Chemistry 618B

Carboxylic AcidsCarboxylic Acids

R CO

OHC

O

O-R + H+

R CO-

O

Chemistry 618B

Nomenclature Nomenclature -- IUPACIUPAC• IUPAC names: drop the -e from the parent

alkane and add the suffix -oic acid• If the compound contains a carbon-carbon

double bond, change the infix -an- to -en-

Propenoic acid (Acrylic acid)

trans-3-Phenylpropenoic acid

(Cinnamic acid)

trans-2-Butenoic acid

(Crotonic acid)

CCO2 H

CH

H3 C H

CH2 =CHCO 2 H CCO2 H

CH

C6 H5 H

Chemistry 618B

NomenclatureNomenclature--CommonCommon

• When common names are used, the letters α, β, γ, δ, etc. are often used to locate substituents

Alanine)(αααα-Aminopropionic acid;(γγγγ-Hydroxybutyric acid)2-Aminopropanoic acid4-Hydroxybutanoic acid

4 3 2 15

δδδδ γγγγ ββββ ααααO

HOCH2 CH2 CH2 CO2 H

C-C-C-C-C-OH

CH3 CHCO2 HNH2

Chemistry 618B

Benzoic acid Benzoic acid Sodium benzoateSodium benzoate

Butyric acidButyric acid Ammonium butyrateAmmonium butyrate

Naming the SaltsNaming the Salts

• To name the salt of the carboxylic acid, name the cation followed by the name of the anion (two words).

• The anion is named by removing -oic acid and adding ate

Boiling PointsBoiling Points

• Intermolecular forces, especially hydrogen bonding, are stronger in carboxylic acids than in other compounds of similar shape and molecular weight

bpbp (1(1 atmatm)) 31°C31°C 80°C80°C 99°C99°C

OH

141°C141°COH

OO

Chemistry 618B

Physical PropertiesPhysical Properties• In the liquid and solid states, carboxylic

acids are associated by hydrogen bonding into dimeric structures

δ- δ+

δ-δ+

CO H O

COHO

CH3H3C

Chemistry 618B

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 both the C=O and OH groups

Chemistry 618B

Physical PropertiesPhysical Properties• Water solubility decreases as the relative

size of the hydrophobic portion of the molecule increases

hydrophobic region; decreases water solubility

hydrophilic region; increases water solubility

C HOCR

O

CH2 O C R

O

CH2 O C

O

R NaOHC OHH

CH2 OH

CH2 OH

glycerolFat

C

O

O- Na+R

Fatty Acid Salt "Soap"

R = CH3(CH2)16COOH Stearic AcidCH3(CH2)7CH CH(CH2)7COOH Oleic acid

etc.

SaponificationSaponification of Fatof Fat

Soaps and DetergentsSoaps and Detergents

CH3(CH2)16CO O - N a+

CH3(CH2)11 SO

OO'Na+

CH2 NCH3

CH3

(CH2)15CH3

Cl

Soap

Anionic detergent

Cationic Detergent

Surface Active Agents = surfactants

Chemistry 618B

Chemistry 618B

•• A carboxylic acid is characterized by peaks due toA carboxylic acid is characterized by peaks due toOH and C=O groups in its infrared spectrum.OH and C=O groups in its infrared spectrum.

•• C=O stretching gives an intense absorptionC=O stretching gives an intense absorptionnear 1700 cmnear 1700 cm--11..

•• OH peak is broad and overlaps with COH peak is broad and overlaps with C——H H absorptions.absorptions.

Infrared SpectroscopyInfrared Spectroscopy

Chemistry 618B

2000200035003500 30003000 25002500 1000100015001500 500500Wave number, cmWave number, cm--11

Infrared Spectrum of 4Infrared Spectrum of 4--PhenylbutanoicPhenylbutanoic acidacid

C=O

O—H and C—H stretch

monosubstitutedbenzene

C6H5CH2CH2CH2CO2H

11H NMR of Carboxylic acidsH NMR of Carboxylic acids

The acidic proton in the HOThe acidic proton in the HO-- croup of a croup of a carboxylic acid is normally the least carboxylic acid is normally the least shielded of all protons in ashielded of all protons in a 11HH nmr nmr spectrum: (d 10spectrum: (d 10--12 12 ppmppm; broad)…; broad)…

Chemical shift (Chemical shift (δδ,, ppmppm))

CCHH22CCHH22CCHH22COCOHH

OO

01.02.03.04.05.06.07.08.09.010.011.012.0

1313C NMR of Carboxylic acidsC NMR of Carboxylic acids

The Carbonyl carbon on the carboxylic acid The Carbonyl carbon on the carboxylic acid group is at low field (group is at low field (δδ 160160--185185 ppmppm), but not ), but not quite as quite as deshieldeddeshielded as the carbonyl carbon of as the carbonyl carbon of anan aldehydealdehyde or ketone (or ketone (δδ 190190--215215 ppmppm). ).

