1.2.4- Triazine 4-oxides, ring contraction

UV irradiation of 3-aminopyrido[4,3-e]-1,2,4-triazine 1-oxides 7 or 1,2,4-triazine 4-oxides 8 leads to deoxygenation, i.e., loss of the 7V-oxide function resulting in the corresponding 3-aminopyrido[4,3-e]-1,2,4-triazines 9 and 1,2,4-triazines 10 (76ACH327, 76LA153). At the same time, UV irradiation of the 1,2,4-triazine 4-oxides unsubstituted at the 5 position proceeds as a ring contraction to form triazoles 11 (76LA153). 

Electrochemical reduction of pyrano-l,2,4-triazin-3-ones (132) and (148) delivered the corresponding dihydro derivatives (134) and (153) in yields of 81% and 85%, respectively. Further electrochemical treatment of the compounds (134) and (153) provoked a ring contraction, leading to the pyranoimidazol-2-ones (154a,b) in 83% and 68% yield, respectively. Unexpectedly, attempted reaction of compounds (134) and (153) with NaBH4 in ethanol resulted in oxidation to the triazin-3-ones (132) and (148) (Scheme 7) (86JHC491). 

In 1,2,4-triazines it is essential that the 5-position is blocked (cf. pyrimidines without 4- or 6-substituents) to prevent nucleophilic ring opening, oxidation, and ring contractions from competing with N-oxidation (72LA111 86H951). Products include l,2,4-triazin-5-ones and -5,6-diones (72LA111). Whereas... 

There are considerable data available on imidazole formation by ring contractions of pyrimidines, pyrazincs and triazines [15, 43, 59-61]. Few of the reactions, however, have synthetic potential except perhaps for the thermolytic conversions of azidopyrimidines and azidopyrazines into 1-cyano-substituled imidazoles, and the reactions of chloropyrimidines and chloropyrazines with potassium amide in liquid ammonia to give 4- and 2-cyanoimidazoles, respectively. Ring contractions of quinoxaline 1-oxides may also have some applications. 

Similar ring contractions in which the nitrogen-nitrogen bond is cleaved are found in the reductive ring contractions of pyridazines to pyrroles [148, 149], phthalazines to isoindoles [150], 5,6-diphenyl-1,2,4-triazinones to imidazolones [151], benzo-l,2,4-triazines to benzimidazoles [71], benzo-l,2,3-triazinone to indazolone [la, 152], benzo-l,2,3-triazin-3-oxide to indazole [la], benzo-2,3-diazepines to isoquinolines [153], benzo-l-pyrano-[4,3-e ]-as-triazin-3-one to benzopyranoimidazolone [154], and 2-methyl-4,5-dihydropyridazin-3-ones to pyrrolin-2-ones [155]. 

Relatively few reactions of quinoxaline derivatives occur with change of ring size. Isolated examples are noted in the following text. For example, ring contraction to benzimidazole derivatives occurs when 2,3-diphenylquinoxaline (Chapter XV) or 2-halogenoquinoxalines (Chapter X) are treated with potassium amide in liquid ammonia and quinoxalin-2-one is treated with hydrazine (Chapter VX It is also found that oxidation of l-aminoquinoxalin-2-ones with lead tetraacetate give benzo-1,2,4-triazines (Scheme 6) (Chapter V). 

Oxidation of the 4a/7-pyrido[2,l-/][l,2,4]triazine (76) with bromine was reported <77LA1718>. The fully conjugated tribromide (77) underwent ring contraction with water to give (78) (Scheme 2). Bromination of the mesoionic (79) with pyridinium hydrobromide perbromide gave 8-mono and 8,10-dibromo derivatives. Compound (79) with DMAD afforded the tetracyclic 1 1 adduct (80) (Equation (6)) <83JCS(P1)349>. 

The reaction of the fervenulin 1-oxides 100 with secondary amines results in contraction of the 1,2,4-triazine ring to form 2-amino-5,7-dimethylimidazo[4,5-e] pyrimidine-4,6(5/7,7//)-diones 101. The reaction of the same fervenulin 1-oxides 100 with ammonia leads to the 1,2,4-triazine ring cleavage product, 1,3-dimethyl-5-imino-6-isonitrosouracil 102 (94KGS1253). 

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