CH 19: Aldehydes and Ketones
Renee Y. Becker
Valencia Community College
CHM 2211
1
Some Generalizations About Carbonyl Compounds
• The most important functional group in
organic chemistry.
O
R C
Acyl group
R = alkyl, aryl, or alkenyl
The other residue my be C, H, O, X, N, S, etc.
2
Some Generalizations About Carbonyl Compounds
• carbonyl compounds are planar about the
double bond with bond angles  120 due to the
sp2 hybridized carbon.
• Many types of carbonyl compounds have
significant dipole moments.
• The polarity of the C-O bond plays a significant
role in the reactivity of carbonyl compounds.
O
C
Nucleophilic oxygen reacts with acids and
electrophiles.
Electrophilic carbon reacts with bases and
3
nucleophiles.
Aldehydes and Ketones
O
O
CH3CH
CH3CCH3
Ethanal
Propanone
4
Aldehydes and Ketones
• Due to the polarity of the carbonyl C-O bond,
aldehydes and ketones have higher BPs than
alkanes with similar molecular weights.
• The lack of H-bonding hydrogens, results in
lower BPs than similar alcohols.
O
CH3CH2CH2CH3
Butane
M.W. = 58 o
BP = -0.45 C
CH3CH2CH
Propanal
M.W. = 58
BP = 49 oC
CH3CH2CH2OH
Propanol
M.W. = 60
BP = 97 oC
5
Naming Aldehydes
• 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 carbaldehyde.
6
Naming Aldehydes
CHO
Cyclopentanecarbaldehyde
CHO
CHO
Benzenecabaldehyde
or
phenylmethanal
or
benzaldehyde
CH3
trans-2-methylcyclohexanecarbaldehyde
7
Naming Aldehydes
8
Example 1: Name
O
1
H
O
H
2
Cl
H
3
O
4
O
H
9
Example 2: Draw
1. 3-Methylbutanal
2. 3-Methyl-3-butenal
3. cis-3-tert-Butylcyclohexanecarbaldehyde
10
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
11
Naming Ketones
O
O
CH3CH2CCH2CCH3
2,4-Hexanedione
O
CH3CHCH2CCH3
CH3
4-Methyl-2-pentanone
H3C
O
4-Methylcyclohexanone
12
Naming Ketones
• Ketones with Common Names
13
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
R
O
C
An acyl group
H3C
O
C
Acetyl
H
O
C
O
C
Formyl
Benzoyl
14
Ketones and Aldehydes as Substituents
• 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
15
Example 3: Name
1.
O
CH3CH2CCH(CH3)2
O
H3C
H
3.
H
CH3
2.
O
O
4.
O
16
Example 4: Draw
1. 4-Chloro-2-pentanone
2. P-bromoacetophenone
3. 3-ethyl-4-methyl-2-hexanone
17
Preparation of Aldehydes
• Oxidize primary alcohols using pyridinium
chlorochromate
18
Preparation of Aldehydes
• Oxidation of alkenes with a vinylic hydrogen
H
O3
O
+
Zn, CH3CO2H
H
O
ketone
H
aldehyde
O3
H
Zn, CH3CO2H
O
+
H
O
aldehyde
aldehyde
O3
O
H
H
Zn, CH3CO2 H
O
Dicarbonyl compound
6-oxoheptanal
19
Preparation of Aldehydes
• The partial reduction of certain carboxylic acid
derivatives. (esters)
R
O
C
H
Y
O
R
O
C
+ Y
H
DIBAH, toluene
O
-78 C
H3O+
O
H
+
CH3O-
H
DIBAH - diisobutylaluminum hydride
Al
20
Example 5
How would you prepare pentanal from the
following:
1. 1-Pentanol
2. 1-Hexene
O
3.