Chemistry 618B

Mass SpectrometryMass Spectrometry– The McLafferty rearrangement gives a

characteristic peak at m/z = 60

•+

•+

+

McLafferty rearrangement

m/z 60

HH2 C

H2 CCH2

C

O

COH

O

CH2

HOHH2 C

H2 C

Chemistry 618B

Chemistry 618B

Acidity Acidity •• Carboxylic acids are weak acidsCarboxylic acids are weak acids

– The pKa of typical aliphatic and aromatic carboxylic acids falls within the range 4 to 5

R CO

OHC

O

O-R + H+

R CO-

O

•The greater acidity of carboxylic acids relative to alcohols, both of which have oxyanions conjugate bases is because:

•the carboxylate anion is stabilized by resonance

Chemistry 618B

Review definitions of:Review definitions of:

KaKapKapKa[H[H++]]pKapKa

Assuming equal molar concentations, which produces the solution with the lower pH, an acid with high or low pKa??

Chemistry 618B

AcidityAcidity• Electron-withdrawing substituents near the

carboxyl group increase acidity through their inductive effect

2.903.184.76 2.86 2.59

CH2 CO2 HCH2 CO2 H CH2 CO2 HCH2 CO2 HCH2 CO2 HFClBrH I

Acid Strength

Chemistry 618B

AcidityAcidity• Substitution by multiple electron-

withdrawing groups further increases acidity

Chloroacetic Trichloroacetic Dichloroacetic Acetic

pKa

: 2.86 0.701.484.7 6

H3CCO2H H2ClCCO2H HCl2CCO2H Cl3CO2H

Acid Strength

Chemistry 618B

AcidityAcidity

pKa: 4.52 3.98 2.83

• The inductive effect of an electron-withdrawing substituent falls off rapidly with its distance from the carboxyl group

4-Chlorobutanoic 3-Chlorobutanoic 2-Chlorobutanoic

Cl Cl Cl

CH2 CH2 CH2 CO2 H CH3 CH2 CHCO2 HCH3 CHCH2 CO2 H

Acid Strength

Chemistry 618B

The key to understanding acid The key to understanding acid strength is in being able to strength is in being able to

understand the stability of the understand the stability of the conjugate base, the anionconjugate base, the anion

R CO

OHC

O

O-R + H+

R CO-

O

Chemistry 618B

Reactions of AcidsReactions of Acids

• Reduction• Decarboxylation• Esterification• Formation of Acid Halides

Chemistry 618B

ReductionReduction• The carboxyl groups is one of the organic

functional groups most resistant to reduction– it is not affected by catalytic hydrogenation

under conditions that easily reduce aldehydesand ketones to alcohols, and reduce alkenes and alkynes to alkanes

– it is not reduced by NaBH4

Chemistry 618B

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

1 . LiAlH 4 , ether2 . H 2 O

COH

O

+ +LiOH Al(OH) 3CH2 OH

Chemistry 618B

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

OOHCHCH2 CH2 CH2 COHCCH2 CH2 CH2 COH

O O1 . NaBH4

2 . H 2 O

Chemistry 618B

DecarboxylationDecarboxylation•• DecarboxylationDecarboxylation:: loss of COloss of CO22 from a from a

carboxyl groupcarboxyl group

• Most carboxylic acids, if heated to a very high temperature (fried), undergo thermal decarboxylation

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

Chemistry 618B

DecarboxylationDecarboxylation•• Exceptions are carboxylic acids that have a Exceptions are carboxylic acids that have a

carbonyl group beta to the carboxyl groupcarbonyl group beta to the carboxyl group– this type of carboxylic acid undergoes

decarboxylation on mild heating

Acetone3-Oxobutanoic acid (Acetoacetic acid)

+warmββββ ααααO O O

CH3 -C-CH2-C-OH CH3 -C-CH 3 CO2

Chemistry 618B

DecarboxylationDecarboxylation•• DecarboxylationDecarboxylation occurs readily if there is any occurs readily if there is any

carbonyl group beta to the carboxylcarbonyl group beta to the carboxyl• Malonic acid and substituted malonic acids, for

example, also undergo thermal decarboxylation

Propanedioic acid (Malonic acid)

