2- Carbamoyl-5,6-diphenyl-3- pyrazine

Normal nucleophilic substitution occurred on treatment of 2-carbamoyl-3-chloropyrazine with alcoholic methylamine at 130° (423, 836) 2-chloro-3-(4 -morpholinocarbonyOpyrazine with morpholine at reflux in benzene (867) 2dimethyl sulfoxide at 65° (857) and cyclohexylamine in benzene at reflux (946) 3-chloro-2-methoxycarbonyl-5-phenylpyrazine with alcoholic methylamine at 140° (375) 2-carboxy-3-chloropyrazine with anhydrous ammonia at 100° for 5 hours (947) 2-carbamoyl-6-chloropyrazine with aqueous methylamine at reflux (940) 2-chloro-6-(4 -morpholinocarbonyl)pyrazine (and other amides) and 2-chloro-6-methoxycarbonylpyrazine with morpholine (and other amines) (870, 948, 949) and 2-chloro-6-methoxycarbonylpyrazine with liquid ammonia at 80° (870). 2-Chloro-3-methoxycarbonylpyrazine fused with guanidine carbonate gave 2-amino4-hydroxypteridine and its 7-methyl-, 7-phenyl, and 6,7-diphenyl analogues were prepared similarly (371,375). 

Replacement of the chloro substituent by methoxide has been observed in the following pyrazines 2-chloro-3-methoxycarbonyl (at <5°) (867) 2-chloro-6-methoxycarbonyl (870) 2-chloro-3-methoxycarbonyl-5,6-diphenyl (371, 837) 2-carboxy-6-chloro (869, 871) 2-carbamoyl-5( )-chloro (839) 2-carbamoyl-6-chloro (805, 839) 2-chloro-6-(4 -morpholinocarbonyl) (870) 2-chloro-3-cyano (810, 811) 5-chloro-3-cyano-2-methoxy (reflux 14h) (881) 2-chloro-5-methoxy-3,6-dimethyl (844) 2-chloro-5-isopropyl-6-methoxy-3-methyl (50, 844) 2-chloro-5-methoxy-3,6-diphenyl (1.1 equivalents of 20% methanolic sodium methoxide at 135° for 20h) (797) 2-benzyloxy-6-chloro(at reflux) (832, cf. 883) 2-chloro-3-pyridinio(pyrazine)chloride (or tosylate) (to give 2,3-dimethoxypyrazine) (765) ... 

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). 

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). 

Heating of l,4-dicyano-2,3-dinitroso-2,3-diphenylpiperazine ( ) (1572, cf. 1573) in mesitylene is claimed to give l,4-dicyano-2,3-diphenyl-1,4,5,6-tetrahydro-pyrazine (1572), and l-carbamoyl-3-hydroxy-2,3-diphenylpiperazine ( )(1572, cf. 1573) with methyl iodide and potassium carbonate in methanol is claimed to give 4-carbamoyl-l,l-dimethyl-2,3-diphenyl-l,4,5,6-tetrahydropyrazinium iodide (1572). 2-Diethylamino-l,4-dimethylpiperazine on thermal treatment gives 1,4-dimethyl-l,2,3,4-tetrahydropyrazine, which was methoxycarbonylated to 5-methoxycarbonyl-1,4-dimethyl-l, 2,3,4-tetrahydropyrazine (1593). 

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