17 17-1 Organic Chemistry William H. Brown & Christopher S. Foote.

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Organic Organic ChemistryChemistry

William H. Brown &William H. Brown &

Christopher S. FooteChristopher S. Foote

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Carboxylic Carboxylic AcidsAcids

Chapter 17Chapter 17

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The functional group of a carboxylic acid is a carboxyl group

• the general formula of an aliphatic carboxylic acid is RCOOH; that of an aromatic carboxylic acid is ArCOOH

StructureStructure

::

COOH CO2HCO H

O

::

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Nomenclature - IUPACNomenclature - IUPAC IUPAC names: drop the -ee from the parent alkane

and add the suffix -oic acidoic acid• if the compound contains a carbon-carbon double

bond, change the infix -anan- to -enen-

Propenoic acid(Acrylic acid)

trans-3-Phenyl-propenoic acid(Cinnamic acid)

trans-2-Butenoic acid(Crotonic acid)

COOH

C6H5

COOHCOOH

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Nomenclature - IUPACNomenclature - IUPAC The carboxyl group takes precedence over most

other functional groups

5-Oxohexanoic acid 4-Aminobutanoic acid

(R)-5-Hydroxyhexanoic acid

COOH

OH

H2N COOHCOOHO

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Nomenclature - IUPACNomenclature - IUPAC• dicarboxylic acids: add the suffix -dioic aciddioic acid to the

name of the parent alkane containing both carboxyl groups

HO OH

O

Propanedioic acid(Malonic acid)

Ethanedioic acid(Oxalic acid)

OHO

OH

O

O

Hexanedioic acid(Adipic acid)

Pentanedioic acid(Glutaric acid)

Butanedioic acid(Succinic acid)

OOH

OHO

OH

O

HO

OHO

OH

O

O

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Nomenclature - IUPACNomenclature - IUPAC• if the carboxyl group is attached to a ring, name the

ring compound and add the suffix -carboxylic acidcarboxylic acid

3

21

2-Cyclohexene-carboxylic acid

trans-1,3-Cyclopentane-dicarboxylic acid

COOHCOOHHOOC

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Nomenclature - IUPACNomenclature - IUPAC• benzoic acid is the simplest aromatic carboxylic acid• use numbers to show the location of substituents

Benzoicacid

2-Hydroxybenzoic acid

(Salicylic acid)

COOH COOHOH

1,2-Benzene-dicarboxylic acid(Phthalic acid)

1,4-Benzene-dicarboxylic acid

(Terephthalic acid)

COOHCOOH

COOH

COOH

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Nomenclature-CommonNomenclature-Common• when common names are used, the letters

etc. are often used to locate substituents

alanine)(-Aminopropionicacid;(-Aminobutyricacid;

GABA)

2-Aminopropanoicacid4-Aminobutanoicacid

4 32

5

H2NOH

O

OH

O

NH2

OH

Oα

βγδ

1

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Physical PropertiesPhysical Properties In the liquid and solid states, carboxylic acids are

associated by hydrogen bonding into dimeric structures

-

δ-

δ+

δ+

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Physical PropertiesPhysical Properties Carboxylic acids have significantly higher boiling

points than other types of organic compounds of comparable molecular weight• they are polar compounds and form very strong

intermolecular hydrogen bonds

Carboxylic acids are more soluble in water than alcohols, ethers, aldehydes, and ketones of comparable molecular weight• they form hydrogen bonds with water molecules

through their C=O and OH groups

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Physical PropertiesPhysical Properties• water solubility decreases as the relative size of the

hydrophobic portion of the molecule increases

hydrophilic region

hydrophobic region

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Acidity Acidity Carboxylic acids are weak acids

• values of pKa for most aliphatic and aromatic carboxylic acids fall within the range 4 to 5

The greater acidity of carboxylic acids relative to alcohols, both compounds containing an OH group is due to resonance stabilization of the carboxylate anion

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AcidityAcidity• electron-withdrawing substituents near the carboxyl

group increase acidity through their inductive effect

pKa:

Increasing acid strength2.86

Chloroaceticacid

0.70

Trichloroacetic acid

1.48

Dichloroacetic acid

ClCH2COOH Cl2CHCOOH Cl3CCOOH

Aceticacid

CH3COOH

4.76

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Reaction with BasesReaction with Bases Carboxylic acids, whether soluble or insoluble in

water, react with NaOH, KOH, and other strong bases to give water-soluble salts

They also form water-soluble salts with ammonia and amines

+ +

Benzoic acid(slightly soluble

in water)

Sodium benzoate(60 g/100 mL water)

COOH COO-Na+NaOHH2 O

H2 O

+

Ammonium benzoate(20 g/100 mL water)

Benzoic acid(slightly soluble

in water)

COOH COO-NH4+

NH3 H2 O

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Reaction with BasesReaction with Bases Carboxylic acids react with sodium bicarbonate

and sodium carbonate to form water-soluble salts and carbonic acid• carbonic acid, in turn, breaks down to carbon dioxide

and water+

+ +

CH3COOH NaHCO3

CH3COO- Na

+CO2 H2 O

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Reaction Reaction with with BasesBases

QuickTime™ and aPhoto - JPEG decompressor

are needed to see this picture.

