Claisen Condensation
Esters having α-hydrogen on treatment with a strong base such as sodium ethoxide undergo self condensation to produce β-ketoesters. This reaction is called Claisen Condensation. Mixed or crossed Claisen Condensation also occurs between two different esters or between ester and a ketone or between ester having enolizable α-hydrogens and the other ester does not (e.g., aromatic esters or carbonates).
Crossed Claisen Condensation
The acidity of β-ketoesters is high enough to allow them to be completely deprotonated by alkoxide base to form a second enolate. This make the equilibrium of this step very favorable, which is enough to drive the whole reaction towards the product.
Esters having only one α-hydrogen does not undergo claisen condensation with EtONa because the ketoester formed in step-3 can not be converted to its enolate anion due to absence of a second α-hydrogen with the result that the equilibrium does not shift to the product side.
However, in the presence of very strong base such tripenylmethyl sodium, such esters undergoes claisen condensation to give β-ketoesters because, the very strong base acts in two ways-
A. It withdraw the weakly acidic α-hydrogen irreversibly from the ester (analogous step-1 is highly reversible)
B. It completely remove one of the equilibrium products so that the equilibrium shifts to the right (Step-3)
Crossed Claisen Condensation
Mechanism of Claisen Condensation
Ethoxide ion abstracts a proton from the α carbon of the ester to produce the anion which is attacked on the carbony lcarbon of the second ester to produce an oxonium ion which eliminates an ethoxide ion to give the β-ketoester.The acidity of β-ketoesters is high enough to allow them to be completely deprotonated by alkoxide base to form a second enolate. This make the equilibrium of this step very favorable, which is enough to drive the whole reaction towards the product.
Esters having only one α-hydrogen does not undergo claisen condensation with EtONa because the ketoester formed in step-3 can not be converted to its enolate anion due to absence of a second α-hydrogen with the result that the equilibrium does not shift to the product side.
However, in the presence of very strong base such tripenylmethyl sodium, such esters undergoes claisen condensation to give β-ketoesters because, the very strong base acts in two ways-
A. It withdraw the weakly acidic α-hydrogen irreversibly from the ester (analogous step-1 is highly reversible)
B. It completely remove one of the equilibrium products so that the equilibrium shifts to the right (Step-3)
