Carboxylic Acids and Nitriles Organic Chemisty 6e

Chapter 20

Introduction to Chapter RCO2H – About Carboxylic Acids

– Serve as starting materials for preparing acyl derivaties;

• Esters• Amides• Acid Chlorides

– Many carboxylic acids are found in Nature

• Acetic Acid, CH3CO2H for vinegar

• Butanoic Acid, CH3(CH2)2CO2H is the rancid oder from sour butter

• Palmitic Acid, CH3(CH2)14CO2H is a biological precursor of fats and other lipids.

– Approx. 2 million tons of acetic acid are produced annually in the United States

Chapte

r 20 Intr

oduct

ion

20.1

Nam

ing C

arb

oxylic

Aci

ds

and N

itri

les

Nomencalture - RCOOHTwo systems have been adopted by IUPAC:

1. Carboxylic acids derived from open-chain alkanes are named by replacing their terminal –e of the alkane with -oic acid

2. Compounds that have a –COOH group bonded to a ring are named using the suffix –carboylic acid

CH3OH

O

Propanoic acid

CH35 4

3

2

1

OH

O

CH3

4-Methylpentanoic acid

3-Bromocyclohexanecarboxylic acid

5

1

4

2

3

CO2H

1-Cyclopentenecarboxylic acid

2

3

1

4

6

5

CO2H

Br

20.1

Nam

ing C

arb

oxylic

Aci

ds

and N

itri

les

Nomencalture – RC NTwo systems have been adopted by IUPAC:1. Nitriles derived from open-chain alkanes are named by adding –nitrile as a suffix to the alkane name, with the nitrile carbon numbered C1:

2. Nitriles are named as derivatives of carboxylic acids by replacing the –ic acid or –oic acid with –onitrile, or replacing –carboxylic acid with -carbonitrile.

Acetonitrile

CH35 4

3

2

CH3

CN1

4-Methylpentanenitrile

CH36 5

4

CH3

CH3

3

2

CN1

4,5-dimethylhexanenitrile

CH3C

N

C N

Benzonitrile3,3-Dimethylcyclohexanecarbonitrile

3

4

2

5

1

6

CH3

CH3NC

20.1

Nam

ing C

arb

oxylic

Aci

ds

and N

itri

les

20.2

Str

uct

ure

and P

hysi

cal Pro

pert

ies

Carboxyl carbon has sp2 hybridization; carboxyl group is therefore planar with C C O and O C O bond angles of ~120°

Carboxylic acids are strongly associated by hydrogen bonds, most existing as cyclic dimers held together by two hydrogen bods

CH3

O

O H

H O

O

CH3

O

O

H

HH

H

20.2

Str

uct

ure

and P

hysi

cal Pro

pert

ies

H OH

O

Formic acid

CH3 OH

O

Acetic acid

OH

O

CH3

Propanoic acidOH

O

CH2

Propenoic acid

C

O

OH

Benzoic acid

20.3

Dis

soci

ati

on o

f C

arb

oxylic

Aci

ds

Carboxylic acids are acidic, Ka ~ 10-5 (pKa ~5), and therefore react readily with a base such as NaOH to give a carboxylate salt.

R OH

O

NaOH

R O-

O

Na+

+ +

Metal-carboxylate salt

R OH

O

+ H3O+H2O

R O-

O

+

][

]][[

2

32

HRCO

OHRCOK a

and pKa = - log Ka

H2O

20.3

Dis

soci

ati

on o

f C

arb

oxylic

Aci

ds

Carboxylic acids are more acidic than alcohols by a factor of ~1011

Relative Acidity of Carboxylic Acids

Acidity

CH3CH2OHpKa = 16

CH3COHpKa = 4.75

O

HClpKa = -7

Explanation: Acidity can be explained in terms of bonding

CH3 OH H3O++ H2O CH3 O- +

Not stabilized

R

O

OH

R

O

O-

R

O-

O

+ H2O

stabilized by resonance

20.4

Subst

ituent

Eff

ect

s on A

cidit

y

Acidity of carboxylic acids varies greatly according to the nature of the substituent attached to the carboxyl group

Generally, any factor that STABILIZES the carboxylate group relative to the undissociated acid will drive the equilibrium toward increased dissociation and result in increased acidity.

