Dieckmann condensation

Theory and Defination :

The Dieckmann condensation is an organic reaction used to form a carbon-carbon bond between two tethered ester groups using an alkoxide base in alcohol to make a cyclic β-keto ester. This reaction is essentially an intramolecular form of the Claisen condensation.
One ester group of the starting material must have an α-hydrogen which is abstracted by the base to form an enolate and alcohol. The enolate then attacks the carbonyl carbon of another ester molecule, an OR group is released to regenerate the base, and the final β-keto ester product is formed. The product in base is then deprotonated again to form another enolate intermediate and acid-workup is required to isolate the final cyclic β-keto ester product.

General Reaction :

 

Mechanism :

 The mechanism is similar to the Claisen Condensation

Examples and Application :

 

 1) Synthesis of Tetronic Acids from Esters

 

2) Synthesis of 4,4-Disubstituted Cyclohexane β-Keto Esters

  

 

 

 

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Claisen Condensation

Theory and Defination :

When treated with a strong base such as sodium ethoxide, two molecules of a carboxylic ester with two α hydrogen combine to give a β-keto ester in a reaction called the Claisen condensation.

It seen that Claisen condensation of esters is very similar to aldol condensation .The enolate form of one ester molecule carries out nucleophilic attack on the carbonyl carbon of another ester molecule.
How Claisen condensation differs from aldol condensation illustrates a general difference in the reactivity of esters vs. aldehyde and ketone.
In Claisen condensation, the enolate form of one ester molecule approaches another, similarly to aldol condensation, but, in this case, the tetrahedral intermediate resolves itself along an acyl substitution pathway. Both the aldol and Claisen condensations begin with an α-substitution, but in aldol condensation the overall pathway corresponds to nucleophilic addition, while Claisen condensation resolves itself in the manner of an acyl substitution reaction with sp2-hybridization returning with the departure of the leaving group.

General Reaction with illustration :

The most commonly used strong base in organic reactions, hydroxide ion, is not suitable for Claisen condensation because it could cause saponification of the ester. The base of choice in Claisen condensation is the alkoxide ion corresponding to the alkoxy group in the ester. Other alkoxides could cause trans-esterification of the ester. Since the β-ketoester formed in Claisen condensation is converted to the corresponding enolate ion by the base, in order to isolate the β-ketoester, when the reaction is complete, the reaction mixture needs to be acidified.

Mechanism:

 

Step 1: The alkoxide ion deprotonates the enolizable ester reversibly.

 

Step 2 and 3: Enolate ion 1 undergoes a nucleophilic acyl substitution with the unreacted ester to give the β-ketoester.



Step 4: The alkoxide ion deprotonates the β-ketoester irreversibly.


Step 5: The acid protonates enolate ion 2.

 Example and Application :

 

1)an intra molecular rearrangement

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Acetoacetic-Ester Condensation

Theory and defination :

 Acetoacetic-Ester Condensation is a chemical reaction where ethyl acetoacetate is alkylated at the α-carbon to both carbonyl groups and then converted into a ketone, or more specifically an α-substituted acetone. This is very similar to malonic ester synthesis. 

 

Acetoacetic ester synthesis is a synthetic procedure used to convert a compound that has the general structural formula 1 into a ketone that has the general structural formula 2.

 R¹ = alkyl  L = leaving group

 

The group —CH₂COCH₃ in 2 is contributed by an acetoacetic ester, hence the term acetoacetic ester synthesis.

 R² = alkyl, aryl

Acetoacetic ester synthesis consists of four consecutive reactions that can be carried out in the same pot.

reaction 1: acid-base reaction
reaction 2: nucleophilic substitution
reaction 3: ester hydrolysis (using saponification)
reaction 4: decarboxylation

Examples are : 

 

 reaction 1:        

 reaction 2:       

reaction 3:            




reaction 4:        

A more direct method to convert 3 to 4 is the reaction of 3 with the enolate ion (5) of acetone.

 

However, the generation of 5 from acetone quantitatively in high yield is not an easy task because the reaction requires a very strong base, such as LDA, and must be carried out at very low temperature under strictly anhydrous conditions.

  

Acetoacetic ester synthesis provides a more convenient alternative to convert 3 to 4.

Acetoacetic ester synthesis can be adapted to synthesize compounds that have the general structural formula 6.

R³, R⁴ = identical or different alkyl groups

 Examples likes are,

reaction 1:        

reaction 2:         


 reaction 1 (repeat):    



 reaction 2 (repeat):   

 reaction 3:    

 reaction 4:    

Mechanism: 

A strong base deprotonates the dicarbonyl α-carbon. This carbon is preferred over the methyl carbon because the formed enolate is conjugated and thus resonancestabilized. The carbon then undergoes nucleophilic substitution. When heated with aqueous acid, the newly alkylated ester is hydrolyzed to a β-keto acid, which isdecarboxylated to form a methyl ketone .

 

                 

 

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