May-Jun 2004
1, 2-Benzisothiazole-3-one-1,1-dioxide Methylsulfonyl Derivatives
437
precipitate was collected by filtration and dried under vacuum
(0.1 mm Hg) at 80 °C.
d ): δ 8.50 (d, J = 7.6 Hz, 1H), 8.41 (d, J = 8.0 Hz, 1H), 8.22 (t, J
13
6
= 8.0 Hz, 1H), 3.60 (s, 3H). C nmr (DMSO-d ): δ 160.2, 143.5,
6
139.9, 137.1, 134.5, 127.2, 127.0, 43.8.
Anal. Calcd. for C H NO S : C, 36.78; H, 2.70; N, 5.36.
4-Methylthio-1,2-benzisothiazole-3-one-1,1-dioxides (3a).
8
Found: C, 36.90; H, 2.74; N, 5.43.
7
5 2
This compound was obtained as white crystals (8.34 g, 91%),
-1
mp 287-289 °C; ir (nujol): 1711, 1459, 1376 cm . H nmr
1
5-Methylsulfonyl-1,2-benzisothiazole-3-one-1,1-dioxides (4b).
This compound was obtained as a white solid (2.34 g, 90%),
(DMSO-d ): δ 7.91 (t, J = 7.6 Hz, 1H), 7.85(d, J = 7.6 Hz, 1H),
13
6
7.73 (d, J = 8.0 Hz, 1H), 2.58 (s, 3H). C nmr (DMSO-d ): δ
6
-1
mp 252-254 °C; ir (nujol): 1729, 1458, 1376 cm ; H nmr
1
160.6, 142.4, 140.5, 135.3, 129.1, 121.1, 115.8, 13.6.
Anal. Calcd. for C H NO S : C, 41.91; H, 3.08; N, 6.11.
13
(DMSO-d ): δ 8.31-8.45 (m, 3H), 3.40 (s, 3H). C nmr (DMSO-
8
Found: C, 41.95; H, 3.01; N, 6.01.
7
3
2
6
d ): δ 161.0, 146.5, 144.3, 133.9, 130.3, 123.8, 122.8, 43.5.
Anal. Calcd. for C H NO S : C, 36.78; H, 2.70; N, 5.36.
6
8
Found: C, 36.82; H, 2.63; N, 5.34.
7
5 2
5-Methylthio-1,2-benzisothiazole-3-one-1,1-dioxides (3b).
This compound was obtained as white crystals (8.24 g, 90%),
6-Methylsulfonyl-1,2-benzisothiazole-3-one-1,1-dioxides (4c).
This compound was obtained as a white solid (2.35 g, 90%),
-1
1
mp 198-200 °C; ir (nujol): 1717, 1456, 1375 cm ; H nmr
(DMSO-d ): δ 8.13 (d, J = 8.4 Hz, 1H), 7.87(d, J = 8.0 Hz, 1H),
13
6
7.82 (s, 1H), 2.71 (s, 3H); C nmr (DMSO-d ): δ 160.4, 148.1,
-1
mp 277-279 °C; ir (nujol) 1744, 1459, 1376 cm ; H nmr
1
6
134.7, 131.2, 128.3, 121.1, 119.7, 14.1.
Anal. Calcd. for C H NO S : C, 41.91; H, 3.08; N, 6.11.
(DMSO-d ): δ 8.71 (s, 1H), 8.36 (d, J = 8.0 Hz, 1H), 8.15 (d, J =
13
6
8.0 Hz, 1H), 3.41 (s, 3H). C nmr (DMSO-d ): δ 160.8, 147.0,
8
7
Found: C, 41.87; H, 3.09; N, 6.08.
3 2
6
141.1, 133.4, 132.7, 126.4, 120.7, 43.2.
Anal. Calcd. for C H NO S : C, 36.78; H, 2.70; N, 5.36.
8
Found: C, 36.81; H, 2.63; N, 5.33.
7
5 2
6-Methylthio-1,2-benzisothiazole-3-one-1,1-dioxides (3c).
This compound was obtained as white crystals (8.44 g, 90%),
mp 264-266 °C (lit. [4], 232-234 °C); ir (nujol): 1714, 1459, 1376
7-Methylsulfonyl-1,2-benzisothiazole-3-one-1,1-dioxides (4d).
This compound was obtained as a white solid (2.37 g, 91%),
-1 1
cm . H nmr (DMSO-d ): δ 8.0 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H),
13
6
7.85 (d, J = 8.4 Hz, 1H), 2.65 (s 3H) C nmr (DMSO-d ): δ
-1
1
mp 264-266 °C; ir (nujol) 1741, 1460, 1376 cm . H nmr
6
161.6, 150.8, 141.3, 131.7, 125.8, 124.3, 117.7, 15.4.
Anal. Calcd. for C H NO S : C, 41.91; H, 3.08; N, 6.11.
(DMSO-d ): δ 8.38 (d, J = 7.2 Hz, 1H), 8.31 (d, J = 7.6 Hz, 1H),
13
6
8.16 (t, J = 7.6 Hz, 1H), 3.40 (s, 3H). C nmr (DMSO-d ): δ
8
Found: C, 41.83; H, 3.10; N, 6.04.
