Reissert indole synthesis

The Reissert indole synthesis by Arnold (1860-1945) is a name of reaction in organic chemistry, as well as, for example, passing the Fischer's indole synthesis in several steps.

Overview reaction

The Reissert indole synthesis is explained in the reaction of nitrotoluenes and oxalate, which is one of the esters of oxalic acid. By ring closure formed in this reaction, an indole.

In the overview reaction, the carbon atom is shown in blue, which hosts the ring closure.

Reaction mechanism

The mechanism of the reaction is explained using the example of the reaction of Nitroluolen with dimethyl oxalate to give the indole step by step:

In nitrotoluene ( 1) the methyl group by the electropositive character of the nitro group is strongly acidified. For this reason, in the presence of strong bases, in this case a Methanolats, the methyl group is deprotonated and thus the nitrotoluene a nucleophile 2, which is a carbanion reaction. This effect can be explained by the vinylogy principle, because aliphatic nitro compounds are in deprotonated form known as strong nucleophiles (See Henry) reaction. 2 the carbanion attack of the oxalic acid methyl ester ( 3), whereby the molecule is 4. Due to the elimination of a Methanolats to 2- oxopropanoate forms 5 This molecule is with tin ( II ) chloride is reduced by a nitro group to an amino group, so that the molecule 6 forms. By intermolekulern ring closure, as is seen in molecule 6, the anion results 7 After a proton migration from nitrogen to oxygen occurs, the molecule 8 Under the nucleophilic attack of a hydroxide ion on the methyl group in the molecule 8 and elimination of water, the carboxylate is formed 9, which in turn is protonated. The thus produced indole -2 -carboxylic acid derivative 10 can be decarboxylated under the action of heat, whereby the indole ( 11); this last step runs completely analogous to the classical Fischer indole synthesis 's.