Chapter 16

Aldehydes and Ketones

1. Introduction

 Carbonyl compounds
2. Nomenclature of Aldehydes &
Ketones
 Rules
● Aldehyde as parent (suffix)
 Ending with “al”;
● Ketone as parent (suffix)
 Ending with “one”
● Number the longest carbon chain
containing the carbonyl carbon,
starting at the carbonyl carbon
 Examples
 group as a prefix: methanoyl
or formyl group

 group as a prefix: ethanoyl or

acetyl group (Ac)

 groups as a prefix: alkanoyl or

acyl groups
3. Physical Properties
4. Synthesis of Aldehydes
o
4A. Aldehydes by Oxidation of 1 Alcohols

Pyridinium chlorochromate (PCC)

 e.g.
4B. Aldehydes by Ozonolysis of
Alkenes
 e.g.
4C. Aldehydes by Reduction of Acyl
Chlorides, and Esters
 LiAlH4 is a very powerful reducing
agent and aldehydes are easily
reduced
● Usually reduced all the way to the
o
corresponding 1 alcohol
● Difficult to stop at the aldehyde
stage
 Not a good method to
synthesize aldehydes using
LiAlH4
 Two aluminum hydride derivatives that
are less reactive than LAH:
 Aldehydes from acyl chlorides: RCOCl
 RCHO

 e.g.
 Examples
5. Synthesis of Ketones
5A. Ketones from Alkenes, Arenes,
o
and 2 Alcohols
 Ketones (and aldehydes) by ozonolysis
of alkenes
 Examples
 Aryl ketones from arenes by Friedel–
Crafts acylations
 Ketones from secondary alcohols by
oxidation
Swern Oxidation

Swern oxidation of a 1°
alcohol to an aldehyde

Swern oxidation of a 2°
alcohol to a ketone
5B. Ketones from Nitriles
 Examples
 Suggest synthesis of

from and
 Retrosynthetic analysis

5 carbons here 4 carbons here

 need to add
one carbon
 Retrosynthetic analysis
disconnection

disconnection
 Synthesis
 Suggest synthesis of

from and
 Retrosynthetic analysis

5 carbons here
5 carbons here

 no need to
add carbon
 Retrosynthetic analysis

disconnection
 Synthesis
6. Nucleophilic Addition to the
Carbon–Oxygen Double Bond
 Structure

⊖
Nu

● Carbonyl carbon: sp2 hybridized

● Trigonal planar structure
 Polarization and resonance structure

● Nucleophiles will attack the

electrophilic carbonyl carbon

● Note: nucleophiles usually do not

attack a non-polarized C=C bond
 With a strong nucleophile:
 catalyzed by an acid (or Lewis acid)

● Note: full positive charge on the carbonyl

carbon in one of the resonance forms
 Nucleophiles readily attack
 Mechanism
 Mechanism
6B. Relative Reactivity: Aldehydes,
Ketones, and Esters

Why?
Again……again and again……………..
 Steric factors

small

large
 Electronic factors
(positive inductive effect from
both R & R' groups)  carbonyl
carbon less d+ (less nucleophilic)

(positive inductive
effect from only
one R group)
6C. Addition Products Can Undergo
Further Reactions

stable product: isolable

 But

unstable
7. The Addition of Alcohols:
Hemiacetals and Acetals
 Hemiacetal & Acetal Formation:
Addition of Alcohols to Aldehydes

Catalyzed
by acid
 Mechanism
 Mechanism (Cont’d)
 Mechanism (Cont’d)
 Note: All steps are reversible. In the
presence of a large excess of
anhydrous alcohol and a catalytic
amount of acid, the equilibrium
strongly favors the formation of acetal
(from aldehyde) or ketal (from
ketone).
 On the other hand, in the presence of
a large excess of H2O and a catalytic
amount of acid, the acetal or ketal will
hydrolyze back to aldehyde or ketone.
This process is called hydrolysis.
 Acetals and ketals are stable in neutral
or basic solution, but are readily
hydrolyzed in aqueous acid
 Aldehyde hydrates: gem-diols
 Mechanism
7A. Hemiacetals

