Extranuclear Alkylidenation

C-Alkylpyrazines undergo extranuclear alkylidenation by aldehydes (or ketones,) with or without isolation of the intermediate (hydroxyalkyl)pyrazines. Several procedures are illustrated in the following examples  

2-Isopropylpyrazine (295) likewise gave 2-((3-hydroxy-a, a-dimethylphenethyl)-pyrazine (296) (IY2NI.i, PhCHO, and so on 21%,801 clearly precluded from dehydration to a styrylpyrazine.801 

Also other examples.755,784,801 Note The first stage is sometimes reversable on thermolysis. 

2-Methylpyrazine 1,4-dioxide (297) gave 2-[2-(pyridin-2-yl)vinyl]pyrazine 1,4-dioxide (298) [2-pyridinecarbaldehyde, NaOH, MeOH—H20, N2, 80°C, 5 min 96%] isomers and analogues likewise.81 

2-Methylpyrazine (300) gave 2-[2-(l-methylpyrrol-2-yl)vinyl]pyrazine (299) [NaH, Me2NCHO, 60°C, N2, 1 h then l-methyl-2-pyrrolecarbaldehyde J, 50°C, 5 h 40% compare conditions with those required for alkylidenation of the more activated methyl group in substrate (297)].1485 

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Many such hydroxyquinoxalines have been made by primary synthesis (see Chapter 1) and some by hydrolysis of extranuclear halogenoquinoxalines (see Section 3.4.2) in addition, during extranuclear alkylidenation of methylquinox-alines (see Section 2.2.1.4) the intermediate secondary alcohols may sometimes be isolated, especially with heavily substituted aldehydes, when dehydration can be difficult or even impossible. ° ... 

Note Hydrolysis removes the alkylidene group as an aldehyde or ketone to afford a nuclear or extranuclear primary aminopyrazine reduction could afford a secondary aminopyrazine of either type, but there appear to be no recent examples. 

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