Chapter 17Chapter 17Aldehydes and Ketones:Aldehydes and Ketones:

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Classes of Carbonyl Compounds

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Resonance

• The first resonance is better because all atoms complete the octet and there are no charges.

• The carbonyl carbon has a partial positive and will react as an electrophile.

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 44

Aldehydes Nomenclature

• The aldehyde carbon is number 1.• IUPAC: Replace -e with -al.• If the aldehyde group is attached to a ring, the suffix

carbaldehyde is used.

when named as a substituent

formyl group carbaldehyde orcarboxaldehyde

when named as a suffix

C H

O

IUPAC Nomenclature of Aldehydes

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 66

Ketone Nomenclature

• Number the chain so that the carbonyl carbon has the lowest number.

• Replace the alkane -e with -one.

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 77

Cyclic Ketone Nomenclature

• For cyclic ketones, the carbonyl carbon is assigned the number 1.

• When the compound has a carbonyl and a double bond, the carbonyl takes precedence.

Functional Class IUPAC Nomenclature of Ketones

CH3CH2CCH2CH2CH3

O O

CH2CCH2CH3

CH CH2

O

H2C CHC

List the groups attached to the carbonyl separately in alphabetical order, and add the word ketone.

CH3CH2CCH2CH2CH3

O

ethyl propyl ketone benzyl ethyl ketone

divinyl ketone

O

CH2CCH2CH3

CH CH2

O

H2C CHC

Functional Class IUPAC Nomenclature of Ketones

Structure and Bonding:Structure and Bonding:The Carbonyl GroupThe Carbonyl Group

planar

bond angles: close to 120°

C=O bond distance: 122 pm

Both C and O are sp2 hybridizes.

Structure of Formaldehyde

The half-filled2p orbitals oncarbon andoxygen overlapto form a bond.

Bonding in Formaldehyde

1-butene propanal

The Carbonyl Group O

dipole moment = 0.3D dipole moment = 2.5D

very polar double bond

2475 kJ/mol

2442 kJ/mol

Alkyl groups stabilize carbonyl groups the sameway they stabilize carbon-carbon double bonds,carbocations, and free radicals.

heat of combustion

Carbonyl Group of a Ketone is MoreStable than that of an Aldehyde

O

O

H

Nucleophiles attack carbon; electrophiles attack oxygen.

Resonance Description ofCarbonyl Group

C

O •• ••

C

O

+

–•••• ••

Physical PropertiesPhysical Properties

boiling point

–6°C

49°C

97°C

Aldehydes and Ketones have Higher Boiling Pointsthan Alkenes, but Lower Boiling Points than Alcohols

More polar than alkenes, but cannot form intermolecular hydrogen bonds to other carbonyl groups.

O

OH

Sources of Aldehydes and KetonesSources of Aldehydes and Ketones

from alkenes

ozonolysis

from alkynes

hydration (via enol)

from arenes

Friedel-Crafts acylation

from alcohols

oxidation

Table 17.1 Synthesis of Aldehydes and Ketones

A number of reactions alreadystudied provide

efficient syntheticroutes to

aldehydes and ketones.

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 2020

Ozonolysis of Alkenes

• The double bond is oxidatively cleaved by ozone followed by reduction.

• Ketones and aldehydes can be isolated as products under these conditions.

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 2121

Friedel–Crafts Reaction

• Reaction between an acyl halide and an aromatic ring will produce a ketone.

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 2222

Hydration of Alkynes

• The initial product of Markovnikov hydration is an enol, which quickly tautomerizes to its keto form.

• Internal alkynes can be hydrated, but mixtures of ketones often result.

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 2323

Grignards as a Source for Ketones and Aldehydes

• A Grignard reagent can be used to make an alcohol, and then the alcohol can be easily oxidized.

C

O

R OH

aldehydes from carboxylic acids

RCH2OH

1. LiAlH4

2. H2OPDC, CH2Cl2

HC

O

R

What About..?

Benzaldehyde from benzoic acid COH

O CH

O

1. LiAlH4

2. H2OPDCCH2Cl2CH2OH

(81%) (83%)

Example

C

O

R H

Ketones from aldehydes

R'RC

O

PDC, CH2Cl21. R'MgX

2. H3O+

RCHR'

OH

What About..?

C

O

CH3CH2 H

3-heptanone from propanal

H2CrO4

1. CH3(CH2)3MgX

2. H3O+

CH3CH2CH(CH2)3 CH3

OH

O

CH3CH2C(CH2)3 CH3

(57%)

Example

Industrial Importance

• Acetone and methyl ethyl ketone are common industrial solvents.

• Formaldehyde is used in polymers like Bakelite and many other polymeric products.

• Also used as flavorings and additives for food.

Reactions of Aldehydes and Reactions of Aldehydes and Ketones:Ketones:

A Review and a PreviewA Review and a Preview

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Already covered in earlier chapters:

Reduction of C=O to CH2

Clemmensen reduction

Wolff-Kishner reduction

Reduction of C=O to CHOH

Addition of Grignard and organolithium reagents

Table 17.2 Reactions of Aldehydes and Ketones

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 3131

Catalytic Hydrogenation

• Widely used in industry• Raney nickel is finely divided Ni powder

saturated with hydrogen gas.• It will attack the alkene first, then the carbonyl.

