William H.

Brown
Christopher S. Foote
Brent L. Iverson
Eric Anslyn
http://academic.cengage.com/chemistry/brown

Chapter 16
Aldehydes and Ketones

William H. Brown • Beloit College

16-1
16-2
The Carbonyl Group
 In this and several following chapters, we study
the physical and chemical properties of classes
of compounds containing the carbonyl C=O
group.
• aldehydes and ketones (Chapter 16)
• carboxylic acids (Chapter 17)
• acid halides, acid anhydrides, esters, and amides
(Chapter 18)

16-3
The Carbonyl Group
• The carbonyl group consists of one sigma bond
formed by the overlap of sp2 hybrid orbitals and one pi
bond formed by the overlap of parallel 2p orbitals
• pi bonding and pi antibonding MOs for formaldehyde

16-4
Structure
• The functional group of an aldehyde is a carbonyl
group bonded to an 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)

16-5
Nomenclature
 IUPAC names:
• The parent chain is the longest chain that contains the
carbonyl group.
• For an aldehyde, change the suffix from -e to -al.
• For an unsaturated aldehyde, change the infix from
-an- to -en-; the location of the suffix determines the
numbering pattern.
• For a cyclic molecule in which -CHO is bonded to the
ring, add the suffix -carbaldehyde.

16-6
Nomenclature: Aldehydes
O O O
7 5 3 1
H H 8 6 4 2
H

3-M ethylbutanal 2-Propenal (2E)-3,7-D imethyl-2,6-octadienal

(A crolein) (Geranial)

4 1
CHO HO CHO
Cyclopentane- trans-4-H ydroxycyclo-
carbaldehyde hexanecarbaldehyde

• The IUPAC naming retains the common names

benzaldehyde and cinnamaldehyde, as well
formaldehyde and acetaldehyde.
CHO CHO
C6 H5

Benzaldehyde trans-3-Phenyl-2-propenal
(Cinnamaldehyde) 16-7
Nomenclature: Ketones
 IUPAC names
• The parent alkane is the longest chain that contains
the carbonyl group.
• Indicate the ketone by changing the suffix -e to -one.
• Number the chain to give C=O the smaller number.
• The IUPAC retains the common names acetone,
acetophenone, and benzophenone.
O O O
O

Propanone A cetophenone Benzophenone 1-Phenyl-1-pentanone

(Acetone)

16-8
Example 16.1

16-9
Example 16.2

16-10
Order of Precedence
 For compounds that contain more than one
functional group indicated by a suffix.

16-11
Example 16.3

16-12
Common Names
• For an aldehyde, the common name is derived from
the common name of the corresponding carboxylic
acid.
• For a ketone, name the two alkyl or aryl groups
bonded to the carbonyl carbon and add the word
ketone.
O O O O
HCH HCOH CH3 CH CH3 COH
Formaldehyde Formic acid A cetaldehyde Acetic acid
O
O O

Ethyl isopropyl ketone D iethyl ketone D icyclohexyl ketone

16-13
Physical Properties
 Oxygen is more electronegative than carbon (3.5
vs 2.5) and, therefore, a C=O group is polar.
δ+ δ- +
C O C O C O –

Polarity of M ore important

a carbonyl contributing
group structure

• Aldehydes and ketones are polar compounds and

interact in the pure state by dipole-dipole interaction.
• They have higher boiling points and are more soluble
in water than nonpolar compounds of comparable
molecular weight.

16-14
Reaction Themes
 One of the most common reaction themes of a
carbonyl group is addition of a nucleophile to
form a tetrahedral carbonyl addition compound.

-
R O
-
Nu + C O Nu C
R R
R
Tetrahedral carbonyl
addition compound

16-15
Reaction Themes
 A second common theme is reaction with a
proton or other Lewis acid to form a resonance-
stabilized cation.
• Protonation increases the electron deficiency of the
carbonyl carbon and makes it more reactive toward
nucleophiles.
R fast R + R
- +
C O + H- B B + C O H C O H
R R R