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PreparationPreparation Carbonation of Grignard reagents

• treatment of a Grignard reagent with carbon dioxide followed by acidification gives a carboxylic acid

MgBr C-O- [MgBr]+ HClH2O

C-OH

Cyclopentane-carboxylic acid

C

O

O

+

Carbondioxide

+ Mg2+

O

O

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Methanol to Acetic AcidMethanol to Acetic Acid Acetic acid is synthesized by carbonylation of

methanol• the carbonylation is exothermic

• the Monsanto process uses a soluble rhodium(III) salt and HI to catalyze the reaction

+

O

CO CH3COHCH3OH ΔH° = -138 kJ(33 kcal)/mol

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Methanol to Acetic AcidMethanol to Acetic Acid• Steps 1 and 2: preparation of the catalyst:

• Steps 3 and 4: the catalytic cycle

+ HI CH3ICH3OH

CH3I + Rh(CO)I2 [CH3-Rh(CO)I3] -

An methyl-rhodiumcarbonyl complex

+ H2O

[CH3-Rh(CO)I3] -CO

[CH3C-Rh(CO)I3]-

An acyl-rhodiumcarbonyl complex

CH3OH

CH3COH

O

O

catalyticcycle (3)(4)

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ReductionReduction The carboxyl group is very resistant to reduction

• it is not affected by catalytic hydrogenation under conditions that easily reduce aldehydes and ketones to alcohols, and reduce alkenes and alkynes to alkanes

• it is not reduced by NaBH4

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Reduction by LiAlHReduction by LiAlH44 Lithium aluminum hydride reduces a carboxyl

group to a 1° alcohol• reduction is carried out in diethyl ether, THF, or other

nonreactive, aprotic solvent

COHO

1. LiAlH4, ether2. H2O

CH2OH LiOH Al(OH)3+ +

4-Hydroxymethyl- cyclopentene

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Selective ReductionSelective Reduction• carboxyl groups are not affected by catalytic reduction

under conditions that reduce aldehydes and ketones

5-Hydroxyhexanoic acid

5-Oxohexanoic acid25°C, 2 atm

+ H2Pt

OH

OO

OH

OOH

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Selective ReductionSelective Reduction• using the less reactive NaBH4, it is possible to reduce

the carbonyl group of an aldehyde or ketone without affecting a carboxyl group

5-Oxo-5-phenyl-pentanoic acid

5-Hydroxy-5-phenylpentanoic acid

1. NaBH4

2. H2OC6H5 OH

OO

C6H5 OH

OOH

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Fischer EsterificationFischer Esterification Esters can be prepared by treatment of a

carboxylic acid with an alcohol in the presence of an acid catalyst, commonly H2SO4 or gaseous HCl

Ethyl ethanoate(Ethyl acetate)

Ethanol(Ethyl alcohol)

Ethanoic acid(Acetic acid)

++

H2 SO4H2 OOH

O

HO O

O

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Fischer EsterificationFischer Esterification Fischer esterification is an equilibrium reaction

• by careful control of experimental conditions, it is possible to prepare esters in high yield

• if the alcohol is inexpensive relative to the carboxylic acid, it can be used in excess to drive the equilibrium to the right

• alternatively, water can be removed by azeotropic distillation and a Dean-Stark trap

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Fischer EsterificationFischer Esterification• a key intermediate in Fischer esterification is the

tetrahedral carbonyl addition intermediate formed by addition of ROH to the C=O group

C OCH3

OH

O

R

H

C OH

O

R C OCH3

O

RHOCH3+ HOH+

H+ H+

TCAI

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DiazomethaneDiazomethane Diazomethane, CH2N2

• a potentially explosive, toxic yellow gas, is best drawn as a hybrid of two contributing structures

• treatment of a carboxylic acid with diazomethane gives a methyl ester

++ether

Diazomethane A methyl ester

O O

CH2N2RCOH RCOCH3 N2

+ +H

H

C N N:

H

N N:CH: :

