ORGANIC CHEMISTRY

Chapter 8
CARBOXILIC ACIDS AND
DERIVATIVES

Hortensia Rodriguez
hmrodriguez@yachaytech.edu.ec
 ORGANIC CHEMISTRY
1. Structure and bonding in organic molecules: Lewis dot structures, hybridization and geometry about atoms
in organic molecules, covalent bonds, acids and bases, dipole moments, formal charges, pKa
considerations, resonance.
2. Alkanes and Cycloalkanes: isomers, IUPAC nomenclature, cycloalkanes, properties of hydrocarbons, other
functional groups, conformational analysis, torsional, steric, and angle strain, chair cyclohexane, axial and
equatorial substituents.
3. Stereochemistry; enantiomers, optical activity, R &S nomenclature, diastereomers, meso compounds, cis-
trans stereoisomerism.
4. Reactions of alkyl halides: nucleophilic substitutions and eliminations, SN2, SN1, E2, and E1 reactions with
stereochemical consequences, mechanisms, transition states, and intermediates.
5. Alkenes: structure and reactivity, nomenclature, stability, electrophilic addition, Markovnikov rule,
halogenation, hydration, hydrogenation; polymerization.
6. Benzene and Aromaticity: aromatic stability, 4n+2 rule, electrophilic aromatic substitution.
7. Alcohols (phenols), aldehydes, and ketones: oxidation of alcohols, carbonyl reduction, grignard additions,
organic synthesis, acetal formation and hydrolysis, carbohydrates.
8. Carboxylic acids and derivatives: acid chlorides, amide and ester synthesis, amide and ester hydrolysis,
saponification.
ORGANIC CHEMISTRY
Chapter 8
CARBOXILIC ACIDS AND
DERIVATIVES

Carboxylic acids and derivatives: acid

chlorides, amide and ester synthesis,
amide and ester hydrolysis, saponification.
INTRODUCTION
Carboxylic acids are abundant in nature and in pharmaceuticals
 INTRODUCTION
The functional group of carboxylic acids consists of a C=O with -OH bonded to the same
carbon.

Carboxyl group is usually written -COOH.

Fatty acids are long-chain

aliphatic acids.

Aliphatic acids have an alkyl group bonded to -COOH.

Aromatic acids have an aryl group.
NOMENCLATURE

Common Names
Many aliphatic acids have historical names.
Positions of substituents on the chain are labeled with Greek letters.
O H
O
O H Ph H 2C
C l O HC
C 2C
H C H
H 2C H 2
3C 3C
C H C H
NOMENCLATURE
IUPAC Names
Remove -e from alkane (or alkene) name, add -oic acid.
The carbon of the carboxyl group is #1.
Ph H
Cl O C C
CH3CH2CHC OH H COOH
trans-3-phenyl-2-propenoic acid
2-chlorobutanoic acid
(cinnamic acid)
NOMENCLATURE
Naming Cyclic Acids
Cycloalkanes bonded to -COOH are named as cycloalkanecarboxylic acids.
Aromatic acids are named as benzoic acids.

COOH COOH

CH(CH3)2 OH
o-hydroxybenzoic acid
2-isopropylcyclopentanecarboxylic acid
(salicylic acid)
NOMENCLATURE
Dicarboxylic Acids
Aliphatic diacids are usually called by their common names (to be memorized).
For IUPAC name, number the chain from the end closest to a substituent.
Two carboxyl groups on a benzene ring indicate a phthalic acid.

Br
HOOCCH2CHCH2CH2COOH
Benzene-1,2-dicarboxylic acid
3-bromohexanedioic acid
Phthalic acid
-bromoadipic acid
STRUCTURE AND PROPERTIES OF
CARBOXYLIC ACIDS
The carbon atom of the carboxylic acid has a trigonal Higher boiling points than
planar geometry. similar alcohols, due to dimer
CA moiety forms strong inter- and intramolecular formation.
hydrogen bonding
Carbon is sp2 hybridized, so bond angles are close to 120.
O-H eclipsed with C=O, to get overlap of orbital with
orbital of lone pair on oxygen.
CAs generally have high boiling points

Boiling point 118 C Boiling point 82 C

STRUCTURE AND PROPERTIES OF
CARBOXYLIC ACIDS
Acidity
CAs function like other acids
In water, the equilibrium generally favors the acid

pKa values mostly range between 4 and 5.

