1.3.4- Benzothiadiazine derivative, from

Benzothiadiazines (162) unsubstituted at C-3 are accessible by the stepwise hydrolysis and decarboxylation of the l-alkyl-3-ethoxycarbonyl derivatives (160) as indicated in Scheme 22 <83JCR(S)64). The carboxylate anions are surprisingly stable, and the anion derived from the parent acid (161 R = H) is recovered unchanged after 20 hours in boiling ethanolic sodium ethoxide. 

Chloro-4//-l,2,4-benzothiadiazine 1,1-dioxides have been made from the oxo or hydroxy derivatives [90AHC(50)256 91CHE343]. Reaction of 27/-1,2,4-benzothiadiazine 1-oxides (106) with chlorine formed the S-chloro products [90AHC(50)256]. 

The availability of o-benzoylbenzenesulfonyl chlorides, prepared by diazotization of o-aminobenzophenones followed by reaction with sulfur dioxide in the presence of cuprous ions, can be exploited in the reaction with hydrazine or methylhydrazine to give 1,2,3-benzothiadiazine 14. Product 14 (R1 = Me) can also be obtained by methylationof 14(R = H) with methyl iodide and sodium hydroxide. The reduced form 15 results from catalytic hydrogenation of 14 (R = H, R2 = H)(68JHC453). Hydra-zobenzene reacts with 2-chlorosulfonylbenzoyl chloride in the presence of triethylamine to give diphenyl derivative 16 (79MI1). 3,1,2-Benzothia-... 

Mesoionic 2,1,3-benzothiadiazine 2,2-dioxide (26) is spontaneously formed from the corresponding 4-methoxy derivative by loss of methanol (79LA1130). 

Bicyclic derivatives 35a have been obtained from benzothiadiazine dioxides 27a and a,a -dibromo-o-xylene (71M1O55) in this case, when R, only one of the two possible stereoisomers is obtained (Sections lI,B,l,c and ni,C,2). 

Benzothiadiazine 1,1-dioxides (e.g., (72)) are generally prepared directly from 2-substituted benzenesulfonamides, or related derivatives (see Section 6.14.9.2.3(ii)), and only rarely by peroxide oxidation of 1,2,4-benzothiadiazine 1-oxides (e.g., (71) <87PS(29)4i>. The 1,2,4-benzothiadiazine... 

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