Boekelheide reaction

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.^[1] 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.^[2]

Overall reaction of the Boekelheide reaction

Boekelheide reaction
Named after	Virgil Carl Boekelheide
Reaction type	Rearrangement reaction

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.

Mechanism of the Boekelheide reaction

Related reactions

2-Chloromethylpyridine can be prepared by treating 2-picoline-N-oxide with phosphoryl chloride or triphosgene.^[3][4]