3- Aryl-l,2,4-triazines

The first case of the use of amino acids as chiral auxiliaries in nucleophilic addition to triazinones was employed in the reaction of C-nucleophiles with 3-aryl-l,2,4-triazin-5(4 )-ones 16 and A-protected amino acids 17, to form l-acyl-6-Nu-3-aryl-l,6-dihydro-l,2,4-triazin-5(4A)-ones 18 in high diastereomeric excess <06TL7485>. 

The reaction of 3-aryl-l,2,4-triazines 100 with thioamides in acetic anhydride was reported to occur regioselectively at room temperature resulting in simultaneous A -acetylation and annelation of the thiazole ring to form 1,4,4 ,7 -tetrahydrothiazolo[4,5-( ][l,2,4]triazines 38 (Scheme 74 Table 8) <2004RCB1279>. 

Ring enlargement of aryl(l,2,3-triazol-l-yl) carbenes, generated from 1-[A -(phenylsulfonyl)benzohydrazonoyl-1,2,3-triazoles 8, into 3-aryl-l,2,4-triazines 9 has been described <05H279>. 

Oxidation of 3-aryl-5,6-dimethyl-1,2,4-triazines (296) with potassium permanganate yielded 3-aryl-6-oxo-1,6-dihydro-l,2,4-triazine-5-carboxylic acids (297), which were transformed into 5-amino-3-aryl-l,2,4-triazin-6(l//)-ones (298) via the carhonyl azides and Curtius rearrangement (Scheme 55) <90H(3i)2i63>. 

Aryl-l,2,4-triazin-5(2//)ones react with indoles, pyrroles, pyrazoles and thiazoles in boiling butanol, and some other solvents, to give addition products e.g. 62. Oxidation results in aromatization <97JHC1013>. They also react with phenols and dialkylanilines to give 6-aryi-l,6-dihydro-l,2,4-triazin-5(2//)ones <97JHC573>. 

There are many examples of the formation of cr -adducts derived from nucleophilic attack by G-nucleophiles at an unsubstituted carbon atom of the 1,2,4-triazine ring. For instance, the reaction of 3-aryl-l,2,4-triazin-5-ones 34 with indole and its methyl derivatives affords 3-aryl-6-(indolyl-3)-l,6-dihydro-l,2,4-triazin-5(2//)-ones 35 (Scheme 21) <1997JHC1013, 1998RJ0297>. In a similar way, adducts of 34 with iV,iV-dimethylaniline, viz. 36, are formed (Scheme 21) <1997JHC573, 1998RJ0297, 2001H(55)2349>. 

In particular, it has been found that the reaction of 3-aryl-l,2,4-triazines 76, activated by acetic anhydride, with /3-aminovinyl ketones or /3-aminocrotonate 77 in acetic anhydride proceeds at room temperature very smoothly and regioselectively, leading to 3a,4,7,7a-tetrahydro derivatives 78 of the l//-pyrrolo[3,2-< ]-l,2,4-triazine ring system (Scheme 41) <2003RCB1740>. 

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>. 

Stabilities of o -adducts derived from nucleophilic addition of alcohols and alkox-ide ions to azaaromatic compounds are varied to a great extent. A whole number of alkoxy adducts of 1,4-diazinium and 1,2,4-triazinium cations have been registered by NMR [114] however, attempts to isolate them failed. Contrary to that, treatment of 3-aryl-l,2,4-triazin-5-ones with primary or secondary alcohols in the presence of acetic anhydride results in the formation of rather stable 6-aIkoxy-l-acetyl-l,6-dihydro-l,2,4-triazin-5-ones (Scheme 38) [117, 140, 141],... 

Pyrazolo[4,3-e][l,2,4]triazine derivatives have been prepared from oximes of 5-aryl- and 5-formyl-l,2,4-triazines <06MI191 >. Novel pyrazolo[5,1 -c][ 1,2,4]triazines incorporating an Af-(2-oxoethyl)phthalimide moiety have been reported <06JCR(S)6>. 

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. 

Thus, 5-aryl-3-hydrazino[l,2,4]triazine 200 was reacted with acid chlorides to yield 201 <2004AF42>, and reaction of 5,6-diphenyl-3-hydrazino[l,2,4]triazine 202 with carbon disulfide yielded a 3-mercapto product 203 <2000PJS214>. 

