1,2,6-Thiadiazine 1,1-dioxides, formation

Alkylation of the exocyclic amino group of the 4-amino-6-phenylpyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxide 95, shown in Equation (14), with ethyl iodide and potassium carbonate in acetone gave the corresponding 4-ethyl-amino derivative 96 in a clean and efficient manner, although the researchers noted that the procedure is not general due to competitive formation of dialkylated products <2000JME4219>. The procedure described in Section 10.20.6.3 (Equations 10 and 11) is, in fact, a more efficient entry to 4-alkylamino pyrazino[2,3-c] [ 1,2,6]thiadiazine 2,2-dioxide. 

An equimolar ratio of a substrate and oxidizing agent gives oxides 23 and 24 in yields of 71% and 4%, respectively, whereas triple the amount of oxidizing agent leads only to dioxide 24 in 93% yield. The intermediate naphtho[nitrogen elimination even at room temperature. Dioxide 24 may be obtained only on oxidation of monoxide 23, and not via the formation of... 

While 1,2,4- and 1,2,6-thiadiazines have been extensively investigated, there is relatively little known about 1,2,3-thiadiazines, and 1,2,5-thiadiazines are the least known. Apart from 1,2,5-thiadiazines, the thiadiazines most commonly exist as 5,5-dioxides. This is in part due to their ease of formation, their stability, and the potential of the sulfonamide group to impart biological activity. 

The use of IV-chlorosulfonyl lactams for the preparation of 3-oxoperhydro-1,2,6-thiadiazine 1,1-dioxides 57 provides a different example of a [5 -F 1]-reaction. These react with a weak base, such as 4-nitroaniline, in combination with triethylamine. The mechanism proposed (Scheme 23) involves formation of an intermediate (55), which is converted to the nucleophile 56 by the action... 

A superior synthesis of 3-amino-4-alkyl- and 3-amino-4-aryl-4//-l,2,4-benzothiadiazine 1,1-dioxides (135), involving the amino-dechlorination of chloro compounds (130 R = alkyl or aryl) with aqueous ammonia in chloroform has been reported <86S864> yields are excellent (86-94%). It has been shown that l,5-diphenyl-6-bromo-lA 2,4-thiadiazine 1-oxide (136) (see Section 6.14.6.3.3) undergoes metal exchange with butyllithium and, on quenching the mixture with ethyl chloro-formate, the 6-ethoxycarbonyl derivative (137) is obtained in moderate yield (31%). Displacement... 

The conversion of a 1,4,3-oxathiazine 4,4-dioxide (268) by ethanolic ammonia into a 4H-l,2,4-thiadiazine 1,1-dioxide (269) is a rare example of the formation of a 1,2,4-thiadiazine by ring transformation from another six-membered heterocyclic system (Equation (23)) <888521 >. 

The formation of 1,2,4-thiadiazine 1,1-dioxides occurs by the addition of carbonitriles to alkyl-sulfonamide dianions followed by carbonylation with phosgene or phenyl chloroformate (Section 6.14.9.2.3(h)), and by the [4-1-2] cycloaddition of 1,3-diaza-1,3-butadienes with sulfene (Section 6.14.9.2.2(iii)). 

Attempts to condense 3,4,5-triamino-2/7-l,2,6-thiadiazine 1,1-dioxide (155) with methyl chloro-formate in dimethylformamide solution gives not the expected 6-oxoimidazo[4,5-c][l,2,6]thiadiazine... 

Catalytic debenzylation of 2-benzyl-4-methyl-6 -l,2,6-thiadiazin-3(2//)-one 1,1-dioxide (165) is effected in high yield (86%) with palladium-charcoal and hydrogen over a short period (1 h) <84CCC840>. However, on prolonged treatment (12 h) debenzylation is followed by reduction of the C-4—C-5 double bond and formation of 4-methyl-5,6-dihydro-4 -l,2,6-thiadiazin-3(2//)-one 1,1-dioxide (166) (Equation (17)). 

The condensation of ) -diketones with sulfamide is a well-established route to 3,5-disubstituted 2//-l,2,6-thiadiazine 1,1-dioxides <52JOC339>. A less used route is the formation of3,3-disubstituted-... 

Treatment of 4//-l,2,4,6-thiatriazine 1,1-dioxide (295) with malononitrile anion leads to the formation of 5-amino-4-cyano-2/7-l,2,6-thiadiazine 1,1-dioxide (296 R = NH2) in 60% yield (see also Section 6.16.9.2.1.1) <84H(22)47i>. This ring transformation is proposed to go by a double carbanion addition at the 2,3- and 5,6- imine bonds followed by ring-opening and ring-closure, with... 

The scope of the reaction was probed by extending the reaction to the synthesis of six-membered cyclic sulphamides. The reaction of 367 with acetamidine gave 1,2,4,6-thiatriazinone-1,1-dioxides 371 (equation 121) in yields of 20%. Fragmentation of the intermediates prior to cyclization is considered to account for the low yields. Modest yields of the pyridothiatriazinone 372 were obtained by condensation of aminopyridine with 367 (equation 122). Aminotriazoles when reacted with 367 yielded the triazolothiatriazinones 373 (equation 123). The reaction of 2-amino-3-ethoxycarbonyl 4,5,6,7-tetrahydro-l-benzothiophen (374) with isopropyl sulphamoyl chloride gives the iV-(isopropyl)-iV -(3-ethoxycarbonyl-4,5,6,7-tetrahydro-l-benzothiophene)sulphamide (375)369. Cyclization of 375 with 5% sodium hydroxide leads to the formation of the cyclic sulphamide 3-isopropyl-4-oxo-3,4,5,6,7,8-hexahydro-1H [ 1 ] -benzothieno [2,3-d] -2,1,3-thiadiazin-2,2-dioxide (376) in 42% yield. Decarboxylation of 375 also occurs in the reaction with the formation of iV-(isopropyl)-iV -(4,5,6,7-tetrahydro-l-benzothiophene)sulphamide 377... 

Cyclocondensation reactions of 3,4,5-triamino-l,2,6-thiadiazine 1,1-dioxide 193 with various acceptors allowed formation of bicyclic compounds. In the first instance, condensations with methyl chloroformate or carbon disulfide provided 6-oxo 194 and 6-thio 195 derivatives of 4-amino-l/f,5/f-imidazo[4,5-f][l,2,6]thiadiazine 2,2-dioxide, respectively (Scheme 17) <1999BMG1617>. 

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