Gould–Jacobs reaction
The ester group is hydrolysed by sodium hydroxide to the carboxylic acid and decarboxylation again by application of heat to 4-hydroxyquinoline.
[1] Further reading:[4][5][6] The mechanism for the Gould–Jacobs reaction begins with a nucleophilic attack from the amine nitrogen follows by the loss of ethanol to form the condensation product.
A 6 electron cyclization reaction with the loss of another ethanol molecule forms a quinoline (ethyl 4-oxo-4,4a-dihydroquinoline-3-carboxylate).
[7] Another example is in the synthesis of antimalarials as aminoalkylamino derivatives of 2,3-dihydrofuroquinolines[9] The Gould reaction is also used to convert 5-aminoindole to quinolines for the purpose of synthesizing pyrazolo[4,3-c]pyrrolo[3,2-f]quinolin-3-one derivatives as modified pyrazoloquinolinone analogs.
These compounds have the potential to act as antagonists at central benzodiazepine receptors (BZRs) in Xenopus laevis oocytes.
![Conversion of 5-aminoindole to quinolines by the Gould–Jacobs reaction for the purpose of synthesizing pyrazolo[4,3-c]pyrrolo[3,2-f]quinolin-3-one derivatives](http://upload.wikimedia.org/wikipedia/commons/thumb/a/ac/Gould-Jacobs_reaction_on_5-aminoindole.png/500px-Gould-Jacobs_reaction_on_5-aminoindole.png)
![Conventional and microwave radiation approach to synthesize ethyl 4‐oxo‐8,10‐substituted‐4,8‐dihydropyrimido[1,2‐c]pyrrolo[3,2‐e]pyrimidine‐3‐carboxylates by the Gould–Jacobs reaction](http://upload.wikimedia.org/wikipedia/commons/thumb/e/e5/Synthesis_of_ethyl_4%E2%80%90oxo%E2%80%908%2C10%E2%80%90substituted%E2%80%904%2C8%E2%80%90dihydropyrimido%281%2C2%E2%80%90c%29pyrrolo%283%2C2%E2%80%90e%29pyrimidine%E2%80%903%E2%80%90carboxylates_by_the_Gould-Jacobs_reaction.png/500px-Synthesis_of_ethyl_4%E2%80%90oxo%E2%80%908%2C10%E2%80%90substituted%E2%80%904%2C8%E2%80%90dihydropyrimido%281%2C2%E2%80%90c%29pyrrolo%283%2C2%E2%80%90e%29pyrimidine%E2%80%903%E2%80%90carboxylates_by_the_Gould-Jacobs_reaction.png)