STRUCTURE AND PROPERTIES OF
CARBOXYLIC ACIDS

Acidity
STRUCTURE AND PROPERTIES OF
CARBOXYLIC ACIDS
Acidity
Electron withdrawing substituents have a great effect on acidity (including
synergistic effects with multiple substituents)
Fluoroacetic, chloroacetic, bromoacetic, and iodoacetic acids are stronger acids than
acetic acid
STRUCTURE AND PROPERTIES OF
CARBOXYLIC ACIDS

Resonance Stabilization
STRUCTURE AND PROPERTIES OF
CARBOXYLIC ACIDS
Melting Points O

More than 8 carbons R

OH
Solids at RT

Double bonds (especially cis) lower the melting point.

Example 18-C acids:

Stearic acid Oleic acid

(one cis double bond) Linoleic acid
(saturated) (two cis double bonds)
72C 16C
-5C
STRUCTURE AND PROPERTIES OF
CARBOXYLIC ACIDS
Solubility
Water solubility decreases with the length of the carbon chain.
Up to 4 carbons, acid is miscible in water.

More soluble in alcohol.

Also soluble in relatively nonpolar solvents like chloroform because it
dissolves as a dimer.
SALTS OF CARBOXYLIC ACIDS
Sodium hydroxide removes a proton to form the salt.
Adding a strong acid, like HCl, regenerates the carboxylic acid.
O O
NaOH _ +
CH3 C OH CH3 C O Na
HCl
Naming Acid Salts
Name the cation.
Then name the anion by replacing the -ic acid with -ate.
Cl
potassium -chlorovalerate
- +
CH3CH2CHCH2COO K potassium 3-chloropentanoate
SALTS OF CARBOXYLIC ACIDS
Properties of Acid Salts
Usually solids with no odor. Carboxylate salts of Na+, K+, Li+, and NH4+ are soluble in water.
Soap is the soluble sodium salt of a long chain fatty acid.
Salts can be formed by the reaction of an acid with NaHCO3, releasing CO2.
SALTS OF CARBOXYLIC ACIDS
 SOME IMPORTANT ACIDS
Acetic acid is in vinegar and other foods, used industrially as solvent, catalyst, and reagent
for synthesis.
Fatty acids from fats and oils.
Benzoic acids in drugs, preservatives.

Aspirine
Adipic acid used to make nylon 66.

Phthalic acid used to make polyesters.

PREPARING CARBOXYLIC ACIDS
Known procedures
Oxidation of primary alcohols and aldehydes with
chromic acid or potassium permanganate
(Na2Cr2O7 orKMnO4).

Alkyl benzene oxidized to benzoic acid by hot KMnO4

or hot chromic acid.

Cleavage of an alkene with hot KMnO4 produces a

carboxylic acid if there is a hydrogen on the
double-bonded carbon (vinylic hydrogen).
PREPARING CARBOXYLIC ACIDS
Carboxylation of Grignard Reagents
Grignard reagents react with dry CO2 to yield a carboxylate salt
Limited to alkyl halides that can form Grignard reagents
The organomagnesium halide adds to C=O of carbon dioxide
Aqueous HCl in a second step protonates the free carboxylic acid
 REACTIONS OF CARBOXYLIC ACIDS
CA can transfer a proton to a
base CA can be reduced by LAH
(produces good nucleophile).

In addition, carboxylic Nucleophile can

acids undergo other add to carbonyl
reactions characteristic carbon of CA.
of neither alcohols nor
ketones
 REACTIONS OF CARBOXYLIC ACIDS
CA can transfer a proton to a
base CA can be reduced by LAH
(produces good nucleophile).

Carboxylic acids undergo Nucleophile can

other reactions add to carbonyl
characteristic of neither carbon of CA.
alcohols nor ketones
REACTIONS OF CARBOXYLIC ACIDS
Reduction
LiAlH4 is a strong reducing agent that can convert an acid to a primary alcohol
The LAH acts as a base first

Then, an aldehyde is produced

REACTIONS OF CARBOXYLIC ACIDS
Reduction
LiAlH4 is a strong reducing agent that can convert an acid to a primary alcohol
The aldehyde is further reduced to the alcohol
REACTIONS OF CARBOXYLIC ACIDS
Reduction
O 1. LiAl(OR)3H O
R Cl R H
2. H3O+

Acid chlorides can be reduced using LAH

To stop the aldehyde from being
reduced to the alcohol, a bulky reducing
agent can be used
REACTIONS OF CARBOXYLIC ACIDS
Reduction
The more mild borane reagent can also be used to promote the reduction

Reduction with borane is selective compared to LAH reduction

 REACTIONS OF CARBOXYLIC ACIDS
CA can transfer a proton to a
base CA can be reduced by LAH
(produces good nucleophile).

