TRIETHYL 1,2,4-TRIAZINE-3,5,6-TRICARBOXYLATE

PREPARATION AND INVERSE ELECTRON DEMAND DIELS-ALDER REACTION OF AN ELECTRON-DEFICIENT HETEROCYCLIC AZAOIENE TRIETHYL 1.2,4-TRIAZINE-3,5,6-TRICARBOXYLATE (l,2,4-Triazine-3,5,6-tricarbo orl 1c acid, triethyl ester)... 

DIELS-ALDER REACTION OF TRIETHYL 1,2,4-TRIAZINE-3,5,6-TRICARBOXYLATE... 

Table I details representative examples of the [4 + 2] cycloaddition of triethyl 1,2, 4-triazine-3,5,6-tricarboxylate with pyrrolidine enamines and related electron-rich olefins. Cycloaddition occurs across carbon-3 and carbon-6 of the 1,2,4-triazine nucleus, and the nucleophilic carbon of the dienophile attaches to carbon-3 (eq 1). Loss of nitrogen from the initial adduct and aromatization with loss of pyrrolidine affords pyridine products.

Dicyclopentadiene, 66, 99 Dieckmann cyclization, 66, 52 DIELS-ALDER REACTION domino, 68, 198 immonium ion-based, 68, 206 INVERSE ELECTRON DEMAND, 66, 142,147, 148 of triethyl 1,2,4-triazine-3,5,6-tricarboxylate, 66, 150 Diels-Alder reactions, 66, 40... 

Tri ethyl 1,2,4-triazine-3,5,6-tri carboxyl ate 1,2,4-Tr1azine-3, 5, 6-tricarboxylic acid, triethyl ester (10) (74476-38-3)... 

Triethyl l,2,4-triazine-3,5,6-tricarboxylate (156) underwent a Diels-Alder reaction with 2-methoxy-l-methyl-l,4,5,6-tetrahydropyridine (157) and subsequent degradation to give triethyl 1-methyl-1,6-naphthyridine-5,7,8-tricarboxylate (158) (reactants, PhH, until N2 [ ceased then 20°C, 12 h ... 

Triethyl l,3,5-triazine-2,4,6-tricarboxylate serves as an azadiene in reaction with 5-aminopyrazoles to produce purine isosteres, pyrazolo[3,4-d]pyrimidines. In order to overcome the relative instability of... 

The reaction of triethyl l,3,5-triazine-2,4,6-tricarboxylate (16) with arylhydrazines proceeds with rearrangement and leads to imidazol-4-ones 18 in yields of 53 to 94%.22,23 These conversions are conducted in refluxing ethanol for 2 hours. 

Triethyl l,3,5-triazine-2,4,6-tricarboxylate and 2,4,6-tris(methylsulfanyl)-1,3,5-triazine react in an inverse electron demand Diels-Alder reaction with several electron-rich dienophiles.6 The tricarboxylate 9 (R1 = C02Et) undergoes a well-defined [4 + 2] cycloaddition reaction with ynamines and enamines. In the case of ynamines, the [4 -1- 2] cycloaddition is followed by a retro Diels - Alder reaction at 40 100 °C with direct formation of the substituted pyrimidines 11. In the case of enamines, the cycloaddition provides stable, isolable [4 + 2] adducts 12. The subsequent retro Diels-Alder reaction and the final aromatization step is catalyzed by a mixture of hydrochloric acid and dioxane, anhydrous p-toluencsulfonic acid or acetic acid. This two-step process can be reduced to a single operation by conducting the reaction in a solution of dichloromethane and acetic acid at 40-100 °C.6 Electron-deficient dienophiles like dimethyl acetylenedicarboxylate or 1,4-naphthoquinone do not react with this triazine. 

When triethyl l,3,5-triazine-2,4,6-tricarboxylate is treated with acetimidamide hydrochloride7 or propionimidamide hydrochloride8,9 in dimethylformamide at 90-100°C the corresponding pyrimidines are formed in 80-85% yield. The reaction proceeds by reversible in-situ tautomerism of the amidine hydrochloride to the alkene-1,1-diamine and its participation in a [4 + 2] cycloaddition with the triazine. The cycloaddition is followed by a retro Diels-Alder reaction with loss of ammonia and ethyl cyanoformate. The thermal conditions (>80°C) required for effecting the retro-Diels-Alder reaction and the deliberate use of the amidine hydrochlorides facilitates the amidine tautomerism and seems to be essential for aromatization of the initially formed cycloadduct.7-9... 

It is worth noting that the C-N-C-C fragment can be derived from heterocyclic compounds. For instance, interaction of triethyl l,3,5-triazin-2,4,6-tricarboxylate 269 with arylhydrazines affords esters of 5-amino-6-oxo-l,6-dihydro-l,2,4-triazin-3-carboxylic acid 270 in good yields (Scheme 160) <2004TL2791>. 

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