Semibenzilic rearrangement

There is also a mechanism that can operate in the absence of an acidic a-hydrogen. This process, called the semibenzilic rearrangement, is closely related to the pinacol rearrangement. A tetrahedral intermediate is formed by nucleophilic addition to the carbonyl group and the halide serves as the leaving group. 

There is also a related mechanism that can operate in the absence of an acidic a. hydrogen, which is called the semibenzilic rearrangement. 

It has been found that the bromo ketones 10-7a-c can rearrange by either the cyclopropanone or the semibenzilic mechanism, depending on the size of the ring and the reaction conditions. Suggest two experiments that would permit you to distinguish between the two mechanisms under a given set of circumstances. 

Quantum mechanical/molecular mechanical study on the Favorskii rearrangement in aqueous media has been carried out.39 The results obtained by QM/MM methods show that, of the two accepted mechanisms for Favorskii rearrangement, the semibenzilic acid mechanism (a) is favored over the cyclopropanone mechanism (b) for the a-chlorocyclobutanone system (Scheme 6.2). However, the study of the ring-size effects reveals that the cyclopropanone mechanism is the energetically preferred reactive channel for the a-chlorocyclohexanone ring, probably due to the straining effects on bicycle cyclopropanone, an intermediate that does not appear on the semibenzilic acid pathway. These results provide new information on the key factors responsible for the behavior of reactant systems embedded in aqueous media. 

Semiempirical calculations on the Favorskii rearrangement of a-chlorocyclobutan-one to cyclopropenecarboxylic acid suggest that it proceeds via a stepwise semibenzilic acid pathway, both in solution and in vacuo, rather than by a cyclopropanone... 

The quasi-Favorskii rearrangement obviously cannot take place by the cyclopropanone mechanism. The mechanism that is generally accepted (called the semibenzilic mechanisml57)... 

Most other systems studied have bridgehead halogens, and special attention has been paid to the reactions of the kind shown in Scheme 35. The yields of rearrangement products are uniformly good, and deuterium incorporation results imply that the semibenzilic mechanism operates for the smaller ring... 

The related dihalo ketone (28) rearranges smoothly at 0 °C, whilst bromo ketone (29) requires prolonged heating at 155 C (Scheme 37). This is anticipated, since formation of the intermediate (30) required for the semibenzilic mechanism is sterically disfavored. 

Mechanism 2 (the semibenzilic acid mechanism) looks better, but labeling studies show that the two C atoms a to the ketone become equivalent in the course of the reaction, which is consistent only with mechanism 1 (the electrocyclic mechanism). The rearrangement of a-chloro-o-phenylacctonc to methyl hydrocinnamate is also consistent only with the electrocyclic mechanism if the semibenzilic mechanism were operative, then methyl 2-phenylpropionate would be the product. 

However, the rearrangement of a-chloroacetophenone to diphenylacetic acid must proceed by a semibenzilic acid mechanism, because a cyclopropane can t be formed. 

In order to distinguish between a mechanism proceeding via a symmetrical cyclopropanone intermediate (Favorskii reaction) and a mechanism closely related to the benzilic acid rearrangement and called semibenzilic (or quasi-Favorskii) rearrangement, the ring contraction of 2-bromocyclobutanone was studied in deuterium oxide using sodium carbonate as base (50 C) or in boiling deuterium oxide only. 

Problem 4.2. Draw both semibenzilic acid and Favorskii rearrangements for a-chloro-a-phenylacetone, and convince yourself that only the Favorskii rearrangement is consistent with the observed product. 

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