1.2- Benzisothiazoles bromination

Bromination follows a similar course, except that 2,1-benzisothiazole produces the 4,5,7-tribromo derivative when excess of reagent is used (72AHC(14)43), and 3,5-disubstituted 1,2-benzisothiazoles are brominated at the 4-position (80JCR(S)197). 7-Amino-4-chloro-l,2-benzisothiazole is brominated at the 6-position (71JCS(C)3994). 

Benzisothiazole, 3-methyl-bromination, 6, 155 nitration, 6, 154 synthesis, 6, 171, 172 Vilsmeier-Haack reaction, 6, 149, 152... 

Pfizer has also prepared both and " C-labelled ziprasidone (Schemes 18 and 19) to detennine its metabolism and tissue distnbution. It was envisioned that tritium could be introduced in the last step of e synthesis utilizing the selective replacement of a bromine atom on the benzisothiazole nng. Therefore, the synthesis began with the bromination of 39 using bromine in acetic acid with FeCls catalysis. The dibrominated regioisomer 60 was isolated by liquid chromatography in 18% yield and reacted with... 

Amino-5-nitro-2,1-benzisothiazole and its 7-substituted derivatives are obtained on oxidation of 5-nitro-2-amino-3-R-thiobenzamides with hydrogen peroxide or bromine (Scheme 2.94) [544—546],... 

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. ... 

---