Quinoxalinones halogenation

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... 

Halogenation of 2-quinoxalinone (60) in acetic acid gives the 7-sub-stituted product almost quantitatively bromine at 20° thus yields 95% of 7-bromo-2-quinoxalinone (61).72... 

Chloro-2(lH)-quinoxalinone 6 the precursor of 2,6-dichloroquinoxaline was our first target. Several methods have been carefully evaluated to prepare this key intermediate which represents the most expensive part of our molecule. The simplest method would certainly be the regioselective chlorination of 2(lH)-quinoxalinone (5). However, the halogenation in acetic acid is known to occur mainly at position 7, (2). Only recently, a direct chlorination of 6 in concentrated sulphuric acid in the presence of silver sulphate has been reported to afford exclusively 6-chloro-2(lH)-quinoxalinone in 51% (3). 

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