The aldol reaction

McMurry, J. Fundamentals of Organic Chemistry, 7th Edition. Chapter 11

The aldol reaction
• The aldol reaction takes place between the carbonyl carbon of one
compound and the a-carbon of the another.
• It involves nucleophilic addition and a-substitution.
• When reaction is between two aldehyde molecules, a b-
hydroxyaldehyde is produced hence the name aldol (‘ald’ for
aldehyde and ‘ol’ for alcohol).
• Reaction of a ketone gives a b-hydroxyketone.
The aldol reaction mechanism
• E.g. reaction of acetaldehyde:
The aldol reaction
• Aldol reaction of acetone:
The aldol reaction
• Reaction is faster for aldehydes (ketones less reactive).
• The aldol addition products are easily dehydrated to a,b-unsaturated
products (enones). The process is then known as aldol condensation.
• Dehydration is catalyzed by base or acid.
• In basic conditions, a base deprotonates the a-carbon to form an
enolate; enolate then eliminates the OH group (OH picks up a proton
and leaves as H2O) to form an enone (see next slide).
The aldol condensation
• Base-catalyzed dehydration:
Mixed aldol reactions
• An aldol reaction between two different carbonyl compounds is called
a mixed aldol.
• In general, four possible products are expected if both partners have
a- hydrogens.
• A single product is possible if one partner doesn’t have a-hydrogens
(can’t form enolate); or if one of the partners is much more acidic
than the other.
• Exercise: Draw four products expected from aldol reaction of ethanal
and propanal in presence of a base.
Intramolecular aldol
• Certain dicarbonyl compounds can undergo intramolecular aldol
reaction when treated with a base. Reaction produces a cyclic
product.
The aldol condensation
• Problem 11:14 Write structures of the enone products you would
obtain from aldol condensation of the following compounds:

• Problem 11.40 The aldol condensation reaction can be carried out

intramolecularly by treatment of a diketone with base. What diketone
would you start with to prepare 3-methylcyclohex-2-enone? Show the
reaction.
The aldol condensation
• Problem 11.42 How might you prepare the following compounds
using an aldol condensation reaction?