5-Cyano-2,3-diphenylpyrazine

Gastaldi (286) first described this synthesis, in which an a-hydroxyimino ketone was treated with aqueous sodium bisulfite saturated with sulfur dioxide, and the bisulfite compound treated with potassium cyanide followed by hydrolysis with hydrochloric acid. By this procedure, Gastaldi prepared 2,5-dicyano-3,6-dimethyl-pyrazine from hydroxyiminoacetone, and 2,5-dicyano-3,6-diphenylpyrazine and some 3-cyano-2,5-diphenylpyrazine from hydroxyiminoacetophenone. He proposed a reaction mechanism involving the intermediate compounds (21) and (22). Sharp and Spring (287) used the same procedure to prepare 2,5-dicyano-3,6-diethyl-pyrazine from ethyl hydroxyiminomethyl ketone. 

The self-condensation of the bisulfite addition compound of an a-oximinoketone followed by reaction with potassium cyanide and hydrochloric acid yields 3,6-dicyano-2,5-dialkylpyrazines or, in the case of oximinoacetophenone, a mixture of 3-cyano-2,5-diphenyl-pyrazine and 3,6-dicyano-2,5-diphenylpyrazines.227... 

Methyl 6-amino-5-cyano-3-methyl-2-pyrazinecarboxylate 1-oxide Methyl 3-amino-5-cyclohexyl-2-pyrazinecarboxylate Methyl 3-amino-6-cyclohexyl-2-pyrazinecarboxylate Methyl 3-amino-6-cyclopropyl-2-pyrazinecarboxylate Methyl 3-amino-5,6-dichloro-2-pyrazinecarboxylate Methyl 3-amino-5-dimethylamino-6-methyl-2-pyrazinecarboxylate Methyl 3-amino-5-dimethylamino-6-phenyl-2-pyrazinecarboxylate Methyl 3-amino-5-dimethylamino-2-pyrazinecarboxylate Methyl 3-amino-5,6-dimethyl-2-pyrazinecarboxylate 2-Methylamino-3,5-diphenylpyrazine 2-Methylamino-3,6-diphenylpyrazine... 

Phenylpyrazine 1-oxide, 2,3-diphenylpyrazine 1-oxide and 2,5-diphenylpyrazine 1 -oxide have been deoxygenated in good yield by aqueous chromium(ll) chloride in methanol, acetone, and chloroform at room temperature (761), and deoxygenation of 5-(substituted aminomethyl)-2-amino-3-cyano-6-methylpyrazine 1-oxide by triethyl phosphite in hot dimethylformamide has been described (762). 

The reactions of various chlorophenylpyrazines with potassium amide in liquid ammonia have been investigated in detail (827). Treatment of 2-chloro-3-phenylpyrazine with potassium amide in liquid ammonia gave only 2-amino-3-phenyl-pyrazine, but 2-chloro-6-phenylpyrazine gave 4(5)-phenylimidazole and 2-cyano-4(5)-phenylimidazole, and 2-chloro-5-phenylpyrazine gave a mixture of 2-amino-5-phenylpyrazine, 4(5)-phenylimidazole, and 2-cyano-4(5)-phenylimidazole. The 2[Pg.125]

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). 

Reaction of 2with hydrazine hydrate is reported to give 2[Pg.284]

Dicyanopyrazine with sodium methoxide in methanol with ammonia at reflux gave 5,7-diimino-6//-pyrrolo[3,4-i)]pyrazine (65) (1442) and 2,3-dicyano-5,6-dimethyl(and 5,6-diphenyl)pyrazine with hydrazine by the procedure of Patel and Castle (1339) gave 2,3-dimethyl(and 2,3-diphenyl)-5,8-diaminopyrazino[2,3-rfJ-pyridazine(s) (66) (1435). Fusion of 2-chloro-3-cyano-5,6-diphenylpyrazine with urea and thiourea was reported to give 4-amino-2-hydroxy(and mercapto)-6,7-diphenylpteridine (848). 

Cyano-2,3-diphenylpyrazine heated with dry ammonium thiocyanate at ISO gave 5-amidino-2,3-diphenylpyrazine (866). 2-Cyano-5-phenylthiopyrazine heated in acetic acid with hydrogen peroxide for 3 hours gave 2-cyano-5-phenylsulfonyl-pyrazine and some 2-carbamoyl-5-phenylsulfonylpyrazine (840) and 2-cyano-pyrazine with hydrogen peroxide in aqueous alkali at 70° gave 2-carbamoylpyrazine... 

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