Pyrazinones and Quinoxalinones

Alkylation of pyrazinones and quinoxalinones may be carried out under a variety of conditions and it is usually observed that while O-alkylation may occur under conditions of kinetic control, to yield the corresponding alkoxypyrazines or alkoxyquinoxalines, under thermodynamic control the A-alkylated products are formed. Alkylation using trialkyl-oxonium fluoroborate results in exclusive O-alkylation, and silylation under a variety of conditions (75MI21400) yields specifically the O-silylated products. Alkylation with methyl iodide or dimethyl sulfate invariably leads to A-methylation. 

Pyrazinones and quinoxalinones both play important roles in the chemistry of pyrazines and quinoxalines respectively, in that they are usually available by direct synthesis and serve as important starting points for halo derivatives, which in turn lead to a range of substitution products (e.g. see Section 2.14.3.3). 

Other synthetic routes to pyrazinones and quinoxalinones are from the halo compounds, by dealkylation of ethers (8lJCS(Pl)3111> or by diazotization of the corresponding amines, but since the halo derivatives are normally derived from the hydroxy compounds, and the amines from the halo derivatives, direct synthesis seems to represent the most practical approach. 

The most convenient synthesis of halogenopyrazines and -quinoxalines is by halogenation of pyrazinones and quinoxalinones with phosphoryl or other acid halides for example, 5-hydroxy-2-pyrazinecarboxylic acid, rather than 5(477)-pyrazinone-2-carboxylic acid, is chlorinated with phosphorus pentachloride/phosphoryl chloride to afford a 63% yield of 5-chloro-2-pyrazinecarbonyl chloride <1994SL814>. Sato and Narita provided an improved synthesis of various halogenopyrazines in which 2(l//)-pyrazinones were activated with chlorotrimethylsilane to give silyl ethers (Section 8.03.7.3). This procedure is most effective for synthesis of bromopyrazines whose overall yields are 62-81% <1999JHC783>. Bromopyrazine is directly prepared by treatment of 2-(l//)-pyrazinone with phosphoryl... 

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