6 -naphthyridinium salts

A-Methylquinolinium iodide gives 1 -methyl-2-imino-1,2-dihydroquin-oline. The intermediacy of the covalent adduct is recorded by NMR spectroscopy (Scheme 38) (84TL3763). A-Methyl-1,5- and A-methyl-1,8-naphthyridinium salt also yield the corresponding 2-imino compounds. The 6-methyl- 1,6-naphthyridinium salt gives imination at C-4 and the 7-methyl-1,7-naphthyridinium salt gives imination at C-8 (Scheme 38) (85JOC3435). In all these reactions the intermediary covalent a-addducts are observed by NMR spectroscopy. 

The 2,7-naphthyridine system 53 (Scheme 8.4.18) was combined with 2,4-dinitrochlorobenzene and 2-amino glycerol for in situ reaction of the resulting Zincke salt. The resulting naphthyridinium 54 was trapped by Bradsher cycloaddition with (Z)-vinyl ether 55, providing tetracycle 56 (X-ray) upon internal addition of one of the diastereotopic hydroxymethyl groups to the resulting iminium. This approach was also extended to the use of chiral 2,7-naphthyridinium salts, prepared via the analogous Zincke process. ... 

Azolo[1,5]naphthyridines. Imidazonaphthyridines can be prepared by the reaction of ammonium acetate with appropriately substituted naphthyridinium salts. For example, reaction of the ketone 236 in acetic acid with iron(m) chloride produces the tetracycle 237 <2001AJC105> (Equation 64). 

Langlois and co-workers have developed a Bradsher cycloaddition route, involving a [2,7]naphthyridinium salt toward the tricyclic core of manzamine A (Scheme 71) <1995TL9475, 1998TL837, 2000TL9251>. 

An unusual ring contraction of 1,6- and 1,7-naphthyridinium salts was observed when treated with liquid ammonia/potassium permanganate (85JOC3435). Thus, 163 gave the azaindolone 164, whose structure was confirmed by X-ray analysis, and 165. 

Most known C-alkyl-1,5-naphthyridines have been made by primary syntheses (see Chapter 1) and most A-alkyl-1,5-naphthyridinium salts by quaternization. Other reported approaches are illustrated in Section 2.1.3 and by the following examples. 

Building on their earlier work and in preparation for an enantioselective approach to manzamine A, 30, the Langlois group examined asymmetric variations on the Bradsher cycloaddition reaction. An initial report focused on using chiral (Z)-enol ether 38 with the previously used naphthyridinium salt 32. The cycloaddition reaction afforded 39 in good yield with 80% de. 

An alternative asymmetric Bradsher cycloaddition reaction reversed the sense of chirality, which resulted in the asymmetric center being incorporated into the naphthyridinium salt 40. " Execution of the cycloaddition reaction with the elaborted enol ether 41 afforded cycloadduct 42. The overall yield and de were found to be similar to the previous example. 

Alkylation of 4-hydroxy-l,7-naphthyridines gives 4-hydroxy-l,7-naph-thyridinium iodides (254) which on treatment with aqueous alkali yield l,7-naphthyridinium-4-olates (253). A number of derivatives (253 R = H, CN, CO2H) have been prepared in this manner. On the basis of IR spectroscopy, the acid derivatives (253 R = CO2H) have been formulated as mesomeric betaines rather than the inner salts 255. 

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