4H,l,3-benzothiazines

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). 

From 4H-l,3-benzothiazines. 2-Arylbenzo-TAs 85 may be synthesized via oxidation of thiazines 84 by means of chromic anhydride (58ACH201) or potassium permanganate (89MI1) (Scheme 26). 

NaOH added to 2,3-dihydro-2-imino-4H-l,3-benzothiazin-4-one, heated several min. on a steam bath to effect complete soln., cooled to 0°, and ethylene oxide added —crude o-(2-hydroxyethylthio) benzoyl cyanamide. Y 90%. F. e. s. J. C. Howard, J. Org. Chem. 29, 761 (1964). 

Thiosalicylic acid added to dicyclohexylcarbodiimide whereupon an exothermic reaction takes place, dry benzene added to make the thickening mixture more fluid, allowed to stand 3 hrs. at room temp., then heated 20 hrs. on a steam bath 3-cyclohexyl-2-cyclohexylimino-2,3-dihydro-4H,l,3-benzothiazin-4-one. Y 56%. F. e. s. B. Loev and M. Kormendy, J. Org. Ghem. 27, 3365 (1962). 

Benzo-l,3>thiazines.—A direct procedure for preparing 2,3-dehydro-4H-l,3-benzothiazines is afforded by the condensation of 2-mercaptobenzylamine and its derivatives with ketones or aldehydes in alkaline medium. Thus, for example, (46) reacts with acetaldehyde to give (47 R = Me) in excellent yields. A somewhat different course is observed in the condensation of (46) with formaldehyde, which gives the methylene bis-derivative (48), resulting from the fast reaction of the primary product (47 R = H) with more of the aldehyde. 

H-l,4-Benzothiazine 7-Fluor-2-methoxycarbonyl-3-methyl- E9a, 457 (4-F — 2-SH-anilin + H3C-CO-CH2-COOR)... 

H-l,4-Benzothiazine 2-Ethoxycar-bonyl-3-methyl-6-sulfo- E9a, 457 (3-NH2 — 4-SH — Ar — SOjH +... 

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. 

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 ... 

Dihydro-1,3-thiazines, dihydro-1,3-thiazinones, 2 i-l,3-benzothiazines, 4H-7,5-benzothiazines, and related compounds... 

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). 

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. 

A soln. of phenacyl chloride in methanol dropped rapidly into a mixture of 3-methylbenzothiazolium methosulfate and triethylamine in methanol, and warmed 0.5 hr. at 60° 4-methyl-2-benzoyl-4H-l,4-benzothiazine. Y 65-97%. F.e. s. 

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... 

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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