Balz–Schiemann reaction explained

The Balz–Schiemann reaction (also called the Schiemann reaction) is a chemical reaction in which a primary aromatic amine is transformed to an aryl fluoride via a diazonium tetrafluoroborate intermediate.^{[1] [2]} This reaction is a traditional route to fluorobenzene and some related derivatives, including 4-fluorobenzoic acid.

The reaction is conceptually similar to the Sandmeyer reaction, which converts diazonium salts to other aryl halides (ArCl, ArBr).^[3] However, while the Sandmeyer reaction involves a copper reagent/catalyst and radical intermediates,^[4] the thermal decomposition of the diazonium tetrafluoroborate proceeds without a promoter and is believed to generate highly unstable aryl cations (Ar⁺), which abstract F⁻ from BF₄⁻ to give the fluoroarene (ArF), along with boron trifluoride and nitrogen as the byproducts.

Innovations

The traditional Balz–Schiemann reaction employs HBF₄ and involves isolation of the diazonium salt. Both aspects can be profitably modified. Other counterions have been used in place of tetrafluoroborates, such as hexafluorophosphates (PF₆⁻) and hexafluoroantimonates (SbF₆⁻) with improved yields for some substrates.^{[5] [6]} The diazotization reaction can be effected with nitrosonium salts such as [NO]SbF₆ without isolation of the diazonium intermediate.^[7]

As a practical matter, the traditional Balz–Schiemann reaction consumes relatively expensive BF₄^- as a source of fluoride. An alternative methodology produces the fluoride salt of the diazonium compound. In this implementation, the diazotization is conducted with a solution of sodium nitrite in liquid hydrogen fluoride:^[8]

History

The reaction is named after the German chemists and Günther Balz.

Examples

4-Fluorotoluene is made in ~89% yield by Balz-Schiemann reaction on p-toluidine.^[9] This is then used as a precursor for 4-fluorobenzaldehyde,^[10]

Additional literature

• Roe A . 1949 . Preparation of Aromatic Fluorine Compounds from Diazonium Fluoborates. 10.1002/0471264180.or005.04 . Org. React. . 5 . 193. 0471264180 .
• Becker H. G. O., Israel G. . 1978 . Ionenpaareffekte bei der Photolyse und Thermolyse von Aryldiazonium-tetrafluoroboraten. J. Prakt. Chem. . 321 . 4. 579–586 . 10.1002/prac.19793210410.

Notes and References

1. Balz . Günther . Schiemann . Günther . Über aromatische Fluorverbindungen, I.: Ein neues Verfahren zu ihrer Darstellung . . 1927 . 60 . 5 . 1186–1190 . 10.1002/cber.19270600539 . Aromatic fluorine compounds. I. A new method for their preparation. . German.
2. Book: Carey . 2007 . Advanced Organic Chemistry: Part B: Reactions and Synthesis . 5th . Springer . New York . Carey, Francis A. . Sundberg, Richard J. . 978-0387683546. 1031.
3. Mechanism of formation of aryl fluorides from arenediazonium fluoborates. Swain, C. G. . Rogers, R. J. . J. Am. Chem. Soc.. 97. 4 . 799–800. 1975. 10.1021/ja00837a019.
4. Book: Carey . 2007 . Advanced Organic Chemistry: Part B: Reactions and Synthesis . 5th . Springer . New York . Carey, Francis A. . Sundberg, Richard J. . 978-0387683546. 1030-1031.
5. Rutherford . Kenneth G. . Redmond . William . Rigamonti . James . The Use of Hexafluorophosphoric Acid in the Schiemann Reaction . . 1961 . 26 . 12 . 5149–5152 . 10.1021/jo01070a089.
6. Sellers . C. . Suschitzky . H. . The use of arenediazonium hexafluoro-antimonates and -arsenates in the preparation of aryl fluorides . Journal of the Chemical Society C: Organic . 1968 . 2317–2319 . 10.1039/J39680002317.
7. Synthesis. 2010. 10.1055/s-0029-1218742. C–F Bond Formation for the Synthesis of Aryl Fluorides. Takeru. Furuya. Johannes E. M. N.. Klein. Tobias. Ritter. 2010. 11. 1804–1821. 20953341. 2953275.
8. Book: 10.1002/14356007.a11_349 . Fluorine Compounds, Organic . Ullmann's Encyclopedia of Industrial Chemistry . 2000 . Siegemund . Günter . Schwertfeger . Werner . Feiring . Andrew . Smart . Bruce . Behr . Fred . Vogel . Herward . McKusick . Blaine . 3527306730 .
9. ((Yu, Z.)), ((Lv, Y.)), ((Yu, C.)), ((Su, W.)) . Tetrahedron Letters . Continuous flow reactor for Balz–Schiemann reaction: a new procedure for the preparation of aromatic fluorides . 54 . 10 . 1261–1263 . March 2013 . 10.1016/j.tetlet.2012.12.084.
10. ((Laali, K. K.)), ((Herbert, M.)), ((Cushnyr, B.)), ((Bhatt, A.)), ((Terrano, D.)) . Journal of the Chemical Society, Perkin Transactions 1 . Benzylic oxidation of aromatics with cerium(IV) triflate; synthetic scope and mechanistic insight . 6 . 578–583 . 2001 . 10.1039/b008843i.