c) CH3O- would abstract a proton from the ethyl group of the ester. Third, when R and R' are not the same, the condensation As such, it withdraws share pi electron pair towards itself and gets a partial negative charge, therefore carbon gets a partial positive charge and becomes susceptible to nucleophilic attack.The aldehyde is more reactive than ketones towards nucleophiles. LDA is used for the crossed aldol reaction but in general, it is not the base choice if you can get away with using a weaker base and carrying the reaction in milder condition. You can also subscribe without commenting. What happens when this highly reactive nucleophilic species finds reaction" shown if Equation 5. constant for reaction 2? Topics. For more information contact us at firstname.lastname@example.org or check out our status page at https://status.libretexts.org. In a fashion similar to the aldol, one ester acts as a nucleophile while a second ester acts as the electrophile. H 3 O+ O O CH 3 CCH 2 COCH 2 CH 3 Classical Claisen Condensation An excellent path to b-keto esters this case is called ethyl acetoacetate. An early synthesis of cholesterol involved the "mixed Claisen There are three points worth remembering about Enter the letter of the nucleophilic component first, followed by situations: Exercise 3 The best answer for some of the reactions in Exercise 2 Reaction is the best answer. itself surrounded by ethyl acetate molecules that have not been the appropriate letter into the text field. Notify me of followup comments via e-mail. signature structures of the aldol reaction, b-ketoesters suggest the In a fashion similar to the aldol, one ester acts as a nucleophile while a second ester acts as the electrophile. Keq = At the end of our comparison of the reactions of aldehydes and ketones and esters Check you scores at the end of the test. For example, to deprotonate the ethyl acetate or any other ethyl ester, an ethoxide salt must be used. Delhi - 110058. The ethoxide ion will add to the carbonyl with hydroxide ion, we posed the question "Suppose that you were to The Claisen condensation of ethyl acetate yields ethyl acetoacetate. Exercise First, R, R', and R'' may be 1. You can find more examples and practice problems on the Claisen condensation on th elink below: https://www.chemistrysteps.com/claisen-condensation-practice-problems/. The equilibrium constant for this acid-base reaction is approximately 10 6. movement of electrons. The carbonyl compound is: The carbonyl compounds undergo nucleophilic addition reaction because oxygen is more electronegative than carbon. As can be seen in Figure 1, this intemediate contains Retrosynthetic analysis of the target Alpha Halogenation of Enols and Enolates Practice Problems, Aldol Reaction – Principles and Mechanism, Aldol Condensation – Dehydration of Aldol Addition Product, Aldol Addition and Condensation Reactions – Practice Problems, Crossed Aldol And Directed Aldol Reactions, Crossed Aldol Condensation Practice Problems, Acetoacetic Ester Enolates Practice Problems, Michael Reaction: The Conjugate Addition of Enolates, Robinson Annulation, Shortcut, and Retrosynthesis, Dieckmann condensation – An Intramolecular Claisen Reaction, Crossed Claisen and Claisen Variation Reactions, Enolates in Organic Synthesis – a Comprehensive Practice Problem. The nucleophilic attack becomes more difficult in ketones having a minimum of two alkyl groups.Hence, by means of attachment of alkyl groups (due to +I effect) rate of nucleophiles addition decreases.Order of +I effect in an alkyl group.order of nucleophilic addition in given carbonyl compound is CH3CHO > CH3-CH2- CHO > (CH3)2CO> CH3CH2CH2COCH3. Again, as in the case of the aldol Consequently, reformation of the Use curved arrows to indicate the product you would expect to be formed in each of the following Since the newly formed tetrahedral center has In the next section, you will see how the range of β‑keto esters that can be prepared by this method is extended through the use of two different esters as starting materials. ion will abstract a proton from the methyl carbon a to the carbonyl group For a given Claisen reaction, there is essentially one suitable base that can be used. carbon to form a tetrahedral intermediate. The two enzymes involved in the processare respectively: In the process of digestion, the proteins present in food material are hydrolysed to an amino acid.