Reactions of Nuclear Halogenopyrazines

A three-dimensional X-ray structure determination of 2,5-dichloro-3-methoxy-pyrazine (915) and 2,3-dichloro-5-ethyIamino-6-methoxypyrazine (916) has been completed. 

2-Chloro-6-(piperazin-l -yl)py2zine inhibits the uptake of H-labeled serotonin in cerebral cortical tissue of rats (917) and dipole moments measured. 

spectra have been used to determine the position of theAf-oxide group in alkylchloropyrazine A-oxides (733b). 

2-Chloropyrazine 1-oxide (66) gave 2-fluoropyrazine 1-oxide (67) (KF, Me2SO, reflux, 2 days 32%).276 Also other examples.1307 

Most halogenopyrazines undergo facile nucleophilic displacement of their halogeno substituent (s),1286 thus making them ideal substrates for the preparation of other pyrazines. 

The conversion of halogeno- into alkyl- or arylpyrazines has been discussed in Section 3.2.1.2. The other important reactions of halogenopyrazines are summarized in the following subsections. 

This convenient indirect process involves conversion of a pyrazinone into the conesponding trimethylsiloxypyrazine, and thence (with phosphorus halide) into the required halogenopyrazine. For example, 5-phenyl-2(lH)-pyrazinone afforded crude 2-phenyl-5-trimethylsiloxypyrazme (neat McsSiNHSiMe , ClSiMc, reflux, 30 min) that reacted with an appropriate phosphorus halide to furnish 2-bromo-(neat PBrj, 150 (1 1 h 77% overall), 2-chloro- (neat PCI5, 2(X) C. 1 h 40%), or 2-iodo-5-phenylpyrazine (PI3, CI2CHCH2CI, reflux, 24 h 12%) homologues were made similarly.  

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