5- Chloro-3-phenyl-2 -pyrazinone

Mcthyl-5-phenyl-2(l//)-pyrazinone (4) gave 2-chloro-3-methyl-5-phenylpyra-zine (5) (P0C13,175°C, sealed, 18 h 92% beware of pressure within the tube even when cooled ) 57 such a sealed reaction also converted 5-chloro-3-phcnyl-2( l//)-pyrazinone into 2,5-dichloro-3-phenylpyrazine (6) (185°C, 5 h 92%).1382... 

Methylthioethyl)-5-phenyl-2(l//)-pyrazinone (20) gave 2-chloro-3-(2-methylthioethyl)-5-phenylpyrazine (21) (COCl2, PhMe—THF, reflux, 4 h >95%) 315 2-chloro-3-isobutyl-5-phenylpyrazine (>80%) similarly.632... 

Benzyl-3,5-dichloro-6-phenyl-2(l//)-pyrazinone (91, R = Cl) gave 1-benzyl-5-chloro-3-(o-iodoanilino)-6-phcnyl-2(l//)-pyrazinonc (91, R = NHC6H4I-o) (H2NC6H4I-o, NaH, THF, N2, 20°C, 30 min substrate J, reflux, <5 h 78%) 1607 analogues likewise.1607 Also other examples.481,1063... 

Chloro-3-isobutylpyrazine 4-oxide gave 3-isobutyl-2( I // )-pyrazinone 4-oxide (111, R = Hu ) (5 M NaOH, reflux, 2 h 39%) 86 2-chloro-3-phenylpyrazine 4-oxide gave 3-phenyl-2( I //(-pyrazinone 4-oxide (111, R = Ph) (KOH, H20—EtOH, reflux, 1 h 30%) 1290 also analogues likewise.1290... 

L-Benzyl-6-(l-bromo-2-methylpropyl)-5-chloro-3-phcnyl-2(l//)-pyrazinonc (256, R = Br) gave 6-(l-azido-2-methylpropyl)-l-benzyl-5-chloro-3-phenyl-2(l//)-pyrazinone (256, R = N3) (NaN3, Mc2NCIIO, 60°C, 5 h 62%).53... 

Dichloro- l-phenyl-2(l//)-pyrazinone (207) and dimethyl acetylenedicarboxy-late gave an unisolated adduct (208) that immediately underwent competitive retro-Diels-Alder reactions to afford dimethyl 2,6-dichloro-3,4-pyridinedicar-boxylate (209) and dimethyl 5-chloro-6-oxo-l-phenyl-l,6-dihydro-2,... 

Acetoxy methyl- 5-phenyl- 2(1 77)-pyrazinone 5-Acetoxy methyl- 3-phenyl- 2(1 77)-pyrazinone 2-(l-Acetoxy-2-methylpropyl)-3-chloro-5-isobutylpyrazine... 

Bromo-5-chloro-6-phenyl-2(177)-pyrazinone 3-Bromo-5-chloro-2-pyrazinamine 5-Bromo-3-chloro-2-pyrazinamine 5-Bromo-3-chloro-2(177)-pyrazinone... 

Bromomethyl-5-chloro-3-methoxyv-l-phenyl-2(117)-pyrazinone 6-Bromomethyl-5-chloro-1 -phenyl-2(lH)-pyrazinone... 

But-3-ynyl)oxy-5-chloro-l-phenyl-2(l//)-pyrazinone 2- (But-3-ynyl)oxypyrazine... 

Chloro-3-methoxy-6-methoxymethyl-1 -phenyl-2n //)-pyrazinone 5-Chloro-6-methoxy methyl-1,3-diphenyl-20 //)-pyrazinone 2-Chloro-6-methoxy-3-methyl-5-phenylpyrazine 2-Chloro-6-methoxy-5-methyl-3-phenylpyrazine 5-Chloro-3-methoxy-6-methyl-l-phenyl-2( 1 //t-pvTa/ini iie... 

Chloro-5-methoxy-6-phenylpyrazine 5-Chloro-3-methoxy-l-phenyl-2(17/)-pyrazinone... 

Chloro-5-phenyl-2(l 7/)-pyrazinone 2-Chloro-6-phenylthiopyrazine 5-Chloro-l-phenyl-3-thioxo-3,4-... 

Note The paucity of examples in this category is surprising. l-Benzyl-3,5-dichloro-2(l//)-pyrazinone (131) gave 1-benzyl-5-chloro-3-phenyl-2( 1//)-pyrazinone (132) [PhMgBr/Et2O (made in situ), THF, -30°C, 10 min 90%]. ... 

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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