General

Organic Chemistry
Two credits
Second Semester 2009

King Saud bin Abdulaziz University for Health Science

Reference Book: Organic Chemistry: A Brief Course,

by Robert C. Atkins and Francis A. Carey
Third Edition

Instructor: Rabih O. Al-Kaysi, PhD.

 Lecture 19

Chapter 11

Aldehydes and
Ketones
Some reactions of aldehydes and ketones progress
beyond the nucleophilic addition stage

Acetal formation
Imine formation
Compounds related to imines
Enamines
The Wittig reaction
Reaction with Primary Amines:
Imines
 Imine (Schiff's Base) Formation

•• ••
H2N •• + C O •• HN C O H
•• ••
R R
a carbinolamine

••
N C (imine) + H2O
R
 Example

CH + CH3NH2

CH=NCH3 + H2O

N-Benzylidenemethylamine (70%)
 Example

CH + CH3NH2 OH

CH
NHCH3
CH=NCH3 + H2O

N-Benzylidenemethylamine (70%)
 Example

O + (CH3)2CHCH2NH2

NCH2CH(CH3)2 + H2O

N-Cyclohexylideneisobutylamine
(79%)
 Example

O + (CH3)2CHCH2NH2

OH
NHCH2CH(CH3)2

NCH2CH(CH3)2 + H2O

N-Cyclohexylideneisobutylamine
(79%)
 Terminology
Terminology

CH3CH2CH2CH
γ β α

The reference atom is the carbonyl carbon.

Other carbons are designated α , β , γ , etc. on the
basis of their position with respect to the carbonyl
carbon.
Hydrogens take the same Greek letter as the
carbon to which they are attached.
 Enol Content
Enol Content

O OH

R2CHCR' R2C CR'

keto enol

percent enol is usually very small

keto form usually 45-60 kJ/mol more stable

than enol
 Enol Content
Enol Content

O OH

CH3CH H2C CH K = 3 x 10-7

O OH

CH3CCH3 H2C CCH3 K = 6 x 10-9

 1,3-Diketones
1,3-Diketones
(also called β -diketones)
(also called β -diketones)

Example: 2,4-pentanedione

O O OH O

CH3CCH2CCH3 CH3C CHCCH3

(20%) (80%)

keto form is less stable than enol form

Base-Catalyzed Enolization:
Enolate Anions
 Acidity of α -Hydrogen
Acidity of α -Hydrogen

•• • ••
O• O ••
–
R2C CR' R2C CR' + H+
••
H

pKa = 16-20

Just for general knowledge, will not be tested on

 Acidity of α -Hydrogen
Acidity of α -Hydrogen

•• • ••
O• O ••
–
R2C CR' R2C CR' + H+
••
H

••
pKa = 16-20 •• O ••–

R2C CR'
Just for general knowledge, will not be tested on
 Acidity of α -Hydrogen
Acidity of α -Hydrogen

•• • ••
O• O ••
–
R2C CR' R2C CR' + H+
••
H
enolate ion

••
pKa = 16-20 •• O ••–

R2C CR'
Just for general knowledge, will not be tested on
 Mechanism of Enolization
Mechanism of Enolization
(Base-catalyzed)
(Base-catalyzed)

•• •
O•

R2C CR'
–
•• –
•• O ••
H
H

Just for general knowledge, will not be tested on

 Mechanism of Enolization
Mechanism of Enolization
(Base-catalyzed)
(Base-catalyzed)

••
•• O ••
–

R2C CR'
••
•• O H
H

Just for general knowledge, will not be tested on

 Mechanism of Enolization
Mechanism of Enolization
(Base-catalyzed)
(Base-catalyzed)

H
••
•• O ••
–
H O ••
••
R2C CR'

Just for general knowledge, will not be tested on

 Mechanism of Enolization
Mechanism of Enolization
(Base-catalyzed)
(Base-catalyzed)

H
••
•• O ••
–
H O ••
••
R2C CR'

Just for general knowledge, will not be tested on

 Mechanism of Enolization
Mechanism of Enolization
(Base-catalyzed)
(Base-catalyzed)

H
••
•• O –
H •• O ••
••
R2C CR'

Just for general knowledge, will not be tested on

 Acidity of α -Hydrogen
Acidity of α -Hydrogen

O O
(CH3)2CHCH CCH3

pKa = 15.5 pKa = 15.8

β -Diketones are much more acidic
β -Diketones are much more acidic

O O
CH3CCH2CCH3

pKa = 9
 β -Diketones are much more acidic
β -Diketones are much more acidic

O O

C C
H3C C CH3
H H

Ka = 10–9

O O

C –
•• C + H+
H3C C CH3

H
The Aldol Condensation

Gives β -hydroxy
aldehydes or ketones
 Some thoughts...
Some thoughts...

O O
–• •• ••
RCH2CH + • OH RCHCH + HOH
•• ••
– ••
pKa = 16-20 pKa = 16

A basic solution contains significant amounts

of the aldehyde and its enolate.
Aldehydes undergo nucleophilic addition.
Enolate ions are nucleophiles.
What about nucleophilic addition of enolate to
aldehyde?
 •• •
O•
–
RCHCH
••

RCH2CH

O ••
••
 •• •
O• •• •
O• •• •
– O•
RCHCH
•• RCHCH RCHCH
RCH2CH RCH2CH RCH2CH
O •• •• O •• •• OH
•• •• – ••
 •• •
O• •• •
O• •• •
– O•
RCHCH
•• RCHCH RCHCH
RCH2CH RCH2CH RCH2CH
O •• •• O •• •• OH
•• •• – ••

O O
NaOH
2RCH2CH RCH2CH CHCH
OH R
 Aldol Addition
Aldol Addition

O
RCH2CH CHCH
OH R

product is called an "aldol" because it is

both an aldehyde and an alcohol
 Aldol Addition of Acetaldehyde
Aldol Addition of Acetaldehyde

O O
NaOH, H2O
2CH3CH CH3CH CH2CH
5°C
OH
Acetaldol
(50%)
 Aldol Addition of Butanal
Aldol Addition of Butanal

2CH3CH2CH2CH

KOH, H2O 6°C

CH3CH2CH2CH CHCH
OH CH2CH3
(75%)
 Aldol Condensation
Aldol Condensation

O O
NaOH
2RCH2CH RCH2CH CHCH
OH R
 Aldol Condensation of Butanal
Aldol Condensation of Butanal

2CH3CH2CH2CH

NaOH, H2O 80-100°C

 Aldol Condensation of Butanal
Aldol Condensation of Butanal

2CH3CH2CH2CH

NaOH, H2O 80-100°C

CH3CH2CH2CH CCH
CH2CH3
(86%)
 Aldol reactions of ketones
Aldol reactions of ketones

O OH O
2%
2CH3CCH3 CH3CCH2CCH3
98%
CH3

the equilibrium constant for aldol addition

reactions of ketones is usually unfavorable
Alkylation of Enolate Anions
 Enolate Ions in SN2 Reactions
Enolate Ions in SN2 Reactions

Enolate ions are nucleophiles and react with

alkyl halides.
However, alkylation of simple enolates does
not work well.

Enolates derived from β -diketones can be

alkylated efficiently.
 Example
Example

O O O O
K2CO3
CH3CCH2CCH3 + CH3I CH3CCHCCH3
CH3

(75-77%)