Key Points

Electron-withdrawing groups stabilize carboxylate ions

Electron-donating groups destabilize carboxylate ions

C

O

O-

EWG C

O

O-

EWG

Electron-withdrawing groupStabilizes carboxylate and

strengthens acid

Electron-donating groupDestabilizes carboxylate and

weakens acid

20.4

Subst

ituent

Eff

ect

s on A

cidit

yRelative Strengths of Acetic Acid and Chloro- Derivatives

Acidity

OH

O

H

HH

OH

O

Cl

HH

OH

O

Cl

ClH

OH

O

Cl

ClCl

pKa = 4.75 pKa = 2.85 pKa = 1.48 pKa = 0.64

Acidity

ClCH2CH2CH2COHpKa = 4.52

O

CH3CHCH2COHpKa = 4.05

OCl

CH3CH2CHCOHpKa = 2.86

OCl

20.5

Su

bst

itu

en

t E

ffect

s in

Su

bst

iru

ted

Ben

zoic

Aci

ds

C

O

OH

CH3O

C

O

OHC

O

OH

O2N

Acidity

p-Methoxybenzoic acid(pKa = 4.46)

Benzoic acid(pKa = 4.19)

p-Nitrobenzoic acid(pKa = 3.41)

Deactivating groups (electron-withdrawing) stabilize carboxylates

Activating groups (electron-donating) destabilize carboxylates

20.6

Pre

para

tion

of

Carb

oxylic

Aci

ds

Five methods of preparation of Carboxylic AcidsI - Oxidation of a substituted alkylbenzene using KMnO4 or Na2Cr2O7

NO2 CH3KMnO4

H2O, 95°CNO2 C OH

O

p-Nitrotoluene p-Nitrobenzoic acid (88%)

* Oxidation occurs for 1° & 2° alkyl groups only, not in 3° alkyl groups

II – Oxidative cleavage of an alkene with KMnO4

CH3(CH2)7CH CH(CH2)7COHOleic acid

OKMnO4

H3O+CH3(CH2)7COH

nonanoic acid

O

HOC(CH2)7COH

O O

+nonanedioic acid

* Alkene must have at least one vinylic hydrogen

20.6

Pre

para

tion

of

Carb

oxylic

Aci

ds

III – Oxidation of a 1° alcohol or an aldehyde

IV – Hydrolysis of nitriles using strong, hot aquious acid or base

CH3(CH2)8CH2COH1-Decanol

CrO3

H3O+CH3(CH2)8COH

Decanoic acid (93%)

O

* 1° alcohols are oxidized with CrO3 in aqueous acid, aldehydes are oxidized with either acidic CrO3 OR Tollen’s reagent

CH3(CH2)4CHHexanal

Ag2O

NH4OHCH3(CH2)4COH

Hexanoic acid (85%)

OO

RCH2BrNa+ CN-

(SN2)RCH2C N

H3O+

RCH2COH

O+ NH3

* Excellent two-step process for the preparation of carboxylic acids from 1° halides

OCH3

Br

1. NaCN

2. –OH/H2O3. H3O

OC

CH3

OH

O

Fenoprofen(an antiarthritic agent)

* Product has one more carbon than the starting alkyl halide

20.6

Pre

para

tion

of

Carb

oxylic

Aci

ds

V – Carboxylation (or carbonation) of Grignard reagents

•Reaction is limited to alkyl halides that can form Grignard reagents (i.e. reactants with specific functional groups)

1-Bromo-2,4,6-trimethyl-benzene

CH3CH3

CH3

Br

Mg

Ether

CH3CH3

CH3

MgBr

1. CO2, ether

2. H3O+

CH3CH3

CH3

CO2H

2,4,6-Trimethylbenzoic acid(87%)

R:- +MgBr+ +

RC

O-

O

RC

O

O

H+MgBr

Reaction of Amide with SOCl2

O C O HO

+

H

H

+

20.7

RN

X o

f C

arb

oxylic

Aci

ds:

An O

verv

iew

CH

OH

O

Carboxylic acid

CR

OX

O

Alpha substitution

CH

O-

O

Deprotonatoin

CH

OH

H H

Reduction

CH

Y

O

Nucleophilic acylsubstitution

General Reactions of Carboxylic Acids

20.8

Reduct

ion o

f C

arb

oxylic

Aci

ds

I – Using LiAlH4 to give 1° alcohols

II – Using borane (BH3) to give 1° alcohols

Carboxylic acids can be reduced using two approaches

CH3(CH2)7CH=CH(CH2)7COHOleic acid

1. LiAlH4, THF

2. H3O+

O

CH3(CH2)7CH=CH(CH2)7CH2OHcis-9-Octadecen-1-ol

(87%)

* Reaction usually requires harsh conditions (i.e. heating)

1. BH3, THF

2. H3O+

NO2

COH

ONO2

OH

H H

p-Nitrophenylacetic acid 2-(p-Nitrophenyl)ethanol(94%)

* Reaction is usually performed under mild conditions and can be used to selectively reduce carboxylic acid functionality

20.9

Chem

istr

y o

f N

itri

les

R NH2

O

ClS

Cl

O

Base

BaseC NR + SO2

R N+

OS

Cl

O

H

HR N

OS

Cl

O

H

The dehydration reaction occurs first with the nucleophilic amide oxygen atom reacting with SOCl2, then a deprotonation of the molecule in a subsequent E2-like elimination reaction.

