And the Claisen condensation

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. 

Deprotonation of the /3-keto ester provides a driving force for the Claisen condensation. The deprotonation is strongly exothermic, making the overall reaction exothermic and driving the reaction to completion. Because the base is consumed in the deprotonation step, a full equivalent of base must be used, and the Claisen condensation is said to be base-promoted rather than base-catalyzed. After the reaction is complete, addition of dilute acid converts the enolate back to the /3-keto ester. 

The 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 aldehvde or ketone and the Claisen condensation of... 

Next, we shall turn to reactions in which the carbonyl group plays both its roles the aldol condensation, in which a carbanion generated from one molecule of aldehyde or ketone adds, as a nucleophile, to the carbonyl group of a second molecule and the Claisen condensation, in which a carbanion generated from one molecule of ester attacks the carbonyl group of a second molecule, with acyl substitution as the final result. 

Ester Enolates and the Claisen Condensation Synthesis of p-Dicarbonyl Compounds Acyl Anion Equivalents... 

As a nucleophile, a carbanion can react readily with a carbon atom bearing a good leaving group, which is a useful method for forming new carbon-carbon bonds. The aldol reaction and the Claisen condensation are familiar examples of carbanions (tis enolates) undergoing nucleophilic addition to carbon-oxygen double bonds. Carbanions may also act as nucleophiles in Sn2 reactions. The reaction of phenylacetic acid (90) with sodium in liquid ammonia leads to a carbanion (91) that reacts with benzyl chloride to produce 23-diphenylpropionic acid (92, equation 5.66). ... 

Nicotellin (Xn-141), a tobacco alkaloid, has been synthesized from XII-138 and the Claisen condensation product of nicotinaldehyde and 3-acetylpyridine. ... 

So far, both mechanisms are almost identical. The only difference is the choice of base (the aldol condensation uses hydroxide, and the Claisen condensation uses an alkoxide), and we will discuss... 

ESTER ENOLATES AND THE CLAISEN CONDENSATION Synthesis of/3-Dicarbonyl Gompounds Acyl Anion Equivalents 1039... 

Some of the steps in the mechanism of the Claisen condensation resemble those of the aldol condensation. For example, both mechanisms have several reversible steps. However, there are important differences. Several equilibria in the Claisen condensation are not favorable. The entire sequence becomes favorable only in the final step in an acid-base reaction. And, the Claisen condensation requires a molar equivalent of base. 

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