R O-H
- + slow
B + H- Nu + C O H Nu C + H- B
R R
R
Tetrahedral carbonyl
addition compound 16-16
Reaction Themes
• Often the tetrahedral product of addition to a carbonyl
group is a new chiral center.
• If none of the starting materials is chiral and the
reaction takes place in an achiral environment, then
enantiomers will be formed as a racemic mixture.
Approach from
the top face Nu Nu
O OH
R R
- R' H3 O + R'
Nu R
C O + +
R' R R
R' R'
O OH
Nu Nu
Approach from A new chiral A racemic mixture
the bottom face center is created
16-17
Addition of C Nucleophiles
 Addition of carbon nucleophiles is one of the
most important types of nucleophilic additions to
a C=O group.
• A new carbon-carbon bond is formed in the process.
• We study addition of these four types of carbon
nucleophiles.
RMgX RLi RC C - -
C N
A Grignard An organolithium A n alk yne Cyanide ion
reagent reagent anion

16-18
Grignard Reagents
 Given the difference in electronegativity between
carbon and magnesium (2.5 - 1.3), the C-Mg bond
is polar covalent, with Cδ- and Mgδ+.
• In its reactions, a Grignard reagent behaves as a
carbanion.
 Carbanion: An anion in which carbon has an
unshared pair of electrons and bears a negative
charge.
• A carbanion is a good nucleophile and adds readily to
the carbonyl group of aldehydes and ketones.

16-19
Grignard Reagents
• Addition of a Grignard reagent to formaldehyde
followed by treatment with H3O+ gives a 1° alcohol.
O
ether
CH3 CH2 -MgBr + H- C-H
Formaldehyde
- +
O [ MgBr] OH
HCl
CH3 CH2 -CH2 CH3 CH2 -CH2 + M g2+
H2 O
A magnesium 1-Propanol
alkoxide (a 1?alcohol)

16-20
Grignard Reagents
• Addition to any other RCHO gives a 2° alcohol.

Mg Br O ether
+
H
Acetaldehyde
(an aldehyde)
- +
O [ MgBr] OH
HCl
+ M g2+
H2 O

A magnesium 1-Cyclohexylethanol
alkoxide (a 2?alcohol;
(racemic)

16-21
Grignard Reagents
• Addition to a ketone gives a 3° alcohol.
O ether
Ph- MgBr +

Phenyl- Acetone
magnesium (a ketone)
bromide
- + OH
O [ MgBr] HCl + M g2+
Ph H2 O Ph
A magnesium 2-Phenyl-2-propanol
alkoxide (a 3?alcohol)

16-22
Example 16.4
Problem: 2-Phenyl-2-butanol can be synthesized by three
different combinations of a Grignard reagent and a
ketone. Show each combination.
OH
C-CH2 CH3
CH3

16-23
Organolithium Compounds
 Organolithium compounds are generally more
reactive in C=O addition reactions than RMgX,
and typically give higher yields.
- +
O Li OH
O
Li
+ HCl
H2 O
Phenyl- 3,3-Dimethyl-2- A lithium alkoxide 3,3-Dimethyl-2-phenyl-
lithium butanone (racemic) 2-butanol
(racemic)

16-24
Salts of Terminal Alkynes
 Addition of an alkyne anion followed by
treatment with H3O+ gives an α-acetylenic
alcohol.
O
HC C O - N a+ HC C OH
-
HC C: N a+ + HCl
H2 O
Sodium Cyclohexanone A sodium 1-Ethynyl-
acetylide alkoxide cyclohexanol

16-25
Hydration of Terminal Alkynes
O
Ch7. page 269
HO CCH3
H2 O α
H2 SO4 , HgSO4
HO C CH
An α-hydroxyketone
O
α
HO CH2 CH
1 . (sia) 2 BH
β
2 . H2 O2 , NaOH
Ch7. page 267 A β-hydroxyaldehyde
B-H

D i-sec-isoamylborane
[(sia)2 BH]
16-26
* Addition of H2O: hydration
• Step 1: Attack of Hg2+ (an electrophile) on the triple
bond (a nucleophile) gives a bridged mercurinium ion.

• Step 2: Attack of water (a nucleophile) on the bridged

mercurinium ion intermediate (an electrophile) opens
the three-membered ring.

16-27
* Addition of H2O: hydration
• Step 3: Proton transfer to solvent gives an
organomercury enol.
H3 C Hg + H3 C Hg
+
H
O + C C C C + H3 O+
O+
H H H O H
H H

• Step 4: Tautomerism of the enol gives the keto form.

