Chapter 19: Carboxyl Derivatives

In this chapter, we study three classes of compounds derived from carboxylic acids; anhydrides, esters, and amides.– Each is related to a carboxyl group by loss of H2O.

RCOHO

RCOR'O

RCOCR'O O

RCNH2

O

RC-OHO

H-OCR'O

RC-OHO

H-OR' RC-OHO

H-NH2

A carboxylic acid An esterAn anhydride An amide

-H2O -H2O -H2O

-C-O-C--C-O-C-==

OO

==

OO

-C-O--C-O-

==

OO

-C-N--C-N-

==

OO

--

Anhydride

The functional group of an anhydrideanhydride is two carbonyl groups bonded to the same oxygen.– The anhydride may be symmetrical (from two identical acyl

groups), or mixed (from two different acyl groups).– To name an anhydride, drop the word "acidacid" from the name of

the carboxylic acid from which the anhydride is derived and add the word "anhydrideanhydride”.

Acetic anhydrideCH3C-O-CCH3

O O

Esters

The functional group of an esterester is a carbonyl group bonded to an -OR group. R may be alkyl or aryl.– Both IUPAC and common names of esters are derived from the

names of the parent carboxylic acids.– Name the alkyl or aryl group bonded to oxygen first, followed by

the name of the acid; replace the suffix -icic acidacid by -ateate.– A cyclic ester is called a lactonelactone.

Ethyl ethanoate(Ethyl acetate)

Diethyl pentanedioate(Diethyl glutarate)

CH3COCH2CH3 O O

OO

O

O

A five-memberedlactone

O

Amide

The functional group of an amideamide is a carbonyl group bonded to a nitrogen atom.– To name an amide, drop the suffix -oic acidoic acid from the IUPAC

name of the parent acid, or -ic acidic acid from its common name, and add -amideamide.

– If the amide nitrogen is also bonded to an alkyl or aryl group, name the group and show its location on nitrogen by N- ; two alkyl or aryl groups by N,N-di-.

CH3CNH2

OCH3CNHCH3

OHCN(CH3)2

O

N-Methylacetamide(a 2° amide)

Acetamide(a 1° amide)

N,N-Dimethylformamide(a 3° amide)

Chapter 19: Carboxyl Derivatives

A cyclic amide is called a lactamlactam.

– The penicillins are referred to as -lactam antibiotics.

O

NH

O

NH

A four-membered lactam(a -lactam)

A seven-membered lactam

N

CH3

NH2

OHO

NHO

S

CH3

COOH

The penicillinsdiffer in the groupbonded to thecarbonyl carbon

The-lactam ring

Amoxicillin

Chapter 19: Carboxyl Derivatives

• The cephalosporins are also -lactam antibiotics.

N

S

COOHO CH3

NHNH2

O

Cephalexin (Keflex)(a -lactam antibiotic)

The cephalosporinsdiffer in the groupbonded to the carbonylcarbon...

...and the group bonded to this carbon of the six-membered ring

Preparation of an ester

Fischer esterificationFischer esterification is the most common method for the preparation of esters (Chapter 18).– In Fischer esterification, a carboxylic acid is reacted with an

alcohol in the presence of an acid catalyst, such as concentrated sulfuric acid.

CH3C-OHO

H-OCH2CH3

H2SO4CH3COCH2CH3

OH2O

Ethanoic acid(Acetic acid)

++

Ethyl ethanoate(Ethyl acetate)

Ethanol(Ethyl alcohol)

Preparation of amides

• In principle, we can form an amide by treating a carboxylic acid with an amine and removing -OH from the acid and an -H from the amine.– In practice what occurs if the two are mixed is an acid-base

reaction to form an ammonium salt.– If this salt is heated to a high enough temperature, water is

eliminated and an amide forms.

