Triazolo triazines, formation

The reaction of 3-hydrazinophenanthro[9,10-e][l,2,4]triazine 742 with carbon disulfide, thiourea, phenyl isothiocyanate, urea, and phenyl isocyanate led [77ZN(B)569] to the formation of phenanthro[9,10-e][l,2,4]-triazolo[4,3-/j][l,2,4]triazines 743. Alkylation of 743 in aqueous alkaline... 

Hydrazine 746 could be a precursor for this ring system through the formation of its respective hydrazones and oxidation with ferric chloride to give 748 (93BCJ00) and not the isomeric [1,2,4]triazolo[4,3-6][l,2,4] triazine ring. 

Two types of addition to pyrimidine bases appear to exist. The first, the formation of pyrimidine photohydrates, has been the subject of a detailed review.251 Results suggest that two reactive species may be involved in the photohydration of 1,3-dimethyluracil.252 A recent example of this type of addition is to be found in 6-azacytosine (308) which forms a photohydration product (309) analogous to that found in cytosine.253 The second type of addition proceeds via radical intermediates and is illustrated by the addition of propan-2-ol to the trimethylcytosine 310 to give the alcohol 311 and the dihydro derivative 312.254 The same adduct is formed by a di-tert-butyl peroxide-initiated free radical reaction. Numerous other photoreactions involving the formation by hydrogen abstraction of hydroxyalkyl radicals and their subsequent addition to heterocycles have been reported. Systems studied include 3-aminopyrido[4,3-c]us-triazine,255 02,2 -anhydrouri-dine,256 and sym-triazolo[4,3-fe]pyridazine.257 The photoaddition of alcohols to purines is also a well-documented transformation. The stereospecific addition of methanol to the purine 313, for example, is an important step in the synthesis of coformycin.258 These reactions are frequently more... 

Some 4,5-dihydro[l,2,4]triazolo[3,4-r-]benzo[l,2,4]triazines 57 easily reacted with aromatic aldehydes to result in the formation of synthetically valuable azomethine imines 58 <2005EJO3553>. The transformation took place at room temperature in the presence of tetrafluoroboric acid in 10 min in high yields. The product 58 was conveniently prepared and stored in the form of tetrafluoroborate salt, and was subjected to further reactions (e.g., 1,3-dipolar cycoadditions see Section 11.19.5.4.) by in situ liberation of the free base prior to transformation. 

In research work on the transformation of [l,2,4]triazolo[4,3-A][l,2,4]triazines, introduction of various moieties into position 7 of this ring system has been elaborated by Chupakhin and co-workers <2001IZV2084, 2002HC075, 2003ZOB862>, as illustrated in Scheme 12. Some of these transformations have been carried out under acidic conditions, and in several cases basic conditions have been applied. In most cases, a formal addition of a CH moiety of the reagent to the C(7) = N(8) bond of the triazine ring occurs to result in the formation of a partially saturated triazine stmcture, and this transformation was followed by spontaneous oxidation to yield heteroaromatic triazine rings. 

Formation of some mesoionic [ 1,3,4]rhiazolo[3,2-z/ [1,3,5]triazines 303 and related [l,2,4]triazolo[2,3- ][l,3,5]tri-azines 305 has been observed by Anders et al. <2005T673>, as shown in Scheme 60. These authors reported that the quaternary salts 302 and 304 containing polyfused delocalized cations easily react with amines to result in ring opening to 303 and 305, respectively. 

A new cyclization method for [l,2,4]triazolo[5,l-c]triazines (ring system 26) starting from trifluoromethylated 1,2,3-triketones and resulting in formation of 4,7-dihydro derivatives has recently been published <2005JFC1230>. The structure of one representative derivative has also been investigated by X-ray crystallography. 

Cleavage of [l]benzofuro[2,3-e][l,2,4]triazine ring was employed to obtain oxygen, nitrogen and sulfur derivatives of 1,2,4-triazines <03JHC805>. The formation of highly reactive triazinium-imidothiolate zwitterions 70 and their role as key intermediates for novel Sn(ANRORC) reaction pathways has been reported. These intermediates, isolated from the reaction between bis([l,3,4]thiadiazolo)[l,3,5]triazinium halides 69 and benzylamines can yield unusual bis([l,2,4]triazolo)[l,3,5]triazinium halides 72,... 

