Aldehydes and Ketones

1
Carbonyl Compounds

2
 Carbonyl Structure

 Carbon is sp2 hybridized.

 C═O bond is shorter, stronger, and more polar
than C═C bond in alkenes.
3
 Carbonyl Structure
 The functional group of an aldehyde is a carbonyl
group bonded to a H atom and a carbon atom
 The functional group of a ketone is a carbonyl
group bonded to two carbon atoms

O O O
HCH CH3 CH CH3 CCH3
Methanal Ethanal Propanone
(Formaldehyde) (Acetaldehyde) (Acetone)
 Ketone Nomenclature
O O
1 3 4 1 3 4
CH3 C CH CH3 CH3 C CH CH2OH
2 2 CH
CH3 3

3-methyl-2-butanone 4-hydroxy-3-methyl-2-butanone

 Number the chain so that carbonyl carbon

has the lowest number.
 Replace the alkane -e with -one.

5
 Ketone Nomenclature (Continued)
1 O

3
Br

3-bromocyclohexanone

 For cyclic ketones, the carbonyl carbon is

assigned the number 1.
6
 Aldehydes Nomenclature

CH3 O
CH3 CH2 CH CH2 C H
5 3 2 1

3-methylpentanal

 The aldehyde carbon is number 1.

 IUPAC: Replace -e with -al.

7
 Nomenclature
Carbonyl as Substituent
 On a molecule with a higher priority
functional group, a ketone is an oxo and an
aldehyde is a formyl group.
 Aldehydes have a higher priority than ketones.
1 COOH
O CH3 O
CH3 C CH CH2 C H 3
4 3 1
CHO

3-methyl-4-oxopentanal 3-formylbenzoic acid

8
 Nomenclature
Common Names for Ketones
 Named as alkyl attachments to —C═O.
 Use Greek letters instead of numbers.

O O
CH3 C CH CH3 CH3CH C CH CH3
CH3 Br CH3

methyl isopropyl ketone bromoethyl isopropyl ketone

9
 Nomenclature
Historical Common Names
O
C
O CH3
CH3 C CH3
acetone acetophenone
O
C

benzophenone
10
 Order of Precedence
 For compounds that contain more than one
functional group indicated by a suffix
Functional Suffix If Higher Prefix If Lower
Group in Precedence in Precedence
Increasing precedence

- COOH -oic acid

- CHO -al oxo-
C= O -one oxo-
- OH -ol hydroxy-
- SH -thiol -sulfanyl
- NH2 -amine -amino
 Boiling Points

 Ketones and aldehydes are more polar, so they

have a higher boiling point than comparable
alkanes or ethers.
 They cannot hydrogen-bond to each other, so
their boiling point is lower than comparable
alcohol.
12
Solubility of Ketones and Aldehydes
 Good solvent for
alcohols.
 Lone pair of electrons on
oxygen of carbonyl can
accept a hydrogen bond
from O—H or N—H.
 Acetone and
acetaldehyde are
miscible in water.

13
 Formaldehyde

H H
C O HO
O O heat H 2O OH
H H C H H C
C C H H
O formaldehyde,
H H formalin
b.p. -21C
trioxane, m.p. 62C

 Gas at room temperature.

 Formalin is a 40% aqueous solution.
14
 Industrial Importance

 Acetone and methyl ethyl ketone are important solvents.

 Formaldehyde is used in polymers
like Bakelite (trademark of phenol-
formaldehyde resin).
 Flavorings and additives like vanilla, cinnamon, and
artificial butter.

15
16
Preparation of Aldehydes and Ketones
Oxidation of Secondary Alcohols to Ketones

 Secondary alcohols are readily oxidized to ketones

with sodium dichromate (Na2Cr2O7) in sulfuric acid
or by potassium permanganate (KMnO4).

17
Mechanism of Oxidation by Chromium(VI)

18
 Preparation of Aldehydes and Ketones
Oxidation of Primary Alcohols to Aldehydes

 Pyridinium chlorochromate (PCC) is

selectively used to oxidize primary
alcohols to aldehydes.
19
20
 Preparation of Aldehydes and Ketones
Ozonolysis of Alkenes

 The double bond is oxidatively

cleaved by ozone followed by
reduction.
21
Mechanism for Oxidation by Ozonolysis

22
 Preparation of Aldehydes and Ketones
Friedel–Crafts Reaction

 Reaction between an acyl halide and an aromatic

ring will produce a ketone.
23
 Preparation of Aldehydes and Ketones
Hydration of Alkynes

 The initial product of Markovnikov hydration is an enol,

which quickly tautomerizes to its keto form.
 Internal alkynes can be hydrated, but mixtures of ketones
often result.
24
Mechanism for Hydration of Alkynes

25
 Preparation of Aldehydes and Ketones
Hydroboration–Oxidation of Alkynes

 Hydroboration–oxidation of an alkyne gives anti-

Markovnikov addition of water across the triple bond.

