Helvetica Chimica Acta ± Vol. 88 (2005)
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(2.991), 380 (3.785). IR: 3108, 1724, 1594. 1H-NMR (B): 6.36 (s, 1 H); 3.83 (s, 3 H); 3.45 (s, 3 H). MS: 265 (M ).
Anal. calc. for C7H7NO4S3 (265.33): C 31.69, H 2.66, N 5.28, S 36.26; found: C 31.76, H 2.72, N 5.09, S 36.21.
Methyl 6-Bromo-4-methyl-4H-1,2-dithiolo[4,3-c]isothiazole-3-carboxylate 5,5-Dioxide (17). A soln. of 15
(0.31 g, 1 mmol) in AcOH (20 ml) and Br2 (0.4 ml) were heated to 1008 for 1 min. The solvent was evaporated
and the residue crystallized from AcOEt: 0.15 g (44%). Yellowish brown crystals. M.p. 1798. UV: 235 (3.643),
386 (3.887). IR: 2955, 1725, 1593, 1344, 1186. 1H-NMR (B): 3.83 (s, 3 H); 3.50 (s, 3 H). MS: 343, 345 (M ).
Anal. calc. for C7H6BrNO4S3 (344.23): C 24.42, H 1.76, Br 23.21, N 4.07, S 27.95; found: C 24.57, H 1.82, Br 22.96,
N 4.11, S 27.95.
Methyl 4-Methyl-6-nitro-4H-1,2-dithiolo[4,3-c]isothiazole-3-carboxylate 5,5-Dioxide (18). A soln. of a) 15
(0.31 g, 1 mmol) or b) 17 ( 0.34 g, 1 mmol) in AcOH (10 ml) and conc. HNO3 soln. (1 ml) were heated to 1008
for 1 min. While cooling, the crude product precipitated and was recrystallized from hexane/AcOEt 20 :1: a)
0.17 g (55%) of 18 or b) 0.12 g (39%) of 18. Yellow-orange crystals. M.p. 2338 . UV: 460 (3.756). IR: 2927, 1729,
1
1582, 1309, 1246, 1179. H-NMR (B): 3.92 (s, 3 H); 3.54 (s, 3 H). M S: 310 (M ). Anal. calc. for C7H6N2O6S3
(310.33): C 27.09, H 1.95, N 9.03, S 31.00; found: C 27.20, H 1.90, N 9.02, S 31.08.
Methyl 6-(Chlorocarbonyl)-4-methyl-4H-1,2-dithiolo[4,3-c]isothiazole-3-carboxylate 5,5-Dioxide (19). A
soln. of 15 (0.3 g, 1 mmol) in dry benzene (20 ml) and PCl5 (0.23 g, 1 mmol) were heated to reflux for 3 h. After
cooling, the soln. was washed with H2O several times, dried (Na2SO4), and evaporated and the residue
i
crystallized from Pr2O: 0.23 g (70%) of 19. Dark green crystals. M.p. 1388. UV: 429 (4.100). IR: 2957, 1728,
1673, 1321, 1170. MS: 299, 301 ([M À 28] ). Anal. calc. for C8H6ClNO5S3 (327.79): C 29.31, H 1.84, N 4.27, S
29.35; found: C 29.43, H 1.94, N 4.36, S 29.45.
Methyl 6-(Benzylcarbamoyl)-4-methyl-4H-1,2-dithiolo[4,3-c]isothiazole-3-carboxylate 5,5-Dioxide (20). A
soln. of 19 (0.33 g, 1 mmol) in dry THF (20 ml) and benzylamine (0.5 ml) were stirred at 08 for 30 min. The soln.
was concentrated to half of its initial volume, acidified with 2n HCl (30 ml) and extracted twice with AcOEt.
The org. phase was dried (Na2SO4) and evaporated: 0.16 g (40%) of 20. Yellow crystals. M.p. 1748 (iPr2O). UV:
206 (4.420), 248 (3.910), 410 (4.187), 431 (4.187). IR: 3371, 1728, 1627, 1312. 1H-NMR (B): 7.35 ± 7.26 (m, 5 H);
6.23 (br. s, 1 H, exchange with D2O); 4.61 (d, J 6.1, 2 H); 3.93 (s, 3 H), 3.54 (s, 3 H). M S: 398 (M ). Anal. calc.
for C15H14N2O5S3 (398.48): C 45.21, H 3.54, N 7.03, S 24.14; found: C 45.21, H 3.47, N 7.06, S 24.10.
