1.2.4- Triazine 1-oxide, 3-hydrazino

Although, 3-hydrazino[l,2,4]triazines have been shown to be versatile precursors for the synthesis of [l,2,4]triazolo[4,3-6][l,2,4]triazines, 3-hydrazino-l, 2,4-triazine-l-oxide 821 cyclized with triethyl orthoformate to give [l,2,4]triazolo[3,4-c][l,2,4]triazine 822. Cyclization takes place at N-4 of 821 (80JOC5421) (Scheme 166). 

Four methods have been published for the introduction of hydrogen into the 1,2,4-triazine ring, i.e. reduction of halo-1,2,4-triazines, oxidation of hydrazino-l,2,4-triazines, treatment of sul-fonylhydrazino-l,2,4-triazines with base, and decarboxylation of 1,2,4-triazinecarboxylic acids. Decarboxylation of l,2,4-triazine-3-carboxylic acid has been used for the synthesis of the parent 1,2,4-triazine (l) 2 120 this method was also used for the synthesis of other 1,2,4-triazines.270 l,2,4-Benzotriazine-3-carboxylic acid was decarboxylated to give the parent 1,2,4-ben-zotriazine (2).151 271... 

Reactions of 3-hydrazino-l,2,4-triazine 1-oxide 31 or 3-hydrazinopyrido [2,3-c]-l,2,4-triazine 1-oxide 32 with diethoxymethyl acetate or triethyl orthoformate proceed as cyclization reactions at the N(4) atom and the amino group to form the corresponding pyrazolo[3,4-c]-l,2,4-triazine 6-oxides 33 and 34 (74MI, 80JOC5421, 80MI). 

The methoxy group is replaced in the reaction of 3-methoxy-5-phenyl-1,2,4-triazine 1-oxide 46 with ammonia, resulting in 3-amino-5-phenyl-1,2,4-triazine 1-oxide 47. The treatment of 3-methoxy-1,2,4-triazine 1-oxide 20 with hydrazine leads to 3-hydrazino-1,2,4-triazine 1-oxide 48 (71JOC787). 

The diazotization of 3-hydrazino-l,2,4-triazine 1-oxides 48results, as expected, in 3-azido-l,2,4-triazine 1-oxides 4 (77JHC1221, 77JOC3498). 

Heteroannelated 1,2,4-triazine 4-oxides—fervenulin 4-oxides 12—were obtained starting from 6-hydrazino-l,3-dimethyl-5-nitrosouracil. Orthocarboxylates, formic acid, dimethyl sulfate, or DMF in the presence of POCI3 were used as cyclization agents (77H273, 78JOC175, 78JOC469). 

Hydrazino-3-methylbutan-2-one oxime reacts with aldehydes and ketones, resulting in l,3,4,6-tetrahydro-l,2,4-triazine 4-oxides 155 (77ZOR2617). 

Substituent exchange in the 1,2,4-triazine ring is an extensively studied reaction, as in other systems. As earlier mentioned, the introduction of a hydrogen atom into the 1,2,4-triazine ring can be achieved by oxidation of hydrazino-l,2,4-triazines (306), as was shown for 3-hydrazino and 5-hydrazino compounds. Another method is by the decarboxylation of carboxylic acids (307). This reaction was used by Paudler and Barton for the preparation of the parent 1,2,4-triazine (1) by decarboxylation of the 3-carboxylic acid (66JOC1720), but decarboxylation of 5- and 6-carboxylic acids are also well-documented reactions. 

Oxidation of hydrazino-1,2,4-triazines, e.g. 3, with manganese(IV) oxide or silver(I) oxide has been used for the synthesis 1,2,4-triazines with a hydrogen in the 3-position, e.g. i,114124 or in the 5-position.I29f 131 a,b... 

Amino-3-hydrazino-5-mercapto-l,2,4-triazine (Purpald ) 402 is a well-established reagent for qualitative and quantitative detection of aldehydes. In the presence of an aldehyde or ketone, Purpald is transformed into a fused tetrahydrotetrazine intermediate 403. However, only with aldehydes, further oxidation of 403 takes place to give a deeply purple colored [l,2,4]triazolo[4,3-. ][l,2,4,5]tetrazine-3-thiol 404 (Scheme 95) <2000ALD28>. 

Tetra(chIoro)hydrazo-l,3,5-triaziiie (prepared from cyanuric triazide [151]) is the starting material for both compounds. Its reaction with excess of hydrazine hydrate in acetonitrile forms 4,4, 6,6 -tetra(hydrazino)hydrazo-l,3,5-tri-azine which undergoes diazotization to TAHT. TAAT forms by oxidation of TAHT by chlorine in a water/chloroform suspension [147,148,150]. Simplified method of preparation of the key intermediate TAHT was pubhshed by Li et al. [152]. Instead of hydrazinolysis and diazotation they used nucleophilic substitution of 4,4, 6,6 -tetra(chloro)hydrazo-l,3,5-triazine with sodium azide for preparation of TAHT which they in the last step oxidized with A-bromosuccinimide. 

A full account of the methods of direct synthesis of the previously inaccessible fervenulin 4-oxides, reported last year, " has appeared. Also noted last year was the value of 6-hydrazino-l,3-dimethyl-5-nitrosouracil (356) as a precursor in purine and pteridine syntheses. Extension of this work has now provided access to 3-aryl-fervenulins (357) and pyrimido[5,4-e]-as-triazines (358), as... 

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