Write a mechanism for the Claisen reaction of ethyl ethanoate (ethyl acetate) to give ethyl acetoacetate?
The Claisen reaction involves the condensation of two ester molecules in the presence of a strong base to form a β-keto ester. In the case of ethyl ethanoate (also known as ethyl acetate) reacting to give ethyl acetoacetate, the reaction can be carried out as follows:
1. Choose a suitable base: The Claisen reaction typically requires a strong base such as sodium alkoxide. In this case, sodium ethoxide (NaOEt) can be used.
2. Prepare the reaction mixture: Combine a stoichiometric amount of ethyl ethanoate and sodium ethoxide in a suitable solvent. The reaction can be performed under reflux conditions to facilitate the removal of any volatile side products.
3. Initiate the reaction: Heat the reaction mixture under reflux. This will cause the ethyl ethanoate and sodium ethoxide to undergo a nucleophilic acyl substitution reaction.
4. Formation of the enolate: The ethoxide ion acts as a nucleophile attacking the carbonyl carbon of the ethyl ethanoate, resulting in the formation of an intermediate alkoxide ion. This intermediate is then protonated, leading to the formation of the enolate ion.
5. Intramolecular condensation: The resulting enolate ion can undergo an intramolecular aldol condensation by attacking the carbonyl carbon of another ethyl ethanoate molecule within the same reaction mixture. This step involves the loss of a ethoxide leaving group and the formation of a new carbon-carbon bond.
6. Workup and product isolation: Upon completion of the reaction, quench the reaction mixture by adding an aqueous solution of an acid, typically hydrochloric acid (HCl). This will neutralize the remaining base and protonate the enolate intermediate, resulting in the formation of ethyl acetoacetate. The product can then be isolated by extraction, purification, and drying techniques.
It is important to note that the Claisen reaction is usually performed under controlled conditions, such as low temperatures or with certain steric constraints, to prevent further reactions (e.g., self-condensation or retro-Claisen) that may occur due to the reactive nature of enolate ions.