Pyrazines, 2,5-dialkyl-, reactions

No systematic study of the mass spectra of pyridopyrazines has been noted, but those of 2,3-dialkyl and 2,3-diaryl derivatives have been recorded 750MS97), and mass spectrometry has been used in the elucidation of problems in the reactions of pyrido[2,3-f ]pyrazines with amide ion (including use of and derivatives) (79JHC305), and of pyrido[2,3-f ]pyrazinium salts with indoles (78ZOR431). The mass spectra of some 1-deazaflavins have been recorded (74JCS(P1)1965). 

Cyclocondensation of pipecolinic acid and malic acid anhydride in pyridine afforded 3-hydroxy-2,3-dimethylperhydropyrido[l,2-a]pyrazine-l, 4-dione (74CB2804). Cyclocondensation of bis(2,4,6-trichlorophenyl) mal-onates with 2-methyl-, 2-benzyl- and 2-ethoxycarbonylmethylquinoxalines and -3-ones at 250°C afforded 8-hydroxy-10//-pyrido[l,2-a]quinoxalin-10-ones and their 5,6-dihydro-6,10-dione derivatives (77M103). Under Horner-Wittig reaction conditions, the reactions of 2-formylquinoxaline and dialkyl phosphonosuccinates (314) also involved cyclization to give alkyl 10-oxo-10//-pyrido[l,2-a]quinoxahne-8-carboxylate (80LA542). 

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. 

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). 

Comparative A -oxide activation was likewise observed when other amines such as hexylamine, aniline, benzylamine, piperidine, and dimethylamine were used. It was also noted, in every example studied, that amination of the chloropyrazine A -oxide or alkylchloropyrazine 7V-oxide at elevated temperatures in a sealed vessel gave mixtures containing greater or lesser amounts of deoxygenated halogeno-pyrazine or aminopyrazine (921). Similar enhanced activation by theTV-oxide group was observed when 3-chloro-2,5-dimethylpyrazine and its 1-oxide in reaction with various amines were compared, although dialkyl substitution further retarded overall aminolysis (793,921). 

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