+
H3 C Hg O
+
C C CH3 -C-CH2 -Hg
HO H Keto form
Enol form

16-28
* Addition of H2O: hydration
• Step 5: Proton transfer to the carbonyl oxygen gives
an oxonium ion. +
H
+ O O
+
H O H + CH3 -C-CH2 -Hg+ CH3 -C-CH2 -Hg + H2 O:
H

• Steps 6 and 7: Loss of Hg2+ gives an enol; tautomerism

of the enol gives the ketone.
H+ H
O O O
+ 2+
CH3 -C-CH2 -Hg Hg + CH3 -C=CH2 CH3 -C-CH3
(enol form) (Keto form)

16-29
Addition of HCN
 HCN adds to the C=O group of an aldehyde or
ketone to give a cyanohydrin.
 Cyanohydrin: A molecule containing an -OH
group and a -CN group bonded to the same
carbon.
O OH
CH3 CH + HC N CH 3 C-C N
H
2-Hydroxypropanenitrile
(Acetaldehyde cyanohydrin)

16-30
Addition of HCN
 Mechanism of cyanohydrin formation
• Step 1: Nucleophilic addition of cyanide to the
carbonyl carbon.
-
H3 C - H3 C O
C O + C N • C
•
H3 C H3 C C N

• Step 2: Proton transfer from HCN gives the

cyanohydrin and regenerates cyanide ion nucleophile.
H3 C O - H3 C O-H -
C + H C N C + C N

•
•
H3 C C N H3 C C N

16-31
Cyanohydrins
 The value of cyanohydrins
• Acid-catalyzed dehydration of the alcohol gives an
alkene.
OH acid
catalyst
CH3 CHC N CH2 = CHC N + H2 O
2-Hydroxypropanenitrile Propenenitrile
(Acetaldehyde cyanohydrin) (Acrylonitrile)

• Catalytic reduction of the cyano group gives a 1°

amine.
OH OH
Ni
CHC N + 2 H2 CHCH2 NH2

Benzaldehyde 2-Amino-1-phenylethanol
cyanohydrin (racemic)
(racemic) 16-32
Wittig Reaction
 The Wittig reaction is a very versatile synthetic
method for the synthesis of alkenes from
aldehydes and ketones.
+ -
O + Ph3 P-CH2 CH2 + Ph 3 P=O

Cyclohexanone A phosphonium M ethylene- Triphenyl-

ylide cyclohexane phosphine oxide

Ylide : A neutral molecule with positive and

negative charges on adjacent atoms

16-33
Phosphonium Ylides
 Phosphonium ylides are formed in two steps:
• Step 1: Nucleophilic displacement of iodine by
triphenylphosphine.
SN 2 +
Ph 3 P + CH3 -I Ph3 P-CH3 I
Triphenylphosphine M ethyltriphenylphosphonium iodide
(an alk yltriphenylphosphine salt)

• Step 2: Treatment of the phosphonium salt with a very

strong base, most commonly BuLi, NaH, or NaNH2.
+
+
CH3 CH2 CH2 CH2 Li + H- CH2 -PPh 3 I
Butyllithium +
CH3 CH2 CH2 CH3 + CH2 -PPh 3 + LiI
Butane A phosphonium
ylide
16-34
Wittig Reaction
 Phosphonium ylides react with the C=O group of
aldehydes and ketones to give alkenes.
• Step 1: Nucleophilic addition of the ylide to the
electrophilic carbonyl carbon.
O CR2 -
:O CR2 O CR2
- +
+
Ph3 P CH2 Ph3 P CH2
Ph3 P CH2
A betaine An oxaphosphetane

• Step 2: Decomposition of the oxaphosphatane.

O CR2
Ph 3 P= O + R2 C= CH2
Ph 3 P CH2
Triphenylphosphine An alkene
oxide
16-35
Wittig Reaction
• Examples:
O + Ph3 P + Ph 3 P=O

Acetone 2-M ethyl-2-heptene

O
Ph + Ph + Ph 3 P= O
H + Ph 3 P Ph
Phenyl- (Z)-1-Phenyl-2- (E)-1-Phenyl-2-
acetaldehyde butene butene
(87%) (13%)

O O O
Ph Ph 3 P Ph + Ph 3 P= O
H + OEt OEt
Phenyl- Ethyl (E)-4-phenyl-2-butenoate
acetaldehyde (only the E isomer is formed)

16-36
Wittig Reaction
• Some Wittig reactions are Z selective, others are E
selective.
• Wittig reagents with an anion-stabilizing group, such
as a carbonyl group, adjacent to the negative charge
are generally E selective.
O O
Ph3 P Ph3 P
OEt OEt
Resonance contributing structures for an
ylide stabilized by an adjacent carbonyl group

• Wittig reagents without an anion-stabilizing group are

generally Z selective.

