1

Ketones and Aldehydes

Adapted from

Organic Chemistry, L. G. Wade, Jr.

C=O

2

C CC

C

C C

O

Violet (Irone)

C

OH

salicylaldehyde

(meadowsweet)

OH

C

O

O

Piperonal

(Heliotrope)

OH

C

CH3(CH2)4C H

O

(Eucalyptus) CH3(CH2)10C H

O

(Citrus Fruits)

CH3 C C CH3

O O

Raspberries

Carbonyl Compounds

� -(CO)-

� -CHO

=>

3

Carbonyl Structure� Carbon is sp2 hybridized.

� C=O bond is shorter, stronger, and more

polar than C=C bond in alkenes.

=>

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.

=>

CH3CH2CCH2CH2CH2

O

CH3CH CHCH2CCH3

O

CH3CH2CCH2CCH3

O O

3-hexanone 4-hexen-2-one 2,4-hexanedione

4

Examples

CH3 C

O

CH

CH3

CH3

O

Br

CH3 C

O

CH

CH3

CH2OH

3-methyl-2-butanone3-bromocyclohexanone

4-hydroxy-3-methyl-2-butanone

=>

Naming Aldehydes

� IUPAC: Replace -e with -al.

� The aldehyde carbon is number 1.

� If -CHO is attached to a ring, use the suffix

-carbaldehyde.

=>

5

CH3CH

O

CH3CH2CH

O

CH3CHCH2CH2CHCH

O

CH2CH3

CH3

ethanal propanal 2-ethyl-5-methylhexanal

Examples

CH3 CH2 CH

CH3

CH2 C H

O

CHO

3-methylpentanal

2-cyclopentenecarbaldehyde

=>

6

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.

CH3 C CH

CH3

CH2 C H

OO

COOH

CHO

3-methyl-4-oxopentanal 3-formylbenzoic acid

=>

Order of Precedence

� For compounds that contain more than one

functional group indicated by a suffix

Suffix Prefix

-COOH -oic acid

-CHO -al oxo-

-C=O -one oxo-

-OH -ol hydroxy

PRECEDENCE

7

Common Names for Ketones� Named as alkyl attachments to -C=O.

� Use Greek letters instead of numbers.

CH3 C

O

CH

CH3

CH3CH3CH C

O

CH

CH3

CH3

Br

methyl isopropyl ketone α−bromoethyl isopropyl ketone

=>

Historical Common Names

CH3 C

O

CH3

CCH3

O

C

O

acetone acetophenone

benzophenone

=>

8

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.

=>

Physical Properties

9

Physical Properties

� Oxygen is more electronegative than carbon

� (3.5 vs 2.5) and, therefore, a C=O group is polar

� aldehydes and ketones are polar compounds and interact in the pure state by dipole-dipole interaction

� they have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight

δδδδ-δδδδ+C O

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.

=>

10

Mole Weight Boiling point oC

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.

=>

11

Formaldehyde

� Gas at room temperature.

� Formalin is a 40% aqueous solution.

O

CO

C

OC

H H

H

H

H

H

heatH C

O

HH2O

H CH

OHHO

trioxane, m.p. 62°C

formaldehyde,

b.p. -21°Cformalin

=>

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.

1850 cm-11780 cm-11745 cm-11715 cm-1

O O OO

12

IR Spectroscopy

� The presence of a carbon-carbon double bond or a benzene ring

in conjugation with the carbonyl group causes a shift in the C=Oabsorption to a lower wave number

1690 cm-1 1700 cm-1

CH

OH3 C

C

O

CH-C-CH 3

H3 C

H3 C

CH-CH 2 -C-CH 3

H3 C

O

1717 cm-1

1H NMR Spectroscopy

=>

13

13C NMR Spectroscopy

=>

MS for 2-Butanone

=>

14

MS for Butyraldehyde

=>

McLaffertyRearrangement

� Loss of alkene (even mass number)

� Must have γ-hydrogen

=>

15

UV Spectra, ππππ →→→→ ππππ*

� C=O conjugated with another double bond.

� Large molar absorptivities (> 5000)

=>

UV Spectra, n →→→→ ππππ*� Small molar absorptivity.

� “Forbidden” transition occurs less frequently.

=>

16

Industrial Importance

� Acetone and methyl ethyl ketone are

important solvents.

� Formaldehyde used in polymers like

Bakelite.

� Flavorings and additives like vanilla,

cinnamon, artificial butter.

=>

Phenol-Formaldehyde Polymers (Bakelite)

• Each formaldehyde molecule reacts with two phenol

molecules to eliminate water. The polymer is then

formed. OH OH

H

C

H

O

+ +

OH OH

H2

C+ H2O

17

Synthesis

Synthesis Review

� Oxidation

� 2° alcohol + Na2Cr2O7 → ketone

� 1° alcohol + PCC → aldehyde

CH2OHPCCCH2Cl2

CHO

18

Synthesis Review

� Ozonolysis of alkenes.

