3- Amino-2,5-dimethylpyrazine 1 -oxide

Aminopyrazine 1-oxide with nitrous acid in sulfuric acid on wanning and dilution with water (108, 547a), and also by treatment with potassium cuprous cyanide (838), has been shown to give 3-hydroxypyrazine 1-oxide. 2-Amino-3,5-dimethylpyrazine 1 -oxide with about 40% sodium hydroxide at reflux in a bath at 140° produced 2-hydroxy-3,5-dimethylpyrazine 1-oxide (524). 

Redox potentials of pentacyanoferrates are often determined in association with kinetic and stability constant determinations. They are also available for 4-methyl- and 4-amino-pyri-dine pentacyanoferrates, and for [Fe(CS )5(2,6-dimethylpyrazine)] in acetonitrile-water mixtures.Oxidation potentials of [Fe(CN)5L] complexes correlate with the electron-withdrawing or -releasing properties of the ligands... 

The marked activation of the iV-oxide function on the chlorine atom of 2-chloropyrazine 4-oxide and 2-ehloro-3,6-dimethylpyrazine 4-oxide is also demonstrated by the milder conditions under which these compounds react with ammonia and amines compared with chloro-pyrazine and 2-chloro-3,6-dimethyl pyrazine, respectively. Although 2-chloropyrazine 4-oxide undergoes the expected displacement reaction with ammonia on heating at 115°-120° for 2.5 hours, reaction at 140° for 16 hours gives 2,3-diaminopyrazine, possibly as a result of an addition-elimination reaction on the initially formed 2-amino-pyrazine 4-oxide (Scheme 47).417... 

Dimethylamino-7V-hydroxy-2-pyrazinecarboxamide 6-Dimethylamino-7V-hydroxy-2-pyrazinecarboxamidine 2-Dimethylamino-5-iodopyrazine 2-Dimethylamino-6-iodopyrazine 2-Dimethylamino-5-iodopyrazine 4-oxide 2-Dimethylamino-3-isobutylpyrazine 2-Dimethylamino-6-isobutylpyrazine 2-Dimethylamino-5-methoxy-3,6-dimethylpyrazine 2-Dimethylaminomethyl-3,6-bismethylthiopyrazine 2-Dimethylamino-6-methyl-5-phenylpyrazine 4-oxide 2-Dimethylamino-3-methylpyrazine 2-Dimethylamino-6-methylpyrazine 2-Dimethylamino-3-methylpyrazine 4-oxide Dimethyl 5-amino-6-oxo-1,6-dihydro-2,3-pyrazinedicarboxylate 2-Dimethylamino-5-phenylpyrazine 2-(3-Dimethylaminopropyl)-6-methylpyrazine... 

The hydrochlorides of esters of glycine and alanine have been reduced with sodium amalgam to the amino carbonyl compounds and then oxidized with mercuric chloride in an excess of alkali to yield pyrazine and 2,5-dimethylpyrazine, respectively (255,256). 

A number of piperazine-2,5-diones (a-amino acid anhydrides ) has been converted to pyrazines by the action of phosphorus halides. Baxter and Spring (312) first described the conversion of isoleucine anhydride (45) with phosphoryl chloride to 2,5-di-s-butyl-3,6-dichloropyrazine (46, X = Cl) and 2,5-di-s-butyl-3-chloropyrazine (46, X = H), and of DL-alanine anhydride (47) similary to 2,5-dichloro-3,6-dimethylpyrazine (48, X = Q) and 3from alanine anhydride does not involve an oxidation step, whereas the formation of 2,5-dichloro-3,6-dimethylpyrazine involves the oxidation of an intermediate dihydropyrazine derivative. Treatment of DL-alanine anhydride with phosphoryl chloride in the presence of a tertiary base (dimethylaniline) gave only the monochloro derivative the intermediate dichlorodihydropyrazine presumably loses hydrogen chloride and gives the stable aromatic 3-chloro-2,5-dimethylpyrazine. 