26
Hydroboration–Oxidation of Alkynes

Chapter 18 27
 Preparation of Aldehydes and Ketones
Solved Problem 1
Show how you would synthesize each compound from starting materials
containing no more than six carbon atoms.
(a (b
) )

Solution
(a) This compound is a ketone with 12 carbon atoms. The carbon skeleton
might be assembled from two six-carbon fragments using a Grignard
reaction, which gives an alcohol that is easily oxidized to the target
compound.

28
 Preparation of Aldehydes and Ketones
Solved Problem 1 (Continued)
Solution (Continued)
An alternative route to the target compound involves Friedel–
Crafts acylation.

(b) Thiscompound is an aldehyde with eight carbon atoms. An aldehyde

might come from oxidation of an alcohol (possibly a Grignard product)
or hydroboration of an alkyne. If we use a Grignard, the restriction to
six-carbon starting materials means we need to add two carbons to a
methylcyclopentyl fragment, ending in a primary alcohol. Grignard
addition to an epoxide does this.

29
 Preparation of Aldehydes and Ketones
Solved Problem 1 (Continued)
Solution (Continued)
Alternatively, we could construct the carbon skeleton
using acetylene as the two-carbon fragment. The
resulting terminal alkyne undergoes hydroboration to
the correct aldehyde.

(b)

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Synthesis of Ketones and Aldehydes Synthesis
of Ketones from Carboxylic Acids

 Organolithiums will attack the lithium salts of

carboxylate anions to give dianions.
 Protonation of the dianion forms the hydrate of
a ketone, which quickly loses water to give the
ketone.
31
Synthesis of Ketones and Aldehydes Ketones
from Nitriles

 A Grignard or organolithium reagent can

attack the carbon of the nitrile.
 The imine is then hydrolyzed to form a ketone.

32
 Synthesis of Ketones and Aldehydes
Aldehydes from Acid Chlorides

 Lithium aluminum tri(t-butoxy)hydride is a

milder reducing agent that reacts faster with
acid chlorides than with aldehydes.

33
 Synthesis of Ketones and Aldehydes
Lithium Dialkyl Cuprate Reagents

 A lithium dialkylcuprate (Gilman reagent)

will transfer one of its alkyl groups to the
acid chloride.
34
 Reactions of Aldehydes and Ketones
Nucleophilic Addition

 A strong nucleophile attacks the carbonyl carbon,

forming an alkoxide ion that is then protonated.
 Aldehydes are more reactive than ketones.

35
 Reactions of Aldehydes and Ketones
The Wittig Reaction

 The Wittig reaction converts the carbonyl

group into a new C═C double bond where
no bond existed before.
 A phosphorus ylide is used as the
nucleophile in the reaction.
36
 Reactions of Aldehydes and Ketones
Preparation of Phosphorus Ylides

 Prepared from triphenylphosphine and an

unhindered alkyl halide.
 Butyllithium then abstracts a hydrogen from
the carbon attached to phosphorus.
37
 Reactions of Aldehydes and Ketones
Mechanism of the Wittig Reaction
Betaine formation

Oxaphosphetane formation

38
 Reactions of Aldehydes and Ketones
Mechanism of the WittigReaction (continued)

 The oxaphosphetane will collapse, forming the

alkene and a molecule of triphenyl phosphine
oxide.
39
 Reactions of Aldehydes and Ketones
Solved Problem 2
Show how you would use a Wittig reaction to
synthesize 1-phenyl-1,3-butadiene.

40
 Reactions of Aldehydes and Ketones
Solved Problem 2 (Continued)
Solution
This molecule has two double bonds that might be formed by Wittig
reactions. The central double bond could be formed in either of two ways.
Both of these syntheses will probably work, and both will produce a
mixture of cis and trans isomers.

