3-Amino-1.2.4-triazine 2-oxide, oxidation

In contrast to the above situation with respect to oxidation of the ring nitrogen atoms of 1,2,3-triazines, oxidation of derivatives of 3-amino-l,2,3-benzotriazin-4-(3/0-one (101a) has proved to be of considerable interest and has been investigated in some detail by Rees and his colleagues. Treatment of 101a with lead tetraacetate at 80° has been shown to give benzyne in very low yield, but at room... 

Amino- (459) and 3-amino-quinazolin-2-ones (460) (75JCS(Pl)3l), as well as 1-amino- and 2-amino-indazoles (92AHC(53)85) can be oxidized to 1,2,3-benzotriazines. C-Amino compounds can also give triazines oxidation of 3-aminoindazole (461) with hydrogen peroxide forms 1,2,3-benzo-triazin-4-one (462) <1899LA(305)289). 

Amino and nitro groups in different rings may be annulated by heating with aqueous potassium hydroxide in pyridine. The triazine oxide ring is also formed when an o-nitro-guanidine is heated with aqueous carbonate. 

There has only been one report of a transformation of a six-membered ring into a 1,2,3-triazine. Oxidation of 1-amino- 1 and 3-aminoquinazolin-2(1//Tones 2 with lead(IV) acetate afforded the 1,2,3-benzotriazines 3 in low yields.82... 

Oxidation of 6-butoxy-l,3,5-triazine-2,4-diamine with MCPBA in ethanol gave an A-oxide (54), but in only 12% yield <91MIP9119701 >. Chlorination of 6-amino-triazine-2,4(l/f,3//)dione in NaOH solution gave (55), with chlorination on the exocyclic nitrogen as well as on the ring (Scheme 6)... 

Triazines.—Oxidation of the 2-amino-4,7-methano-indazole (340) with lead tetra-acetate produces the 5,8-bridged tetrahydrobenzotriazine (341) in 75.5% yield. a-Diketone oxime-hydrazones, i.e. HON=C(R )C(R )=NNH2, condense with orthoformates R C(OEt)3 to yield a-(l-ethoxyalkylidenehy-drazono)-oximes HON=C(R )C(R )=NN=C(R )OEt, which on thermolysis at 200 °C ring-close to 1,2,4-triazine 4-oxides (342). ° The iV-oxides are also accessible directly by heating the oximino-hydrazones with an imidate hydrochloride R"(RO)C=NHHCl. 

Phenanthro[l,2-d][l,2,3]selenadiazole, 10,11 dihydro- H NMR, 6, 348 synthesis, 6, 353 Phenanthro[b]thiophenes synthesis, 4, 914 Phenanthro[4,5-bcd]thiophenes synthesis, 4, 883, 907, 914 Phenanthro[9,10-ej[l, 2,4]triazines synthesis, 3, 434 Phenarsazin synthesis, 1, 561 Phenazine dyes, 3, 196-197 nitration, 3, 177 UV Spectra, 2, 127 Phenazine, 3-amino-2-hydroxy-in colour photography, 1, 374 Phenazine, 1-chloro-nucleophilic substitution, 3, 164-165 5-oxide... 

Triazole has been prepared by the oxidation of substituted 1,2,4-triazoles, by the treatment of urazole with phosphorus pentasulfide, by heating equimolar quantities of formyl-hydrazine and formamide, by removal of the amino function of 4-amino-l,2,4-triazole, by oxidation of l,2,4-triazole-3(5)-thiol with hydrogen peroxide, by decarboxylation of 1,2,4-triazole-3(5)-carboxylic acid, by heating hydrazine salts with form-amide,by rapidly distilling hydrazine hydrate mixed with two molar equivalents of formamide, i by heating N,N -diformyl-hydrazine with excess ammonia in an autoclave at 200° for 24 hours, and by the reaction of 1,3,5-triazine and hydrazine monohydrochloride. ... 

When it was found later that enzymatic oxidation of 2-azaadenine yields its 8-hydroxy derivative (4-amino-6-hydroxyimidazo [4,5-d]-u-triazine), its synthesis was also achieved by the procedure already described/ ... 

The amino-imino tautomerism in 3-amino-1,2,4-triazine 2-oxides 1 was suggested as the reason for the oxidation of 3-amino-1,2,4-triazines 2, predominantly at N(2) (77JOC546). 

The presence of an TV-oxide group activates the 1,2,4-triazine ring toward electrophilic attack, for instance, in halogenation reactions. Thus, 3-methoxy- and 3-amino(alkylamino)-1,2,4-triazine 1-oxides 16 react easily with chlorine or bromine to form the corresponding 6-halo-1,2,4-triazine 1-oxides 17 (77JOC3498, 78JOC2514). 

The halogenation of 3-methoxy- or 3-methyl(dimethyl)amino-1,2,4-triazine 2-oxides 18 was found to proceed in a similar manner, resulting in 6-halo-1,2,4-triazine 2-oxides 19 (77JOC3498, 78JOC2514). 