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

Reaction of 4-aryl-3-methylthio-l,2,4-triazin-5-ones (342) with hydrazine led to 4-amino-3-arylamino-l,2,4-triazin-5-ones (343) instead of the expected 4-aryl-3-hydrazino derivatives (344). This is explained by nucleophilic attack of the hydrazine at the 5-position, ring opening and subsequent reclosure. The same result was obtained when 4-aryl-3-thioxo-... 

Hydrolysis in acid of compounds assigned the a-cyanoazoacetophenone structures (681) affords arylglyoxal semicarbazones (682). These can be cyclized in hot sodium hydroxide to 5-aryl-l,2,4-triazin-3-ones (683) <02LA(325)129). 

The Diels-Alder reaction of 5-acetyl-3-methylthio-l,2,4-triazine with cyclic enam-ines produces 3-acetyl-l-methylthiocycloalka[c]pyridines, which are synthons for the preparation of sempervirine and its analogues.126 Cycloadditions of aryl-substituted 1,2,4-triazines (117) with 2-cyclopropylidene-l,3-dimethylimidazolidine (118) yield Diels-Alder adducts (120) that eliminate N2 to form dispiropyridines (121), which rearrange to pyrrolo[3,2-c]pyridines (122). At low temperatures, zwitterions (119) formed by nucleophilic attack of (118) on the triazines could be detected spectroscopically and, in some reactions, isolated (Scheme 34).127... 

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. 

Ring-degenerate transformations initiated by the nucleophilic addition at C-5 of the 1,2,4-triazine ring have also been reported to occur in reactions of 4-aryl-substituted 3-methylthio-l,2,4-triazine-3,5-diones with hydrazine hydrate (Scheme 80). This ANRORC mechanism involves the open-chain compound 138 as intermediate (80JHC1733 81JHC953). 

Aryl-l,2,4-triazin-3-ones and 2-Aryl-l,2,4-triazepin-3-ones... 

New 2-aryl-l,2,4-triazin-3-ones and 2-aryl-l,2,4-tri-azepin-3-ones were prepared in a three step reaction sequence from readily available aryl isocyanates and aminoacetals or ketals. The key step in the reaction scheme was the formation of 2-arylsemicarbazides by the treatment of arylureas with the aminating reagent 0-(4-nitrophenyl)hydroxylamine. 2-Aryl-1,2,4-triazin-3-ones... 

The synthesis and testing of heterocyclic compounds for herbicidal activity has been of continuous interest in our laboratories. As one phase of this program, a search of the literature indicated only a relatively few 2-aryl-l,2,4-triazin-3-ones (1, n-0) and 2-aryl-1,2,4-triazepin-3-ones (2) had been reported, and of those, none appeared to have been examined for herbicidal properties. A synthesis program was therefore initiated in order to access their potential as weed control agents. 

Treatment of 2-arylsemicarbazides with dicarbonyl or alpha-substituted carbonyl compounds is a common method for the formation of 2-aryl-l,2,4-triazin-3-ones (Scheme 1) (2). Reduction and then alkylation in the case of 3 or alkylation in the case of 4 would provide access to compounds with substituents at the 4-, 5- and 6-positions of the heterocyclic ring. Neither approach, however, has been reported to give triazin-3-ones where the heterocyclic ring is unsubstituted at the 5- and 6-positions. 

Efficient synthetic routes for 2-, 4- and 6-aryl-l,2,4-triazine-3,5-diones have been reported. Cyclization of 2,6-difluorophenylpyruvic acid 16 with 2-aryl-5,5-... 

The mass spectrum of the unsubstituted 1,2,4-triazine shows peaks at mjz = 81, 53, 52, 51, 40, 39, 38, 28, 27, 26, and 25, being accounted for in part by the fragmentation pattern given below. The fragmentation pattern was confirmed by the mass spectrum of [2H3]-l,2,4-tri-azine.105 [4-15N]-3-Methyl-l,2,4-triazine shows a similar fragmentation pattern,106 as do most alkyl- and aryl-substituted 1,2,4-triazines. From these data it follows that the fragmentation starts with loss of nitrogen. 

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