Huisgen pyrrole synthesis
The Huisgen pyrrole synthesis is a name reaction in organic chemistry . The reaction was discovered by the chemist Rolf Huisgen (1920–2020) in 1960 and named after him. The aim of the reaction is the synthesis of substituted pyrroles .
Overview reaction
During the synthesis, an α-amino acid reacts with a carboxylic acid and an alkyne to form a substituted pyrrole:
In the product pyrrole, the radicals R 4 and R 5 are not regioselective in monocyclic Münchnonen, mesoionic oxazolones so called by Huisgen. Both R 4 and R 5 can be found at these positions on the pyrrole.
Reaction mechanism
The reaction mechanism of the Huisgen pyrrole synthesis is based on the reaction of an α-amino acid with a carboxylic acid and an alkyne as follows:
The α-amino acid 1 is reacted with a carboxylic acid to form the amide 2 with elimination of water . Amide 2 also has a carboxy group which reacts with acetic anhydride to form an acid anhydride group 3 . In this case, acetic acid split off. An intramolecular ring closure creates the molecule 4 , a rearrangement of electrons and the formation of an acetate form the heterocyclic five-membered ring 5 . The carbanion 6 is formed by deprotonation . This reacts with an alkyne to form the transition state 7 . By splitting off carbon dioxide , the pyrrolide 8 is formed , which aromatizes to the substituted pyrrole 9 through electron migration .
Individual evidence
- ^ Zerong Wang: Comprehensive Organic Name Reactions and Reagents, 3 Volume Set . John Wiley & Sons, Hoboken, New Jersey 2009, ISBN 978-0-471-70450-8 , p. 2035.