Thiazine 1,1-Dioxides

Among the heterocyclic systems that have been used to provide a backbone for acidic, nonsteroidal antiinflammatory agents are benzo-1,2-thiazine dioxides, such as 193-195. Entry to the ring system is gained by an interesting ringenlarging rearrangement. 

Dibenzo[l,2]dithiins 54 are prepared by oxidation of appropriate dithiols 53 and related starting materials (e.g., Scheme 27). Dibenzo[l,2]thiazine dioxide 56 is obtained by thermolysis of the azide 55 (Scheme 28) <1969JA1219>. 

Intermediates of type 42 may be generated by cycloaddition reactions. Thus, when the thiirene 1,1-dioxide 45 was treated with the mesoionic compound 46 at ambient temperature, the sulfone 44b was produced in high yield the thiazine dioxide 44a was prepared in a similar manner. It is noteworthy that the intermediate cycloadducts 47a and 47b lost carbon dioxide in preference to sulfur dioxide. 

When heated, thiazine dioxides are reported to lose sulfur dioxide and to afford pyrroles for example, 2,5-diphenylpyrrole is formed when compound 43a is heated at 300°C over copper. 

Persuasive evidence that iV-unsubstituted thiazine dioxides exist as the 4H-tautomers is provided by IR spectroscopy " " thus the compounds 40, 43a, and 44a show absorptions in the 3360-3380 cm region, attributable to N—H stretching vibrations. Bands ascribable to C=C stretching vibrations are observed in the 1675-1645 cm" region. The symmetrical and asymmetrical stretches of the sulfone group typically cause strong absorptions at 1130-1160 and 1310-1335 cm"S respectively. In the case of thiazine dioxides, such absorptions occur in the 1105-1135 and 1280-1295 cm regions. 

The protons at positions 2 and 6 of symmetrical thiazine dioxides resonate in the 5 5.95-6.36 region in the case of the anion 48, the protons are shifted upheld by 0.45 ppm (to 5 5.91). The parent compound 40 provides the only example of a 4H-l,4-thiazine dioxide, unsubstituted at positions 3 and 5, whose NMR spectrum has been reported the 3- and 5-protons appear as a multiplet centered at S 1.06f ... 

Scheme 7 Approach to the synthesis of the naphthoquinone thiazine dioxide conicaqunone B.

Normally, decompositions of azides in hydrogen-rich solvents are avoided in order to minimize the formation of products based on triplet nitrene. Surprising, therefore, is the report that 6i/-dibenzo[c ,e][l,2]thiazine 5,5-dioxide (335) is obtained in optimum yield (80.6%) from the thermolysis of biphenyl-2-sulphonyl azide in cyclohexane at 120 Decomposition of o-(2-thienyl)benzenesul-phonyl azide under similar conditions furnishes the thieno[3,2-c]benzo-l,2-thiazine dioxide (336), in practicable yield (61%). Whereas, in POCla-pyridine... 

In the course of biological screening programmes, numerous benzo-thiazine dioxide derivatives have been produced by variations of... 

Similar transformations are based upon 1,2-thiazine 2,2-dioxides (5-sultones), easily obtained by treating a,/3- or /3,y-unsaturated ketones with acetic anhydride and sulfuric acid. These compounds can be converted subsequently into furans, thiophenes or pyrroles (Scheme 115). 

Chemical Name 2-(4-Chlorophenyl)tetrahydro-3-methyl-4H-1,3-thiazin-4-one 1,1-dioxide Common Name Chloromethazanone Structural Formula ... 

Chemical Name 4-Hydroxy-3-(5-methyl-3-isoxazolocarbamyl)-2-methyl-2H-1,2-benzo-thiazine 1,1 -dioxide... 

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). 

Thiazepinones, as photolytic products 883 Thiazine 1-oxides, synthesis of 323, 352 Thiene dioxides formula of 382 synthesis of 469 Thiene oxides formula of 382 synthesis of 469... 

CN (4R)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-27/-thieno[3,2-e]-l,2-thiazine-6-sulfonamide 1,1-dioxide... 

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