The alpha-carbons of ketones, esters, and other related molecules are orders of magnitude more acidic than the C-H bonds of alkanes since the resulting negative charge on carbon can be delocalized to oxygen via resonance. The pKa of the alpha-carbon of esters are about 25, which makes them about 10 6 to 10 7 less acidic than ketones pKa about When treated with a strong base like NaOCH 3 , deprotonation of the alpha carbon can occur, resulting in its enolate.
Even though the equilibrium favors the starting material vs. The alkoxide base RO- is usually chosen to match the ester -OR group.
Why do you think that might be? The enolate carbon will attack the best electrophile present, which happens to be the carbonyl carbon of another equivalent of ester. As the nucleophile forms a new bond with the carbonyl carbon, the carbon-oxygen pi bond breaks, producing a tetrahedral intermediate.
There is an equilibrium between the tetrahedral intermediate and the starting materials i. Now we come to the second-most important reaction of the carbonyl functional group: elimination or, alternatively, 1,2-elimination. The negative charge in the oxygen of the tetrahedral intermediate can re-form the C-O pi bond , and in so doing break the C—O sigma bond. The result is a new ketone and an alkoxide RO — leaving group:.
This punch of addition-elimination is a characteristic reaction of acyl groups RC O — and we will see it again and again and again.
Having shown how nucleophilic acyl substitution occurs in the Claisen, our reaction mechanism is nearly complete. However, there is still one pesky loose end to tie up. It so happens that the product of the Claisen, the beta-keto ester, is a considerably stronger acid pKa 11 than the conjugate acid of RO - , ROH pK a That means that the alkoxide base will easily deprotonate the resulting beta-keto ester, giving a new enolate — that of the beta-keto ester.
Why is the beta-keto ester pKa 11 so acidic? Note that the negative charge on carbon can now be delocalized through carbon to two different oxygens, which are more electronegative and better able to stabilize negative charge:. Once formed, the equilibrium going back to starting materials is so unfavorable that the enolate just sits around in the reaction flask, not undergoing any significant reaction.
Just as all rivers run to the sea, in the Claisen condensation, all our ester starting material eventually converts to the enolate of the beta-keto ester. This is why that in order for the reaction to proceed, we must use at least one full equivalent of base. Having nothing to do once formed, the enolate of the beta keto ester just sits around in the reaction flask until mild acid is added to quench the reaction.
Combining two identical esters is nice, but what would be even better is to join together two different esters. This simplifies things considerably, since only one enolate nucleophile can be formed. We can improve the chances of a crossed Claisen even more by adding an excess of the non-enolizable ester. In this reaction, five and six-membered rings form due to the steric stability.
For example, 1,6-diesters can form five-membered beta-keto ester rings while 1,7-diesters form six-membered beta-keto ester rings. Therefore, the key difference between Claisen and Dieckmann condensation is that Claisen condensation reaction is a type of coupling reaction, whereas Dieckmann condensation reaction is a type of ring formation reaction. Below infographic lists more details of the difference between Claisen and Dieckmann condensation.
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Your email address will not be published. Figure Chemical Equation for Claisen Condensation. Figure Dieckmann Condensation Reaction. Leave a Reply Cancel reply Your email address will not be published. Dieckmann Condensation A diester can undergo an intramolecular reaction called a Dieckmann condensation. Example 2: Dieckman Condensation.
Crossed Claisen Condensation Claisen condensations between different ester reactants are called Crossed Claisen reactions. Example 3: Crossed Claisen Condensation.
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