2- pyrazine, with ethanolic potassium hydroxide

The reaction of 2,3-dichloropyrido[2,3-0]pyrazine (9) with ethanolic potassium hydroxide is reported to give 3-ethoxypyrido[2,3-( ]pyrazin-2(1 H)-one (10), whereas by the same treatment 2,3,7-trichloropyrido[2,3-0]pyrazine is converted into 2,3-diethoxy-7-chloropyrido[2,3-fr]pyrazine.46... 

The condensation of a, dicarbonyl compounds (49) with aj3-diamino compounds (50), which proceeds through the dihydropyrazine (51), has been much used for the synthesis of alkyl- and arylpyrazines (52). These reactions are usually carried out in methanol, ethanol, or ether in the presence of sodium or potassium hydroxide. The dihydropyrazines may be isolated, or oxidized directly to the pyrazine. Dehydrogenating agents that have been employed include oxygen in aqueous alkali (329), air in the presence of potassium hydroxide (330), sodium amylate in amyl alcohol (330a), alcoholic ferric chloride (24), and copper chromite catalyst at 300° (331) (see also Section 1). Pyrazines prepared by this method and modifications described below are listed in Table II.8 (2, 6, 24, 60, 80,195, 329-382) and some additional data are provided in Sections VI. 1 A, VlII.lA(l), and IX.4A(1). 

Cyano-6-methylaminopyrazine was also prepared from the chloro compound with methylamine hydrochloride and sodium hydroxide in aqueous dioxane (945) and 2-cyano-6-(2, 2 -dimethylhydrazino)pyrazine was prepared similarly (945). 2-Chloro-6-cyanopyrazine with methanol (and similarly with ethanol) and triethylamine gave 2-methoxy-6-(C-methoxyformidoyl)pyrazine (32) [see Section 5D(2)], and 2-chloro-6-carbamoylpyrazine with concentrated aqueous ammonia at 170-175° gave 2 -amino-b-carboxypyrazine (744). 2-Chloro-3-cyano-5,6-diphenylpyrazine with ammonium hydroxide and potassium iodide formed 2-amino-3-carbamoyl-5,6-diphenylpyrazine, but on fusion with ammonium acetate it gave 2-amino-3-cyano-5,6-diphenylpyrazine (848). 

Bis(azidocarbonyl)pyrazine heated with anhydrous benzyl alcohol at 180° for 30 minutes, and then at 220° for 15 minutes gave 2,5-bis(benzyloxycarbonyl-amino)pyrazine (5), which with concentrated sulfuric acid foUowed by pouring onto ice afforded 2,5-diaminopyrazine (1176) but 2,5-bis(azidocarbonyl)pyrazine refluxed with ethanol gave 2,5-bis(ethoxycarbonylamino)pyrazine, which could not be converted into the amine with (fuming) hydrochloric acid to 210°, with concentrated sulfuric acid, or with potassium hydroxide (1172). 

Dehydrogenations of some 2,3-dihydropyrazines to the corresponding pyrazines have been effected as follows 2,3-dimethyI-5,6-dihydro [reflux with potassium hydroxide in ethanol (333) heat in ethylene glycol at 197° (653, 1558) reflux with potassium hydroxide and manganous oxide in ethanol (633a) vapor phase reaction in the presence of a catalyst, such as copper chromite, and clay (472) heat... 

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