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):
| Vilsmeier–Haack reaction | |
|---|---|
| Named after | Anton Vilsmeier Albrecht Haack |
| Reaction type | Substitution reaction |
| Identifiers | |
| Organic Chemistry Portal | vilsmeier-reaction |
| RSC ontology ID | RXNO:0000055 |
- 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.[1][2][3]
For example, benzanilide and dimethylaniline react with phosphorus oxychloride to produce an unsymmetrical diaryl ketone.[4] Similarly, anthracene is formylated at the 9-position.[5] The reaction of anthracene with N-methylformanilide, also using phosphorus oxychloride, gives 9-anthracenecarboxaldehyde:
N-Methylformanilide and anthracene and phosphorus oxychloride
Reaction mechanism edit
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.[6]
The Vilsmeier–Haack reaction
Procedure edit
Used in edit
The Vilsmeier-Haack reaction is widely used in organic chemistry for the synthesis of various compounds and is particularly useful for introducing carbonyl groups into aromatic compounds.
See also edit
Further reading edit
- Mallegol, T.; Gmouh, S.; Aït Amer Meziane, M.; Blanchard-Desce, M.; Mongin, O. (2005). "Practical and Efficient Synthesis of Tris(4-formylphenyl)amine, a Key Building Block in Materials Chemistry". Synthesis. 2005 (11): 1771–1774. doi:10.1055/s-2005-865336.
- Bélanger, G.; Larouche-Gauthier, R.; Ménard, F.; Nantel, M.; Barabé, F. (2005). "Addition of Tethered Nonaromatic Carbon Nucleophiles to Chemoselectively Activated Amides". Org. Lett. 7 (20): 4431–4. doi:10.1021/ol0516519. hdl:11143/17289. PMID 16178551.
References edit
- ^ 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.
- ^ 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.
- ^ Campaigne, E.; Archer, W. L. "Formylation of dimethylaniline". Organic Syntheses. 33: 27. doi:10.15227/orgsyn.033.0027; Collected Volumes, vol. 4, p. 331.
- ^ Hurd, C. D.; Webb, C. N. (1927). "Vilsmeyer–Haack reaction of benzanilide and dimethylaniline". Organic Syntheses. 7: 24. doi:10.15227/orgsyn.007.0024.
- ^ 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.
- ^ 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.
- ^ doi.org/10.1055/sos-SD-213-00191