L,2,4-Triazine-5-carboxamides

Analogously, 5-unsubstituted 1,2,4-triazines with cyanide ions afford bi-l,2,4-triazin-5,5 -yls (311) and l,2,4-triazine-5-carboxamides (312) (84CHEC-(3)369, 87CPB1378). 

Triazine and some of its 3-methoxy, 3-methylthio or 3-amino derivatives (103) with the 5-position unsubstituted react with potassium cyanide to afford two products, the i-triazinyls (105) and the l,2,4-triazine-5-carboxamides (104). These are proposed to be formed via a cyanide adduct (73JHC343, 74JHC43). The bi-l,2,4-triazinyls (105) were also isolated when the triazines (103) were treated with sodium methoxide or potassium in liquid ammonia. It is suggested that the methoxide-catalyzed dimerization proceeds via an anionic intermediate (106), while the reaction with potassium in liquid ammonia occurs via a free radical process. 

Several examples of SN reactions with 1,2,4-triazine substrates containing at C-3 and C-6 the same leaving groups indicate that the displacement of a nucleofugic group at C-3 is somewhat more preferred. Thus, only the substituted 3-ethoxy-1,2,4-triazine 92 is formed from reaction of 3,6-dimethylthio-l,2,4-triazine-5-carboxamide (91) with sodium methoxide (Scheme 58) (85JHC1329). In the reaction between triazine 91 and ammonia the 3-amino derivative 93 is the major product, and 6-amino-3-methyl-thio-1,2,4-triazine-5-carboxamide 94 is formed only in poor yield (Scheme 58) (85JHC1329). 

The reactivity of 4-phenylimidazo[5,l-c][l,2,4]triazin-8-carboxamide 485 toward hydrazine has been studied [82JCS(P 1) 1811], whereby pyrazol-4-ylidenehydrazino)imidazole-4-carboxamide 486 was formed (Scheme 102). 

A similar process was found to occur with the fervenulin-3-carboxyl chloride 54, which upon treatment with an amine gave the bis-adduct intermediate 55, which ring-closed to the imidazo[4,5- ]-l,2,4-triazine bis-carboxamides 56 as shown in Scheme 5 <1996JHC949>. The structure of the products 56 was confirmed by X-ray crystallographic analysis. 

The pyrimido[4,5- ][l,2,4]triazines (6-azapteridines) 18a and 18b, shown in Scheme 18, were formed upon the reaction of the ethyl l,2,4-triazine-6-carboxylates 121 with benzamidine, a reaction which proceeds via the action of boiling acetic acid upon the characterized intermediate salt 122 <2003CCC965>. The same researchers (Scheme 19) also showed that the 5-amino-l,2,4-triazine-6-carboxamide 123 (R =OMe) can undergo reaction in neat benzaldehyde to furnish a low yield of the 6-azapteridine 18b. More importantly, the 5-amino-l,2,4-triazine-6-carboxamides 123 were found to undergo reaction with triethyl orthoformate to yield the 6-unsubstituted-3-arylpyr-imido[4,5-( ][l,2,4]triazines 18c and 18d, also shown in Scheme 19 (R = H) <2003CCC965>, one of only a few entries to such compounds. 

The diazotization of 5-amino-4-carbamoyl-l-(a-styryl)-l,2,3-triazole (30) gave 5-phenyl-1.2,3-triazolo[l,5-h][l,2,4]triazine-3-carboxamide (32) as a result of rearrangement of the initially formed 7-phenyl-l,2,3-triazolo[5,J-c][l,2,4]triazine-3-carboxamide (31). Compound 32 is favored thermodynamically and its structure was confirmed by an X-ray crystallographic study (88BSB179) (Scheme 10). 

Lithiation at the 5-position of 1,2,4-triazines was observed in the reactions of l,2,4-triazine-6-carboxamides (135) and of 3,6-diphenyl-1,2,4-triazine 4-oxide (136) with LiTMP. 5-Lithio-1,2,4-triazines can also be trapped by electrophiles. (Scheme 23) <95UP6ii-02>. 

