3- Cyano-2,5-dimethylpyrazine

Dicyano-3,6-dimethylpyrazine shaken with sodium ethoxide at room temperature for 10 hours produced 2-cyano-5-ethoxy-3,6-dimethylpyrazine (288). Bromination of 2-methoxy-3-sulfanilamidopyrazine (39) in methanol led to 5-(4 -amino-3, 5 -dibromobenzenesulfonimido)-6-hydroxy-2,3-dimethoxy-2,3,4,5-tetrahydropyrazine (32) which with 2 N sodium hydroxide gave 3-(4 -amino-3, 5 -dibromobenzenesulfonamido)-2-hydroxy-5 nethoxypyrazine (40) (816). The preparation of 2-amino-3,5-dicyano-6-methoxy(and ethoxy)pyrazine from a-(p-toluenesulfonyloxyiminomalononitrile and malononitrile has been described in Section II.7 (484). 2-Methoxycarbonyl(and cyano)-5-pyridiniopyrazine chloride (41) is reported (conditions not stated) to give 2-carboxy(and carbamoyl)-5-methoxypyrazine (765). 

Alkoxypyrazine A-oxides may also be prepared by oxidation of the alkoxypyrazine with peroxyacetic acid. In this way the following have been prepared 3-ethoxypyrazine 1-oxide (100°/20h) (978) 3-(trideuteromethoxy)pyrazine 1-oxide (757l9h) (975) 3-ethoxy-2-methylpyrazine 1-oxide (65-75724h) (978) 3-methoxy-2-phenylpyrazine 1-oxide (55720 h) (817) 3-ethoxy-2,5-dimethyl-pyrazine 1-oxide (56716 h) (872) 3-carbamoyl-2-methoxypyrazine 1-oxide (80720h) (881) and 2-cyano-5-ethoxy-3,6-dimethylpyrazine A-oxide (55720h) (288). 

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). 

Cyano-5-ethoxy-3,6-dimethylpyrazine refluxed with 50% sulfuric acid gave 3-hydroxy-2,5-dimethylpyrazine (288) but when refluxed with 5A potassium hydroxide for 10 hours gave 2-carboxy-5-hydroxy-3,6-dimethylpyrazine (288). 

Iminoethers have been hydrolyzed to esters and iminothioethers to thioesters. Some examples follow 2-cyano-3-(C-ethoxy-C-iminomethyl)-5,6-dimethylpyrazine [2-cyano-3-(C-ethoxyformidoyl)-5,6-dimethylpyrazine] (26) in boiling water gave... 

Treatment of diphenylacetonitrile in toluene with sodium amide and 2-chloro-pyrazine gave 2-(C-cyano-C,C-diphenylmethyl)pyrazine (1021), and 2-vinylpyrazine with phenylacetonitrile and sodium heated at 120-130° for 10 minutes gave 2-(3 -cyano-3 -phenylpropyl)pyrazine (731). 2-Amino-5-bromomethyl-3-cyano-pyrazine with sodium hydride and methyl cyanoacetate in tetrahydrofuran formed the dialkylated product (56) (1031). 2-Amino-3-mercapto-5,6-dimethylpyrazine in methanol with potassium hydroxide and chloroacetonitrile gave 2-amino-3-cyanomethyIthio-5,6-dimethylpyrazine (1229), and 2-carboxypyrazine refluxed with chloroacetonitrile and triethylamine in ethyl acetate for 45 minutes gave the cyanomethyl ester (1317). 2-Hydroxy 5-methyl-3-propylpyrazine with cyanogen halides in aqueous sodium hydroxide-dimethylformamide at 0-5° gave l-cyano-5-methyl-2-oxo-3-propyl-l, 2-dihydropyrazine (1123). 

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... 

---