C

H

R

C

R'

R''

1)

2)

O3

(CH3)2SC

H

R

O + CO

R'

R''

=>

1. O3

2. Zn, CH3COOH CH3CCH2CH2CH2CH2CH

O O

Synthesis Review

� Friedel-Crafts acylation

� Acid chloride/AlCl3 + benzene → ketone

� CO + HCl + AlCl3/CuCl + benzene →benzaldehyde (Gatterman-Koch)

CCH3

O

CH3CCl

O AlCl3HEAT

19

Synthesis Review

� Hydration of alkynes

=>

Synthesis Review

� Hydration of alkynes

=>

20

Synthesis Using 1,3-Dithiane� Remove H+ with n-butyllithium.

S S

H H

BuLi

S S

H

_

• Alkylate with primary alkyl halide,

then hydrolyze.

S S

H

_

CH3CH2BrS S

H CH2CH3

H+, HgCl2

H2O H

C

O

CH2CH3

=>

Ketones from 1,3-Dithiane� After the first alkylation, remove the second

H+, react with another primary alkyl halide,

then hydrolyze.

BuLi

S S

H CH2CH3

H+, HgCl2

H2OCH3

C

O

CH2CH3_

S S

CH2CH3

CH3Br

S S

CH3 CH2CH3

=>

21

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.

C

O

O Li_

+

CH3Li

C

O

CH3

O

Li_ +

Li+

_

H3O+

C

OH

CH3

OHH2O_ C

O

CH3

=>

Ketones from Nitriles

� A Grignard or organolithium reagent

attacks the nitrile carbon.

� The imine salt is then hydrolyzed to form a

ketone.

H3O+

CH3CH2MgBr +

C N

ether

CCH2CH3

N MgBr

CCH2CH3

O

=>

22

Aldehydes from Acid ChloridesUse a mild reducing agent to prevent reduction

to primary alcohol.

=>

CH3CH2CH2C

O

HLiAlH(O-t-Bu)3

CH3CH2CH2C

O

Cl

Ketones from Acid ChloridesUse lithium dialkylcuprate (R2CuLi), formed by

the reaction of 2 moles of

R-Li with cuprous iodide.

CH3CH2CH2Li2CuI

(CH3CH2CH2)2CuLi

(CH3CH2CH2)2CuLi + CH3CH2C

O

Cl CH3CH2C

O

CH2CH2CH3

=>

23

Reactivity� Nucleophic attack (addition)

� Oxidation of CHO (KMnO4/HNO3

;CrO3; Ag2O/NH3)

� Reduction (MH; Hydrazine;)

=>

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.

=>

24

Nucleophilic Addition

Either alcohol or a compound with C=Nu is formed

-H2OH+

H+

-:Nu-H

:Nu-

R RC

Nu

C

O

Nu HC

O

Nu H

H

C

O

Nu

H

C

O

Nu

R RC

O

Nucleophilic Addition

CH3C CH3

O

C N CH3CH3C

O

C N

The alkoxide addition product shows how electron density is transferred.

25

Nucleophilic Addition

� Attacking nucleophile

can be negatively

charged (:Nu-) or

neutral (:Nu)

� If neutral usually has

hydrogen attached

(:Nu-H)HOH

ROH

H3N

RNH2

HO-

H-

R3C-

RO-

NC-

Negatively chargednucleophiles

Neutral nucleophiles

Relative Reactivity

C

H

HR1 deg carbocation

(less stable, more reactive)

C

H

RR2 deg carbocation

(more stable, less reactive)

C

O

HRAldehyde

(less stabilizaton of δδδδ++++, more reactive)

C

O

RRKetone

(more stabilizaton of δδδδ−−−−, less reactive)

26

Relative Reactivity

CH

O

CH

O

CH

O

CH

O

Electron-donating resonance effect of aromatic ring makes the carbonyl less electrophilic than the carbonyl group in an aliphatic aldehyde.

Wittig Reaction� Nucleophilic addition of phosphorus ylides.

� Product is alkene. C=O becomes C=C.

=>

27

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

+_

Ph3P CHCH3BuLi

+

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 CHCH3

+C O

H3C

Ph

Ph3P

CH

CH3

C

O

CH3

Ph

+

Ph3P O

C CCH3

Ph

H

H3C

Ph3P

CH

CH3

C

O

CH3

Ph

_+Ph3P

CH

CH3

C

O

CH3

Ph=>

28

Wittig Reaction

O

1. CH3MgBr

2. POCl3

(C6H5)3P+_CH2

-

THF

CH2

CH2

CH3

Wittig Reaction

(C6H5)3P+_CHCH3

-

THF

CH3CH2C=O

CH2CH3

CH3CH2C=CHCH3

CH2CH3

29

Wittig Reaction

� Examples:

++ -

+

2-Methyl-2-heptene

+

O

CH3

CH3 CCH3 Ph 3 P-CH(CH 2 ) 3 CH3

CH3 C=CH(CH 2 ) 3 CH3 Ph 3 P-O-

Cannizzaro Reaction(not an addition)

HC

O:OH

C

O H

OH

C

O

H

1.