Carboxylic acids undergo Nucleophile can

other reactions add to carbonyl
characteristic of neither carbon of CA.
alcohols nor ketones
 REACTIONS OF CARBOXYLIC ACIDS
CA can transfer a proton to a
base CA can be reduced by LAH
(produces good nucleophile).

Carboxylic acids undergo Nucleophile can

other reactions add to carbonyl
characteristic of neither carbon of CA.
alcohols nor ketones
CARBOXYLIC ACID DERIVATIVES
Carboxylic acids can be modified without changing the oxidation state

Nucleophilic acyl
substitution

Because it has the same oxidation state, a nitrile is also an acid

derivative despite not having a carbonyl group.
Nitriles and CAs are electrophiles.
CARBOXYLIC ACID DERIVATIVES
Acid halides and anhydrides are relatively unstable, so they are not common in nature
Some naturally occurring esters are known to have pleasant odors

Amides are VERY common in nature

CARBOXYLIC ACID DERIVATIVES
Carboxylic acids can be modified without changing the oxidation state

Nucleophilic acyl
substitution

Because it has the same oxidation state, a nitrile is also an acid

derivative despite not having a carbonyl group.
Nitriles and CAs are electrophiles.
CARBOXYLIC ACID DERIVATIVES
Acid Halides
To name an acid halide, replace ic acid with yl halide

Alternatively, the suffix, carboxylic acid can be replaced with carbonyl halide
REACTIVITY OF CARBOXYLIC ACID
DERIVATIVES

CA derivatives have electrophilic

carbonyl carbons
Reactivity can be affected by
Induction
Resonance
Sterics
Quality of leaving group
REACTIVITY OF CARBOXYLIC ACID
DERIVATIVES
Reactivity of Acid Chlorides
The electronegative chlorine enhances the electrophilic character
of the carbonyl
There are 3 resonance contributors to the acid chloride
Chloride affects the sterics of the nucleophilic attack on the carbonyl
The chloride is a good leaving group, which also enhances its reactivity
REACTIVITY OF CARBOXYLIC ACID
DERIVATIVES
Reactivity of Amides
Amides are the least reactive acid derivative
Amino group presents steric hindrance
Is not a strong leaving group
Resonance contribution pulls positive charge away from carbon

Aldehydes and ketones

Reactivity of Aldehydes and Ketones

Aldehydes and ketones

Aldehydes and ketones are also electrophilic, but they do not undergo
substitution
H and R do not qualify as leaving groups.
Reactivity of Carboxylic Acid
Derivatives
Nucleophilic acyl substitution mechanism
Nucleophilic acyl substitution is a two-step process

Because C=O double bonds are quite stable, the loss of leaving group step should
occur if a leaving group is present
A nucleophile that is a weaker leaving group can replace a stronger leaving group.
Reactivity of Carboxylic Acid
Derivatives
Nucleophilic acyl substitution mechanism
Not an SN2 mechanism

Sometimes a proton transfer will be necessary in the mechanism

Reactivity of Carboxylic Acid
Derivatives
Nucleophilic acyl substitution mechanism
Under acidic conditions, (-) charges rarely form

The first step will NOT be

nucleophilic attack
The electrophile and nucleophile
are both low in energy
Reactivity of Carboxylic Acid
Derivatives
Nucleophilic acyl substitution mechanism

H3O+ is unstable and drives

the equilibrium forward by
starting the reaction
mechanism
Now that the electrophile
carries a (+) charge, it is much
less stable (higher in energy).
Reactivity of Carboxylic Acid
Derivatives
Nucleophilic acyl substitution mechanism
The first step will NOT be
nucleophilic attack
The electrophile and nucleophile
are both low in energy
Reactivity of Carboxylic Acid
Derivatives
Nucleophilic acyl substitution mechanism
Under basic conditions, (+) charges rarely form.
The OH- is the most unstable species in the reaction and drives the
equilibrium forward.
PREPARATION OF ESTERS
Fischer esterification
Fischer esterification combines a carboxylic acid and an alcohol using an
acid catalyst, with multiple proton transfers
Acid + alcohol yields ester + water.
Acid catalyzed for weak nucleophile.
All steps are reversible.
Reaction reaches equilibrium.
O
COOH + COCH2CH3
H
+ CH3CH2OH + HOH
PREPARATION OF ESTERS
Fischer esterification
REACTIVITY OF CARBOXYLIC ACID
DERIVATIVES
DIAZOMETHANE
CH2N2 reacts with carboxylic acids to produce methyl esters quantitatively.
Very toxic, explosive. Dissolve in ether.

