Pyrazine jV-Oxides

Methylpyridine 2,6-Dimethylpyridine Isoniazid Cyanoacetate Pyrazine JV-oxide... 

The primary syntheses of pyrazine JV-oxides from aliphatic components only are described in this chapter. The preparations of pyrazine JV-oxides by oxidation of pyrazines are dealt with under the reactions of the appropriately substituted pyrazines for example, those of pyrazine and alkylpyrazine TV-oxides are described in Chapter IV, and of halogenopyrazine JV-oxides in Chapter V. The cleavage of JV-oxides of pteridines and related systems to aminopyrazine JV-oxides is described in Section VIII.3A(2). 

Pyrazine JV-Oxides, their C-Alkyl and C-Aryl Derivatives 91... 

Pyrazine JV-oxides and 2,3-dihydropyrazines also rearrange photochem-ically into imidazoles. From 2,5-disubstituted pyrazine 1-oxides (73) two products, 2-acyl(or aroyl) 4-substituted imidazole (74) and 2,4-disubstituted imidazole (75), result.The reaction (Scheme 16) presumably takes place through two isomeric oxaziridine derivatives. 

A new primary synthesis of 2-amino-3-arylpyrazines is accomplished by reaction of aroyl cyanides with 1,2-diaminoethane (Scheme 33). An important synthesis is that of 2-amino-3-cyano-5-sub-stituted pyrazines, which are conveniently synthesized by condensation of aminomalononitrile with a-oximino ketones and then deoxygenation of the resulting pyrazine jV-oxides (Scheme 37). 

The polarographic behavior of the 1-oxides and 1,4-dioxides of pyrazine, 2,5-dimethylpyrazine, and tetramethylpyrazine at various pH values has been investigated. It was assumed that at lower pH values, the A -oxide group was reduced in its protonated form. In acid media the 1-oxides exhibited double waves, the first of which is attributable to the reduction of jV-oxide groups and the second to that of the pyrazine nucleus (production of 1,4-dihydro compounds). Reduction of both A -oxide groups of pyrazine-1,4-dioxide proceeded simultaneously (588). Half-wave potentials of the voltammetric oxidation and reduction of pyrazine mono- and di-A -oxides have been measured in dimethylformamide, and in acetonitrile by the technique of a rotating platinum electrode (750). 

Bis(methylamino)-2,6-bis(Af-methylcarbamoyl)pyrazine 1-oxide was deoxy-genated by refluxing with triethyl phosphite (462) and 2-amino-3-cyano-5-[A -(p-carboxyphenyl)-JV-methyl]aminomethylpyrazine 1 -oxide (56, R = OH) (and some derivatives) and similar compounds were deoxygenated with triethyl phosphite alone or with dimethylformaraide at 120 (762, 1038-1040). Catalytic reduction has been employed with 2-amino-5-methyIpyrazine 1-oxide (Pd/C) (535) and 23-diamino-5,6-dimethylpyrazine 1,4-dioxide (Raney Ni) in ethanol (907). 

For example, good yields of 2-chloropyrazine 4-oxide,391,392 2-carbox-amidopyrazine 4-oxide,392 and 2-methylpyrazine 1,4-dioxide,391 have been obtained by oxidation of the appropriate pyrazine. In general, the preferred product from oxidation of monosubstituted pyrazines at lower temperatures is the monooxide formed by oxidation on the nitrogen remote from the substituent, whereas 1,4-dioxides are obtained by prolonged heating at higher temperatures.165 Pertrifluoro-acetic acid oxidation of 2,5-dichloro-3,6-dimethylpyrazine furnishes the di-AT-oxide, whereas permaleic acid gives only the mono-JV-oxide.393... 

Irradiation of an aqueous solution of [Os(NH3)5(N2)] by electrons or y-rays gives [Os(NH3)4(NH2XN2)] by action of OH radicals. Complexes involving heterocyclic ligands [Os(NH3)4(N2)L] (L = pyrazine, JV-methylpyrazium, isonicotinamide, and isonicotinic acid) have been synthesized by displacement of N2 from [Os(NH3)4(N2)2] under Ar. Aerial oxidation of these complexes in the presence of HX (L = pyr or isonicotinic acid) leads to the reversible formation of [Os(NH3)4X(L)]X2 (X = Cl or Br) pK, measurements indicate marked back bonding from osmium to the heterocycle. 

Pyrazine 93 was prepared by reductive cyclodimerization of 2-nitro-methylenehexahydroazocine.125 o-( 1 -Perhydroazocinyl)acetophenone was ring opened by Hg(II)fEDTA) to the aminoaldehyde 94.126 The reaction probably proceeds via JV-aryliminium ions in a manner similar to that of photocyclization of 64. Mercuric acetate oxidation of /V-methylperhydro-azocine, followed by HC1 and H2S, afforded trithiane (95).127 This was... 

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