Vilsmeier–Haack reaction

{{Short description|Chemical reaction}}

{{Use dmy dates|date=July 2023}}

{{Reactionbox

| Name = Vilsmeier–Haack reaction

| Type = Substitution reaction

| NamedAfter = Anton Vilsmeier
Albrecht Haack

| Section3 = {{Reactionbox Identifiers

| OrganicChemistryNamed = vilsmeier-reaction

| RSC_ontology_id = 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):

:{{awrap|RC({{=}}O)NR{{prime}}R{{pprime}} +}} HArZ + POCl₃ + H₂O → RC(=O)ArZ + {{awrap|NR{{prime}}R{{pprime}}H +}} HCl + H₃PO₄

The reaction is named after Anton Vilsmeier and {{interlanguage link|Albrecht Haack|de}}.{{cite journal|authorlink=Anton Vilsmeier|last1=Vilsmeier|first1=Anton|last2=Haack|first2=Albrecht|title=Über die Einwirkung von Halogenphosphor auf Alkyl-formanilide. Eine neue Methode zur Darstellung sekundärer und tertiärer p-Alkylamino-benzaldehyde|trans-title=On the reaction of phosphorus halides with alkyl formanilides. A new method for the preparation of secondary and tertiary p-alkylaminobenzaldehydes|journal=Berichte der Deutschen Chemischen Gesellschaft zu Berlin|volume=60|date=1927|pages=119–122|doi=10.1002/cber.19270600118|language=de}}{{cite journal|last1=Meth-Cohn|first1=O.|last2=Stanforth|first2=S. P.|title=The Vilsmeier–Haack Reaction (Review)|journal=Compr. Org. Synth.|date=1991|volume=2|pages=777–794|doi=10.1016/B978-0-08-052349-1.00049-4}}{{orgSynth|prep=cv4p0331|title=Formylation of dimethylaniline|last1=Campaigne|first1=E.|last2=Archer|first2=W. L.|collvol=4|collvolpages=331|volume=33|page=27|date=1953|doi=10.15227/orgsyn.033.0027}}

For example, benzanilide and dimethylaniline react with phosphorus oxychloride to produce an unsymmetrical diaryl ketone.{{orgSynth|title=Vilsmeyer–Haack reaction of benzanilide and dimethylaniline|last1=Hurd|first1=C. D.|last2=Webb|first2=C. N.|volume=7|page=24|year=1927|doi=10.15227/orgsyn.007.0024}} Similarly, anthracene is formylated at the 9-position.{{orgSynth|title=Formylation of anthracene|last1=Fieser|first1=F. L.|last2=Hartwell|first2=J. L.|last3=Jones|first3=J. E.|last4=Wood|first4=J. H.|last5=Bost|first5=R. W.|volume=20|page=11|year=1940|doi=10.15227/orgsyn.020.0011}} The reaction of anthracene with N-methylformanilide, also using phosphorus oxychloride, gives 9-anthracenecarboxaldehyde:

:Image:Vilsmeier reaction example2.svg

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.{{cite book|page=664|title=March's Organic Chemistry|edition=8th|first1=Michael B.|last1=Smith|publisher=Wiley|year=2020}}