Applications of Stobbe Condensation reaction/synthesis of acid, Tetralone and phenanthrene derivativ

1. TUMKUR UNIVERSITY DEPARTMENT OF PG STUDIES IN CHEMISTRY UNIVERSITY COLLEGE OF SCIENCE,TUMAKURU By PRUTHVI RAJ K III SEM MSc CHEMISTRY Guide:- Dr. M.K SHIVANANDA 1
2. CONTENTS Introduction. General mechanism. General features of Stobbe condensation. Synthetic applications. Drawbacks of Stobbe condensation. Reference. 2
3. Hans Stobbe (1860–1938) was born in Tiehenhof, Germany. He earned his Ph.D. In 1889 at the University of Leipzig where he became a professor in 1894. 3
4. Introduction In 1893 H.Stobbe reported an unexpected reaction b/w “acetone and diethyl succinate in the presence of a one equivalent of sodium ethoxide”. The major isolated product was found to be “tetraconic acid, an α,β-unsaturated acid, and its monoethtyl ester”. This result was surprising since they expected the formation of a 1,3-diketone via Claisen reaction. 4
5.  Further work on such kind of reactions by Stobbe and co-workers revealed that the transformation was common for esters of succinic acid with aldehydes and ketones.  “The formation of alkylidene succinic acids or their monoesters by the base-mediated condensation of ketones and aldehydes with dialkyl succinate is known as the Stobbe condensation”. 5
6. General Mechanism 6
7. General features of Stobbe condensation reaction There is no restriction on the carbonyl component, it may contain α-hydrogen atom. Aliphatic, aromatic or α,β-unsaturated aldehydes and ketones are commonly used. The diesters are mainly limited to succinic esters and their derivatives. Certain α,ω-diesters that do not undergo competitive Dieckmann condensation will afford Stobbe condensation. 7
8. Symmetrical ketones yields only one alkene stereoisomer, but unsymmetrical ketones afford a mixture of alkene stereoisomers. When carbonyl part contains α-protons, a variety of products may be formed as a result of double bond migration under the reaction conditions. 8
9. Synthetic applications Stobbe condensation has been used to prepare a large number of varieties of unsaturated & saturated acids. The condensation has also been useful for the synthesis of many types of policylic ring systems. 1) Synthesis of acid; 9
10. 2)Synthesis of polycylic rings; a. Napthol and Indenone derivatives- Stobbe condensation product with aryl ketones on cyclodehydration gives polycyclic rings. Since the reaction yields a substituted olefin, the aryl group may be cis to –CH2COOH or to COOH so that two products may be obtained. 10
11. b. Tetralone derivative; c. Phenanthrene derivative; 11
12. 3) Synthesis of estrone; 12
13. 4) The asymmetric total synthesis of (+)-Codeine the unnatural enantiomer; 13
14. References 1) Strategic applications of named reactions in organic synthesis – background and detailed mechanism by Laszlo kurti and Barbara czako. University of Pennesylvania 2) Reactions, rearrangements and reagents – S N Sanyal 3) Principle of organic synthesis- R.O.C Norman and J.M Coxon. 14
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