16-37
Example 16.5

16-38
Addition of H2O
 Addition of water (hydration) to the carbonyl
group of an aldehyde or ketone gives a geminal
diol, commonly referred to a gem-diol.
• A gem-diol is also referred to as a hydrate.
acid or
base OH
C O + H2 O C
OH
Carbonyl group A hydrate
of an aldehyde (a gem-diol)
or k etone

16-39
Addition of H2O
• When formaldehyde is dissolved in water at 20°C, the
carbonyl group is more than 99% hydrated.
H H
OH
O + H2 O
H OH
H
Formaldehyde Formaldehyde hydrate
(>99%)

• The equilibrium concentration of a hydrated ketone is

considerably smaller.
OH
O + H2 O
OH
Acetone 2,2-Propanediol
(99.9%) (0.1%)

16-40
Addition of Alcohols
 Addition of one molecule of alcohol to the C=O
group of an aldehyde or ketone gives a
hemiacetal.
 Hemiacetal: A molecule containing an -OH and
an -OR or -OAr bonded to the same carbon.
acid or
base OH
O + H-OEt
OEt
A hemiacetal

16-41
Addition of Alcohols
 Formation of a hemiacetal is base catalyzed
• Step 1: Proton transfer from HOR gives an alkoxide.
fast and
reversible
B -
+ H OR B H + -
OR
• Step 2: Attack of RO- on the carbonyl carbon.
O O:–
–
CH3 -C-CH3 + :O-R CH3 -C-CH3
OR
• Step 3: Proton transfer from the alcohol to O- gives the
hemiacetal and generates a new base catalyst.
O:– OH
CH3 -C-CH3 + H OR CH3 -C-CH3 + -
OR
OR OR 16-42
Addition of Alcohols
 Formation of a hemiacetal is also acid catalyzed.
Step 1: Proton transfer to the carbonyl oxygen.
+ H
O fast and O
reversible -
CH3 -C-CH3 + H-A CH3 -C-CH3 + A

Step 2: Attack of ROH on the carbonyl carbon.

+ H
O O-H
CH3 -C-CH3 + H-O-R CH3 -C-CH3
O+
H R
Step 3: Proton transfer from the oxonium ion to A- gives
the hemiacetal and generates a new acid catalyst.
OH OH
CH3 -C-CH3 CH3 -C-CH3 + H-A
+ OR
O
A
- H R 16-43
Addition of Alcohols
 Hemiacetals react with alcohols to form acetals.
Acetal: A molecule containing two -OR or -OAr groups
bonded to the same carbon.
+
OH H OEt
+ H-OEt + H2 O
OEt OEt
A hemiacetal A diethyl acetal

16-44
Addition of Alcohols
Step 1: Proton transfer from HA gives an oxonium ion.
H + H
HO O
R-C-OCH3 + H A R-C-OCH3 + A:-
H H
An oxonium ion
Step 2: Loss of water gives a resonance-stabilized
cation.
+H
H
O + +
R-C OCH3 R-C OCH3 R-C OCH3 + H2 O
H H H
A resonance-stabilized cation

16-45
Addition of Alcohols
Step 3: Reaction of the cation (an electrophile) with
methanol (a nucleophile) gives the conjugate acid of
the acetal.
H + CH3
+ O
CH3 -OH + R-C OCH3 R-C OCH3
H H
A protonated acetal

Step 4: Proton transfer to A- gives the acetal and

generates a replacement acid catalyst.
H + CH3 OCH3
O
(4)
A:- + R-C OCH3 R-C-OCH3 + H-A
H H
An acetal
16-46
Example 16.6

16-47
Addition of Alcohols
• With ethylene glycol and other glycols, the product is a
five-membered cyclic acetal.

H
+ O
O + HO OH + H2 O
O
Cyclic acetal

16-48
Acetals as Protecting Groups
 Suppose you wish to bring about a Grignard
reaction between these compounds.
O OH O
O
H Br ?? H
+ H

Benzaldehyde 4-Bromobutanal 5-Hydroxy-5-phenylpentanal

(racemic)

16-49
Acetals as Protecting Groups
 The Grignard reagent prepared from 4-
bromobutanal will self-destruct! To avoid this,
• First protect the -CHO group as an acetal.
O + O
H
Br OH Br + H2 O
H + HO O
A cyclic acetal

• Then do the Grignard reaction.

