2.7- Naphthyridine quaternization

Quaternization of benzo[/][l,7]naphthyridine with halogenoacyl halides occurs at N-7, and the quaternary salts may then be deprotonated to give the ylides. These ylides can then react with a variety of dienophiles to give the corresponding pyrrolonaphthyridines (Scheme 72) <1996PJC1324, 1999AJC149>. 

Naphthyridine chemistry has been well reviewed by Allen1 (up to 1947), and by Weiss and Hauser2 (up to 1958). It has also been considered incidentally by Duffin8 (quaternization reactions) and by Campbell4 in The Chemistry of Carbon Compounds. ... 

As previously mentioned, the quaternization of the naphthyridines has been considered by Duffin,8 and the reader should refer to this work for additional references. 

Quaternization of 1,6-naphthyridine with methyl iodide takes place at the 6-nitrogen atom.5 0 The position of methylation was proven by the structure determination of the alkaline oxidation product (138) obtained from the salt (137). 

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. 

Note. Quaternization of unsubstituted 1,5-naphthyridine has been exemplified in Section 2.1.3 other quatemizations are illustrated here. 2,6-Dimethyl-l,5-naphthyridine (34) gave l,2,6-trimethyl-l,5-naphthyridinium iodide (33) (Mel, MeCN, reflux, 5 h 82%) or 1,2,5,6-tetramethyl-l, 5-naphthyridinedium bisperchlorate (35) (neat Me2S04, 125°C, 1 h solid, HC104 95%).1169... 

Naphthyridine underwent quaternization by l-chloro-2,4-dinitrobenzene in methanol or acetone under reflux to afford 2-(2,4 dinitrophenyl)-2,7-naphthyr-idinium chloride (58) accompanied by either 2-(2,4-dinitrophenyl)-l-meth-oxy- (59, R=OMe) (10%) or l-acetonyl-2-(2,4-dinitrophenyl)-l,2-dihydro-... 

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