CAVENDISH UNIVERSITY ZAMBIA

SCHOOL OF MEDICINE
OCM 202

Aldehydes and Ketones (2021)

Prepared by GBM
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 ALDEHYDES: KETONES:
§General formula: General formula:
RCHO or RCH=O RCOR’ (R and R’=alkyl or aryl)

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 Aldehydes and Ketones
O
• Carbonyl Group C=O C H
! Present in aldehydes and ketones

O O
R C H R C R'
Aldehydes Ketones
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 Aldehydes
• Aldehydes
! Sometimes abbreviated RCHO
! Contain at least one H connected to the C

H2 C O

formaldehyde
O
C H
O
O
CH3 CH
R C H
acetaldehyde

benzaldehyde Aldehydes

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 Ketones
• Ketones
! Carbonyl C is connected to two alkyl groups
! RCOR’

O
O
CH3 C CH3
acetone CH3
R C R'
CH3 CH2 C O
methyl ethyl ketone
Ketones

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 Nomenclature
• IUPAC
• Suffix is “-al” for the aldehydes
• Suffix is “-one” for the ketones
• # indicates position of ketone

O O
CH3 CH2 CH CH3 CH2 CH2 C CH2 CH3
propanal 3-hexanone

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 Nomenclature
• An Aldehyde or Ketone takes precedence over any
previously considered group

OH O
Cl CH2 CH CH2 CH2 CH
5-chloro-4-hydroxypentanal O
H2C CH CH2 C CH2 Cl
1-chloro-4-penten-2-one

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 Nomenclature
• Common names - aldehydes

H2 C O
O
formaldehyde C H
O
CH 3 CH

acetaldehyde

benzaldehyde

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 Nomenclature QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.

• Common names - ketones

• Some are always used
O
O C
CH3 C CH3
acetone benzophenone

- Others name each R group and end with “ketone”

CH3 O
CH3 CH3 C C CH3
CH3 CH2 C O CH3
methyl ethyl ketone methyl t-butyl ketone
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 O OH O O
CH3CHBrCH2C H CH3CHCH2CH2C H CH2C H

3-bromobutanal 4-hydroxypentanal 2-phenylethanal

Cl O HO O O

H3C CH H C H H3CHC=HC C H

2-Chloropropanal 3-Hydroxypropanal 2-Butenal

O O
HO CHO
C H C H

benzenecarbaldehyde 3-hydroxycyclopentanecarbaldehyde

cyclohexanecarbaldehyde

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 - +
d d
O C
C O + -
C O
C O-
+ d
d

§ Because the polarity of the carbonyl group, aldehydes and ketones are
polar compounds.
§ Dipole-dipole attractions, although important, are not as strong as
interactions due to hydrogen bonding. As a result, the boiling points of
aldehydes and ketones are higher than those of nonpolar alkanes, but
lower than those of alcohols.
O
- + + -
d d d d
C O H H O C

§ The lower aldehydes and ketones are soluble.

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 Physical Properties
Carbonyls:
• Cannot form H bonding with each other:
• Aldehydes and Ketones are POLAR molecules and form
dipole interactions
• Gives higher boiling and melting points

d-
d+C O
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 Physical Properties
• Aldehydes and Ketones
• can form H bonds with water!
• solubility in water is about the same as alcohols

yes!
C O C O

C O H O
H
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 Physical Properties
• Strong odors
• Ketones generally have pleasant odors
• perfumes, flavoring agents
• Aldehydes odors vary
• some pleasant
• cinnaminaldehyde, vanillin
• some not pleasant
• formaldehyde
Many are found in natural products

http://www.youtube.com/watch?v=KDohVakqkic
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PREPARATION

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Ketones and aldehydes are often made by oxidizing alcohols. When we need to make a carbonyl compound, we can often
use a Grignard reagent to synthesize an alcohol with the correct structure and oxidize it to the final product.

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Ketones and Aldehydes from Ozonolysis of Alkenes

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 Phenyl Ketones and Aldehydes: Friedel–Crafts Acylation
Friedel–Crafts acylation is an excellent method for making alkyl aryl
ketones or diaryl ketones. It cannot be used, however, on strongly
deactivated aromatic systems.

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 PREPARATIONS SUMMARY
Oxidation of primary alcohols

Ozonolysis of alkenes

Hydroboration-oxidation of terminal alkynes

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 Oxidation of secondary acohols

Ozonolysis of alkenes

Acid catalyzed hydration of terminal alkynes

Friedel acylation

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 THE RELATIVE REACTIVITIES OF CARBONYL COMPOUNDS

The carbonyl carbon is electron deficient (it is an electrophile). Therefore, it reacts with nucleophiles. The electron
deficiency of the carbonyl carbon in formaldehyde, acetaldehyde, and acetone is indicated by the faint blue region in each
compound’s electrostatic potential map.

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 PRACTICE PROBLEM
Which ketone in each pair is more reactive?
a. 2-heptanone or 4-heptanone
b. bromomethyl phenyl ketone or chloromethyl
phenyl ketone

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REACTIONS

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 Nucleophilic Acyl Substitution
The carbonyl group of a carboxylic acid or a carboxylic acid derivative is attached to a group
that can be replaced with another group. Therefore, these compounds undergo nucleophilic acyl
substitution reactions—they react with nucleophiles to form substitution products.

