Meth-Cohn quinoline synthesis

What is Meth-Cohn quinoline synthesis?

The Meth-Cohn quinoline synthesis entails treating acylanilides with Vilsmeier’s reagent ([(CH3)2NCHCl]Cl) in phosphorus oxychloride (POCl3) solvent under warm conditions, leading to the formation of 2-chloro-3-substituted quinolines.

Meth-Cohn quinoline synthesis - general reaction scheme
Meth-Cohn quinoline synthesis

The Vilsmeier-Haack reaction is a widely used method for the formylation of diverse electron-rich substrates, including aliphatic, aromatic, and heteroaromatic compounds. Although it is primarily used for aromatic formylation, this reaction also provides access to a broad range of heterocyclic systems.

In 1978, Meth-Cohn’s team developed a straightforward procedure in which acetanilide was efficiently converted into 2-chloro-3-quinolinecarboxaldehyde with a yield of 68 %. This quinoline synthesis was later termed the “Vilsmeier approach” by Meth-Cohn or Meth-Cohn quinoline synthesis.