Balz-Schiemann reaction
The Balz-Schiemann reaction (also known as the Schiemann reaction) is a name reaction in organic chemistry that was named after its discoverers Günther Balz and Günther Schiemann (1899–1967) .
Overview reaction
The Balz-Schiemann reaction is the most important reaction for introducing a fluorine substituent into an aromatic which has an amino group . The reaction proceeds with the addition of nitrous acid and tetrafluoroboric acid .
Reaction mechanism
The following reaction mechanism has been proposed by Jie Jack Li, among others. First , the tetrafluoroboric acid dissociates in an inert solvent to form a tetrafluoroborate anion and a proton . The hydroxyl group of nitrous acid is protonated. After water has been split off from the oxonium ion that is formed, a nitrosyl cation is formed . The tetrafluoroborate anion (blue) remains in solution.
As an example of an aryl group , a is phenyl having a substituted amino group 1 used. The non-bonding electron pair on the nitrogen atom of the amino group attacks the nitrosyl cation. Structure 2 is formed with deprotonation . Intramolecular rearrangement reactions result in structure 3 , which is then protonated to form oxonium ion 4 .
The diazonium salt 5 is formed with elimination of water . This is precipitated, washed and dried. Subsequently, nitrogen (N 2 ) can be split off by careful heating , whereby the secondary carbenium ion 6 is formed.
In the last step, a fluorine atom is added to 6 , which also releases gaseous boron trifluoride . This can be recovered as hydrofluoric acid or potassium borofluoride.
Practical meaning
The Sandmeyer reaction enables aryl residues to be brominated and chlorinated. The fluorination of aryl residues is achieved by the Balz-Schiemann reaction. The advantage of this reaction is the very calm and smooth decomposition of the diazonium borofluoride, which is sparingly soluble, easy to isolate and can even be recrystallized. In addition, no side reactions occur, so that high yields can be achieved. Comparable diazonium boron halides, especially diazonium boron chlorides, are highly explosive. The carbon-fluorine bond increases the lipophilicity of a compound and therefore plays an important role in processes of the blood-brain barrier in relation to psychotropic drugs . In addition, fluorine is a strong hydrogen bond acceptor that can favor certain conformations of a compound (e.g. the 3D structure of proteins ).
Individual evidence
- ↑ Flood, DT: Fluorobenzene In: Organic Syntheses . 13, 1933 , p. 46, doi : 10.15227 / orgsyn.013.0046 ; Coll. Vol. 2, 1943, p. 195 ( PDF ).
- ↑ Günther Balz, Günther Schiemann: In About aromatic fluorine compounds, I .: A new method for their representation, Chemical Reports 1927 , 5 , 1186–1190, doi : 10.1002 / cber.19270600539 .
- ↑ Michael P. Doyle, William J. Bryker: Alkyl Nitrite-Metal Halide Deamination Reactions.6.Direct Synthesis of Arenediazonium Tetrafluoroborate Salts from Aromatic Amines, tert-Butyl Nitrite, and Boron Trifluoride Etherate in Anhydrous Media , The Journal of Organic Chemistry 1978 , 9 , 1572-1574, doi : 10.1021 / jo01323a048 .
- ↑ C. Gardner Swain, Randall J. Rogers: Mechanism of Formation of Aryl Fluorides from Arenediazonium Fluoborates , Journal of the American Chemical Society 1974 , 4 , 799-800, doi : 10.1021 / ja00837a019 .
- ↑ Günther Balz, Günther Schiemann: In About aromatic fluorine compounds, I .: A new method for their representation, Chemical Reports 1927 , 60 , 1186–1190, doi : 10.1002 / cber.19270600539 .
literature
- L. Gattermann, H. Wieland: The practice of organic chemists , 43rd edition, de Gruyter, Berlin 1982 , p. 617 ISBN 3-11-006654-8 .
- Jie Jack Li: Name reactions, a collection of detailed reaction mechanism .Vol 1.Springer 2002 . ISBN 3-540-43024-5 .
- Z. Wang: Comprehensive Organic Name Reactions and Reagents , Vol 1. John Wiley & Sons, Hoboken, New Jersey 2009 , pp. 185-190, ISBN 978-0-471-70450-8 .