- +
O Mg Br O
O
1 . Mg, e t he r O
Br
O 2 . C H CHO
6 5
A chiral magnesium alkoxide
(produced as a racemic mixture)

• Hydrolysis (not shown) gives the target molecule.16-50

Acetals as Protecting Groups
 Tetrahydropyranyl (THP) protecting group.
THP group
H+
RCH2 OH +
O RCH2 O O
Dihydropyran A tetrahydropyranyl
ether

• The THP group is an acetal and, therefore, stable to

neutral and basic solutions, and to most oxidizing and
reducing agents.
• It is removed by acid-catalyzed hydrolysis.

16-51
Example 16.7

16-52
Addition of Nitrogen Nucleophiles
 Ammonia, 1° aliphatic amines, and 1° aromatic
amines react with the C=O group of aldehydes
and ketones to give imines (Schiff bases).
O +
H + H2 O
CH3 CH + H2 N CH3 CH =N

Acetaldehyde Aniline An imine

(a Schiff base)

+
H
O + N H3 N H + H2 O
Cyclohexanone Ammonia An imine
(a Schiff base)

16-53
Addition of Nitrogen Nucleophiles
 Formation of an imine occurs in two steps:
Step 1: Carbonyl addition followed by proton transfer.

O O: H
- H
O
+
C + H2 N-R C N-R C N-R
H H

Step 2: Loss of H2O and proton transfer to solvent.

+
H H H H
H O O +
+ C N-R + H O + H2 O
O H + C N-R C N-R
H H H A n imine H
H O
H

16-54
Addition of Nitrogen Nucleophiles
• A value of imines is that the carbon-nitrogen double
bond can be reduced to a carbon-nitrogen single bond.
H+
O + H 2N - H2 O
Cyclohexanone Cyclohexylamine

H
H2 / N i
N N

(An imine) Dicyclohexylamine

16-55
Addition of Nitrogen Nucleophiles
 Rhodopsin (visual purple) is the imine formed in
the eye between 11-cis-retinal (vitamin A
aldehyde) and the protein opsin.
11
12
+ H2 N-opsin

Rhodopsin
11-cis-Retinal O N-opsin
H (V isual purple) H

Humane retina

Photon  cis to trans isomerization of C #11

 change in molecular shape  nerve impulse

16-56
Example 16.8

16-57
Addition of Nitrogen Nucleophiles
 Secondary amines react with the C=O group of
aldehydes and ketones to form enamines.
+
H
O + H-N N + H2 O

Cyclohexanone Piperidine An enamine

(a secondary amine)

• The mechanism of enamine formation involves

formation of a tetrahedral carbonyl addition compound
followed by its acid-catalyzed dehydration.
• We discuss the chemistry of enamines in more detail
in Chapter 19.

16-58
Addition of Nitrogen Nucleophiles
• The carbonyl groups of aldehydes and ketones react
with hydrazine and its derivatives in a manner similar
to their reactions with 1° amines.
O + H2 NNH2 NNH2 + H2 O
Hydrazine A hydrazone

Reagent, H 2N -R N ame of Reagent N ame of D erivative Formed

H2 N-OH H ydroxylamine Oxime

H2 N-NH Phenylhydrazine Phenylhydrazone

H2 N-NH NO2 2,4-D initrophenyl- 2,4-D initrophenylhydrazone

hydrazine
O2 N
O
H2 N-NHCNH2 Semicarbazide Semicarbazone
16-59
Acidity of α-Hydrogens
 Hydrogens alpha to a T ype of Bond pK a

carbonyl group are more CH3 CH2 O-H 16

acidic than hydrogens of O

CH3 CCH2 -H 20
alkanes, alkenes, and CH3 C C-H 25
alkynes but less acidic than CH2 =CH-H 44
the hydroxyl hydrogen of CH3 CH2 -H 51
alcohols.

16-60
Acidity of α-Hydrogens
 α-Hydrogens are more acidic because the
enolate anion is stabilized by:
1. Delocalization of its negative charge.
2. The electron-withdrawing inductive effect of the
adjacent electronegative oxygen.

