Gould-Jacobs reaction

Gould-Jacobs reaction

The Gould-Jacobs reaction is a chemical reaction used in organic chemistry for the synthesis of quinoline derivatives. This reaction involves the construction of the quinoline ring by the reaction of an aniline with a β-dicarbonyl compound, typically in the presence of an acid catalyst. The Gould-Jacobs reaction is named after the American chemists Maurice Gould and Lewis Jacobs, who first reported the method in 1939.

Mechanism

The mechanism of the Gould-Jacobs reaction begins with the formation of an enamine from the aniline and the β-dicarbonyl compound. This enamine then undergoes an electrophilic aromatic substitution to form an intermediate, which upon cyclization forms the quinoline core. Finally, the reaction is completed by the removal of a water molecule and aromatization of the ring.

Applications

The Gould-Jacobs reaction is particularly valuable for the synthesis of quinoline derivatives due to its high efficiency and the broad availability of starting materials. Quinolines are important compounds in both pharmaceuticals and materials science, serving as core structures in various drugs and functional materials. This reaction has been utilized in the synthesis of antimalarial, antibacterial, and anticancer agents, among other pharmaceutical applications.

Variations

Several variations of the Gould-Jacobs reaction have been developed to improve its scope and efficiency. These include modifications of the reaction conditions, such as the use of different acid catalysts or solvents, as well as the introduction of new starting materials to access a wider range of quinoline derivatives.

See also

• Skraup synthesis
• Doebner-Miller reaction
• Friedländer synthesis