Chapter 11 Chapter 11 Carboxylic Anhydrides, Esters, and Carboxylic Anhydrides, Esters, and

AmidesAmides

Carboxyl DerivativesCarboxyl DerivativesIn 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.

AnhydridesAnhydridesThe 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”.

ExamplesExamples

H3C C

O

O C

O

CH3

Ethanoic anhydrideor acetic anhydride

F3C C

O

O C

O

CF3

Trif luoroethanoic anhydride

O

O

O

2-butenoic anhydride1

2

EstersEstersThe 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.

C

O

R' OR

carbonyl Oxygen

carboxyl oxgyen

ExamplesExamples

CH3CH2

C O

O

phenyl propanoate

CH3CHCH2

COCH3

O

Br

methyl 3-bromobutanoate

methyl -bromobutanoate

AmidesAmidesThe 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.

ClCH2CH2CH2

CNH2

O

4-chlorobutanamide

C NH2

O

benzenecarboxamide

ExamplesExamples 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-.

C

O

H3CH2CNH

N-cyclohexylpropanamide

C

O

H3CH2CH2CH2C NCH2CH3

CH3N-ethyl-N-methylpentanamide

C

O

H3CH2CH2CH2C NCH2CH3

CH2CH3N,N-diethylpentanamide

AmidesAmidesA cyclic amide is called a lactamlactam.

AmidesAmides

The penicillins are referred to as -lactam antibiotics

AmidesAmides• The cephalosporins are also -lactam antibiotics.

Fischer EsterificationFischer EsterificationFischer esterificationFischer esterification is the most common method for the preparation of esters• In Fischer esterification, a carboxylic acid is reacted

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

R1 C

O

OH+ R2 OH H+

R1 C

O

O R2+ H2O

AlcoholCarboxylic ester

ExamplesExamples

OH

O

+

OH

H+

Preparation of AmidesPreparation 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.

R1 C

O

OH+ R2 NH2

R1 C

O

O

amineCarboxylic

R2 NH2+

H

R1 C

OHN

Amide

R2heat

ExamplesExamples

COOH

+ CH3CH2NH2

Predict the amide product

How to synthesize the following compound

NHC

O

CH3

Preparation of AmidesPreparation of Amides• It is much more common, however, to prepare

amides by treating an amine with an anhydride.

R C

O

O C

O

R+R2 NH R C

O

NR2

+HO C

O

Ramine

amideacidacid anhydride

ExamplesExamples

NH2

+ H3C C

O

O C

O

CH3

Hydrolysis of AnhydridesHydrolysis of AnhydridesHydrolysisHydrolysis 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.

R C

O

O C

O

R

acid anhydride

+ H2O

R C

O

OH

+

R C

O

OH

carboxylic acids

ExampleExample

Hydrolysis of EstersHydrolysis 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).

ExamplesExamples

O

O O

+ H2O

H+

Hydrolysis of EstersHydrolysis 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.

ExamplesExamples

CH3C

O

OCH2CH3+ NaOH

H2OCH3C O

O

Na+ + CH2CH3OH

Ehthyl acetate SodiumHydroxide

Sodium acetate Ethanol

COCH3

O

COCH3

O

+ 2 NaOHH2O

Hydrolysis of AmidesHydrolysis of AmidesAmides 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.

Hydrolysis of AmidesHydrolysis 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.

ExamplesExamples

NHCCH3

O

acetanilide

+ NaOHH2O

heatCH3CO

O

Na+ H2N

Sodium acetate aniline

+

CH3CN(CH3)2

O

+ H2O + HClheat

CH3COH

O

+ (CH3)2NH

H

Cl-

Reaction with AlcoholsReaction with AlcoholsAnhydrides react with alcohols and phenols to give an ester and a carboxylic acid.

Reaction with AlcoholsReaction with AlcoholsAspirin is prepared by the reaction of salicylic acid with acetic anhydride.

R C

O

O C

O

R+R2 OH R C

O

OR2

+HO C

O

Ralcohol

esteracidacid anhydride

Reaction with AminesReaction with AminesAnhydrides react with ammonia and with 1° and 2° amines to form amides. ◦ Two moles of amine are required; one to form the

amide and one to neutralize the carboxylic acid by-product.

Reaction with AminesReaction with Amines Esters react with ammonia and with 1° and 2°

amines to form amides.

Thus, an amide can be prepared from a carboxylic acid by first converting the carboxylic acid to an ester by Fischer esterification and then reaction of the ester with an amine.

Amides do not react with ammonia or with amines

Phosphoric AnhydridesPhosphoric AnhydridesThe functional group of a phosphoric anhydridephosphoric anhydride is two

phosphoryl (P=O) groups bonded to the same oxygen atom.

Phosphoric EstersPhosphoric Esters• Phosphoric acid forms mono-, di-, and triphosphoric

esters.• In more complex phosphoric esters, it is common to

name the organic molecule and then indicate the presence of the phosphoric ester by either the word "phosphate" or the prefix phospho-.

• Dihydroxyacetone phosphate and pyridoxal phosphate are shown as they are ionized at pH 7.4, the pH of blood plasma.

Step-Growth Step-Growth PolymerizationPolymerization

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.• in this section, we discuss three types of step-

growth polymers; polyamides, polyesters, and polycarbonates.

PolyamidesPolyamidesNylon-66Nylon-66 was the first purely synthetic fiber.

• It is synthesized from two six-carbon monomers.

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

PolyestersPolyesters

The first polyester involved polymerization of this diester and diol.

PolycarbonatesPolycarbonatesLexan, the most familiar polycarbonatepolycarbonate, is formed by reaction between the disodium salt of bisphenol A and phosgene.