11 11-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic...

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11-1Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.

Introduction to Introduction to Organic Organic

ChemistryChemistry2 ed2 ed

William H. BrownWilliam H. Brown

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Aldehydes Aldehydes & &

KetonesKetones

Chapter 15

Chapter 11Chapter 11

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The Carbonyl GroupThe Carbonyl Group• In this and three following chapters we study the

physical and chemical properties of classes of compounds containing the carbonyl group, C=O• aldehydes and ketones (Chapter 11)• carboxylic acids (Chapter 12)• carboxyl derivatives (Chapter 13)• enolate anions (Chapter 14)

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The Carbonyl GroupThe Carbonyl Group• Consists of

• one sigma bond formed by overlap of sp2 hybrid orbitals

• one pi bond formed by overlap of parallel 2p orbitals

C Oσ

electron pairs in

sp2 hybrid orbitals

π

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Structure of AldehydesStructure of Aldehydes• The functional group of an aldehyde is a carbonyl

group bonded to a H atom • in methanal, it is bonded to two H atoms• in all other aldehydes, it is bonded to one H and one

carbon atom

H

C

H

O

H3C

C

H

O

Methanal(formaldehyde)

Ethanal(acetaldehyde)

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Structure of KetonesStructure of Ketones• The functional group of a ketone is a carbonyl

groups bonded to two carbon atoms

CH3-C-CH3

O O

Propanone(Acetone)

Cyclohexanone

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Nomenclature - AldehydesNomenclature - Aldehydes• IUPAC namesIUPAC names: select as the parent alkane the

longest chain of carbon atoms that contains the carbonyl group• because the carbonyl group of the aldehyde must be

on carbon 1, there is no need to give it a number

• For unsaturated aldehydes, show the presence of the C=C by changing the infix -anan- to -enen- • the location of the suffix determines the numbering

pattern

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Nomenclature - AldehydesNomenclature - Aldehydes

3-Methylbutanal

2-Propenal(Acrolein)

O

O

CH3CHCH2CH

CH2=CHCH H

O

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

1

2

3

4

5

6

7

8

1

1

2

2

3

34O

CH3CH2CH2CH2 CHPentanal

12345CH3

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Nomenclature - AldehydesNomenclature - Aldehydes• For cyclic molecules in which the -CHO group is

attached to the ring, the name is derived by adding the suffix -carbaldehydecarbaldehyde to the name of the ring

2-Cyclopentene- carbaldehyde

2,2-Dimethylcyclo-hexanecarbaldehyde

CHO

CH3CH3

CHO

3

1

122

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Nomenclature - KetonesNomenclature - Ketones• IUPAC names:

• select as the parent alkane the longest chain that contains the carbonyl group,

• changing the suffix -ee to -oneone • number to give C=O the smaller number

5-Methyl-3-hexanonePropanone (Acetone)

O O

CH3CCH3 CH3CH2CCH2CHCH31 2 3 4 5 6

CH3 CH3

O

2-Methylcyclo-hexanone

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Nomenclature - KetonesNomenclature - Ketones• The IUPAC system retains these names

BenzophenoneAcetophenone

CCH3

OO

C-CH3CCH3

O

Acetone

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Order of PrecedenceOrder of Precedence• For compounds that contain more than one

functional group indicated by a suffix

mercapto-amino-

oxo-

hydroxy-

oxo-

-thiol-amine-ol

-one

-al-oic acid

Prefix if Lowerin Precedence

Suffix if Higherin Precedence

FunctionalGroup

C=O

-CHO

-CO2H

-OH-NH2-SH

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Physical PropertiesPhysical Properties• Oxygen is more electronegative than carbon (3.5

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

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

δ-δ+C O

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Reaction ThemeReaction Theme• One of the most common reaction themes of the

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

Tetrahedral carbonyl addition compound

+ CR

RO CNu

OH

RR

H-Nu

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Add’n of C NucleophilesAdd’n of C Nucleophiles• 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 reagents• Victor Grignard was awarded the Nobel Prize for

Chemistry in 1912 for their discovery and application to organic synthesis

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Grignard ReagentsGrignard Reagents• Magnesium metal reacts with alkyl and aryl

halides to give organomagnesium halides

+

1-Chlorobutane

Butylmagnesium chloride

ether

CH

3

CH

2

CH

2

CH

2

Cl

Mg

CH

3

CH

2

CH

2

CH

2

MgCl

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Grignard ReagentsGrignard Reagents• Given the difference in electronegativity between

carbon and magnesium (2.5 - 1.3), the C-Mg bond is polar covalent, with Cδ and Mgδ

