Pyridones phosphorus halides

The carbonyl tautomers deprotonate at N-H, generating ambident anions that can react at either oxygen or nitrogen, depending on the exact conditions for example 0-alkylation can be achieved with silver carbonate. They are converted, as with the pyridones, into halo-quinolines and halo-isoquinolines by reaction with phosphorus halides. 

Diazinones, like pyridones, react with phosphorus halides with overall conversion into halides. Anions produced by A-deprotonation of diazinones are ambident, with phenolate-like resonance contributors, but they generally react with electrophilic alkylating agents at nitrogen, rather than oxygen, giving A-alkyl diazinones. 

Several pyridine-containing drugs are prepared by taking advantage of the easy displacement of halogen at the alpha- and gamma-positions by nucleophiles or metals. The halo compounds are generated from pyridones or pyridine N-oxides with phosphorus halides as presented in Chapter 6. An example is the antihypertensive ofomine, 9.91, which is summarized in Scheme 9.47. 

The most important modification of the reaction between phosphorus halides and 2- or 4-hydroxypyridines is that in which 1-alkyl- or l-aryl-2-or -4-pyridones are used. The reaction is especially valuable in its application to l-alkyl-2-pyridones because of the ready availability of these compounds. Introduced by Fischer 42 it has often been applied ... 

Halopyrido[2,3-(/]pyrimidines suitable for nucleophilic exchange reactions are accessible by the conversion of the corresponding pyridone or pyrimidone functions with halogenating agents such as phosphoryl halides or phosphorus pentachloride (see Section 7.2.2.1.1.5.5.). 

Where pyridones differ from phenols is in their interaction with phosphorus and sulfur halides, where transformation of the oxygen substituent into halide occurs. Here, the pyridones react in an amide-like fashion, the inorganic reagent reacting first at the amide-like oxygen. 

---