The Willgerodt-Kindler Reaction: mechanistic reality check 2.
Continuing an exploration of the mechanism of this reaction, an alternative new mechanism was suggested in 1989 (having been first submitted to the journal ten years earlier!).[cite]10.1002/jhet.5570260518[/cite] Here the key intermediate proposed is a thiirenium cation (labelled 8 in the article) and labelled Int3 below.
The model chosen is the same as before (B3LYP+GD3+BJ/Def2-TZVPP/Solvent=water) but now includes a specific base (ammonia) to help remove and add protons. Species 8 (Int3) sits in the middle of the rearrangement mechanism and can account for isomerisation in which (above) the Ph and H substituents of the starting ketone end up transposed. It also has the apparent merit that cations such as 8 are known as crystal structures[cite]10.1021/jo991731o[/cite],[cite]10.1002/anie.201307161[/cite]+ DOI: 10.5517/cc112bct,[cite]10.1002/anie.201307161[/cite]+DOI: 10.5517/cc112bfw. As you can see from the relative free energies (FAIR data at DOI: 10.14469/hpc/7336) that of Int3 is 50 kcal/mol higher than the reactant, and the transition state leading to it is even higher. So whereas species such as 8 (Int3) can exist (albeit substituted with sterically hindering groups), they probably play no actual role in the mechanism of this reaction.
The hunt continues for a mechanism for which the computed energies along the reaction path are ≤ 31 kcal/mol at 403K, which would correspond approximately to a half life of ~60 minutes.
The Willgerodt reaction[cite]10.1002/cber.18870200278[/cite], discovered in 1887 and shown below, represents a transformation with a once famously obscure mechanism. A major step in the elucidation of that mechanism came[cite]10.1021/ja01157a034[/cite] using the then new technique of 14C radio-labelling, shortly after the atom bomb projects during WWII made 14CO2 readily available to researchers.…
In 2013, I created an iTunesU library of 115 mechanistic types in organic and organometallic chemistry, illustrated using video animations of the intrinsic reaction coordinate (IRC) computed using a high level quantum mechanical procedure. Many of those examples first derived from posts here. That collection is still available and is viewable…
My previous dissection of the mechanism for ester hydrolysis dealt with the acyl-oxygen cleavage route (red bond). There is a much rarer[cite]10.1039/jr9550001522[/cite] alternative: alkyl-oxygen cleavage (green bond) which I now place under the microscope. Here, guanidine is used as a general acid/base, which results in a reasonable activation barrier for…
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