2,1-Benzisothiazoles electrophilic substitution

Both the 1,2- and 2,1-benzisothiazoles are attacked by electrophiles in the carbocyclic ring. Electrophilic substitution in analogous azine fused systems is therefore dependent on the presence of strongly electron donating substituents. 

Benzisothiazole undergoes nitration at its 5- and 7-positions.1 Electrophilic substitution of 3-methyl-1,2-benzisothiazole (2) and its 5-amino, 5-... 

Electrophilic Substitution. Bromination of 2,1-benzisothiazole under conditions where Br is the electrophilic species gives a mixture of 5- and 7-bromo-2,l-benzisothiazole, together with a little of the 4,7-dibromo-compound. The bromination products differ in basicity and may be separated by taking advantage of this fact. The orientation of the substituents may be deduced from n.m.r. studies. ... 

Both 1,2- and 2,1-benzisothiazoles react with electrophiles to give 5- and 7-substituted products (see Section 4.02.3.2). The isothiazole ring has little effect on the normal characteristics of the benzene ring. C-Linked substituents react almost wholly normally, the isothiazole ring having little effect except that phenyl substituents are deactivated (see Section 4.17.2.1). There are, however, considerable differences in the ease of decarboxylation of the carboxylic acids, the 4-isomer being the most stable (see Section 4.02.3.3). 

Benzisothiazoles are best prepared by oxidative cyclization of o-aminothiobenz-amides (see Section 4.17.9.1.1), reaction of o-toluidines with thionyl chloride (see Section 4.17.9.2.1) or by sulfuration of 2,1-benzisoxazoles (see Section 4.17.10.2). 1,2-Benzisothiazoles can also be prepared from o-disubstituted benzene compounds, cyclodehydration of o-mercaptobenzaldoximes or oxidative cyclization of p-mercaptobenzylamines (see Section 4.17.9.1.1) being the most convenient. Both series of benzo compounds are readily substituted at the 5- and 7-positions by electrophilic reagents. 

Few examples of functionalization on the benzene ring of benzisothiazole have been reported (see Section 4.05.7.2). Studies on the reactivity of unsaturated chains in cycloaddition reactions have been reported (see Section 4.05.7.3). The high reactivity of 4-vinylisothiazolin-3-one A-oxides in Diels-Alder cycloadditions, both as diene and dienophile, is illustrated by their tendency to dimerize. 5-Vinylisothiazole A,A-dioxides react at the vinyl function with different 1,3-dipoles. Isothiazolo-3-sulfolenes 265 give an o-quinodimethane which can be trapped with a dienophile. Different isothiazole derivatives substituted with a carbon chain functionalized with heteroatoms have been prepared as ligands for the formation of complexes. 3-Oxocamphorsulfonimide reacts with the anion of alkynes and several studies on the reactivity of the products with electrophiles are reported. 

A neat use of lithiation methods allows the synthesis of 7-substituted benzisothiazole S,S-dioxides, thus when two mol equivalents of the lithiating agent are used, two successive lithiations ortho to the sulfonamide unit take place, the first leading to ring closure and the second allowing introduction of an added electrophile at C-7. ... 

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