2-Bromo-6-cyanopyrazine

Bromination of 2-amino-3-cyanopyrazine in acetic acid gave 2-amino-5-bromo-... 

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 preparation of cyanopyrazines by primary synthesis has been described in Section II.IH (286-288) and Section 11.2 (353-360). Further data have been recorded on the condensation of diaminomaleonitrile with glyoxal (1434, 1435), with a variety of 1,2-dicarbonyl compounds (1435, 1436), and Bredereck and Schmotzer (1044) have described the preparation from the tetramer of hydrocyanic acid with /J,p -dibromobenzil and p,p -diphenoxybenzil of 2,3-bis(p-bromo-phenyl)-5,6-dicyanopyrazine and 2,3-dicyano-5,6-bis(p-phenoxyphenyl)pyrazine, and with phosgene in dioxane of 2,3-dicyano-5,6-dihydropyrazine. Other preparations are described in Section II.3 (158, 383-387), with further data given in references 1050, 1154 and 1180, Section 11.5 (454) and Section 11.7 (484-486, 488-490). 

Amino-5-bromo-3-cyanopyrazine is an intermediate in the construction of pteridines. Before forming the fused pyrimidine ring, the pyrazine is alkynylated in the 5-position (82) in moderate to good yields (87JOC3997 88JOC35). 

Intermolecular cyclization of 4-dialkylamino-2-aza-l,3-diene-1,1-dicarbonitriles proceeds on treatment with hydrogen bromide in acetic acid to yield 2-bromo-3-cyanopyrazine <90HCA1210>. Tetraalkyl or -arylpyrazines are synthesized by reductive cyclization of the corresponding nitriles with titanium tetrachloride and zinc in modest to good yields (Equation (18)) <90S70l>. 

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