Chapter 10

Reactions of Carboxylic Acids

and Carboxylic Acid
Derivatives

Carbonyl Overview
The next three chapters cover the chemistry of the carbonyl group
that are focused on:
carboxylic acid & derivative chemistry
aldehyde & ketone chemistry
enol/enolate chemistry

chapter 18

Nomenclature of carboxylic acids

Carboxylic acids

Nomenclature of Carboxylate Ions

Carboxylic acids

Two basic reactions of carbonyl compounds

Nucleophilic acyl substitution

Carboxylic acids and

Derivatives
R

O H

c a rb o x y lic a c id

c a rb o x y la te

O
R

th io e s te r

O
a c y l p h o s p h a te

a m id e R

e ste r

O
O

C l

a c y l c h lo rid e

a c id a n h y d rid e

The structure of a carbonyl compound

The carbonyl carbon is electrophilic

For carboxylic acids and derivatives, Y is a leaving group

Carbonyl resonance contributors

A Nucleophilic acyl substitution reaction

Y = Leaving Group
Z = nucleophile

The relative reactivities towards nucleophilic acyl

substitution depend on the Leaving Group

Acid/Base and properties

pKa values, solubility - review

Carboxylic acids

Synthesis of acids
Oxidative cleavage (review)
Oxidation of primary alcohol (review)
Grignard with CO2 (new reaction)
Hydrolysis of derivatives (new reaction,
covered throughout the chapter)

Carboxylic acids

New synthesis of a carboxylic acid

Add to your Grignard notecards:

Grignard + formaldehyde = primary alcohol
Grignard + epoxide = primary alcohol
Grignard + aldehyde = secondary alcohol
Grignard + ketone = tertiary alcohol
Grignard + CO2 = acid

Carboxylic acids

Closer look at
Carboxylic acid derivatives
Carboxylic acids can be converted into the
following derivatives
carboxylic acid chlorides
carboxylic acid anhydrides
esters
amides
anhydrides
nitriles

All carboxylic acid derivatives can be

hydrolyzed back to carboxylic acids

Synthesis & Reactions of acid chlorides

Carboxylic acid chlorides are easily synthesized from carboxylic
acids upon reaction with thionyl chloride (SOCl2).
Acid chlorides can themselves be used to synthesize:
acid anhydrides, esters, & amides

Acid chlorides

Nomenclature of acid chlorides

Acid chlorides

Ester synthesis via acid chloride

Acid chlorides

Amide synthesis via acid chloride

Acid chlorides

Amides cannot be synthesized by

combining an acid and amine directly

A carboxylic acid is an acid and an amine is a base,

so an acid-base reaction occurs.

Anhydride synthesis via acid chloride

Acid chlorides

Nomenclature of acid anhydrides

Acid anhydrides

Acid Anhydrides are Less Reactive than Acyl Chlorides

but More Reactive Than Esters

Acid anhydrides

Reactions of Acid Anhydrides

As you will see, acid anhydrides are for the

most part, interchangeable with acid chlorides
Acid anhydrides

The Mechanism

Acid anhydrides

Esters can be prepared using a concentrated

acid-catalyst
(H+, e.g., H2SO4)

This ester synthesis is called Fischer esterification and complements

your prior synthesis via an acid chloride

Nomenclature of Esters named as

carboxylates

Cyclic ester = lactone

esters

The Reaction of an Ester with Water

esters

The Carbonyl Oxygen is the Oxygen That is Protonated

+ H3O+ ClProtonation of the carbonyl carbon increases the electrophilic character of the carbon

Less electrophilic

More electrophilic

Resonance forms

Resonance forms
esters

The Mechanism for the

Acid-Catalyzed Hydrolysis of an Ester

Proton Transfer
P.T.

esters

Protonation Makes the Leaving Group

a Better Leaving Group

esters

Use Excess Water

to Drive the Reaction to the Right

esters

The Mechanism for Hydroxide-Ion Promoted

Hydrolysis of an Ester

esters

The Reaction of an Ester with an Alcohol

important in biochemistry and biodiesel fuel production

esters

The Reaction of an Ester with a Grignard

From chapter 12

Esters react with two equivalents of Grignard to give tertiary alcohols via a
ketone intermediate

esters

Summary of Grignard Reactions

for 345
For final exam
Grignard + formaldehyde = primary alcohol
Grignard + epoxide = primary alcohol
Grignard + aldehyde = secondary alcohol
Grignard + ketone = tertiary alcohol
Grignard + CO2 = acid
2 equivalents of Grignard + ester = tertiary alcohol

Nomenclature of Amides

Cyclic amide = lactam

amides

Nomenclature of Amides

The substituent attached to the nitrogen is stated first.

Amide bonds are peptide bonds

amides

The Mechanism for the

Acid-Catalyzed Hydrolysis of an Amide

amides

Amide Hydrolysis Can Be Promoted

by Hydroxide Ion

Draw a mechanism. Which do you think is more resistant to basic

hydrolysis, an ester or an amide?

amides

Nomenclature of Nitriles

Nitriles dont look like other carboxylic acid derivatives but

they can be considered a dehydrated amide

nitriles

Acid-Catalyzed Hydrolysis of a Nitrile

Amide tautomer

nitriles

Another synthesis of a carboxylic acid

Compare to Grignard and CO2

nitriles

Reduction of carbonyl systems

Chainsaw

reduction

Reduction of carbonyl systems

LAH is strong enough to reduce all common carbonyl systems

LAH is strongly basic and must be used under anhydrous conditions like
Grignard reagents
LAH transfers two hydride atoms per carbonyl group
reduction

Fats and Oils are Formed by

Esterifying Glycerol with Fatty Acids

Fats/soaps

Fats/soaps
2014 Pearson Education, Inc.

Hydrolysis of Fat or Oil in a

Basic Solution Forms a Soap

A soap is a sodium or potassium salt of a fatty acid.

The reaction is called saponification and you
will run this reaction in lab.

Fats/soaps

A Micelle

Long-chain carboxylate ions form micelles.

Fats/soaps

Summary
Lots of substitution and hydrolysis reactions all the same mechanism

All carboxylic acid derivatives can be made from the acid chloride by choosing
the appropriate nucleophile
All carboxylic acids can be hydrolyzed with the nucleophile is water (aq acid
conditions) or hydroxide (aq base conditions)

Summary
Nitriles can be installed via SN2 chemistry and although they do not
look like other carbonyl compounds, they react the same.
Nitriles can be considered dehydrated amides

You have two methods of synthesizing esters: via the acid chloride
and an alcohol and by using Fischer esterification
Lithium aluminum hydride LiAlH4 is a source of nucleophilic hydride
and can reduce all carboxylic acids and derivatives. LiAlH4 must be
used under anhydrous conditions.