Dihydro-1,4-thiazine 1,1-dioxides

In principle, dihydro-1,4-thiazine 1,1-dioxide may exist as the tautomer 246 or 247 only derivatives of the former compound have been reported. 

Peracids are the normal reagents for effecting the conversions of dihydro-thiazines and their oxides into dihydrothiazine dioxides. Thus the compound 82 was transformed into the sulfone 248 by peracetic acid61 and the sulfoxide 219 afforded the derivative 249 when treated with ro-chloroperbenzoic acid.95 Unpublished studies, performed in the author s laboratory, have shown that compounds of type 199 are readily converted into the sulfones 250 by m-chloroperbenzoic acid.24 In one instance, oxygen has been reported to act... 

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

Sulfonyl imides (78) are, like sulfenes, prepared by dehydrohalogenation of the corresponding sulfonyl chlorides (79) (usually called sulfamoyl chlorides). Like sulfenes, they take part in [2 + 2] and [4 + 2] cycloaddition reactions with electron-rich alkenes or with 1,3-dienes, yielding 1,2-thia-zetidine 1,1-dioxides (80)104 or dihydro-1,2-thiazines (81),105 respectively. 

Similar ring systems were prepared <97JHC1693> by Coppo and Fawzi from the reaction of substituted ethyl 5-[methyl(methylsulfonyl)amino]-l 7/-pyrazole-4-carboxylates 119 with sodium hydride. This gave the 7-substitued 1,7-dihydro-l-methylpyrazolo[3,4-c][l, 2]thiazin-4(37/)-one 2,2-dioxides 120 in fair to good yield (Scheme 30). They also extended this synthesis by treating methyl 2-[methyl(methylsulfonyl)amino]-6-(trifluoromethyl)-3-pyridinecarboxylate 121 with sodium hydride in dimethylformamide to yield l-methyl-7-(trifhioromethyl)-l//-pyrido[2,3-c][l,2]thiazin-4(3//)-one 2,2-dioxide 122 in 79% yield (Scheme 31) <98JHC499>. 

Four regioisomeric dihydrothiazine 1,1-dioxides are possible depending upon the position of the double bond. The most common examples of this subclass include 5,6-dihydro-4//-l,2-thiazine 1,1-dioxides 5, 3,4-dihydro-2//-l,2-thiazine 1,1-dioxides 6, and 3,6-dihydro-2//-l,2-thiazine 1,1-dioxides 7. Scant interest has been paid to 5,6-dihy-dro-2/7-l,2-thiazine 1,1-dioxides 8 or their substituted derivatives. Related 3,6-dihydro-2//-l,2-thiazine 1-oxides 9 are also an important subclass of compounds due to their ease of preparation via [4-f2] cycloaddition reactions. 

The formation of thiazine systems by ring contractions of 2,3-dihydro-l,4-thiazepine 303 (Equation 108) <1971CC698>, 2,3>4,7-tetrahydro-l,4,5-thiadiazepin-3-one 3, 3 -dioxide 304 (Equation 109) <1972T2307>, 2,3-dihy-drobenzo[ ][l,4]thiazepin-4(57/)-ones 305 and 306 (Scheme 78) <1992LA403>, and 6,7-dihydro-1,4-thiazepin-5(477)-one. -oxide 307 (Equation 110) <1999H(51)1639> has been published. 

Hydroxy-2-methyl-1,1dioxo-1,2-dihydro-U6-benzo[e][1,2]thiazine-3-carboxylic acid isoxazo-3-ylamide, 4-hydroxy-2-methyl-/V-(5-methyl-3-isoxa-zolyl)-2H-1,2-benzothiazine-3-carboxamide 1,1 dioxide, Ci4H13N305S, Mr 335.34, mp 265-271 °C (decomp.) sodium salt,... 

Dihydro-1,4-thiazine 1-oxides or 1,1-dioxides can be made from the parent heterocycles by oxidation, or from alkynylcysteine 1-oxides or 1,1-dioxides by treatment with aqueous ammonia (Scheme 121) (71JOC611). 

