Using Condensation Reactions for Synthesis

or How to Analyze the Product to Identify Reagents

You may use these essays, summaries and problems but you may NOT download them for use at another site, nor may you charge for access to them. Copyright Linda M. Sweeting 1999

The aldol, Claisen and related condensation reactions are very powerful synthetic tools, because they make new corbon-carbon bonds while preserving reactive sites for other transformations. Often, though, it is difficult to detect in the product structure the clues that suggest that a condensation reaction might help assemble the structure. This summary is designed to help you analyze the product structure to identify when a condensation might be useful and which reagents would make good starting materials. In each of the examples below the new bond is colored red, and the positions relative to the unreacted carbonyl group are labelled in blue.
  1. To make monocarbonyl compounds, use the aldol condensation.

    Note: crossed or mixed aldol condensations (2 different aldehydes or ketones), work much better if one of the reagents has no alpha-hydrogens.

    1. beta-hydroxyaldehydes and ketones

      The product can also be transformed by:
      elimination (see b),
      addition to the carbonyl by all the normal reagents, e.g. Grignard, LiAlH4, alchols, amines.

    2. alpha,beta - unsaturated (conjugated) aldehydes and ketones

      The product can also be transformed by:
      1. reduction to a saturated alcohol by H2, Pt, heat and pressure;
      2. addition by a nucleophile (Nuc-) to the unsaturated carbonyl compound either at the carbonyl carbon or the beta-carbon, both of which are somewhat positive.

      The common nucleophilic reagents react as follows:
      beta only, mostly reversible reactions either C=O or beta, depending on steric factors, irreversible carbonyl only, irreversible reactions
      OH-, CH3O- RMgX LiAlH4
      NH2R, NC- RLi Wittig, Ph3P=CHR
      enolates

      R2CuLi (irrev)

  2. To make beta-dicarbonyl compounds, use the Claisen condensation.

    Notes:

    1. crossed or mixed Claisen condensations (2 different esters), work much better if one of the reagents has no alpha-hydrogens.
    2. the base catalyst must be the conjugate base of the alcohol used tomake the ester, to prevent hydrolysis or exchange
    3. the product does not react further because it is immediately converted to its conjugate base, the weakest base in the reaction mixture.
    4. esters, aldehydes and ketones may be used together in condensation reactions, and either one may be the source of the enolate.

    The product can also be transformed by:
    1. reduction (it is possible to reduce both carbonyls or to selectively reduce either the ester or the ketone)
    2. hydrolysis and decarboxylation
    3. SN2 reactions of its enolate.

  3. To make delta-dicarbonyl compounds, use the Michael condensation

    Notes:

    1. be sure only one enolate can form (or one is formed very preferentially); a good way to do this is by using an R2 which begins with another carbonyl
    2. be sure your base catalyst is consumed or not nucleophilic (not the reactive ones listed in the table in 1b)
    3. esters, aldehydes and ketones undergo this reaction in either role

    The product can also be transformed by:
    1. reduction of the carbonyls
    2. other reactions at the carbonyls or alpha carbons, e.g. further condensations such as the Robinson annulation
Back to the Organic Chemistry Main Menu