Introduction to Advanced Organic Chemistry 3.

Reaction of nucleophile (C=C from enolate

Addition and Condensation Reactions
Aldol Reaction
• Aldol reactions are base-catalyzed reactions
that involve carbon-carbon bond formation
between reacting aldehydes and ketones
• The name “aldol” comes from the products
of the reaction, which contains an aldehyde
and an alcohol
 General reaction  formation of the enolate
ion) with an electrophilic C (C=O of the other
aldehyde)
 All of the C’s that is part of the carbonyl is
partially + (electrophilic)
 When the base has reacted to the aldehyde,
the intermediate reacts with any excess
aldehyde in the solution
 A nucleophilic double bond (C=C) attaches
to the acetaldehyde
4. Formation of new C-C bond and OH bond
 This formation happens in the presence of
H2O
 After the C=C attacks C=O, the oxygen lost
its bond with C , and so it pulls one H on the
H2O floating around in the solution, that will
form the OH bond
 The excess OH- from H2O is release

 It’s called enolate because of the

presence of the double bond and the
presence of the negative charge in the
oxygen (olate)

1. Treatment of aldehyde with a base

 Focus on the alpha carbon
 Alpha carbon is the allylic carbon which is
situated right next to a carbon involved in a
double bond
 Looking at the acidity of the H in the
aldehyde, the aldehyde hydrogen is
technically more acidic (it is easier to
stabilize)
 Between the aldehyde hydrogen and the
alpha carbon hydrogen the alpha-H is more
acidic because the lone pair e- that is left in
the alpha-C is easily resonance stabilize
 The alpha-H will more likely to react with Direct aldol condensation
the base because it forms the stable enolate
ion

2. Formation of the Enolate

 The enolate has an extra pair of e- that are
readily given away
 The electrons between C=C will act as a
nucleophile

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 The carbonyl compound forms an enolate
when a base is added to the aldehyde
 The enolate picks up on another aldehyde
molecule which creates a new C-C bond
 When the new C-C is formed, the lone pair
electrons of O attacks a base (the same base
that was added to the first aldehyde)
Aldol Reaction Equilibrium
 The presence of phenyl group enhances the
stability of the enolate ion, it allows for
more acidic hydrogens to react to the base
 All of the reactions are relatively reversible
 The O from NaOH will attack one of the
alpha-Hydrogen
 The electrons from the alpha-C-H bond will
move to the C=O bond and it will push the
e- up to the oxygen, forming the enolate ion
 The enolate ion will attack another
phenylacetaldehyde
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 Similar rxn with the aldehydes but are less
favored
 The relative distribution of percentages is
low for ketones when reacted to NaOH
 Ketones are not as reactive as aldehydes in
terms of aldol condensation
Aldol dehydration / Enone synthesis
 The alcoholic functional group in an aldol
can be dehydrated to form a conjugated
enone
 Enone is a double bond in the alpha-carbon
that is next to an ketone
 Conjugated portion is very important
because it allows different kinds of chemical
reactions and resonance as well as stability
 The source of rxn in an organic chemistry is
always a nucleophilic e-
Mechanism
 Dehydration can happen in both acids and
bases
Base Catalyzed
 The base OH- will pick-up the hydrogen
attached to the alpha-C and movement of e-
happens to form the C=C
 The C=O bond will push e- to the O (the
lone pair of O will be resonance stabilize)
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  The OH in the intermediate can accept the  The presence of CH3 to the other alpha-C
e-
 By product is OH- as a leaving group

Acid Catalyzed
 The acid will be reacted upon by the C=O
 C=O will push the pi bond to the next
carbon
 The acidic hydrogen from the alpha carbon
will attack the OH group

makes it possible for the formation of a two

products

Ketone Dehydration Crossed/Mixed aldol condensation

 Aldol condensations that happen between
different carbonyl reactants
 Reaction of acetaldehyde and propanal

 Dehydration of the aldol drives the

equlibirum of ketones used in aldol
synthesis to the products side
 Dehydration of ketone is a lot more stable
than its intermediate
 When you treat the ketone with a base, and
form the intermediate, immediately  Symmetrical products  acetaldehyde or
dehydrate it to form a stable product propanal can react with itself

Other considerations:
Draw the two enone products, excluding double-  Reaction is still possible even if one of the
bond isomers, that result in the aldol condensation carbonyls have no α-H
of 3-methylcyclohexanone
 The product is not identical because the
position of the methyl group indicates a
certain kind of stereoisomerism
 The position of the alpha-C contains two
different functional groups
 For ketones  2 alpha carbons
 Aldehyde  one alpha carbon

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Intramolecular aldol condensation
 Aldol condensations that happen when a
molecule has two carbonyl functional
groups within itself

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