William H. Brown Thomas Poon

www.wiley.com/college/brown

Chapter ThirteenAldehydes and Ketones

13-2

The Carbonyl Group• In this and several following chapters, we

study the physical and chemical properties of classes of compounds containing the carbonyl group, C=O.• aldehydes and ketones (Chapter 13)• carboxylic acids (Chapter 14)• acid halides, acid anhydrides, esters, and amides

(Chapter 15)• enolate anions (Chapter 16)

13-3

Structure• The functional group of an aldehyde is a carbonyl

group bonded to a H atom. • The functional group of a ketone is a carbonyl

group bonded to two carbon atoms.

Propanone(Acetone)

Ethanal(Acetaldehyde)

Methanal(Formaldehyde)

O O OCH3CHHCH CH3CCH3

13-4

Nomenclature• IUPAC names:

• The parent chain is the longest chain that contains the carbonyl group.

• For an aldehyde, change the suffix from -e-e to -al-al.• For an unsaturated aldehyde, show the carbon-

carbon double bond by changing the infix from --an-an- to -en--en-; the location of the suffix determines the numbering pattern.

• For a cyclic molecule in which -CHO is bonded to the ring, add the suffix -carbaldehydecarbaldehyde.

13-5

Nomenclature

CHO HO CHOCyclopentane-carbaldehyde

trans-4-Hydroxycyclo-hexanecarbaldehyde

14

3-Methylbutanal 2-Propenal(Acrolein)

H

O

(2E)-3,7-Dimethyl-2,6-octadienal(Geranial)

1

2

3

4

5

6

78

1122

33

4 H

O

H

O

2-Methyl-cyclohexanone

5-Methyl-3-hexanone

Benzophenone Acetophenone

OO

O O

13-6

Nomenclature• Table 13.1 Increasing Order of Precedence of

Six Functional Groups.

13-7

Nomenclature• Common names

• For an aldehyde, the common name is derived from the common name of the corresponding carboxylic acid.

• For a ketone, name the two alkyl or aryl groups bonded to the carbonyl carbon and add the word ketone.FormaldehydeFormic acid Acetaldehyde Acetic acid

Ethyl isopropyl ketoneDiethyl ketoneDicyclohexyl ketone

O OO

H H

O

H OH

O

H

O

OH

O

13-8

Number Prefixes for Common Number Prefixes for Common NamesNames

PREFIX # C PREFIX # C FORM 1 CAPRO 6

ACET 2 CAPRYL 8 PROPIO 3 CAPR 10 BUTYR 4 LAUR 12 VALER 5

SO.... BUTYRALDEHYDE IS AN ALDEHYDE OF 4 CARBONS.….. THE SAME PREFIXES ARE USED FOR ACIDS.

13-9

Physical Properties• Oxygen is more electronegative than carbon

(3.5 versus 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 interactions.

• They have higher boiling points and are more soluble in water than nonpolar compounds of comparable molecular weight.

13-10

Physical Properties• In liquid aldehydes and ketones, there are weak

intermolecular attractions are between the partial positive charge on the carbonyl carbon of one molecule and the partial negative charge on the carbonyl oxygen of another molecule.

• No hydrogen bonding is possible between aldehyde or ketone molecules.

• Aldehydes and ketones have lower boiling points than alcohols and carboxylic acids, compounds in which there is hydrogen bonding between molecules.

CH

HO +-

C HHO

CHH

O+

-CH

H O-+

+-

13-11

Physical Properties

•Formaldehyde, acetaldehyde, and acetone are infinitely soluble in water.•Aldehydes and ketones become less soluble in water as the hydrocarbon portion of the molecule increases in size.

13-12

Reactions• The most common reaction theme of a carbonyl

group is addition of a nucleophile to form a tetrahedral carbonyl addition compound.

13-13

Grignard Reagents• Addition of carbon nucleophiles is one of the

most important types of nucleophilic additions to a C=O group.• A new carbon-carbon bond is formed in the

process.• We study addition of carbon nucleophiles

called Grignard reagentsGrignard reagents.• Victor Grignard was awarded the Nobel Prize for

chemistry in 1912 for their discovery and application to organic synthesis.

