Here's what I read about which base to use in Claisen Condensation reaction (two esters or ester + carbonyl compound forming a beta keto-ester or beta-diketone):

The base used must not interfere with the reaction by undergoing nucleophilic substitution or addition with a carbonyl carbon. For this reason, the conjugate sodium alkoxide base of the alcohol formed (e.g. sodium ethoxide if ethanol is formed) is often used, since the alkoxide is regenerated. In mixed Claisen condensations, a non-nucleophilic base such as lithium diisopropylamide, or LDA, may be used, since only one compound is enolizable. LDA is not commonly used in the classic Claisen or Dieckmann condensations due to enolization of the electrophilic ester.

Here's what I didn't understand, particularly -

  1. Why is the conjugate sodium alkoxide base of alcohol generated, used? The paragraph talks about regeneration of alkoxide ion; but I didn't really understand that part. (Seems like something related to chemical equilibrium?)

  2. They said that Lithium Diisopropylamide is NOT generally used due to enolisation of electrophilic ester. What do they mean by it? Why can't we use LDA? Which bases can we use instead?

Could someone please answer the above two questions, with proper explanation? Thanks a lot!


1 Answer 1

  1. Consider that there may be other reactions also going on, not just acid-base chemistry. So, for instance in the Claisen reaction of ethyl acetate, if methoxide was used instead of ethoxide then you may get methyl acetate formed as well.
  • $\begingroup$ Are there other advantages? I thought that formation of the alcohol and its successive ionisation (negligible, but non zero) in aqueous solution maybe a way of regenerating the catalyst so that the reaction is thereafter self sustaining. Is it true? $\endgroup$ Commented Feb 2, 2018 at 11:39
  • 4
    $\begingroup$ This is NOT done in aqueous soln. If an ester group is part of the reaction then the leaving group is the alkoxide of the ester, this is how the alkoxide is regenerated. $\endgroup$
    – Waylander
    Commented Feb 2, 2018 at 11:48
  • $\begingroup$ The Claisen condensation of ethyl acetate (pKa=~25) is usually conducted in concentrated EtONa/EtOH (pKa=~16) or EtONa in an inert solvent such as toluene. The product, ethyl acetoacetate (AAE; pKa=~11) , is deprotonated by the EtONa generated in the condensation. Unlike the aldol condensation, which is catalytic in base, the Claisen condensation must be conducted with stoichiometric base. $\endgroup$
    – user55119
    Commented Feb 21, 2018 at 0:45

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