Benzilic acid rearrangement
From Wikipedia, the free encyclopedia
The benzilic acid rearrangement is the rearrangement reaction of benzil with potassium hydroxide to benzilic acid. First performed by Justus Liebig in 1838 this reaction type is displayed by 1,2-diketones in general. The reaction product is an α-hydroxy-carboxylic acid.
Certain acyloins also rearrange in this fashion.
This diketone reaction is related to other rearrangements: the corresponding keto-aldehyde (one alkyl group replaced by hydrogen) rearranges in a Cannizzaro reaction, the corresponding 1,2-diol reacts in a pinacol rearrangement.
[edit] Reaction mechanism
The reaction is a representative of 1,2-rearrangements. These rearrangements usually have migrating carbocations but this reaction is unusual because it involves a migrating carbanion. The long established reaction mechanism updated with in silico data is outlined in scheme 2.
A hydroxide anion attacks one of the ketone groups in 1 in a nucleophilic addition to the hydroxyl anion 2. The next step requires a bond rotation to conformer 3 which places the migrating group R in position for attack on the second carbonyl group in a concerted step with reversion of the hydroxyl group back to the carbonyl group. This sequence resembles a nucleophilic acyl substitution. Calculations show that when R is methyl the charge build-up on this group in the transition state can be as high as 0.22 and that the methyl group is positioned between the central carbon carbon at a separation of 209 pm.
The carboxylic acid in intermediate 4 is less basic than the hydroxyl anion and therefore proton transfer takes place to intermediate 5 which can be protonated in acidic workup to the final α-hydroxy-carboxylic acid 6. Calculations show that an accurate description of the reaction sequence is possible with the participation of 4 water molecules taking responsibility for the stabilization of charge buildup. They also provide a shuttle for the efficient transfer of one proton in the formation of intermediate 5.
From a molecular orbital point of view this rearrangement may at a first glance not obvious. Contrary to a carbocationic rearrangement as in the Wagner-Meerwein rearrangement in which the empty carbocationic orbital interacts positively and symmetry allowed with the filled pi orbital HOMO of the central C-C bond (situation A in scheme 3), a filled carbanionic orbital should not be able to escape a symmetry forbidden MO overlap with the LUMO which is the empty antibonding pi orbital having one node (situation B).
In reality a 1,2-diketone LUMO is a 4 electron system without any nodes in the central C-C bond and a symmetry allowed transition is possible (Situation C). In other words the transition states of both a carbocationic rearrangement and the benzilic rearrangement obey the Woodward-Hoffmann rules because the involves respectively 2 electrons and 6 electrons (n=0 and 1 in the 4n+2 Hückel's rule).
[edit] External links
- Lab procedure I
- Lab procedure II
- Lab procedure III
- Benzilic acid from benzoin, sodium bromate and sodium hydroxide, Organic Syntheses, Coll. Vol. 1, p.89 (1941); Vol. 1, p.29 (1921) Link
[edit] References
- ↑ Liebig, J. Justus Liebigs Ann. Chem. 1838, 25, 27.
- ↑ A FMO-Controlled Reaction Path in the Benzil-Benzilic Acid Rearrangement Shinichi Yamabe, Noriko Tsuchida, and Shoko Yamazaki J. Org. Chem.; 2006; 71(5) pp 1777 - 1783 Abstract
