Claisen Condensation

The Claisen condensation is a C–C bond-forming reaction between one ester and another carbonyl compound in the presence of a strong base. The transformation delivers a β-keto ester or a β-diketone.

Claisen Condensation

Claisen Condensation

Reaction Mechanism

Claisen Condensation

1. Formation of the enolate. 2. Nucleophilic attack to the carbonyl carbon.  3. And further removal of the alkoxy group to generate the β-keto ester.

Experimental Procedure

Claisen Condensation
Claisen Condensation

Solution A: A flame dried round bottom flask was charged with anhydrous THF (240 mL) under nitrogen atmosphere. Diisopropylamine (1.36 eq) was added via syringe, and the solution was cooled to -78 °C. n-Butyllithium in hexanes (2.45 M, 1.36 eq) was added, and the solution was stirred for 30 minutes at -78 °C. Tert-Butylacetate (1.42 eq) was then added via syringe over 10 minutes, and the solution was stirred for 1 h at -78 °C.

Solution B: A flame dried round bottom flask was charged with anhydrous THF (280 mL) under nitrogen atmosphere. Ethyl 3-chloropropanoate (0.20 mol, 1.0 eq) was then added via syringe, and the solution was cooled to -78 °C.

After preparing the two solutions, Solution A was added to Solution B via a cannula using nitrogen overpressure over 30 minutes. The resulting solution was stirred for an additional 15 minutes at -78 °C, then quenched with glacial acetic acid. The cooling bath was then removed, and the suspension was left to warm to room temperature. Diethyl ether and distilled water were added, and the phases were separated. The organic phase was washed with aqueous K2CO3 (20 m/m%) and brine, dried over Na2SO4, and upon filtration used directly in the following step.

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