Chapter 21: Carboxylic acid Derivatives I. Introduction

Chapter 21: Carboxylic acid Derivatives
I. Introduction
R C O-R'
R C NH 2
II. Nomenclature of Carboxylic Acid Derivatives
A) Esters
Cyclic Esters
 Cyclic esters are called lactones.
Names of lactones are derived by adding the term lactone at the end of the name
of the parent carboxylic acid it came from:
B. Amides of Carboxylic Acids
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Nomenclature of Amides
1) Name the related carboxylic acid.
2) Replace the “-oic acid” (for IUPAC names) or the “-ic acid” suffix (for common
names) with “-amide”.
3) If the are alkyl groups on the nitrogen, put the name of each alkyl group in front
with an “N-” prefix (for example: N-ethyl).
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Cyclic amides are known as Lactams.
Lactams are produced from amino acids, where the amino and the carboxylic acid
groups react together to form an amide linkage.
C. Nitriles of Carboxylic Acids
Nitriles are technically not derivatives of carboxylic acids, but they can be
converted to carboxylic acids by hydrolysis, so they have been included in this
Nomenclature of Nitriles
1) Count the number of carbons in the longest carbon chain that contains the nitrile
(CN) carbon. Include the nitrile carbon in the count.
2) Name the alkane that has the same number of carbons.
3) Add the suffix “-nitrile” to the alkane name, with no space in between.
D. Acid Halides
Observed Reaction: (mechanism in chapter 20)
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The halogen atom inductively withdraws electron density away from the already
electrophilic carbon of the carbonyl group.
Nomenclature of Acid Halides
1) Name the related carboxylic acid.
2) Replace the “-ic acid” suffix with “-yl halide”.
E. Anhydrides of Carboxylic Acids
The word anhydride literally means without water, and an acid anhydride is the
combination of two molecules of carboxylic acid with the elimination of one
molecule of water.
Nomenclature of Acid Anhydrides
To name acid anhydrides:
1) Name each carboxylic acid half, then drop the “acid” part of the names.
2) Put the names in alphabetical order, separated by a space.
3) Add the word “anhydride”, separated by a space, following the names.
4) If the two halves are the same, only write the name once.
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F. Nomenclature of Multifunctional Compounds
 We have now covered a wide variety of functional groups. Many molecules
contain more than one of these different functionalities.
In choosing the principal group for the root name, the following priorities are
III. Interconversion of Acid Derivatives
There are a lot of transformations, but only one general mechanism:
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A. Reactivity of Acid Derivatives
A) Mechanism(s) of acid chloride reactions
Acid chloride to an anhydride
Acid chloride to ester
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Acid chloride to amide
B. Anhydrides
Anhydride to an ester
Anhydride to an Amide
C. Esters
 Ester to an Amide
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V. Leaving groups in Nucleophilic Acyl Substitutions
CASE #1: SN2
CASE #2: Acyl Substitution
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Ester + alcohol (in the presence of a strong acid) = transesterification
This reaction can proceed either by the acid catalyzed mechanism or by the base
catalyzed route.
CASE #1 Acid Catalyzed:
CASE #2 Base Catalyzed
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VII. Hydrolysis of Carboxylic Acids Derivatives
A) Hydrolysis of Acid Halides and Anhydrides
Acid halides are more reactive than anhydrides.
Acid anhydrides are less reactive and can be handled in the atmosphere for brief
periods without a large amount of hydrolysis.
Acid Chlorides are not stable in water. They react instantly with water. Even
moisture in the air will cause reaction when they are exposed to the atmosphere.
1. Hydrolysis of acid chlorides (acid, base, or neutral solutions work)
2. Hydrolysis of Anhydrides (acid, base, or neutral solutions work)
B. Hydrolysis of Esters
The acid catalyzed hydrolysis of an ester is simply the reverse reaction of the Fischer
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The basic hydrolysis of esters is also known as saponification, and this does not
involve the equilibrium process observed for the Fischer esterification.
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C. Hydrolysis of Amides
CASE #1:
Acidic conditions, the hydrolysis of an amide resembles the acid catalyzed
hydrolysis of an ester, with protonation of the carbonyl group giving rise to an
activated carbonyl group, that undergoes nucleophilic attack by water.
CASE #2:
(BASE)Amides are the most reluctant derivatives to undergo hydrolysis, but they
can be forced to by the use of vigorous conditions such as heating with 6M HCl or
40% NaOH for prolonged periods of time.
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D. Hydrolysis of Nitriles
Nitriles are hydrolyzed to primary amides, and then on to carboxylic acids.
Mild conditions only take this hydrolysis to the amide stage, and more vigorous
conditions are required to convert the amide to a carboxylic acid.
CASE #1: Acidic conditions
Mechanism: Formation of the Amide and acid-catalyzed hydrolysis
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CASE #2  Basic conditions
VIII. Reduction of Acid Derivatives
1. Reduction to Alcohols
Lithium aluminum hydride will reduce acids, acid chlorides and esters to primary
alcohols (Ch 20).
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Esters and acid chlorides react through the addition elimination mechanism,
generating aldehydes, that are quickly reduced to the primary alcohols.
2. Reduction to Aldehydes
3. Reduction TO Amines
Lithium aluminum hydride reduces amides, azides and nitriles to amines.
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IX. Acid Derivatives and Organometallic Reagents
Esters and acid chlorides will react twice with Grignard (and organolithium)
reagents to produce alkoxides (Ch 10).
Protonation of the alkoxides generates alcohols.
 Organometallic reagents attack the electrophilic carbon of the nitrile group, and
generate the metal salt of an imine.
Acid hydrolysis of this salt not only protonates the salt to form an amine, but also
hydrolyses the imine to a ketone (Ch 18).
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