2-Cyano-3-phenylpyrazine

Displacement of the chloro substituent from pyrazines by the cyano group has not been satisfactorily accomplished (866), but many cyanopyrazines have been prepared from the bromo analogues. Karmas and Spoerri (866) prepared 11 cyanopyrazines with mono-, di-, or trialkyl or phenyl substituents from the corresponding bromo compounds and cuprous cyanide in refluxing dry 4-picoline, but the procedure was not suitable for the preparation of 2-cyanopyrazine (866). It was prepared in 29% yield when the reaction was performed in pyridine (866). Another preparation of 2-cyano-3-phenylpyrazine from the bromo analogue has also been reported (1024). 

The reductive decyanation of cyanopyrazine using H2 and Pt/C under acidic conditions has been reported <2002TL6747>, that is, 2-amino-3-cyano-5-phenylpyrazine 1-oxide 73 is hydrogenated to 2-amino-5-phenylpyra-zine 74 in 90% yield (Equation 11). The double reduction has also been shown to be realized with sodium dithionite. 

Cyano-3-diallylamino-2-pyrazinecarboxamide 5-Cyano-3-diethylamino-2-pyrazinecarboxamide 3-Cyano-5,6-diphenyl-2-pyrazinecarboxamide 5-Cyano-3-dipropylamino-2-pyrazinecarboxamide 5-Cyano-3-ethylthio-2-pyrazinecarboxamide 5-Cyano-3-isobutylamino-2-pyrazinecarboxamide 5-Cyano-3-isopropylthio-2-pyrazinecarboxamide 2- (1-Cyano-1 -methylethyl)pyrazine 2- Cyanomethyl-3 -phenylpyrazine 2-(l-Cyano-2-methylpropyl)pyrazine 2- Cyanomethylpyrazine... 

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]

Chloropyrazine and derivatives have been shown to react with alkali metal derivatives of a phenylacetonitrile or of a phenylacetamide for example, 2-chloropyrazine treated with diphenylacetonitrile in toluene with sodium amide gave 2-(T-cyano-r,r-diphenylmethyl)pyrazine (68, R = H) (1021, 1022). 2-Chloro-5-phenylpyrazine(s) with diethyl methylmalonate and sodium hydride gave 2-(r,l -di(ethoxycarbonyl)ethyl]-5-phenylpyrazine(s) (363-365, 824, 825), and a similar reaction occurred with 2-chloropyrazine (364, 365,1023). 

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). 

Finally, 3-amino-2-cyano-5-phenylpyrazine and ethyl chloroformate gave the N-ethoxy carbonyl derivative 128, which cyclized with loss of ammonia to l-methyl-7-phenylpteridine-2,4-dione in boiling methanolic sodium methoxide (moderate yield).181... 

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