• a Grignard reagent behaves as a carbanion and as a nucleophile

• CarbanionCarbanion: an anion in which carbon has an unshared pair of electrons and bears a negative charge

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Grignard ReagentsGrignard Reagents• Grignard reagents are very strong bases and

react with a variety of acids to give alkanes

Weaker acid

Stronger acid

pKa 51pKa 15.7++ H-OHCH3CH2-MgBr Mg(OH)BrCH3CH2-H

δ+δ-

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Grignard ReagentsGrignard Reagents• they also react with these acids ( proton donors) to

give alkanes

Amines Alcohols

pKa 16-18pKa 38-40R2NH ROH

Phenols Thiols Carboxylic acids

pKa 4-5pKa 8-9pKa 9-10ArOH RSH RCO2H

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Grignard ReagentsGrignard Reagents• Grignard reagents provide a way to form new

carbon-carbon bonds• a carbanion is a good nucleophile and adds to the

carbonyl group of an aldehyde or ketone to form a tetrahedral carbonyl addition compound

• the driving force for this reaction is the attraction of the partial negative charge on the carbon of the Grignard reagent for the partial positive carbon of the carbonyl group

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Grignard ReagentsGrignard Reagents• addition of a Grignard reagent to formaldehyde

followed by H3O+ gives a 1° alcohol

ether

1-Propanol(a primary alcohol)

Formaldehyde

Mg2++

+δ+

δ- δ+

δ-O

OH

CH3 CH2 -MgBr H-C-H

CH3 CH2 -CH2 HClH2 O A magnesium alkoxide

CH3 CH2 -CH2

O- [ MgBr ] +

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Grignard ReagentsGrignard Reagents• addition to any other RCHO gives a 2° alcohol

ether

A magnesium alkoxide

Acetaldehyde(an aldehyde)

1-Cyclohexylethanol(a secondary alcohol)

+ Mg2+

+δ-

δ+

δ+

δ-

MgBr

O

CHCH3

O- [ MgBr ] +

OH

CHCH3

CH3 -C-H

HClH2 O

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Grignard ReagentsGrignard Reagents• addition to a ketone gives a 3° alcohol

ether

2-Phenyl-2-propanol (a tertiary alcohol)

Acetone

Mg2++

+δ-δ+

δ+

δ-

A magnesiumalkoxide

C6 H5 MgBr

O

C6 H5 CCH3

CH3

O- [ MgBr] + OH

CH3

C6 H5 CCH3

CH3 -C-CH3

HClH2 O

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Grignard ReagentsGrignard Reagents• addition to CO2 gives a carboxylic acid

MgBr CO-[MgBr]+

O

HClH2O

COH

O

Cyclopentane-carboxylic acid

δ- δ+

δ-

C

O

O

+

Carbondioxide + Mg 2 +

ether

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Grignard ReagentsGrignard Reagents• addition to ethylene oxide gives a 1° alcohol

etherSN2

+

2-Phenylethanol

CH2CH2

O

C6 H5-MgBr

C6 H5CH2 CH2 O-[MgBr]+ HCl

H2 OC6 H5CH2 CH2 OH

Ethylene oxide

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Grignard ReagentsGrignard Reagents• ProblemProblem: 2-phenyl-2-butanol can be synthesized

by three different combinations of a Grignard reagent and a ketone. Show each combination

C-CH2CH3

OH

CH3

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Addition of AlcoholsAddition of Alcohols• Addition of one molecule of alcohol to the C=O

group of an aldehyde or ketone gives a hemiacetal

• HemiacetalHemiacetal: a molecule containing an -OH and an -OR or -OAr bonded to the same carbon

A hemiacetal

+

O OHH

CH3

CH3CCH3 OCH2CH3 CH3COCH2CH3

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Addition of AlcoholsAddition of Alcohols• Hemiacetals are only minor components of an

equilibrium mixture, except where a five- or six-membered ring can form• (the trans isomer is shown here)

4-Hydroxypentanal A cyclic hemiacetal(major form present

at equilibrium)

