Crossed aldol condensation

1. Crossed aldol condensation

2. In the presence of a strong base, two different molecules of aldehyde or ketone combine to form a β - hydroxyaldehyde or a β- hydroxyketone . This reaction is called as the aldol condensation . Introduction

3. The enolate ion ( carbanion ) is the actual nucleophilic reagent. The reaction breaks down to the following: The α -carbon of the donor attaches itself to the carbonyl carbon of the acceptor. Steps in Crossed aldol condensation

4. Rate limiting step: Formation of alkoxide ion

5. The carbonyl group plays two roles in this reaction: 1. It provides a site for nucleophilic attack by the enolate ion. 2. It makes the a - hydrogens sufficiently acidic to enable the formation of reasonable concentrations of enolate ion . NOTE: There must be a - hydrogens in order to undergo aldol condensation . Without a - hydrogens , the only possible reaction is Cannizarro reaction Carbonyl group in Aldol reactions

6. If both carbonyl compounds have α - hydrogens , then the donor and acceptor could be controlled. If one carbonyl compound that does not have α - hydrogens is chosen, it can only act as an acceptor. Then, but adding the donor to a dilute solution of acceptor, we can control the reaction to give only one product.

7. CROSSED ALDOL CONDENSATION CINNAMALDEHYDE

8. Step 1: Deprotonation and formation of nucleophile. Mechanism of Crossed Aldol condensation Step 2: Attack by nucleophile: Formation of alkoxide ion.

9. Step 3: Hydrolysis and formation of Aldol type product Mechanism continued… Step 4: Intramolecular dehydration

10. The aldol condensation is very useful in the preparation of large molecules from simple starting materials. In biosynthesis, where large molecules are products, condensation reactions provide the only reasonable route, since all of the starting materials are small molecules containing only two or three carbons. In synthesis of insect repellants such as 2-Ethyl-3-hydroxy hexanal Applications of Crossed Aldol reactions

11. Biological synthesis of fructose

12. THANK U by B.Yeswanth Prasasnna Kumar pharmD Ist year