Naphthyridines covalent amination

The first paper on the addition of water to the C=N bond in naphthyridines (covalent hydration) appeared in 1963,9 but it was not until 1976 that the first report concerning covalent amination of naphthyridines using potassium amide in liquid ammonia was published.10... 

Extensive studies have shown that covalent amination is a more general phenomenon than covalent hydration systems that are not able to undergo covalent hydration may easily undergo covalent amination. The 1,X- and 2,X-naphthyridines illustrate this phenomenon clearly. Whereas all parent naphthyridines do not give covalent fT-adducts with water (in basic as well as in acidic mediums), addition of the amide ions easily takes place using potassium amide in liquid ammonia, and the corresponding fT-adducts easily formed. 

Studies have been made of the covalent amination of 3-nitro-l,X-naph-thyridines (X = 5,6, and 8).27 35 In contrast to the parent systems and their halogen and methyl derivatives, 3-nitronaphthyridines undergo covalent amination with weak nucleophilic liquid ammonia at — 45 C. The electrophilic character of the naphthyridine system is enhanced by the presence of the nitro group. 3-Nitro-l,8-naphthyridine (41a) undergoes addition at... 

Amino-2-bromo-1,5-naphthyridine (84) may be an intermediate (see Section III,B,l,a for its formation) that undergoes a covalent amination at C-4, yielding the gem 4,4-diamino-2-bromodihydro-l,5-naphthyridinide (153) and an amino debromination at C-2, yielding 85. Ring opening of 153... 

There is only one study concerning the covalent amination of methyl-naphthyridines. It has been reported that both 2-methyl- (37a) and 4-methyl-... 

The mechanism of the Chichibabin amination of pyridine has been discussed in terms of an addition-elimination mechanism via a covalent a-adduct.38 39 The possible formation of 2,3-didehydropyridine (2,3-pyridyne) as intermediate in the Chichibabin amination has been advocated, but this is now definitely rejected.38 39 In this section we discuss the Chichibabin amination of the parent naphthyridines and their derivatives and the products that are obtained in these aminations. The formation of their precursors (the covalent n-adducts) has already been discussed in Section II,A and II,B. 

Other work has been carried out concerning the amination of 3-nitro-1,5-naphthyridine (46a) with liquid ammonia containing potassium permanganate.27 The 4-amino-3-nitro- 1,5-naphthyridine (50) is obtained in 50% yield. Its precursor, the covalent rr-adduct (47a), has been detected by NMR spectroscopy (see Section II,B,3). 

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