2.1- Benzisothiazoline 2,2-dioxides

Isothiazolidinones have been desulfurized by Raney nickel (74JOC1210). The 2,1-benzisothiazoline 2,2-dioxide (158) undergoes photocycloaddition with dimethyl acetyl-enedicarboxylate and loss of sulfur dioxide to give a compound of probable structure (168) (80CC471). 

The sulfonamide 82 is readily cyclized by potassium amide in liquid ammonia, affording 1-methyl-2,1-benzisothiazoline 2,2-dioxide (83).112-114... 

Benzisothiazoline 2,2-dioxides incorporating a 1-amino-alkyl group (76 Ri = R2 = Me, R = Me, R = CHaPh = 2 or 3) have, after several unsuccessful attempts, been synthesized from 2-chloro-sulphonanilides (75) by condensation with the appropriate amino-alkyl chloride in DMF and subsequent ring-closure with potassamide in liquid ammonia. ... 

Saccharin is the generic name for l,2-benzisothiazolin-3-one-1,1-dioxide and has been used for over 100 years, since its discovery by Fahlberg and Remsen in 1879 and the first production patent granted in 1885. Saccharin is a white crystalline product the sodium salt of saccharin is the commonly used form in the soft drinks industry. Solubility is excellent and stability under food and drink processing conditions is also excellent. 

The same treatment of A-methyl(<9-methyl)arenesulfonamide (38) generates the corresponding 1,2-benzisothiazoline-3-one 1,1,-dioxide (A-methylsaccharins) (39), through triple 1,5-H shift and hydrolysis of the formed A-methyl(<9-triiodomethyl)ar-enesulfonamides [55]. This method is very useful, since biologically attractive 1,2-benzisothiazoline-3-one 1,1-dioxides bearing various kinds of substituents on the aromatic ring can be prepared under neutral conditions. 

The mechanism of electron-impact-induced sulfur dioxide elimination from the molecular ions of 4-nitro-2,l-benzisothiazoline and 6-nitro-2,l-benzisothiazoline 2,2-dioxide derivatives has been examined [1359], The light fastness of dyes based on 3-amino-5-nitro-2,l-benzisothiazole was studied in relation to mass spectral data [1251],... 

AT-p-acetoxyphenyl", tetraacetate JV-acetyl-iV-p-bromophenyl-, 2,3,4,6-tetraaeetate N-(2-amino-3,4-dimethylphenyl)-, tetraacetate Af-(2-amino-4,5-dimethylphenyl)-, tetraacetate i f-(2-amino-4-methylphenyl)-, tetraacetate AT-o-aminophenyl-, 2,3,4,6-tetraacetate AT-(2-benzisothiazolin-3-one-l, 1-dioxide)-,... 

General features of the conformations of isothiazole derivatives were discussed in CHEC-II(1996) <1996CHEC-11(3)319>. Isothiazole and the benzisothiazoles are planar molecules, as are the corresponding A,A-dioxides, saccharin, thiosaccharin, and their salts. 1,2-Benzisothiazoline A,A-dioxide in the crystalline state exists as a 1 1 mixture of two conformers. 

Benzisothiazolin-3-one 1,1-dioxide benzoic sulfimide benzosulfimide l,2-dihydro-2-ketobenzisosulfonazole 2,3-dihydro-3-oxobenzisosulfonazole E954 Garantose gluside Hermesetas sacarina saccharin insoluble o-sulfobenzimide o-sulfobenzoic acid imide. 

Benzisothiazolin-3-one 1,1-dioxide, sodium salt Crystal-lose E954 sodium o-benzosulfimide soluble gluside soluble saccharin sucaryl sodium. 

The Su rez modification of the HLF reaction was the basis of the new synthetic method developed by H. Togo et al. The authors prepared A/-alkyl-1,2-benzisothiazoline-3-one-1,1-dioxides (A/-alkylsaccharins) from A/-alkyl(o-methyl)-arenesulfonamides using (diacetoxyiodo)arenes in the presence of iodine via sulfonamidyl radicals. The transformations did not work in the dark, indicating the radical nature of the reaction. The yields varied from moderate to excellent and the nature of the aromatic substituents on both the substrate and the (diacetoxyiodo)arenes were important. It should be noted that the oxygen atom at the C3 position most likely arises from the hydrolysis of a C3 diiodo intermediate (not isolated). 

Katohgi, M., Togo, H., Yamaguchi, K., Yokoyama, M. New synthetic method to 1,2-benzisothiazoline-3-one-1,1-dioxides and 1,2-benzisothiazoline-3-one-1-oxides from N-alkyl(o-methyl)arenesulfonamides. Tetrahedron 1999, 55,14885-14900. 

Benzisothiazole 2,2-dioxide is prepared by treating the 2-aminobenzoylsulfonic acid sodium salt with phosphorus oxychloride <86JHC1645>. The sodium dithiocarboxylate (230) on treatment with an acid or iodine gives the 2,1-benzisothiazoline 3-thione (231) <82JOC5255>. 

A versatile synthetic approach to 4-hydroxy-1,2-benzothiazines was discovered by Abe and co-workers3-. 2-phenacyl-l,2-benzisothiazolin-3-ones (8 R = Ar) with strong base produce 3-benzoyl-4-hydroxy-2//-l,2-benzo-thiazine 1,1-dioxides (9 R = Ar) (Eq. 2). Yields up to 93% could be obtained using sodium ethoxide in ethanol. 

A number of sulfamoyl-substituted 3-acyl-4-hydroxy-l,2-benzothiazine 1,1-dioxides were prepared13 by base-catalyzed isomerization of sulfamoyl derivatives of benzisothiazolin-3-ones by essentially the method of Abe (Eq. 2). 

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