-
O O O
CH3 -C-CH2 - H + :A- CH3 -C CH2 CH3 -C=CH2 + H-A
Resonance-stabilized enolate anion

16-61
Example 16.9

16-62
Keto-Enol Tautomerism
• Protonation of the enolate anion on oxygen gives the
enol form; protonation on carbon gives the keto form.

O O-
-
CH3 - C-CH2 CH3 - C= CH2
Enolate anion
H- A H- A
O OH
- -
A + CH3 - C-CH3 CH3 - C= CH2 + A
Keto form Enol form

16-63
Keto-Enol Tautomerism
• Acid-catalyzed equilibration of keto and enol
tautomers occurs in two steps.
Step 1: Proton transfer to the carbonyl oxygen.
+ H
O fast and O
•
•

reversible -
CH3 -C-CH3 + H-A CH3 -C-CH3 + A
Keto form The conjugate acid
of the ketone

Step 2: Proton transfer to the base A-.

+ H
O OH
-
slow
CH3 -C-CH2 -H + :A CH3 -C=CH2 + H-A
Enol form

16-64
Keto-Enol Tautomerism
 Keto-enol % Enol at
equilibria for Keto form Enol form Equilibrium

simple O OH
aldehydes CH3 CH CH2 = CH 6 x 10-5
and ketones O OH
lie far toward CH3 CCH3 CH3 C= CH2 6 x 10-7
the keto O OH
1 x 10-6
form.
O OH
4 x 10-5

16-65
Keto-Enol Tautomerism
 For certain types of molecules, however, the enol
is the major form present at equilibrium:
• For β-diketones, the enol is stabilized by conjugation
of the pi system of the carbon-carbon double bond and
the carbonyl group.
• For acyclic β-diketones, the enol is further stabilized
by hydrogen bonding.

16-66
Example 16.10

16-67
Oxidation of Aldehydes
 Aldehydes are oxidized to carboxylic acids by a
variety of oxidizing agents, including H2CrO4.
CHO H2 Cr O4 COOH
Hexanal Hexanoic acid
 They are also oxidized by Ag+.
• In one method, a solution of the aldehyde in aqueous
ethanol or THF is shaken with a slurry of silver oxide.
O O
CH3 O CH CH3 O COH
T HF, H 2 O HCl + Ag
+ A g2 O
HO N aOH H2 O HO
Vanillin Vanillic acid

16-68
Oxidation of Aldehydes
 Aldehydes are oxidized by O2 in a radical chain
reaction.
• Liquid aldehydes are so sensitive to air that they must
be stored under N2.
O O
2 CH + O2 2 COH

Benzaldehyde Benzoic acid

16-69
Oxidation of Ketones
• Ketones are not normally oxidized by chromic acid.
• They are oxidized by powerful oxidants at high
temperature and high concentrations of acid or base.
O OH O
HN O 3 HO
OH
O
Cyclohexanone Cyclohexanone H exanedioic acid
(keto form) (enol form) (Adipic acid)

16-70
Reduction
• Aldehydes can be reduced to 1° alcohols.
• Ketones can be reduced to 2° alcohols.
• The C=O group of an aldehyde or ketone can be
reduced to a -CH2- group.
Can Be Can Be
Aldehydes Reduced to Ketones Reduced to
OH
O RCH2 OH O
RCHR'
RCH RCR'
RCH3 RCH2 R'

16-71
Metal Hydride Reduction
 The most common laboratory reagents for the
reduction of aldehydes and ketones are NaBH4
and LiAlH4.
• Both reagents are sources of hydride ion, H:-, a very
powerful nucleophile.
H H
+
Na H- B- H Li +
H- A l- H H:
H H
Sodium Lithium aluminum H ydride ion
borohydride hydride (LAH)

16-72
NaBH4 Reduction
• Reductions with NaBH4 are most commonly carried
out in aqueous methanol, in pure methanol, or in
ethanol.
• One mole of NaBH4 reduces four moles of aldehyde or
ketone.
O
methanol
4 RCH + NaBH4

- + H2 O
( RCH2 O) 4 B Na 4 RCH2 OH + borate
A tetraalkyl borate salts

16-73
NaBH4 Reduction
 The key step in metal hydride reduction is
transfer of a hydride ion to carbon of the C=O
group to form a tetrahedral carbonyl addition
compound. This H comes from water
during hydrolysis
+
H O O BH3 Na O-H
+ H2 O
Na H-B-H + R-C-R' R-C-R' R-C-R'
H H H
This H comes from the
hydride reducing agent