O
21
Preparing Ketones
• Oxidation of secondary alcohols
OH
PCC
RCHR'
CH2Cl2
O
RCR'
22
Preparing Ketones
• Oxidation of alkenes if one unsaturated carbon
is disubstituted
H
O3
O
Zn, CH3CO2H
+
O
ketone
H
aldehyde
23
Preparing Ketones
• Friedel-Crafts acylation of aromatic compounds
with an acid chloride.
ArH
O
+ RCCl
AlCl3
O
ArCR + HCl
Occurs only once!
24
Preparing Ketones
• Hydrations of terminal alkynes
– Methyl ketone synthesis
– Hg2+ catalyst
O
H3O+
HgSO4
25
Example 6
How would you carry out the following reactions?
More than 1 step might be necessary.
1. 3-Hexyne  3-Hexanone
2. Benzene  m-Bromoacetophenone
3. Bromobenzene  Acetophenone
26
Reactions of Aldehydes and Ketones
• Oxidation reactions
• Nucleophilic addition reactions
• Conjugate nucleophilic addition reactions
27
Oxidation of Aldehydes
• Jones’ Reagent (preferred)
– Preferred over other oxidation reagents due to
Room temp. reaction with high yields
– Run under acidic conditions (con)
• Will react with C=C and any acid sensitive
functionality
CrO3, H3O+
O
H
acetone, 0 C
O
OH
28
Oxidation of Aldehydes
• Tollen’s reagent
• For use with C=C double bonds
O
O
H
Ag2O
OH
+
Ag
NH4OH, H2O
29
Oxidation of Ketones
• Ketones are resistant toward oxidation due to
the missing hydrogen on the carbonyl carbon
• Treatment of ketones with hot KMnO4 will cleave
the C-C bond adjacent to the carbonyl group:
O
KMnO4, H2O, NaOH
O
H3O
O
+
KMnO4, H2O, NaOH
H3O+
OH
+
H
OH
O
CO2H
CO2H
30
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
31
32
Nucleophiles
• Nucleophiles can be negatively charged ( : Nu)
or neutral ( : Nu) at the reaction site
• The overall charge on the nucleophilic species is
not considered
33
Nucleophilic Addition Reactions
34
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)
35
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
36
Reactivity of Aromatic Aldehydes
• Aromatic aldehydes are less reactive in nucleophilic
addition than straight chain aldehydes
– Due to electron-donating resonance effect of aromatic
ring
• Makes carbonyl group less electrophilic
37
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
38
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
39
Acid & 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
• Acid-Catalyzed Addition of Water
• Protonation of C=O makes it more electrophilic
40
Mechanism 1: Base catalyzed hydration of an aldehyde/ketone
O
OH
NaOH
+
H2O
OH
O
H
+
Na+
NaOH
O
H
O–
-OH
+
OH
-
OH
OH
NaOH
+
OH
41
Mechanism 2: Acid catalyzed hydration of an aldehyde/ketone
O
OH
H3O+
+
H2O
O
OH
H
H
+
H
O+
O
H
H
O+
+
H
H
O
H
OH
OH
+
OH
H3O+
H3O+
O+
H
H
42
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
43
Nucleophilic Addition of HCN: Cyanohydrin Formation
• Aldehydes and unhindered ketones react with
HCN to yield cyanohydrins, RCH(OH)CN
R
O
C
+ HC N
R'
Aldehyde or
ketone
OH
C N
R
R' a cyanohydrin
Hydrogen
cyanide
44
Mechanism of Formation of Cyanohydrins
• Addition of HCN is reversible and basecatalyzed, generating nucleophilic cyanide ion,
CN
• Addition of CN to C=O yields a tetrahedral
intermediate, which is then protonated
• Equilibrium favors adduct
45
Mechanism 3: Formation of Cyanohydrins
O
HO
H--CN
H
CN
H
+
-
CN
+
NH4+
NH3
H--CN
-
NH3
CN
O
+
–
O
H
+
-
CN
NH4 +
CN
H
H--CN
HO
CN
H
+
-
CN
46
Uses of Cyanohydrins
• Nitriles can be reduced with LiAlH4 to yield
primary amines:
Cl
Cl
O
CH
Cl
HCN
Cl
OH
CCN
2,4-Dichlorobenzaldehyde
cyanohydrin
Cl
Cl
OH
CCH2NH2
1. LiAlH4, THF
2. H2O
(2,4-Dichloro-phenyl)-2-aminoethanol
47
Uses of Cyanohydrins
• Nitriles can be hydrolyzed with hot aqueous acid
to yield carboxylic acids:
Cl
Cl
O
CH
Cl
HCN
Cl
OH
CHCN
2,4-Dichlorobenzaldehyde
cyanohydrin
H3O+, heat
Cl
Cl
OH
CHCOOH
(2,4-Dichloro-phenyl)-2-hydroxy-ethanoic acid
48
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 +.
