13-1 chemistry 2060, spring 2060, lsu chapter 13: aldehydes and ketones sections 13.1-13.8

13-1Chemistry 2060, Spring 2060, LSU

Chapter 13:Chapter 13:Aldehydes and KetonesAldehydes and Ketones

Sections 13.1-13.8

13-2Chemistry 2060, Spring 2060, LSU

SectionsSectionsChapter 13: Aldehydes and KetonesChapter 13: Aldehydes and Ketones

1. Introduction

2. Structure and bonding

3. Nomenclature

4. Physical properties

5. Reactions

6. Addition of Grignard Reagents

7. Addition of alcohols

8. Addition of ammonia and amines

13-3Chemistry 2060, Spring 2060, LSU

The Carbonyl GroupThe Carbonyl GroupIn this and several following chapters, we study the In this and several following chapters, we study the

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

15)• enolate anions (Chapter 16)

13-4Chemistry 2060, Spring 2060, LSU

StructureStructure• 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 O

CH3CHHCH CH3CCH3

13-5Chemistry 2060, Spring 2060, LSU

NomenclatureNomenclatureIUPAC names: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

13-6Chemistry 2060, Spring 2060, LSU

NomenclatureNomenclature

CHO HO CHO

Cyclopentane-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

7

8

11

223

3

4H

O

H

O

2-Methyl-cyclohexanone

5-Methyl-3-hexanone

Benzophenone Acetophenone

OO

O O

13-7Chemistry 2060, Spring 2060, LSU

NomenclatureNomenclature

HCOOH

O

COOHO

COOHHO

OHHS

COOHNH2

-al oxo-

Ketone -one oxo-

Alcohol -ol hydroxy-

Amino -amine amino-

3-Oxopropanoic acid

3-Oxobutanoic acid

4-Hydroxybutanoic acid

3-Aminobutanoic acid

Example of When the FunctionalGroup Has a Lower Priority

Sulfhydryl -thiol mercapto- 2-Mercaptoethanol

Functional Group Suffix Prefix

Carboxyl -oic acid

Aldehyde

13-8Chemistry 2060, Spring 2060, LSU

NomenclatureNomenclatureCommon namesCommon 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

13-9Chemistry 2060, Spring 2060, LSU

Physical PropertiesPhysical PropertiesOxygen is more electronegative than carbon (3.5 vs Oxygen is more electronegative than carbon (3.5 vs

2.5) and, therefore, a C=O group is polar2.5) 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

C O C O –

Polarity of acarbonyl group

-+C O

+

More importantcontributing

structure

::: : :

13-10Chemistry 2060, Spring 2060, LSU

ReactionsReactionsThe most common reaction theme of a carbonyl The most common reaction theme of a carbonyl

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

Tetrahedral carbonyl addition compound

+ CR

R

O CNu

O -

RR

Nu -: :

::

:

:

13-11Chemistry 2060, Spring 2060, LSU

Grignard ReagentsGrignard ReagentsAddition of carbon nucleophiles is one of the most Addition of carbon nucleophiles is one of the most

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

We study addition of carbon nucleophiles called 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 alkl or aryl group and X is a halogen

13-12Chemistry 2060, Spring 2060, LSU

Grignard ReagentsGrignard ReagentsGrignard reagents are prepared by adding an alkyl Grignard reagents are prepared by adding an alkyl

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

Br Mg MgBr+1-Bromobutane Butylmagnesium bromide

ether

Br Mg MgBr+ ether

Bromobenzene Phenylmagnesium bromide

13-13Chemistry 2060, Spring 2060, LSU

Grignard ReagentsGrignard ReagentsGiven the difference in electronegativity between carbon Given the difference in electronegativity between carbon