Treatment of 3-amino-5-hydrazino-l,2,4-triazole with benzil produced 2-amino-6,7-diphenyl-[l,2,4]triazolo[5,l-c][l,2,4]triazine via either direct formation involving cycliz-ation on the triazole N-1 or attack at N-4 of the triazole to yield the [3,4-c] compound which rearranged to the [5,1-c] isomer (76JCS(P1)1492). Ring closure of 3,4-diamino-1,2,4-triazines with carboxylic acids is also a route to various [l,2,4]triazolo[5,l-c][l,2,4]triazines (64CB2173). 

The hydrazino group in 89 is more nucleophilic than the 5-amino group, therefore, formylhydrazino derivative 90 is usually formed at the first stage. This compound, depending on conditions and on the type of cyclizing agent, can be converted then to triazolo[4,3-c]pyrimidine 91 [pathway a in Eq. (27)], l,2-dihydropyrimido[5,4-e]-fls-triazine (92) (pathway b), or diformyl derivative (93) (pathway c). Compound 93 is the precursor of 9-acylaminopurine (94). There is also much evidence of the formation of 9-acylaminopurines via dihydroazines (92) (pathway d). 

The destruction of heterocycles condensed to the 1,2,4-triazine ring can also be treated as a method of substituent modification. For example, the formation of 3-[acetoxy(phenyl)-methyl]-l,2,4-triazines 24 by treatment of [l,2,3]triazolo[5,l-c][l,2,4]triazines with acetic acid,340 and the degradation of the pyrimido[5,4-c]-1.2,4-triazines353 and pyrimido[4,5-e]-1,2,4-triazines to afford 25 and 26, respectively.331 354 Further reactions of this type are discussed in a previous review.8 For a synthesis of l,2,4-triazine-3,5,6-tricarboxylic acid from pyrrolo[2,l-c]benzo-l,2,4-triazine, see also Houben-Weyl, Vol. 4/1 b, p 643. 

The 7-imino[l,2,4]triazolo[3,2-Z)][l,3]triazine compounds (71) when deprotonated, were found to form a ring-chain equilibrium with (72) (Equation (1)) <88KGS992>. Opening of the thiadiazole ring of (73) and formation of (74) was observed in the reaction with hydrazine hydrate (Equation (2))... 

Interaction of 3-nitro- and 3-ethoxycarbonyl-l,2,4-triazolo[5,l-f][l,2,4]triazin-4-ones 187 with adamantanyl cation, generated from the corresponding alcohol or adamantylnitrate in sulfuric acid, results in the formation of compounds 188 (Scheme 116) <2002RJ0294, 2002RJ0272>. 

The synthesis of the triazine ring from [3+3] fragments is not as widely used as the [4+2] approach nevertheless, several successful examples have been reported during the last decade. One of these is the reaction of nitrilimines, generated from chloroamidrazones 204, with ethyl isocyanoacetate, which results in the formation of either 2-aryl-3-ethoxycarbo-nyl-2,3-dihydro-l,2,4-triazines 205 or l,2,4-triazolo[4,5- -l,2,4-triazines 206 (Scheme 119) <2002M1165>. 

Saloutin, Chupakhin et al. applied a related condensation involving 1,2,4-triazolyldiazonium resulting in the formation of 6-benzoyl-7-hydroxy-7-triflu-oromethyl-4,7-dihydro[l,2,4]tiiazolo[5,l-c][l,2,4]triazine 151 (59 %) [132], Rusinov et al. reported on another successful example of this reaction involving lithium p-diketonates and 3-amino-l,2,4-triazole and affording 7-fluoromethyl-l,2,4-triazolo[l,5-a]pyrimidine 152 [133]. 

The synthesis of azoloannelated fluoro-l,2,4-triazines - 2-R-6-fluoro-1,2,4-triazolo[5,l-c][l,2,4]triazin-7(4H)-ones 10 has been recently described [16]. The coupling of l,2,4-triazolyl-5-diazonium salts 11 with ethyl 2-fluoroacetate and the accompanied deacetylation leads to the formation of hydrazones 12 followed by cyclization on heating in aqueous alcohol in the presence of sodium acetate into the target fluoro compounds 10 (Scheme 9). 

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