2. H3O+

COH

H H

(reduced)

C

O

OH

(oxidized)

Limited to aldehydes like formaldehyde and benzaldehyde, which have no hydrogen on the carbon next to the –CHO group.

30

Addition of Grignard reagents

� Grignard reagents are usually made by

reacting an organic halide and magnesium

metal in an ether solvent:

RX + Mg RMgXether

ArX + Mg ArMgXether

X = Cl, Br, or I

X = Br

Examples

Grignard reagent + formaldehyde → 1º ROH

Grignard reagent + other aldehydes → 2º ROH

Grignard reagent + ketones → 3º ROH

H2C O + CH3MgBr H2C OMgBr CH3CH2OH

CH3

ether H2O

Formaldehyde

31

Examples

C O + CH3MgBr C OMgBr

H H

CH3

ether

CHOH + Mg(OH)Br

CH3

H2OBenzaldehyde

Examples

CH3CCH3 + CH3CH2MgBr CH3CCH3 CH3CCH3 + Mg(OH)Br

O

CH2CH3

OMgBr

ether H2OCH2CH3

OH

Acetone

32

CH3CCH3 + CH3CH2MgBr CH3CCH3

O

CH2CH3

O_

+MgBr

CH3CCH3

CH2CH3

O_

+MgBr

+ H OH CH3CCH3 + Mg(OH)Br

OH

CH2CH3

33

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.

K = 2000C

H H

HOOH

H2O+H

C

O

H

=>K = 0.002

C

CH3 CH3

HOOH

H2O+CH3

C

O

CH3

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.

CH3CH2

C

O

CH3 + C

CH3CH2 CH3

HOCN

HCN

=>

34

Formation of Imines

� Nucleophilic addition of ammonia or primary amine, followed by elimination of water molecule.

� C=O becomes C=N-R

C O

H3C

PhRNH2

C

CH3

O

Ph

H2N

R

+

_ C

CH3

OH

Ph

N

R

H

C

CH3

Ph

N

R

C

CH3

OH

Ph

N

R

H =>

pH Dependence

� Loss of water is acid catalyzed, but acid

destroys nucleophiles.

� NH3 + H+ → NH4+ (not nucleophilic)

� Optimum pH is around 4.5

=>

35

Other Condensations

=>

36

Addition of Alcohol

=>

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.

=>

37

Mechanism for Hemiacetal

OH

+

+ OH

H+

O

=>

HO OCH3+

HO OCH3

H

HOCH3

OH

+ HOCH3H2OCH3+

+

Hemiacetal to Acetal

+

OCH3HO OCH3

H+

H+

HO OCH3

HOH+

=>

OCH3CH3OOCH3CH3O

H

+

OCH3+

HOCH3

HOCH3

38

Cyclic Acetals

� Addition of a diol produces a cyclic acetal.

� Sugars commonly exist as acetals or

hemiacetals.

O

CH2 CH2

HO OH+

O O

CH2CH2

=>

Acetals as Protecting Groups� Hydrolyze easily in acid, stable in base.

� Aldehydes more reactive than ketones.

O

C

O

H

CH2 CH2

HO OH

O

CO

O

H+

=>

39

Selective Reaction of Ketone� React with strong nucleophile (base)

� Remove protective group.

O

CO

O

CH3MgBr

CO

O

O CH3MgBr

+ _

H3O+

C

O

H

HO CH3

=>

Oxidation of AldehydesEasily oxidized to carboxylic acids.

=>

40

Tollens Test

� Add ammonia solution to AgNO3 solution until

precipitate dissolves.

� Aldehyde reaction forms a silver mirror.

R C

O

H + 2 + 3Ag(NH3)2+

OH_ H2O

+ 2+ 4+2 Ag R C

O

O_

NH3 H2O

=>

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.

=>

41

Catalytic Hydrogenation

� Widely used in industry.

� Raney nickel, finely divided Ni powder

saturated with hydrogen gas.

� Pt and Rh also used as catalysts.

ORaney Ni

OH

H

=>

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.

=>

42

Clemmensen Reduction

C

O

CH2CH3 Zn(Hg)

HCl, H2O

CH2CH2CH3

CH2 C

O

H HCl, H2O

Zn(Hg)CH2 CH3

=>

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

O

HH2N NH2

CH2 C

NNH2

H KOH

heat

CH2 CH3

=>

43

Chapter 18 85

Wolff-Kishner Reduction

http://www.organic-

chemistry.org/namedreactions/wolff-

kishner-reduction.shtm