Doebner–Miller reaction

Survey

In this acid-catalyzed reaction of aniline form ( here, unsubstituted aniline) and α, β -unsaturated carbonyl compounds, 2,3- disubstituted derivatives of quinoline.

As the acid, concentrated hydrochloric acid are used.

Mechanism

The mechanism of reaction is illustrated here by the example of the reaction of aniline and an α, β -unsaturated aldehyde. At the end of iodine is used as oxidizing agent. R1 and R2 are organic radicals.

At the beginning of the amino group of the aniline accesses (1 ) to the polarized C = C double bond in the α, β -unsaturated aldehyde is 2, resulting in the formation of an enolate 3. A 1,5- proton transfer 3 follows from the resulting enol tautomerization 4 to the corresponding ketone 5 protonation of the carbonyl group and the amino group of 5 results in a 6 Subsequently, in the course of an intramolecular electrophilic aromatic substitution of an intermediate state 7 heterocyclic six-membered ring closed 8 When heat is water split off and a C = C double bond formed 9 Finally, the molecule is 9 oxidized with iodine to a 2,3- disubstituted quinoline derivative 10.

Modification

In 1886, the reaction was then Carl Beyer ( Beyer Method) modified to the extent that 2,4 -disubstituted quinoline derivatives arise. In this case, anilines may be reacted with α, β -unsaturated carbonyl compounds, which are prepared in situ from a mixture of aldehydes or aldehydes and methyl ketones. R1 and R2 are organic radicals.