6-Aryl-1,2,4-triazine-4-oxide, oxidative

Kurabayashi and Grundmann have reported the preparation of the 1,2,4-oxadiazoles (34) from 1,3,5-triazine and aryl nitrile oxides in the presence of boron trifluoride. The mechanism has not been fully elucidated, but it is most likely that the initial stage is the formation of the complex (33) (78BCJ1484). 

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... 

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. 

Furo[3,4-c][l,2,4]triazines 201 were prepared (75USP3962240 77USP-4013767) by condensing furandione 199 with the respective 2-aryl or pyri-dylcarboximidic acid hydrazide 200. Compound 201 (X = N) was oxidized to its N-oxide. Both 200 and 201 have sedative and tranquilizer properties (Scheme 42). 

Ethyl formate34,52 or orthoformate5 3,54 reacts with two equivalents of phenylhydrazine to yield 1,5-diphenylformazan (11) the reaction takes place under acidic conditions and involves an oxidation. Under basic conditions, ethyl nitrate reacts at the methylene position to yield 3-methyl-1,5-diphenylformazan (37) which can also be obtained from the reaction of phenyl-azoethane (38) with isoamyl nitrite (Scheme 4).8,68 Aryl hydrazines react with a variety of s-triazines (39) to yield 1,5-diaryl formazans with hydrogen, methyl, or phenyl groups in the 3-position as in 40 (Eq. 6).56 Hydrazines have also been reported to react with benzotrichloride55,658 and sym-diamino tetrazine659 to yield formazans. 

A series of 3-aryl-5,8-dihydro-6,6,8-trimethyl-5,8-ethano-6H-pyrano [4, 3-e][l,2,4]triazine-4-oxides 193 was prepared (79JHC1389) by boiling a mixture of 192 and trimethyl orf/io-arylates. The effect of substituents on the chemical shifts of their 13C NMR spectra was studied. 

Acid hydrolysis of 3-methyl-6-phenyl-l,2,4-triazine 4-oxide (827) yields 4-phenyl-1,2,3-triazole through an acyclic intermediate (828) (Scheme 168) <89AHC(46)73>. 1,2,4-Triazine 2-oxides (829) undergo rearrangement in basic conditions (Equation (80)) to form 4-substituted 2//-1,2,3-triazoles <89AHC(46)73>. l-(2-Nitrophenyl)-5-aryltetrazoles (830) and l-aryl-5-(2-nitrophenyl)tetrazoles are converted into 2-arylbenzotriazoles (831) by refluxing in nitrobenzene (Equation (81)) <81AJC69l>. 

Alternative procedures for the preparation of 4-alkyl- and 4-aryl-1,2,3-benzotriazines have also been investigated by Rees. Thus, the diazoazide (11) undergoes smooth decomposition in refluxing benzene to give 4-methyl-1,2,3-benzotriazine (8, R = Me) in 70% )deld. Oxidation of the o-aminohydrazones (12, R = Me, Ph,p-MeOCsH4) with lead tetraacetate also gives the corresponding triazines (8) in moderate yield. 

Treatment of condensed 1,2,3-triazine 3-oxides (15) with either acid or base results in formation of o-azido carbonyl compounds. " Alkaline hydrolysis of the betaines 77, on the other hand, gives the triazenes 53, R = aryl, possibly via rearrangement of the aryl group from Nj to Nj to give 10, R = aryl, followed by ring cleavage. The... 

Very little is known about the susceptibility of the ring nitrogen atoms in 1,2,3-triazine derivatives to N-oxidation. Attempts to oxidize the N-aryl- 77 and iV-alkyltriazinium (79) betaines to the corresponding 1-oxides under a variety of conditions were unsuccessful, and the betaines were recovered unchanged even after prolonged exposure to powerful oxidants.It has been reported that oxidation of the 4-arylthio-1,2,3-benzotriazine (109) takes place at nitrogen rather than sulfur, and the product has been formulated as the Nj-oxide (110) or the N,-isomer. The evidence in favor of structure 110— the lack of bands... 

A convenient approach to the synthesis of 2-aryl-4-alkyl-13 -triazino[l,2-ajbenzimidazoles 113 from 2-aminobenzimidazole has been reported <98IJC(B)1283>. New 8-cyanopyridothieno[l,23]triazines 114 as inhibitors of nitric oxide and eicosanoid biosynthesis have been described <99JMC4720>. Synthesis of pyridodithienotriazines 115, from dithienopyrimidine derivatives, and their antihistaminic and cytotoxic activities have been reported <98EJM887>. 

Chinoxalino[2,3-c]f urazan)-l-oxide reagieren ausschlieBlich unter Bildung von 3-Aryl-[Pg.805]

Interesting results were obtained in the SNH oxidative dialkylaminations of 6-aryl-1,2,4-triazine-4-oxides (98ZOK423), When these compounds are subjected to a reaction with a series of dialkylamines at —40°C in the presence of potassium permanganate, they are converted into 3-dialkylamino-l,2,4-triazine-4-oxides (Scheme 28). 

It has been successful to isolate intermediates and to identify them by NMR spectroscopy as 3-aryl-6-dialkylamino-l-hydroxy-1,4,5-triaza-1,3,5-hexatriene. Treatment with potassium permanganate of these open-chain structures gave ring closure into 3-dialkylamino-l,2,4-triazine-4-oxides. Also, in these reactions it was observed that the regiospecificity of the addition is temperature dependent. Whereas at —40°C the addition occurs at C-3, at -70 °C the addition takes place at C-5 (01H127). Whether on oxidation at —70°C the 5-dialkylamino-6-phenyl-l-2-4-triazine-4-oxide is formed is unknown. 

Eight examples of 3-aryl pyrido[3,2-e]-1,2,4-triazines were prepared via a reductive cyclization route. Thus, 3-phenylpyrido[3,2-e]-l,2,4-triazine (65) was prepared from the aminopyridine (234) by cyclization followed by oxidation <76CR(C)487>. In another study, seven 3-substituted pyrido-1,2,4-triazines were prepared via an analogous route <76MI 717-04). This work mirrored the earlier investigations of Lewis and Shepherd <7lJHC4l>. 

Cyclohepta[4,5)pyrrolo[l,2-fl]imidazoles, 2-aryl-, halogenation. 59, 283 Cyclohepta[4,5)pyrrolo[3,2-e][l,2,4]triazine, 3-chloro- 10-(4-chlorobutyD-5,6,7,8,9,10-hexahydro-, 59, 50 3//-Cyclohept(e]isoxazoles, 3a,4,5,6,7,8-hexahydro-, 60, 311-3 Cyclohex-2-en-l-ones, 2- and 3-bromo-, regioselectivity of nitrile oxide cycloaddition, 60, 304 Cyclols, piperazine-2,5-dione-related, 57, 211-7... 

Yamanaka has used the reaction of Grignard reagents with 3,6-disub-stituted 1,2,4-triazines 259 to prepare 5-aryl-1,2,4-triazines 261 via oxidation of the intermediate 2,5-dihydrotriazines 260 (85H28O7). 

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