49
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
50
Mechanism 4: Addition of Grignard Reagents
O
C
R
R'
adehyde or
ketone
R" MgX
O
R C R"
R'
alkoxide
H3O
+
OH
R C R"
R'
an alcohol
51
Hydride Addition
• Convert C=O to CH-OH
• LiAlH4 and NaBH4 react as donors of
hydride ion
• Protonation after addition yields the alcohol
O
H-
O–
H3O+
OH
+
NaBH4 or LiAlH4
H
H2O
H
52
Nucleophilic Addition of Amines: Imine and Enamine Formation
RNH2 (primary amines) adds to C=O to form
imines, R2C=NR (after loss of HOH)
R2NH (secondary amines) yields enamines,
R2NCR=CR2 (after loss of HOH) (ene +
amine = unsaturated amine)
53
54
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
55
Mechanism 5: Imine Formation
56
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 2,4dinitrophenylhydrazones
– These are usually solids and help in
characterizing liquid ketones or aldehydes by
melting points
57
58
Mechanism 6: Enamine Formation
59
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
60
Mechanism 7: The Wolff–Kishner Reaction
61
Nucleophilic Addition of Alcohols: Acetal Formation
• 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
62
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)
63
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
64
Mechanism 8: The Wittig Reaction
65
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
66
The Cannizaro Reaction
• The adduct of an aldehyde and OH can transfer
hydride ion to another aldehyde C=O resulting in
a simultaneous oxidation and reduction
(disproportionation)
67
Conjugate Nucleophilic Addition to ,b-Unsaturated Aldehydes and
Ketones
• A nucleophile can add to the C=C double bond of
an ,b-unsaturated aldehyde or ketone
(conjugate addition, or 1,4 addition)
• The initial product is a resonance-stabilized
enolate ion, which is then protonated
68
69
70
Conjugate Addition of Amines
• Primary and secondary amines add to , bunsaturated aldehydes and ketones to yield bamino aldehydes and ketones
71
Conjugate Addition of Alkyl Groups: Organocopper Reactions
• Reaction of an , b-unsaturated ketone with a
lithium diorganocopper reagent
• Diorganocopper (Gilman) reagents from by
reaction of 1 equivalent of cuprous iodide and 2
equivalents of organolithium
• 1, 2, 3 alkyl, aryl and alkenyl groups react
but not alkynyl groups
72
73
2 Li
RX
2 RLi
pentane
CuI
ether
RLi + Li
+
+X
+
-
Li (RCuR) + Li + I
Gilman Reagent
74
Mechanism of Alkyl Conjugate Addition
• Conjugate nucleophilic addition of a
diorganocopper anion, R2Cu, an enone
• Transfer of an R group and elimination of a
neutral organocopper species, RCu
75
Example 7
O
CH3CCH CH2
3-Buten-2-one
1. Li(CH3)2Cu, ether
2. H3O+
O
1. Li(H2C=CH)2Cu, ether
2. H3O+
2-Cyclohexenone
76