3.5 -Dichloro-1 -phenyl-2 -pyrazinone

Heating with phosphoryl chloride converted 1 -hydroxy-3-phenyl-2( 1H )-pyrazinone (52) into the 2,5-dichloro derivative (53) via the 5-monochIoro species. It had been expected that chlorination would take place at C-6, but this occurred only to a minor extent. The observed chloride attack /3 to the oxygen function might be accounted for in terms of the sequence illustrated in Scheme 46 (86JHC149). Reaction mechanisms have been proposed to explain the observed a- and /3-chlorination when 2- and 3-substituted pyrazine Af-oxides are subjected to the Meisenheimer reaction. /3-Chlorination was rationalized in terms of electron withdrawal by the unoxidized nitrogen atom [84JCR(S)318] (Scheme 46). 

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... 

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... 

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,... 

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%]. ... 

The behavior of halogeno substituents on 1-substituted 2(lT/)-pyrazinones is similar to that in the fully aromatic systems. Thus, 1-methyl- and 1-phenyl-3,5-dichloro-2(17/)-pyrazinones undergo nucleophilic substitution at C-3 with hydrazine and thiourea, whereas in a 5-chloro compound displacement is suppressed <86JHC113>. 

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