Hydrogenolysis of Nuclear Halogenopyrazines

The displacement of nuclear halogeno substituents in favor of hydrogen is usually done by catalytic hydrogenation in the presence of a base under a variety of conditions. However, it can be done in other ways, notably by treatment witli sodium formate in the presence of tetrakis(triphenylphosphino)palladium (the Helquist method for hydrogenolysis of halogenoarenes). The following examples typify tlie various procedures used recently in the pyrazine series. 

3-Bromo-5-methyl-2-pyrazinaniine (174) gave 5-rnelhyl-2-pyraziriaininc (175) (H2, Pd/C, EtsN, MeCN, 20°C, 20 min or in AcOEt or in MeOH/KOH yields all 

Methyl 3 -bromo-6-chloro-5-(4-methylpiperazin-1 -yl)-2-pyrazinecartx)xylate (177) gave methyl 6-chloro-5-(4-methylpiperazin-l-yl)-2-pyrazinecarboxy-late (178) (H, Pd/C, THF, 20°C, 7. days IWo, note selective debromination and intramolecular supply of the base)  

Both 2-chloro-3,6-diisobutylpyrazine 1-oxide (181) and the isomeric 4-oxide (183) gave 2,5-diisobutylpyrazine 1-oxide (182) [Pd(PPh j4, HC02Na, Me2NCH0, 100°C, A, 2 h 90 and 87%, respectively note survival of the oxide entity) also analogous dechlorinations However, if HCO2Na was replaced by MeCO Na, hydrogen appeared to be necessary for dehalo- 

2-Chloropyrazine gave piperazine (Ca, excess of MeOH, reflux, briefly then 20°C, 12 h % note additional ring reduction).  

2-Chloro-3,6-diisobutylpyrazine (179) gave 2,5-diisobutylpyrazine (180) [Pd(PPh3)4, HC02Na, Me2NCHO, 100°C, A, 2 h 89% note lack of H2] analogues likewise.245 

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