Reissert indole synthesis
The indole synthesis according to Arnold Reissert (1860–1945) is a name reaction in organic chemistry which, like the Fischer indole synthesis, takes place over several stages.
Overview reaction
The Reissert indole synthesis is explained by the reaction of nitrotoluene and dimethyl oxalate , which is one of the esters of oxalic acid . An indole is formed in this reaction through ring closure .
In the overview reaction, the carbon atom at which the ring closure takes place is shown in blue .
Reaction mechanism
The mechanism of the reaction is explained step by step using the example of the reaction of nitrotoluenes with dimethyl oxalate to form indole:
In nitrotoluenes ( 1 ) the methyl group is strongly acidified due to the electropositive character of the nitro group . For this reason, in the presence of strong bases , in this case a methanolate, the methyl group can be deprotonated and the nitrotoluene can thus react to form a nucleophile 2 , namely a carbanion . This effect can be explained by the principle of vinylogy , because aliphatic nitro compounds are also known in deprotonated form as strong nucleophiles (cf. Henry reaction ). The carbanion 2 attacks the methyl oxalate ( 3 ), whereby the molecule 4 is formed. By splitting off a methanolate, 2-oxopropanoate 5 is formed . This molecule is reduced from a nitro group to an amino group with tin (II) chloride , so that molecule 6 is formed. Anion 7 is formed through an intermolecular ring closure, as can be seen in molecule 6 . After a proton rearrangement from nitrogen to oxygen , the molecule 8 is formed . The nucleophilic attack of a hydroxide ion on the methyl group in molecule 8 and elimination of water results in the carboxylate 9 , which in turn is protonated . The indole-2-carboxylic acid derivative 10 produced in this way can be decarboxylated under the action of heat , whereby the indole ( 11 ) is formed; this last step is completely analogous to the classical Fischer indole synthesis.
literature
- KPC Vollhardt , NE Schore: Organic Chemistry . 4th edition. Wiley-VCH, Weinheim 2005, ISBN 978-3-527-31380-8 .
Individual evidence
- ↑ A. Reissert : Effect of oxalate and sodium ethylate on nitrotoluenes. Synthesis of nitrated phenylpyruvic acids . In: Reports of the German Chemical Society . tape 30 , no. 1 , 1897, p. 1030-1053 , doi : 10.1002 / cber.189703001200 .
- ^ JJ Li: Name Reactions in Heterocyclic Chemistry . John Wiley & Sons, 2004, ISBN 978-0-471-30215-5 , p. 154.
- ↑ Reactivity Scales. (PDF; 61 kB) LMU Munich
- ^ Z. Wang: Comprehensive Organic Name Reactions and Reagents, 3 Volume Set . John Wiley & Sons, Hoboken NJ 2009, ISBN 978-0-471-70450-8 , p. 2341