Methyl 6-(Azidocarbonyl)-4-methyl-4H-1,2-dithiolo[4,3-c]isothiazole-3-carboxylate 5,5-Dioxide (21). A
soln. of NaN3 (0.70 g, 1.1 mmol) in H2O (5 ml) was added dropwise to a stirred soln. of 19 (0.33 g, 1 mmol) in
acetone (10 ml). After further stirring for 45 min, the mixture was diluted with AcOEt ( 30 ml) and washed with
H2O. The org. layer was dried (Na2SO4) and evaporated and the residue purified by FC (petroleum ether/
AcOEt 1:1): 0.25 g (75%) of 21. Yellow crystals. M.p. 1688 (iPr2O). UV: 254 (3.916), 446 (4.337). IR: 2190,
2143, 1727, 1621. 1H-NMR (B): 3.95 (s, 3 H); 3.57 (s, 3 H). MS: 334 (M ). Anal. calc. for C8H6N4O5S3 (334.36):
C 28.74, H 1.81, N 16.76, S 28.77; found: C 28.66, H 1.71, N 16.72, S 28.79.
Methyl 6-(Acetylamino)-4-methyl-4H-1,2-dithiolo[4,3-c]isothiazole-3-carboxylate 5,5-Dioxide (22). A soln.
of a) 21 (0.33 g, 1 mmol) or b) 24 (0.28 g, 1 mmol) in Ac2O (15 ml) was heated to 1408 for 4 h. The solvent was
evaporated and the residue purified by FC (petroleum ether/AcOEt 2 :1): a) 0.12 g (37%) of 22 or b) 0.19 g
(59%) of 22. Yellow crystals. M.p. 2168 (iPr2O). UV: 245 (3.816), 394 (3.901). IR: 3289, 1729, 1673, 1613, 1357,
1179. 1H-NMR (B): 7.36 (s, 1 H, exchange with D2O); 3.81 (s, 3 H); 3.41 (s, 3 H); 2.15 (s, 3 H). MS: 322 (M ).
Anal. calc. for C9H10N2O5S3 (322.38): C 33.53, H 3.13, N 8.69, S 29.84; found: C 33.60, H 3.09, N 8.69, S 29.89.
Methyl 6-{[(tert-Butoxy)carbonyl]amino}-4-methyl-4H-1,2-dithiolo[4,3-c]isothiazole-3-carboxylate 5,5-Di-
t
oxide (23). A soln. of 21 (0.33 g, 1 mmol) in freshly distilled BuOH (50 ml) was heated to reflux for 3 d. The
solvent was evaporated and the residue purified by FC (petroleum ether/AcOEt 1 :1): 0.17 g (45%) of 23.
Yellow crystals. M.p. 1798 (iPr2O). UV: 244 (3.892), 389 (3.967). IR: 3285, 1728, 1706, 1626, 1600. 1H-NMR (B):
6.45 (br., 1 H, exchange with D2O); 3.87 (s, 3 H); 3.47 (s, 3 H); 1.51 (s, 9 H). MS: 380 (M ). Anal. calc. for
C12H16N2O6S3 (380.46): C 37.88, H 4.24, N 7.36, S 25.28; found: C 37.90, H 4.46, N 7.39, S 25.19.
Methyl 6-Amino-4-methyl-4H-1,2-dithiolo[4,3-c]isothiazole-3-carboxylate 5,5-Dioxide (24). A soln. of 23
(0.33 g, 1 mmol) in benzene (50 ml) was heated to reflux for 2 d. The solvent was evaporated and the residue
purified by FC (petroleum ether/AcOEt 3 :1): 0.12 g (42%) of 24. Red-brown crystals. M.p. 1498 (iPr2O). UV:
1
239 (3.926 ), 401 (3.842). IR: 3402, 3328, 3219, 1706, 1646. H-NMR (B): 3.78 (s, 3 H); 3.41 (s, 3 H). MS: 280
(M ). Anal. calc. for C7H8N2O4S3 (280.35): C 29.99, H 2.88, N 9.99, S 34.31; found: C 29.90, H 3.01, N 9.95, S
34.25.
6-Methyl 3-Hydrogen 4-Methyl-4H-1,2-dithiolo[4,3-c]isothiazole-3,6-dicarboxylate 5,5-Dioxide (25). As
described for 26, 25 was obtained as a by-product in the alkaline aq. phase. The latter was separated, acidified
with 2n HCl, and extracted twice with CH2Cl2. The combined org. phase was dried (Na2SO4) and evaporated
and the residue crystallized from AcOEt: 30 mg (10%) of 25. Orange crystals. M.p. 130 ± 1358 (dec.). UV: 212