16-74
LiAlH4 Reduction
• Unlike NaBH4, LiAlH4 reacts violently with water,
methanol, and other protic solvents.
• Reductions using it are carried out in diethyl ether or
tetrahydrofuran (THF).
O OH
ether - + H2 O
4 RCR + LiAlH4 ( R2 CHO) 4 Al Li 4 RCHR + aluminum
H or OH-
+
A tetraalk yl salts
aluminate

16-75
Catalytic Reduction
 Catalytic reductions are generally carried out at
from 25° to 100°C and 1 to 5 atm H2.
O OH
Pt
+ H2
25 o C, 2 atm
Cyclohexanone Cyclohexanol

16-76
Catalytic Reduction
 A carbon-carbon double bond may also be
reduced under these conditions.
O
2 H2
H Ni OH
trans- 2-Butenal 1-Butanol
(Crotonaldehyde)
• By careful choice of experimental conditions, it is
often possible to selectively reduce a carbon-carbon
double in the presence of an aldehyde or ketone.
O OH
1 . NaBH4
RCH=CHCR' RCH=CHCHR'
2 . H2 O

O O
Rh
RCH=CHCR' + H2 RCH2 CH2 CR'
16-77
Example 16.12

16-78
Clemmensen Reduction
• Refluxing an aldehyde or ketone with amalgamated
zinc in concentrated HCl converts the carbonyl group
to a methylene group.
OH O OH
Zn( H g) , HCl

Erik Christian Clemmensen (1876 - May 21, 1941) was a Danish-American chemist.

16-79
Wolff-Kishner Reduction
• In the original procedure, the aldehyde or ketone and
hydrazine are refluxed with KOH in a high-boiling
solvent.
• The same reaction can be brought about using
hydrazine and potassium tert-butoxide in DMSO.
O
KOH
+ H2 NN H2
diethylene glycol
H ydrazine (reflux)

+ N 2 + H2 O

16-80
Example 16.13

16-81
Racemization
 Racemization at an α-carbon may be catalyzed
by either acid or base.
O OH O

Ph Ph Ph
(R)-3-Phenyl-2- An achiral (S)-3-Phenyl-2-
butanone enol butanone

16-82
Deuterium Exchange
 Deuterium exchange at an α-carbon may be
catalyzed by either acid or base.
O + O
D
CH 3 CCH 3 + 6 D2 O -
CD 3 CCD 3 + 6 HOD
Acetone or OD Acetone-d 6

16-83
α-Halogenation
 α-Halogenation: aldehydes and ketones with at
least one α-hydrogen react at an α-carbon with
Br2 and Cl2 .
O O
Br
+ Br2 + HBr
CH3 COOH
Acetophenone α-Bromo-
acetophenone
• Reaction is catalyzed by both acid and base.

16-84
α-Halogenation
 Acid-catalyzed α-halogenation
Step 1: Acid-catalyzed enolization.
OH H-O R
slow
R'-C-C-R C C
R R' R
Step 2: Nucleophilic attack of the enol on halogen.
H-O R H O Br
fast Br:-
C C + Br Br C C R +
R' R R'
R

Step 3: (not shown) Proton transfer to solvent completes

the reaction.
16-85
α-Halogenation
 Base-promoted α-halogenation
Step 1: Formation of an enolate anion.
-
OH O - R O: R
slow ••
R'-C-C-R + - :OH C C C C + H2 O
R R' R R' R
Resonance-stabilized enolate anion
Step 2: Nucleophilic attack of the enolate anion on
halogen.
-
O: R O Br
fast
C C + Br Br C C R + Br
R' R R' R

16-86
α-Halogenation
 Acid-catalyzed halogenation:
• Introduction of a second halogen is slower than the
first.
• Introduction of the electronegative halogen on the α-
carbon decreases the basicity of the carbonyl oxygen
toward protonation.
 Base-promoted α-halogenation:
• Each successive halogenation is more rapid than the
previous one.
• The introduction of the electronegative halogen on the
α-carbon increases the acidity of the remaining α-
hydrogens and, thus, each successive α-hydrogen is
removed more rapidly than the previous one.
16-87
Aldehydes
&
Ketones
End Chapter 16

16-88