Nucleophilic Addition
The addition of a nucleophile to the carbonyl carbon of an aldehyde or a ketone forms a
tetrahedral compound. If the nucleophile is a strong base, such as R- or H-, then the
tetrahedral compound will be stable because it will not have a group that can be
eliminated. Thus, the reaction will be an irreversible nucleophilic addition reaction.
Recall that generally a tetrahedral compound is unstable if the sp3 carbon is attached to
two oxygens or an oxygen and another electronegative atom (a nitrogen or a halogen)
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Because organometallic reagents react as their corresponding carbanion, they are excellent nucleophiles. The basic reaction
involves the nucleophilic attack of the carbanionic carbon in the organometallic reagent with the electrophilic carbon in the carbonyl
to form alcohols.

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STEPS

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Wittig reaction

O- P(C 6 H 5 ) 3
O
THF
+ CH 2=P(C 6H 5) 3 C CH 2
C

O P(C 6 H 5 ) 3

C CH 2 C CH 2 + (C 6H 5) 3P=O

O
O

H + (Ph)3P=CH C OC 2H 5

OC 2H 5

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Addition of Ammonia and Ammonia Derivatives

NH3
C NH
Imine

NH2OH
C N OH
Hydroxylamine
Oxime

H2N NH2
C N NH2
Hydrazine
Hydrazone

C O
H2N NH
C N NH
Phenylhydrazine
Phenylhydrazone
O2N NO2
O2N
NO2
H2N NH
C N NH
-
O 2,4 Dinitrophenylhydrazone
O
H2N NH C NH2
C N NH C NH2
Semicarbazide
Semicarbazone 34
 SUMMARY ON SOME REACTIONS

1.Hydrate Formation

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CONDENSATION

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 ALDOL CONDENSATION

§ Condensation between two molecules of an Aldehyde or a

ketone to form a β-hydroxyl aldehyde or a β-hydroxy ketone is
known as a ALDOL CONDENSATION.
§ ALDOL CONDENSATION is possible only when the carbonyl
compound contains atleast one α-hydrogen atom.

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MECHANISM

enolate
ion

v An enolate ion is the anion formed when

an alpha hydrogen in the molecule of
an aldehyde or a ketone is removed as a
hydrogen ion.
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The alkoxide ion is the conjugate
base of alcohols.

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Alkoxide ion is protonated by water.

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Crossed aldol condensation

I n 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 aldol
condensation.

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T h e enolate ion (carbanion)Is the actual
nucleophilic reagent.
The reaction breaks down to the
following:
The α-carbon of the donor attaches itself to
the carbonyl carbon of the acceptor.

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 S t e p 1: Deprotonation and formation of
nucleophile.

• Step 2: Attack by nucleophile: Formation of alkoxide

ion.

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§ Step 3: Hydrolysis and formation of Aldol type product

Step 4: Intramolecular dehydration

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 Claisen Schmidt or Claisen reaction

is the condensation between an aromatic aldehyde or ketone and

an aliphatic aldehyde or ketone in presence of dilute alkali to form
an aldol product.

LIMITATIONS
Aldol chemistry is an exceptional method for quickly assembling
larger molecules from ketones and aldehydes. The chemistry does,
however, have some limitations. First, both the aldol reaction and
condensation work best when an aldehyde is used as the
electrophile in the reaction. Second, in the aldol condensation, the
aldehyde should not have any alpha-protons. Otherwise, the
aldehyde is at risk of forming an enolate and acting as a nucleophile
in the reaction.

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Claisen Schmidt or Claisen reaction

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Cannizzaro reaction
Aldehyde which does not contain α hydrogen undergoes Cannizzaro
reaction.
CH2OH
CHO COO-Na+
D
+ NaOH (30 %) +
O

O O- C
H

CH C
OH
+ OH-
H

O
O
C CH2O-
C CH2OH
OH
+ O-
+

more stable anion

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9u

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OXIDATION AND REDUCTION

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Oxidation reactions
a-
KMnO4
R-CHO or Ar-CHO RCOOH or ArCOOH
or K2Cr2O7

b- Tollens test

RCHO + 2 Ag(NH3)+2 + OH- RCOO- + 2 Ag + 4 NH3 + 3 H2O

c- Iodoform reaction

H3C O
C O + 3 I2 + 4 NaOH R
O Na
- + + CHI3 + 3 NaI
R

CH3
H3C I2 / NaOH
H3C
COONa
+ CHI3

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Reduction of carbonyl group
a- Addition of metal hydride

H 2O
C O + M+H- H C O-M+ H C OH
H+

O OAl OH
H2 O
LiAlH4 H
H+

2 H2 / Pd OH
H3C

O
H3C
H
1) NaBH4 OH
H3C
2) H2O 51
b- Addition of Grignard Reagents: Formation of alcohols

R'
O
1) Dry ether
R C + R'MgX
2) H 2 O
R CH OH
H
HO
O
1) Dry ether
H 3C C + C 2H 5MgX
2) H 2O
H 3C CH C2H5
H

R'
O
1) Dry ether
R C R' + R''MgX
2) H 2 O
R C OH
R''
CH3
O
1) Dry ether
+ CH 3MgX
2) H 2 O
OH

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c- Clemmenson reduction

O H
H

COOH HCl / Zn(Hg) COOH

d- The Wolf-kishner reduction

O
N-NH2

NH2NH2
COOH
COOH

H
H
NaOH
D COOH 53
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