Boekelheide reaction
{{Short description|Reaction in Organic Chemistry}}
{{Reactionbox
| Name = Boekelheide reaction
| Type = Rearrangement reaction
| NamedAfter = Virgil Carl Boekelheide
}}
The Boekelheide reaction is a rearrangement of α-picoline-N-oxides to hydroxymethylpyridines. It is named after Virgil Boekelheide who first reported it in 1954.{{cite journal|last1=Boekelheide|first1=V.|last2=Linn|first2=W. J.|title=Rearrangements of N-Oxides. A Novel Synthesis of Pyridyl Carbinols and Aldehydes|journal=Journal of the American Chemical Society|date=March 1954|volume=76|issue=5|pages=1286–1291|doi=10.1021/ja01634a026}} Originally the reaction was carried out using acetic anhydride, which typically required a period at reflux (~140 °C). The reaction can be performed using trifluoroacetic anhydride (TFAA), which often allows for a room temperature reaction.{{cite journal|last1=Fontenas|first1=C.|last2=Bejan|first2=E.|last3=Haddou|first3=H. Aït|last4=Balavoine|first4=G. G. A.|title=The Boekelheide Reaction: Trifluoroacetic Anhydride as a Convenient Acylating Agent|journal=Synthetic Communications|date=23 September 2006|volume=25|issue=5|pages=629–633|doi=10.1080/00397919508011399}}
Mechanism
The mechanism of the Boekelheide reaction begins by an acyl transfer from the trifluoroacetic anhydride to the N-oxide oxygen. The α-methyl carbon is then deprotonated by the trifluoroacetate anion. This sets the molecule up for a [3.3]-sigmatropic rearrangement which furnishes the trifluoroacetylated methylpyridine. Hydrolysis of the trifluoroacetate releases the hydroxymethylpyridine.
Related reactions
2-Chloromethylpyridine can be prepared by treating 2-picoline-N-oxide with phosphoryl chloride or triphosgene.{{cite journal |doi=10.1002/jhet.5570180518 |title=The Synthesis of 2-Chloromethylpyridine from 2-Picoline-N-Oxide |date=1981 |last1=Ash |first1=Mary Lynne |last2=Pews |first2=R. Garth |journal=Journal of Heterocyclic Chemistry |volume=18 |issue=5 |pages=939–940 }}{{cite journal |doi=10.1081/SCC-120028642 |title=Facile and Selective Synthesis of Chloromethylpyridines and Chloropyridines Using Diphosgene/Triphosgene |date=2004 |last1=Narendar |first1=P. |last2=Gangadasu |first2=B. |last3=Ramesh |first3=Ch. |last4=China Raju |first4=B. |last5=Jayathirtha Rao |first5=V. |journal=Synthetic Communications |volume=34 |issue=6 |pages=1097–1103 }}
{{Commons category|Boekelheide reaction}}