Ring Transformations of Pyridazines and Other Heterocycles to Pyrazines

RING TRANSFORMATIONS OF PYRIDAZINES AND OTHER HETEROCYCLES TO PYRAZINES 

Ultraviolet irradiation of tetrafluoropyridazine (113, Rp = F) has been shown to give a nearly quantitative yield of tetrafluoropyrazine, and 3,6-difluoro-4,5- 

4-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). 

Various other heterocycles have also been converted to pyrazines. Thus tetra-phenylpyrrole with lead tetraacetate and potassium carbonate in chloroform has been shown to give a 20% yield of tetraphenylpyrazine (498) 5-amino-3,4-dimethyl-isoxazole (117) and 50% hydrazine hydrate, when heated on a water bath and the product treated with hot concentrated hydrochloric acid, pve tetramethylpyrazine (499). Treatment of 3-amino-24iydroxy-4,4-dimethyltetrahydrofuran (118) with strong alkali gave 2,5-bis(hydroxy-f-butyl)pyrazine (119) (500) and catalytic hydrogenation of furylamines (120) over platinum at 220-225° gave alkylpyrazines (121) (500a). 

Hydrogenation of 4-hydroxy-3-methoxycarbonyl-6-oxo-l, 2(6/f)-oxazine (122) in methanol over palladium-charcoal has been shown to give 2,5-dimethoxy-carbonyl-3,6-dimethylpyrazine (501) and 3-amino-4-hydroxycoumarin (123, R = r2 = H), 3-amino4-hydroxy-6,8-dimethylcoumarin and 3-acetamido-4-hydroxy-6-methylcoumarin, when heated vrith 2N sodium hydroxide, gave 

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