5- Carbamoyl-2,3-diphenylpyrazine

Acetyl-2-carbamoyl-3-methyl-6-phenyl-2,5-dihydropyridazine (115) when heated with potassium hydroxide has been shown to give 2,5-diphenylpyrazine (497), and 2,6-dihydroxymorpholine (116) has been converted smoothly by hydrazine or hydroxylamine in aqueous hydrochloric acid to pyrazine in good yield (28). 

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). 

Pyrolyses and thermal stabilities of 2-hydroxy-, 2-ethoxy-, and 2-isopropoxy-pyrazines have been studied. 2-Hydroxypyrazine was very stable, but the alkoxy-pyrazines underwent thermal elimination of olefin to yield 2-hydroxypyrazine (668a). Electrochemical reductions of l-methyl-2-oxo-5,6-diphenyl-l,2-dihydro-pyrazine and 54iydroxy(and 5-methoxy)-2,3-diphenylpyrazine are reported to involve the intermediate enamine, for example, 6-hydroxy-1-methyl-2,3-diphenyl-1,4-dihydropyrazine (54) (1096, cf. 1097). When tested on mice 2-carbamoyl-5-methoxypyrazine had less anti tubercular activity than did pyrazinamide (1098). 

Amino-3-aminomethylpyrazine and ethyl chloroformate (Et3N/CHQ3) gave 2-amino-3-ethoxycarbonylaminomethylpyrazine (1184) 2-amino-3rA(-benzyl(and butyl)carbamoyl-5,6-diphenylpyrazine refluxed with ethyl chloroformate gave 2-N-benzyl(and butyl)carbamoyl-3-ethoxycarbonylamino-5,6-diphenylpyrazine (455) and 2-amino-3-Af-methylcarbamoyl-5,6-diphenylpyrazine refluxed with ethyl chloroformate for 20 hours gave 2-ethoxycarbonylamino-3-7V-methylcarbamoyl-... 

Some ureido- and thioureidopyrazines have been prepared from aminopyrazines with phenyl isocyanate in pyridine, potassium thiocyanate in acid solution, and with phenyl or isopropyl isothiocyanate in pyridine. Thus 2-amino-3-carbamoyl(and jV-benzylcarbamoyl)-5,6-diphenylpyrazines refluxed with phenyl isocyanate in... 

Carbamoyl-3-hydroxypyrazine refluxed with aniline gave 2-hydroxy-3-7V-phenylcarbamoylpyrazine (1055) and 2-amino-3-carbamoyl-5,6-diphenylpyrazine refluxed with benzylamine gave 2-amino-3-A -benzylcarbamoyl-5,6-diphenylpyrazine but a similar reaction with piperidine was unsuccessful (451). 3-Methylamino-2-yV-methylcarbamoyl-5-phenylpyrazine was unchanged when heated with liquid ammonia in dry ethanol at 210° for 2 hours (453). 2,6-Diamino-3-carbamoyl-5-chloropyrazine in isopropanol with 1 mol of potassium hydroxide and 1 -amidino-... 

A -Alkyl(thiocarbamoyl)]pyrazines have also been obtained by heating the 2-(A -alkylcarbamoyl)pyrazine with phosphorus pentasulfide and potassium sulfide in xylene at 100° (1268) and 2-amino-3-carbamoyl-5,6-diphenylpyrazine refluxed with phosphorus pentasulfide in pyridine gave 2-amino-5,6-diphenyl-3-thiocarbamoylpyrazine and the 3-A -butyl(thiocarbamoyl) analogue was prepared similarly (455). 2-Amino-5-chloro-3-(C-imino-C-methylthiomethyl)pyrazine with hydrogen sulfide in pyridine gave 2-amino-5-chloro-3-thiocarbamoylpyrazine (1218). 

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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