1.2.3- Triazino thiadiazines

The compound 7-(4-chloro-benzyl)-2-(4-chloro-phenyl)-3,8a-dihydro-pyridazino[4,3-( ][l,3,4] thiadiazin-8-one 42 has been reported to be active against Bacillus Escherchia coli, Staphylococcus aureus, and Pseudomonas aeruginosa by a serial dilution method <2001IJB475>. Triazino-thiadiazines 24f, 25b, 25c, and 25f <2002IJH287> have been reported to be active against S. aureus-, sydnone derivatives of triazino-thiadiazine 24f <2002IJH287> are more reactive than coumarin derivatives. 

Another cyclisation involving 4-amino-6-methyl-3-thioxo-l,2,4-tiiazin-5-one 82 is the reaction with propargyl bromide followed by palladium(II) catalysis to yield a [1,2,4] triazino[3,4-f ][l,3,4]thiadiazine 83, or with phenacyl bromide to give 84 <96MI03 96CA(125)195597 96MI04 96CA(125)247767 >. 

Reports of bicyclic systems with one nitrogen atom containing two additional heteroatoms in each ring are scant in the literature. Fourteen such ring systems have been reported previously 1-14 <1996CHEC-II(8)733>. The literature examples available during the last decade include 1,2,4-triazino[3,4-Z ][ l,3,4]thiadiazine-4,7-dione 15, [l,2,4]tri-azino[3,4-/d [ 1,3,4]thiadiazinc 16, l,9a-dihydro-8//-l, 2,4-triazino-[3,4-Z ] [1,3,4] thiadiazine-4-oncs 17, [l,3,5]tria-... 

Amino-8-cyano-3-methyl-4-oxo-6/7-[l,2,4]triazino[3,4-7][l,3,4]thiadiazine 16 when reacted with phenacyl bromide in the presence of triethylamine in acetonitrile afforded a novel heterocyclic system 27 (Equation 1) <2004IJH181>. 

Most of the reported triazinothiadiazines have been prepared from 1,2,4-triazine derivatives. Treatment of amino-1,2,4-triazine 28 with chloroacetyl chloride in dioxane in the presence of triethylamine at 10 °C resulted in the formation of 6-methyl-4-(A -chloroacetamido)-3-thioxo-5-oxo-2,3,4,5-tetrahydro-l,2,4-triazine 29 and 3-methyl-4,7-dioxo-4,6,7,8-tetrahydro-l,2,4-triazino[3,4-A][l,3,4]thiadiazine 15 (Scheme 1) <2005JHC935>. 

Alkyl-8H-7-aryl-l,2,4-triazino[3,4-3]-[l,3,4]thiadiazine-4-oncs 19 have been prepared from the reactions of tri-azines 30 with various phenacyl bromides. The intermediates 31 formed in such reactions underwent loss of HzO to form 19 (Scheme 2) <2003CHE809>. 

A series of 4//.8//-1,2-4-triazino[3,4-//]-l,3,4-thiadiazin-4-ones 17 <2001IJB475> has been reported and obtained by condensation of 4-amino-6-substituted-3-mercapto-l,2,4-triazin-5(4//)-ones 35 with various phenacyl bromides (Equation 2) <2001IJB475>. 

There are only two examples in which a heterobicyclic ring system is synthesized in a one-pot procedure from acyclic precursors. The first involves formation of the rare [l,2,4]triazino[6,5-e]-1,2,3-oxathiazine ring system (486) by condensation of the aryl hydrazone (485) with chlorosulfonyl isocyanate (Equation (98)) <91SC1695>. The second involves formation of the [l,3,4]thiadiazino[6,5-e][l,3,4]-thiadiazine (488) as a minor by-product when (487) is heated with triethyl orthoformate (Equation (99)) <71TL4985>. 

The electrochemical oxidation of catechols in the presence of 6-methyl-l,2,4-triazin-3-thion-5-one and 4-amino-6-methyl-l,2,4-triazin-3-thion-5-one as nucleophiles in aqueous solutions provided an efficient electrosynthesis of thiazolo[3,2-fi][l,2,4]triazin-7-one and l,2,4-triazino[3,4- ]l,3,4-thiadiazine derivatives respectively <06TL1713> <06TL8553>. 

Substituted 6-chloropyrimidino[4,5-e][l,3,4]thiadiazine reacted with hydrazine hydrate to give the corresponding 6-hydrazino derivative which was transformed into various substituted [ 1,2,4]triazino[ 1,2-o]pyrimido[4,5-e][ 1,3,5]thiadiazines <05PS2477>. 

The [l,2,4]triazino[3,4-6][l,3,4]thiadiazine (58) was found to be hght sensitive in photographic recording and is used in producing photographic images <82EUP45427>. 

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