Hydrolysis of Nuclear Halogenopyrazines

The hydrolysis of halogenopyrazines to pyrazinones has never been used much, perhaps because most halogenopyrazines are themselves made from pyrazinones. Such hydrolysis can be done under acidic or basic conditions but sometimes it seems to be more rewarding to proceed in two stages via an alkoxy intermediate. The following examples illustrate all three hydrolytic procedures  

2-Chloro-3-isobutyl-6-isopropylpyrazine 1-oxide (109) gave l-hydroxy-3-isobutyl-6-isopropyl-2(l//)-pyrazinone (110) (KOH, H20—MeOH, reflux, 2 h 84%) 92 homologues likewise.1250 

2-Chloro-3-isobutylpyrazine 4-oxide gave 3-isobutyl-2( I // )-pyrazinone 4-oxide (111, R = Hu ) (5 M NaOH, reflux, 2 h 39%) 86 2-chloro-3-phenylpyrazine 4-oxide gave 3-phenyl-2( I //(-pyrazinone 4-oxide (111, R = Ph) (KOH, H20—EtOH, reflux, 1 h 30%) 1290 also analogues likewise.1290 

3-Chloro-2-pyrazinecarboxylic acid gave 3-oxo-3,4-dihydro-2-pyrazinecar-boxylic acid (0.5 M NaOH, reflux, 1 h 95%).1271 

5-Dichloro-3,6-diethylpyrazine 1,4-dioxide (112) gave 3,6-diethyl-l,4-dihy-droxy-3,6-dihydro-2,5(l//, 4//)-pyr tzinedionc (114), presumably via the dimethoxy intermediate (113) (MeONa, dioxane, 110°C (reflux ), 4 h then 10 M HC1J, 52%).1283 

2-Chloro-3-isobutylpyrazine 4-oxide gave 3-isobutyl-2(l//)-pyrazinone 4-oxide (111, R = Bu ) (5 M NaOH, reflux, 2 h 39%) 2-chloro-3-phenylpyrazine 

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