Organic Chemistry

Chapter 18
Ketones and Aldehydes
Carbonyl Compounds

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Carbonyl Structure
• Carbon is sp2 hybridized.
• C=O bond is shorter, stronger, and
more polar than C=C bond in alkenes.

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IUPAC Names
for Ketones
• Replace -e with -one. Indicate the
position of the carbonyl with a number.
• Number the chain so that carbonyl
carbon has the lowest number.
• For cyclic ketones the carbonyl carbon
is assigned the number 1.

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Examples
O O

CH3 C CH CH3
CH3
Br
3-methyl-2-butanone
3-bromocyclohexanone
O
CH3 C CH CH2OH
CH3
4-hydroxy-3-methyl-2-butanone
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Naming Aldehydes

• IUPAC: Replace -e with -al.

• The aldehyde carbon is number 1.
• If -CHO is attached to a ring, use the
suffix -carbaldehyde.

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Examples

CH3 O
CH3 CH2 CH CH2 C H

3-methylpentanal
CHO

2-cyclopentenecarbaldehyde

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Name as Substituent
• On a molecule with a higher priority
functional group, C=O is oxo- and -CHO
is formyl.
• Aldehyde priority is higher than ketone.
COOH

O CH3 O
CH3 C CH CH2 C H
CHO

3-methyl-4-oxopentanal 3-formylbenzoic acid

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Common Names
for Ketones
• Named as alkyl attachments to -C=O.
• Use Greek letters instead of numbers.

O O
CH3 C CH CH3 CH3CH C CH CH3
CH3 Br CH3

methyl isopropyl ketone bromoethyl isopropyl ketone

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Historical Common
Names O
C
O CH3
CH3 C CH3
acetone acetophenone
O
C

benzophenone
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Aldehyde Common
Names
• Use the common name of the acid.
• Drop -ic acid and add -aldehyde.
– 1 C: formic acid, formaldehyde
– 2 C’s: acetic acid, acetaldehyde
– 3 C’s: propionic acid, propionaldehyde
– 4 C’s: butyric acid, butyraldehyde.

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Boiling Points
• More polar, so higher boiling point than
comparable alkane or ether.
• Cannot H-bond to each other, so lower
boiling point than comparable alcohol.

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Solubility
• Good solvent for alcohols.
• Lone pair of electrons on oxygen of
carbonyl can accept a hydrogen bond from
O-H or N-H.
• Acetone and acetaldehyde are miscible in
water.

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Formaldehyde
• Gas at room temperature.
• Formalin is a 40% aqueous solution.

H H
C O HO
O O heat H2O OH
H H C H H C
C C H H
O formaldehyde,
H H formalin
b.p. -21C
trioxane, m.p. 62C
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IR Spectroscopy

• Very strong C=O stretch around 1710 cm-1.

• Conjugation lowers frequency.
• Ring strain raises frequency.
• Additional C-H stretch for aldehyde: two
absorptions at 2710 cm-1 and 2810 cm-1.

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1
H NMR Spectroscopy

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C NMR Spectroscopy
13

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MS for 2-Butanone

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MS for Butyraldehyde

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McLafferty
Rearrangement
• Loss of alkene (even mass number)
• Must have -hydrogen

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UV Spectra,   *
• C=O conjugated with another double bond.
• Large molar absorptivities (> 5000)

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UV Spectra, n  *
• Small molar absorptivity.
• “Forbidden” transition occurs less frequently.

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Industrial Importance

• Acetone and methyl ethyl ketone are

important solvents.
• Formaldehyde used in polymers like
Bakelite.
• Flavorings and additives like vanilla,
cinnamon, artificial butter.

