Halogeno-1,8-naphthyridines preparation

Some halogeno-1,5-naphthyridines have been made by primary syntheses (see Chapter 1), but several other preparative routes have been more widely used, as indicated in the following subsections. 

Although alkoxy ion is a more powerful nucleophile than aryloxy ion, both types react vigorously with activated halogeno-l,5-naphthyridines and even (albeit sluggishly) with 3(7)-halogeno-l,5-naphthyridines. In the absence of kinetic data, the following preparative examples illustrate the practicalities of such displacement reactions. 

Most such naphthyridinones have been made by primary synthesis (see Chapter 1) and some by hydrolysis of halogeno-1,5-naphthyridines (see Section 3.2.3). Other preparative routes are illustrated by the following examples. 

Halogeno-l,6-naphthyridines have also been made by the Meissenheimer reaction from 1,6-naphthyridine N-oxides and by a (copperless) Sandmeyer-type reaction from 1,6-naphthyridinamines. However, neither route has been developed into a practical preparative procedure, as indicated in the following examples. 

Note Reported preparative routes have been covered already primary synthesis (Chapter 22), by thiolysis of halogeno-1,8-naphthyridines (at the end of Section 24.2), or by thiation of 1,8-naphthyridinones (Section 25.1.2). 

The literature contains some basic information on the preparation and reactions of halogeno-2,7-naphthyridines. In this system, halogeno substituents are active at the 1-, 3-, 6-, and 8-positions but inactive at the 4- and 5-positions. The effect of fluoro substituents on the ultraviolet spectra of 2,7-naphthyridines has been investigated.1313 Reviews have appeared.1266,1363... 

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