Synthesis of Indole Derivatives

Author: Ioseb Chikvaidze
Keywords: Indole, Deformylation, Hydrazone, Indalization
Annotation:

The process of unusual deformylation reaction is investigated on the basis of some aromatic and heteroaromatic aldehydes. It is shown that by heating π-Sur¬plus heteroaromatic aldehydes in the ethylenglycole to 150℃, de¬for¬my¬la¬ti¬on is processing, this reaction does not process in case of Nitro-derivatives of Benzaldehyde and Acetophenone even by refluxing in ethylenglycole, which is explained by the influence of electron-acceptor groups. Indolization reactions of phenylhydrazones of acetophenone derivatives are carried out in different condensation areas in order to study electronic influence of substituents based on some steps of Fischer reaction mechanism in particular indolization of arylhydrazones under acidic conditions. It has been established that acceptor substituents in carbonyl cause the reduction of the temperature conditions in Fischer indolization reaction. Among several known methods for synthesis of Indole rings, the most popular one is the classical reaction of E.Fischer Indolization reaction of Arylhydrazones in the presence of acid catalyst. Several articles regarding this mechanism are present, among them are synoptic articles. Nowadays accepted mechanism is the one shown on the scheme. For a while, one of the step in Fischer’s reaction (III) – formation of new C-C bond was subject of discussion: To count it as [3,3’] sigmatropic rearrangement, as intermolecular nucleophilic reaction, as process where N-protonated N-hydrazine electrocyclic reaction etc. Authors of the article published in 2011, are confirming the argument regarding the importance of electric factors of this step. In particular, electron donors present in carbonyl fragment suspend the formation of indole ring [1]. Results of our observations are corresponding well with these data. Correspondence of optimal temperatures with the electronic nature of a substituent during the indolization of aryl hydrazones became clear. We conducted comparative analysis of these temperatures. We ge¬ne¬ralized literature and our experimental data [2,3], as well as the results of quantum-chemical calculations. In the report, obtained data, on an example of acetophenone derivatives and some oxo compounds, is discussed. In particular, peculiarity of influence from groups R, R1, and R2.