+140-150°CO O O

HOCCH2 COH CH3 COH CO2

Chemistry 618B

DecarboxylationDecarboxylation•• ThermalThermal decarboxylationdecarboxylation of a of a ββ--ketoacidketoacid

involves rearrangement of six electrons in a involves rearrangement of six electrons in a cyclic sixcyclic six--memberedmembered transition state transition state

(A cyclic six-membered transition state)

CH

O

C C

OH

H3 C OH

enol of a ketone

HO

CC

C

O

H3 C OH H

+

O

CH3 -C-CH 3 CO2

Chemistry 618B

DecarboxylationDecarboxylation•• ThermalThermal decarboxylationdecarboxylation ofof malonicmalonic acids acids

also involves rearrangement of six electrons also involves rearrangement of six electrons in a cyclic sixin a cyclic six--memberedmembered transition statetransition state

enol of a carboxylic acid

CHH

CH

CO

CHO

HOO

H

CO

CHO

OOH

+O

CH3 -C-OH CO2

Chemistry 618B

FischerFischer EsterificationEsterification•• Esters can be prepared by treatment of a Esters can be prepared by treatment of a

carboxylic acid with an alcohol in the presence of carboxylic acid with an alcohol in the presence of an acid catalyst, commonly Han acid catalyst, commonly H22SOSO44 or gaseousor gaseous HClHCl

Ethanol (Ethyl alcohol)

Ethanoic acid (Acetic acid)

+

OCH3 COH CH3 CH2 OH

H2 SO 4

Ethyl ethanoate (Ethyl acetate)

+

OCH3 COCH2 CH3 H2 O

Chemistry 618B

FischerFischer EsterificationEsterification• The key intermediate in Fischer esterification is

the tetrahedral 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

R••

••HOCH3+ ••

••HOH+

H+ H+

tetrahedral carbonyl addition intermediate

Chemistry 618B

Reaction of Esters with OH Reaction of Esters with OH --• Hydrolysis of an esters is aqueous base is called

saponification• Each mol of ester hydrolyzed requires 1 mol of base; for

this reason, ester hydrolysis in aqueous base is said to be “base-promoted” (not catalyzed)

• Hydrolysis of an ester in aqueous base involves formation of a tetrahedral carbonyl addition intermediate followed by collapse and proton transfer (Nucleophilic acyl substitution)

++

O ORCOCH3 NaOH RCO- Na + CH3 OH

H2 O

Chemistry 618B

SaponificationSaponification• Base-promoted ester hydrolysis• Irreversible due to deprotonation of the

acid

••

••

••

••

••

••

••

••

••

••

••

••

••

•• ••

••

••

••

••

•• ••

••

••

••

••

•• ••

••++

-

+

O O

OH

O CH 3

O

O H HO

O

R-C-O-CH 3 OH R-C

R-C O-CH 3 R-C O-CH 3

--

-

-

Chemistry 618B

Hydrolysis of AmidesHydrolysis of Amides

Hydrolysis of amides is also irreversible. In acid Hydrolysis of amides is also irreversible. In acid solution the amine product issolution the amine product is protonatedprotonated to to give an ammonium salt.give an ammonium salt.

++ R'R'NNHH33++

RCOHRCOH

OO

RCRCNNHR'HR'

OO

++ HH22OO HH++++

Chemistry 618B

GrignardGrignard ReagentsReagents• Addition to CO2 gives a carboxylic acid

• This is a great way to add a carbon and make an acid

Mg+2H3O+

CH3CH2- MgBr+ CH3CH2 C O- MgBr+

O

+THF dil.

CH3CH2 C OH

O

C OO

Chemistry 618B

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 OCH2 N2RCOH RCOCH3 N2

•• •••••• + +H

H

C N N

H

N NCH

Chemistry 618B

DiazomethaneDiazomethane• Esterification occurs in two steps

Step 1: proton transfer from the carboxyl group to diazomethane

••

••

••

•• ••

••

••

++

++

A carboxylate anion

R C O H

O

N NO

NC OR N

CH2

CH3

••

Chemistry 618B

DiazomethaneDiazomethane

Step 2: nucleophilic displacement (SN2) of N2, an extraordinarily good leaving group, by thecarboxylate anion

••

•• ••••

•• ••

••

••

++

+

N NR C O

O

R C O

O

CH 3 N N

CH 3S N 2