1.3.4- Thiadiazines, fused synthesis

More intensive investigations have been carried out with synthesis of t-fused [l,3,5]thiadiazines, and the transformations are shown in Scheme 32. 

The synthesis of this ring system by condensation of 3,4,5-triamino-l,2,6-thiadiazine-l,1-dioxide with formic acid equivalents to give the fused imidazole ring dates back to the review by Montgomery and Secrist <1984GHEC(5)607>. This methodology was extended to cyclocondensation reactions of 3,4,5-triamino-l,2,6-thiadia-zine-1,1-dioxide with electrophiles such as methyl chloroformate and carbon disulfide to yield 6-oxo 98 and 6-thioxo 99 derivatives of 4-aminoimidazo[4,5-d-l,2,6-thiadiazine-2,2-dioxide respectively (Scheme 72) <1999BMC1617>. 

Functional derivatives of 1,3,4-thiadiazines and of fused systems on their base, synthesis and properties 91KGS1443. 

The same type of synthesis affords pyrazino[2,3-e]-1,2,4-triazines (329) and (330) from the diamino precursor (328), by reaction of the latter with glyoxal or phenylglyoxal, respectively. Product (329) is a dihydrate. The fully aromatic intermediate could not be isolated. Formation of (330) involves not only covalent solvation, but also an unusual TV-methylation of the presumed first-formed intermediate, and the suggested mechanism is outlined in Scheme 24 <86JHC33,93H(36)2577>. Reversing the order of polarities of the components allows [4 + 2] cyclization of pyrimidine (331) with orr/io-phenylenediamine (332), giving the benzo fused pyrazino[2,3-c][l,2,6]thiadiazine (333) (a [l,2,6]thiadiazino[3,4-6]quinoxaline]) (Equation (52)) <72ZN(B)1471>. 

An aza-Wittig reaction may be adapted to the synthesis of a fused thiadiazine ring under mild conditions with a two-molar proportion of an isothiocyanate. The reactions of isothiocyanates have been reviewed [3990]. In this way, an iminophosphorane is annulated to a neighbouring sp ring-carbon atom. 

Principally, three different routes have been described for the angularly fused pyrido[2,l-c][l,2,4]benzothiadiazines. In the first route, the thiadiazine ring is formed in the final step of the synthesis, as exemplified by ring closure of appropriately orr/io-functionalized piperidinobenzenes. By thermolysis of the sulfonyl azide (245) in DMSO, in the presence of copper, the hexahydro derivative (246) was formed as main product, whereas photolytic decomposition afforded the tetrahydro derivative (247) (Scheme 23) <71CC1319,74JCS(Pl)245l>. 

Several reports have dealt with fused [6+5] derivatives containing sulfur atoms. Thus, the synthesis and evaluation of the antibacterial and antifungal activity of i-triazolo [3,4 b][ 13,4]thiadiazoles, s-triazolo[3,4-b][ 1,3,4 thiadiazincs and s-triazolo[3, 4 /23][ 13,4]-thiadiazino-[5,6-b]quinoxaline have been reported <01IJC(B)368>. A series of 3,6-substituted-7//-5-triazolo[3,4-6][l,3,4]thiadiazines has been prepared through condensation of suitable 3-substituted-4-amino-5-mercapto-1,2,4-triazoles with phenacyl bromides and... 

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