Reactions at the Compounds: α-Carbon of Carbonyl

Chapter 11
Reactions at the
-Carbon of Carbonyl
Compounds
What is an carbon?
enolate and enol considerations
carbon reactivity
a base can remove a proton from an carbon to form an

enolate ion
KEY POINT = electron delocalization is possible with
enolates
KEY POINT = enolate ions are nucleophiles
A Hydrogen Attached to an sp3 Carbon adjacent to a

Carbonyl Carbon have pKa values from 16-25
You can approximate the pKa value of any -hydrogen

to be 20
A hydrogen attached to an sp3 carbon adjacent to TWO

carbonyl carbon have pKa values of about 10
More electron delocalization

More stable conjugate base
Electron delocalization
Why?
Electron delocalization
in both compounds, the non-bonding electron can be delocalized

onto an electronegative atom
Enol equilibrium - tautomers
Tautomers differ in the location of a double bond and a hydrogen

Tautomers are in equilibrium
Tautomers are not resonance structures
Acid catalysis promotes enol formation
Enolates are nucleophiles
NaNH2
this method can be used to alkylate the -carbon of

ketones, esters, and nitriles
5 reactions from Chapter 11

halogenation
-acidic conditions
-basic conditions
2. aldol condensation
3. Claisen condensation
4. malonic ester synthesis
5. acetoacetic ester synthesis
6. Michael reaction (not new)
-you have already seen this reaction in chapter 9
Halogenation
only one -hydrogen is replaced by Br
Mechanism for
Acid-Catalyzed Halogenation
The halogen of the -carbon of an aldehyde

or ketone can undergo SN2
strong bases cannot be used for this reaction otherwise

E2 would predominate
-halogenation products can also eliminate to

give conjugated double bonds
Pyridine is a non-nucleophilic base
Methyl ketones the Haloform reaction

-halogenation under basic conditions
Each successive enolate is more stable

Final step is simple hydrolysis
Aldol reaction
aldehydes and ketones undergo aldol addition reactions

one molecule of the carbonyl carbon is an electrophile
and the other is a nucleophile
Aldol addition reactions
the product has twice as many carbons as the reactant
Aldol mechanism
recall
Same mechanism enolate is nucleophile
-hydroxyaldehydes and ketones can

undergo elimination
Crossed/Mixed Aldol additions

can give a mess
the crossed/mixed aldol addition forms 4 possible products
Some crossed/mixed aldols

will form 1 major product
the carbonyl compound with -hydrogens is added slowly

to a solution of the carbonyl compound without -hydrogens
and a base
Some crossed/mixed aldols

will form 1 major product
Your lab
A Claisen Condensation
a condensation reaction of two molecules of an ester
Mechanism for the Claisen Condensation
1,3-dicarbonyl
A Crossed Claisen Condensation

to a solution of the carbonyl compound without -hydrogens
and a base
A Crossed Condensation Between

a Ketone and Diethyl Carbonate

to a solution of the carbonyl compound without -hydrogens and a
base
Intramolecular Claisen condensations
1,3-dicarbonyl
Intramolecular Claisen condensations
Same mechanism
Intramolecular Aldol Additions
No!
Followed
by
Dehydration
2 different enolate ions can be formed

formation of a 5-membered ring is favored over formation of
a 3-membered ring

No!
2 different enolate ions can be formed
Followed
by
Dehydration
formation of a 5-membered ring is favored over formation of

a 7-membered ring
Followed
by
Dehydration
Followed
by
Dehydration
3-Oxocarboxylic Acids Can be

Decarboxylated
Mechanism decarboxylation
You will not be tested on the mechanism for decarboxylation.

But know that 3-oxocarboxylic acids will decarboxylate when heated
The Malonic Ester Synthesis
a malonic ester synthesis forms a carboxylic acid

with two more carbons than the alkyl halide used in the synthesis
The Steps in the

Malonic Ester Synthesis
Malonic ester forming rings
The Acetoacetic Ester Synthesis
an acetoacetic ester synthesis forms a methyl ketone with three

more carbons than the alkyl halide used in the synthesis
The Steps in the Acetoacetic

Ester Synthesis
Same mechanism as
Malonic Ester Synthesis
Acid/base chemistry to enolate, Sn2 (or two), saponification, decarboxylation
,-unsaturated aldehydes and ketones

undergo direct addition and conjugate addition
From Chapter 9
1,2 addition
1,4 addition
REVIEW ALERT FROM CHAPTER 9:

Weak Bases Form
Conjugate Addition Products
Michael Reactions
Look for the
1,5-dicarbonyl
substructure
when the nucleophile is an enolate ion,

the reaction is called a Michael Reaction
The Mechanism for a Michael Reaction
Robinson Annulation a Michael

reaction followed by an aldol
condenations
a Robinson annulation forms a product with a

fused 2-cyclohexenone ring
retrosynthetic analysis

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Chapter 11

a base can remove a proton from an carbon to form an

A Hydrogen Attached to an sp3 Carbon adjacent to a

You can approximate the pKa value of any -hydrogen

A hydrogen attached to an sp3 carbon adjacent to TWO

More electron delocalization

in both compounds, the non-bonding electron can be delocalized

Enol equilibrium - tautomers

Tautomers differ in the location of a double bond and a hydrogen

Acid catalysis promotes enol formation

Enolates are nucleophiles

this method can be used to alkylate the -carbon of

5 reactions from Chapter 11

only one -hydrogen is replaced by Br

The halogen of the -carbon of an aldehyde

strong bases cannot be used for this reaction otherwise

-halogenation products can also eliminate to

Pyridine is a non-nucleophilic base

Methyl ketones the Haloform reaction

Each successive enolate is more stable

aldehydes and ketones undergo aldol addition reactions

Aldol addition reactions

the product has twice as many carbons as the reactant

Same mechanism enolate is nucleophile

-hydroxyaldehydes and ketones can

Crossed/Mixed Aldol additions

the crossed/mixed aldol addition forms 4 possible products

Some crossed/mixed aldols

the carbonyl compound with -hydrogens is added slowly

Some crossed/mixed aldols

a condensation reaction of two molecules of an ester

Mechanism for the Claisen Condensation

A Crossed Claisen Condensation

the carbonyl compound with -hydrogens is added slowly

A Crossed Condensation Between

the carbonyl compound with -hydrogens is added slowly

Intramolecular Claisen condensations

Intramolecular Claisen condensations

Intramolecular Aldol Additions

2 different enolate ions can be formed

Intramolecular Aldol Additions

2 different enolate ions can be formed

formation of a 5-membered ring is favored over formation of

Intramolecular Aldol Additions

3-Oxocarboxylic Acids Can be

You will not be tested on the mechanism for decarboxylation.

The Malonic Ester Synthesis

a malonic ester synthesis forms a carboxylic acid

The Steps in the

Malonic ester forming rings

The Acetoacetic Ester Synthesis

an acetoacetic ester synthesis forms a methyl ketone with three

The Steps in the Acetoacetic

Acid/base chemistry to enolate, Sn2 (or two), saponification, decarboxylation

,-unsaturated aldehydes and ketones

REVIEW ALERT FROM CHAPTER 9:

when the nucleophile is an enolate ion,

The Mechanism for a Michael Reaction