O O
C OH C OCH
+ CH2N2 3 + N2
REACTIVITY OF CARBOXYLIC ACID
DERIVATIVES
Mechanism for Diazomethane
REACTIVITY OF CARBOXYLIC ACID
DERIVATIVES
Alkylation to Form Ketones

React 2 equivalents of an organolithium reagent with a carboxylic acid.

O
COOH 1) 2 CH3CH2 Li C CH CH
2 3

2) H2O
ACID CHLORIDES
An activated form of the carboxylic acid.

Chloride is a good leaving group, so undergoes acyl substitution easily.

To synthesize acid chlorides use thionyl chloride or oxalyl chloride with the acid.
O O
C OH O O C Cl
+ C C + HCl + CO + CO2
Cl Cl
ESTERS FROM ACID CHLORIDES
Acid chlorides react with alcohols to give esters in good yield.
Mechanism is nucleophilic addition of the alcohol to the carbonyl as chloride ion
leaves, then deprotonation.
AMIDES FROM ACID CHLORIDES
Acid chlorides react with ammonia and amines to give amides.
A base (NaOH or pyridine) is added to remove HCl by-product.
Amides are formed through reaction of primary and secondary amines with
acid chlorides and acid anhydrides.
Similar to esterification reactions.
AMIDES FROM CARBOXILIC ACIDS

Amine (base) removes a proton from the carboxylic acid to form a salt.
Heating the salt above 100C drives off steam and forms the amide.

O O O
C OH CH NH C O- +NH CH C NHCH
+ 3 3 3
3 2
heat
+ H2O
REACTION OF ACID CHLORIDES
Esters and acid chlorides can be attacked by Grignard nucleophiles
REACTION OF ACID CHLORIDES
Two equivalents of the Grignard yield a 3 alcohol
REACTIONS OF ESTERS
Esters can be fully reduced using reagents such as LiAlH4
Two equivalents of reducing agent are required
Two alcohols are produced
Can use water or acid for second step (source of proton)

When performed at low temperature, reduction with DIBAH yields an aldehyde.

REACTIONS OF ESTERS
Basic Hydrolysis
Saponification
REACTIONS OF AMIDES
LiAlH4 can reduce an amide to an amine

The iminium is reduced with a second equivalent of hydride

REACTIONS OF ACID CHLORIDES
REACTIONS OF ACID ANHYDRIDES
Acetic anhydride is often used to acetylate an amine or an alcohol
REACTIVITY OF CARBOXYLIC ACID
DERIVATIVES

Neutral nucleophiles are generally less reactive, but they can still react if
given enough time.
An intermediate with both (+) and (-) charge forms
PREPARATION AND REACTIONS OF
NITRILES
When a 1 or 2 alkyl halide is treated with a cyanide ion, the CN- acts as a
nucleophile in an SN2 reaction

Nitriles can also be made by dehydrating an amide using a variety of reagents

including SOCl2
REACTIONS OF NITRILES
RCN is strongly polarized and with an electrophilic carbon atom
Attacked by nucleophiles to yield sp2-hybridized imine anions
HYDROLYSIS: CONVERSION OF NITRILES
INTO CARBOXYLIC ACIDS

Hydrolyzed with acid or base catalysis to a carboxylic acid and ammonia

MECHANISM OF HYDROLYSIS OF NITRILES
Nucleophilic addition of hydroxide
to CN bond.

Protonation gives a hydroxy imine,

which tautomerizes to an amide.

A second hydroxide adds to the

amide carbonyl group and loss of a
proton gives a dianion.

Expulsion of NH2 gives the

carboxylate
Reduction: Conversion of Nitriles
into Amines
Reduction of a nitrile with LiAlH4 gives a primary amine

Nucleophilic addition of hydride ion to the polar CN bond, yielding an imine anion
The C=N bond undergoes a second nucleophilic addition of hydride to give a dianion,
which is protonated by water
REACTION OF NITRILES WITH
ORGANOMETALLIC REAGENTS

Grignard reagents add to give an intermediate imine anion that is

hydrolyzed by addition of water to yield a ketone
ORGANIC CHEMISTRY
Chapter 8
CARBOXILIC ACIDS AND
DERIVATIVES

Carboxylic acids and derivatives: acid

chlorides, amide and ester synthesis,
amide and ester hydrolysis, saponification. Bibliography: Organic Chemistry,
F.A. Carey, Chapter 19 and 20