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DiazomethaneDiazomethane Esterification occurs in two steps

Step 1: proton transfer to diazomethane

Step 2: nucleophilic displacement of N2

:+

+ +

A carboxylateanion

R C O H N N C O:–RCH2

Methyl-diazonium

cation

O OCH3-N N

+

+ + N NSN2

R-C-O-CH3

O

R-C-O:-O

CH3-N N+

:

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Acid ChloridesAcid Chlorides The functional group of an acid halide is a

carbonyl group bonded to a halogen atom• among the acid halides, acid chlorides are by far the

most common and the most widely used

Functional group of an acid halide

Acetylchloride

Benzoylchloride

-C-X CH3CCl

O OC-Cl

O

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Acid ChloridesAcid Chlorides• acid chlorides are most often prepared by treatment of

a carboxylic acid with thionyl chloride

+ + +

Butanoicacid

Thionylchloride

Butanoylchloride

SOCl2 SO2 HClOH

O

Cl

O

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Acid ChloridesAcid Chlorides The mechanism for this reaction is divided into

two steps. Step 1: OH-, a poor leaving group, is transformed into a

chlorosulfite group, a good leaving group

A chlorosulfite group

++

O O

S ClOCR

O

R-C-O-H H-ClCl-S-Cl

O

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Acid HalidesAcid HalidesStep 2: attack of chloride ion gives a tetrahedral

carbonyl addition intermediate, which collapses to give the acid chloride

A tetrahedral carbonyl addition intermediate

++

+

OO

R C O S Cl

O

R C O S Cl

Cl

O-

O

Cl-

R-C-Cl SO2 Cl-

:

:

:

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DecarboxylationDecarboxylation Decarboxylation:Decarboxylation: loss of CO2 from a carboxyl

group• most carboxylic acids, if heated to a very high

temperature, undergo thermal decarboxylation

• most carboxylic acids, however, are quite resistant to moderate heat and melt or even boil without decarboxylation

decarboxylation +RCOH RH CO2heat

O

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DecarboxylationDecarboxylation Exceptions are carboxylic acids that have a

carbonyl group beta to the carboxyl group• this type of carboxylic acid undergoes decarboxylation

on mild heating

OH

OO O

Acetone3-Oxobutanoic acid(Acetoacetic acid)

+warm CO2

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DecarboxylationDecarboxylation• thermal decarboxylation of a -ketoacid involves

rearrangement of six electrons in a cyclic six-membered transition state

O+

enol ofa ketone

(A cyclic six-membered transition state)

CO2(1) (2)

O OH

O

O

C

OH

O

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DecarboxylationDecarboxylation• decarboxylation occurs if there is any carbonyl group

beta to the carboxyl• malonic acid and substituted malonic acids, for

example, also undergo thermal decarboxylation

Propanedioic acid (Malonic acid)

+140-150°C

O O

HOCCH2COH CH3COH CO2

O

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DecarboxylationDecarboxylation• thermal decarboxylation of malonic acids also

involves rearrangement of six electrons in a cyclic six-membered transition state

O OH

HO O

OH

HOC

O

O HO

OCO2+

Enol of acarboxylic acid

A cyclic six-membered transition state

(1) (2)

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Prob 17.17Prob 17.17Each compound shows strong absorption between 1720 and 1700 cm-1, and strong broad absorption over the region 2500-3500 cm-1. Propose a structural formula for each compound.

1H-NMR 13C-NMR 13C-NMR1H-NMR

(a) (b)

0.94 (t, 3H)1.39 (m, 2H)1.62 (m, 2H)

2.35 (t, 2H)

12.0 (s 1H) 13.6922.2126.76

33.89180.71 179.29

47.8230.62

29.57

12.1 (s, 1H)2.23 (s, 2H)1.08 (s, 9H)

C6H1 2O2C5H1 0O2

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Prob 17.17 (cont’d)Prob 17.17 (cont’d)1H-NMR 13C-NMR

(c)

170.9453.2821.90

11.8112.7 (s, 2H)

3.10 (t, 1H)1.80 (m, 2H)0.93 (t, 3H)

C5H8 O413C-NMR1H-NMR

(d)

1.29 (s, 6H)12.8 (s, 2H)

22.5648.77174.01

C5H8 O4

13C-NMR1H-NMR 1H-NMR 13C-NMR

(e) (f)

172.26147.53

122.2418.1112.4 (s, 1H)

7.10 (m, 1H)5.86 (d, 1H)1.91 (d, 3H) 2.34 (s, 3H)

11.3 (s, 1H)