O

OH O OHH3CCH3CHCH2CH2CH

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Addition of AlcoholsAddition of Alcohols• Hemiacetals react with alcohols to form acetals• AcetalAcetal: a molecule containing two -OR or -OAr

groups bonded to the same carbon

A diethyl acetal

+

+

A hemiacetal

OH

CH3

CH3

OCH2CH3

CH3COCH2CH3 CH3CH2 OHH

+

CH3COCH2CH3 H2 O

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Addition of AlcoholsAddition of Alcohols• Steps 1 and 2: proton transfer from the acid catalyst,

HA, to the carbonyl oxygen followed by loss of H2O

+••

+

++

•• ••

••

••

••

••

••

••

••

••

(1) (2)

An oxonium ion

HO

H

HA

HHO

H

H

OCH3

R-C-OCH3

A -

R-C-OCH3

R-C H2 O

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Addition of AlcoholsAddition of Alcohols• Steps 3 and 4: reaction of the oxonium ion with ROH

followed by proton transfer to A-

••

++

••••

••+

+

••

••

••

••

••

••••

(3) (4)OCH3

H

H

H

OH CH3

O-CH3

H

A -

R-CCH3 -O R-C-OCH3

R-C-OCH3 H-A

An acetal

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Addition of AlcoholsAddition of Alcohols• with a glycol, such as ethylene glycol, the product is a

five-membered cyclic acetal

A cyclic acetalO CH2

CH2O

+O HOCH2CH2OHH

+

+ H2O

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Add’n of N NucleophilesAdd’n of N Nucleophiles• Ammonia, 1° aliphatic amines, and 1° aromatic

amines react with the C=O group of aldehydes and ketones to give imines (Schiff bases)

An imine(a Schiff base)

Methylamine

Cyclopent-anone

++O NCH3H

+

H2NCH3 H2O

+ +

Ethanal Aniline An imine(A Schiff base)

H2NO

CH3CH=NCH3CHH+

H2 O

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Add'n of N NucleophilesAdd'n of N Nucleophiles• Formation of an imine occurs in two steps

• Step 1: formation of a TCAI • Step 2: loss of water

••••

••+ N-R

H

C

O -

H2 N-R

••••

••N-R

H

C

OH

TCAI

••H+

C

O••••

••••

••N-R

H

C

O H

C NR

••+ H2O

••••

(1) (1)

(2)

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Add'n of N NucleophilesAdd'n of N Nucleophiles• Rhodopsin (visual purple) is the imine formed

between 11-cis-retinal (vitamin A aldehyde) and the protein opsin

123

5

67

8

9

10

1112

1314

15 Rhodopsin(Visual purple)

4

C=N-OPSINH

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RhodopsinRhodopsin

OPSIN

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Keto-Enol TautomerismKeto-Enol Tautomerism• A carbon adjacent to a carbonyl group is called

an -carbon-carbon, and a hydrogen atom bonded to it is called an -hydrogen-hydrogen.

-carbons

α-hydrogens

CH3 -C-CH2-CH3

O

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Keto-Enol TautomerismKeto-Enol Tautomerism• A carbonyl compound with an a-hydrogen is in

equilibrium with a constitutional isomer called an enol (an alkene + an alcohol)

CH3-C-CH3

O

CH3-C=CH2

OH

Acetone(keto form)

Acetone(enol form)

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Keto-Enol TautomerismKeto-Enol Tautomerism• keto-enol

equilibria for simple aldehydes and ketones lie far toward the keto form

OH

O

O

CH3CH CH2=CH

CH3CCH3

Keto form Enol form% Enol at

Equilibrium

6 x 10-5

OH

CH3C=CH2 6 x 10-7

O OH4 x 10-5

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Keto-Enol TautomerismKeto-Enol Tautomerism• Keto-enol tautomerism is acid catalyzed

Step 1: proton transfer from H-A

Step 2: proton transfer to A-

O

CH3-C-CH3 + H-A

O

CH3-C-CH3

H+

fast+ A-

keto form

••

•• ••••

the conjugate acidof the ketone

Enol form

OH

CH3-C=CH2+ A-

O

CH3-C-CH2-H

H+

slow+ H-A

••

••••••

1111


RacemizationRacemization• Racemization at an -carbon is catalyzed by acid

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

(S)-3-Phenyl-2-butanone

C C

O

CH3

Ph

HH3C

CH

H3C

Ph

C

CH3

OOH

CCCH3

Ph

H3C

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Oxidation of AldehydesOxidation of Aldehydes• Aldehydes are oxidized to carboxylic acids by a

variety of oxidizing agents, including chromic acid

CH3(CH2)4CH

OH2CrO4

O

Hexanal Hexanoic acid

CH3(CH2)4COH

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Oxidation of AldehydesOxidation of Aldehydes• Aldehydes are also oxidized by Ag(I)