A -Amination of pyrazine 1-oxide and 2,5-dimethylpyrazine 1-oxide has been effected with hydroxylamine-O-sulfonic acid and hydriodic acid to give 4-aminopyrazinium 1-oxide iodide (40, R = = H) and 4-amino-2,5-dimethyl-... 

Crystal structures of 3,5,6-tri-t-butyl-2-hydroxypyrazine (1093) 2,5-dichloro-3-methoxypyrazine (915) and 2,3-dichloro-5-ethylamino-6-methoxypyrazine (916) have been determined. The dipole moment of 2-amino-5-bromo-3-methoxypyrazine (2.94D in benzene) is consistent with the S-cis configuration (52) (749) and the polarographic behavior of 3-hydroxy(and methoxy)-2,5-dimethylpyrazine (and their A(-oxides) at various pH values has been investigated (588). 

Aminopyrazine was oxidized by hydrogen peroxide in acetic acid at 20° to 3-aminopyrazine 1 -oxide and at 50° for 15 hours to 2-aininopyrazine 1,4-dioxide (51%) (also obtained by similar oxidation of 3-aminopyrazine 1-oxide) (1189). m-Chloroperoxybenzoic acid was also used for the oxidation of 2-aminopyrazine to its 1-oxide (1258). The following aminopyrazine TV-oxides have been prepared by oxidation (reagent and conditions) 2-amino-3-methoxycarbonylpyrazine 1-oxide (m-chloroperoxybenzoic acid in chloroform at reflux) (880, 1222) 2-amino-5-chloro-3-methoxycarbonyl(and methylcarbamoyl)pyrazine 1-oxide (m-chloroperoxybenzoic acid in chloroform at reflux) (1222) 2-amino-5-bromo-3-methoxycarbonylpyrazine 1-oxide (wperoxyacetic acid) (906) 2-amino-3-bromo-5,6-dimethylpyrazine 1-oxide (peroxyacetic acid) (907) and 2,3-bis(pyridin-2 -yl)pyrazine 1,4-dioxide (hydrogen peroxide in sulfuric acid at room temperature) (754). 

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). 

Dimethylamino-23-dimethylpyrazine 1-oxide in boiling acetic anhydride gave 2-acetoxymethyl-3-dimethylamino-5-methylpyrazine (793) which was not isolated but saponified directly to 3-dimethylamino-2-hydroxymethyl-5-methylpyrazine (793). 2-Amino-3-cyano-5-methylpyrazine 1,4-dioxide refluxed with (a) acetic anhydride gave 3-acetamido-2-cyano-5-hydroxy-6-methylpyrazine 1-oxide (532) and (6) sodium methoxide gave 3-amino-2-cyano-5-methoxy-6-methylpyrazine 1-oxide (532). 

Cyanopyrazine A -oxides have been prepared from a-amino nitriles and a-hydroxyimino carbonyl compounds as summarized in Section III. 1 (528-530, 532-534, 537, 540, 542). Oxidation of 2-cyanopyrazine with perhydrol gave 3-cyanopyrazine 1-oxide (575), 2-cyano-5-ethoxy-3,6-dimethylpyrazine with 30% hydrogen peroxide in acetic acid at 55° gave 2-cyano-5-ethoxy-3,6-dimethylpyrazine iV-oxide (288), and the oxidations of 2-amino-3-cyanopyrazine 1-oxide (538) and... 

Dawes and Edwards (1966) isolated it from the volatiles obtained by heating a mixture of D-fructose and glycine or L-3-phenylalanine. Wang et al. (1969) presented a model reaction in which the product of condensation of pyruvaldehyde with any amino acid degraded by a Strecker reaction can form an aminoketone which by subsequent steps of self-condensation and oxidation formed 2,5-dimethylpyrazine (Wang et al., 1969 Manley et al., 1974). It was found in a heated cysteine/glucose model system (Sheldon et al., 1986). 

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