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

carbanion

CarbanionCarbanion:: an anion in which carbon has an unshared pair an anion in which carbon has an unshared pair of electrons and bears a negative chargeof electrons and bears a negative charge• a carbanion is a good nucleophile and adds to the

carbonyl group of aldehydes and ketones

13-14Chemistry 2060, Spring 2060, LSU

Grignard ReagentsGrignard ReagentsReaction with protic acidsReaction 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 RNH2

AminesAlcoholsWater Phenols ThiolsCarboxylicacids

13-15Chemistry 2060, Spring 2060, LSU

Grignard ReagentsGrignard Reagents• reaction with formaldehyde gives a 1° alcohol

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

Ph MgBr CH3-C-H

O

Ph CHCH3

O [MgBr]+HCl

H2OPh CHCH3

OHMg2+ether

A magnesium alkoxide

Acetaldehyde 1-Phenylethanol(a 2° alcohol)

++

CH3CH2-MgBr H-C-H

O

CH3CH2-CH2

O [MgBr]+ HClH2O

CH3CH2-CH2

OH

Mg2+

Formaldehyde

+

A magnesiumalkoxide

+ ether

1-Propanol(a 1° alcohol)

13-16Chemistry 2060, Spring 2060, LSU

Grignard ReagentsGrignard 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

O

Ph CCH3

CH3

O [MgBr]+

HCl

H2OPh CCH3

OH

CH3

Mg2+ether

2-Phenyl-2-propanol(a 3° alcohol)

Acetone

++

A magnesiumalkoxide

CH3

C-CH2CH3

OH

13-17Chemistry 2060, Spring 2060, LSU

Addition of AlcoholsAddition of AlcoholsHemiacetal:Hemiacetal: a molecule containing an -OH group a molecule containing an -OH group

and an -OR group bonded to the same carbonand 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

CH3CCH3

O H

OCH2CH3H+

CH3C-OCH2CH3

CH3

OH

A hemiacetal

+

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

OHH

O

OH

O

Hredraw to showthe OH close tothe CHO group O OH1

23

45

1

23

451

23

45

13-18Chemistry 2060, Spring 2060, LSU

Addition of AlcoholsAddition of AlcoholsAcetal:Acetal: a molecule containing two -OR groups a molecule containing two -OR groups

bonded to the same carbonbonded to the same carbon

CH3C-OCH2CH3

CH3

OH

CH3CH2OHH

+CH3C-OCH2CH3

CH3

OCH2CH3

H2O

A diethyl acetal

++

A hemiacetal

OHH

O

O OHCH3OH

H+ O OCH3H2O

4-Hydroxypentanal

+

A cy clic acetal

13-19Chemistry 2060, Spring 2060, LSU

Acetal FormationAcetal Formation1. Proton transfer from HA to the hemiacetal oxygen

2. Loss of H2O gives a cation

HO

H

R-C-OCH3 H A

H

H

O

R-C-OCH3

H

A -+

+

An oxonium ion

+

H O

R-C-OCH3

H

H

R-C

H

OCH3

H

R-C OCH3 H2O+

+

A resonance-stabilized cation

+

+

13-20Chemistry 2060, Spring 2060, LSU

Acetal FormationAcetal 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-O

H

R-C OCH3

H

H

H

O

R-C-OCH3

CH3+

+

A protonated acetal

+

A

H O

R-C-OCH3

CH3

H

HAH

O

R-C-OCH3

CH3

A protonated acetal An acetal

++

+

13-21Chemistry 2060, Spring 2060, LSU

AcetalsAcetalsDraw a structural formula for the acetal formed in Draw a structural formula for the acetal formed in

each reactioneach reaction

O HOOH H2SO4+

Ethyleneglycol

(a)

OH

OH

O H2SO4(b) +

13-22Chemistry 2060, Spring 2060, LSU

Acetals as Protecting GroupsAcetals as 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