Various methods can be used to prepare dihydro- 1,4-benzoxazines and -benzothiazines (B-78MI22701). A recent approach to the first group of compounds is to react 2-hydroxyacetanilides (279) with 1,2-dibromoethane and sodium hydroxide in acetonitrile containing the phase transfer catalyst Aliquat 336 (Scheme 122) (79S541). 1,1-Dioxides of dihydrobenzo-l,4-thiazines (281) are generated through the cyclization of imines (280) with methanesulphonyl chloride in the presence of triethylamine (79CI(L)26). 

H,3 H-Oxazolo[4,3-c][ 1,4]thiazine-6-carboxylic acid, 8,8a-dihydro-3,3-dimethyl-methyl ester X-ray diffraction, 6, 647 Oxazolo[2,3-h]thiazol-3(2H) -one 1,1-dioxide synthesis, 6, 1005... 

A solution of the above product (19.2 g, 0.093 mol) in DMF (125 mL) was added to a suspension of sodium hydride (3.08 g, 80% oil dispersion, 0.103 mol) in DMF at 006. When the addition was completed the ice bath was removed and the reaction 20 mixture stirred at ambient temperature for 1 h. The reaction mixture was cooled to 0°C and 2-bromoethyl methylether (13.6 mL, 0.14 mol) was added. The reaction mixture was stirred at ambient temperature for 18 h after which time it was evaporated to dryness. The residue was suspended in brine (100 mL) and extracted with methylene chloride (4x80 mL). The combined extracts were dried (MgS04), filtered and evaporated to a solid which was recrystallized from ethyl acetate to give the desired subject (17.4 g). Chromatography of the mother liquor (silica, 3% ethanol/methylene chloride) furnished more subject which was combined with the first batch to give a total of 19.3 g (78%) of 3,4-dihydro-4-hydroxy-2-(2-methoxy)ethyl-2H-thieno[3,2-e]-l,2-thiazine 1,1-dioxide. 

Dihydro-4-hydroxy-2-(2-methoxy)ethyl-2H-thieno[3,2-e]-l,2-thiazine 1,1-dioxide (4.9 g, 50 18.6 mmol) was converted to the 4-(l-ethoxy)ethoxy-3,4-dihydro-2-(2-methoxy)ethyl-2H-thieno[3,2-e]-l,2-thiazine 1,1-dioxide (6.2 g, 99%) using the reaction with p-toluensulfonic acid and ethylvinyl ether at 0°C in tetrahydrofuran for 2 hrs. 

Dihydro-2-(2-methoxy)ethyl-4-propylamino-2H-thieno[3,2-e]-l,2-thiazine-6-sulfonamide-l,1-dioxide hydrochloride was obtained by the reaction of 3,4-dihydro-4-hydroxy-2-(2-methoxy)ethyl-2H-thieno[3,2-e]-l,2-thiazine-6-sulfonamide-1,1-dioxide in THF containing triethylamine with tosyl chloride at -16°C and the next stirring for 18 hrs at room temperature. After which time the mixture was cooled to 0°C and propylamine was added, the desired product (0.57 g, 46%) was obtained m.p. 178°-181°C. 

C yHlyClN2 100643-71-8) see Loratadine (4.V)-6-chloro-3,4-dihydro-2//-thieno[3,2-c]-l,2-thiazin-4-ol 1,1-dioxide... 

Cyclisation of 5-benzylsulfonyl-3-chloro-4-methoxycarbonylaminoisothiazole (18) using an excess of NaOMe in DMF gave 3-methoxy-5-oxo-6-phenyl-5,6-dihydro-4//-isothiazolo[5,4-f>]-1,4-thiazine 7,7-dioxide 19, which was the first representative of a new heterocyclic ring system. Compound 18 was prepared in good yield (81%) by the reaction of 17 with PhI(OAc)2 in methanol <02RCB187>. 

E)-6-chloro-3-[hydroxy(pyridine-2-ylamino)methylene]-2-methyl-2,3-dihydro-4H-thieno [2,3-e] [1,2] thiazin-4-one, 1,1 -dioxide. 

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