Chapter 19.

Aldehydes and
Ketones: Nucleophilic
Addition Reactions

Based on McMurry’s Organic Chemistry, 6th

edition
©2003 Ronald Kluger
Department of Chemistry
University of Toronto

Based on McMurry, Organic Chemistry, Chapter 1

19, 6th edition, (c) 2003
Aldehydes and Ketones
 Aldehydes and ketones are characterized by the the
carbonyl functional group (C=O)
 The compounds occur widely in nature as
intermediates in metabolism and biosynthesis
 They are also common as chemicals, as solvents,
monomers, adhesives, agrichemicals and
pharmaceuticals

Based on McMurry, Organic Chemistry, Chapter 2

19, 6th edition, (c) 2003
19.1 Naming Aldehydes and Ketones
 Aldehydes are named by replacing the terminal -e of
the corresponding alkane name with –al
 The parent chain must contain the CHO group
 The CHO carbon is numbered as C1
 If the CHO group is attached to a ring, use the
suffix See Table 19.1 for common names

Based on McMurry, Organic Chemistry, Chapter 3

19, 6th edition, (c) 2003
Naming Ketones
 Replace the terminal -e of the alkane name with –one
 Parent chain is the longest one that contains the
ketone group
 Numbering begins at the end nearer the carbonyl
carbon

Based on McMurry, Organic Chemistry, Chapter 4

19, 6th edition, (c) 2003
Ketones with Common Names
 IUPAC retains well-used but unsystematic names for
a few ketones

Based on McMurry, Organic Chemistry, Chapter 5

19, 6th edition, (c) 2003
Ketones and Aldehydes as Substituents
 The R–C=O as a substituent is an acyl group is used
with the suffix -yl from the root of the carboxylic acid
 CH3CO: acetyl; CHO: formyl; C6H5CO: benzoyl
 The prefix oxo- is used if other functional groups are
present and the doubly bonded oxygen is labeled as a
substituent on a parent chain

Based on McMurry, Organic Chemistry, Chapter 6

19, 6th edition, (c) 2003
 19.2 Preparation of Aldehydes and
Ketones
 Preparing Aldehydes
 Oxidize primary alcohols using pyridinium
chlorochromate
 Reduce an ester with diisobutylaluminum
hydride (DIBAH)

Based on McMurry, Organic Chemistry, Chapter 7

19, 6th edition, (c) 2003
Preparing Ketones
 Oxidize a 2° alcohol (see Section 17.8)
 Many reagents possible: choose for the specific
situation (scale, cost, and acid/base sensitivity)

Based on McMurry, Organic Chemistry, Chapter 8

19, 6th edition, (c) 2003
Ketones from Ozonolysis
 Ozonolysis of alkenes yields ketones if one of the
unsaturated carbon atoms is disubstituted (see
Section 7.8)

Based on McMurry, Organic Chemistry, Chapter 9

19, 6th edition, (c) 2003
Aryl Ketones by Acylation
 Friedel–Crafts acylation of an aromatic ring with an
acid chloride in the presence of AlCl3 catalyst (see
Section 16.4)

Based on McMurry, Organic Chemistry, Chapter 10

19, 6th edition, (c) 2003
Methyl Ketones by Hydrating Alkynes
 Hydration of terminal alkynes in the presence of Hg2+
(catalyst: Section 8.5)

Based on McMurry, Organic Chemistry, Chapter 11

19, 6th edition, (c) 2003
19.3 Oxidation of Aldehydes and
Ketones
 CrO3 in aqueous acid oxidizes aldehydes to
carboxylic acids efficiently
 Silver oxide, Ag2O, in aqueous ammonia (Tollens’
reagent) oxidizes aldehydes (no acid)

Based on McMurry, Organic Chemistry, Chapter 12

19, 6th edition, (c) 2003
Hydration of Aldehydes
 Aldehyde oxidations occur through 1,1-diols
(“hydrates”)
 Reversible addition of water to the carbonyl group
 Aldehyde hydrate is oxidized to a carboxylic acid by
usual reagents for alcohols

Based on McMurry, Organic Chemistry, Chapter 13

19, 6th edition, (c) 2003
Ketones Oxidize with Difficulty
 Undergo slow cleavage with hot, alkaline KMnO4
 C–C bond next to C=O is broken to give carboxylic
acids
 Reaction is practical for cleaving symmetrical ketones

Based on McMurry, Organic Chemistry, Chapter 14

19, 6th edition, (c) 2003
19.4 Nucleophilic Addition Reactions of
Aldehydes and Ketones
 Nu- approaches 45° to the plane of C=O and adds
to C
 A tetrahedral alkoxide ion intermediate is produced

Based on McMurry, Organic Chemistry, Chapter 15

19, 6th edition, (c) 2003
Nucleophiles
 Nucleophiles can be negatively charged ( : Nu) or
neutral ( : Nu) at the reaction site
 The overall charge on the nucleophilic species is not
considered

