2.1- Benzothiazine 2,2-dioxides

Benzothiazine 1,1-dioxides can be synthesized from sulfones (e.g., 355) by base-induced cyclization as exemplified in Scheme 192 <2005BMC141, CHEC-III(8.09.9.1.3)653>. 

Hydroxy-3,4-dihydro-2,l-benzothiazine 2,2-dioxide 15 can be synthesized in a convenient manner <94TL2911>. Blondet and co-workers used a cyclization of an ortho-(chloromethyl or carboxaldehyde) A-protected sulfonanilide 13 or 16 with sodium hydride in DMF to give the benzothiazine dioxide 14 or 17 in 35% and 47% yields, respectively (Scheme 4). Finally, removal of the methoxy group and hydrogenation led to the formation of 5-hydroxy-3,4-dihydro-2,l-benzothiazine 2,2-dioxide 15 in good yield over two steps. 

Routes to 3,4-dihydro-2/7-1,2-benzothiazine dioxides (253) include the cyclization of aminosulfonic acids (252) or cyanosulfonamides (254). 2,4-Dihydro-1H-2,1 -benzothiazine dioxides (256) are normally prepared by thermolysis of the sodium sulfonates (255) or amino sulfonamides (257)... 

Benzo-l,2-thiazines.— As usual, work in this area is limited, and is mainly occasioned by the search for biologically or chemotherapeutically active compounds. In addition to several patents, which, for reasons of space, are not considered, two reports have appeared describing various alkylation and amination reactions of some benzothiazine dioxides, e.g. (2), available by base-induced rearrangement of appropriately jV- -keto-substituted saccharins (1). 

Benzo>l,2-thiazines.—A novel route to benzothiazine dioxides, e.g. (8), is based upon the facile cyclization of o-diazoacetylbenzenesulphonamide (7)... 

An attempt to achieve the ring-expansion of the benzothiazine epoxide (14) via benzoyl migration with boron trifluoride etherate in dichloro-methane is reported to yield, instead of the desired -diketone (IS), the keto-aldehyde (16), arising apparently by phenyl migration this is an alternative pathway that has already been observed. Existing syntheses of the 2,1-benzothiazine dioxide (18) have been supplemented by an improved... 

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. 

Treatment of 1-arylsulfonylpipecolinamides 46 with excess EDA gave pyrido[l,2-ft][l,2]benzothiazine 5,5-dioxides 47 in a carbanion-mediated reaction (97SL1079, 98MI2). When the reaction mixture of 46 (R = Me, R = H) was quenched with Mel an ethyl derivative 47 (R = Et, R = H) was obtained. 

Bromo atom of ethyl (3S)-10-bromo-3-methyl-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate was change for hetaryl groups with tributylstannyl derivatives of heterocycles in the presence of (Ph3P)2Pd(II)Cl2 in boiling toluene (OOMIPIO). 7-Aryl-5-oxo-2,3-dihydro-5//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylates, 6-carboxamides and their 1,1-dioxide derivatives were prepared from 7-chloro derivatives in the... 

Aryl-5-oxo-2,3-dihydro-5//-pyrido[l,2,3- e]-l,4-benzothiazine-6-carbox-amides and their 1,1-dioxides were prepared from the respective... 

Carbethoxy-4-hydrOxy-2-methyl-2H-1 -benzothiazine-1,1-dioxide 3-Amino-5-methyl-isoxazole... 

A mixture of 40.5 g (0.15 mol) of 3-carbethoxy-4-hydroxy-2-methyl-2H-1.2-benzothiazine 1,1 -dioxide, 20.6 g (0.21 mol) of 3-amino-5-methylisoxazole, and 2,500 ml of xylene was refluxed for 24 hours in a Soxhiet apparatus, the thimble of which contained 60 g of Linde type 4A molecular sieve. The mixture was cooled to 25°C and the resulting crystalline precipitate was collected and washed with ether to give 44 g of crude product. Recrystallization from 1,6(X) ml of 1,4-dioxan gave 34.7 g of material, MP 265°C to 271°C dec. 

Carbethoxy-4-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1 -dioxide Isoxicam... 

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). 

CN 4-hydroxy-2-methyl-//-(5-methyl-3-isoxazolyl)-2/7-1,2-benzothiazine-3-carboxamide 1,1-dioxide... 

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