Preparation of Extranuclear Halogenopyrazines

A variety of reagents have been used to achieve this transformation, as illustrated in the following classified examples  

2-Benzyloxy-3-isobutyl-6-mesyloxymethyl- (217) gave 2-benzyloxy-6-iodomethyl-3-isobutyl-5-methoxypyrazine 4-oxide (218) (Bu4NI, PhH, 20°C, dark, 90 min  

2-Isopropyl-3,6-dimethoxy-5-(2-tosyloxyethyl)-2,5-dihydropyrazine (219, R = OTs) gave 2-(2-iodoethyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (219, R = I) (Nal, AcMe, reflux, 2 h 95%).1614 Also other examples.1259 

2-(a-Hydroxybenzyl)pyrazine (220) gave 2-(a-chlorobenzyl)pyrazine (221) (SOCl2, CHC13, 0°C, 3 h 82%).181 

2-Benzyloxy-6-hydroxymethyl- (225, R = OH) gave 2-benzyloxy-6-chloromethyl-3-isobutyl-5-methoxypyrazine (225, R = Cl) (MeS02Cl, Et2N, CH2C12, 0°C, 12 h 76%) 329 also an analogous examples using TsCl/BuLi.333 

2-( 1 -Hydroxy-2-rnclhylclhyl)- gave 2-( 1 -fluoro-2-methylethyl)-5-isopropyl-3,6-dirnethoxy-2,5-dihydropyrazine [lithiation then Et2NSF3, CH2CI2, 

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Many such hydroxypyrazines have been made by primary synthesis (see Chapters 1 and 2), some by C- or N-hydroxyalkylation procedures (see Sections 3.1.1.1 and 3.2.2.1), and a few by hydrolysis of extranuclear halogenopyrazines (see Section 4.4). Other preparative routes are illustrated in the following classified examples ... 

Some preparations of extranuclear aminopyrazines from extranuclear halogenopyrazines and amines have been described in Section V.6B (542, 679, 932,1029-1031). 2-Chloromethylpyrazine also reacted with sodium azide and gave 2-azidomethylpyrazine, which was hydrogenated in 95% ethanol over Adams catalyst to 2-aminomethylpyrazine (690). 

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