Benzisothiazole 1,1-Dioxides

2- benzisothiazole 1,1-dioxides (86) have been synthesized by the method 

For Summary see S. Hiinig, W. Brenninger, H. Geiger, G. Kaupp, W. Kniese, W. Lampe, H. Quasi, R. D. Rauschenbach, and A. Schiitz, Angew Chem., 1968, M, 343. 

2-MethoxybenzisothiazoIine 1,1-dioxides (90) are formed by cyclization, in DMF-triethylamine, of the corresponding sulphonhydroxamic acids (89), c.g. a-bromo-N-methoxy-o-toluenesulphonamide (89 X = H).  

The photoisomerization of N-alkoxyisosulphobenzimides (91) to the corresponding 1,2-benzisothiazole derivatives (92) (N-alkoxysaccharins) has been briefly reported.  

Synthesis.—A series of 4-substituted 6-carboxy-3-phenyl-1,2-benzisothiazole 1,1-dioxides (58) has been produced in almost quantitative yields by the thermolysis of 3-substituted 4-benzoyl-5-sulphamoylbenzoic acids (57). The diuretic 

Chemical Properties.—The action of Grignard reagents on saccharin has been reinvestigated. It affords 3-alkyl- (or aryl-)substituted 1,2-benzisothiazole 1,1-dioxide derivatives (59), together with the tertiary alcohols (60), the relative amounts depending on the proportions of the reagents employed and the experi- 

An alternative approach to 3-substituted 1,2-benzisothiazole 1,1-dioxides bearing substituents in the benzene ring is to allow the appropriately substituted benzenesulphonamide to react successively with an acyl chloride and n-butyl-lithium.  

The action of nucleophiles (MNuc M = H or Na) on 3-alkoxy-l,2-benziso-thiazole 1,1-dioxides (62 R = Me or Pr ) yields either 3-substituted 1,2-benziso-thiazole 1,1-dioxides (63) or saccharin (61) as main products. The nature of the nucleophile determines which pathway predominates.  

The action of sodium alkyl carbonates on 3-chloro-l,2-benzisothiazole 1,1-dioxide (64) produces mixtures of AT-alkoxycarbonylsaccharins (65) and pseudosaccharin anhydride (66), together with dialkyl pyrocarbonates. The product ratio of (65) to (66) decreases in the order (R = ) Me Et Pr Bu. The initial step in the reaction is considered to be a nucleophilic displacement of chlorine by ROCOO ion.  

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Benzisothiazoles also suffer N—S bond cleavage, following attack at sulfur, but 1,2-benzisothiazole 1,1-dioxides are cleaved at the C—N bond. Saccharin derivatives are attacked at the carbonyl function. In cases where N—S bond cleavage occurs, recyclization can sometimes occur, often producing thiophene compounds. 

Borohydride reduction of 3-aryl-l,2-benzisothiazole 1,1-dioxides gives the 2,3-dihydro compounds 73JMC1170). Reduction of either 2-methylsaccharin or 2-hydroxymethylsac-charin with lithium aluminum hydride gives the same product, iV-methyl-o-hydroxymethyl-benzenesulfonamide (73AHC(15)233). 

Substituted 1,2-benzisothiazole 1,1-dioxides form benzo-1,2-thiazepines (86) with 1-diethylaminoprop-l-yne (76H(5)95). 2,1-Benzisothiazole does not react with maleic... 

When saccharin is treated with diethyl phosphorothiolothionate, the 3-ethylmercapto compound is obtained, rather than the expected organophosphorus compound (77 ACS(B)460). Treatment of saccharin with phosphorus pentoxide and amines gives 3-(substituted-amino)-1,2-benzisothiazole 1,1-dioxides, via an intermediate phosphate (81ZN(B)1640). Reduction of saccharin with zinc and hydrochloric acid gives 2,3-dihydro-l,2-benzisothiazole 1,1-dioxide, the method being used to estimate saccharin in foodstuffs (75MI41701). 

Benzisothiazole 1,1-dioxides and saccharin derivatives are best prepared by cyclization of o-substituted benzenesulfonamides (see Section 4.17.9.1.2). 

Allyloxy-l,2-benzisothiazole 1,1-dioxide (232), known as Probenazole or Oryzaemate, is useful in the control of rice blast fungus under field conditions (75SST(3)54l). 

The succinimide derivative (234) can be used in peptide synthesis for conversion of amino acids into their succinimide esters (235 Scheme 41) (79CL1265). 3-Substituted mercapto-1,2-benzisothiazole 1,1-dioxides (236) have been recommended as an odourless means of storage of thiols. The latter are readily regenerated by the action of piperidine (81CL1457). 

An unusual thermal rearrangement of 3-allyloxy-l,2-benzisothiazole 1,1-dioxides 4 was described by Cristiano et al. Heating in a non-polar solvent, such as toluene at 85° C gave the A-allyl derivative 5 which was proposed to have formed via a [3,3] sigmatropic shift. In polar solvents, at similar temperatures, the compound... 

Bassin et al. reported a convenient synthesis of 3-methylsulphonamido-l,2-benzisothiazole-1,1 -dioxide 15 from 14 via initial condensation with ammonia followed by an internal Michael reaction <00JHC181>. 

The reaction of 3-benzisothiazolylaminomethylenemalonate (1561) with morpholine at 100°C for 1 hr gave 3-(4-morpholinyl)-l,2-benzisothiazole-1,1-dioxide (1562) (701JC499). 

Ethers of the 1,2-benzisothiazole 1,1-dioxides (35 R = Et, Me3Si) have been shown to form 1,2-benzothiazepines 12 (R = Et, Mc Si) when treated with 1-diethylamino-l-propyne 37 <1996T3339>. These ethers 12 may be hydrolyzed to the ketone 13 (see also Section 13.07.2.1), which in the solid state is in equilibrium with the enol 12 (R = H) on the basis of infrared (IR) evidence (Scheme 3). In solution (CDCI3), only the keto form 13 was detectable by H nuclear magnetic resonance (NMR). 

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