1,8-Naphthyridine ring

The Balz-Schiemann reaction continues to attract attention, with much of it generated by the interest in fluoroquinolones, e.g., (7), which is a potential antibacterial. Two approaches to its synthesis are possible—introduction of fluorine prior to or post ring construction. Decomposition of the tetrafluoroborate salt was unsuccessful, whereas the PF6 salt (8) gave only a poor yield (84JMC292). A more successful approach was the introduction of F into the pyridine nucleus prior to formation of the 1,8-naphthyridine ring (84JHC673). A comparison of decomposition media showed that cyclohexane was the best with regard to yield and time. 

A binuclear complex of 4-methyl-l,8-naphthyridine (150) has been prepared.1 100 Its structure, as determined by X-ray diffraction, shows two nearly equivalent copper atoms in a pseudotetrahedral environment bridged by one chlorine and two 4-methyl-1,8-naphthyridine rings. 

A large number of 4-oxo derivatives of the 1,8-naphthyridine ring system have been synthesized and screened for their antibacterial activity. In general, the active compounds are similar to the 1,5-naphthyridine derivative nalidixic acid.114-117... 

COMPLEXES WITH FUNCTIONALIZED DERIVATIVES OF THE 1,8-NAPHTHYRIDINE RING 56... 

OTHER MULTIDENT ATE LIGANDS DERIVED FROM THE 1,8-NAPHTHYRIDINE RING 59... 

Several approaches to the synthesis of nitronaphthyridines and their derivatives are reported. Very common ones are those in which the construction of the nitronaphthyridine system was achieved by using nitro synthons (see Section II,A) or by nitration of the naphthyridine ring, although a successful nitration requires the presence of electron-donating substituents (see Section II,B). Furthermore, the oxidation of the amino group in aminonaphthyridines... 

Tlie products of nitration of 2-amino-5-phenyl-l,8-naphthyridin-7(8H)-one (63) vary depending on whether the reaction is carried out with nitric acid in sulfuric acid or in acetic anhydride (74GCI499). In sulfuric acid the phenyl ring was found to be nitrated more easily than the naphthyridine ring, yielding a mixture of 3- and 4-nitrophenyl derivatives (64) in acetic... 

In the naphthyridine ring with its 10 delocalized 7r-electrons located on five distorted molecular orbitals, due to an electron drift toward the nitro-... 

Though no naphthyridine rings are formed when copolymers of AN with vinylidene chloride (50 50) or with vinyl chloride (50 50) are treated with ammonium sulfide solutions, it is, however, probable that, as a result of a considerable number of intermolecular chemical bonds being formed in the macromolecules or copolymers, the heat resistance of these modified copolymers... 

Representatives of the pyrrolo[3,2-/][l,7]naphthyridine ring system, viz. 61, have been obtained by palladium-catalyzed cyclization of the corresponding 5-alkenyl-6-amino[l,7]naphthyridines (Scheme 19) <2002H(56)443>, although this reaction appears not to be general and its scope is as yet undefined. 

The first derivative of the naphthyridine ring system was prepared by Reissert5 in 1893, who suggested the use of the name. No unsubstituted naphthyridine was known until 1926, when 1,5-naphthyridine ... 

The condensation and cyclization of EMME with 4-aminopyridine and 4-aminoquinoline affords, in each case, the 1,6-naphthyridine ring system.59 Albert11 used this reaction to prepare the hydroxy ester (34), which he converted into the parent 1,6-naphthyridine by the following sequence of reactions. 

The discovery of the alkaloid halozine, which contains the 1,6-naphthyridine ring skeleton, has led to the syntheses of some per-hydro derivatives. These transformations will be discussed in Section VI. 

Treatment of the pyranopyridine (50) with methanolic ammonia gave compound 51.93 This is the same reaction used earlier by Ikekawa to form the 1,6-naphthyridine ring system. 

Early literature references cite the photochemical contraction of naphthyridine rings to generate all four pyrrolopyridine isomers (e.g., Scheme 51) <58LA(612)153>. This method involves a multistep reaction sequence which can only be carried out on a very small scale. 

The naphthyridine ring system is found in numerous alkaloids, nauclefine (420) <76H(4)247> and angustine (423) <75H(3)627> being two relevant examples. 

Special interest was focused on the photochemistry and redox properties of mononuclear ruthenium complexes.20 Examples show the nucleophilic attack of one of the N atoms of 1,8-naphthyridine on the coordinated CO in [Ru(bipy)2(napy)(CO)]2+ upon le reduction of the napy moiety (Scheme 2). Such a type of metallacyclization enables the reduction of the CO group, derived from the electrochemical reduction of C02 catalyzed by [Ru(bipy)(napy)2(CO)2](PF6)2, to produce acetone in the presence of Me4NBF4.21,22 An unusual result is the simultaneous formation of a carbene ligand and the addition of the methoxo group to the naphthyridine ring upon reaction of [Ru(bipy)2(napy)]2+ with propiolic acid in methanol (Scheme 2).23... 

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