Functional Derivatives

Chapter 15:
Functional Derivatives of
Carboxylic Acids
© 2005 John Wiley & Sons, Inc.

All rights reserved 15-1
Carboxyl Derivatives
• In this chapter, we study four classes of organic
compounds
• under the general formula of each is a drawing to help you see
how it is related to the carboxyl group

Acid Chlorides
• The functional group of an acid halide is an acyl group
bonded to a halogen
• the most widely used are the acid chlorides
• to name, change the suffix -ic acid to -yl chloride

Acid Anhydrides
• The functional group of an acid anhydride is two acyl
groups bonded to an oxygen atom
• the anhydride may be symmetrical (two identical acyl groups)
or mixed (two different acyl groups)
• to name, replace acid of the parent acid by anhydride

Acid Anhydrides
• A phosphoric acid anhydride contains two phosphoryl
groups bonded to an oxygen atom
• shown here are two phosphoric anhydrides
• each is shown on the right as it would be ionized at pH 7.4,
the pH of blood

Esters
• The functional group of an ester is an acyl group
bonded to -OR or -OAr
• name the alkyl or aryl group bonded to oxygen followed by
the name of the acid
• change the suffix -ic acid to -ate

Lactones
• Lactone: a cyclic ester
• IUPAC: name the parent carboxylic acid, drop the suffix -ic
acid, and add -olactone
• the location of the oxygen atom on the carbon chain is
commonly indicated by a Greek letter

Phosphoric esters
• Phosphoric acid forms mono-, di-, and triesters
• name by giving the name of the alkyl or aryl group(s) bonded
to oxygen followed by the word phosphate
• in more complex phosphate esters, it is common to name the
organic molecule followed by phosphate

Amides
• The functional group of an amide is an acyl group
bonded to a trivalent nitrogen
• IUPAC: drop -ic acid from the name of the parent acid and
add -amide
• if the amide nitrogen is bonded to an alkyl or aryl group,
name the group and show its location on nitrogen by N-

Lactam
• Lactam: a cyclic amide
• name the parent carboxylic acid, drop the suffix -ic acid and
add -lactam
• the location of the nitrogen atom in the ring is commonly
indicated by a Greek letter, α, β, etc.
• 6-hexanolactam is an intermediate in the synthesis of nylon 6

(Section 17.5A)

The Penicillins
• The penicillins are a family of β-lactam antibiotics
• one of the first discovered was penicillin G

The Penicillins
• amoxicillin, a β-lactam antibiotic

Cephalosporins
• The cephalosporins are also β-lactam antibiotics

Characteristic Reactions
• Nucleophilic acyl substitution: an addition-elimination
sequence resulting in substitution of one nucleophile for
another
• the reaction depends on having a suitable leaving group
bonded to the acyl carbon, here indicated Lv

• in the general reaction, we showed the nucleophile as an
anion; this need not be the case
• neutral molecules such as water, alcohols, ammonia, and
amines can also serve as nucleophiles
• in the general reaction, we showed the leaving group as an
anion to illustrate an important point about them: the weaker
the base, the better the leaving group

• halide ion is the weakest base and the best leaving group; acid
halides are the most reactive toward nucleophilic acyl
substitution
• amide ion is the strongest base and the poorest leaving group;
amides are the least reactive toward nucleophilic acyl
substitution

Hydrolysis - Acid Chlorides
• low-molecular-weight acid chlorides react rapidly with water
• higher molecular-weight acid chlorides are less soluble in
water and react less readily

Hydrolysis - Acid Anhydrides
• low-molecular-weight acid anhydrides react readily with
water to give two molecules of carboxylic acid
• higher-molecular-weight acid anhydrides also react with
water, but less readily

Hydrolysis - Esters
• Esters are hydrolyzed only slowly, even in boiling water
• Hydrolysis becomes more rapid if they are heated with
either aqueous acid or aqueous base
• Hydrolysis in aqueous acid is the reverse of Fischer
esterification

