2.3- Diphenylpyrazine 1,4-dioxide

Diphenylpyrazine 1,4-dioxide (46) gave a separable mixture of 2,3-dichloro-5,6-diphenylpyrazine (47) and (unexpectedly) 2-chloro-5,6-diphenylpyrazine... 

The simple phenyl-substituted pyrazines do undergo nitration in the phenyl ring for example, 2-phenylpyrazine yields the 4-nitrophenyl derivative (mixed acid), although 5-phenyl-2-pyrazinone forms the 3-nitropyra-zinone under similar conditions (75MI1). However, 2,5-dimethyl-3,6-diphenylpyrazine and its /V,A -dioxide are both reported to be nitrated to give the bis-(3-nitrophenyl) products (55JCS3094). 

Diphenylpyrazine 1-oxide (236) and the 1,4-dioxide (237) (90% H202, maleic anhydride, CHC13, reflux, 2 h 73 and 23%, respectively).1272 several analogues likewise.1065,1272... 

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. 

Quaternization of the four dimethylpyrazine A(-oxides and 2,3-diphenylpyrazine 1-oxide with methyl iodide in a sealed tube at 80 gave the 4-methylpyrazinium 1-oxide iodides, but 3-phenyl-, 2,5-diphenyl- and 3,5-diphenylpyrazine 1 -oxides and dimethylpyrazine 1,4-dioxides could not be quaternized. The quaternary salts were reduced by sodium borohydride to A -hydroxypiperazines (766). 

The reactions of 2,5-dimethyl-3,6-diphenyl-2,5-dihydropyrazine 1,4-dioxide and 3,6-diphenyl-2,5-dihydropyrazine 1,4-dioxide with acetic anhydride and a small amount of sulfuric acid afforded 2,5-dimethyl-3,6-diphenylpyrazine 1-oxide and... 

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