3- Hydroxy-2,5-diphenylpyrazine nitration

As already mentioned, hydroxypyrazines exist in tautomeric equilibria with the corresponding pyrazinones which are normally the predominant species in the equilibria. Some of the reactions of hydroxypyrazines are reminiscent of those of phenols they can, for example, be coupled with diazonium salts and brominated and nitrated in either the ortho or para position to the hydroxyl group. Coupling with diazonium salts occurs in neutral or weakly alkaline solution, but if the reaction is carried out in 1 M sodium hydroxide solution, arylation of the pyrazine ring takes place. From hydroxy-pyrazine and benzenediazonium chloride 47% 2-hydroxy-3-phenyl-and 4% 2-hydroxy-3,6-diphenylpyrazine are obtained. 

A notable characteristic of the pyrazine nucleus is its resistance to electrophilic substitution but some hydroxypyrazines may be nitrated. Nitration of 5-hydroxy-23-diphenylpyrazine with fuming nitric acid in acetic acid gave the readily purified 2-hydroxy-3-nitro-5,6-diphenylpyrazine (71) (1065) [which reacts readily with hydrazine to give 2-hydrazino-3-hydroxy-5,6-diphenylpyrazine (1124)]. 3-Hydroxy-2,5-diphenylpyrazine undergoes random nitration under a variety of strongly acidic conditions (1065) but brief boiling of an acetic acid solution of equivalent amounts of 34iydroxy-2,5-diphenylpyrazine and nitric acid produced 2-hydroxy-5-nitro-3,6-diphenylpyrazine (75%) (817). 

Hydroxy-3-nitro-5,6-diphenylpyrazine was converted with 72% sulfuric acid at 82° to benzil (24%), 23-dihydroxy-5,6-diphenylpyrazine (41%), and an unidentified solid (20%) (1065). The formation of benzil under these conditions was proof that neither of the phenyl groups in the starting material was nitrated (1065). 2-Hydroxy-3-nitro-5,6-diphenylpyrazine refluxed with acetic-6Af hydrochloric acid (1 1) for 1 hours also gave 2,3-dihydroxy-5,6-diphenylpyrazine (94%) (817). 

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