Ring hydrogenation pyrazine rings

The structure of lumazine has been studied more precisely by X-ray analysis (72AX(B)659). The crystal structure is built up of almost coplanar, hydrogen-bonded dimers of lumazine with the oxygens of the pyrimidine moiety in the keto form and the observed bond distances indicating the pyrazine ring electrons to be delocalized. 

The Sonogashira reaction is of considerable value in heterocyclic synthesis. It has been conducted on the pyrazine ring of quinoxaline and the resulting alkynyl- and dialkynyl-quinoxalines were subsequently utilized to synthesize condensed quinoxalines [52-55], Ames et al. prepared unsymmetrical diynes from 2,3-dichloroquinoxalines. Thus, condensation of 2-chloroquinoxaline (93) with an excess of phenylacetylene furnished 2-phenylethynylquinoxaline (94). Displacement of the chloride with the amine also occurred when the condensation was carried out in the presence of diethylamine. Treatment of 94 with a large excess of aqueous dimethylamine led to ketone 95 that exists predominantly in the intramolecularly hydrogen-bonded enol form 96. 

The pyrazine ring is stable toward permanganate oxidation, and this explains a variety of pyrazinecarboxylic acids that have been prepared from quinoxalines or benzo-fused quinoxalines. In contrast, alkyl side chains on pyrazines are effectively oxidized by permanganate, selenious acid, selenium dioxide, or dichromate to afford the corresponding carboxylic acids (Section 8.03.7.1). Oxidation of pyrazines with hydrogen peroxide or percarboxylic acids gives pyrazine A -oxides and/or A, A -dioxides (Section 8.03.5.2). 

Stepwise pyrazine ring-formation using 5-nitropyrimidine was applied to the synthesis of 4a-hydroxytetrahydrobiopterin (95), which is an interesting intermediate in the metabolism of aromatic amino acids (see Sect. 5.2). As illustrated in Scheme 18, the 5-aminopyrimidine 97 prepared from chloroni-tropyrimidine 96 by nucleophilic substitution followed by catalytic hydrogenation was oxidized under acidic conditions to o-quinone derivative 98. 

The reaction conditions employed for cyclization may be important. For example, in sulfuric acid both the oximes 11 cyclized in about 15% yield, whereas in ethanolic hydrogen chloride only 11a did so, in 94% yield. The difference was attributed to the influence of the nitrogen of the pyrazine ring.32... 

The methyl donor is methylene-tetrahydrofolate. The reaction involves formation of a methylene bridge between A(-5 of the coenzyme and C-5 of dUMP, followed by transfer of hydrogen from the pyrazine ring of tetrahydrofolate,... 

Diastereoseiective Hydrogenation of C=N Double Bonds. Immobilized Rh-NORPHOS catalysts have been employed for diastereoseiective heterogeneous hydrogenation of the C=N double bonds in the pyrazine ring of folic acid (eq 2) With (S,S)-NORPHOS, optically active tetrahy-drofolic acid that possesses the (65)- configuration at the newly formed asymmetric center was obtained in 96-98% chemical yield (18-21% de). When (RR)-NORPHOS was used for this purpose, tetrahydrofolic acid with the (6R)- configuration at the new asymmetric center was... 

Hydrogenation solvent. The acid is preferred as solvent for hydrogenation (Pt or Rh) of pterines, since complete and selective hydrogenation of the pyrazine ring of pterine, its N-methylated derivative, and of folic acid is effected in short time. ... 

Although there are a number of possible reduced forms of pteridines, in practice only a few of these are commonly available. Reductive methods usually result in hydrogenation of the pyrazine ring and lead first to 7,8-dihydropteridines, then to 5,6,7,8-tetrahydropteridines. 

The title compounds are stable tautomers of the corresponding 2-hydroxypyrazine 1-oxides, and in fact l-acetoxy-2(lH)-pyrazinones, not 2-acetoxypyrazine A -oxides, are obtained on treatment with acetyl chloride in the presence of pyridine at room temperature <87JHC187>. Nevertheless, these compounds resemble the N-oxides in most of their reactions. Representative examples are deoxidative acetoxylation and chlorination. Treatment of l-hydroxy-3,5-diphenyl-2(l//)-pyr-azinone (100) with a refluxing mixture of acetic anhydride and acetic acid affords 2,6-diacetoxy-3,5-diphenylpyrazine (101), which is deacetylated with potassium hydrogen carbonate to give 2,6-dihydroxy-3,5-diphenylpyrazine (102) (or tautomer) (Scheme 23) <7UCS(C)2977>, Acetoxylation of a methyl substituent occurs exclusively and then that of the pyrazine ring is suppressed completely. 

Catalytic hydrogenation of the imide 24 (R = H) over palladium on charcoal results in partial reduction of the pyrazine ring to give the tetrahydro compound 37. The anomalous products 31 and 32 from the reaction of the anhydride of pyrazine-2,3-dicarboxylic acid and hydrazine were presumed to have been formed by reduction of the pyrazine ring by diimide. This could have been formed in situ by oxidation of hydrazine... 

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