KOT 222 ORGANIC CHEMISTRY II
CHAPTER 18
KETONES
and
ALDEHYDES
1
Carbonyl Compounds
Compounds containing carbonyl group, C=O
2
Structure of Carbonyl Group
Ø Carbonyl carbon is sp2 hybridized.
Ø C=O bond is shorter, stronger, and more polar
than C=C bond in alkenes.
as nucleophile
as electrophile
3
IUPAC Names for Ketones
Ø Replace -e with -one. Indicate the position of
the carbonyl with a number.
Ø Number the chain so that carbonyl carbon has
the lowest number.
Ø For cyclic ketones the carbonyl carbon is
assigned the number 1.
O
O
CH3
C CH CH2OH
CH3
4-hydroxy-3-methyl-2-butanone
4-hydroxy-3-methylbutan-2-one
Br
3-bromocyclohexanone
4
Naming Aldehydes
Ø IUPAC: Replace -e with -al.
Ø The aldehyde carbon is number 1.
Ø If -CHO is attached to a ring, use the suffix carbaldehyde.
CH3
CH2
CH3
O
CH CH2
C H
3-methylpentanal
CHO
2-cyclopentenecarbaldehyde
cyclopent-2-en-1-carbaldehyde
5
Name as Substituent
Ø On a molecule with a higher priority functional
group, C=O is oxo- and -CHO is formyl.
Ø Aldehyde priority is higher than ketone.
CH3
O
CH3
O
C
CH CH2
C H
3-methyl-4-oxopentanal
COOH
CHO
3-formylbenzoic acid
6
Common Names for Ketones
Ø By naming the two alkyl groups bonded to C=O.
Ø Use Greek letters instead of numbers for
substituents.
O
CH3
C CH CH3
CH3
methyl isopropyl ketone
α
O
CH3CH C CH CH3
Br
CH3
α−bromoethyl isopropyl ketone
7
Historical Common Names
O
O
CH3
C
C CH3
CH3
acetone
acetophenone
O
C
benzophenone
8
Aldehyde Common Names
Ø Use the common name of the acid.
Ø Drop -ic acid and add -aldehyde.
v 1 C: formic acid, formaldehyde
v 2 C’s: acetic acid, acetaldehyde
v 3 C’s: propionic acid, propionaldehyde
v 4 C’s: butyric acid, butyraldehyde
CH3
Br
O
CH CH2
C H
-bromobutyraldehyde
3-bromobutanal
9
Boiling Points
Ø More polar, so higher boiling point than
comparable alkane or ether.
Ø Cannot form H-bond with each other, so lower
boiling point than comparable alcohol.
10
Solubility
Ø Lone pair of electrons on oxygen of carbonyl can
accept a hydrogen bond from O-H or N-H.
Ø Good solvent for alcohols.
Ø Acetone and acetaldehyde are miscible in water.
11
IR Spectra of Ketones and Aldehydes
Ø Very strong C=O stretch around 1710 cm-1
Ø Conjugation lowers frequency.
Ø Ring strain raises frequency.
12
1H NMR
Spectra of Ketones and Aldehydes
13
13C
Spectra of Ketones and Aldehydes
14
MS of Ketones and Aldehydes
Ø Loss of an alkyl group to give the acylium ion.
15
MS for Butyraldehyde
McLafferty
rearrangement
16
McLafferty Rearrangement
Ø Cyclic intramolecular transfer of a γhydrogen to
the carbonyl oxygen.
Ø Equivalent to α, cleavage + transfer of one
mass unit for the hydrogen.
Ø Loss of alkene (even mass number).
17
18
UV Spectra of Ketones and Aldehydes
π to π* transition:
Ø Observable only when the C=O group
conjugated with with another double bond.
Ø Large molar absorptivities, > 5000.
19
n to π* transition
Ø Excitation of one of the nonbonding electrons
on oxygen to a π* antibonding orbital.
Ø Required less energy, longer wavelength.
Ø The λmax is between 280 and 300 nm.
20
Industrial Importance
Ø Acetone and methyl ethyl ketone are important
solvents.
Ø Formaldehyde used in polymers like Bakelite .
