Ester carbonyl condensation reactions

Ketones, esters, and nitriles can all be alkylated using LDA or related dialkyl-amide bases in THE. Aldehydes, however, rarely give high yields of pure products because their enolate ions undergo carbonyl condensation reactions instead of alkylation. (We ll study this condensation reaction in the next chapter.) Some specific examples of alkylation reactions are shown. 

Esters, like aldehydes and ketones, are weakly acidic. When an ester with an a- hydrogen is treated with 1 equivalent of a base such as sodium ethoxide, a reversible carbonyl condensation reaction occurs to yield a /3-keto ester. For example, ethyl acetate yields ethyl acetoacetate on base treatment. This reaction between two ester molecules is known as the Claisen condensation reaction. (We ll use ethyl esters, abbreviated "Et," for consistency, but other esters will also work.)... 

Carbonyl condensation reactions are widely used in synthesis. One example of their versatility is the Robinson anuulation reaction, which leads to the formation of an substituted cyclohexenone. Treatment of a /3-diketone or /3-keto ester with an a,/3-unsaturated ketone leads first to a Michael addition, which is followed by intramolecular aldol cyclization. Condensation reactions are also used widely in nature for the biosynthesis of such molecules as fats and steroids. 

The Knoevenagel reaction is a carbonyl condensation reaction of an ester with an aldehyde or ketone to yield an a,j8-unsaturated product. Show the mechanism of the Knoevenagel reaction of diethyl malonate with benzaldchyde. 

The Darzens reaction involves a two-step, base-catalyzed condensation of ethyl chloroacetate with a ketone to yield an epoxy ester. The first step is a carbonyl condensation reaction, and the second step is an SK2 reaction. Write both steps, and show their mechanisms. 

Claisen condensation reaction (Section 23.7) The carbonyl condensation reaction of an ester to give a /3-keto ester product. 

Two additional carbonyl condensation reactions which made their appearence in the 1950 s provide ring closure capability of synthetic value. The first has been described by Paul and Wendel and utilizes 2-chlorocyclopentanone as starting material.39 Subsequent to alkylation with an acetoacetic ester and deesterification, the... 

All kinds of carbonyl compounds, including aldehydes, ketones, esters amides, acid anhydrides, and nitriles, enter into condensation reactions, Nature uses these same carbonyl condensation reactions in the biosynthesis of many naturally occurring compounds. 

As the text continues to develop the chemistry of aldehydes and ketones, you will now see how the carbon adjacent to a carbonyl group can become nucleophilic. First, reactions of these new nucleophiles with common electrophiles like luiloalkiines will be covered alkylation reactions. More important arc reactions of the nucleophilic a-carbons of one carbonyl compound with electrophilic carbonyl carbons of another. They are generically termed carbonyl condensation reactions. You see them here for aldehydes and ketones the aldol condensation. (In a later chapter you will be introduced to the analogous reaction of carboxylic esters the Claisen condensation.) The products of aldol condensations are a, j3-un.saturatcd aldehydes and ketones, which contain additional sites of electrophilic and potential nucleophilic character. 

In the next step the diester is treated with base and a carbonyl condensation reaction occurs of the type you will meet in Chapter 26. There is a real question of regioselectivity here an enolate could form next to either ester (as shown by the orange circles) and would then attack the other ester as a nucleophile. There is little to choose between these alternatives but the first was wanted and was selected by careful experimentation, although only in 50% yield. This was acceptable on a large scale as the product could be separated by crystallization, the most practical of all methods. 

A carbonyl condensation reaction between two esters to give a /3-ketoester. 

How To Name an Ester (RCO2R ) Using the lUPAC System 831 How To Name a 2° or 3° Amide 831 Carbonyl Condensation Reactions... 

The Claisen condensation is reversible and favors the reactant since it is more stable than the S-keto ester. The condensation reaction can be driven to completion, however, if a proton is removed from the S-keto ester (Le ChStelier s principle Section 5.7). A proton is easily removed because the central a-carbon of the 8-keto ester is flanked by two carbonyl groups, making its a-hydrogen much more acidic than the a-hydrogen of the ester. 

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