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Synthesis Review

• Oxidation
– 2 alcohol + Na2Cr2O7  ketone
– 1 alcohol + PCC  aldehyde
• Ozonolysis of alkenes.
H R' H R'
1) O3
C C C O + O C
2) (CH3)2S
R R'' R R''

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Synthesis Review (2)

• Friedel-Crafts acylation
– Acid chloride/AlCl3 + benzene  ketone
– CO + HCl + AlCl3/CuCl + benzene 
benzaldehyde (Gatterman-Koch)
• Hydration of terminal alkyne
– Use HgSO4, H2SO4, H2O for methyl ketone
– Use Sia2BH followed by H2O2 in NaOH for
aldehyde.
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Synthesis Using
1,3-Dithiane
• Remove H+ with n-butyllithium.
BuLi
S S S S
_
H H H

• Alkylate with primary alkyl halide,

then hydrolyze.
+
O
CH3CH2Br H , HgCl2
C
S S S S H2O H CH2CH3
_
H CH2CH3 =>
H
Ketones from
1,3-Dithiane
• After the first alkylation, remove the
second H+, react with another primary alkyl
halide, then hydrolyze.

+ O
BuLi CH3Br H , HgCl2
S S S S C
S S _ H2O
CH3 CH2CH3
CH3 CH2CH3
H CH2CH3 CH2CH3

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Ketones from
Carboxylates
• Organolithium compounds attack the
carbonyl and form a diion.
• Neutralization with aqueous acid
produces an unstable hydrate that loses
water to form a ketone.
_ +
O O Li OH O
_ +
C _ C O Li C
O Li + C OH _
H3O
+ H2O CH3
CH3 CH3
CH3Li

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Ketones from Nitriles
• A Grignard or organolithium reagent
attacks the nitrile carbon.
• The imine salt is then hydrolyzed to
form a ketone.
N MgBr O
C N C
CH2CH3 + C
CH3CH2MgBr + H3O CH2CH3
ether

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Aldehydes from
Acid Chlorides
Use a mild reducing agent to prevent
reduction to primary alcohol.

O O
LiAlH(O-t-Bu)3
CH3CH2CH2C Cl CH3CH2CH2C H

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Ketones from
Acid Chlorides
Use lithium dialkylcuprate (R2CuLi), formed
by the reaction of 2 moles of
R-Li with cuprous iodide.

CuI
2 CH3CH2CH2Li (CH3CH2CH2)2CuLi

O O
(CH3CH2CH2)2CuLi + CH3CH2C Cl CH3CH2C CH2CH2CH3

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Nucleophilic Addition
• A strong nucleophile attacks the
carbonyl carbon, forming an alkoxide
ion that is then protonated.
• A weak nucleophile will attack a
carbonyl if it has been protonated,
thus increasing its reactivity.
• Aldehydes are more reactive than
ketones.

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Ylide – “ill’-id”

• A phosphorous-stabilized carbanion!
– A neutral molecule
– Contains a positively charged heteratom (in this case P)
– Contains a negatively charged C-atom
– See “Wade” pg. 801for more details
Wittig Reaction
• Nucleophilic addition of phosphorus ylides.
• Product is alkene. C=O becomes C=C.

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Phosphorus Ylides
• Prepared from triphenylphosphine and an
unhindered alkyl halide.
• Butyllithium then abstracts a hydrogen
from the carbon attached to phosphorus.
+ _
Ph3P + CH3CH2Br Ph3P CH2CH3 Br
_
+ +
BuLi
Ph3P CH2CH3 Ph3P CHCH3
ylide =>
Mechanism for Wittig
• The negative C on ylide attacks the
positive C of carbonyl to form a betaine.
• Oxygen combines with phosphine to
form the phosphine oxide. +
_ Ph3P O
+ H3C
Ph3P CHCH3 C O H C C CH3
Ph CH3 Ph
+ _ Ph3P O
Ph3P O Ph3P O
H CH3
H C C CH3 H C C CH3 C C
H3C Ph
CH3 Ph CH3 Ph
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Addition of Water
• In acid, water is the nucleophile.
• In base, hydroxide is the nucleophile.
• Aldehydes are more electrophilic since
they have fewer e--donating alkyl groups.
O OH
HO
C + H2O C
H H H H K = 2000