+

H2OHOOH+ Br O

O

Ethylene glycol

13-23Chemistry 2060, Spring 2060, LSU

An Acetal as a Protecting GroupAn Acetal as a Protecting Group

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

• hydrolysis gives the hydroxyaldehyde

BrO

OMg BrMg

O

O

A cyclic acetal A Grignard reagentether

+

Ph

O

H BrMg O

O

O

O

Ph

O-MgBr

+

+

A magnesium alkoxide

O

O

Ph

O-MgBr

+

HCl, H2OOH O

Ph H HOOH+

13-24Chemistry 2060, Spring 2060, LSU

IminesIminesImine:Imine: a compound containing a C=N bond; also a compound containing a C=N bond; also

called a Schiff basecalled a Schiff base• formed by the reaction of an aldehyde or ketone with

ammonia or a 1° amine

An imineAmmoniaCyclohexanone

++ NH3 H2OO NHH+

CH3CH

O

H2N CH3CH=N H2O+ +

Ethanal Aniline An imine

H+

13-25Chemistry 2060, Spring 2060, LSU

IminesImines1. addition of the amine to the carbonyl carbon followed

by proton transfer

2. two proton-transfer reactions and loss of H2O

C

O

H2N-R C

O

HN-R

H

C

OH

N-RH

-

+

A tetrahedral carbonyladdition intermediate

+

H

O H

H

C

OH

N-RH

C

OHH

N-R

H

H

OH

C N-R H2O H OH

H

An imine

+

+

+ ++

13-26Chemistry 2060, Spring 2060, LSU

RhodopsinRhodopsin• 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)

13-27Chemistry 2060, Spring 2060, LSU

Reductive AminationReductive AminationReductive amination:Reductive amination: the formation of an imine the formation of an imine

followed by its reduction to an aminefollowed 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)

NH2/Ni

NH

13-28Chemistry 2060, Spring 2060, LSU

Keto-Enol TautomerismKeto-Enol TautomerismEnol:Enol: a molecule containing an -OH group on a a molecule containing an -OH group on a

carbon-carbon double bond of an alkenecarbon-carbon double bond of an alkene

the keto form

predominates

for most

simple

aldehydes and

ketones

CH3-C-CH3

O OHCH3-C=CH2

Acetone(keto form)

Acetone(enol form)

CH2=CHOH

CH3C=CH2

OH

OH

CH3CHO

O

CH3CCH3

O

Keto form Enol form% Enol atEquilibrium

6 x 10-5

6 x 10-7

4 x 10-5

13-29Chemistry 2060, Spring 2060, LSU

Keto-Enol TautomerismKeto-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)

13-30Chemistry 2060, Spring 2060, LSU

Keto-Enol TautomerismKeto-Enol TautomerismInterconversion of keto and enol forms is catalyzed Interconversion of keto and enol forms is catalyzed

by both acid and baseby both acid and base• following is a mechanism for acid catalysis

1. proton transfer to the carbonyl oxygen

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

CH3-C-CH3

O

H-A CH3-C-CH3

OH

A-+

+

fast+

Keto form

• •

• • ••••

The conjugate acidof the ketone

CH3-C-CH2-H

OH

A-CH3-C=CH2

OHH-A

Enol form+

+

slow+

• •

• • ••••

13-31Chemistry 2060, Spring 2060, LSU

Racemization an at Racemization an at -Carbon-Carbon

when an enantiomerically pure aldehyde or ketone when an enantiomerically pure aldehyde or ketone with at least one with at least one -hydrogen is treated with a -hydrogen is treated with a trace of acid or base, it gradually becomes a trace of acid or base, it gradually becomes a racemic mixture; it loses all optical activityracemic mixture; it loses all optical activity

C C

O

CH3

Ph

HH3C

OH

CH3

C CPh

H3C

C C

O

CH3

Ph

H3CH

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

(S)-3-Phenyl-2-butanone

H+

or OH-

H+

or OH-

13-32Chemistry 2060, Spring 2060, LSU

-Halogenation-HalogenationAldehydes and ketones with an Aldehydes and ketones with an -hydrogen react -hydrogen react

with Brwith Br22 and Cl and Cl22 to give an to give an -haloaldehyde or an -haloaldehyde or an