Hydrolysis - Esters
• Hydrolysis of an ester in aqueous base is often called
saponification
• each mole of ester hydrolyzed requires 1 mole of base; for this
reason, ester hydrolysis in aqueous base is said to be base
promoted
• base-promoted ester hydrolysis involves formation of a

tetrahedral carbonyl addition intermediate followed by its
collapse

Hydrolysis - Esters
• step 1: addition of hydroxide ion to the carbonyl carbon
• step 2: collapse of the addition intermediate
• step 3: proton transfer completes the reaction

Hydrolysis - Esters
• There are two major differences between
acid-catalyzed and base-promoted ester hydrolysis
1. for acid-catalyzed hydrolysis, acid is required in only
catalytic amounts; for base-promoted hydrolysis, base is
required in equimolar amounts
2. hydrolysis of an ester in aqueous acid is reversible;
base-promoted hydrolysis is irreversible

Hydrolysis - Amides
• Hydrolysis of an amide requires much more vigorous
conditions than hydrolysis of an ester
• hydrolysis in aqueous acid requires 1 mole of acid for each
mole of amide
• the products are a carboxylic acid and an ammonium or an
amine salt

Hydrolysis - Amides
• hydrolysis of an amide in aqueous base requires 1 mole of
base per mole of amide
• the products are a carboxylate salt and an amine

Hydrolysis
• A summary

Reaction with Alcohols
• Acid chlorides react with alcohols to give an ester and
HCl

• Acid anhydrides react with alcohols to give 1 mole of
ester and 1 mole of carboxylic acid
• aspirin is prepared by the following reaction:

• Esters undergo an exchange reaction called
transesterification
• the exchange is acid catalyzed
• the original -OR group is exchanged for a new -OR group

• Amides to not react with alcohols under any conditions
• Summary of reactions with alcohols

Reaction with NH3 and Amines
• Acid halides react with ammonia, 1° amines, and 2°
amines to form amides
• 2 moles of the amine are required per mole of acid chloride;
one to form the amide and one to neutralize the HCl formed

• Acid anhydrides react with ammonia, and with 1° and
2° amines to form amides
• 2 moles of ammonia or amine are required; one to form the
amide and one to neutralize the carboxylic acid byproduct
• here the reaction is broken into two steps

• Esters react with ammonia, and with 1° and 2° amines
to form amides
• esters are less reactive than either acid halides or acid
anhydrides
• Amides do not react with ammonia, or with 1° or 2°

amines

Reaction with NH3 & Amines
• Summary

Interconversion
• interconversion of functional groups

Esters with Grignard Reagents
• a formic ester with 2 moles of Grignard reagent
followed by hydrolysis gives a 2° alcohol
• reaction of an ester other than a formate gives a 3°

alcohol

Esters with Grignard Reagents
• Steps 1 and 2
• Steps 3 and 4

Reduction
• esters are reduced by LiAlH4 to two alcohols
• the alcohol derived from the carbonyl group is primary
• NaBH4 does not normally reduce esters, but it does reduce

aldehydes and ketones

Reduction
• LiAlH4 reduction of an amide gives a 1°, 2°, or 3° amine,
depending on the degree of substitution of the amide

Some Interconversions
• from Example 15.7

Functional
Derivatives of Carboxylic
Acids
End Chapter 15


Functional Derivatives

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Chapter 15:

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

• 6-hexanolactam is an intermediate in the synthesis of nylon 6

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

• base-promoted ester hydrolysis involves formation of a

© 2005 John Wiley & Sons, Inc.

• step 2: collapse of the addition intermediate

• step 3: proton transfer completes the reaction

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

• aspirin is prepared by the following reaction:

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

• Amides do not react with ammonia, or with 1° or 2°

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

• reaction of an ester other than a formate gives a 3°

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

• NaBH4 does not normally reduce esters, but it does reduce

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

© 2005 John Wiley & Sons, Inc.

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