Camps quinoline synthesis

The Camps quinoline synthesis was discovered first by Icilio Guareschi (1847-1918) in 1894. Guareschi had had ortho- amino acetophenone react with ethyl cyanoacetate in a condensation reaction to give 2-hydroxy -3-cyano -4- methylquinoline. This reaction then camps Rudolf extended to synthesize hydroxyquinolines transposed by N-acyl -ortho- acylanilines with a base. The reaction is sometimes referred to as camp - reaction or camps cyclization.

Survey

N-acyl -ortho- acylanilines react in the presence of a base to give 4- hydroxyquinoline (middle) and 2- hydroxyquinoline:

The reaction can thus, for example, ortho- amino derivatives of acetophenone, benzophenone, benzyl acetate or propiophenone perform and leads to a mixture of the two products. Should one of the groups electron-withdrawing properties ( for example, cyano group, acyl group or phenyl group) The result is only the product:

• R1 is an electron withdrawing group → 4- hydroxyquinolines (center)
• R2 is an electron withdrawing group → 2 hydroxyquinolines (right)

Mechanism

The following are the two different reaction mechanisms are presented that take place depending on where the deprotonation. R1 and R2 are also organic radicals or hydrogen.

Form 2,3 -dialkyl- 4-hydroxyquinoline

This product was formed when the deprotonation of the methyl group at the R1 radical, that is, when R1 is an electron withdrawing group, or a mixture of the two products formed:

First, the base deprotonates the methyl group of N-acyl- ortho acylanilins 1, thereby forming the enolate of 2. With the re- formation of the carbonyl group of the recently formed C = C double bond attacks the carbon atom of the other nucleophilic carbonyl group and thus forms a heterocyclic six-membered ring 3 from. The resulting alkoxide 3 is protonated by alcohol molecule 4 and then splits off water. In the ketone 5 is then tautomerization occurs resulting in the formation of the 2,3- dialkyl-4- hydroxyquinoline 6.

Formation of 3,4- dialkyl-2 -hydroxyquinoline

The 3,4- dialkyl-2 -hydroxyquinoline constituting the other hand, if the methyl group of the amino acyl group is deprotonated (R2 is electron withdrawing group or as part of the product mixture ):

Here the methyl group is deprotonated at the nitrogen 1 of the base. Here, too, an alcoholate formed 7 In the formation of a carbonyl group, the double bond formed 7 engages the carbon atom of the acyl group, and forms a heterocyclic six-membered ring 8 The resulting alcoholate 8 is an alcohol protonated 9 is then formed by elimination of water, a double bond. Here too, finally takes a keto -enol tautomerism of ketone 10 to give 3,4 -dialkyl -2 -hydroxyquinoline 11.