1.2.3- Triazino tetrazines

For the synthetic studies on the bicyclic 6-6 systems 1-3, with one ring junction nitrogen and five extra heteroatoms, refer to CHEC-II(1996) <1996CHEC-II(8)743>. In the studies of the newly available compounds, a one-pot procedure for the synthesis of [l,2,4]triazino-[4,3- ][l,2,4,5]tetrazine 4 derivatives is discussed below. Refluxing of hydrazonoyl halides 10 in chloroform (or ethanol) in the presence of triethylamine for 6h with either 4-amino-2,3-dihydro-6-substituted-3-thioxo-[l,2,4]triazin-5(4//)-ones 8 or 4-amino-3-methylthio-6-substituted-[l,2,4]-triazin-5(4//)-ones 9 yielded compounds 4 (Equation 1) <2000JPR342>. 

Most of the l,2,4-triazino-l,2,4,5-tetrazine derivatives 4 have been evaluated in vitro for antitumor activity. Results showed that these compounds exhibited a moderate anticancer activity toward leukemia <2003PS2055>. For biological activities of the previous compounds discussed in CHEC-II(1996), please refer to the same <1996CHEC-II(8)743>. 

The iminophosphorane 560 reacts with acyl chlorides in the presence of triethylamine in benzene at a reflux to give (88T2249) the corresponding [1,2,4]triazino[4,3-6][ 1,2,4,5]tetrazines 563. When the reaction was carried... 

Reaction of hydrazonoyl halides 40 with 4-amino-23-dihydro-6-substituted-3-thioxo-1,2,4-triazinones 39 gives l,2,4-triazino[43-h][l,2,4,5]tetrazine derivatives 41 <00JPR96>. 

The iminophosphorane (352) reacts with acyl chlorides to give the corresponding 3-substituted 1,7-dimethyl-l,4-dihydro-6//-[l,2,4]triazino[4,3-6][l,2,4,5]tetrazin-6-ones (353). The same compounds were obtained by reaction of the amino-hydrazine (354) with aldehydes and dehydrogenation of the... 

Only one such bicyclic 6-6 system, [l,2,4]triazino[4,3-A][l,2,4,5]tetrazine, such as structure (1) has been reported in literature. 

Based on the H NMR and NOE experiments data, it was concluded that the tetrahydrotetra-zine ring of 3-phenyl-1,2,3,4-tetrahydro-1,7-dimethyl-6-oxo-27/,47/-[l,2,4]triazino-[4,3-h][ 1,2,4,5] tetrazine (2) adopts a half-chair conformation (Figure 1). The ring is found to be more flattened in DMSO-dfi than in CDCI3 <88T2249>. 

The [l,2,4]triazino[4,3-h][l,2,4,5]tetrazines reported <8872249, 89JCS(Pl)247> have been prepared from 4-amino-6-methyl-3(l-methylhydrazino)-5-oxo-4,5-dihydro[l,2,4]triazine (4). The cyclocondensation of triazine (4) with carbonyl compounds such as aldehydes, ketones and 1,2-dicarbonyl compounds in ethanol at reflux temperature gave the corresponding 1,2,3,4-tetrahydro [l,2,4]triazino[4,3-h][l,2,4,5]tetrazines (5) (Scheme 1). The benzene solutions of these compounds on heating in presence of DDQ, gave the corresponding l,4-dihydro[l,2,4]triazino[4,3-h][l,2,4,5]... 

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