Claisen Condensation of Ethyl Propanoate

Claisen Condensation of Ethyl Propanoate THE OVERALL REACTION  

Step 1 Proton abstraction from the a carbon of ethyl propanoate gives the corresponding enolate. 

Step 2 The ester enolate undergoes nucleophilic addition to the carbonyl group of the keto form of the ester. The product of this step is the anionic form of the tetrahedral intermediate. 

Step 3 The tetrahedral intermediate dissociates by loss of ethoxide and gives the p-keto ester. 

Step 4 Under the conditions of its formation, the p-keto ester is deprotonated. The equilibrium constant for this step is favorable and drives the equilibrium toward product formation. 

---

What product would you obtain from Claisen condensation of ethyl propanoate ... 

Draw a structural formula for the /3-ketoester formed in the crossed Claisen condensation of ethyl propanoate with each ester (See Example 15.8)... 

PROBLEM 10.36 Using eqs. 10.48 through 10.50 as a model, write out the steps in the mechanism for the Claisen condensation of ethyl propanoate. 

In a novel procedure, chemical modification of uncrosslinked atactic polystyrene by acetylation followed by a Claisen condensation with ethyl perfluoro-propanoate has been used to prepare a macromolecular ligand bearing phenyl,... 

The Claisen condensation of two molecules of ethyl propanoate gives the following /3-ketoester ... 

Once an ester enolate is generated, it can react with another ester in a Claisen condensation however, it may also react with the carbonyl of an aldehyde or ketone. The ester enolate anion is a nucleophile and it reacts with an aldehyde or ketone via acyl addition. Kinetic control conditions are the most suitable for this reaction in order to minimize Claisen condensation of the ester with itself (self-condensation). If ester 74 (ethyl propanoate, in green in the illustration) is treated first with LDA and then with butanal (21, in violet), for example, the initial acyl addition product is 78. The new carbon-carbon bond is marked in blue and treatment with dilute aqueous acid converts the alkoxide to an alcohol in the final product of this sequence, 79. Compound 79 is a P-hydroxy ester, which is the usual product when an ester enolate reacts with an aldehyde or a ketone. Ester enolate anions react with ketones in the same way that they react with aldehydes. 

When a 1 1 mixture of ethyl propanoate and ethyl butanoate is treated with sodium ethoxide, four Claisen condensation products are possible. Draw a structural formula for... 

Give the products of Claisen condensation of (a) ethyl propanoate (b) ethyl 3-methylbutanoate (c) ethyl pentanoate. For each, the base is sodium ethoxide, the solvent ethanol. 

Linderberg, M.T., Moge, M. and Sivadasan, S. Claisen Condensation as a Eacile Route to an ot-Alkoxy-cinnamate S3mthesis of Ethyl (2S)-2-Ethoxy-3-(4-hydrox)q)henyl)propano-ate. Org. Process Res. Dev. 2004, 8, 838-845. 

For esters with only one a-hydrogen, such as ethyl 2-methyl propanoate (ethyl isobutyrate), a more powerful base (e.g. sodium triphenylmethide, Ph3CeNa ) is required to affect the condensation reaction [the forced Claisen ester condensation, e.g. the synthesis of ethyl 2,2,4-trimethyl-3-oxopentanoate (ethyl iso-butyrylisobutyrate), Expt 5.176]. In this case the reaction sequence is completed in the step corresponding to (ii) above since the /1-keto ester (24) has no a-hydro-gen for step (iii), and the powerful base is required to force the equilibrium (i) to the right. 

Let s try a synthesis. Suppose the target is ethyl 2-methyl-3-oxo-2-propylpentanoate. The presence of the /3-ketoester functionality suggests employing an alkylation reaction and/or an ester condensation. In one potential pathway, the propyl group can be attached by alkylation of a simpler /3-ketoester. Further retrosynthetic analysis suggests that the new target (ethyl 2-methyl-3-oxopentanoate) can be prepared from ethyl propanoate by a Claisen ester condensation. 

Apart from sotolon, the other compounds in Fig. 5 can be explained as the products of a Maillard reaction, and their carbon skeletons simply originate from the active Amadori intermediate in other words, they still preserve the straight carbon chain structure of monosaccharides. In spite of being a simple Cg lactone, sotolon has a branched carbon skeleton, which implies another formation process in the Maillard reaction. Sulser e al.(6) reported that ethyl sotolon (ll) was prepared from threonine with sulfuric acid, and that 2-oxobutyric acid, a degradation product of threonine, was a better starting material to obtain II. This final reaction is a Claisen type of condensation, which would proceed more smoothly under alkaline conditions. As we(lO) obtained II from 2-oxobutyric acid (see figure 6) with a high yield in the presence of potassium carbonate in ethanol, a mixed condensation of 2-oxobutyric and 2-oxo-propanoic (pyruvic) acids was attempted under the same conditions, and a mixture of sotolon (22% yield) and II were obtained however, the... 

Give all the Claisen condensation products that would result from treatment of a mixture of ethyl acetate and ethyl propanoate with sodium ethoxide in ethanol. 

---