Organic Chemistry

Anmol upadhyay

Unit 2
Ketones and Aldehydes
Carbonyl Compounds

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2
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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3
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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4
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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5
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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6
Examples
CH3 O
CH3 CH2 CH CH2 C H

3-methylpentanal
CHO

2-cyclopentenecarbaldehyde

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7
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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8
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 a-bromoethyl isopropyl ketone

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9
Historical Common
Names O
C
O CH3
CH3 C CH3
acetone acetophenone
O
C

benzophenone
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10
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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11
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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Chapter 18 12
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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13
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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14
Chapter 18 15
Chapter 18 16
Chapter 18 17
Chapter 18 18
Chapter 18 19
Chapter 18 20
Synthesis/ Preparation
• 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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21
Ozonolysis
Alkene Cleavage

CH3 CH3 1) O3 in CH2Cl2 CH3 CH3

C=C C O +O C
2) CH3SCH3 + DMSO
H CH3 H CH3
or Zn/HOAc
DMS
O
O O O
O O O O
CH3 CH3
C=C H O
H
H CH3
ozonide
Synthesis
• 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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23
Friedel-Crafts Acylation
aldehydes from carboxylic
acids

O O

C C
R OH R H

1. LiAlH4 PDC, CH2Cl2

2. H2O
RCH2OH
Example

benzaldehyde from benzoic acid

O O

COH CH

1. LiAlH4 PDC
2. H2O CH2Cl2
CH2OH
(81%) (83%)
What about..?

ketones from aldehydes

O O

C C
R H R R'

1. R'MgX OH PDC, CH2Cl2

2. H3O+
RCHR'
Example

3-heptanone from propanal

O O

C CH3CH2C(CH2)3 CH3
CH3CH2 H
(57%)
1. CH3(CH2)3MgX
H2CrO4
2. H3O + OH

CH3CH2CH(CH2)3 CH3
SYNTHESIS DIBAH
Diisobutyl Aluminum Hydride
Reduction of an Ester to an Aldehyde
O O
COCH2CH3 CH
1) DIBAH
+ CH3CH2OH
in toluene
+
2) H3O

H
DIBAH
Al
(CH3)2CHCH2 CH2CH(CH3)2
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
30
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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31
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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32
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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33
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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34
Gatterman-Koch
Formylation O
CH
CO, HCl
AlCl3/CuCl
benzene or activated benzene needed
in situ preparation of formyl chloride
O
C O + HCl HCCl
Oxymercuration Hydration
Markovnikov

OH
HgSO4, H2SO4
CH3CH2C CH CH3CH2C=CH2
H2O
an enol

O
CH3CH2CCH3
a ketone
Hydroboration Hydration
Anti-Markovnikov
OH
1) disiamyl borane
CH3CH2C CH CH3CH2CH=CH2
2) H2O2, NaOH
an enol

B O
H CH3CH2CH2CH
(sia) 2BH an aldehyde
Gilman Reagent with
Acid Chlorides
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.

Chapter 18 39
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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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40
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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41
Addition of Alcohol

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42
Chapter 18 43
Chapter 18 44
Chapter 18 45
Chapter 18 46
47
Chapter 18 48
Use of acetal as a protecting

No direct way of reducing ester 49

group
Chapter 18 50
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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51
Oxidation of Aldehydes
Easily oxidized to carboxylic acids.

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Chapter 18 52
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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53
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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54
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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55
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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56
Clemmensen Reduction
O
C CH2CH2CH3
CH2CH3 Zn(Hg)
HCl, H2O

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

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57
Wolff-Kisher Reduction
• CO----CH2
• 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

58 =>
Wittig Reaction
• Nucleophilic addition of phosphorus ylides.
• Product is alkene. C=O becomes C=C.

Chapter 18 59
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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 =>
60
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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61
Chapter 18 62
Chapter 18 63
Chapter 18 64
Chapter 18 65
CANNIZARO REACTION

66
Chapter 18 67
Chapter 18 68
Oxidation of carbonyl compounds

oxidation of aldehydes and ketones by

Baeyer – Villiger oxidation peroxyacids to esters

O O
C CH O C CH3
3
+ R-CO-OOH

O H O OH O OH O H
H
C O O C R Ph C O O C R Ph C O O C R
Ph CH3
CH3 CH3

OH
-R C
O

O O H
C o Ph C O
H3C O Ph CH3
PERKIN REACTION

Chapter 18 70
Chapter 18 71
KNOEVENAGEL RXN

Chapter 18 72
MANNICH REACTION

Chapter 18 73
HALOGINATION

Chapter 18 74
Chapter 18 75
Chapter 18 76
α β UNSATURATED
ALDEHYDE

Chapter 18 77
KETONE

Chapter 18 78
REACTION

Chapter 18 79
Chapter 18 80
Chapter 18 81
Chapter 18 82