4/7-1,4-benzothiazin

Reactions with aromatic binucleophiles form fused ring heterocycles (00T7267). Thus, when the reaction is performed with 2-aminothiophenol, compound 99 is converted into 2-trifluoroacety 1-4/7-1,4-benzothiazine (identified by X-ray crystallography) (Scheme 106). In the case of thioethanolamine hydrochloride, the product is 2-trifluoroacetyl-47/-1,4-thiazine. 

Benzothiazin-4-ones, dihydrosynthesis, 3, 1028 Benzothiazole, acetoacetylamino-azo pigments from, 1, 334 Benzothiazole, 2-acyl-synthesis, 6, 265 Benzothiazole, 2-alkoxy-synthesis, 6, 323 Benzothiazole, 2-alkyl-synthesis, 6, 265 Benzothiazole, 2-alkyl-6-nitro-reactions... 

The most widely used variant of the Gabriel-Colman is the conversion of saccharine derivatives to benzothiazine derivatives. The reaction has been extensively studied as benzothiazines are important pharmacophores, particularly in the oxicam class of antiinflammatories. The first reported instance of this transformation was in 1956 where 43 was treated with sodium methoxide to provide 44. The rearrangement also works with esters " and some amides " in addition to ketones. 

The mechanism of this variant of the Gabriel-Colman reaction has been investigated. Treatment of saccharine derivatives 45-48 with 1-2 equivalents of sodium alkoxide at room temperature provides esters 49-52 in good yields treatment of 45-48 with sodium alkoxide at reflux provides the expected benzothiazines 53-56. Increased concentration leads to higher yields. 

The benzothiazine equivalent of a 1,7 naphthyridine (58) has also been prepared. The reaction did not work in alcoholic solvents, but when DMF was used 57 rearranged to provide the desired product in moderate yield. 

Tire mesoionie l,2,4-triazolo[l,5-c]quinazolines 59 were obtained upon eyelization of the 4-thioxo-l,3-benzothiazines 57 with thioearbohydra-zine through the intermediate 3-(4-thiosemiearbazido)pyrimidines 58 (86-JHC43) (Seheme 19). 

When bromoacetyl chloride is used instead of bromoacetic acid, the anilide 33 is formed at the first stage. Its subsequent cyclization also leads to 32. This approach to benzotellurazinone is similar to that developed for the synthesis of 2//-l,4-benzothiazin-3(4//)-ones (66CJC1247). Significantly, attempts to isolate the intermediate sulfonium salts analogous to 30 were unsuccessful. 

Cyclization of A -methyl-3-phenyl-propanesulfonamide 95 afforded 3-phenyl-A -methyl-isothiazolidine 5,5-dioxide 96 (OOJOC(65)926). The photochemical treatment in dichloroethane with diacetoxyiodobenzene in the presence of iodine was carried out at room temperature. By using 2-phenyl-ethanesulfon-amide 97, the cyclization occurred giving the corresponding benzothiazine 5,5-dioxide 98. 

Reaction of 5n,6,7,8,9,l l-hexahydropyrido[2,l-f ][l,3]benzothiazine-7,l 1-dione (47, X = S, R = H) and 2-amino-6-fluorobenzamidine dihydrochloride in boiling EtOH yielded a diastereomeric mixture of spiro derivatives 48 (X = S, R = H), which were separated by flash column chromatography (OOMIPl). 

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