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The Darzens reaction (also known as the Darzens condensation or glycidic ester condensation) is the chemical reaction of a ketone or aldehyde with an haloketone in the presence of a base to form an α,β-epoxide ester, also called a "glycidic ester". This reaction was discovered by the organic chemist Auguste Georges Darzens in 1904.
If the starting halide is an α-halo amide, the product is an α,β-epoxy amide. If an α-halo ketone is used, the product is an α,β-epoxy ketone.
Any sufficiently strong base can be used for the initial deprotonation. However, if the starting material is an ester, the alkoxide corresponding to the ester side-chain is commonly chosen in order to prevent complications due to potential acyl exchange .
The initial stereochemistry of the reaction sequence is established in the step where the carbanion attacks the carbonyl. Two sp3 (tetrahedral) carbons are created at this stage, which allows two different possibilities of the halohydrin intermediate. The most likely result is due to chemical kinetics: whichever product is easier and faster to form will be the major product of this reaction. The subsequent SN2 reaction step proceeds with stereochemical inversion, so the cis or trans form of the epoxide is controlled by the kinetics of an intermediate step. Alternately, the halohydrin can epimerize due to the basic nature of the reaction conditions prior to the SN2 reaction. In this case, the initially formed diastereomer can convert to a different one. This is an equilibrium process, so the cis or trans form of the epoxide is controlled by chemical thermodynamics—the product resulting from the more stable diastereomer, regardless of which one was the kinetic result.
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