Gould–Jacobs reaction

The Gould–Jacobs reaction is an organic synthesis for the preparation of quinolines (more specifically, a 4-Quinolinol).^[1] In this reaction aniline or an aniline derivative first reacts with malonic acid derivative ethyl ethoxymethylenemalonate with substitution of the ethoxy group by nitrogen. A benzannulation takes place by application of heat to a quinoline. The ester group is hydrolysed by sodium hydroxide to the carboxylic acid and decarboxylation again by application of heat to 4-hydroxyquinoline.

Examples

An example is the synthesis of 4,7-dichloroquinoline ^[2]

• Floctafenine and Glafenine are a pair of fenamate NSAIDs whose synthesis rely on the Gould–Jacobs reaction.
• A lot of quinolone antibiotic structures such as Rosoxacin, Oxolinic acid, Droxacin, etc.

References

1. The Synthesis of Certain Substituted Quinolines and 5,6-Benzoquinolines R. Gordon Gould, , Walter Abraham Jacobs J. Am. Chem. Soc.; 1939; 61(10); 2890-2895. doi:10.1021/ja01265a088
2. Organic Syntheses, Coll. Vol. 3, p.272 (1955); Vol. 28, p.38 (1948). Link