Acyloin Condensation

Acyloin Condensation is a coupling reaction in which two carboxylic acid esters couple in the presence of metallic sodium under inert atmosphere to yield an α-hydroxyketone (also known as acyloin).

This reaction is favoured when R is an long chain alkyl group and also when high boiling solvents are used. Intramolecular condensation also takes place leading to closed rings of different sizes (like paracyclophanes or catenanes). But again this all depends on ring size and steric properties, but independent from high dilution. Intramolecular cyclisation over intermolecular polymerisation in diesters.

If the condensation is carried out in the presence of proton donor like alcohol then reduction of ester to alcohol takes place. This reaction is also called as Bouveault-Blanc Reduction.

Mechanism of Acyloin Condensation

Above mechanism involves

(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 Würtz 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.

The enediolate intermediate is trapped as the bis-silyl derivative by the use of trapping agent chlorotrimethylsilane. This intermediate can be isolated and subsequently hydrolysed under acidic condition to the acyloin, which gives a better overall yield. Toluene, dioxane, THF or dialkylethers may be used and in some cases NMP (I am not sure of this) may also be used.

Literature references:

(1) Acyloin condensation in which chlorotrimethylsilane is used as a trapping agent
     Organic Syntheses, Coll. Vol. 6, p.167 (1988); Vol. 57, p.1 (1977).

(2) The Acyloin Condensation of Aralkyl Esters
      J. Am. Chem. Soc., 1952, 74 (19), pp 4861–4864

(3) The Formation of Five- and Six-membered Rings by the Acyloin Condensation.
      J. Am. Chem. Soc., 1957, 79 (22), pp 6050–6055

(4) Mechanism of the acyloin condensation
     J. Org. Chem., 1975, 40 (4), pp 393–402