Alkylation at nuclear carbon

The alkylation of pyrazine at a nuclear carbon atom has been discussed in detail in Section 1C (612-615, 617, 634). For example, 2-butylpyrazine was prepared from pyrazine and butyllithium in ether at —20 (612), 2-s-butylpyrazine was prepared from pyrazine, ethyl methyl ketone, and alkali or alkaline earth metals in liquid ammonia (614) the effect of temperature on the products, specificity, and yields from the alkylation of pyrazine by ethyllithium (and other alkyllithiums) in ether or hexane solutions between — 25° and 34° has been examined (615). 

Nuclear C-alkylation of alkyl pyrazines has been extensively studied methyl-pyrazines react with organolithium reagents to form products resulting from ring alkylation (or arylation) and side chain metalation (635). 

Ring aUylation and propenylation of methylpyrazine has been described (634) acetonylpyrazine with phenyllithium gives 2-acetonyl-6-phenylpyrazine (639) and 2,5-dimethylpyrazine with isopentylUthium gave 3-isopentyl-2,S-dimethylpyrazine (70). Aldehydes and ketones in the presence of a solution of an alkali or alkaline earth metal in liquid ammonia, or a suspension of these metals in other solvents, can be used to alkylate the pyrazine ring in moderate to good yields (614, 640, 641). This alkylation has been successfully applied to alkyl- and dialkyl(amino- and methoxy)pyrazines, and a mechanism has been proposed for the reaction (614). For example, the reaction of potassium with methylpyrazine and ethyl methyl ketone, catalyzed by sodamide (0.25 mol) gave 88% of 2 -butyl-6-methylpyrazine. 

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