2 -Quinoxalinone, chlorination

Amino-5(l/i)-quinoxalinone (123) gave 6,7-dichloro-5,8-quinoxalinequinone (124) (substrate sulfate, HCl, NaClOs, 0°C, 3 h >63% note additional chlorination). 

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... 

Treatment of the dihydroimidazo[l,2-a]quinoxaline 19 with sodium hydroxide solution results in opening of the five-membered ring and formation of the quinoxalinone 20. The 4-chloro derivative 21 is susceptible to nucleophilic attack, and displacement of the chlorine has been achieved with sodium methoxide, sodium alkoxides in benzene, and hydrazine. The 4-hydrazino derivative was not isolated but was treated with copper sulfate and sodium hydroxide to give the 4-unsubstituted compound. ... 

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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