Reactivity in Chemistry

Substitution at Carboxyloids

CX7.  Enolates:  Claisen Condensation

Alkylmagnesium reagents, alkylcuprates and complex hydrides can all react with carboxyloids.  When they do, a carbon or hydrogen nucleophile bonds to the carbonyl carbon, usually replacing the leaving group at that position.

Another common carbon nucleophile is an enolate ion.  Enolate ions can also react with carboxyloids, although not typically with amides.

Probably the most common enolate reaction involving carboxyloids is the reaction of esters.  If a strong base is added to solution of ester, some of the esters will become deprotonated, forming enolate anions.  These ions will be nucleophiles. 

Some esters will remain protonated.  These esters will be electrophiles.  Donation of the enolate to the ester, with subsequent loss of the leaving group, leads to a beta-ketoester.

 

You are familiar with the term "alpha-position".  That's the position next to a carbonyl.  The "beta-position" is the next one after the alpha position.  In a beta-ketoester, there is a ketone in the beta position of the ester.  The formation of a beta-ketoester from two esters is called a "Claisen condensation". 

In principle, this reaction could conceivably go backwards.  The enolate ion could potentially be displaced by an alkoxide to get back to an ester and an enolate ion.  That's because the enolate ion is a relatively stable ion, and a moderately good leaving group.  However, that generally doesn't happen.

Under basic conditions, the beta-ketoester is usually deprotonated, forming a particularly stable ion. This ion formation acts as a "thermodynamic sink" for the reaction, pulling it forward until all of the ester has been consumed.

Problem CX7.1.

Show why the ion that results from deprotonation of the beta-ketoester is particularly stable.

 

Problem CX7.2.

FIll in the products of the following reactions.

 

Problem CX7.3.

Predict the reactants needed to make these products via a Claisen, Aldol or Crossed Aldol reaction.

 

This site is written and maintained by Chris P. Schaller, Ph.D., College of Saint Benedict / Saint John's University (with contributions from other authors as noted).  It is freely available for educational use.

Creative Commons License
Structure & Reactivity in Organic, Biological and Inorganic Chemistry by Chris Schaller is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License

Send corrections to cschaller@csbsju.edu

This material is based upon work supported by the National Science Foundation under Grant No. 1043566.

Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

 

Navigation:

Back to Carboxyl Substitution Index

Back to Structure & Reactivity Web Materials