- Vilsmeier-Haack reaction
The Vilsmeier-Haack reaction (also called the Vilsmeier reaction) is the
chemical reaction of a substitutedamide (1) withphosphorus oxychloride and an activatedarene (3) to produce anaryl aldehyde orketone (5).Ref|Vilsmeier1927Ref|Meth-Cohn1991Ref|Campaigne1953 The reaction of a substituted amide with phosphorus oxychloride gives a substituted chloroiminium ion (2), also called the Vilsmeier reagent. The initial product is animinium ion (4b), which ishydrolyze d to the correspondingaromatic ketone oraldehyde .For example, benzanilide and dimethylaniline react with phosphorus oxychloride to produce an unsymmetrical diaryl ketone.Ref|3 Similarly,
anthracene can be formylated exclusively at the 9-position.Ref|4Reaction mechanism
The reaction of the amide with phosphorus oxychloride produces an electrophilic
iminium cation . The subsequentelectrophilic aromatic substitution produces an iminium ion intermediate, which ishydrolyze d to give the desired aryl ketone or aryl aldehyde.Applications
One recent application of this reaction involved a new synthetic route to tris(4-formylphenyl)amine Ref|5 from triphenylamine which by known procedures only resulted in a modest
chemical yield of 16%. It was found that this low yield was caused by deactivation of the remaining benzene ring by the imine groups on the other two phenyl groups in the third formylation step. The procedure was modified by taking the reaction to di-imine compound followed by hydrolysis to the di-formyl compound and then (with final position reactived) a separate formylation to the tri substituted compound.References
*
Anton Vilsmeier ; Haack, A. "Ber. " 1927, "60", 119.
* Meth-Cohn, O.; Stanforth, S. P. "Comp. Org. Syn." 1991, "2", 777-794. (Review)
* "Formylation ofdimethylaniline ." Campaigne, E.; Archer, W. L. "Org. Syn. ", Coll. Vol. 4, p.331 (1963); Vol. 33, p.27 (1953). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0331 Article] )
* "Vilsmeyer-Haack reaction ofbenzanilide anddimethylaniline ." Hurd, C. D.; Webb. C. N. "Org. Syn. ", Coll. Vol. 1, p.217 (1941); Vol. 7, p.24 (1927). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv1p0217 Article] )
* "Formylation ofanthracene ." Fieser, F. L.; Hartwell, J. L.; Jones, J. E.; Wood, J. H.; Bost, R. W. "Org. Syn. ", Coll. Vol. 3, p.98 (1955); Vol. 20, p.11 (1940). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv3p0098 Article] )
* "Practical and Efficient Synthesis of Tris(4-formylphenyl)amine, a Key Building Block in Materials Chemistry" Thomas Mallegol, Said Gmouh, Mohamed Aït Amer Meziane, Mireille Blanchard-Desce, Olivier Mongin "Synthesis" 2005, 1771-1774. (DOI|10.1055/s-2005-865336)ee also
*
Formylation reaction
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