Advanced Aldol Condensations
Chapter 18: Enols
The more advanced topics are : Dehydration,
Mixed and Intramolecular Aldol reactions.
of Aldol products
The dehydration of the initial Aldol
products can occur, it is often favoured by the following factors:
- The Aldol product must
still have an α-hydrogen between the carbonyl and
the -OH group.
- Look for extended
conjugated in the product (i.e. increased stability).
- Heating the reaction often favours
elimination of water (dehydration).
- Non-aqueous reaction conditions
favour the removal of water (equilbrium shifts to dehydration products).
A mixed Aldol reaction means
that the enolate and the carbonyl are not from the same aldehyde or ketone.
The most useful mixed Aldols are
Otherwise there are selectivity problems
that give rise to complex mixtures of products.
- Only one reactent can form an
- This means the other reactent
lacks α-hydrogens (for examples, see below) and
therefore must be the electrophilic carbonyl component.
reactent is more electrophilic than the other and functions as the electrophilic
that in general, aldehydes are more reactive (electrophilic) than ketones
and will usually be the electrophile.
||Neither of these
aldehydes has α-hydrogens and therefore they
cannot form an enolate.
||Only one of this
pair of aldehydes has an α-hydrogen
||In the above example, which aldehyde forms the enolate ?
Why can't the aldol product dehydrate ?
How can you deduce this product ?
- Dicarbonyl compounds can be used
to give intramolecular Aldol reactions.
- This means the enolate component
and the carbonyl component are parts of a single larger molecule.
- The selectivity is typically
controlled by the stability of the cyclic Aldol product.
- This favours the formation of
the more stable 5- or 6-membered rings (review)
- To work out the best product,
check the permutations that are possible and look for the favourable ring
- Since aldehydes are more electrophilic than ketones, the aldehyde will be the electrophile and the ketone the nucleohile (i.e. the enolate) (see above)
- There two possible enolates (at
C5 or C7)
- The more favourable ring size
will the 5-membered ring.
When doing intramolecular reactions, it is a good idea to count carbons
to avoid silly errors.
If you start numbering at the electrophilic C=O C atom, then it will "show you" the rings sizes...