6-Aryl-1,2,4-triazine 4-oxide, reaction with

An amino group can also be acylated <84JHC697, 86JHC935) it reacts with sulfonyl chlorides and aryl isocyanates <86JHC935>, and also with nitrous acid to give, via the diazonium salt (281), either the triazinone by reaction with water or the chloro-triazine by reaction with chloride ions (Scheme 50). Nitrosation of 3-amino-1,2,4-triazine 2-oxides (282) and subsequent thermolysis of the diazonium tetrafluoroborate salts (283) afforded 3-fluoro-1,2,4-triazine 2-oxides (284) (Scheme 51). In one instance the diazonium tetrafluoroborate was isolated <85H(23)1969>. 

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... 

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). 

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. 

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. 

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. 

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). 

Starting from ort/w-aminoarene imines 1. 4-aryl-substituted condensed 1,2,3-triazines 2 can be obtained.7,8 Using the oximes 3 instead of imines, condensed 1,2,3-triazine 3-oxides 4 can be isolated.7,8,127-129,241 Reaction of ort/io-aminoarenecarbamidoximes 3 (R — NH2) with nitrous acid afforded condensed l,2,3-triazin-4-amine 3-oxides 4 (R = NH2).7,8,195... 

A new, mild and general method for the synthesis of aryl-substituted-1,3,5-triazines from aromatic aldehydes and ammonia has been found. Treatment of a 1 1 pyridine, concentrated ammonia solution of aromatic aldehyde with excess of Fremy s salt at room temperature gave a readily separable mixture of a primary amide and 1,3,5-triazine (189). A,A-Dibenzylidenephenyl-methanediamine (190) on similar treatment produced almost identical results (Scheme 56) <85S95>. Extension of the reaction to aliphatic aldehydes does not appear to be possible as attempts to oxidize 2,4,6-trimethyl-hexahydro-1,3,5-triazine with Fremy s salt gave rise to complex mixtures, in low yield. 

The (7 -adducts 110 derived from the reaction of 3-aryl-l,2,4-triazin-5(2//)-ones 34 with 2,6-dimethylphenol in TFA can be characterized by H NMR however, if potassium hexacyanoferrate is added to the reaction mixture, the adducts 110 are transformed into 3-aryl-6-hydroxyphenyl-l,2,4-triazin-5-ones 111 (Scheme 59) <97JHC537>. In addition, the reaction of 34 with anisole on reflux in TFA affords 3-aryl-6-(4-methoxyphenyl)-l,2,4-triazin-5-ones 112, through oxidation of the intermediate rr -adducts by air oxygen (Scheme 59) <1997JHC537>. 

The initial success of the inverse electron demand [4 + 2]cycloaddition reaction of electron deficient, 1,2,4-triazine (61) with a-aryl enamine (60) to formulate the 4-arylpyridine forms the basis of a complementary approach to the CDE ring system of lavendamycin. In this strategy the oxidative insertion of aryl halide bond to provide the p-carboline derivative in the presence of palladium (0) was the notable feature. In a recently published article by Boger, a total synthesis of lavendamycin starting from the precursor 63 has been presented. The utility of... 

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