7
3 2
6
161.8, 138.9, 137.0, 136.8, 135.6, 132.1, 130.9, 45.0.
Anal. Calcd. for C H NO S : C, 36.78; H, 2.70; N, 5.36.
8
7
5 2
Found: C, 36.80; H, 2.78; N, 5.34.
7-Methylthio-1,2-benzisothiazole-3-one-1,1-dioxides (3d).
This compound was obtained as white crystals (8.34 g, 91%),
-1 1
mp 250-252 °C; ir (nujol) 1717, 1459, 1376 cm . H nmr (DMSO-
REFERENCES AND NOTES
13
d ): δ 7.87 (m, 2H), 7.74 (m, 1H), 2.69 (s, 3H). C nmr (DMSO-
6
d ): δ 160.8, 135.8, 135.6, 135.3, 132.0, 128.8, 120.8, 14.9.
Anal. Calcd. for C H NO S : C, 41.91; H, 3.08; N, 6.11.
6
[1] C. Subramanayam, M. R. Bell, P. Carabates, J. J. Court, J. A.
Dority Jr., E. Ferguson, R. Gordon, D. J. Hlasta, and V. Kumar, J. Med.
Chem., 37, 2623 (1994).
8
7
3 2
Found: C, 41.86; H, 3.12; N, 6.08.
[2] S. Y. Choi, Y. J. Yoon, and K. W. Kim, J. Heterocyclic Chem.,
26, 1073 (1989).
General Procedure for the Preparation of Methylsulfonyl-1,2-
benzisothiazole-3-one-1,1-dioxides (4a-d).
[3] U. Misslitz, E. Baumann, W. VonDeyn, S. Kudis, K.
Langemann, G. Mayer, U. Neidlein, M. Witschel, R. Gotz, M. Rack, P.
Plath, M. Otten, K. O. Westphalen, and H. Walter, PTC Int. Appl. WO 00
53590, (2000); Chem. Abstr., 133, 237993d (2000).
[4] C. L. Hillemann, US Patent 4849010, (1989); Chem. Abstr.,
112, 179033u (1990).
[5] J. R. Huff, H. Y. Lee, J. B. Nerenberg, and W. J. Thompson,
PTC Int. Appl. WO 95 28397, (1995); Chem. Abstr., 124, 176079a
(1996).
[6] P.J. Kukkola, L. A. Robinson, J. Sakaki, and M. Nakajima,
PTC Int. Appl. WO 99 42443, (1999); Chem. Abstr., 131, 184961s
(1999).
[7] C. E. Sunkel, M. F. de Casa-Juana, F. J. Cillero, J. G. Priego,
and M. P Ortega, J. Med. Chem., 31, 1886 (1988).
[8] H. T. Nagasawa, S. P. Kawle, J. A. Elberling, E. G. DeMaster,
and J. M. Fukuto, J. Med. Chem. 38, 1865 (1995).
[9] R. C. Desai, J. J. Court, and D. J. Hlasta, US Patent 5296496
(1994); Chem. Abstr., 121, 205668n (1994).
[10] D. J. Hlasta, C. Subramanyam, M. R. Bell, P. M. Carabateas,
J. J. Court, R. C. Dasai, M. L. Drozd, W. M. Eickhoff, E. W. Ferguson, R.
J. Gordon, J. A. Johnson, V. Kumar, A. L. Maycock, K. R. Mueller, E. D.
Pagani, D. T. Robinson, M. T. Saindane, P. J. Silver, and S. Subramanian,
J. Med. Chem., 38, 739 (1995).
Periodic acid (9.1 g, 40 mmol) was dissolved in acetonitrile
(120 ml) by vigorous stirring at room temperature for 30 minutes.
Then chromium (VI) oxide (20 mg, 0.2 mmol, 2 mol%) was
added to the solution and the mixture was stirred at room temper-
ature for 5 minutes to give a clear orange solution. To this solu-
tion was added the corresponding methylthio-1,2-benzisothia-
zole-3-one-1,1-dioxide (3a-d, 2.3 g, 10 mmol) in one portion. A
precipitate formed immediately with an exothermic reaction. The
mixture was stirred at room temperature for 2 hours followed by
the addition of isopropyl alcohol (15 ml). The reaction mixture
was stirred at room temperature for additional 1 hour, filtered and
the filtered cake was washed with acetone (30 ml). The filtrate
was concentrated in vacuo at room temperature. The residue was
dissolved in saturated aqueous sodium bicarbonate (40 ml), fil-
tered and the filtrate was acidified with concentrated hydrochlo-
ric acid to pH 1. The resulting precipitate was filtered and dried
under vacuum (0.1 mm Hg) at 80 °C.
4-Methylsulfonyl-1,2-benzisothiazole-3-one-1,1-dioxides (4a).
This compound was obtained as a white solid (2.35 g, 90%),
-1 1
mp >350 °C; ir (nujol): 1748, 1457, 1375 cm . H nmr (DMSO-
[11] M. Zimmerman, H. Morman, D. Mulvey, H. Jones, R.