The document discusses the crossed aldol condensation reaction. It describes the 5 step mechanism where the hydroxide ion deprotonates an aldehyde to form an enolate ion, which then adds to the carbonyl carbon of a non-enolizable aldehyde. This forms an aldol product that can further react. The carbonyl group plays a role in providing a site for nucleophilic attack and making the alpha hydrogens acidic. Crossed aldol condensation allows control over donor and acceptor molecules. It is useful for synthesizing large molecules from small starting materials and occurs in biological synthesis of fructose from glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.

1. BY
VANA JAGAN MOHAN RAO M.S.Pharm, MED.CHEM
NIPER-KOLKATA
Asst.Professor, MIPER-KURNOOL
e-mail: jaganvana6@gmail.com

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 crossed aldol
condensation.
INTRODUCTION

3. REACTION:
STEPS IN CROSSED ALDOL CONDENSATION
Step 1: The hydroxide ion deprotonates the enolizable aldehyde reversibly.

4. Step 3: Alkoxide ion (2) is protonated by water.
Step 2: Enolate ion (1) preferentially adds to the non-enolizable
aldehyde,which has the sterically less hindered and therefore more
accessible carbonyl carbon.

5. Step 4: Aldol (3) is an enolizable aldehyde. A small amount of it is converted
to the corresponding enolate ion (4) by the hydroxide ion.
Step 5: Enolate ion (4) loses a hydroxide ion.

6.  Thecarbonyl group plays two roles in this reaction:
 1. It provides a site for nucleophilic attack by the
enolate ion.
 2. It makes the -hydrogens sufficiently acidic to
enable the formation of reasonable
concentrations of enolate ion.
 NOTE: There must be -hydrogens in order to
undergo aldolcondensation.
 Without -hydrogens, the only possible reaction is
Cannizarro reaction
CARBONYL GROUP IN ALDOL REACTIONS:

7.  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.

8.  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 CONDENSATION

9. CH2 CH C H
O
OHO
O O
O
OOOH
OH H
CH2 CH C CH C CH2 O P OH
O
P
OH
O O
+
O P O
OH
Glyceraldehyde-3-phosphate
Dihydroxyacetone phosphate
OH O
Fructose-1,6-diphosphate

CH2 C CH2 O P OH
OH
ALDOL
CONDENSATION
enzyme
BIOLOGICAL SYNTHESIS OF FRUCTOSE

10. by
B.Yeswanth Prasasnna Kumar
pharmD Istyear