2-Ethyl-3-hydroxypyrazine

Iodopyrazine and six mono- and dialkyl- and phenyl-substituted 2-iodopyrazines have been prepared (30-60% yield) by displacement of the chloro substituent from the corresponding chloro compounds with a solution of sodium iodide and hydriodic acid in ethyl methyl ketone (887). Attempts to prepare iodopyrazine by treating the hydroxypyrazine with phosphorus triiodide were unsuccessful (887). 

Methoxypyrazines (31) have been prepared by diazomethane methylation of 2-hydroxy-3-isobutylpyrazine (60, 311, 367), 2-hydroxy-3-isopropylpyrazine (59, 367), 2-hydroxy-3-propyl(ethyl or hexyl)pyrazine (367), 3-hydroxy-2-isobutyl-5(and 6)methylpyrazine and 2-hydroxy-3-isobutyl-5,6-dimethylpyrazine (368), 2,3-dihydroxypyrazine (832), 2-hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenyl-pyrazine (832), 2-hydroxy-6-methoxy(and benzyloxy)pyrazine (832), 2,6-dihydroxy-3,5-diphenylpyrazine (873), 2,3,5-trifluoro-6-hydroxypyrazine (851), 2-chloro-6-hydroxy-3,5-diphenylpyrazine (873), 2-chloro-6-hydroxy-5-methyl-3-phenylpyrazine (873), 2-chloro-6-hydroxy-3-methyl-5-phenylpyrazine (873), 5,6-dichloro-1 -cyclohexyl-34iydroxy-2-oxo-l, 2-dihydropyrazine (853), 2-chloro-5-hydroxy-3-methoxy-6-methoxycarbonylpyrazine (881), 2-(4 -amino-3, 5 -dibromo-phenylsulfonamido)-3Tiydroxy-6-methoxypyrazine (881), 2-amino-3-hydroxy-... 

Many hydroxypyrazine A oxides have been A(-deoxygenated to pyrazines with a variety of reducing agents which include heating with hydrazine hydrate in alcohols hydriodic acid and red phosphorus in acetic or phosphoric acid iodine and red phosphorus in refluxing acetic acid phosphorus tribromide in ethyl acetate sodium dithionite catalytic reduction with hydrogen over Raney nickel dry distillation with copper-chromite catalyst and titanium trichloride in tetrahydrofuran at room temperature. 

Amino-5-carboxypyrazine in anhydrous dimethylformamide with triethyl-amine and ethyl chloroformate and then diethyl glutamate and stirred at room temperature gave 2-amino-5-(l, 3 -diethoxycarbonylpropyl)carbamoylpyrazine (24) (1244). Similarly a mixture of 2-carboxypyrazine and triethylamine in methylene dichloride with ethyl chloroformate and morpholine gave 2-( -morpholinocarbonyl)-pyrazine (1351). 2-Carboxy-3-hydroxypyrazine refluxed with phosphorus tris(A-methylanilide) in toluene gave 2-hydroxy-3-(A-methyl-A-phenyIcarbamoyl)pyrazine (1055), and 2-hydroxy-3-(A -methyl-A -p-tolylcarbamoyl)pyrazine was prepared similarly (1055). Tetracarboxypyrazine heated with sulfur tetrafluoride (SF4) at 150° gave tetra(trifluoromethyl)pyrazine (899). 

The irradiation of pyrazine derivatives with an a-carbonyl substituent under an atmosphere of nitrogen gave hydroxypyrazines and 1,4-dihydropyrazines (solvent adducts). Thus irradiation of 2,5-dimethoxycarbonyl-3,6-dimethylpyrazine in diethyl ether with a 450-W high-pressure mercury lamp gave two significant photoproducts, 2-hydroxy-5-methoxycarbonyl-3,6-dimethylpyrazine and l(r-ethoxy-ethyl)-2,5-dimethoxycarbonyl-3,6-dimethyl-l,4-dihydropyrazine (1064). The mechanism of the reaction has been investigated and discussed (1064). 

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