H2OCH3C-NHCH2CH3

O

CH3C-O- H3NCH2CH3

OH2NCH2CH3CH3C-OH

O+

Aceticacid

Ethanamine(Ethylamine)

An ammonium salt

heat +

An amide

+

Preparation of amides

• It is much more common, however, to prepare amides by treating an anhydride with an amine.

CH3C-O-CCH3

O OH2NCH2CH3 CH3C-NHCH2CH3

OCH3COH

O+ +

Acetic anhdyride An amide

Hydrolysis of Anhydrides

HydrolysisHydrolysis is a chemical decomposition involving breaking a bond and the addition of the elements of water.

– Carboxylic anhydrides, particularly the low-molecular- weight ones, react readily with water (hydrolyze) to give two carboxylic acids.

CH3COCCH3

O OH2O CH3COH

OHOCCH3

O+ +

Acetic anhydride Acetic acid Acetic acid

Hydrolysis of Esters

– Esters hydrolyze only very slowly, even in boiling water.– Hydrolysis becomes considerably more rapid, however, when

the ester is heated in aqueous acid or base.– Hydrolysis of esters in aqueous acid is the reverse of Fischer

esterification.– A large excess of water drives the equilibrium to the right to

form the carboxylic acid and alcohol (Le Châtelier's principle).

CH3COCH2CH3

O

H2OH+

CH3COHO

CH3CH2OH+ +

Ethyl acetate Acetic acid Ethanol

Hydrolysis of Esters

– We can also hydrolyze an ester using a hot aqueous base, such as aqueous NaOH.

– This reaction is often called saponificationsaponification, a reference to its use in the manufacture of soaps.

– The carboxylic acid formed in the hydrolysis reacts with hydroxide ion to form a carboxylic acid anion.

– Each mole of ester hydrolyzed requires one mole of base.

CH3COCH2CH3

ONaOH

H2OCH3CO-Na+

O

CH3CH2OH

Sodiumhydroxide

+ +

Ethyl acetate Sodiumacetate

Ethanolheat

Hydrolysis of amides

Amides require more vigorous conditions for hydrolysis in both acid and base than do esters.

– Hydrolysis in hot aqueous acid gives a carboxylic acid and an ammonium ion.

– Hydrolysis is driven to completion by the acid-base reaction between ammonia or the amine and the acid to form an ammonium ion.

– Each mole of amide hydrolyzed requires one mole of acid.

CH3CH2CH2CNH2

OH2O HCl

H2OCH3CH2CH2COH

ONH4

+Cl

-

Butanoic acidButanamide

++ +heat

Hydrolysis of amides

– Hydrolysis of an amide in aqueous base gives a carboxylic acid salt and ammonia or an amine.

– Hydrolysis is driven to completion by the acid-base reaction between the carboxylic acid and base to form a salt.

– Each mole of amide hydrolyzed requires one mole of base.

CH3CNHO

NaOHH2O

CH3CO-Na+O

H2N

AnilineSodiumacetate

Acetanilide

++heat

Step-Growth Polymerization

Step-growth polymersStep-growth polymers are formed by reaction between two molecules, each of which contains two functional groups. Each new bond is created in a separate step.

Polyamides: Nylon-66Polyamides: Nylon-66 was the first purely synthetic fiber.– It is synthesized from two six-carbon monomers.

-H2O+

Hexanedioic acid(Adipic acid)

1,6-Hexanediamine(Hexamethylenediamine)

heat

n

Nylon-66(a polyamide)

O

HOOH

O

NN

ON

ON

H

HH

Hremove H2O

H

H

Step-Growth Polymerization

The polyaromatic amide known as KevlarKevlar is made from an aromatic dicarboxylic acid and an aromatic diamine.

COHnHOCO O

N NH

HH

H

NHCNHCO O

-H2O

1,4-Benzenediamine(p-Phenylenediamine)

1,4-Benzenedicarboxylicacid

(Terephthalic acid)

nKevlar

(a polyaromatic amide)

+ heat

remove H2O