You should complete this solution by drawing out the

syntheses indicated by this analysis 41
 Reactions of Aldehydes and Ketones
Hydration of Ketones and Aldehydes

 In an aqueous solution, a ketone or an

aldehyde is in equilibrium with its hydrate, a
geminal diol.
 With ketones, the equilibrium favors the
unhydrated keto form (carbonyl).
42
 Reactions of Aldehydes and Ketones
Mechanism of Hydration of Ketones and Aldehydes

 Hydration occurs through the nucleophilic

addition mechanism, with water (in acid) or
hydroxide (in base) serving as the
nucleophile.
43
 Reactions of Aldehydes and Ketones
Cyanohydrin Formation

 The mechanism is a base-catalyzed

nucleophilic addition: Attack by cyanide ion
on the carbonyl group, followed by
protonation of the intermediate.
 HCN is highly toxic.
44
 Reactions of Aldehydes and Ketones
Formation of Imines

 Ammonia or a primary amine reacts with a ketone or

an aldehyde to form an imine (Schiff base)
 Imines are nitrogen analogues of ketones and
aldehydes with a C═N bond in place of the carbonyl
group.
 Optimum pH is around 4.5
45
 Reactions of Aldehydes and Ketones
Mechanism of Imine Formation
Acid-catalyzed addition of the amine to the carbonyl
group leads to a carbinolamine

Acid-catalyzed dehydration of the carbinolamine gives the imine

46
Reactions of Aldehydes and Ketones
Other Condensations with Amines

47
Reactions of Aldehydes and Ketones
Formation of Acetals

48
 Reactions of Aldehydes and Ketones
Mechanism for Hemiacetal Formation

 Must be acid-catalyzed.
 Adding H+ to carbonyl makes it more
reactive with weak nucleophile, ROH.
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Reactions of Aldehydes and Ketones
Acetal Formation

50
 Reactions of Aldehydes and Ketones
Cyclic Acetals

 Addition of a diol produces a cyclic acetal.

 The reaction is reversible.
 This reaction is used in synthesis to protect
carbonyls from reaction
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 Reactions of Aldehydes and Ketones
Acetals as Protecting Groups

O O
HO O
OH
H +
H
H
O O

 Hydrolyze easily in acid; stable in base.

 Aldehydes are more reactive than ketones.
52
 Reactions of Aldehydes and Ketones
Reaction and Deprotection
O
O O
1) NaBH4
H 2) H3O+ H
O OH

 The acetal will not react with NaBH4, so only the

ketone will get reduced.
 Hydrolysis conditions will protonate the alcohol
and remove the acetal to restore the aldehyde.
53
 Reactions of Aldehydes and Ketones
Oxidation of Aldehydes

Aldehydes are easily oxidized to carboxylic acids.

54
 Reactions of Aldehydes and Ketones
Reducing Reagents
 Sodium borohydride, NaBH4, can reduce ketones
to secondary alcohols and aldehydes to primary
alcohols.
 Lithium aluminum hydride, LiAlH4, is a powerful
reducing agent, so it can also reduce carboxylic
acids and their derivatives.
 Hydrogenation with a catalyst can reduce the
carbonyl, but it will also reduce any double or
triple bonds present in the molecule.
55
 Reactions of Aldehydes and Ketones
Sodium Borohydride
O OH
NaBH4
R R(H) CH3OH R R(H)
H
aldehyde or ketone

• NaBH4 can reduce ketones and

aldehydes, but not esters, carboxylic
acids, acyl chlorides, or amides.
56
 Reactions of Aldehydes and Ketones
Lithium Aluminum Hydride
O OH
LiAlH4
R R(H) ether R R(H)
H
aldehyde or ketone

 LiAlH4 can reduce any carbonyl because it is

a very strong reducing agent.
 Difficult to handle.

57
 Reactions of Aldehydes and Ketones
Catalytic Hydrogenation
O OH

H2
Raney Ni

 Widely used in industry.

 Raney nickel is finely divided Ni powder saturated
with hydrogen gas.
 It will attack the alkene first, then the carbonyl.
58
 Reactions of Aldehydes and Ketones
Deoxygenation of Ketones and Aldehydes

 The Clemmensen reduction or the Wolff–

Kishner reduction can be used to
deoxygenate ketones and aldehydes.
59
Reactions of Aldehydes and Ketones
Clemmensen Reduction
O
C CH2CH2CH3
CH2CH3 Zn(Hg)
HCl, H2O

O
Zn(Hg)
CH2 C CH2 CH3
H HCl, H2O

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 Reactions of Aldehydes and Ketones
Wolff–Kishner Reduction

 Forms hydrazone, then heat with strong base like

KOH or potassium tert-butoxide.
 Use a high-boiling solvent: ethylene glycol,
diethylene glycol, or DMSO.
 A molecule of nitrogen is lost in the last steps of
the reaction.
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