Combes quinoline synthesis

The Combes quinoline synthesis is a name reaction in organic chemistry. It was first the French chemist Alphonse Combes (1854-1907) published in 1888. The response describes one way quinoline derivatives of aniline and β -diketones to synthesize:

As sulfuric acid can or better yet polyphosphoric acid can be used.

Mechanism

The reaction involves a condensation reaction between aniline and a β -diketone, followed by an acid-catalyzed cyclization to a quinoline derivative. The radicals R1, R2 and R3 correspond again an alkyl or aryl group.

In this acid-catalysed reaction initially respond aniline ( 1) and a β -diketone 2 via the intermediates 3 ​​and 4 to the Schiff base 5 (see also: imine production). On protonation of the carbonyl group 5 to molecule 6 follows an electrophilic aromatic substitution via the intermediate 7 ( here is only a Canonical structure given) bicyclic compound 8 elimination of water a further C produced = C double bond and thus the quinoline derivative 9

Since the ring closure can take place ( in the course of electrophilic aromatic substitution) at two different ortho positions, results in a mixture of two quinoline derivatives with the swapped residues R1 and R3.