Preparation of Pyrazine V-Oxides

Some pyrazine /V-oxidcs have been made by primary synthesis (see Chapters 1 and 2). Other preparative routes are discussed in the following subsections. 

This minor route to pyrazine N-oxides involves either reductive or hydrolytic debenzylation of l-benzyloxy-2(l//)-pyrazinones, often available by primary synthesis. 

For example, I -bcnzyloxy-2(l //)-pyrazinone (217, R = H) afforded 70% of 1-hydroxy-2( I //)-pyrazinone (218, R = H) [sometimes written as its tautomer, 2-pyrazinol 1-oxide (218a, R = H) on catalytic hydrogenation over palladium-on-charcoal in methanol for 20 min.588 The homologous l-benzyloxy-5,6-dimethyl-2( I //(-pyrazinone (217, R = Me) gave l-hydroxy-5,6-dimethyl-2(l//)-pyrazinone (218, R = Me), either by a similar hydrogenation (76%) or by hydrolysis in acetic acid-hydrogen bromide under reflux for 10 min (81%, as hydrobromide).588 1085 

This reaction is the most used route to pyrazine /V-oxidcs. The choice of oxidant is not always clear208 but the following classified examples may afford some help. In each case, the substrate was the corresponding A/-deoxypyrazine, unless stated otherwise. 

2-Chloro-5,6-diethylpyrazine 1-oxide (219) (K2S2Os, H2S04, 20°C, 24 h 84%) 1250 2-chloro-3-isobutyl-6-methylpyrazine 1-oxide (220) (likewise 78%) 295 and 2-fluoropyrazine 1-oxide (likewise 40%).276 

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