Based on McMurry, Organic Chemistry, Chapter 16

19, 6th edition, (c) 2003
19.5 Relative Reactivity of Aldehydes
and Ketones
 Aldehydes are generally more reactive than ketones
in nucleophilic addition reactions
 The transition state for addition is less crowded and
lower in energy for an aldehyde (a) than for a ketone
(b)
 Aldehydes have one large substituent bonded to the
C=O: ketones have two

Based on McMurry, Organic Chemistry, Chapter 17

19, 6th edition, (c) 2003
Electrophilicity of Aldehydes and
Ketones
 Aldehyde C=O is more polarized than ketone C=O
 As in carbocations, more alkyl groups stabilize +
character
 Ketone has more alkyl groups, stabilizing the C=O
carbon inductively

Based on McMurry, Organic Chemistry, Chapter 18

19, 6th edition, (c) 2003
Reactivity of Aromatic Aldehydes
 Less reactive in nucleophilic addition reactions than
aliphatic aldehydes
 Electron-donating resonance effect of aromatic ring
makes C=O less reactive electrophilic than the
carbonyl group of an aliphatic aldehyde

Based on McMurry, Organic Chemistry, Chapter 19

19, 6th edition, (c) 2003
19.6 Nucleophilic Addition of H2O:
Hydration
 Aldehydes and ketones react with water to yield 1,1-
diols (geminal (gem) diols)
 Hyrdation is reversible: a gem diol can eliminate
water

Based on McMurry, Organic Chemistry, Chapter 20

19, 6th edition, (c) 2003
Relative Energies
 Equilibrium generally favors the carbonyl compound
over hydrate for steric reasons
 Acetone in water is 99.9% ketone form
 Exception: simple aldehydes
 In water, formaldehyde consists is 99.9% hydrate

Based on McMurry, Organic Chemistry, Chapter 21

19, 6th edition, (c) 2003
Base-Catalyzed Addition of Water
 Addition of water is catalyzed by
both acid and base
 The base-catalyzed hydration
nucleophile is the hydroxide ion,
which is a much stronger
nucleophile than water

Based on McMurry, Organic Chemistry, Chapter 22

19, 6th edition, (c) 2003
Acid-Catalyzed Addition of Water
 Protonation of C=O makes it
more electrophilic

Based on McMurry, Organic Chemistry, Chapter 23

19, 6th edition, (c) 2003
Addition of H-Y to C=O
 Reaction of C=O with H-Y, where Y is
electronegative, gives an addition product (“adduct”)
 Formation is readily reversible

Based on McMurry, Organic Chemistry, Chapter 24

19, 6th edition, (c) 2003
19.7 Nucleophilic Addition of HCN:
Cyanohydrin Formation
 Aldehydes and unhindered ketones react with HCN
to yield cyanohydrins, RCH(OH)CN

Based on McMurry, Organic Chemistry, Chapter 25

19, 6th edition, (c) 2003
Mechanism of Formation of
Cyanohydrins
 Addition of HCN is reversible and base-catalyzed,
generating nucleophilic cyanide ion, CN
 Addition of CN to C=O yields a tetrahedral
intermediate, which is then protonated
 Equilibrium favors adduct

Based on McMurry, Organic Chemistry, Chapter 26

19, 6th edition, (c) 2003
Uses of Cyanohydrins
 The nitrile group (CN) can be reduced with LiAlH4
to yield a primary amine (RCH2NH2)
 Can be hydrolyzed by hot acid to yield a carboxylic
acid

Based on McMurry, Organic Chemistry, Chapter 27

19, 6th edition, (c) 2003
19.8 Nucleophilic Addition of Grignard Reagents
and Hydride Reagents: Alcohol Formation

 Treatment of aldehydes or ketones with Grignard

reagents yields an alcohol
 Nucleophilic addition of the equivalent of a carbon
anion, or carbanion. A carbon–magnesium bond is
strongly polarized, so a Grignard reagent reacts for all
practical purposes as R :  MgX +.

Based on McMurry, Organic Chemistry, Chapter 28

19, 6th edition, (c) 2003
Mechanism of Addition of Grignard
Reagents
 Complexation of C=O by Mg2+, Nucleophilic addition
of R : , protonation by dilute acid yields the neutral
alcohol
 Grignard additions are irreversible because a
carbanion is not a leaving group

Based on McMurry, Organic Chemistry, Chapter 29

19, 6th edition, (c) 2003
Hydride Addition
 Convert C=O to CH-OH
 LiAlH4 and NaBH4 react as donors of hydride ion
 Protonation after addition yields the alcohol

Based on McMurry, Organic Chemistry, Chapter 30

19, 6th edition, (c) 2003
19.9 Nucleophilic Addition of Amines: Imine
and Enamine Formation
RNH2 adds to C=O to form imines, R2C=NR (after loss
of HOH)
R2NH yields enamines, R2NCR=CR2 (after loss of
HOH)
(ene + amine = unsaturated amine)