O OH
HO
C + H2O C
CH3 CH3 CH3 CH3 K = 0.002
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Addition of HCN
• HCN is highly toxic.
• Use NaCN or KCN in base to add
cyanide, then protonate to add H.
• Reactivity formaldehyde > aldehydes >
ketones >> bulky ketones.
O
CN
C HO
CH3CH2 CH3 + HCN C
CH3CH2 CH3

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Formation of Imines
• Nucleophilic addition of ammonia or
primary amine, followed by elimination
of water molecule.
• C=O becomes C=N-R
CH3 CH3
H3C R R
_
RNH2 C O H2N C O N C OH
Ph + Ph H Ph

CH3 CH3
R R
N C OH N C
H Ph Ph =>
pH Dependence
• Loss of water is acid catalyzed, but acid
destroys nucleophiles.
• NH3 + H+  NH4+ (not nucleophilic)
• Optimum pH is around 4.5

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Other Condensations

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Addition of Alcohol

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Mechanism

• Must be acid-catalyzed.
• Adding H+ to carbonyl makes it more
reactive with weak nucleophile, ROH.
• Hemiacetal forms first, then acid-
catalyzed loss of water, then addition of
second molecule of ROH forms acetal.
• All steps are reversible.
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Mechanism for
Hemiacetal
O + OH OH

H+ +

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

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

HOCH3
H
OCH3 +
CH3O OCH3 CH3O OCH3
+
HOCH3

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Cyclic Acetals

• Addition of a diol produces a cyclic acetal.

• Sugars commonly exist as acetals or
hemiacetals.
CH2 CH2
O O
O
CH2 CH2
+
HO OH

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Acetals as
Protecting Groups
• Hydrolyze easily in acid, stable in base.
• Aldehydes more reactive than ketones.

O
O CH2 CH2
HO OH
+ O
H H C
C
O
O
=>
Selective Reaction
of Ketone
• React with strong nucleophile (base)
• Remove protective group.

+ _
O MgBr O CH HO CH3
3
+
CH3MgBr H3O

O H
O C C
C
O O
O
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Oxidation of Aldehydes
Easily oxidized to carboxylic acids.

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Tollens Test
• Add ammonia solution to AgNO3 solution
until precipitate dissolves.
• Aldehyde reaction forms a silver mirror.

O O
+
_ H2O _
R C H + 2 Ag(NH3)2 + 3 OH 2 Ag + R C O + 4
O
+
_ H2O _
NH3)2 + 3 OH 2 Ag + R C O + 4 NH3 + 2 H2O

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Reduction Reagents

• Sodium borohydride, NaBH4, reduces

C=O, but not C=C.
• Lithium aluminum hydride, LiAlH4, much
stronger, difficult to handle.
• Hydrogen gas with catalyst also
reduces the C=C bond.

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Catalytic Hydrogenation

• Widely used in industry.

• Raney nickel, finely divided Ni powder
saturated with hydrogen gas.
• Pt and Rh also used as catalysts.

O OH
Raney Ni
H
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Deoxygenation
• Reduction of C=O to CH2
• Two methods:
– Clemmensen reduction if molecule is stable in
hot acid.
– Wolff-Kishner reduction if molecule is stable in
very strong base.

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Clemmensen Reduction
O
C CH2CH2CH3
CH2CH3 Zn(Hg)
HCl, H2O

O
Zn(Hg)
CH2 C CH2 CH3
H HCl, H2O

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Wolff-Kisher Reduction
• Form hydrazone, then heat with strong
base like KOH or potassium t-butoxide.
• Use a high-boiling solvent: ethylene
glycol, diethylene glycol, or DMSO.

CH2 C H CH2 C H KOH CH2 CH3

H2N NH2
heat
O NNH2

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End of Chapter 18