Chapter 18

Ketones and Aldehydes

Sections 18.5, 18.8-18.9, 18.13 omitted
Section 14.10B included
Chapter 18 Practice Problems

In-Chapter
18.1, 18.6, 18.10a-e, 18.11, 18.15-18.16,
18.20-18.21, 18.23, 18.26-18.28, 18.30, 18.33-
18.34, 18.36.

End of Chapter
18.37-18.38, 18.39a-b, d-f, h-j 18.47a, d, f-h 18.48-
18.49, 18.50a-c, 18.51a-g, 18.52-18.54, 18.65-
18.66
 Carbonyl Compounds

anhydrides

Chapter 18 3
 IUPAC Names for Ketones
Replace -e on parent hydrocarbon with -one.
Number the chain so that carbonyl carbon has the lowest
number.
For cyclic ketones the carbonyl carbon is always located at
position 1, and is not designated in the name.

Br

3-bromocyclohexanone 4-hydroxy-3-methylbutan-2-one

5
 Historical Common Names

O
C
O CH3
CH3 C CH3
acetone acetophenone
O
C

benzophenone

Chapter 18 6
 IUPAC Names for Aldehydes
Replace -e on parent hydrocarbon with -al.
The aldehyde carbon is always number 1 and is not
designated in the name.
If -CHO is attached to a ring, add the suffix carbaldehyde
to the name of the cyclic compound

3-methylpentanal cyclopent-2-enecarbaldehyde

7
 Aldehyde/Ketone as a Substituent
See inside back cover of your text or slide 6 of chapter 10
notes for priority in nomenclature.
On a molecule with a higher priority functional group, C=O
is oxo- and -CHO is formyl.
Aldehyde priority is higher than ketone.

COOH

CHO

3-methyl-4-oxopentanal 3-formylbenzoic acid

8
 Synthesis of aldehydes/ketones review
Ozonolysis of alkenes (chapter 8)

H R' H R'
1) O3
C C C O + O C
2) (CH3)2S
R R'' R R''

Oxidation (chapter 11)

2 alcohol + Na2Cr2O7/H2SO4 ketone
1 alcohol + PCC aldehyde

Friedel-Crafts acylation (chapter 17)

Acid chloride/AlCl3 + benzene phenyl ketone

Chapter 18 9
 Synthesis of aldehydes/ketones review
Hydration of terminal alkyne (chapter 9)
a) Use HgSO4, H2SO4, H2O for methyl ketone

b) Use Sia2BH followed by H2O2 in NaOH for aldehyde.

 Other methods of synthesizing
aldehydes and ketones

Relative reactivities of carbonyl compounds

Acyl (acid) halide > Acid anhydride > Aldehyde > Ketone >
Ester ~ Carboxylic acid > Amide > Carboxylate anion
 Aldehydes from Acid Chlorides
Recall from chapter 10: LiAlH4 (strong reducing agent) reduces
aldehydes and ketones to alcohols
Use a mild reducing agent to prevent reduction of the aldehyde
to primary alcohol.
Lithium tri-tert-butoxyaluminum hydride: replacing some of the hydrogens
of LiAlH4 with OR groups decreases reactivity. Reaction stops at the aldehyde,
since the acid chloride is more reactive under these conditions.

The reaction is conducted at

low temperature to prevent
reduction of the aldehyde.
More reactive Less reactive

Acid chloride made by

treating carboxylic acid
with thionyl chloride, SOCl2
Activated carboxylic acid 12
 Aldehydes from Esters
Recall from chapter 10: LiAlH4 (strong reducing agent) reduces esters to
primary alcohols
Like lithium tri-tert-butoxyaluminum hydride, DIBAL-H
(diisobutylaluminum hydride) stops reduction at the aldehyde without
forming a primary alcohol
DIBAL-H

Hydrolysis
Reduction step

Less reactive Aluminum complex is More reactive

stable to further reduction

Note: Unlike acid chlorides (previous slide), aldehydes are more reactive than esters.
The aldehyde is not reduced because the DIBAL-H is destroyed upon hydrolysis.
 Ketones from Acid Chlorides
Recall from chap 10: Lithium dialkyl cuprates do not readily
add to ketones and aldehydes.

Acid chlorides are susceptible to reaction with lithium

dialkylcuprate (R2CuLi)
Reaction stops at the ketone.

O O
(CH3CH2CH2)2CuLi + CH3CH2C Cl CH3CH2C CH2CH2CH3

Chapter 18 14
 Relative reactivities of carbonyl compounds
Polarized double bond susceptible to
nucleophilic attack

Aldehydes are more reactive than ketones because:

1. Electronics: alkyl groups are electron releasing and decrease
electrophilicity of the carbonyl carbon.
2. Sterics: Additional alkyl group in ketone makes the carbonyl carbon
less accessible to a nucleophile.
Acyl (acid) halide > Acid anhydride > Aldehyde > Ketone >
Ester ~ Carboxylic acid > Amide > Carboxylate anion
15
 Reactions of Aldehydes and Ketones:
Nucleophilic Addition
A strong nucleophile attacks the carbonyl carbon, forming an
alkoxide ion that is then protonated.
A weak nucleophile will attack a carbonyl if it has been
protonated (increased reactivity).

Chapter 18 16
Previous examples of Nucleophilic Addition (Ch. 10)
NaBH4/LiAlH4 reduction of aldehydes and ketones

Grignard/alkyl lithium addition to aldehydes and ketones

Chapter 18 18
 1. Wittig Reaction
Nucleophilic addition of phosphonium ylides (strong nucleophile).
Product is alkene. C=O becomes C=C.
Reaction is regioselective double bond in one place.
(only E,Z isomers formed)
Cf. dehyrohalogenation E1 and E2 mechanisms

Ylide has opposite charges

on adjacent covalently bonded
atoms that have complete octets.

