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. 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:
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.
See also Formylation reaction
Further reading 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. A widely-recommended procedure: doi:10.1055/sos-SD-213-00191
References