1.7- Naphthyridinones tautomerism

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. 

The term oxy-1,5-naphthyridine includes the tautomeric and nontautomeric 1,5-naphthyridinones, extranuclear hydroxy-l,5-naphthyridines, alkoxy-and aryloxy-... 

Note The alkylation of tautomeric 1,5-naphthyridinones usually gives /V-alkyl derivatives, but (9-alkylation has been achieved by treatment of the substrate silver salt with an alkyl halide the other likely route to (9-alkylation, treatment with an diazoalkane, has not been used in this series. 

Note Most of these naphthyridinones have been made by either primary synthesis (see Chapter 1) or alkylation of tautomeric 1,5-naphthyridinones (see Section 4.1.2). A third route, involving direct oxylation, is illustrated here. 

Note The rearrangement of such a fixed naphthyridinone to a tautomeric C-alkylnaphthyridinone has been described in Section 2.2.1. The halogenolysis of a fixed naphthyridinone with concomitant /V-dealkylation has been exemplified in Section 3.1.4. 

TAUTOMERIC/NONTAUTOMERIC 1,6-NAPHTHYRIDINONES AND EXTRANUCLEAR HYDROXY-1,6-NAPHTHYRIDINES... 

Many tautomeric and nontautomeric naphthyridinones have been made by primary synthesis (see Chapter 8) and a few by ozonolysis of alkylidene-l,6-naphthyridines (see Section 9.2.2) or by hydrolysis of halogeno-l,6-naphthyridines (see Section 10.4.2). Other preparative routes are illustrated by the following examples. 

Note Alkylation or arylation of any tautomeric 1,6-naphthyridinone probably affords a mixture of O- and /V-derivatives, but the latter usually predominates. 

Most known tautomeric and nontautomeric 1,7-naphthyridinones have been made by primary synthesis (see Chapter 15). Of the many potential indirect preparative routes, only two appear to have been used, as indicated in the following examples. 

The most important reaction of tautomeric 1,7-naphthyridinones, halogenolysis, has been covered in Section 17.1. Only a few of the other possible reactions have been reported, as illustrated by the following examples. 

Note This reaction amounts to the conversion of a nontautomeric to a tautomeric 1,7-naphthyridinone. 

Naphthyridinones are usually tautomeric with corresponding naphthyridi-nols, but they may be fixed (become nontautomeric) by /V-alkylation. As in related series, 1,8-naphthyridinones prefer to exist as oxo rather than hydroxy... 

The halogenolysis of tautomeric 2,7-naphthyridinones has been covered in Section 30.3.1. 

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