Triazine-3-ones, reduction

Data on the structures of monocyclic dihydro- or hexahydro-1,2,3-triazines, on 1,2,3-triazine tV-oxides and 1,2,3-triazinones are not yet available. From studies on the one-electron reduction of the tetrahydro-l,2,3-triazinium salts (7) it was concluded that the heterocyclic ring is flexible and not planar (80LA285). No detailed information on the structure of 3-benzyl-l,5-diphenyl-l,2-dihydro-l,2,3-triazine-4,6(3//,5f/)-dione (8) or of the 6-hydroxy-4-oxo-l,4-dihydro-l,2,3-triazinium hydroxide inner salts (9) seems to be available. 

Reduction of l,2,4-triazin-3-ones (84) with Raney nickel, zinc and acetic acid, lithium aluminum hydride, sodium borohydride, titanium(III) chloride, p-toluenethiol, hydrogen and a palladium catalyst, or electrochemically, produces 4,5-dihydro-l,2,4-triazin-3-ones (268) (78HC(33)189, p. 246, 80JHC1237), which may be further reduced to 1,4,5,6-tetrahydro-l,2,4-triazin-3-ones (269). l,2,4-Triazin-3-ones (84) with hydriodic acid and phosphorus yielded imidazoles (05LA(339)243). 3-Alkoxy-l,2,4-triazines (126) and sodium borohydride gave the 2,5-dihydro derivatives (270) (80JOC4594). 

Methyl-1,2,4-triazin-5-one (271) with lithium aluminum hydride formed the 1,2,5,6-tetrahydro-l,2,4-triazine (272), and reduction of the 2,6-dimethyl-l,2,4-triazin-5-one (273) and 4,6-dimethyl-l,2,4-triazin-5-one (274) led to the dimethyl-3,4-dihydro-l,2,4-triazin-5(2//)-ones (275) and (276), respectively (73JHC559). 

Reduction of 4-amino-1,2,4-triazin-5-ones (291) affords compounds which were formulated (rather improbably) as 4-amino-5-hydroxy-3,4-dihydro-l,2,4-triazines (292)... 

Perhaps the most useful part of the reported synthesis is the facile preparation of (—)-pyrimidoblamic acid (12 Scheme 3). A key to this synthesis is the preparation of the fully substituted pyrimidine 8. This was done by a one-pot inverse electron demand Diels-Alder reaction between the symmetrical triazine 7 and prop-1-ene-1,1-diamine hydrochloride, followed by loss of ammonia, tautomerization, and loss of ethyl cyanoformate through a retro-Diels-Alder reaction. Selective low-temperature reduction of the more electrophilic C2 ester using sodium borohydride afforded 9, the aldehyde derivative of which was condensed with 7V -Boc-protected (3-aminoalaninamide to give the imine 10. Addition of the optically active A-acyloxazolidinone as its stannous Z-enolate provided almost exclusively the desired anti-addition product 11, which was converted into (—)-pyrimidoblamic acid (12). Importantly, this synthesis confirmed Umezawa s assignment of absolute configuration at the benzylic center. 

Anderson RF, ShindeSS, Elay MP, GamageSA, Denny WA (2003b) Activation of 3-amino-1,2,4-benzo-triazine 1,4-dioxide antitumor agents to oxidizing species following their one-electron reduction. J Am Chem Soc 125 748-756... 

Reduction of the pyrano-l,2,4-triazin-3-one (131), as a mixture with the isomer (132), gave the dihydro compounds (133) and (134) in an overall yield of 60% <85JHC33>. 

Reduction of the pyrano-l,2,4-triazin-3-one (132) using zinc powder in AcOH gave the dihydro compound (134) (85%). Analogous reduction of pyrano-l,2,4-triazin-3-thione (151) delivered com-... 

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