Ø Flavorings and additives like vanilla, cinnamon,
artificial butter.
21
Synthesis Review
Oxidation of alcohols
22
Ozonolysis of alkenes
Ø Ozonolysis, followed by mild reduction.
Unlike strong oxidation:
23
Friedel-Crafts acylation
Ø Gives alkyl aryl ketones or diaryl ketones.
Ø Not with strongly deactivated aromatic rings.
24
Hydration of terminal alkynes
Catalyzed by acid and mercuric salts
Ø Use HgSO4, H2SO4, H2O for methyl ketone.
25
Hydroboration-oxidation of alkynes
Ø Anti-Markovnikov addition of water across the
triple bond.
Ø Use Sia2BH followed by H2O2 in NaOH for
aldehyde.
26
Synthesis Using 1,3-Dithiane
Ø Deprotonation by strong base, n-butyllithium.
Ø Monoalkylation with 1o alkyl halide and removal
of the thioacetal via hydrolysis gives an aldehyde.
27
Ketones from 1,3-Dithiane
Ø Monoalkylation and hydrolysis give aldehyde.
Ø After the first alkylation, remove the second H+,
react with another primary alkyl halide, then
hydrolyze to give the ketone.
thioacetal
thioketal
28
Ketones from Carboxylic Acids
Ø Organolithium compounds attack the carbonyl
and form a dianion.
Ø Neutralization with aqueous acid produces an
unstable hydrate that loses water to form a
ketone.
29
Ketones from Nitriles
Ø A Grignard or organolithium reagent attacks the
nitrile carbon.
Ø The imine salt is then hydrolyzed to form a
ketone.
Example
N MgBr
C N
CH3CH2MgBr +
ether
C
CH2CH3
O
H3O
+
C
CH2CH3
30
Aldehydes from Acid Chlorides
Ø Acids can be reduced to aldehydes by first
converting them to acid chlorides.
Ø Mild reducing agent, lithium aluminium
tri(t-butoxy)hydride is used to prevent reduction to
primary alcohol.
31
Ketones from Acid Chlorides
Ø Use weaker organometallic like lithium
dialkylcuprate (Gilman reagent).
2 CH3CH2CH2Li
CuI
(CH3CH2CH2)2CuLi
Organocuprate transfers one of its alkyl groups to
the acid chloride.
O
(CH3CH2CH2)2CuLi +
CH3CH2C Cl
O
CH3CH2C
CH2CH2CH3
Grignard and organolithium react with ketone to give
tertiary alcohol (after hydrolysis)
32
Nucleophilic Addition
Ø Addition of a nucleophile and a proton across
the C=O double bond.
Ø Examples are like attack of Grignard reagent
and hydride reduction to give alcohols
Ø Can take place under acid-catalyzed or basecatalyzed condition.
33
General mechanism
Acid-catalyzed addition
Base-catalyzed addition
34
Ø An aldehyde has a greater partial positive
charge on its carbonyl carbon than does a
ketone.
Ø The carbonyl carbon of an aldehyde is more
accessible to the nucleophile
35
Wittig Reaction
Ø converts the carbonyl group of a ketone or an
aldehyde into a new C=C double bond.
Ø A phosphorus ylide is used as the nucleophile.
36
Preparation of Phosphorus Ylides
Ø From nucleophilic attack of triphenylphosphine
on an unhindered alkyl halide.
Ø Butyllithium then abstracts a hydrogen from the
carbon attached to phosphorus.
Major contributor, strong Nuc:-
37
Mechanism of Wittig Reaction
Step 1: the ylide attacked the C=O group to form betaine
Step 2: the betaine closes to a four-membered ring
oxaphosphetane
Step 3: the ring collapses to the products
triphenylphosphine oxide
38
Hydration of Ketones and Aldehydes
Ø In an aqueous solution, a ketone or an aldehyde
is in equilibrium with its hydrate, a geminal diol.
Ø In acid, water is the nucleophile.
Ø In base, hydroxide is the nucleophile.
Ø Aldehydes are more electrophilic since they
have fewer e--donating alkyl groups.
39
Formation of Cyanohydrins
Ø Addition of HCN.
