Vilsmeier–Haack reaction

Vilsmeier–Haack reaction
Named after Anton Vilsmeier
Albrecht Haack
Reaction type Substitution reaction
Identifiers
Organic Chemistry Portal vilsmeier-reaction
RSC ontology ID RXNO:0000055

The Vilsmeier–Haack reaction (also called the Vilsmeier reaction) is the chemical reaction of a substituted formamide (1) with phosphorus oxychloride and an electron-rich arene (3) to produce an aryl aldehyde or ketone (5):

RC(=O)NR′R″ + HArZ + POCl3 + H2O → RC(=O)ArZ + NR′R″H + HCl + H3PO4

The reaction is named after Anton Vilsmeier and Albrecht Haack [de].

For example, benzanilide and dimethylaniline react with phosphorus oxychloride to produce an unsymmetrical diaryl ketone. Similarly, anthracene is formylated at the 9-position. The reaction of anthracene with N-methylformanilide, also using phosphorus oxychloride, gives 9-anthracenecarboxaldehyde:

N-Methylformanilide and anthracene and phosphorus oxychloride

In general, the electron-rich arene (3) must be much more active than benzene for the reaction to proceed; phenols or anilines are good substrates.

Reaction mechanism

The reaction of a substituted amide with phosphorus oxychloride gives a substituted chloroiminium ion (2), also called the Vilsmeier reagent. The initial product is an iminium ion (4b), which is hydrolyzed to the corresponding ketone or aldehyde during workup.

The Vilsmeier–Haack reaction

See also

Further reading

References

  1. ↑ Carey, Francis A.; Sundberg, Richard J. (2007). Advanced Organic Chemistry. Part B: Reactions and Synthesis (5th ed.). p. 1024. ISBN 978-0-387-44899-2.
  2. ↑ Vilsmeier, Anton; Haack, Albrecht (1927). "Über die Einwirkung von Halogenphosphor auf Alkyl-formanilide. Eine neue Methode zur Darstellung sekundärer und tertiärer p-Alkylamino-benzaldehyde" [On the reaction of phosphorus halides with alkyl formanilides. A new method for the preparation of secondary and tertiary p-alkylaminobenzaldehydes]. Berichte der Deutschen Chemischen Gesellschaft zu Berlin (in German). 60: 119–122. doi:10.1002/cber.19270600118.
  3. ↑ Meth-Cohn, O.; Stanforth, S. P. (1991). "The Vilsmeier–Haack Reaction (Review)". Compr. Org. Synth. 2: 777–794. doi:10.1016/B978-0-08-052349-1.00049-4.
  4. ↑ Campaigne, E.; Archer, W. L. "Formylation of dimethylaniline". Organic Syntheses. 33: 27. doi:10.15227/orgsyn.033.0027; Collected Volumes, vol. 4, p. 331.
  5. ↑ Hurd, C. D.; Webb, C. N. (1927). "Vilsmeyer–Haack reaction of benzanilide and dimethylaniline". Organic Syntheses. 7: 24. doi:10.15227/orgsyn.007.0024.
  6. ↑ Fieser, F. L.; Hartwell, J. L.; Jones, J. E.; Wood, J. H.; Bost, R. W. (1940). "Formylation of anthracene". Organic Syntheses. 20: 11. doi:10.15227/orgsyn.020.0011.
  7. ↑ Smith, Michael B. (2020). March's Organic Chemistry (8th ed.). Wiley. p. 664.
  8. ↑ Jones, G.; Stanforth, S. P. (2000). "The Vilsmeier Reaction of Non-Aromatic Compounds". Org. React. 56 (2): 355–686. doi:10.1002/0471264180.or056.02.