Ethyl butanoate, Claisen condensation

Ethyl bromide, H NMR spectrum, 503—504 Ethyl butanoate, Claisen condensation of, 851 Ethyl chloride, 48, 156. See also Chloroethane Ethyl cinnamate, 788 Ethyl cyanoacetate, 857 Ethylene, 168. See also Ethene acidity of, 343, 345, 552 biosynthesis of, 168 bond dissociation energies in, 343 bonding in, 14, 38-40, 47, 54, 170-171,... 

You attempt a Claisen condensation with ethyl butanoate by adding the ester to methanol containing NaOMe and you reflux the reaction before hydrolysis. Draw the normal Claisen product when ethyl butanoate is condensed with itself Is this the product you obtain Explain. 

B.I. The Claisen Condensation. A classical reaction is the condensation of an ester enolate with an ester, illustrated by the self-condensation of ethyl butanoate in the presence of sodium ethoxide to give 3-keto-ester 167. Initial reaction with the base, under thermodynamic control in this case, generates the enolate anion (165). This anion attacks the carbonyl of a second molecule of ethyl butanoate to give 166. Displacement of ethoxide generates ketone 167. As shown here, this reaction is known as the Claisen condensation. A synthetic example is taken from Lubell s synthesis of indolizidine alkaloids, in which diester 168 was treated with LiN(SiMe3)2 in THF at -78°C to give the self-condensation product 169, in 52% yield. 

The reaction described for ethyl butanoate is a self-condensation, but as with the aldol condensation, Claisen condensation of two different esters can result in a mixture of products under thermodynamic control conditions. The reaction of two different esters is called the crossed-Claisen (or a mixed Claisen) condensation. A generalized reaction involving RC02Et and RlC02Et can lead to at least four different condensation... 

Show the product of the Claisen condensation of ethyl butanoate in the presence of sodium ethoxide followed by acidifica tion with aqueous HCI. 

Draw two molecules of ethyl butanoate. Convert one of the molecules to an enolate anion and show it adding to the carbonyl carbon of the other. Because Claisen condensations occur with nucleophilic acyl substitution, the —OR group of the carbonyl being attacked is eliminated from the final product. It often helps to number the atoms in the enolate anion and the ester being attacked. 

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 each product. (See Example 15.8)... 

The Claisen condensation, like the aldol condensation (Sec. 9.17), is useful for making new carbon-carbon bonds. The resulting /3-keto esters can be converted to a variety of useful products. For example, ethyl acetate can be converted to ethyl butano-ate by the following sequence. 

The typical / -keto ester is ethyl acetoacetate (ethyl 3-oxo-butanoate). A retro-synthetic disconnection on this compound points to one of the most common methods for its synthesis, namely the Claisen ester condensation. 

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