CROSSED ALDOL CONDENSATION BY VANA JAGAN MOHAN RAO

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