Acyloin Condensation-Name reaction
The acyloin condensation usually involves the reductive dimerization of a carboxylic ester, although acid chlorides and the anhydrides have been used. The reducing agent is in an alkali metal and the product is an ene-diolate. Two gram-atoms of metal are required for each mole of ester with the concomitant formation of a mole of akoxide and one-half mole of the ene-diolate. Oxidation of acyloins to diketoes can be accomplished by a variety of reagents. Acyloins can be reduced to ketones by various modifications of the Clemmenson technique. Under mild conditions the ketone will dominate. This chapter presents a complete picture of both the linear and cyclic acyloin condensation with particular emphasis on developments since 1960. The discussion is closely limited to the acyloin condensation and its modifications
Acyloin Condensation
Acyloin condensation is a reductive coupling of two carboxylic esters using metallic sodium to yield an α-hydroxyketone, also known as an acyloin
The bimolecular reductive coupling of carboxylic esters by reaction with metallic sodium in an inert solvent under reflux gives an α-hydroxyketone, which is known as an acyloin. This reaction is favoured when R is an alkyl. With longer alkyl chains, higher boiling solvents can be used. The intramolecular version of this reaction has been used extensively to close rings of different sizes, e.g. paracyclophanes or catenanes.
The reaction is carried out in the presence of a proton donor, such as alcohol, simple reduction of the ester to the alcohol takes place (Bouveault-Blanc Reduction).
The Benzoin Condensation produces similar products, although with aromatic substituents and under different conditions.
When the acyloin condensation is carried out in the presence of chlorotrimethylsilane, the enediolate intermediate is trapped as the bis-silyl derivative. This can be isolated and subsequently is hydrolysed under acidic condition to the acyloin, which gives a better overall yield.
Mechanism of Acyloin Condensation
The mechanism consists of four steps:
(1) Oxidative ionization of two sodium atoms on the double bond of two ester molecules.
(2) Free radical coupling between two molecules of the homolytic ester derivative (A Wurtz type coupling). Alkoxy-eliminations in both sides occur, producing a 1,2-diketone.
(3) Oxidative ionization of two sodium atoms on both diketone double bonds. The sodium enodiolate is formed.
(4) Neutralization with water to form the enodiol, which tautomerizes to acyloin
Rühlmann-method
The method according to Rühlmann employs trimethylchlorosilane as a trapping reagent; by this, competing reactions are efficiently subdued. Generally, yields increase considerably. The hydrolytic cleavage of the silylether gives the acyloin. To achieve a mild cleavage methanol can be used in several cases.
Usually toluene, dioxane, tetrahydrofuran or acyclic dialkylethers are employed as solvents. Advantageously also N-methyl-morpholine has been used. It allowed in some cases a successful reaction, in which otherwise the reaction failed in less polar media.
Related Reactions
Bouveault-Blanc Reduction
Synthesis of Acyloins
Books related to Acyloin Condensation
1.March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure
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2.Organic Syntheses Based on Name Reactions, Third Edition: a practical guide to 750 transformations
Organic Syntheses Based on Named Reactions is an indispensable reference companion for chemistry students and researchers. Building on Hassner & Stumer’s highly regarded 2e, this new work reviews 750 reactions, with over 100 new stereoselective and regioselective reactions. Each A-Z entry provides a carefully condensed summary of valuable information that a chemist needs to understand and utilize these fundamental reactions in their work, including brief practical details. The book is illustrated with real synthetic examples from the literature and about 3,400 references to the primary literature to aid further reading. Extensive indexes (name, reagent, reaction) and a very useful functional group transformation index help the reader fully navigate this extensive collection of important reactions. With its comprehensive coverage, superb organization and quality of presentation, this long-awaited new edition belongs on the shelf of every organic chemist.
3.Organic Syntheses Based on Name Reactions, Volume 22, Second Edition (Tetrahedron Organic Chemistry)
Since the publication of “Organic Syntheses Based on Name Reactions and Unnamed Reactions”(Volume 11 in the Tetrahedron Organic Chemistry series), there has been a proliferation of discoveries of name reactions in the field of organic chemistry. Hence, this, the second, revised, edition of the text has focused on the ongoing development in this area of research. The revised title reflects the notion whereby many new reagents and reactions are now being referred to by their names. The inclusion of over 155 new stereoselective and regioselective reagents or reactions including asymmetric syntheses, brings the total to over 540. Features that should be valuable to the reader include over 3000 references, a names index, reagent index, reaction index and a functional group transformation index. The latter of these indexes will allow the reader to search for conversions of one functional group to another and has proved a much utilized tool for the synthetic chemist, searching for pathways to perform synthetic procedures.
Sample reactions
1.This reaction is from the synthesis of Corannulene by Richard G. Lawton(Read more)
2.Acyloin Condensation
Similar to ester dimerisation, used traditionally to make large rings.
Now improved by addition of Me3SiCl which traps the intermediate dianion.
3.Acyloin Condensation examples (More)
Esters undergo a dimerization reduction reaction that is called an acyloin condensation. This name comes from the common name of the simplest reaction product, acyloin, which is an α-hydroxy
ketone. The initial product of the reaction is the disodium salt of an enediol. To form the acyloin product, the disodium salt hydrolyzes in aqueous acid.
The acyloin condensation is one of the best methods to use when synthesizing medium to large sized rings. The synthesis begins with the metal and solvent. Then the diester substrate is added very
slowly. This procedure allows the two ends of the substrate to find each other in an intramolecular reaction, while it suppresses any intermolecular reactions.
4.Preparation of cyclic acyloins
References
- Bouveault, L., and R. Loquin (1905). “Action du sodium sur les éthers des acides monobasiques à fonction simple de la série grasse”. Compt. Rend. 140: 1593–1595.
- Finley, K. T. (1964). “The Acyloin Condensation as a Cyclization Method”. Chemical Reviews 64 (5): 573–589. doi:10.1021/cr60231a004.
- Bloomfield, J. J.; Owsley, D. C.; Nelke, J. M. Org. React. 1976, 23.Acyloin condensation
- Rühlmann K. (1971). “Die Umsetzung von Carbonsäureestern mit Natrium in Gegenwart von Trimethylchlorsilan” [Reaction of carboxylic acid esters with sodium in the presence of trimethylchlorosilane Synthesis 1971
- Acyloin Ester Condensation(File PDF)
- Chemistry 144 Organic Synthesis M. E. Jung
APPLICATION
- Preparation of cyclic acyloins – This condensation has been used for preparation cyclic acyloins. Long chain dicarboxylic esters have been converted to large ring compounds without the use of dilution technique. It is used best for closing rings of ten members or more.
- Preparation of CATENANE – CATENANE is a very interesting & unique compound with interlocking rings. It is formed when acyloin condensation was employed for ring closure with esters of 34-carbon dicarboxylic acids.
