CH 19: Aldehydes and Ketones Renee Y. Becker Valencia Community College CHM 2211 1.

CH 19: Aldehydes and Ketones

Renee Y. Becker

Valencia Community College

CHM 2211

1

Some Generalizations About Carbonyl Compounds

• The most important functional group in organic chemistry.

O

CRAcyl group

R = alkyl, aryl, or alkenyl

The other residue my be C, H, O, X, N, S, etc.

2

Some Generalizations About Carbonyl Compounds

• carbonyl compounds are planar about the double bond with bond angles 120 due to the sp2 hybridized carbon.

• Many types of carbonyl compounds have significant dipole moments.

• The polarity of the C-O bond plays a significant role in the reactivity of carbonyl compounds.

O

C

Nucleophilic oxygen reacts with acids and electrophiles.

Electrophilic carbon reacts with bases and nucleophiles. 3

Aldehydes and Ketones

CH3CH

O

Ethanal

CH3CCH3

O

Propanone

4

Aldehydes and Ketones

• Due to the polarity of the carbonyl C-O bond, aldehydes and ketones have higher BPs than alkanes with similar molecular weights.

• The lack of H-bonding hydrogens, results in lower BPs than similar alcohols.

CH3CH2CH2CH3 CH3CH2CH CH3CH2CH2OH

O

ButaneM.W. = 58BP = -0.45 oC

PropanalM.W. = 58BP = 49 oC

PropanolM.W. = 60BP = 97 oC

5

Naming Aldehydes

• Aldehydes are named by replacing the terminal-e of the corresponding alkane name with –al

• The parent chain must contain the CHO group– The CHO carbon is numbered as C1

• If the CHO group is attached to a ring, use the suffix carbaldehyde.

6

Naming Aldehydes

CHO

CH3trans-2-methylcyclohexanecarbaldehyde

CHO

Cyclopentanecarbaldehyde

CHO

Benzenecabaldehydeor

phenylmethanalor

benzaldehyde 7

Naming Aldehydes

8

Example 1: Name

9

1

2

3

4

H

O

H

O

Cl

H

O

O

H

1

2

3

4

H

O

H

O

Cl

H

O

O

H

Example 2: Draw

1. 3-Methylbutanal

2. 3-Methyl-3-butenal

3. cis-3-tert-Butylcyclohexanecarbaldehyde

10

Naming Ketones

• Replace the terminal -e of the alkane name with –one

• Parent chain is the longest one that contains the ketone group– Numbering begins at the end nearer the

carbonyl carbon

11

Naming Ketones

CH3CH2CCH2CCH3

O O

2,4-Hexanedione

CH3CHCH2CCH3

O

CH3

4-Methyl-2-pentanone

H3C O

4-Methylcyclohexanone

12

Naming Ketones

• Ketones with Common Names

13

Ketones and Aldehydes as Substituents

• The R–C=O as a substituent is an acyl group is used with the suffix -yl from the root of the carboxylic acid

– CH3CO: acetyl; CHO: formyl; C6H5CO: benzoyl

CR

O

An acyl group

CH3C

OC

H

O

Acetyl Formyl

C

O

Benzoyl

14

Ketones and Aldehydes as Substituents

• The prefix oxo- is used if other functional groups are present and the doubly bonded oxygen is labeled as a substituent on a parent chain

15

Example 3: Name

CH3CH2CCH(CH3)2

O

O O

O

HHH3C

CH3

O

1.

2.

3.

4.

16

Example 4: Draw

1. 4-Chloro-2-pentanone

2. P-bromoacetophenone

3. 3-ethyl-4-methyl-2-hexanone

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Preparation of Aldehydes

• Oxidize primary alcohols using pyridinium chlorochromate

18

Preparation of Aldehydes

• Oxidation of alkenes with a vinylic hydrogen

19

O3

Zn, CH3CO2H

aldehydeketone

Dicarbonyl compound

6-oxoheptanal

O3

aldehyde aldehyde

O3

Zn, CH3CO2H

Zn, CH3CO2H

H

OH

O

H

H

OH

O

HO

H

O

+

+

O

3

Zn, CH3CO2H

aldehydeketone

Dicarbonyl compound

6-oxoheptanal

O3

aldehyde aldehyde

O3

Zn, CH3CO2H

Zn, CH3CO2H

H

OH

O

H

H

OH

O

HO

H

O

+

+

Preparation of Aldehydes

• The partial reduction of certain carboxylic acid derivatives. (esters)

