Stobbe condensation
From Wikipedia, the free encyclopedia
The Stobbe condensation entails the reaction of an aldehyde or ketone with an ester of succinic acid to generate alkylidene succinic acid or related derivatives.[1] The reaction consumes one equivalent of metal alkoxide. Commonly, diethylsuccinate is a component of the reaction. The usual product is salt of the half-ester. The Stobbe condensation is named after its discoverer, Hans Stobbe [de], whose work involved the sodium ethoxide-induced condensation of acetone and diethyl succinate.[2]
An example is the reaction of benzophenone with diethyl succinate:[3]
A reaction mechanism that explains the formation of both an ester group and a carboxylic acid group is centered on a lactone intermediate (5):
Reaction mechanism
The Stobbe condensation is also illustrated in the synthesis of some drugs:
- Pridefine
- Doisynoestrol
- Tametraline[4]
- Sertraline (discovery route)
- Pregabalin (discovery route c.f. [51615-30-6])
- Y-39677 [312688-85-0][5][6]
- Splitomicin
See also
References
- ↑ Smith, Michael B.; March, Jerry (2006). March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. p. 1452-1455. doi:10.1002/0470084960. ISBN 9780470084960.
- ↑ Stobbe, H. (1899). "Condensation des Benzophenons mit Bernsteinsäureester". Justus Liebigs Annalen der Chemie. 308 (1–2): 89–114. doi:10.1002/jlac.18993080106.
- ↑ Johnson, W. S.; Schneider, W. P. (1950). "β-Carbethoxy-γ,γ-Diphenylvinylacetic Acid". Organic Syntheses. 30: 18. doi:10.15227/orgsyn.030.0018.
- ↑ Sarges R (1975). "Synthesis of Phenyl-Substituted 1-Aminotetralines". The Journal of Organic Chemistry. 40 (9): 1216–1224. doi:10.1021/jo00897a008.
- ↑ Kitajima, Hiroshi; Nakamura, Mitsuharu; Tamakawa, Hiroki; Goto, Nobuharu (2000). "Hybridization of non-sulfonylurea insulin secretagogue and thiazolidinedione-derived insulin sensitizer". Bioorganic & Medicinal Chemistry Letters. 10 (21): 2453–2456. doi:10.1016/S0960-894X(00)00491-1.
- ↑ https://adisinsight.springer.com/drugs/800016298
External links
- "Claisen Condensation". Organic Chemistry Portal.