Of naphthyridines

A number of naphthyridines have been converted into their quaternary salts, but no systematic study has been reported. 

These results made it possible to arrive at a sufficiently well-grounded conclusion that the effect of raised heat resistance caused by the formation of intermolecular chemical bonds is not very significant, and that the usually observed considerable increase of heat resistance of PAN fibres as a result of a crosslinkage with bifunctional compounds, is caused not by the formation of intermolecular chemical bonds, as it has usually been thought45, 46, but by cyclization reactions of the nitrile groups with the formation of naphthyridine cycles47. ... 

A series of naphthyridine- and quinoline-3-carbonitriles, compounds 1, 2 have been reported to be potent Tpl-2 inhibitors with IC50 values = 2 and 19 nM, respectively [10,11]. 

Amides of aminopyridines have also been widely used to direct lithiation, and are most effective when lithiated with BuLi in the absence of TMEDA (Scheme 38) . The lithiation of 80 can be used as a key step in the synthesis of naphthyridines and other condensed polycyclic heterocycles" . 

A similar strategy can also be applied for the analogous synthesis of naphthyridine derivatives [93]. Here A-allyl derivatives of o-aminobenzaldehyde,... 

MI21104, 75JSP(54)167>. Correlation between molecular orbital energies calculated using the MIEH method and photoelectron spectra of naphthyridines showed more recognizable lone pair orbitals than did the extended Hiickel method (74MI21100). 

The NMR spectra of all of the parent naphthyridines (l)-(6) can be interpreted by first order splitting rules including meta, para and cross-ring spin-spin coupling. The various chemical shifts are shown in Table 4. As it is now common practice to report H NMR data of naphthyridine derivatives, which are far too numerous to list individually, further information can be obtained from the references given in the table as well as from references in the sections on reactivity (2.11.3) and synthesis (2.11.4). 

ESR spectroscopy measurements in various solvents have provided information on the spin density distributions in the radical anions of naphthyridines (l)-(6) 71MI21100, 71MI21101, 71MI21102, 74MI21102, 77IJC(A)371, 78MI21102). 

Nitration of naphthyridines occurs only when electron-donating groups are present in the 2- or (and) 4-position. Thus l,7-naphthyridine-4(l//)-one (40) can be mononitrated to give the 3-nitro compound (41) in 74% yield (60JCS1794) whilst the presence of two... 

Substituted-3-aryl[l,6]naphthyridin-2-amines and 7-substituted-3-aryl[l,6]naphthyridin-2(l//)-ones have been prepared by diazotization of 3-aryl[l,6]naphthyridine-2,7-diamines, themselves obtained by the condensation cycli-zation of 4,6-diaminonicotinaldehyde and phenylacetonitrile <2000J(P1)1843>. Derivatives of cyanoacetic acid have rarely been used in the synthesis of naphthyridines, although a recent study has shown that they may be reacted with 4-piperidone derivatives to give [l,6]naphthyridines <2000CHE496>. 

All four pyrrolo[2,3]pyridines can be prepared by photochemical ring contraction of naphthyridine derivatives, e.g. (210). Although reliable, multistep syntheses are needed for the photolysis substrates, which can only be irradiated in small quantities (Scheme 67) <58LA(612)153>. 

The use of PMR spectroscopy in the structure determination of a large number of naphthyridines has greatly facilitated investigations involving cyclizations and substitution reactions. 

The dehalogenation of naphthyridines with hydrogen over palladium on calcium carbonate in a weakly basic alcoholic solution gives excellent yields (90-95%) of reduced compounds.38,45,134,137,138 This method for removal of halogens has been extensively used and generally surpasses the classic hydrazine-copper sulfate reduction method. 

It is not surprising that the behavior of naphthyridines toward nucleophiles has been a subject of numerous studies1 8 and that nucleophilic substitution in naphthyridines has become a very valuable and efficient method to synthesize substituted naphthyridines. In the last decade many important and new features of nucleophilic substitution in naphthyridines using nitrogen nucleophiles (especially liquid ammonia and potassium amide/liquid ammonia) have been found. In view of these recent results it seems worthwhile to review this area of research. The present chapter is concerned with the reactions of naphthyridine with nitrogen nucleophiles for a full review of naphthyridine chemistry, see the chapter by Paudler and Sheets, p. 147 of this volume. 

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... 

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