Preparation of Nitriles

Reaction of Amide with SOCl2

20.9

Chem

istr

y o

f N

itri

les

Nitrile groups are strongly polarized, thus resulting in a electrophilic carbon atom. Therefore they are attacked by nucleophiles and yield an sp2-hybridized imine anions.

This reaction is analogous to the formation of an sp3-hybridized alkoxide ion by nucleophilic addition to a carbonyl group.

Reactions of Nitriles

δ+

R R

Oδ-

R Nu

O

R

Products

R

Nδ-

δ+

R Nu

N-

Products

Carbonyl Compound

Nitrile

Imine anion

Nu--

Nu--

20.9

Chem

istr

y o

f N

itri

les

General Reactions of Nitriles

Nitrile

Amine

Amide Carboxylic Acid

Ketone

R N

O

H2R OH

O

RC

N

HH

H2R R'

O

R

C

N

H2O

H2O

LiAlH4 R’MgX

20.9

Chem

istr

y o

f N

itri

les

A nitrile can be hydrolyzed in either basic or acidic aqueous solution to yield a carboxylic acid and ammoniz or an amine

Hydrolysis: Conversion of Nitriles into Carboxylic Acids

H3O+

Basic hydrolysis of a nitrile

Amide

C NROr NaOH, H2O

R OH

O

+ NH3

C NR

RC

N-

OH

RC

N

OH

H

+

--OH

NH

RC

O

H

--OH

RC

N

O-

O-

H2

RC

N

OHO-

H2+

H2O

O-

RC

O+NH2

-

Carboxylate

--OH

OH H

Dianion

20.9

Chem

istr

y o

f N

itri

les

A nitrile can be reduced with LiAlH4 to give a primary amine

Reduction: Conversion of Nitriles into Amines

o-Methylbenzonitrile

C N

CH3

1. LiAlH4, ether2. H2O

C

CH3

NH2H2

o-Methylbenzylamine

The following example illistrates a reaction that occurs by nucleophilic addition of hydride ion to the polar C≡N bond, yielding an imine anion. The imine anion undergoes another nucleophilic addition to yield a dianion.

R C NLiAlH4

ether

RC

H

N-

LiAlH4

ether

H2O

RC

N

HH

H2RC

N2-

HH

Nitrile Imine anion Dianion Amine

20.9

Chem

istr

y o

f N

itri

les

A nitrile can add a Grignard reagent to give an intermediate imine anion that is further hydrolyzed by water to yield a ketone:

Reaction of Nitriles with Organometallic Reagents

R C N:R’- +MgX H2O

Nitrile Imine anion Ketone

R'RC

N-

RC

R'

O

+ NH3

This type of reaction is similar to the reduction of a nitrile to an amine, however only one nucleophilic addition occurs and the nucleophile is a carbanion (R:-) rather than a hydride ion:

C N

1. CH3CH2MgBr, ether2. H3O+

C

O

CH2CH3

Benzonitrile Propiophenone (89%)

20.1

0 S

pect

rosc

opy o

f C

arb

oxylic

Aci

ds I. O-H gives broad band in the range of 2500 – 3300 cm-1

II. C=O gives band in the range 1710 – 1760 cm-1

Infrared Spectroscopy – Two characteristic IR absorptions

Monomer Hydrogen-bonded dimer

* Position depends on whether the acid exists as a monomer or hydrogen-bonded dimer

CH3

O

O H

H O

O

CH3CH3 C

O

O H

IR Spectrum of Butanoic Acid

20.1

0 S

pect

rosc

opy o

f C

arb

oxylic

Aci

ds

NMR Spectroscopy• Acidic –COOH proton absorbs as a singlet near 12 δ • Carboxyl carbon atoms absorb in the range 165 - 185 δ• Aromatic / saturated near 165 ∂, aliphatic near 185 δ

NMR spectrum of phenylacetic acid