General Procedures for C-Alkylation

The following classified examples illustrate the methods that have been used recently for C-alkylation of pyrazines and hydropyrazines (see also Section 3.1.3 for the alkylation of unsubstituted pyrazine). 

Note It is probably fortuitous that nearly all recent examples of such nuclear C-alkylation have employed substrates bearing electron-withdrawing substituents. 

3-Dimethylpyrazine (21, R = H) gave 2,3-dimethyl-5-phenethylpyrazine (21, R = CH2CH2Ph) [PhCH2CH2C02H, H2S04, AgN02, (NH4)2S208, H20, 95°C, no further details 45%].1462 

5-Methyl-2,3-pyrazinedicarbonitrile (26, R = H) gave 5-hydroxymethyl-6-methyl-2,3-pyrazinedicarbonitrile (26, R = CH2OH) [H0CH2C02H, AgN03, (NH4)2S208, MeCN—H20, 75°C — reflux, 5 h 74% note incorrect name in original experimental section].1599 

Note Such alkylations appear to proceed by initial addition of the reagent to afford an alkyl dihydro product that may or may not undergo subsequent oxidation to an alkylpyrazine. 

2-pyrazinecarbonitrile (23, R = H) likewise gave 5-tert-butyl-2-pyrazinecar-bonitrile (23, R = Bu ) (69%) and analogues were made similarly  

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