• in one method, a solution of the aldehyde in aqueous ethanol or THF is shaken with a slurry of silver oxide

Vanillic acid

Vanillin

+

+CH

HO

CH3O

O

O

CH3O

HO

COH

Ag2OTHF, H2O

NaOH

Ag

HClH2O

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Oxidation of AldehydesOxidation of Aldehydes• Tollens’ reagent, another form of Ag(I), is

prepared by dissolving silver nitrate in water, adding NaOH to precipitate Ag(I) as Ag2O, and then adding aqueous ammonia to redissolve Ag(I) as a silver-ammonia complex ion

+Ag+NO3

-2NH3 Ag(NH3)2

+ NO3-NH3, H2O

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Oxidation of AldehydesOxidation of Aldehydes• Tollens’ reagent oxidizes an aldehyde to a carboxylic

anion and silver(1) is reduced to metallic silver• this reaction is used to silver mirrors

Precipitates as silver mirror

++

+

ONH3, H2O

RCH 2Ag(NH3)2+

RCO2-

2Ag 4NH3

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Oxidation of AldehydesOxidation of Aldehydes• aldehydes are oxidized by molecular oxygen and by

hydrogen peroxide

• liquid aldehydes are so sensitive to air that they must stored under N2

Benzoic acidBenzaldehyde

+CH

O O

COH2O22

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ReductionReduction• An aldehyde can be reduced to a 1° alcohol and a

ketone to a 2° alcoholO

O OH

RCH RCH2 OH

RCR' RCHR'

reduction

An aldehyde

A ketone

A 1° alcohol

A 2° alcohol

reduction

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Catalytic ReductionCatalytic Reduction• Catalytic reductions are generally carried out

from 25° to 100°C under 1 to 5 atm H2

+25oC, 2 atm

Pt

Cyclohexanone Cyclohexanol

O OH

H2

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Catalytic ReductionCatalytic Reduction• A carbon-carbon double bond may also be

reduced under these conditions

• by careful choice of experimental conditions, it is often possible to selectively reduce a carbon-carbon double in the presence of an aldehyde or ketone

1-Butanol trans-2-Butenal(Crotonaldehyde)

2H2

NiCH3 CH2CH2 CH2 OH

HC C

CH

H3C H

O

1111


Metal Hydride ReductionMetal Hydride Reduction• The most common laboratory reagents for the

reduction of aldehydes and ketones are NaBH4 and LiAlH4

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

Hydride ionLithium aluminumhydride (LAH)

Sodium borohydride

••H

H H

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

+H

1111


NaBHNaBH44 Reduction Reduction• Reductions with NaBH4 are most commonly

carried out in aqueous methanol, in pure methanol, or in ethanol• one mol of NaBH4 reduces four mol of aldehyde or

ketone

A tetraalkyl borateborate salts

+

+methanol

O

4RCH NaBH4

(RCH2O)4B-

Na+ 4RCH2 OH

H2 O

1111


NaBHNaBH4 4 ReductionReduction• the key step in metal hydride reduction is transfer of a

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

from water

from the hydride reducing agent

+

H

H O O-BH3 Na+

OH

H

H

H-B-HNa+

R-C-R' R-C-R'H2 O

R-C-R'

1111


LiAlHLiAlH4 4 ReductionReduction• Unlike NaBH4, LiAlH4 reacts violently with water,

methanol, and other protic solvents • reductions using this reagent are carried out in diethyl

ether or tetrahydrofuran (THF)

+

+ aluminum salts

etherO

OH

4RCR LiAlH4

4RCHRA tetraalkyaluminate

(R2CHO)4Al- Li+ H2 O

1111


Metal Hydride ReductionMetal Hydride Reduction• 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 O

RCH=CHCR' RCH2 CH2CR'H2

1111


Reductive AminationReductive Amination• A value of imines is that the carbon-nitrogen

double bond can be reduced to a carbon-nitrogen single bond

+

Dicyclohexylamine

Cyclohexanone

(An imine)

Cyclohexylamine

O H2N

N N

H

-H2O

H2/Ni

H+

1111


Aldehydes Aldehydes & &

KetonesKetonesEnd Chapter 11End Chapter 11

11 11-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic...

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Transcript of 11 11-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic...