Aryl-substituted 1,2,4-triazines

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... 

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. 

Most 1,2,4-triazines are crystalline compounds, the melting points depending on the structure and the substituents present. Alkyl-substituted 1,2,4-triazines are yellow and melt at low temperatures, or in a few cases they are liquids at room temperature but they are reasonably stable. They can be stored at 0°C or lower, but in time they become dark. They can usually be distilled under reduced pressure, and can be purified by vapor-phase chromatography, by which isomeric alkyl-1,2,4-triazines can be separated. Aryl-substituted 1,2,4-triazines have melting points around 100°C, while all heterosubstituted (oxo, thioxo, amino, etc.) 1,2,4-triazines have melting points in the 200 °C region. These compounds are usually very stable. 

Alkyl- and aryl-substituted 1,2,4-triazines are soluble in most organic solvents, while heterosubstituted 1,2,4-triazines need highly polar solvents for solution. In most cases there are no problems in purifying 1,2,4-triazines by chromatography on silica gel. 

Trepanier DL, Shriver KL, Eble JN (1969) Aryl-substituted triazines with antidepressant activity. J Med Chem 12 257-260... 

Stabilizers UVA dialkyl aryl substituted triazine Screener carbon black Phenolic antioxidant isotridecyl-3-(3,5-di-tert-butyl-4-hydroxy-phenyl) propionate 2,2 -isobutylidenebis(2,4-dimethylphenol) phenol, 4-methyl-, reaction products with dicyclopentadiene and isobutene Thiosynergist 4,6-bis(dodecylthiomethyl)-o-cresol Amine nonylated diphenylamine ... 

In the case of the 3-methylsulfanotriazine derivative 198, a simple treatment with arylhydrazides allowed the ring closure to the 3-aryl-substituted products 199 <2003KGS950>. In other cases, the hydrazine function was first introduced to position 3 of the [l,2,4]triazine ring and these compounds were then cyclized by using various reagents. 

The fused tetrazoles 10 containing various aryl groups in position 6 were boiled in acetic acid in the presence of either triphenylphosphine or copper and gave rise to the amino-substituted triazines 12. The reaction proceeds obviously via valence bond isomerization of 10 to the azide 11 and is regarded as a useful synthetic route to the diamino compounds 12. 

Hydrolytic cleavage of condensed 1,2,3-triazine derivatives is normally a straightforward, high-jneld process which results in production of one or other of several distinct types of product. 3-Alkyl- and 3-aryl-3,4-dihydro-l,2,3-benzotriazines, for example, undergo facile hydrolysis in concentrated hydrochloric acid to give, via the diazonium compound, A(-alkyl- and W-aryl-substituted o-chlorobenzylamines (100, R = Cl). If the reaction is carried out in water or in dilute mineral acid, the corresponding -alkyl and iV-aryl-substituted o-hydroxybenzylamines (100, R = OH) are obtained. 

Aryl-substituted amides 39, when treated with triethyl orthoformate, give the corresponding N-arylated pyrimidine-fused rings 40 (Scheme 4) <2000PS(164)299> as well as one example of the triazine 41 <2000PS(164)299>. 

A number of 8-aryl substituted pyrido[3,4-t/]-l,2,3-triazin-4(3//)-ones have been found to be most efficacious as inhibitors of xanthine oxidase, potential compounds for the treatment of ischemia and gout <88EUP274654>. A number of 3//,4//-pyrido[3,2-e]-l,2,4-triazine and 3/f,4//-pyrido[3,4-e]-1,2,4-triazine 3-acetamides have shown antiinflammatory, diuretic, antihypertensive, and psychotropic effects <89FES279>. During a search for potential antidepressant compounds, the pyrido-1,2,3-triazinone (399) was found to be more active than its isomer (400) <87EJM337>. 

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). 

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... 

Protonation on ring nitrogen does not seem to proceed in alkyl and/or aryl substituted monocyclic triazines due to their low basicity. 4,6-Diamino- and 4,5,6-triaminotriazines (62) have relatively high nucleophilicity at N-2, and have been found to undergo various kinds of reactions with electrophiles <79CB1535>. The triazinium tetrafluoroborate salts (63) showed symmetrical NMR spectra, indi-... 

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. 

Base-catalyzed Dimroth rearrangements of l-aryl-4,6-diamino-1,3,5-triazines or triflic acid-induced decomposition of 6-anilino-1,3,5-triazines led to the formation of the corresponding substituted 1,2-dihydro-l,3,5-triazines, whose structure was established on the basis of H NMR spectra (93JHC849). 

Synthetic strategies to generate 2-aryl- 27, 2-alkyl- 28 and 2-acetylenyl- 29 -substituted 4,6-diamino-l,3,5-triazines from the corresponding 2-chloro compound 26 have been reported <06TL5973>. 

Another growing technique is super-critical fluid chromatography. Recent references to soil analysis include the following applications aliphatic hydrocarbons, polyaromatic hydrocarbons, polychlorobiphenyls, dioxins, alkyl and aryl phosphates, chloro, organophosphorus, triazine, substituted urea, phenoxy acetic acid, Dacthal herbicides and insecticides and mixtures of herbicides and pesticides and mixtures of organic compounds. 

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