Darzens Condensation

The Darzens condensation, also known as the Darzens reaction or glycidic ester condensation, is a chemical reaction that involves the reaction of a ketone or aldehyde with an α-haloester in the presence of a base to form an α,β-epoxy ester, also known as a glycidic ester[1][13]. This reaction was discovered by the organic chemist Auguste Georges Darzens in 1904[1][13].

The reaction mechanism begins with the deprotonation at the halogenated position when a strong base is used, forming a carbanion[1][13]. This carbanion then attacks the carbonyl group of the aldehyde or ketone, leading to the formation of an intermediate halohydrin[13]. The halohydrin then undergoes an intramolecular nucleophilic substitution reaction to form the final product, the α,β-epoxy ester[13].

The product of the Darzens reaction can be further reacted to form various types of compounds. For instance, hydrolysis of the ester can lead to decarboxylation, which triggers a rearrangement of the epoxide into a carbonyl[1]. Alternatively, other epoxide rearrangements can be induced to form other structures[1].

The Darzens condensation is a pivotal step in methods for the one-carbon homologation of ketones to afford carboxylic acids[4]. It is also a unique technique for the conversion of ketones to aldehydes[6]. The yields from aliphatic aldehydes are typically low, likely due to the formation of aldol compounds, whereas aromatic aldehydes and ketones or α,β-unsaturated ketones provide good glycidic ester yields[13].

Citations:

[1] https://en.wikipedia.org/wiki/Darzens_reaction

[2] https://www.youtube.com/watch?v=MiNGMwVfRiQ

[3] https://pubs.acs.org/doi/10.1021/jo01167a004

[4] https://www.sciencedirect.com/topics/chemistry/darzens-condensation

[5] https://www.youtube.com/watch?v=ATniqJ4--3g

[6] https://www.youtube.com/watch?v=snYWj0VzE7U

[7] http://www.lscollege.ac.in/sites/default/files/e-content/Darzens_reaction.pdf

[8] https://pubs.acs.org/doi/10.1021/cr50002a002

[9] https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/darzens-reaction

[10] https://www.youtube.com/watch?v=LeSqIhlctBY

[11] https://pubs.acs.org/doi/10.1021/jacs.8b01657

[12] https://www.rsc.org/publishing/journals/prospect/ontology.asp?id=RXNO%3A0000077

[13] https://www.studocu.com/en-us/document/laguardia-community-college/organic-chemistry-i/darzens-reaction-definition-mechanism-stereochemistry-synthetic-applications/46312504

[14] https://homework.study.com/explanation/the-darzens-reaction-requires-the-addition-of-the-enolate-of-an-alpha-halo-carbonyl-compound-to-an-aldehyde-or-ketone-depict-this-process-with-curved-arrows-and-draw-the-anionic-product-that-results.html