Replacement of Halogeno Substituents by Other Groups

Deuterolysis of 3-chloro-2-chloromethyl-5-methoxypyrazine over 5% palladium on alumina in the presence of sodium isopropoxide in 2-propanol afforded 3-deutero-2-monodeuteromethyl-5-methoxypyrazine (687) and methylation of the bromomagnesium derivative from 2-bromomethyl-3,5,6-trimethylpyrazine with methyl sulfate or methyl iodide gave 2-ethyl-3,5,6-trimethylpyrazine (330). 

2-Amino-5-bromomethyl-3-cyanopyrazine with the sodium salt of diethyl malonate in tetrahydrofuran at room temperature gave 2-amino-3-cyano-5-(2, 2 -diethoxycarbonylethyl)pyrazine together with a little dialkylated product (1031). Similar reactions were observed with the sodium salts of ethyl acetoacetate and ethyl 7-ethoxyacetoacetate, but methyl cyanoacetate gave only dialkylated product (1031). 2-Amino-5-chloromethyl-3-cyanopyrazine and 1-pyrroIidino-l-cyclohexene in tetrahydrofuran have been shown to give 2-amino-3-cyano-5-(2 -oxocyclohexyl-methyOpyrazine (542). 

2-Amino-5-chloromethyl-3-cyanopyrazine on treatment with potassium acetate in propan-2-ol at 80-90° gave 5-acetoxymethyl-2-amino-3-cyanopyrazine(542),and 2-amino-6-chIoro-5-chloromethyl-3-cyanopyrazine with anhydrous sodium acetate in dimethylformamide gave 2-acetoxymethyl-5-amino-3-chloro-6-cyanopyrazine (874). 

2-Chloromethylpyrazine with sodium azide in refluxing aqueous acetonitrile gave 2-azidomethylpyrazine (690), and 2-amino-5-bromomethyl-3-cyanopyrazine with sodium cyanide in dimethyl sulfoxide at 40° gave 2-amino-3-cyano-5-cyano-methylpy razine (1031). 

Irradiation of the liquid phase of perfluoro-2,5-diisopropylpyrazine (87) caused slow rearrangement to the 2,6-isomer (88) plus some perfluoro-4,5-diisopropyl-pyrimidine (89), and prolonged irradiation of (88) gave a small amount of (87) (494). 

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