Bernthsen reaction

The Bernthsen reaction or Bernthsen acridine synthesis is a name reaction in organic chemistry. It was first published in 1878 by August Bernthsen (1855-1931). It is one of the first acridine syntheses by heating diphenylamines with benzonitrile . However, this is an outdated twist on this response. Today, instead of benzonitrile, a carboxylic acid and zinc chloride are preferred . The acridines produced in this way can be further processed in quinolines.

Overview of the Bernthsen reaction, R denotes a hydrogen atom, an alkyl or aryl group .

mechanism

The following describes a mechanism that is postulated for this reaction:

Mechanism of the Bernthsen reaction, R denotes a hydrogen atom, an alkyl or aryl group

First, zinc chloride is added to carboxylic acid 1 , whereby a carboxylic acid chloride 2 is formed with splitting off of zinc oxide and water (for reasons of stoichiometry , two molecules of the carboxylic acid must come to one particle of zinc chloride). This carboxylic acid chloride reacts with diphenylamine 3 in a Friedel-Crafts acylation via intermediate 4 to give ketone 5 . Zinc chloride polarizes the carbonyl group of the ketone with the formation of the intermediate state 6 - here indicated by the dashed line. Intramolecular electrophilic substitution then leads to the tricyclic alcohol 8 via intermediate 7 . The nitrogen atom in 8 is protonated with hydrogen chloride, whereby the salt 9 is formed. The gradual elimination of hydrogen chloride and water leads to the formation of the substituted acridine 10 .

recycling

Zinc chloride can be recovered from the zinc oxide and hydrogen chloride produced in the reaction :

${\ displaystyle \ mathrm {HCl + ZnO \ {\ xrightarrow {\ triangle}} \ ZnCl_ {2} + H_ {2} O}}$

Individual evidence

^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ 2006, ISBN 0-911910-00-X , p. ONR-10.
^ ^A ^b Zerong Wang: Comprehensive Organic Name Reactions and Reagents. Vol. 1, John Wiley & Son Publication, 2008, ISBN 978-0-471-70450-8 , pp. 362-363.

[MERCK_Index-1] The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th edition. Merck & Co., Whitehouse Station, NJ 2006, ISBN 0-911910-00-X , p. ONR-10.

[Wang-2] A ^b Zerong Wang: Comprehensive Organic Name Reactions and Reagents. Vol. 1, John Wiley & Son Publication, 2008, ISBN 978-0-471-70450-8 , pp. 362-363.