Darzens reaction
Darzens reaction | |
---|---|
Named after | Auguste Georges Darzens |
Reaction type | Ring forming reaction |
Identifiers | |
Organic Chemistry Portal | darzens-reaction |
RSC ontology ID | RXNO:0000077 |
The Darzens reaction (also known as the Darzens condensation or glycidic ester condensation) is the chemical reaction of a ketone or aldehyde with an
Reaction mechanism[edit]
The reaction process begins with deprotonation at the halogenated position.[3] Because of the ester substituents, this carbanion is a resonance-stabilized enolate. This nucleophile next attacks the carbonyl reagent, forming a carbon–carbon bond. These two steps are similar to a base-catalyzed aldol reaction. The oxygen anion in this aldol-like product then SN2 attacks on the formerly-nucleophilic halide-bearing position, displacing the halide to form an epoxide.[2] This reaction sequence is thus a condensation reaction since there is a net loss of HCl when the two reactant molecules join.[7]
![Arrow-pushing mechanism for the Darzens reaction.](https://upload.wikimedia.org/wikipedia/commons/thumb/5/5f/Darzens_reaction_mechanism.svg/800px-Darzens_reaction_mechanism.svg.png)
If the starting halide is an
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 side reactions.
Stereochemistry[edit]
Depending on the specific structures involved, the epoxide may exist in cis and trans forms. A specific reaction may give only cis, only trans, or a mixture of the two. The specific stereochemical outcome of the reaction is affected by several aspects of the intermediate steps in the sequence.
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 diastereomeric 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.[8]
Alternative reactions[edit]
Glycidic esters can also be obtained via nucleophilic epoxidation of an
Subsequent reactions[edit]
The product of the Darzens reaction can be reacted further to form various types of compounds. Hydrolysis of the ester can lead to decarboxylation, which triggers a rearrangement of the epoxide into a carbonyl (4). Alternately, other epoxide rearrangements can be induced to form other structures.
See also[edit]
References[edit]
- ^ Newman, M. S; Magerlein, B. J (1949). "The Darzens Glycidic Ester Condensation". Organic Reactions. 5 (10): 413–440. doi:10.1002/0471264180.or005.10.
- ^ a b c Jie Jack Li (2006). "Darzens glycidic ester condensation". Name Reactions (3rd. expanded ed.). Springer-Verlag. pp. 183–184. doi:10.1007/3-540-30031-7. ISBN 978-3-540-30030-4.
- ^ a b Ballester, Manuel (April 1955). "Mechanisms of The Darzens and Related Condensations Manuel Ballester". Chemical Reviews. 55 (2): 283–300. doi:10.1021/cr50002a002.
- ^ Darzens, G. (1904). "Method generale de synthese des aldehyde a l'aide des acides glycidique substitues". Compt. Rend. (in French). 139: 1214.
- ^ Darzens, G. (1905). "Methode generale de synthese des d'esters glycidiques
α β substitues et de cetones". Compt. Rend. (in French). 141: 766. - ^ Darzens, G. (1906). "Condensation glycidique des aldehydes avec l'ether alpha-chloropropionique". Compt. Rend. (in French). 142: 214.
- ^ Hunt, Richard H.; Chinn, Leland J.; Johnson, William S. (1954). "Ethyl
β ,β -Pentamethyleneglycidate". Organic Syntheses. 34: 54. doi:10.15227/orgsyn.034.0054. - ^ a b Tung, C. C.; Speziale, A. J.; Frazier, H. W. (June 1963). "The Darzens Condensation. II. Reaction of Chloroacetamides with Aromatic Aldehydes". Journal of Organic Chemistry. 28 (6): 1514–1521. doi:10.1021/jo01041a018.