Bouveault-Blanc reduction

Theory and Defination :

The reduction of esters into alcohols with sodium in ethanol, in which sodium serves as a single electron reducing agent and ethanol is the proton donor, is generally known as the Bouveault–Blanc reduction. Other alcohols have also been applied as proton donors. In the absence of proton donor, the reduction of esters with sodium leads to the formation of acyloins. It has also been pointed out that the Bouveault–Blanc reduction under appropriate conditions effects the ring reduction of aromatic compounds. This reaction is an inexpensive substitute for lithium aluminum hydride reductions of esters in industrial production before the development of the metal hydride. It has been proved in the present study that the ketyl radical can cyclize to form cyclic or Spiro cyclic molecules if a double bond exists in the appropriate location of the ester.

The Bouveault–Blanc reduction is a chemical reaction in which an ester is reduced to primary alcohols using absolute ethanol and sodium metal.

General Reaction : 

This reaction is an inexpensive and large-scale alternative to lithium aluminium hydride reduction of esters.

Mechanism:

Sodium metal is a single-electron reducing agent, meaning the sodium metal will transfer electrons one at a time. Four sodium atoms are required to fully reduce each ester to alcohols. Ethanol serves as a proton source. 

 Example & Applications :

 1) Sodium Dispersion Reagent for the Bouveault-Blanc Reduction of Esters



 2)  Sodium in silica gel (Na-SG) - a safe, free-flowing powder - has been used for the Bouveault-Blanc reduction of various aliphatic esters. Primary alcohols were prepared in excellent yield under mild reaction conditions.

 

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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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