Nuclear Halogenopyrazines by Direct Halogenation

The direct nuclear chlorination, bromination, or iodination of pyrazines is usually done with elemental halogen or /V-halogeno succinimide but direct fluorination 

2-Pyrazinamine gave 5-chloro-2-pyrazinamine (27) [substrate, CHC13—pyridine, Cl2(1.2 mol)/CHCl3 [ slowly, 20°C, dark, 3 h 26% after purification].1280 

2-Chloromethyl-3-methoxy-5-methylpyrazine 1-oxide (28, R = H) gave 2-chloro-6-chloromethyl-5-methoxy-3-methylpyrazine 1-oxide (28, R = Cl) OV-chIorosuccinimide, Me2NCHO, 20°C, 12 h 90%).333 Also other examples.321,599,1460 

3-Amino-2-pyrazinecarbonitrile (29, R = H) gave regioselectively 3-amino-6-bromo-2-pyrazinecarbonitrile (29, R = Br) (substrate, AcOH, Br2/AcOH- slowly, 60°C, 4 h 85%).802 

5-Methyl-2-pyrazinamine 4-oxide (33, R = H) gave 3-bromo-5-methyl-2-pyraz-inamine 4-oxide (33, R = Br) (NBS, Me2SO—H20,15°C, 4 h 79%, initially as a complex).1508 

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