34.02

79.36171.82

C4H6 O2 C3H4 Cl2 O2

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Prob 17.17 (cont’d)Prob 17.17 (cont’d)

13C-NMR1H-NMR

1H-NMR 13C-NMR13C-NMR1H-NMR

13.24

2.62 (t, 2H)3.38 (s, 3H)3.68 (s, 2H)

11.5 (s, 1H) 34.75

58.7267.55

177.33

(i)

180.1577.78

51.8820.71

12.4 (s, 1H)6.10 (s, 1H)1.42 (s, 6H)

(h)(g)

176.3645.08

36.4920.48

12.1 (s 1H)

4.25 (t, 1H)

2.05 (m, 2H)1.50 (m, 2H)0.97 (t, 3H)

C5H9 BrO2C5H8 Cl2 O2

C4H8 O3

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Prob 17.18Prob 17.18Complete these reactions.

CH2OHK2Cr2O7, H2SO4

H2 O, acetone(a)

1. Ag(NH3)2+

(b)2. H2O, HCl

HOOH

CHO

1. Cl2 , KOH in water/dioxane

2. HCl, H2 O(c)

(d)

1. Mg, ether2. CO2

3. HCl, H2 O

Br

OCH3

O

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Prob 17.19Prob 17.19Show how to bring about each conversion.

(b)

(a)

O

OH

O

Cl COOH

(c)

(d)

OH

CH2OH

O

COOH

C6H5OH

C6H5 COOH

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Prob 17.21Prob 17.21Draw a structural formula for each starting compound.

(b)oxidation

oxidation(a)C6H1 4O

C6H1 2O

OH

O

OH

O

oxidation(c)C6H1 4O2

OOH

OHO

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Prob 17.22Prob 17.22Show reagents to bring about each conversion.

(b)

(a) OH COOH

CH3

CH3

CH3

CH3COH CH3CCOOH

CH3

(d)

(c)

CH3

CH3 CH3

CH3

CH3

CH3

CH3COH CH3CHCOOH

CH3COH CH3CHCH2COOH

CH3CH=CHCH3 CH3CH=CHCH2COOH(e)

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Prob 17.23Prob 17.23Show how to synthesize butanedioic acid starting with acetylene and formaldehyde.

Butanedioic acid(Succinic acid)

Acetylene 2-Butyne-1,4-diol

1,4-Butanediol

OHHO

HOOH

HOOH

O

O

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Prob 17.24Prob 17.24Propose a mechanism for the rearrangement of benzil to sodium benzilate.

OO

Ph-C-C-Ph NaOHH2O

OHO

Ph

Ph-C-C-O-Na

+ HCl

H2OPh

HOO

Ph-C-C-OH

(an -diketone)

+

Benzil

BenzilicacidSodiumbenzilate

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Prob 17.33Prob 17.33Show how to convert trans-3-phenyl-2-propenoic (cinnamic acid) to each compound.

(a)

(b)

(c)

C6H5 OH

C6H5 OH

O

C6H5 OH

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Prob 17.34Prob 17.34Show how to convert 3-oxobutanoic acid to these compounds.

OH

O(a)

(b)

(c)

OH

OH

OH

OH

O

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Prob 17.35Prob 17.35Complete each example of Fischer esterification.

+

+

COOH

COOH

CH3OH

(a)H+

(b)H+

+H+

(c) OH

OHO

O

OH

O

HO

OH

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Prob 17.37Prob 17.37Name the carboxylic acid and alcohol from which each ester is derived.

(b)O

O

(a)O

OO

O

OO

O

OO

O(d)(c)

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Prob 17.39Prob 17.39Propose a mechanism for this reaction.

RCOH

O CH3

CH2=CCH3H

+ O CH3

CH3

RCOCCH3+

2-Methylpropene(Isobutylene)

A tert-butyl ester

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Prob 17.40Prob 17.40Draw a structural formula for the product of thermal decarboxylation of each compound.

(a)C6H5CCH2COOH (b)C6H5CH2CHCOOHCOOH

(c)COOH

CCH3

O

O

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Prob 17.41Prob 17.41Propose a mechanism for each decarboxylation. Compare your mechanisms with the mechanism for decarboxylation of a -ketoacid.

(a)Br-CH2-C COO- Na+

CH3

CH3

heat

CH2=C(CH3)2 + CO2 + Na+Br-

(b) CH-CH-COO-Na+

Br Brheat

CH=CHBr + CO2 + Na+Br-

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Prob 17.43Prob 17.43Show how to convert cyclohexane to cyclohexanecarboxylic acid.

COOH

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Carboxylic Carboxylic AcidsAcids

End Chapter 17End Chapter 17