By Halogenolysis of 1,6-Naphthyridinones or the Like

The conversion of a tautomeric 1,5-naphthyridinone into the corresponding chloro- or bromo-l,5-naphthyridine is usually done by heating for several hours with neat phosphoryl chloride or phosphoryl bromide, respectively. A mixture of phosphoryl chloride and phosphorus pentachloride has been used for a few difficult cases. In addition, exceptional reactions have been reported in which a nontautomeric /V-alkyl-1,5-naphthyridinone or a hydroxymethyl-1,5-naphthyridine was used successfully as substrate. The following examples illustrate the foregoing possibilities. 

5-Naphthyridin-4(1 //)-one (5) gave 4-chloro-l,5-naphthyridine (6) (POCl3, 100°C 60%) 101 somewhat similarly, l,5-naphthyridin-2(l//)-one gave 2-chloro-l,5-naphthyridine (POCl3, reflux, 30 min 95%).87 

4-Hydroxy-1,5-naphthyridin-2( 1 //)-one (10) gave 2,4-dichloro-l,5-naphthyridine (11) (POCl3, reflux, 6h 70-80%) 1023 1151 l,5-naphthyridine-4,8 (1//.5//)-dione gave 4,8-dichloro-l,5-naphthyridine (12) (POCl3, 180°C, sealed, 6h 82%).301 

Ethyl 4-oxo-1,4-dihydro-l,5-naphthyridine-3-carboxylate (13, R = H) gave ethyl 4-chloro-l,5-naphthyridine-3-carboxylate (14, R = H) (POCl3 for details, see original) 433 ethyl 6-p-chlorophenoxy-4-oxo-l,4-dihydro-1, 5-naphthyridine-3-carboxylate (13, R = OC,H Cl-p) gave ethyl 4-chloro-6- 

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