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 3232

Deoxygenation of Ketones and Aldehydes

• The Clemmensen reduction or the Wolff–Kishner reduction can be used to deoxygenate ketones and aldehydes.

Clemmensen Reduction

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 3434

Wolff–Kishner Reduction

• Forms hydrazone, then heat with strong base like KOH or potassium tert-butoxide

• Use a high-boiling solvent: ethylene glycol, diethylene glycol, or DMSO.

• A molecule of nitrogen is lost in the last steps of the reaction.

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 3535

Sodium Borohydride

• NaBH4 can reduce ketones and aldehydes, but not esters, carboxylic acids, acyl chlorides, or amides.

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 3636

Lithium Aluminum Hydride

R R(H)

OH

HR R(H)

OLiAlH4

ether

aldehyde or ketone

• LiAlH4 can reduce any carbonyl because it is a very strong reducing agent.

• Difficult to handle

Principles of Nucleophilic Addition:Principles of Nucleophilic Addition:

Hydration of Aldehydes and Hydration of Aldehydes and

KetonesKetones

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 3838

• In an aqueous solution, a ketone or an aldehyde is in equilibrium with its hydrate, a geminal diol.

• With ketones, the equilibrium favors the unhydrated keto form (carbonyl).

Hydration of Ketones and Aldehydes

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 3939

Acid-Catalyzed Hydration of Carbonyls

• Hydration occurs through the nucleophilic addition mechanism, with water (in acid) or hydroxide (in base) serving as the nucleophile.

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 4040

• The hydroxide ion attacks the carbonyl group. • Protonation of the intermediate gives the hydrate.

Base-Catalyzed Hydration of Carbonyls

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 4141

Cyanohydrin Formation

• The mechanism is a base-catalyzed nucleophilic addition: Attack by cyanide ion on the carbonyl group, followed by protonation of the intermediate.

• HCN is highly toxic.

2,4-Dichlorobenzaldehydecyanohydrin (100%)

Example

Cl Cl CH

OCl

Cl CHCN

OHNaCN, water

then H2SO4

Example

CH3CCH3

ONaCN, water

then H2SO4

CH3CCH3

OH

CN

(77-78%)

Acetone cyanohydrin is used in the synthesis of methacrylonitrile.

Acetal FormationAcetal Formation

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Some reactions of aldehydes and ketones progressbeyond the nucleophilic addition stage

Acetal formation

Imine formation

Enamine formation

Compounds related to imines

The Wittig reaction

Recall Hydration of Aldehydes and Ketones

HOH

C••O ••

HO C O H••

••

••

••

R

R'

R

R'

Alcohols Under Analogous Reactionwith Aldehydes and Ketones

R”OH

C••O ••

R

R'

R"O C O H••

••

••

••

R

R'

Product is called a hemiacetal.

Product is called a hemiacetal.

R”OH, H+

Hemiacetal reacts further in acid to yield an acetal

R"O C O H••

••

••

••

R

R'

R"O C OR”••

••

••

••

R

R'

Product is called an acetal.

HCl

2CH3CH2OH+

+ H2O

Benzaldehyde diethyl acetal (66%)

Example

CH

O CH(OCH2CH3)2

HOCH2CH2OH+CH3(CH2)5CH

O

p-toluenesulfonic acid

benzene

+ H2O

(81%) H (CH2)5CH3

H2C CH2

O O

C

Diols Form Cyclic Acetals

In general:

Position of equilibrium is usually unfavorablefor acetal formation from ketones.

Important exception: Cyclic acetals can be prepared from ketones.

HOCH2CH2OH+

O

p-toluenesulfonic acid

benzene

+ H2O

H2C CH2

O O

C(78%)

C6H5CH2CCH3

CH3C6H5CH2

Example

© 2013 Pearson Education, Inc.© 2013 Pearson Education, Inc. Chapter 18Chapter 18 5353

Mechanism for Hemiacetal Formation

• Must be acid-catalyzed.• Adding H+ to carbonyl makes it more reactive

with weak nucleophile, ROH.

Acetal Formation

CR R'

O

2R"OH+

OR"

R R'C

OR"

+ H2O

mechanism:

reverse of acetal formation;hemiacetal is intermediate

application:

Aldehydes and ketones can be "protected" as acetals.

Hydrolysis of Acetals

Acetals as Protecting GroupsAcetals as Protecting Groups

The conversion shown cannot be carried outdirectly...

CHCH3CCH2CH2C

O

CCH3CH3CCH2CH2C

O

1. NaNH2

2. CH3I

Example

because the carbonyl group and thecarbanion are incompatible functionalgroups.

