Crossed Aldol Condensation
Crossed aldol condensation happens when the reaction takes place between two different carbonyl compounds (two different aldehydes, two different ketones, or one aldehyde and one ketone). When the reacting molecules are different, the number of possible products increases, so the reaction is useful only when conditions favour the formation of a single major product.
1. Crossed Aldol Condensation Between Two Different Aldehydes
If both aldehydes contain α-hydrogen, then both molecules can form carbanions. This leads to the formation of four possible products, and therefore this type of reaction has very little synthetic value.
But if only one aldehyde has α-hydrogen, it alone forms the carbanion. The other aldehyde (without α-hydrogen) can only act as an acceptor, so only two products are possible.
A useful trick is to add the aldehyde containing α-hydrogen slowly to the reaction mixture. This gives better yield of the desired crossed product.
Formaldehyde (no α-hydrogen) is a powerful acceptor due to:
- No steric hindrance
- No +I effect
For example, acetaldehyde with excess formaldehyde in Ca(OH)₂ gives a reaction that continues repeatedly until a tri-hydroxymethyl aldehyde is formed, which later undergoes crossed Cannizzaro reaction to form pentaerythritol.
2. Crossed Aldol Condensation Between Two Different Ketones
Ketones are generally:
- Poor carbanion acceptors (due to +I effect)
- Sterically crowded
So the reaction gives very low yields, making it rarely used.
3. Crossed Aldol Condensation Between an Aldehyde and a Ketone
(a) Both contain α-hydrogen
A ketone forms the carbanion more easily, whereas aldehydes are more reactive electrophiles. Thus:
- Aldehyde acts as the acceptor
- Ketone provides the carbanion
Two possible products are obtained, but the crossed product is the major product. Slow addition of the aldehyde improves selectivity.
(b) Aldehyde has no α-hydrogen
Only one product is formed because:
- Ketone cannot undergo self-condensation
- Aldehyde (without α-hydrogen) cannot form carbanion
Thus, the ketone provides carbanion and aldehyde acts as acceptor. The reaction may continue until all α-hydrogens of the ketone are replaced by hydroxymethyl groups.
Dehydration of Aldols
Aldols formed in the reaction can easily lose water to give: α,β-unsaturated aldehydes or ketones.
Dehydration can occur:
- Under acidic or basic conditions
- On heating
Applications
Aldol and crossed aldol condensations play a major role in organic synthesis. Important uses:
- Preparation of unsaturated aldehydes and ketones
- Synthesis of intermediates like β-ionone (used in Vitamin A synthesis)
- Formation of mesityl oxide and phorone from acetone
- Production of monosaccharides from glycolaldehyde
- Formation of dyes like cyanine dyes
- Ethynylation reactions to form valuable acetylenic alcohols
Crossed aldol condensation is one of the most important carbon–carbon bond-forming reactions in organic chemistry.
Detailed Notes:
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