Conrad–Limpach synthesis

The mechanism concludes with the removal of an alcohol, a series of proton transfers, and a keto/enol tautomerization to form a 4-hydroxyquinoline, the final product of the Conrad–Limpach synthesis.

When Conrad and Limpach first observed this reaction in 1887, it was run at room temperature, and gave high yields of β-aminoacrylate: the kinetic product.

However, Ludwig Knorr observed that under higher temperatures (approximately 140 °C) the aniline would actually attack the ester group of the β-ketoester, leading to the thermodynamically preferred β-keto acid anilide product (albeit in less than ideal yields).

The synthesis of 4-hydroxyquinolines and 4-quinolones is of great importance to a variety of fields, but most notably to the medical sciences due to their use as chemotherapeutic bactericidal drugs through their ability to kill bacteria.

The majority of drugs in clinical use are actually quinoline derivatives that belong to the subset fluoroquinolones, which have a fluorine atom attached to the central ring system, often at the C-6 or C-7 position.