Vilsmeier–Haack reaction explained

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):

HArZ + POCl₃ + H₂O → RC(=O)ArZ + HCl + H₃PO₄The reaction is named after Anton Vilsmeier and .^{[1] [2]}

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:

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.^[3]

Used in

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

• Formylation reaction

Further reading

• Practical and Efficient Synthesis of Tris(4-formylphenyl)amine, a Key Building Block in Materials Chemistry. 2005. T.. Mallegol. S.. Gmouh. M.. Aït Amer Meziane. M.. Blanchard-Desce. O.. Mongin. Synthesis. 2005. 11. 1771–1774. 10.1055/s-2005-865336.
• Addition of Tethered Nonaromatic Carbon Nucleophiles to Chemoselectively Activated Amides. Bélanger. G.. Larouche-Gauthier. R.. Ménard. F.. Nantel. M.. Barabé. F.. Org. Lett.. 2005. 7. 20. 4431–4. 10.1021/ol0516519. 16178551. 11143/17289. free.
• A widely-recommended procedure:

Notes and References

1. Anton Vilsmeier. Vilsmeier. Anton. Haack. Albrecht. 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. 60. 1927. 119–122. 10.1002/cber.19270600118. de.
2. Meth-Cohn. O.. Stanforth. S. P.. The Vilsmeier–Haack Reaction (Review). Compr. Org. Synth.. 1991. 2. 777–794. 10.1016/B978-0-08-052349-1.00049-4.
3. The Vilsmeier Reaction of Non-Aromatic Compounds. G.. Jones. S. P.. Stanforth. Org. React.. 2000. 56. 2. 355–686. 10.1002/0471264180.or056.02.