Benzothiazines bromination

Much more is known about the sulfur analogues, especially the benz derivatives of 1,4-thiazine. Bromination of AH-1,4-benzothiazine 1,1-dioxide occurred in the 2-position (68TL1041). 

A convenient method for the synthesis of trioxo-benzothiazine 181 involves a ring expansion reaction of benzoisothiazole 180 <07H1843>. Directed ort/ o-mctalation of benzenesulfonamide 176 coupled with carboxylation gives rise to 2-carboxybenzene-sulfonamide 178 which is then converted to benzoisothiazole 179 under the TMSCl-Nal deprotective-cyclization conditions. Bromination of 179 followed by ring expansion mediated by 20% KOH according to the Abramovitch procedures furnishes the benzo-thiazine 181. Optical resolution of 181 using (-)-menthoxyacetyl chloride yields its (+) and (-) enantiomers. 

Bromination of 239, even with limited amounts of the brominating reagent, afforded complex mixtures containing a tribromo derivative tentatively identified as 3(or 4),6,8-tribromo-lH-2,l-benzothiazine 2,2-dioxide. However, bromination of the iV-methyl analog 261 using N-bromosuccinimide cleanly gave 6-bromo-l-methyl-lH-2,l-benzothiazine 2,2-dioxide (262) (Eq. 54). 

---