Semibenzilic acid mechanism

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. 

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. 

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. 

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. 

The unsymmetrical mechanism is also called the semibenzilic mechanism. Generally, a weakly acidic hydrogen is present a to the carbonyl. When there is no such a -hydrogen, the reaction is called a quasi-Favorskii, and involves the same type of mechanism. The geometry which is necessary for this process to occur is the same in both the acyclic and cyclic series. Obviously in the latter case the reactivity will be directly related to the halogen stereochemistry. Ring strain will also play an important role and will often be the decisive factor in determining which of the semibenzilic and the cyclopropanone mechanisms obtain. 

Several structural requirements appear to be necessary in order to be able to observe the semibenzilic mechanism. Thus the acidity of the a hydrogen plays an important role. Indeed, it should be weakly acid in order to favor nucleophilic attack at the carbonyl carbon. Of course, this kind of mechanism will be facilitated by the absence of an a hydrogen the rearrangement is then known under the name of quasi-Favorskii. Since both substrates just discussed react via the semibenzilic mechanism, we shall discuss them simultaneously. 

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