I have blogged before about the mechanism of this classical oxidation reaction. Here I further explore computed models, and whether they match the observed kinetic isotope effects (KIE) obtained using the natural-abundance method described in the previous post. There is much previous study of this rearrangement, and the issue can be reduced to deciding whether TS1 or TS2 is rate-limiting.

A reader asked me about the mechanism of the reaction of 2-picoline N-oxide with acetic anhydride to give 2-acetoxymethylpyridine (the Boekelheide Rearrangement[cite]10.1002/ejoc.201000936[/cite]). He wrote “ I don’t understand why the system should prefer to go via fragmentation-recombination (… the evidence being that oxygen labelling shows scrambling) when there is an easy concerted pathway available (… a

Thalidomide is a chiral molecule, which was sold in the 1960s as a sedative in its (S,R)-racemic form. The tragedy was that the (S)-isomer was tetragenic, and only the (R) enantiomer acts as a sedative. What was not appreciated at the time is that interconversion of the (S)- and (R) forms takes place quite quickly in aqueous media.