Naphthyridinecarboxylic Acids

This chapter summarizes the sparse existing data on those 1,5-naphthyridines that bear functional groups that are joined to the nucleus through their carbon atoms carboxylic acids, esters, amides, nitriles, aldehydes, and ketones. 

The marked antimalarial activity of some derivatives of oxodihydro-1, 5-naphthyridinecarboxylic acids were noted at the beginning of Chapter 4. 

The reported chemistry of such carboxylic acids is summarized by the following list of examples. 

Note 1,5-Naphthyridinecarboxylic acids have been made by primary synthesis (see Chapter 1) and by oxidation of alkyl-1,5-naphthyridines (see Section 2.2.2). The remaining routes involving oxidation of aldehydes or hydrolysis of esters are exemplified here. 

5- Naphthyridine-2-carbaldehyde 1,5-dioxide (1) underwent oxidation to 1, 5-naphthyridine-2-carboxylic acid 1,5-dioxide (2) (30% H202, AcOH, 25°C, 

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Note Most such carboxamides have been made directly by primary synthesis (see Chapter 8) others from 1,6-naphthyridinecarboxylic acids or esters (see Sections 14.1.2 and 14.2, respectively or by minor routes exemplified here. 

A brief review of antibacterial naphthyridinecarboxylic acids has appeared.542... 

Note Most amides have been made by primary synthesis (see Chapter 15) or from 1,7-naphthyridinecarboxylic acids (see Section 21.1.2). In addition, some have been made by hydrolysis of nitriles as illustrated here. 

The 1,8-naphthyridinecarboxylic acids are well represented in the literature, mainly because the powerful antimicrobial nalidixic acid (1) was adopted as a lead compound for a myriad of analogs,e.g.,154,547,965... 

Naphthyridinecarboxylic acids undergo the usual reactions, as illustrated in the following examples. 

These esters have been reduced to hydroxymethyl-1,8-naphthyridines (see Section 25.1.1) and hydrolyzed to 1,8-naphthyridinecarboxylic acids (see Section 28.1.1). Other reactions are illustrated by the following examples. 

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