-haloketone-haloketoneO

Br2CH3COOH

OBr

HBr+ +

Acetophenone -Bromoacetophenone

13-33Chemistry 2060, Spring 2060, LSU

-Halogenation-Halogenationthe key intermediate in the key intermediate in -halogenation is an enol-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+ +

13-34Chemistry 2060, Spring 2060, LSU

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

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

OBr

NH+

ON

+ HBr

An -bromo-ketone

An -diethylaminoketoneDiethyl-amine

13-35Chemistry 2060, Spring 2060, LSU

OxidationOxidationAldehydes are one of the most easily oxidized of all Aldehydes are one of the most easily oxidized of all

functional groupsfunctional groups

CHO

HO

MeOAg2O

THF, H2O

NaOHHClH2O

COOHMeO

HOAg

Vanillic acidVanillin

++

CHO H2CrO4 COOH

Hexanal Hexanoic acid

2 CHO O2 2 COOH

Benzoic acidBenzaldehyde

+

13-36Chemistry 2060, Spring 2060, LSU

OxidationOxidationKetones are not normally oxidized by HKetones are not normally oxidized by H22CrOCrO44; in ; in

fact this reagent is used to oxidize 2° alcohols to fact this reagent is used to oxidize 2° alcohols to ketonesketones• 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 OH

HNO3

O

HOOH

O

Hexanedioic acid(Adipic acid)

Cyclohexanone(keto form)

Cyclohexanone(enol form)

13-37Chemistry 2060, Spring 2060, LSU

ReductionReduction• aldehydes can be reduced to 1° alcohols• ketones can be reduced to 2° alcohols

R-CH

O

R-C-R'O

R-CH-R'OH

R-CH2OHA primaryalcohol

A secondaryalcohol

An aldehyde

reduction

A ketone

reduction

13-38Chemistry 2060, Spring 2060, LSU

Catalytic ReductionCatalytic ReductionCatalytic reductions are generally carried out from Catalytic reductions are generally carried out from

25° to 100°C and 1 to 5 atm H25° to 100°C and 1 to 5 atm H22

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

+25oC, 2 atm

Pt

Cyclohexanone Cyclohexanol

O OH

H2

1-Butanol trans-2-Butenal(Crotonaldehyde)

2H2

NiH

O

OH

13-39Chemistry 2060, Spring 2060, LSU

Metal Hydride ReductionsMetal Hydride ReductionsThe most common laboratory reagents for the The most common laboratory reagents for the

reduction of aldehydes and ketones are NaBHreduction of aldehydes and ketones are NaBH44

and LiAlHand LiAlH4 4

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

Hydride ionLithium aluminum hydride (LAH)

Sodium borohydride

H

H H

H

H-B-H H-Al-HLi +Na+

H:

13-40Chemistry 2060, Spring 2060, LSU

NaBHNaBH44 Reductions 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

4RCHO

NaBH4

(RCH2O)4B- Na

+ H2O4RCH2OH

A tetraalkyl borateborate salts

+

+ methanol

13-41Chemistry 2060, Spring 2060, LSU

NaBHNaBH44 Reductions 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-H

H

R-C-R'

O

H

R-C-R'

H

O BH3 Na+

H2O

R-C-R'

H

O-H

from water

from the hydride reducing agent

+

13-42Chemistry 2060, Spring 2060, LSU

Metal Hydride ReductionsMetal 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 OH

RCH=CHCR' RCH=CHCHR'1. NaBH4

2. H2O

+Rh

O

RCH=CHCR' RCH2 CH2CR'H2

O

13-43Chemistry 2060, Spring 2060, LSU

Aldehydes andAldehydes andKetonesKetones

End Chapter 13End Chapter 13