• Grignard reagents have the general formula RMgX, where R is an alkyl or aryl group and X is a halogen.

13-14

Grignard Reagents• Grignard reagents are prepared by adding an

alkyl or aryl halide to a suspension of Mg metal in diethyl ether.

Br Mg MgBr+1-Bromobutane Butylmagnesium bromide

ether

Br Mg MgBr+ ether

Bromobenzene Phenylmagnesium bromide

13-15

Grignard Reagents• Given the difference in electronegativity

between carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with C- and Mg+.• in its reactions, a Grignard reagent behaves as a

carbanion.• Carbanion:Carbanion: An anion in which carbon has an

unshared pair of electrons and bears a negative charge.• A carbanion is a good nucleophile and adds to the

carbonyl group of aldehydes and ketones

13-16

Grignard Reagents• Reaction with protic acids

• Grignard reagents are very strong bases and react with proton acids to form alkanes.

• Any compound containing an O-H, N-H, or S-H group reacts with a Grignard reagent by proton transfer.

CH3CH2-MgBr H-OH CH3CH2-H Mg2+ OH- Br-

Weaker base

Stronger base

Weaker acid

Stronger acid

pKa 51pKa 15.7+++-

+ +

ArOH RSHRCOOHROHHOH RNH2AminesAlcoholsWater Phenols ThiolsCarboxylic

acids

13-17

Grignard Reagents• Reaction with formaldehyde gives a 1° alcohol.

• Reaction with any aldehyde other than formaldehyde gives a 2° alcohol.

Ph MgBr CH3-C-HO

Ph CHCH3

O [MgBr]+HClH2O

Ph CHCH3OH

Mg2+ether

A magnesium alkoxide

Acetaldehyde 1-Phenylethanol(a 2° alcohol)

++

CH3CH2-MgBr H-C-HO

CH3CH2-CH2

O [MgBr]+ HClH2O CH3CH2-CH2

OHMg2+

Formaldehyde

+

A magnesiumalkoxide

+ ether

1-Propanol(a 1° alcohol)

13-18

Grignard Reagents• Reaction with a ketone gives a 3° alcohol.

• Problem: Show how to synthesize this 3° alcohol by three different routes.

Ph MgBr CH3-C-CH3

OPh CCH3

CH3

O [MgBr]+

HClH2O

Ph CCH3

OH

CH3Mg2+ether

2-Phenyl-2-propanol(a 3° alcohol)

Acetone

++

A magnesiumalkoxide

CH3

C-CH2CH3

OH

13-19

Addition of Alcohols• Hemiacetal: A molecule containing an -OH

group and an -OR group bonded to the same carbon.

• Hemiacetals are minor components of an equilibrium mixture except where a 5- or 6-membered ring can form.

CH3CCH3O H

OCH2CH3H+

CH3C-OCH2CH3CH3

OH

A hemiacetal

+

4-Hydroxypentanal A cyclic hemiacetal(major form present at equilibrium)

OHH

O

OH

OHredraw to show

the OH close tothe CHO group O OH12

34

51

2345

1

2345

13-20

Addition of Alcohols• Acetal: A molecule containing two -OR groups

bonded to the same carbon.

CH3C-OCH2CH3CH3

OHCH3CH2OH H+

CH3C-OCH2CH3CH3

OCH2CH3

H2O

A diethyl acetal

++

A hemiacetal

OHH

O

O OHCH3OH

H+ O OCH3H2O

4-Hydroxypentanal

+

A cy clic acetal

13-21

Acetal Formation1. Proton transfer from HA to the hemiacetal

oxygen.

2. Loss of H2O gives a cation.

HO

HR-C-OCH3 H A

H

H

OR-C-OCH3

H

A -+

+

An oxonium ion

+

H OR-C-OCH3

H

HR-C

HOCH3

HR-C OCH3 H2O

+ +

A resonance-stabilized cation

+

+

13-22

Acetal Formation3. Reaction of the cation (an electrophile) with an

alcohol (a nucleophile).

