Pyrazine 1-oxide, deoxidative

Deoxidative chlorination of alkyl- or aryl-substituted pyrazine A -oxides with refluxing phosphoryl chloride for 1 h provides 76-78% yields of the chloropyrazines <1997MI1076>. 

Nuclear Halogenopyrazines by Deoxidative Halogenadon of Pyrazine iV-Oxides (H105)... 

All the major routes to pyrazinecarbonitriles have been discussed already by primary synthesis in Chapters 1 and 2 by cyanolysis of halogenopyrazines in Sections 4.2.8 and 4.4 by deoxidative cyanation of pyrazine N-oxides in Section 5.5.2.4 by the rare cyanolysis of nitropyrazines in Section 7.1.2 by cyanolysis of trimethylammoniopyrazine salts no recent examples by dehydration of pyrazinecarboxamides in Section 8.4.2 and by passenger introduction of a cyano group in a variety of ways, for example, by cyanoalkylation. 

The title compounds are stable tautomers of the corresponding 2-hydroxypyrazine 1-oxides, and in fact l-acetoxy-2(lH)-pyrazinones, not 2-acetoxypyrazine A -oxides, are obtained on treatment with acetyl chloride in the presence of pyridine at room temperature <87JHC187>. Nevertheless, these compounds resemble the N-oxides in most of their reactions. Representative examples are deoxidative acetoxylation and chlorination. Treatment of l-hydroxy-3,5-diphenyl-2(l//)-pyr-azinone (100) with a refluxing mixture of acetic anhydride and acetic acid affords 2,6-diacetoxy-3,5-diphenylpyrazine (101), which is deacetylated with potassium hydrogen carbonate to give 2,6-dihydroxy-3,5-diphenylpyrazine (102) (or tautomer) (Scheme 23) <7UCS(C)2977>, Acetoxylation of a methyl substituent occurs exclusively and then that of the pyrazine ring is suppressed completely. 

Direct chlorination of pyrazine in 52% yield is easily effected by treatment of pyrazine with 1.2 equivalents of chlorine in DMF at 65-68 °C <94JAP(K)73026>. 2,3-Dichloropyrazine is synthesized in a similar manner using 2.5 equiv. of chlorine in 74% best yield. Deoxidative chlorination of the N-oxides is a good preparative method for chloropyrazines and chloroquinoxalines . This reaction with monosubstituted pyrazine A -oxides occasionally leads to the less regioselective formation of chloropyrazines (see Section 6.03.5.4.3) but the regioselectivities are considerably improved, and furthermore each isomer can be effectively separated by HPLC. Electrophilic bro-mination of aminopyrazines (see Section 6.03.5.3) and 2(lFT)-pyrazinones (see Section 6.03.6.3) provides the ortho- or para-hromo derivatives. 

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