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). 

Deoxygenative autoaromatization was reported to occur in the reaction of 3-amino-1,2,4-triazine 2-oxides 42 with alcohols in the presence of HCl or acetyl chloride. In this case the intermediate cr -adducts undergo elimination of water or acetic acid, resulting in 6-alkoxy-3-amino-l,2,4-triazines 75 (77JOC3498). 1,2,4-Triazine 1-oxides do not react with alcohols under these conditions (77JOC3498). 

Chloro(bromo)-3-amino-l,2,4-tiiazines 76 were obtained by the reaction of the 3-amino-1,2,4-triazine 2-oxides 42 with HCl or HBr (78JOC2514). 

Another pathway for the aromatization of the cr -adducts was found in the reactions of 3-pyrrolidino-l,2,4-triazine 4-oxide 81 with amines. Thus the treatment of 1,2,4-triazine 4-oxide 81 with ammonia leads to 5-amino-1,2,4-triazine 4-oxides 54—products of the telesubstitution reaction. In this case the cr -adduct 82 formed by the addition of ammonia at position 5 of the heterocycle undergoes a [l,5]sigmatropic shift resulting in 3,4-dihydro-1,2,4-triazine 83, which loses a molecule of pyrrolidine to yield the product 54. This mechanism was supported by the isolation of the key intermediates for the first time in such reactions—the products of the sigmatropic shift in the open-chain tautomeric form of tiiazahexa-triene 84. The structure of the latter was established by NMR spectroscopy and X-ray analysis. In spite of its open-chain character, 84 can be easily aromatized by refluxing in ethanol to form the same product 54 (99TL6099). 

Similarly, ring opening was found in reactions of 6-aryl-1,2,4-triazine 4-oxides 53 with aliphatic amines, yielding open-chain 6-amino-1-hydroxy- 1,4,5-triazahex-atrienes 85. In this case, however, the nucleophile adds to the 3 position of the... 

Open-chain tautomerism is a general feature of 4-hydroxy-3,4-dihydro-1,2,4-triazines, including cr -adducts at position 3 of the 1,2,4-triazine 4-oxides. Thus triazahexatrienes 85 are the open-chain form of cr -adducts 86 and can be aromatized by oxidation with KMn04, yielding 3-amino-1,2,4-tiiazine 4-oxides 88 (98ZOR418). 

The increase in thermodynamic stability of 85 is achieved by easy ring opening (01H127). This knowledge allows one to control the regioselectivity of the oxidative amination of the 6-aryl-l,2,4-tiiazine 4-oxides 53, obtaining either (i) the 5-amino-1,2,4-triazine 4-oxides 56 in the reaction of 53 with amines at low temperature in the presence of the oxidant or (ii) the 3-amino-1,2,4-triazine 4-oxides 88, provided the reaction is carried out in two steps (addition and oxidation) at room temperature or higher. 

The reaction of the fervenulin 1-oxides 100 with secondary amines results in contraction of the 1,2,4-triazine ring to form 2-amino-5,7-dimethylimidazo[4,5-e] pyrimidine-4,6(5/7,7//)-diones 101. The reaction of the same fervenulin 1-oxides 100 with ammonia leads to the 1,2,4-triazine ring cleavage product, 1,3-dimethyl-5-imino-6-isonitrosouracil 102 (94KGS1253). 

The treatment of 3-amino-1,2,4-triazine 2-oxides 1 or 3-amino-1,2,4-benzotri-azine 1-oxides 29 with nitrous acid proceeds as a diazotization reaction, but the diazo compounds have never been isolated owing to the easy displacement of the di-azo group with nucleophiles. Thus the reaction of 3-amino-1,2,4-triazine 2-oxides 1 with sodium nitrite in hydrochloric or hydrobromic acids leads to the corresponding 3-halogen-1,2,4-tiiazine 2-oxides 119 or 3-bromo-l,2,4-benzotriazine 1-oxides 120 (77JOC546, 82JOC3886). 

The reaction of 3-amino-1,2,4-triazine 1-oxide 1 with methyl iodide in the presence of sodium bicarbonate leads to the methylation of the amino group to afford 3-methylamino-l,2,4-tiiazine 1-oxide 123. This iV-oxide 123, under neutral conditions in the presence of Mel, undergoes methyl group migration to the N(2) atom of the 1,2,4-triazine ring, yielding 3-imino-2-methyl-1,2,4-triazine 1-oxide 124. The same product 124 was obtained by direct methylation of compound 1 under neutral conditions (84TL1677). 

When 5-methylthiosemicarbazide is used instead of amidrazone, 3-amino-1,2,4-triazine 4-oxides can be obtained. In this way 3-amino-5-methyl-6-phenyl-1,2,4-triazine 4-oxide 138 was synthesized from isonitrosopropiophenone [52CIL907, 89IJC(B)556]. 

---