Halogeno-1,8-naphthyridines aminolysis

The ease of aminolysis of halogeno-l,5-naphthyridines is governed by several factors already outlined for nucleophilic displacement in general (Section 3.2) and alcoholysis (Section 3.2.1). The examples that follow are divided according to the number and position(s) of the halogeno substituent(s). 

Many amino-1,5-naphthyridines have been made by primary synthesis (see Chapter 1), by aminolysis of halogeno-1,5-naphthyridines (see Section 3.2.2), or by aminolysis of 1,5-naphthyridinones (see Section 4.1.2). Others have been made by direct amination, as illustrated in the following examples. 

The aminolysis of halogeno-l,7-naphthyridines is fairly well represented in the literature, but other potential reactions have seldom been used. Reported reactions are illustrated in the following examples. 

Note Potassium amide in liquid ammonia can be used for aminolysis of halogeno-1,7-naphthyridines, but it also induces fe/e-aminolysis.54 For example, 2-chloro-l,7-naphthyridine gave a separable mixture of 1,7-naphthyridin-2-amine and both the 4- and 8-isomers (KNH2, NH3, Et20, —33°C, 4 h 70% yield of the mixture) from which each product was isolated in low yield 834 also analogous examples.332 808 834... 

Halogeno substituents at the 2-, 4-, 5-, and 7-positions of 1,8-naphthyridine will be activated toward aminolysis and similar reactions those at the 3- and 6-positions will be only mildly so activated and extranuclear halogeno substituents will resemble at best that in benzyl chloride. 

Note The conversion of 1,8-naphthyridinones into amino-1,8-naphthyridines is usually done via a halogeno intermediate, but direct aminolysis is possible sometimes. 

Several methods of preparation have been covered already by primary synthesis (Chapter 22) and by aminolysis of halogeno-1,8-naphthyridines (Section 34.2),... 

Of the many possible reactions of halogeno-2,7-naphthyridines, only alcoholysis, aminolysis, and dehalogenation have been reported.01 60... 

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