View source for Vilsmeier–Haack reaction

{{Short description|Chemical reaction}}
{{Use dmy dates|date=July 2023}}
{{Reactionbox
| Name = Vilsmeier–Haack reaction
| Type = Substitution reaction
| NamedAfter = [[Anton Vilsmeier]] <br/> 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 [[activating group|electron-rich]] [[arene]] ('''3''') to produce an [[aryl]] [[aldehyde]] or [[ketone]] ('''5'''): 
:{{awrap|RC({{=}}O)NR{{prime}}R{{pprime}} +}} HArZ&nbsp;+ POCl<sub>3</sub>&nbsp;+ H<sub>2</sub>O&nbsp;→ RC(=O)ArZ&nbsp;+ {{awrap|NR{{prime}}R{{pprime}}H +}} HCl&nbsp;+ H<sub>3</sub>PO<sub>4</sub>
The reaction is named after [[Anton Vilsmeier]] and {{interlanguage link|Albrecht Haack|de}}.<ref>{{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}}</ref><ref>{{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}}</ref><ref>{{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}}</ref>

For example, [[benzanilide]] and [[dimethylaniline]] react with [[phosphorus oxychloride]] to produce an unsymmetrical diaryl ketone.<ref>{{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}}</ref> Similarly, [[anthracene]] is formylated at the 9-position.<ref>{{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}}</ref> The reaction of anthracene with ''N''-methylformanilide, also using phosphorus oxychloride, gives [[9-Anthracenecarboxaldehyde|9-anthracenecarboxaldehyde]]:

:[[Image:Vilsmeier reaction example2.svg|thumb|650px|none|''N''-Methylformanilide and anthracene and phosphorus oxychloride]]

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.<ref>{{cite book|page=664|title=March's Organic Chemistry|edition=8th|first1=Michael&nbsp;B.|last1=Smith|publisher=Wiley|year=2020}}</ref>

== 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 [[hydrolyze]]d to the corresponding [[ketone]] or [[aldehyde]] during [[workup (chemistry)|workup]].<ref>{{cite journal|title = The Vilsmeier Reaction of Non-Aromatic Compounds|first1 = G.|last1 = Jones|first2 = S. P.|last2 = Stanforth|journal = [[Org. React.]]|year = 2000|volume = 56|issue = 2|pages = 355–686|doi = 10.1002/0471264180.or056.02}}</ref>
:[[Image:Vilsmeier Haack Reaction Scheme.png|thumb|none|650px|The Vilsmeier–Haack reaction]]

==See also==
* [[Formylation reaction]]

==Further reading==
*{{cite journal|title=Practical and Efficient Synthesis of Tris(4-formylphenyl)amine, a Key Building Block in Materials Chemistry|date=2005|first1=T.|last1=Mallegol|first2=S.|last2=Gmouh|first3=M.|last3=Aït Amer Meziane|first4=M.|last4=Blanchard-Desce|first5=O.|last5=Mongin|journal=Synthesis|volume=2005|issue=11|pages=1771–1774|doi=10.1055/s-2005-865336}}
*{{cite journal|title=Addition of Tethered Nonaromatic Carbon Nucleophiles to Chemoselectively Activated Amides|last1=Bélanger|first1=G.|last2=Larouche-Gauthier|first2=R.|last3=Ménard|first3=F.|last4=Nantel|first4=M.|last5=Barabé|first5=F.|journal=[[Org. Lett.]]|date=2005|volume=7|issue=20|pages=4431–4|doi=10.1021/ol0516519|pmid=16178551|hdl=11143/17289|hdl-access=free}}
* A widely-recommended procedure: {{doi|10.1055/sos-SD-213-00191}}

== References ==
{{reflist}}

{{DEFAULTSORT:Vilsmeier-Haack reaction}}
[[Category:Addition reactions]]
[[Category:Name reactions]]
[[Category:Formylation reactions]]