2-Chloropyrazine with alkoxide

Although there have been few new developments in the period since 1993, halogenopyrazines 42 have been convenient precursors for a variety of pyrazine derivatives. For example, the halogenopyrazines 42 are cyanated by palladium-catalyzed cross-coupling with alkali cyanide or by treatment with copper cyanide in refluxing picoline, to yield cyanopyrazines 48. Alkoxypyrazines 49 are produced by treatment with alkoxide-alcohol, and aminopyrazines 50 are prepared by amination with ammonia or appropriate amines. The nucleophilic substitution of chloropyrazine with sodium alkoxide, phenoxide, alkyl- or arylthiolate is efficiently effected under focused microwave irradiation <2002T887>. 

Replacement reactions of chloropyrazines with a large number of alkoxides have been observed. Some examples are 2-chloropyrazine with methoxide (974), perdeuteromethoxide (975), ethoxide and isopropoxide ions (668a), and as follows. Methoxide ion 2-chloro-3-methyl (49, 686, 687, 735, 736, 976) 2-chloro-5-deutero-3-methyl (687) 2-chloro-5-methyl (686, 735, 736) 2-chloro-6-methyl (686, 735, 736) 2-chloro-3,5-dimethyl (687, 844) 3-chloro-2,5-dimethyl (844, 977-979) 2-chloro-3-s-butyl (80, 649, 693) 2-chloro-3-isobutyl (80, 693) ... 

Nucleophilic substitution of the chlorine atom in 2-chloropyrazine and 2-chloroquinoxa-lines has been effected with a variety of nucleophiles, including ammonia and amines, oxygen nucleophiles such as alkoxides, sodium azide, hydrazine, sulfur containing nucleophiles, cyanide, etc., and reactions of this type are typical of the group (see Chapter 2.02). 

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