Hemiacetal: OH & OR groups

bonded to the same carbon
Hemiacetal: OH & OR
groups bonded to the
same carbon
7B. Acetals
A ketal

An acetal
 Cyclic acetal formation is favored when
a ketone or an aldehyde is treated with
an excess of a 1,2-diol and a trace of
acid
 This reaction, too, can be reversed by
treating the acetal with lots of an
aqueous acid
7C. Acetals Are Used as Protecting
Groups
 Although acetals are hydrolyzed to aldehydes
and ketones in aqueous acid, acetals are
stable in basic solutions
 Acetals are used to protect aldehydes
and ketones from undesired reactions
in basic solutions
 Example
● Synthetic plan

 This route will not work

Reason:
(a) Intramolecular nucleophilic addition

(b) Homodimerization or polymerization

 Thus, need to “protect” carbonyl group first
7D. Thioacetals
 Aldehydes & ketones react with thiols
to form thioacetals
8. The Addition of Primary and
Secondary Amines
o
 Aldehydes & ketones react with 1
o
amines to form imines and with 2
amines to form enamines
o o
From a 1 amine From a 2 amine
8A. Imines
o
 Addition of 1 amines to aldehydes &
ketones
 Mechanism
 Similar to the formation of acetals and
ketals, all the steps in the formation of
imines are reversible.

 Hydrolysis of imines is also possible by

adding excess water in the presence of
catalytic amount of acid
8B. Oximes and Hydrazones
o
 Imine formation – reaction with a 1 amine

 Oxime formation – reaction with

hydroxylamine
 Hydrazone formation – reaction with
hydrazine

o
 Enamine formation – reaction with a 2
amine
8D. Enamines
 Mechanism
 Mechanism (Cont’d)
 Mechanism (Cont’d)
9. The Addition of Hydrogen
Cyanide: Cyanohydrins
 Addition of HCN to aldehydes & ketones
 Mechanism
 Synthetic applications
10. The Addition of Ylides:
The Wittig Reaction
 Phosphorus ylides
 Example
 Mechanism of the Wittig reaction
10A. How to Plan a Wittig Synthesis

 Synthesis of

using a Wittig reaction

 Retrosynthetic analysis
 Synthesis – Route 1
 Synthesis – Route 2
11. Oxidation of Aldehydes
12. The Baeyer-Villiger Oxidation
13. Conjugate Nucleophilic Addition to
-Unsaturated Aldehydes and Ketones
 1,2-addition: Addition of a nucleophile
directly to the carbonyl group
● Grignards; Organolithiums, NaBH4, LiAlH4.
13. Conjugate Nucleophilic Addition to
-Unsaturated Aldehydes and Ketones
 Conjugate addition (1,4-addition): Addition of a
nucleophile to the C=C double bond
● Cyanide, 1 ̊ & 2 ̊ amines, enolates and enamines.
 Organocopper Reactions
● Reaction of an -unsaturated ketone with a
Gillman reagent
15. Spectroscopic Properties of
Aldehydes and Ketones
15A. IR Spectra of Aldehydes and Ketones
15B. NMR Spectra of Aldehydes and
Ketones
 C NMR spectra
13

● The carbonyl carbon of an aldehyde

or ketone gives characteristic NMR
signals in the d 180–220 ppm
region of 13C spectra
 1
H NMR spectra
● An aldehyde proton gives a distinct 1H
NMR signal downfield in the d 9–12 ppm
region where almost no other protons
absorb; therefore, it is easily identified

● Protons on the a carbon are deshielded

by the carbonyl group, and their signals
generally appear in the d 2.0–2.3 ppm
region
16. Summary of Aldehyde and
Ketone Addition Reactions