RC

Y

OH

RC

H

O+ Y

20

DIBAH, toluene

-78 C H3O+

DIBAH - diisobutylaluminum hydride

CH3O-

O

O O

H

Al

H

+DIBAH, toluene

-78 C H3O+

DIBAH - diisobutylaluminum hydride

CH3O-

O

O O

H

Al

H

+

Example 5

How would you prepare pentanal from the following:

1. 1-Pentanol

2.1-Hexene

3. O

O

21

Preparing Ketones

• Oxidation of secondary alcohols

RCHR'

OHPCCCH2Cl2

RCR'

O

22

Preparing Ketones

• Oxidation of alkenes if one unsaturated carbon is disubstituted

23

O3

Zn, CH3CO2H

aldehydeketone

OH

O

H

+

O

3

Zn, CH3CO2H

aldehydeketone

OH

O

H

+

Preparing Ketones

• Friedel-Crafts acylation of aromatic compounds with an acid chloride.

ArH + RCClO

AlCl3 ArCRO

+ HCl

Occurs only once!

24

Preparing Ketones

• Hydrations of terminal alkynes– Methyl ketone synthesis– Hg2+ catalyst

25

H3O+

HgSO4

OH3O+

HgSO4

O

Example 6

How would you carry out the following reactions? More than 1 step might be necessary.

1. 3-Hexyne 3-Hexanone

2. Benzene m-Bromoacetophenone

3. Bromobenzene Acetophenone

26

Reactions of Aldehydes and Ketones

• Oxidation reactions

• Nucleophilic addition reactions

• Conjugate nucleophilic addition reactions

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Oxidation of Aldehydes

• Jones’ Reagent (preferred)– Preferred over other oxidation reagents due to

Room temp. reaction with high yields– Run under acidic conditions (con)

• Will react with C=C and any acid sensitive functionality

28

CrO3, H3O+

acetone, 0 CH

O

OH

OC r O

3, H3O+

acetone, 0 CH

O

OH

O

Oxidation of Aldehydes

• Tollen’s reagent

• For use with C=C double bonds

29

Ag2O

NH4OH, H2O

Ag

O

H

O

OH +A g

2O

NH4OH, H2O

Ag

O

H

O

OH +

Oxidation of Ketones

• Ketones are resistant toward oxidation due to the missing hydrogen on the carbonyl carbon

• Treatment of ketones with hot KMnO4 will cleave the C-C bond adjacent to the carbonyl group:

30

KMnO4, H2O, NaOH

H3O+

KMnO4, H2O, NaOH

H3O+

O

OH

O

O

OHH

CO2H

CO2H

O

+KMnO4, H2O, NaOH

H3O+

KMnO4, H2O, NaOH

H3O+

O

OH

O

O

OHH

CO2H

CO2H

O

+

Nucleophilic Addition Reactions of Aldehydes and Ketones

• Nu- approaches 45° to the plane of C=O and adds to C

• A tetrahedral alkoxide ion intermediate is produced

31

32

Nucleophiles

• Nucleophiles can be negatively charged ( : Nu) or neutral ( : Nu) at the reaction site

• The overall charge on the nucleophilic species is not considered

33

Nucleophilic Addition Reactions

34

Relative Reactivity of Aldehydes and Ketones

• Aldehydes are generally more reactive than ketones in nucleophilic addition reactions

• The transition state for addition is less crowded and lower in energy for an aldehyde (a) than for a ketone (b)

35

Electrophilicity of Aldehydes and Ketones

• Aldehyde C=O is more polarized than ketone C=O

• As in carbocations, more alkyl groups stabilize + character

• Ketone has more alkyl groups, stabilizing the C=O carbon inductively

36

Reactivity of Aromatic Aldehydes

• Aromatic aldehydes are less reactive in nucleophilic addition than straight chain aldehydes– Due to electron-donating resonance effect of aromatic

ring• Makes carbonyl group less electrophilic

37

Nucleophilic Addition of H2O: Hydration

• Aldehydes and ketones react with water to yield 1,1-diols (geminal (gem) diols)

• Hyrdation is reversible: a gem diol can eliminate water

38

Relative Energies

• Equilibrium generally favors the carbonyl compound over hydrate for steric reasons– Acetone in water is 99.9% ketone form

