane/EtOAc 20:1–5:1) to give N-benzylsulfonamide 5a; yield:
2.06 g (83%).
13C NMR (CDCl3) d = 24.0 (t), 24.2 (t), 25.3 (t), 30.2 (t), 31.6 (t), 49.1
(d), 56.8 (d), 65.9 (t), 126.5 (d), 128.8 (d), 129.0 (d), 139.0 (s).
IR (KBr): n = 1310, 1140 cm–1 (SO2).
N-Benzyl-p-toluenesulfonamide (5d) by Amidation of p-Toluene-
sulfonic Acid (12):
To a suspension of Ph3P·Cl2 (2) (420 mg, 1.3 mmol) in MeCN (2 mL)
p-toluenesulfonic acid (172 mg, 1 mmol) was added in portions at r.t.
The mixture was stirred overnight at r.t. and benzylamine (107 mg,
1 mmol) and Et3N (0.14 mL, 1 mmol) were added dropwise at 0°C.
After 1 h at r.t., water (10 mL) was added to the mixture and it was
extracted with EtOAc (3 ´ 10 mL). The extracts were combined,
washed with sat. brine (2 ´ 10 mL), dried (MgSO4) and evaporated
under reduced pressure. The residue was purified by preparative TLC
(silica gel, hexane/EtOAc, 5:1) to give N-benzylsulfonamide 5d;
yield: 228 mg (87%).
N-Benzylbenzenesulfonamide (5a); Typical Procedure with Sodi-
um Sulfonates and Ph3P·Cl2 (2):
To a suspension of Ph3P·Cl2 (2) (323–420 mg, 1–1.3 mmol) in MeCN
(2 mL) sodium benzenesulfonate (180 mg, 1 mmol) was added in por-
tions at r.t. The mixture was stirred overnight at r.t. and benzylamine
(107 mg, 1 mmol) and Et3N (0.14 mL, 1 mmol) were successively
added dropwise at 0°C. After 30 min, water (10 mL) was added to the
mixture and it was extracted with EtOAc (3 ´ 10 mL). The extracts
were combined, washed with sat. brine (2 ´ 10 mL), dried (MgSO4)
and evaporated under reduced pressure. The residue was purified by
preparative TLC (silica gel, hexane/EtOAc, 5:1) to give N-benzylsul-
fonamide 5a; yield: 1.59 g (64%).
Methyl p-Toluenesulfonate (13) by Esterification of Sodium p-
Toluenesulfonate:
To a suspension of Ph3P·Cl2 (2) (840 mg, 2.6 mmol) in MeCN (4 mL)
sodium p-toluenesulfonate (388 mg, 2 mmol) was added in portions
at r.t. The mixture was stirred overnight at r.t. and MeOH (0.41 mL,
10 mmol) and pyridine (0.65 mL, 8 mmol) were added dropwise at
–15°C. After 30 min at –15°C, water (20 mL) was added to the mix-
ture and it was extracted with EtOAc (3 ´ 20 mL). The extracts were
combined, washed with sat. brine (2 ´ 20 mL), dried (MgSO4) and
evaporated under reduced pressure. The residue was purified by pre-
parative TLC (silica gel, hexane/EtOAc, 5:1) to give 13; yield:
334 mg (90%).
2H,4H-1,3,4-Benzodithiazine 3,3-Dioxide (9):
A mixture of 6 (0.458 g, 3 mmol), o-aminobenzenethiol (0.451 g,
3.6 mmol) and NaOH (0.120 g, 3 mmol) in degassed water (12 mL)
was heated at 160–170°C under N2 in a sealed tube for 12 h. The mix-
ture was cooled and evaporated under reduced pressure. The resultant
solid was washed well with EtOAc to remove excess o-aminoben-
zenethiol and it’s oxidized product, 2,2¢-diaminodiphenyl disulfide.
The crude sodium salt 7 was added to a suspension of Ph3P·Br2 [1,
prepared from 0.786 g (3 mmol) of Ph3P and ca. 0.15 mL (0.3 mmol)
of Br2 as described above] in MeCN (10 mL) in portions at 0°C. The
mixture was stirred at the same temperature for 1 h and Et3N
(0.42 mL, 3 mmol) was added dropwise. After 30 min, water (40 mL)
was added to the mixture and it was extracted with EtOAc (3 ´ 40
mL). The extracts were combined, washed with sat. brine (2 ´ 40
mL), dried (MgSO4) and evaporated under reduced pressure. The res-
idue was purified by preparative TLC (silica gel, hexane/EtOAc, 3:1)
to give 1,3,4-benzodithiazine 3,3-dioxide 9 as colorless leaves (Et2O/
hexane); yield: 81 mg (13%); mp 144–146°C.
This work was supported in part by Grant-in-Aid for Scientific
Research No. 08304037 and 09771915 from the Ministry of Educa-
tion, Science, Sports, and Culture.
(1) Brooks, G. T. In Sulphur-Containing Drugs and Related Or-
ganic Compounds; Vol. 1, part A; Damani, L. A., Ed.; Ellis Hor-
wood: New York, 1989; pp 60–93.