Extranuclear C-Alkylation and Acylation

The reactions of pyrazinylmethylsodium (8), prepared from methylpyrazine (7) and sodium amide in liquid ammonia, with a series of aliphatic, aromatic, and heterocyclic esters have been shown to give in most cases 2-(acylmethyl)pyrazines 

Tetramethylpyrazine, in the presence of sodium amide and phenyllithium, has been alkylated with several alkyl halides to give mixtures of alkyltrimethylpyrazines and perhaps 2,5-dialkyl-3,6-dimethylpyrazines (648). 

Reactions of the isomeric dimethylpyrazines and trimethylpyrazines with methyllithium have been studied in detail (635). Metalation of the side chain of 

5-dimethylpyrazine was observed, as well as ring methylation. In ether solvent vicinally dimethylated pyrazines gave products exclusively from side chain metal-ation (635). The chain alkylation of methylpyrazine has been patented (649), and methylpyrazine has been acylated with benzoate (and phthalate) esters using sodium hydride as the condensing agent to afford phenacylpyrazine (650). 

6-Dimethoxyphenyllithium has been found to be more effective than phenyl-lithium (642) in the preparation of phenacylpyrazine from methylpyrazine and methyl benzoate (651). 

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