4H-3,1-Benzothiazines

Reduction of 02NC6H4S02CH2C0R under analogous conditions gave 3-substituted 4-hydroxy-4H-1,4-benzothiazine 1,1-dioxide (14) [Eq. (27)].67... 

Keywords 2-aminobenzenethiol, /i-kctocstcr, /Ldiketone, basic alumina, micro-wave irradiation, 4H-1,4-benzothiazin... 

H- 1,4-Benzothiazine 1,1-dioxide may be synthesized from the sulfone (260) by ozonoly-sis and hydrogenation of the ozonide over palladium on carbon (Scheme 117) (68TL1041). Phenothiazine 5,5-dioxides are produced when 2-nitrodiphenyl sulfones are reduced with triethylphosphite, this being simply an extension of a method described earlier (see Scheme 113). 

C8H7NO2S, 4H-1,4-Benzothiazine 1,1-dioxide, 40B, 343 C8H7NS2r 2-Methylthiobenzothiazole, 27, 980 CsH7NS2r 3-Methylbenzothiazoline-2-thione, 26, 7l9 C8H7NS2 r 6-Methyl-5-thioformylpyrrolo[2,1-b]thiazole, 41B, 435 C8H7N30aS, 6a-Hydroxy-5,6,6a,7-tetrahydro-8-thia-l,4-diazacycl-[3.3.2]azin-2,5-dione, 45B, 424... 

H—1,3—Benzothiazines (e.g. 375) have been prepared by a modified Ritter reaction and characterised by methiodide formation (Scheme 84). 4H-1,4-Benzothiazines(377) are... 

There are several methods for the construction of 1,4-benzothiazines 2//-forms can be obtained by the cyclization of acetals (240 X = S) in the same manner as the corresponding oxazines (76T1407), and the 4H isomers are conveniently prepared by the cycloaddition of 2-aminothiophenol and disubstituted alkynes (80JHC793). Alternative syntheses also utilize 2-aminothiophenols, by their reactions either with a-bromocarbonyl compounds <70AC(R)383) or with active methylene compounds (Scheme 109) (76JCS(P1)1146). 

Whereas the lactam salts reacted to form the target 2-mercapto-2H-l,4-benzoxazin-3 (4H)-onQ and 2-mercapto-2.W-1,4-benzothiazin-3 (4H)-om, respectively, their 4-hydroxy analogues underwent decomposition [126]. 

The first synthesis of a derivative was reported by Unger,11 who claimed that reaction of phenacyl bromide with 2-aminobenzenethiol gave 3-phenyl-2H- 1,4-benzothiazine (10a). Nearly 70 years later Friedrich et al. proposed the 4H structure (10b).12... 

Dioxo-2,3-dihydro-4H-l,4-benzothiazin lagert sich bei Einwirkung von Natronlauge zu 2-Carboxy-1,3-benzothiazol um323 ... 

Dagegen wird ausgehend von 1,3-Benzothiazol u. a. 2-Benzyliden-3-phenyl-2,3-dihydro-l, 3-benzothiazol er-halten, das sich jedoch beim Stehen in Chloroform in 3,4-Diphenyl-4H-l,4-benzothiazin umwandelt425 ... 

Phenacyl o-nitrophenyl sulfone hydrogenated with 10%-Pd-on-charcoal in ethyl acetate-acetic acid at room temp, and atmospheric pressure until 2 moles of hydrogen are absorbed 3-phenyl-4-hydroxy-4H-l,4-benzothiazine 1,1-dioxide. Y 11%. - Further hydrogenation leads to deoxygenation of the nitrogen. F. e. s. G. Pagani, G. 97, 1804 (1967). 

Vysokov V, Charushin V, Afanasyeva G, Chupakhin O (1993) The synthesis of fluorinated 4H-l,4-benzothiazine-2-carboxyhc add 1,1-dioxides - thionated analogues of Pefloxacin. Mendeleev Commun 3 159-160... 

Reaction of 2-cyanomethyl-4H-l,3-benzothiazin-4-one with benzoylace-tonitrile at 160°C yielded 8-cyano-7-imino-9-phenyl-7//,ll//-pyrido[2,l-6][l,3]benzothiazin-l 1-one (85MI1 86MI2). Reaction of 2-ethoxy-2,3 dihydro-4//-l,3-benzothiazin-4-one with 1,2,3,4-tetramethylbutadiene and 2,4-dimethyl-l,3-pentadiene in the presence of boron trifluoride in diethyl ether gave rise to 6,7,8,9-tetramethyl- and 7,9)9-trimethyl-5a,6,9,ll-tetrahydropyrido[2,l-6][l,3]benzothiazin-ll-one, respectively (73JHC149). 

Oxidation of 3-acyl-4-hydroxy-2H-l,2-benzothiazine 1,1-dioxide (9) in methanol by silver carbonate or terf-butyl hypochlorite produced 3-methoxy-4H-l,2-benzothiazin-4-one 1,1-dioxide (35),32 apparently by a free radical mechanism with participation of solvent. 

A soln. of 4-diloro-N-methyl-2-sulfamoylphenylacetic acid and a little p-toluene-sulfonic acid in dry toluene refluxed 1 hr. under a Dean-Stark trap -> 7-diloro-2-methyl-4H-l,2-benzothiazin-3(2H)-one 1,1-dioxide. Y 81%. F. e. s. J. G. Lom-bardino and E. H. Wiseman, J. Med. Chem. 14, 973 (1971) with PCI5 s. P. Catsou-lacos, J. Heterocyclic Chem. 8, 947 (1971). 

Ring closure with diazo compds. 2,3-Dihydro-4H-l,2-benzothiazin-4-one 1,1 dioxides... 

Formic acid added all at once at 21° to o-diazoacetyl-N-phenylbenzene-sulfonamide, and the product isolated after 5 min. 2,3-dihydro-2-phenyl-4H-l,2-benzothiazin-4-one 1,1-dioxide. Y 70%. Also with p-toluenesulfonic acid, and 2-methyl analog s. G. Heyes, G. Holt, and A. Lewis, Soc. Perkin I 1972, 2351. 

Carboxy-3-hydroxy- E7a, 395 (2,3-Dioxo— 2,3-H2 —indol + Cl-CH2-CO-COOH) 7-Carboxy-8-hydroxy- Vl/lc, 1087 2-Hydroxy-6,7-methylendioxy- E7a, 442 (N-oxid-Red./H - OH) Quinolin-1-oxid 6,7-Methylendioxy-E7a, 512 (N-Oxidat.) 4H-(Thieno 3,2-c -l,2-benzothiazin) -5,5-dioxid E16c, 285 (R — S02 - N 3/intra)... 

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