Camps quinoline synthesis

What is Camps quinoline synthesis?

The Camps quinoline synthesis is a versatile reaction that allows for the formation of hydroxyquinolines from o-acylamino-acetophenones in an alcoholic sodium hydroxide solution. This reaction was first reported by Guareschi in 1894 as a method of preparing 2-hydroxy-3-cyano-4-methylquinoline through the condensation of o-amino-acetophenone with ethyl cyanoacetate. The synthesis was later extended by Camps, who treated N-acyl o-acylanilines with a base in alcohol solution, resulting in the formation of hydroxyquinolines.

This reaction, commonly known as the Camps reaction or Camps quinoline synthesis, allows for the introduction of various substituents at positions 3 and 4, and is effective with o-amino derivatives of acetophenone, benzophenone, benzoylacetic ester, benzoylcarbinol, propiophenone, and others.

Camps quinoline synthesis - Camps reaction - Camps reaction
Camps quinoline synthesis

The distribution of the two isomers produced by the reaction is mainly dependent on the residue present on the amino nitrogen. When o-amino acetophenone is reacted with esters of aliphatic acids, two isomers are formed simultaneously due to the subtle acidity difference between the methyl group (on the acetyl group) and the methylene group (from the acyl group on nitrogen). However, the presence of an electron-withdrawing group such as CN, COCH3, COC6H5, CO2Et, or C6H5 on the methylene group results in the formation of only one product.

References

  • Guareschi, I., Ann. Chim. Pharmac., 1894, 19, 339
  • Camps, R. (1899), Synthese von α- und γ-Oxychinolinen. [Synthesis of α- and γ-oxyquinolines.] Arch. Pharm. Pharm. Med. Chem., 237: 659-691. https://doi.org/10.1002/ardp.18992370902
  • Camps, R. (1901), Synthese von α- und γ-Oxychinolinen. [Synthese von α- und γ-Oxychinolinen.] Arch. Pharm. Pharm. Med. Chem., 239: 591-610. https://doi.org/10.1002/ardp.19012390805
  • Camps., Rudolf. “Ueber Liebig’s Kynurensäure und das Kynurin, Constitution und Synthese beider.” , [On Liebig’s kynurenic acid and kynurenine, constitution and synthesis of both.] Zeitschr. F. Physiol. Chem. 33, 3-4, 1901, 390-411. https://doi.org/10.1515/bchm2.1901.33.3-4.390
  • Camps, R. (1901), Von der Amidophenylpropiolsäure zur Kynurensäure und deren Verwandten. [From amidophenylpropiolic acid to kynurenic acid and its relatives.] Ber. Dtsch. Chem. Ges., 34: 2703-2718. https://doi.org/10.1002/cber.190103402221
  • Camps, R. (1902), Synthese von α- und γ-Oxychinolinen. [Synthesis of α- and γ-oxyquinolines.] Arch. Pharm. Pharm. Med. Chem., 240: 135-146. https://doi.org/10.1002/ardp.19022400204
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