Phosgene, complexed with pyridine,261 and 6-amino-l,2,4-triazine-5-car-boxamide, warmed in dioxane, gave a moderate yield of pyrimidino[5,4-e]-as-triazine (157).262 Thiophosgene acted on l-methyl-4-methylaminoimida-zole-5-(lV-methyl)carboxamide to produce, not a thioxopurinone as had been claimed earlier, but an imidazo[4,5-d][l,3]thiazine.263... 

Diethyl carbonate in boiling ethanolic sodium ethoxide has occasionally been used to convert oaminoamides to annelated pyrimidine-2,4-diones—for example, 2-amino-5-cyanopyridine-3-carboxamide to 6-cyanopyrido[2,3-d] pyrimidine-2,4-dione (see 3)245 4-amino-3-benzyl-l,2,3-triazole-5-carboxamide to 9-benzyl-8-azapurine-2,6-dione (see 21)268 4-amino-3-ribofuranosidoimidazole-5-carboxamide to 9-ribofuranosidopu-rine-2,6-dione (xanthosine) (see 19)269 and l,2,4-triazine-6-carboxamide to... 

There is considerable interest in the chemistry of triazines as some of these compounds show pronounced antimalarial, antimicrobial and antiviral activity (76JCS(Pl)252l). Therefore two types of thiophenes annelated with a triazine ring will be mentioned. Thieno[2,3-d]-1,2,3-triazines were synthesized by cyclization of diazotized 2-aminothiophene-3-carboxamides (equation 55) (73M1586). Treatment of 3-alkylthio-6-styryl-5-oxo-2,5-dihydro-l,2,4-triazines with phosphorus pentasulfide in pyridine yields thieno[2,3-e]-l,2,4-triazines (equation 56) (78CI(L)585). Probably a thiation with subsequent cycloaddition and elimination of a hydride ion is involved. 

A number of 1,2,4-triazines can be lithiated, such as 5-methoxy-l,2,4-triazines 18, 1,2,4-tri-azine-6-carboxamides or 1,2,4-triazine 4-oxides and the thus formed lithio-l,2,4-triazines reacted with electrophiles. This reaction method has been used to introduce the following substituents into the 6-position iodo, carbaldehyde, hydroxyalkyl groups. The reaction of 5-lithio-l,2,4-triazines with electrophiles results in the formation of dimers and no substitution products are formed.44,2 9... 

A soln. of 3-p-dilorophenyl-2-phenyl-2H-azirine-2-carboxamide in methanol mixed with hydrazine hydrate, and refluxed 2 hrs. 3-p-dilorophenyl-5-phenyltetra-hydro-l,2,4-triazin-6-one. Y 36%. F. e. s. T. Nishiwaki and T. Saito, Soc. (C) 1971, 2648. 

Analogous to the synthesis of imidazo[4,5-,y [l,2,3]triazin-4-ones (Scheme 41), diazotization is the method of choice for making this ring system, and involves treatment of the 5-aminopyrazole-4-carboxamides with nitrous acid (Scheme 43) <1995JHC1417, 1996CHEC-II(7)489>. 

All attempts to lithiate 5-bromo-l,2,3-triazine and A, A -diethyl-l,2,3-triazine-4-carboxamide with LTMP at -100°C, followed by reaction with electrophiles, were unsuccessful <1998MI119>. 

Attack of the 1,2,3-triazine system by an organic radical is used in the introduction of a carboxamide function at C-5 by the treatment of 4,6-disubstituted l,2,3-triazin-2-ium 2-dicyanomethylides 34 (R = H R, R = Me, Ph, Et) with formamide in the presence of ammonium persulfate at 80 °C. Under these conditions, the 1,2,3-triazine is restored by loss of dicyanomethyl radical. The corresponding 2-methyl-l,2,3-triazin-2-ium iodides gave the demethylated... 

HPA = (4-pyridylthio)aceticacid 2-fur = 2-furoate a-fur = a-furoate = ([Pg.116]

A novel photoactive thermally stable polymer (xv) containing the triazine moiety has been synthesized by Khoee and Zamani [27] by the reaction of A,A-(4,4 -oxy bis (4,l-phenylene))-bis-(l,3-dioxo-l,3-dihydroisobenzofuran-5-carboxamide) and A-(4,6-diamino-l,3,5-triazin-2-yl) anthracene-9-carboxam-ide in presence of a small amount of o-cresol as a solvent under microwave condition. 

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