Mechanism Claisen ester condensation

The mechanism of the Claisen Ester condensation has been suggested along the following lines ... 

Mechanism of the Claisen ester condensation. Test yourself on the concepts in this figure at OrganicChemistryNow. 

Ester Condensations Active Figure 20.4 Mechanism of the Claisen Ester Condensation (page 882)... 

Key Mechanism 22-12 The Claisen Ester Condensation 1071 22-13 The Dieckmann Condensation A Claisen Cyclization 1074 22-14 Crossed Claisen Condensations 1074 22-15 Syntheses Using /3-Dicarbonyl Compounds 1077 22-16 The Malonic Ester Synthesis 1079 22-17 The Acetoacetic Ester Synthesis 1082 22-18 Conjugate Additions The Michael Reaction 1085 Mechanism 22-13 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085... 

The reactions use thiol esters rather than ordinary esters. The esterifying group is a thiol called coenzyme A, and we shall just represent this molecule as R (you can find its full structure on p. 1386). The first reaction is between a malonate half-thioester and an acetate thioester of coenzyme A Look at the mechanism and you will see how similar it is to the Claisen ester condensation. 

So far the mechanism is almost the same as that of the Robinson annelation but the cyclization is now the attack of a ketone enolate on an ester group (it doesn t matter which one as they are equivalent) and so it is an intramolecular Claisen ester condensation (Chapter 28). The intermediate must be redrawn to allow cyclization. 

The mechanism of the reaction between aromatic aldehydes and esters probably involves the intermediate formation of an aldol (hence the name— Claisen aldol condensation) ... 

In all the acetyl coenzyme-A-utilising enzymes which catalyse Claisen-type condensations the reaction involves the conversion of the acetyl methyl into a methylene group. A simple example illustrates the use of thiol esters both as carbanion-stabilis-ing systems and as readily hydrolysable esters. The conversion of glyoxalate to malate uses acetyl coenzyme. A probable mechanism is outlined below ... 

Clearly, the nex.t step will be to investigate the physicochemical effects, such as charge distribution and inductive and resonance effects, at the reaction center to obtain a deeper insight into the mechanisms of these biochemical reactions and the finer details of similar reactions. Here, it should be emphasized that biochemical reactions arc ruled and driven basically by the same effects as organic reactions. Figure 10.3-22 compares the Claisen condensation of acetic esters to acctoacctic esters with the analogous biochemical reaction in the human body. 

Tire mechanism of the Claisen condensation is similar to that of the aldol condensation and involves the nucleophilic addition of an ester enolate ion to the carbonyl group of a second ester molecule. The only difference between the aldol condensation of an aldeiwde or ketone and the Claisen condensation of an ester involves the fate of the initially formed tetrahedral intermediate. The tetrahedral intermediate in the aldol reaction is protonated to give an alcohol product—exactly the behavior previously seen for aldehydes and ketones (Section 19.4). The tetrahedral intermediate in the Claisen reaction, however, expels an alkoxide leaving group to yield an acyl substitution product—exactly the behavior previously seen for esters (Section 21.6). The mechanism of the Claisen condensation reaction is shown in Figure 23.5. 

The mechanism of the Dieckmann cyclization, shown in Figure 23.6, is the same as that of the Claisen condensation. One of the two ester groups is converted into an enolate ion, which then carries out a nucleophilic acyl substitution on the second ester group at the other end of the molecule. A cyclic /3-keto ester product results. 

An important group of acylation reactions involves esters, in which case the leaving group is alkoxy or aryloxy. The self-condensation of esters is known as the Claisen condensation.216 Ethyl acetoacetate, for example, is prepared by Claisen condensation of ethyl acetate. All of the steps in the mechanism are reversible, and a full equivalent of base is needed to bring the reaction to completion. Ethyl acetoacetate is more acidic than any of the other species present and is converted to its conjugate base in the final step. The (3-ketoester product is obtained after neutralization. 

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