C:CH3CCH2CH2C

O–

1) protect C=O

2) alkylate

3) restore C=O

Strategy

HOCH2CH2OH+

p-toluenesulfonic acid

benzene

H2C CH2

O O

C

CH3

CH3CCH2CH2C

O

CH

CH2CH2C CH

Example: Protect

H2C CH2

O O

C

CH3CH2CH2C CH

1. NaNH2

2. CH3I

H2C CH2

O O

CCH3

CH2CH2C CCH3

Example: Alkylate

H2C CH2

O O

C

CH3CH2CH2C CCH3

H2O

HCl

HOCH2CH2OH

(96%)

CCH3CH3CCH2CH2C

O

+

Example: Deprotect

Reaction with Primary Amines:Reaction with Primary Amines:

IminesImines

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Formation of Imines

• Ammonia or a primary amine reacts with a ketone or an aldehyde to form an imine.

• Imines are nitrogen analogues of ketones and aldehydes with a C═N bond in place of the carbonyl group.

• Optimum pH is around 4.5.

CH3NH2CH

O

+

CH=NCH3 + H2O

N-Benzylidenemethylamine (70%)

Example

CH3NH2CH

O

+

CH=NCH3 + H2O

N-Benzylidenemethylamine (70%)

Example CH

OH

NHCH3CH3

© 2013 Pearson Education, Inc. Chapter 18 67

Mechanism of Imine FormationAcid-catalyzed addition of the amine to the carbonyl compound group

Acid-catalyzed dehydration

© 2013 Pearson Education, Inc. Chapter 18 68

Other Condensations with Amines

CH3(CH2)5CH + H2NOH

O

CH3(CH2)5CH + H2O

NOH

(81-93%)

Example

+ H2NNH2

+ H2O

(73%)

Example OC NNH2

C

CCH3

Example O

+ H2NNH

phenylhydrazine

+ H2O

CCH3

NNH

a phenylhydrazone (87-91%)

CH3(CH2)9CCH3

O

H2NNHCNH2

O

+

H2OCH3(CH2)9CCH3

NNHCNH2

O

+

Example

semicarbazide

a semicarbazone (93%)

17.11Reaction with Secondary Amines:

Enamines

R2NH••

+ H2O

(enamine)

C••R2N

C

Enamine Formation

••C

••OR2N H

H C

••C O

••

H C

••

+

(heat in benzene)

Example O NH

viaviaOOHH

N

(80-90%)

N

© 2013 Pearson Education, Inc. Chapter 18 76

The Wittig Reaction

The Wittig reaction converts the carbonyl group into a new C═C double bond where no bond existed before.

A phosphorus ylide is used as the nucleophile in the reaction.

© 2013 Pearson Education, Inc. Chapter 18 77

Preparation of Phosphorus Ylides

Prepared from triphenylphosphine and an unhindered alkyl halide.

Butyllithium then abstracts a hydrogen from the carbon attached to phosphorus.

© 2013 Pearson Education, Inc. Chapter 18 78

Mechanism of the Wittig ReactionBetaine formation

Oxaphosphetane formation

© 2013 Pearson Education, Inc. Chapter 18 79

Mechanism for Wittig

The oxaphosphetane will collapse, forming alkene and a molecule of triphenyl phosphine oxide.

Retrosynthetic Analysis

There will be two possible Wittig routes toan alkene.

Analyze the structure retrosynthetically.

Disconnect the doubly bonded carbons. One will come from the aldehyde or ketone, theother from the ylide.

C C

R

R'

A

B

Retrosynthetic Analysis of Styrene

C6H5CH CH2

HCH

O

+(C6H5)3P CHC6H5

+ –

••

C6H5CH

O

+ (C6H5)3P CH2

+ –

••

Both routesare acceptable.

© 2013 Pearson Education, Inc. Chapter 18 82

Oxidation of Aldehydes

Aldehydes are easily oxidized to carboxylic acids.

© 2013 Pearson Education, Inc. Chapter 18 83

Infrared (IR) Spectroscopy

Very strong C═O stretch around 1710 cm-1 for ketones and 1725 cm-1 for simple aldehydes

Additional C—H stretches for aldehyde: Two absorptions at 2710 cm-1 and 2810 cm-1

© 2013 Pearson Education, Inc. Chapter 18 84

IR Spectra

Conjugation lowers the carbonyl stretching frequencies to about 1685 cm-1.

Rings that have ring strain have higher C═O frequencies.

© 2013 Pearson Education, Inc. Chapter 18 85

Proton NMR Spectra

Aldehyde protons normally absorb between 9 and 10.

Protons of the α carbon usually absorb between 2.1 and 2.4 if there are no other electron-withdrawing groups nearby.

© 2013 Pearson Education, Inc. Chapter 18 86

1H NMR Spectroscopy

Protons closer to the carbonyl group are more deshielded. The , and protons appear at values of that decrease with

increasing distance from the carbonyl group.

© 2013 Pearson Education, Inc. Chapter 18 87

Carbon NMR Spectra of Ketones

The spin-decoupled carbon NMR spectrum of 2-heptanone shows the carbonyl carbon at 208 ppm and the α carbon at 30 ppm (methyl) and 44 ppm (methylene).

© 2013 Pearson Education, Inc. Chapter 18 88

Mass Spectrometry (MS)

© 2013 Pearson Education, Inc. Chapter 18 89

MS for Butyraldehyde