• Exception: simple aldehydes– In water, formaldehyde consists is 99.9%

hydrate

39

Acid & Base-Catalyzed Addition of Water

• Addition of water is catalyzed by both acid and base

• The base-catalyzed hydration nucleophile is the hydroxide ion, which is a much stronger nucleophile than water

• Acid-Catalyzed Addition of Water• Protonation of C=O makes it more electrophilic

40

Mechanism 1: Base catalyzed hydration of an aldehyde/ketone

41

NaOH

H2O

Na+ -OH-OH

NaOH

NaOH

O OH

OH

O O–

OH

OHH

OH

OH

+

+

+

+

N a O H

H

2O

Na+ -OH-OH

NaOH

NaOH

O OH

OH

O O–

OH

OHH

OH

OH

+

+

+

+

Mechanism 2: Acid catalyzed hydration of an aldehyde/ketone

42

H2O

H3O+

H3O+

H3O+O OH

OH

O O+H

OH

O+

H H

O+H

H

H OH H

OH H

OH

OH

+

+

+

+

H2O

H3O+

H3O+

H3O+O OH

OH

O O+H

OH

O+

H H

O+H

H

H OH H

OH H

OH

OH

+

+

+

+

Addition of H-Y to C=O

• Reaction of C=O with H-Y, where Y is electronegative, gives an addition product (“adduct”)

• Formation is readily reversible

43

Nucleophilic Addition of HCN: Cyanohydrin Formation

• Aldehydes and unhindered ketones react with HCN to yield cyanohydrins, RCH(OH)CN

RC

R'

O+

OHC

R'R

HC N N

a cyanohydrinAldehyde or

ketoneHydrogencyanide

44

Mechanism of Formation of Cyanohydrins

• Addition of HCN is reversible and base-catalyzed, generating nucleophilic cyanide ion, CN

• Addition of CN to C=O yields a tetrahedral intermediate, which is then protonated

• Equilibrium favors adduct

45

Mechanism 3: Formation of Cyanohydrins

46

H--CN

NH3

-CN NH4+

H--CN NH3 -CN

H--CN

NH4+

-CN-CN

O

H H

OH CN

O

H

O–

H

CN

H

OH CN

++

+

++

H - - C N

N H

3

-CN NH4+

H--CN NH3 -CN

H--CN

NH4+

-CN-CN

O

H H

OH CN

O

H

O–

H

CN

H

OH CN

++

+

++

Uses of Cyanohydrins

• Nitriles can be reduced with LiAlH4 to yield primary amines:

Cl

Cl

CH

O HCNCl

Cl

CCN

OH

1. LiAlH4, THF2. H2O

Cl

Cl

CCH2NH2

OH

2,4-Dichlorobenzaldehydecyanohydrin

(2,4-Dichloro-phenyl)-2-aminoethanol 47

Uses of Cyanohydrins

• Nitriles can be hydrolyzed with hot aqueous acid to yield carboxylic acids:

Cl

Cl

CH

O HCNCl

Cl

CHCN

OH

H3O+, heat

Cl

Cl

CHCOOHOH

2,4-Dichlorobenzaldehydecyanohydrin

(2,4-Dichloro-phenyl)-2-hydroxy-ethanoic acid 48

Nucleophilic Addition of Grignard Reagents and Hydride Reagents: Alcohol Formation

• Treatment of aldehydes or ketones with Grignard reagents yields an alcohol– Nucleophilic addition of the equivalent of a carbon

anion, or carbanion. A carbon–magnesium bond is strongly polarized, so a Grignard reagent reacts for all practical purposes as R : MgX +.

49

Mechanism of Addition of Grignard Reagents

• Complexation of C=O by Mg2+, Nucleophilic addition of R : , protonation by dilute acid yields the neutral alcohol

• Grignard additions are irreversible because a carbanion is not a leaving group

50

Mechanism 4: Addition of Grignard Reagents

51

RC

R'

OR" MgX

OC R"

R'R

H3O+ OHC R"

R'R

adehyde orketone

an alcoholalkoxide

Hydride Addition

• Convert C=O to CH-OH

• LiAlH4 and NaBH4 react as donors of hydride ion

• Protonation after addition yields the alcohol

52

H-

NaBH4 or LiAlH4

H3O+

H2O

O O–

H H

OH

+

H -

NaBH4 or LiAlH4

H3O+

H2O

O O–

H H

OH

+

Nucleophilic Addition of Amines: Imine and Enamine Formation

RNH2 (primary amines) adds to C=O to form imines, R2C=NR (after loss of HOH)

