Stobbe condensation

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, 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):

Applications

The Stobbe condensation is also illustrated in the synthesis of some drugs:

  1. Pridefine
  2. Doisynoestrol
  3. Tametraline[4]
  4. Sertraline (discovery route)
  5. Pregabalin (discovery route c.f. [51615-30-6])
  6. Y-39677 [312688-85-0][5][6]
  7. Splitomicin

See also

References

  1. ^ Smith, Michael B.; March, Jerry (2006). March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. p. 1452-1455. doi:10.1002/0470084960. ISBN 9780470084960.
  2. ^ Stobbe, H. (1899). "Condensation des Benzophenons mit Bernsteinsäureester". Justus Liebigs Annalen der Chemie. 308 (1–2): 89–114. doi:10.1002/jlac.18993080106.
  3. ^ Johnson, W. S.; Schneider, W. P. (1950). "β-Carbethoxy-γ,γ-Diphenylvinylacetic Acid". Organic Syntheses. 30: 18. doi:10.15227/orgsyn.030.0018.
  4. ^ Sarges R (1975). "Synthesis of Phenyl-Substituted 1-Aminotetralines". The Journal of Organic Chemistry. 40 (9): 1216–1224. doi:10.1021/jo00897a008.
  5. ^ 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.
  6. ^ https://adisinsight.springer.com/drugs/800016298
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