2- 2 -Hydroxyimino-2 - ethyl pyrazine

Typical preparations have been described for 2-(r-hydroxyiminomethyl)pyrazine (138) 2-(4 -dimethylamino-T-hydroxyiminobutyl)pyrazine (1186) 2-(2 -hydroxy-iminopentyl)-6-methylpyrazine (645) 2-(2 -hydroxyimino-3, 3 -dimethylbutyl)-6-methylpyrazine (645) 2-[r-hydroxyimino-2-(pyridin-2"-yl) (hyl]pyrazine (642) 2-[2 -hydroxyimino-2 -(pyridin-2"-yl, pyrazin-2"-yl, or pyrimidin-4 -yl)ethyl]pyrazine (642) 2-[l, 2 -bishydroxyimino-2 -(pyridin-2"-yl)ethyl]pyrazine (642) 2-12 -(2",4"-dinitrophenylhydrazono)-3 -methylbutyl]-6-methylpyrazine (645) 2-[ 1-(substituted hydrazono)ethyl]pyrazine (1196) 2-[l -phenyl-1 -(substituted hydrazono)methyl]-pyrazine (1196) 2-(r-thiosemicarbazonoethyl)pyrazine (138) 2-(2 -chloro-l -thiosemicarbazonoethyOpyrazine (138) and 2,5-dimethyl-3,6-bis(r-semicarbazono-ethyl)pyrazine (1196). 

Gastaldi (286) first described this synthesis, in which an a-hydroxyimino ketone was treated with aqueous sodium bisulfite saturated with sulfur dioxide, and the bisulfite compound treated with potassium cyanide followed by hydrolysis with hydrochloric acid. By this procedure, Gastaldi prepared 2,5-dicyano-3,6-dimethyl-pyrazine from hydroxyiminoacetone, and 2,5-dicyano-3,6-diphenylpyrazine and some 3-cyano-2,5-diphenylpyrazine from hydroxyiminoacetophenone. He proposed a reaction mechanism involving the intermediate compounds (21) and (22). Sharp and Spring (287) used the same procedure to prepare 2,5-dicyano-3,6-diethyl-pyrazine from ethyl hydroxyiminomethyl ketone. 

Aminomethyl phenyl ketone oximes, such as ethyl 6-amino-5-nitro-4- [2-(hydroxyimino)-2-phenylethyl]amino pyridine-2-carbamate, bearing various substituents in the phenyl group are converted into the corresponding ketones 12, and then cyclized by hydrogenating the nitro function to yield 5-amino-3-aryl-1,2-dihydropyrido[3,4-5]pyrazine-7-carbamates 13.104 1°9... 

To a solution of ethyl 5(R)-2-(hydroxyimino)-5-(benzyloxy carbonylamino)-3-oxododecanoate (27, 600 mg, 1.47 mmol) in 10 mL acetic acid was added zinc dust (965 mg, 14.7 mmol) in small portions. The reaetion mixture was stirred for 12 h at room temperature, then filtered through a pad of Celite, and the solid washed with CH2CI2. The solvents were evaporated, and the residue dissolved in 20 mL dichloromethane. To this solution was added triethylamine (0.62 mL, 4.44 mmol) and the mixture was stirred for 1 h at room temperature. Additional water (10 mL) was added, and the solution extracted with dichloromethane (3 x 50 mL). The organic layer was washed with brine (30 mL), dried over anhydrous MgS04 and the solvent evaporated. The crude produet was purified by column chromatography (petroleum ether-AcOEt, 7 3), giving diethyl 3(/ ),6(/ )-3,6-di(benzyloxycarbonyl-amino)-pyrazine-2,5-dicarboxylate (400 mg, 70%), as a white solid, mp 89-91 °C. 

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