Alpha Carbon Reactions



Alpha carbons undergo a variety of useful reactions in organic chemistry. Halogenation with an acid catalyst provides a monohalogenated product. In the aldol addition reaction, an alkoxide base deprotonates an alpha carbon, which attacks a second carbonyl, synthesizing a beta-hydroxy aldehyde, hence the name aldol (aldehyde alcohol). Claisen condensations are analogous to aldol additions, with an ester as a reactant instead of an aldehyde and an alkoxide base that matches the ester. Claisen reactions yield a beta-keto ester.

Direct alkylation of an ester or aldehyde can be accomplished by adding lithium diisopropylamide (LDA) followed by the appropriate alkyl halide. Direct alkylation of a ketone can be accomplished with NaH for addition to the more-substituted side or with LDA for addition to the less-substituted side. When alpha,beta unsaturated carbonyls are attacked by nucleophiles, the nucleophile will attack either the carbonyl carbon or the beta carbon of the double bond. Attack on the carbonyl carbon is called simple addition, or 1,2 addition. An attack on the beta carbon is called conjugate addition, or 1,4 addition. In the Michael reaction, a stabilized enolate attacks the beta carbon.

At A Glance

  • The simplest reactions of alpha carbon are the halogenation of the alpha carbon of a ketone or aldehyde, the Hell-Volhard-Zelinsky reaction, and direct alkylation.
  • In aldol addition reactions, an enolate and aldehyde react to create the aldol addition product.
  • Crossed aldol addition reactions are when two different carbonyls mix to form an aldol product. The carbonyls are mixed at the same time (practical) or mixed stepwise (directed). If the two carbonyls are part of the same molecule, an intramolecular aldol reaction occurs.
  • Claisen reactions are the ester analogue of an aldol reaction except that in the Claisen reaction, an ester undergoes self-condensation instead of an aldehyde (aldol). An intramolecular Claisen is called a Dieckmann condensation.
  • In alkylation reactions, an alkyl group attaches to another molecule, usually in the place of an acidic hydrogen. Alkylation reactions include the acetoacetic ester and malonic ester synthesis, the Stork enamine synthesis, and Michael additions.
  • When an alpha,beta-unsaturated carbonyl reacts with a nucleophile, either 1,2 addition (simple addition) or 1,4 addition (conjugate addition) occurs. A 1,4 addition of an enolate is referred to as a Michael reaction.