R2NH (secondary amines) yields enamines, R2NCR=CR2 (after loss of HOH) (ene + amine = unsaturated amine)

53

54

Mechanism of Formation of Imines

• Primary amine adds to C=O

• Proton is lost from N and adds to O to yield a neutral amino alcohol (carbinolamine)

• Protonation of OH converts into water as the leaving group

• Result is iminium ion, which loses proton

• Acid is required for loss of OH – too much acid blocks RNH2

Note that overall reaction is substitution of RN for O 55

Mechanism 5: Imine Formation

56

Imine Derivatives

• Addition of amines with an atom containing a lone pair of electrons on the adjacent atom occurs very readily, giving useful, stable imines

• For example, hydroxylamine forms oximes and 2,4-dinitrophenylhydrazine readily forms 2,4-dinitrophenylhydrazones

– These are usually solids and help in characterizing liquid ketones or aldehydes by melting points

57

58

Mechanism 6: Enamine Formation

59

Nucleophilic Addition of Hydrazine: The Wolff–Kishner Reaction

• Treatment of an aldehyde or ketone with hydrazine, H2NNH2 and KOH converts the compound to an alkane

• Originally carried out at high temperatures but with dimethyl sulfoxide as solvent takes place near room temperature

60

Mechanism 7: The Wolff–Kishner Reaction

61

Nucleophilic Addition of Alcohols: Acetal Formation

• Alcohols are weak nucleophiles but acid promotes addition forming the conjugate acid of C=O

• Addition yields a hydroxy ether, called a hemiacetal (reversible); further reaction can occur

• Protonation of the OH and loss of water leads to an oxonium ion, R2C=OR+ to which a second alcohol adds to form the acetal

62

Uses of Acetals

• Acetals can serve as protecting groups for aldehydes and ketones

• It is convenient to use a diol, to form a cyclic acetal (the reaction goes even more readily)

63

Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction

• The sequence converts C=O is to C=C• A phosphorus ylide adds to an aldehyde or ketone to

yield a dipolar intermediate called a betaine • The intermediate spontaneously decomposes through a

four-membered ring to yield alkene and triphenylphosphine oxide, (Ph)3P=O

• Formation of the ylide is shown below

64

Mechanism 8: The Wittig Reaction

65

Uses of the Wittig Reaction

• Can be used for monosubstituted, disubstituted, and trisubstituted alkenes but not tetrasubstituted alkenes The reaction yields a pure alkene of known structure

• For comparison, addition of CH3MgBr to cyclohexanone and dehydration with, yields a mixture of two alkenes

66

The Cannizaro Reaction

• The adduct of an aldehyde and OH can transfer hydride ion to another aldehyde C=O resulting in a simultaneous oxidation and reduction (disproportionation)

67

Conjugate Nucleophilic Addition to -Unsaturated Aldehydes and Ketones

• A nucleophile can add to the C=C double bond of an ,-unsaturated aldehyde or ketone (conjugate addition, or 1,4 addition)

• The initial product is a resonance-stabilized enolate ion, which is then protonated

68

69

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Conjugate Addition of Amines

• Primary and secondary amines add to , -unsaturated aldehydes and ketones to yield -amino aldehydes and ketones

71

Conjugate Addition of Alkyl Groups: Organocopper Reactions

• Reaction of an , -unsaturated ketone with a lithium diorganocopper reagent

• Diorganocopper (Gilman) reagents from by reaction of 1 equivalent of cuprous iodide and 2 equivalents of organolithium

• 1, 2, 3 alkyl, aryl and alkenyl groups react but not alkynyl groups

72

73

RX2 Li

pentaneRLi + Li + X

RLi2CuIether

Li+(RCuR) + Li+ + I-

Gilman Reagent

74

Mechanism of Alkyl Conjugate Addition

• Conjugate nucleophilic addition of a diorganocopper anion, R2Cu, an enone

• Transfer of an R group and elimination of a neutral organocopper species, RCu

75

Example 7

CH3CCHO

CH23-Buten-2-one

1. Li(CH3)2Cu, ether

2. H3O+

O

2-Cyclohexenone

1. Li(H2C=CH)2Cu, ether

2. H3O+

76