4. Proton transfer to A- gives the acetal and regenerates the acid catalyst.

CH3-OH

R-C OCH3H

H

H

OR-C-OCH3

CH3++

A protonated acetal

+

A

H OR-C-OCH3

CH3

H

HAH

OR-C-OCH3

CH3

A protonated acetal An acetal

++

+

13-23

Acetals• Draw a structural formula for the acetal formed

in each reaction.O HO OH H2SO4+

Ethyleneglycol

(a)

OH

OH

O H2SO4(b) +

13-24

Acetals as Carbonyl-Protecting Groups

• One way to synthesize the ketoalcohol on the right is by a Grignard reaction.

• But first the aldehyde of the bromoaldehyde must be protected; one possibility is as a cyclic acetal.

Ph H

O

H

OBr Ph H

OH O

5-Hydroxy-5-phenylpentanal4-BromobutanalBenzaldehyde+ ??

H

OBr

A cyclic acetal+

H+H2OHO OH+ Br O

O

Ethylene glycol

13-25

An Acetal as a Carbonyl-Protecting Group

• Now the Grignard reagent can be prepared and the new carbon-carbon bond formed.

• Hydrolysis gives the hydroxyaldehyde.

Br OO

Mg BrMg OO

A cyclic acetal A Grignard reagentether

+

Ph

O

H BrMg OO

OO

Ph

O-MgBr++

A magnesium alkoxide

OO

Ph

O-MgBr+HCl, H2O

OH O

Ph H HO OH+

13-26

Imines• Imine: A compound containing a C=N bond;

also called a Schiff base.• Formed by the reaction of an aldehyde or ketone

with ammonia or a 1° amine.

An imineAmmoniaCyclohexanone

++ NH3 H2OO NHH+

CH3CHO

H2N CH3CH=N H2O+ +

Ethanal Aniline An imine

H+

13-27

Formation of Imines1. Addition of the amine to the carbonyl carbon

followed by proton transfer gives an aminoalcohol.

2. Two proton-transfer reactions and loss of H2O.

CO

H2N-R CO

HN-RH

CO H

N-RH

-

+

A tetrahedral carbonyladdition intermediate

+

HO H

HCO H

N-RH

CO HH

N-RH

HO

HC N-R H2O H O

HH

An imine

+

+

+ ++

13-28

Rhodopsin• Reaction of vitamin A aldehyde (retinal) with an

amino group on the protein opsin gives rhodopsin.

C=OH

H2N-Opsin+

C=H N-Opsin

1112

11-cis-Retinal

Rhodopsin(Visual purple)

13-29

Reductive Amination• Reductive amination: The formation of an imine followed

by its reduction to an amine.

• Reductive amination is a valuable method for the conversion of ammonia to a 1° amine, and a 1° amine to a 2° amine.

+

Cyclohex-anone

Cyclohexyl-amine

(a 1° amine)

O -H2OH+

H2N

Dicyclohexylamine(a 2° amine)

An imine(not isolated)

N H2/Ni

NH

13-30

Keto-Enol Tautomerism• Enol: A molecule containing an -OH group

bonded to a carbon of a carbon-carbon double bond.

The keto form predominates for most simple aldehydes and ketones

CH3-C-CH3

O OHCH3-C=CH2

Acetone(keto form)

Acetone(enol form)

13-31

Keto-Enol Tautomerism• Problem: Draw two enol forms for each ketone.

• Problem: Draw the keto form of each enol.

(a) (b)

OO

OCHOH OH

OH

OH(c)(b)(a)

13-32

Keto-Enol Tautomerism• Interconversion of keto and enol forms is

catalyzed by both acid and base.• Following is a mechanism for acid catalysis1. Proton transfer to the carbonyl oxygen.

2. Proton transfer from the -carbon to A:-

13-33

Racemization an at -Carbon• When an enantiomerically pure aldehyde or

ketone with at least one -hydrogen is treated with a trace of acid or base, it gradually becomes a racemic mixture; it loses all optical activity.

C CO

CH3

Ph

HH3C

OH

CH3

C CPh

H3CC C

O

CH3

Ph

H3CH

An achiral enol(R)-3-Phenyl-2-butanone

(S)-3-Phenyl-2-butanone

H+

or OH-

H+

or OH-

13-34

-Halogenation• Aldehydes and ketones with an -hydrogen

react with Br2 and Cl2 to give an -haloaldehyde or an -haloketone.O

Br2CH3COOH

OBr

HBr+ +

Acetophenone -Bromoacetophenone

13-35

-Halogenation• The key intermediate in -halogenation is an

enol.1. Formation of the enol.

