Phenyllithium with 2,5-dimethylpyrazine

Tetramethylpyrazine can be converted into its monoanion by the use of sodamide in liquid ammonia or phenyllithium in ether.192 Thus, when phenyllithium, tetramethylpyrazine, and methyl benzoate are reacted in 2 2 1 molar proportion, a 67% yield of the monoacylated product, phenacyltrimethylpyrazine, is formed. A lower yield of monoacylated product is obtained when sodamide and liquid ammonia is used as the condensing agent, but reaction of sodamide, tetramethylpyrazine, and methyl benzoate in 6 1 1 molar proportion gives the optimum yield of diacylated derivative, formulated as 2,6-diphenacyl-3,5-dimethylpyrazine (39), by UV spectral comparison with 2,6-dimethylpyrazine and by the formation of a dioxime. 

The reaction of tetramethylpyrazine with alkyl halides using either sodamide in liquid ammonia or phenyllithium in ether as condensing agent gives mixtures of alkyltrimethylpyrazines and 2,5-dialkyl-3,6-dimethylpyrazines. A number of carbinols were also prepared from... 

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. 

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). 

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