Organic Chemistry, 5th Edition L. G. Wade, Jr.

Chapter 18 Ketones and Aldehydes

Jo Blackburn Richland College, Dallas, TX Dallas County Community College District 2003,Prentice Hall

Carbonyl Compounds

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Chapter 18 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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Chapter 18 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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Chapter 18 4

Examples
O CH3 C CH CH3
Br O

CH3 3-methyl-2-butanone
O CH3 C CH CH2OH CH3

3-bromocyclohexanone

4-hydroxy-3-methyl-2-butanone =>
Chapter 18 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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Chapter 18 6

Examples
CH3 CH3 CH2 CH CH2 O C H

3-methylpentanal

CHO
2-cyclopentenecarbaldehyde

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Chapter 18 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 C

CH3 CH CH2

O C H
CHO

3-methyl-4-oxopentanal

3-formylbenzoic acid
Chapter 18

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8

Common Names for Ketones

Named as alkyl attachments to -C=O. Use Greek letters instead of numbers.
O CH3 C CH CH3 CH3
Br O CH3CH C CH CH3 CH3

methyl isopropyl ketone

a-bromoethyl isopropyl ketone =>

Chapter 18 9

Historical Common Names

O CH3 C CH3
acetone
O C

O C CH3

acetophenone

benzophenone =>
Chapter 18 10

Aldehyde Common Names

Use the common name of the acid. Drop -ic acid and add -aldehyde.
1 C: formic acid, formaldehyde 2 Cs: acetic acid, acetaldehyde 3 Cs: propionic acid, propionaldehyde 4 Cs: butyric acid, butyraldehyde. =>
Chapter 18 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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Chapter 18 13

Formaldehyde
Gas at room temperature. Formalin is a 40% aqueous solution.
H H O H C O O heat H C H H2O HO OH H C H

C C H O H H

formaldehyde, b.p. -21C

formalin =>

trioxane, m.p. 62C

Chapter 18

14

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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Chapter 18 15

1H

NMR Spectroscopy

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Chapter 18 16

13C

NMR Spectroscopy

Chapter 18

17

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MS for 2-Butanone

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Chapter 18 18

MS for Butyraldehyde

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Chapter 18 19

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

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Chapter 18 20

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

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Chapter 18 21

UV Spectra, n *
Small molar absorptivity. Forbidden transition occurs less frequently.

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Chapter 18 22

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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Chapter 18 23

Synthesis Review
Oxidation
2 alcohol + Na2Cr2O7 ketone 1 alcohol + PCC aldehyde

Ozonolysis of alkenes.
H C C R R'' R' 1) O3 2) (CH3)2S H C O R + O C R''
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Chapter 18 24

R'

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. =>
Chapter 18 25

Synthesis Using 1,3-Dithiane

Remove H+ with n-butyllithium.
BuLi S H S H S _ H S

Alkylate with primary alkyl halide, then hydrolyze.

CH3CH2Br S _ H S S H S H , HgCl2 H2O H
+

O C

CH2CH3

CH2CH3
Chapter 18 26

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Ketones from 1,3-Dithiane

After the first alkylation, remove the second H+, react with another primary alkyl halide, then hydrolyze.
BuLi S H S CH2CH3 S _ S CH3Br S CH3 S CH2CH3 H , HgCl2 H2O CH3
+

O C CH2CH3

CH2CH3

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Chapter 18 27

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 C O Li + CH3Li _ _ + O Li _ + C O Li CH3 H3O OH
+

O C CH3

C OH _ H2O CH3

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Chapter 18 28

Ketones from Nitriles

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

O C CH2CH3

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Chapter 18 29

Aldehydes from Acid Chlorides

Use a mild reducing agent to prevent reduction to primary alcohol.
O CH3CH2CH2C Cl LiAlH(O-t-Bu)3 O CH3CH2CH2C H

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Chapter 18 30

Ketones from Acid Chlorides

Use lithium dialkylcuprate (R2CuLi), formed by the reaction of 2 moles of R-Li with cuprous iodide.
2 CH3CH2CH2Li CuI
O (CH3CH2CH2)2CuLi + CH3CH2C Cl

(CH3CH2CH2)2CuLi
O CH3CH2C CH2CH2CH3

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Chapter 18 31

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

32

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

Chapter 18

33

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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

+ Ph3P

CH2CH3

BuLi
Chapter 18

+ Ph3P
ylide

_ CHCH3
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34

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
+ Ph3P _ O

_ CHCH3

H3C C O Ph
Ph3P O

Ph3P H C

C CH3 CH3 Ph
Ph3P H H3C C O C CH3 Ph
35

H C C CH3 CH3 Ph

H C C CH3 CH3 Ph
Chapter 18

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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 H C + H2O H
O CH3 C + H2O CH3

HO H
HO CH3
Chapter 18

OH C H
OH C CH3 K = 0.002
36

K = 2000

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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 CH3CH2 C HO CH3 + HCN CH3CH2 C CH3
37

CN

Chapter 18

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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
H3C RNH2 C O Ph R _ C H2N O + Ph CH3 R CH3 N C OH H Ph

CH3

CH3 N C Ph

N C OH H Ph
Chapter 18

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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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Chapter 18 39

Other Condensations

Chapter 18

40

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Addition of Alcohol

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Chapter 18 41

Mechanism
Must be acid-catalyzed. Adding H+ to carbonyl makes it more reactive with weak nucleophile, ROH. Hemiacetal forms first, then acidcatalyzed loss of water, then addition of second molecule of ROH forms acetal. All steps are reversible. =>
Chapter 18 42

Mechanism for Hemiacetal

O H+ + OH OH +

OH + HOCH3

H HO HO OCH3 + HOCH3 OCH3 + + H2OCH3

Chapter 18

43

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

HOCH3 OCH3 HOCH3 + + CH3O H OCH3 CH3O OCH3

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Chapter 18 44

Cyclic Acetals
Addition of a diol produces a cyclic acetal. Sugars commonly exist as acetals or hemiacetals.
O + CH2 HO CH2 OH CH2 CH2 O O

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Chapter 18 45

Acetals as Protecting Groups

Hydrolyze easily in acid, stable in base. Aldehydes more reactive than ketones.
O O CH2 HO C O
Chapter 18

CH2 OH
+

C O

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46

Selective Reaction of Ketone

React with strong nucleophile (base) Remove protective group.
O + _ MgBr O CH 3 CH3MgBr C O O C O H3O O
+

HO

CH3

C O

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Chapter 18 47

Oxidation of Aldehydes
Easily oxidized to carboxylic acids.

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Chapter 18 48

Tollens Test
Add ammonia solution to AgNO3 solution until precipitate dissolves. Aldehyde reaction forms a silver mirror.
O R C H + 2
+ Ag(NH3)2

_ + 3 OH

O H2O 2 Ag + R C O

_ + 4

+ NH3)2

_ + 3 OH

O H2O 2 Ag + R C O
Chapter 18

_ + 4 NH3 + 2 H2O

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49

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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Chapter 18 50

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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Chapter 18 51

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. =>
Chapter 18 52

Clemmensen Reduction
O C CH2CH3 Zn(Hg) HCl, H 2O CH2CH2CH3

O CH2 C H

Zn(Hg) HCl, H 2O

CH2

CH3

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Chapter 18 53

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 O H2N NH2 CH2 C H NNH2 KOH heat CH2 CH3

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Chapter 18 54

End of Chapter 18

Chapter 18

55