Nenitzescu indole synthesis

The Nenitzescu indole synthesis is a name reaction in organic chemistry. It is also called Nenitzescu reaction Nenitzescu synthesis Nenitzescu cyclization or condensation Nenitzescu. This reaction was named after the Romanian chemist Costin C. Nenintzescu (1902-1970), who published them in 1929. The reaction can be 5 - hydroxyindoles of 1,4- benzoquinone and β -amino- α, β -unsaturated carbonyl compounds synthesized (eg, β - aminocrotonic esters ).

Overview reaction

A substituted 1,4-benzoquinone reacts with a β - amino - α, β -unsaturated carbonyl compounds with ring closure to a 5 -hydroxyindole.

The reaction works with substituted benzoquinone in the alkoxy, aryloxy, hydroxy, and chloro-, bromo- or ester substituents. For the other groups, the following groups are allowed:

• R2 = cycloalkyl, benzyl
• R3 = alkyl, alkoxy groups
• R4 = aryl and amino groups

Mechanism

The exact reaction mechanism is not known. A plausible mechanism is described herein with reference to the reaction between 2 -methyl-1 ,4-benzoquinone and β - Aminoacrylsäuremethylester:

In the first step the C = C double bond geift of β - Aminoacrylsäuremethylester ( 2) to the 2 -methyl-1 ,4-benzoquinone (1), resulting in the molecule 3. A proton is rearranged to the 3 alkoxide, which also leads to the fact that from the iminium 3 again an amino group 4. The latter now attacks intramolecularly the carbonyl group of the benzoquinone to, resulting in the formation of a five-membered ring 5 to the result. The resulting negative gelagene oxygen atom is protonated by ammonium group, and thus the hydroxyl group 6 of the six-membered ring under the elimination of water flavored product 7, a 5-hydroxy -6-methyl -3 -1H-indole -carboxylate.

This reaction is especially important for the preparation of 5- Hydroxyindolderivaten.