So, well keep changing partners.

Chapter 18 19
 Phosphorus Ylides
Alkyl halide should be unhindered.

Chapter 18 20
 Mechanism for Wittig

The formation of the especially stable triphenylphoshine oxide drives

the reaction forward.
Chapter 18 21
 2. Formation of Cyanohydrins
HCN is highly toxic.
Use NaCN or KCN in base (strong nucleophile) to add cyanide,
then protonate to add H.
Reactivity formaldehyde > aldehydes > ketones >> bulky ketones.

Cyano groups (nitriles) can undergo acidic hydrolysis to give

carboxylic acids

22
 3. Formation of Imines
Nucleophilic addition of ammonia or primary
amine, followed by elimination of water molecule.
Forms imine, nitrogen analogue of ketones and
aldehydes with a CN bond in place of the carbonyl
group
C=O becomes C=N-R (Loss of H2 and O)

Chapter 18 23
Formation of Imines
 Mechanism of Imine Formation
Acid-catalyzed addition of the amine to the carbonyl compound group.

(Amine can act as strong nueclophile, so the first step can also be base catalyzed)
Acid-catalyzed dehydration.

Strongly acidic conditions destroy nucleophilic character of amines.

RNH2 + H+ RNH3+ (not nucleophilic)
Optimum pH is around 4.5 (catalytic acid required) 25
 Hydrolysis of imine
Imine formation is reversible. Imine can be hydrolyzed by
excess water under acidic conditions
Other Condensations

Chapter 18 27
 2,4-Dinitrophenylhydrazine (2,4-DNP) test for
aldehydes and ketones.

Yellow to red precipitate

Formation of yellow to red precipitate indicates the presence of

aldehyde or ketones.
The test cannot distinguish between the two functional groups.
The exact color depends on the degree of conjugation in the
carbonyl compound.
4. Addition of Alcohol: Acetal formation

Chapter 18 29
 Mechanism
Must be acid-catalyzed.
Adding H+ to carbonyl makes it more reactive with ROH (weak
nucleophile).
Hemiacetal forms first, then acid-catalyzed loss of water, then
addition of second molecule of ROH forms acetal.
All steps are reversible.

Chapter 18 30
Hemiacetal to Acetal

Chapter 18 31
 Cyclic Acetals
Addition of a diol produces a cyclic acetal.
Sugars commonly exist as acetals or hemiacetals.

Chapter 18 32
Each of the following compounds can be made using carbonyl compounds.
Give the structures of the carbonyl compounds and other starting materials
that are required to synthesize these compounds.
 Protecting Groups
Protecting group: temporarily protects a reactive functional group
(Recall: blocking groups block a position on an aromatic ring)
Protecting groups, like blocking groups, must be easily introduced and
also easily removed.

34
 Protecting for C=O groups: Acetals
Acetals hydrolyze easily in acid, but are stable in base.

Chapter 18 35
 Acetals as Protecting Groups
Aldehydes are more reactive than ketones.
Acetal can be used to selectively carry out reaction on
ketone in the presence of an aldehyde
Acetal can be used to selectively protect an aldehyde or
ketone from reacting in the presence of other
electrophiles, e.g . ester C=O.
Proposed synthesis

36
 Actual Synthesis

Protect aldehyde so it doesnt react with nucleophilic Grignard reagent

Since Grignard reagents are basic, Acetal cleaved

they wont affect the acetal in the presence of an acid.
Protecting for O-H groups: Silyl ethers (14.10B)

TIPS: Tri-Iso-Propyl-Silyl

Ethers based on silicon are much easier to remove than

carbon-based ethers.
Uses much gentler conditions than the strong acid used for
carbon-based ethers.
The silyl ether group can be removed in aqueous or organic
solvents, using TBAF (tetrabutylammonium fluoride).
Strong Si-F bond formed.
Chapter 18 38
 Protecting for O-H groups: Silyl ethers (14.10B)
Recall from chapter 10 that Grignard reagents are not compatible with OH groups.
Grignard reagents are both nucleophilic and basic.

Grignard reagent can selectively react with C=O if the reactive OH is protected first.
Show how you would carry out the following
transformations.

40
Oxidation and Reduction reactions of
aldehyde/ketone
 Oxidation of Aldehydes
Easily oxidized to carboxylic acids.

Chapter 18 42
 Tollens Test
Tollens reagent: silver-ammonia complex in basic solution.
Reaction with aldehdye forms a silver mirror.
Tollens reagent does not affect ketones.

O O
+
_ H2O _
R C H + 2 Ag(NH3)2 + 3 OH 2 Ag + R C O + 4

O
2O
_
2 Ag + R C O + 4 NH3 + 2 H2O

Chapter 18 43
 Reduction Reagents
(review from chapter 10)
Sodium borohydride, NaBH4, reduces C=O of aldehyde or
ketone, but not C=C.
Lithium aluminum hydride, LiAlH4, much stronger, difficult to
handle.
Hydrogen gas with Raney nickel also reduces the C=C bond.

Chapter 18 44
 Deoxygenation
Reduction of C=O to CH2
Two methods:
Clemmensen reduction if molecule is stable in hot acid.
Wolff-Kishner reduction if molecule is stable in very strong
base.
Clemmensen Reduction
O
C CH2CH2CH3
CH2CH3 Zn(Hg)
HCl, H2O
Heat
O
Zn(Hg)
CH2 C CH2 CH3
H HCl, H2O
Heat
45
 Wolff-Kishner Reduction
Hydrazine (H2N-NH2) forms hydrazone
Heat with strong base like KOH or potassium t-butoxide.
Use a high-boiling solvent: ethylene glycol, diethylene
glycol, or DMSO.

Chapter 18 46