Based on McMurry, Organic Chemistry, Chapter 31

19, 6th edition, (c) 2003
Mechanism of Formation of Imines
 Primary amine adds to C=O
 Proton is lost from N and adds to O to yield a neutral
amino alcohol (carbinolamine)
 Protonation of OH converts into water as the leaving
group
 Result is iminium ion, which loses proton
 Acid is required for loss of OH – too much acid blocks
RNH2

Note that overall reaction is substitution of RN for O

Based on McMurry, Organic Chemistry, Chapter 32

19, 6th edition, (c) 2003
Imine Derivatives
 Addition of amines with an atom containing a lone
pair of electrons on the adjacent atom occurs very
readily, giving useful, stable imines
 For example, hydroxylamine forms oximes and 2,4-
dinitrophenylhydrazine readily forms 2,4-
dinitrophenylhydrazones
 These are usually solids and help in characterizing
liquid ketones or aldehydes by melting points

Based on McMurry, Organic Chemistry, Chapter 33

19, 6th edition, (c) 2003
Enamine Formation
 After addition of R2NH, proton is lost from adjacent
carbon

R R R
R R R R R
O O
NH HO H2O N
+ R2NH N H+ N C
C + H3O+
C H C C
C C H C
H H C C H
H H H H

Based on McMurry, Organic Chemistry, Chapter 34

19, 6th edition, (c) 2003
 19.10 Nucleophilic Addition of Hydrazine: The
Wolff–Kishner Reaction
 Treatment of an aldehyde or ketone with hydrazine,
H2NNH2 and KOH converts the compound to an
alkane
 Originally carried out at high temperatures but with
dimethyl sulfoxide as solvent takes place near room
temperature

See Figure 19.11 for

a mechanism
Based on McMurry, Organic Chemistry, Chapter 35
19, 6th edition, (c) 2003
19.11 Nucleophilic Addition of
Alcohols: Acetal Formation
 Two equivalents of ROH in the presence of an acid
catalyst add to C=O to yield acetals, R2C(OR)2
 These can be called ketals if derived from a ketone

Based on McMurry, Organic Chemistry, Chapter 36

19, 6th edition, (c) 2003
Formation of Acetals
 Alcohols are weak nucleophiles but acid promotes
addition forming the conjugate acid of C=O
 Addition yields a hydroxy ether, called a hemiacetal
(reversible); further reaction can occur
 Protonation of the OH and loss of water leads to an
oxonium ion, R2C=OR+ to which a second alcohol
adds to form the acetal

Based on McMurry, Organic Chemistry, Chapter 37

19, 6th edition, (c) 2003
Uses of Acetals
 Acetals can serve as protecting groups for aldehydes
and ketones
 It is convenient to use a diol, to form a cyclic acetal
(the reaction goes even more readily)

Based on McMurry, Organic Chemistry, Chapter 38

19, 6th edition, (c) 2003
Mechanism for
Hemiacetal
O + OH OH

H+ +

H
OH HO OCH3
HO OCH3
+
+ HOCH3
HOCH3 +
+ H2OCH3

39 =>
Hemiacetal to Acetal
H
+ OCH3
HO OCH3 HO OCH3
+
H+ + HOH

HOCH3
H
OCH3 +
CH3O OCH3 CH3O OCH3
+
HOCH3

=>
40
19.12 Nucleophilic Addition of Phosphorus
Ylides: The Wittig Reaction
 The sequence converts C=O is to C=C
 A phosphorus ylide adds to an aldehyde or ketone to
yield a dipolar intermediate called a betaine
 The intermediate spontaneously decomposes
through a four-membered ring to yield alkene and
triphenylphosphine oxide, (Ph)3P=O
 Formation of the ylide is shown below

Based on McMurry, Organic Chemistry, Chapter 41

19, 6th edition, (c) 2003
Uses of the Wittig Reaction
 Can be used for monosubstituted, disubstituted, and
trisubstituted alkenes but not tetrasubstituted alkenes
The reaction yields a pure alkene of known structure
 For comparison, addition of CH3MgBr to
cyclohexanone and dehydration with, yields a mixture
of two alkenes

Based on McMurry, Organic Chemistry, Chapter 42

19, 6th edition, (c) 2003
Mechanism of the Wittig Reaction

Based on McMurry, Organic Chemistry, Chapter 43

19, 6th edition, (c) 2003
19.13 The Cannizzaro Reaction:
Biological Reductions
 The adduct of an aldehyde and OH can transfer
hydride ion to another aldehyde C=O resulting in a
simultaneous oxidation and reduction
(disproportionation)

Based on McMurry, Organic Chemistry, Chapter 44

19, 6th edition, (c) 2003
The Biological Analogue of the
Canizzaro Reaction
 Enzymes catalyze the reduction of aldehydes and ketones using
NADH as the source of the equivalent of H-
 The transfer resembles that in the Cannizzaro reaction but the
carbonyl of the acceptor is polarized by an acid from the
enzyme, lowering the barrier

Enzymes are chiral

and the reactions are
stereospecific. The
stereochemistry
depends on the
particular enzyme
involved.

Based on McMurry, Organic Chemistry, Chapter 45

19, 6th edition, (c) 2003