Ø Base-catalyzed nucleophilic addition: attack by
cyanide ion on the carbonyl group, followed by
protonation of the intermediate.
Ø Reactivity formaldehyde > aldehydes > ketones
>> bulky ketones.
40
Formation of Imines
Ø Acid-catalyzed nucleophilic addition of ammonia
or 1o amine, followed by elimination of water
molecule.
Ø C=O becomes C=N-H / C=N-R (Schiff base).
Ø The reaction is pH dependance.
v Loss of water is acid-catalyzed.
v Too acidic will protonate the ammonia or
amine.
v Optimum pH is around 4.5
NH3 + H+ → NH4+ (not nucleophilic)
41
Mechanism
Part 1: Acid-catalyzed addition of amine
Part 2: Acid-catalyzed dehydration
42
Formation of Imine Derivatives
Condensation with other ammonia derivatives.
43
Formation of Acetals
Ø Involves addition of two alcohol molecules and
elimination of one water molecule.
Ø Must be acid-catalyzed.
44
Mechanism
Part 1: Acid-catalyzed addition of alcohol.
Hemiacetal is too unstable to be isolated and
purified.
45
Part 2: Acid-catalyzed dehydration
HO
OCH3
+
HO
S N1
H
OCH3
OCH3
+
H+
+ HOH
HOCH3
Attack of second alcohol
OCH3
HOCH3
+
CH3O
H
OCH3
CH3O
OCH3
+
acetal
46
Ø Part 2 must be in acidic condition.
Ø Protonation will give a good leaving group.
In basic condition:
∴ Formation of acetal is acid-catalyzed!!!
47
Hydrolysis of Acetals
The carbonyl carbon is the one with two bonds to oxygen.
48
49
Cyclic Acetals
Ø Addition of diol on the C=O group.
CH2 CH2
O
O
O
+
CH2
HO
CH2
OH
benzaldehyde ethylene acetal
Sugars commonly exist as acetals or hemiacetals.
50
Acetals as Protecting Groups
Ø Acetals hydrolyzed easily in acid, but stable to
strong bases and nucleophiles.
Ø Prevent ketones or aldehydes from reacting with
strong bases or nucleophiles.
LiAlH4 will reduce the ester to yield an alcohol, but
the keto group will also be reduced
51
The keto group is protected as a ketal in this synthesis
The more reactive aldehyde is protected with the diol
before reaction with the Grignard reagent
52
Oxidation of Aldehyde
Ø Aldehydes are easily oxidized to carboxylic acids
by common oxidants.
53
Tollens Test
Ø Qualitative test for aldehyde.
Ø Aldehyde reacts with the silver-ammonia
(Tollens reagent) complex to form a silver mirror.
O
R C H +
+
2 Ag(NH3)2 +
_
3 OH
O
2 Ag + R C O
H2O
_
+
4 NH3 + 2 H2O
54
Reductions of Ketones and Aldehydes
Reduction of C=O to C-OH
Reducing agents:
Ø Sodium borohydride, NaBH4, reduces C=O, but
not C=C.
Ø Lithium aluminum hydride, LiAlH4, much
stronger, difficult to handle.
Ø Hydrogen gas with catalyst also reduces the
C=C bond.
55
Deoxygenation
Ø Reduction of C=O to CH2
Ø Two methods:
– Clemmensen reduction if molecule is
stable in hot acid.
– Wolff-Kishner reduction if molecule is
stable in very strong base.
56
Clemmensen Reduction
Ø Carbonyl compound is heated with an excess of
amalgamated zinc and HCl.
O
C
CH2CH3
Zn(Hg)
CH2CH2CH3
HCl, H2O
O
CH2
C
Zn(Hg)
H
CH2
CH3
HCl, H2O
57
Wolff-Kishner Reduction
Ø Form hydrazone, then heat with strong base like
KOH or potassium t-butoxide.
Ø Use a high-boiling solvent: ethylene glycol,
diethylene glycol, or DMSO.
CH2
C H
O
H2N NH2
CH2
C H
NNH2
KOH
heat
CH2
CH3
58
Mechanism
The actual reduction step involves two tautomeric
proton transfers from N to C atom.
59
60