2. Nucleophilic attack of the enol on the halogen.

O OH

Keto form Enol form

H+

OH

Br Br

OBr

H-Br+ +

13-36

-Halogenation• A value of -halogenation is that the carbon

adjacent to the aldehyde or ketone now bears a good leaving group and is susceptible to nucleophilic attack.

OBr

NH+

ON

+ HBr

An -bromo-ketone

An -diethylaminoketoneDiethyl-amine

13-37

Oxidation• Aldehydes are one of the most easily oxidized

of all functional groups.

CHO

HO

MeOAg2O THF, H2O

NaOHHClH2O

COOHMeO

HOAg

Vanillic acidVanillin

++

CHO H2CrO4 COOHHexanal Hexanoic acid

2 CHO O2 2 COOHBenzoic acidBenzaldehyde

+

13-38

Oxidation• Ketones are not normally oxidized by H2CrO4; in

fact this reagent is used to oxidize 2° alcohols to ketones.• They are oxidized by HNO3 at higher temperatures.• Oxidation is via the enol.

• Adipic acid is one of the starting materials for the synthesis of nylon 66.

O OHHNO3

O

HO OH

O

Hexanedioic acid(Adipic acid)

Cyclohexanone(keto form)

Cyclohexanone(enol form)

13-39

Oxidation• Tollens’ reagent: Prepared by dissolving AgNO3

in water, adding NaOH to precipitate Ag2O and then adding aqueous ammonia to redissolve silver ion as the silver-ammonia complex ion. Tollens’ reagent is specific for the oxidation of aldehydes. If done properly, silver deposits on the walls of the container as a silver mirror.

R-C-HO

2Ag(NH3)2+ 3OH-

R-C-O-O

2Ag 4NH3 2H2O

+ +

+ + +

Tollens'reagent

Carboxylicanion

Silvermirror

Aldehyde

13-40

Reduction• Aldehydes are reduced to 1° alcohols.• Ketones are reduced to 2° alcohols.

R-CHO

R-C-R'O

R-CH-R'OH

R-CH2OHA primaryalcohol

A secondaryalcohol

An aldehydereduction

A ketone

reduction

13-41

Catalytic Reduction• Catalytic reductions are generally carried out

from 25° to 100°C and 1 to 5 atm H2.

• A carbon-carbon double bond may also be reduced under these conditions.

+ 25oC, 2 atmPt

Cyclohexanone Cyclohexanol

O OH

H2

1-Butanol trans-2-Butenal(Crotonaldehyde)

2H2NiH

OOH

13-42

Metal Hydride Reductions• The most common laboratory reagents for the

reduction of aldehydes and ketones are NaBH4 and LiAlH4.

• Both reagents are sources of hydride ionhydride ion, H:H:--, a very strong nucleophile.

Hydride ionLithium aluminum hydride (LAH)

Sodium borohydride

H

H H

HH-B-H H-Al-HLi +Na+ H:

13-43

NaBH4 Reductions• Reductions with NaBH4 are most commonly carried

out in aqueous methanol, in pure methanol, or in ethanol.

• One mole of NaBH4 reduces four moles of aldehyde or ketone.4RCH

ONaBH4

(RCH2O)4B- Na+ H2O 4RCH2OHA tetraalkyl borate

borate salts

+

+ methanol

13-44

NaBH4 Reductions• The key step in metal hydride reductions is

transfer of a hydride ion to the C=O group to form a tetrahedral carbonyl addition compound.

Na+H-B-HH

R-C-R'O

HR-C-R'

H

O BH3 Na+

H2O

R-C-R'H

O-H

from water

from the hydride reducing agent

+

13-45

Metal Hydride Reductions• Metal hydride reducing agents do not normally

reduce carbon-carbon double bonds, and selective reduction of C=O or C=C is often possible.

O OHRCH=CHCR' RCH=CHCHR'

1. NaBH42. H2O

+ RhO

RCH=CHCR' RCH2 CH2CR'H2

O

13-46

Aldehydes andKetones

End Chapter 13End Chapter 13