Topic 6:

NUCLEOPHILIC ACYL
SUBSTITUTION FOR
CARBONYL GROUPS

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 LEARNING OBJECTIVES

1. Draw and name structures of carboxylic acid and its

derivatives according to IUPAC names.

2. Recognize, differentiate and explain reactivity of carboxylic

acid and derivatives.

3. Recognize, differentiate and explain reactions of carboxylic

acid and derivatives.

4. Illustrate and draw mechanisms and examples.

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 Carboxylic acid & derivatives
Posses a carbonyl group bonded to electronegative atom.

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 Structure of carboxyl
Carbon is sp2 hybridized.
Bond angles are close to 120º.
O-H eclipsed with C=O, to get overlap of phi orbital with
orbital of lone pair on oxygen.

O O O
H H H
R O R O R O

Boiling points
Higher boiling points than similar alcohols, due to dimer
formation.

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 Melting points
Aliphatic acids with more than 8 carbons are solids at room
temperature.
Double bonds (especially cis) lower the melting point.
Note these 18C acids:
Stearic acid (saturated): 72ºC
Oleic acid (one cis double bond): 16ºC
Linoleic acid (two cis double bonds): -5ºC

Some important acids

Acetic acid is in vinegar and other foods, used industrially as
solvent, catalyst, and reagent for synthesis.
Benzoic acid in drugs, preservatives.
Adipic acid used to make nylon 66.
Phthalic acid used to make polyesters.
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Salts of carboxylic acids - Purifying an acid
Carboxylic acid react with bases, such as NaOH or NaHSO4 to
give metal carboxylate salt, RCOO-M+.
Sodium hydroxide removes a proton to form the salt.
Adding a strong acid, like HCl, regenerates the carboxylic acid.

Acid >6C
atoms only
slightly soluble
in water.
But alkali
metal salts of
carboxylic acid
are generally
quite soluble
because they
are ionic.
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 Preparation of carboxylic acid
1. Oxidation of alcohol or aldehyde
CrO3
CH3(CH2)7CH2OH +
CH3(CH2)7COOH
H3O

Ag2O
CH3(CH2)4CHO CH3(CH2)4COOH
NH2OH

2. Oxidative cleavage of an alkene

Reaction with KMnO4 for alkene has at least one vinylic

hydrogen.

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 Preparation of carboxylic acid
3. Hydrolysis of nitrile

Reaction with strong, aqueous hot acid or base.

The nitrile is prepared by SN2 reaction between an alkyl
halide and cyanide ion.

4. Oxidation of substituted alkylbenzene

Reaction with KMnO4 or K2Cr2O7.

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 Preparation of carboxylic acid
5. Carboxylation of Grignard reagent

Reaction of Grignard reagent with carbon dioxide will give a

metal carboxylate, followed by acid hydrolysis to give
carboxylic acid.
This carboxylation is carried out by pouring the reagent
over dry ice (solid CO2) or by bubbling dry CO2 gas through
a solution containing Grignard reagent. Yield is good.

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Reaction of carboxylic acid & derivatives
Nucleophilic acyl substitution reaction.

Mechanism:

a) Direct nucleophilic substitution.

b) Acid catalysed nucleophilic substitution.

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Reactivity of carboxylic acid & derivatives

Because of
these
reactivity
differences, it
is possible to
convert a
more reactive
acid
derivative
into a less
reactive one.

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Interconversion reactions between
carboxylic acid & derivatives

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 Nucleophilic acyl substitution reactions
1. Hydrolysis

Reaction of all carboxylic acid derivatives with water under

acidic or basic conditions.

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Nucleophilic acyl substitution reactions
Mechanism :

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 Nucleophilic acyl substitution reactions
2. Conversion to anhydride

Reaction of acid chloride with a carboxylate anion.

3. Conversion to acid chloride

Reaction of carboxylic acid with thionyl chloride.

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 Nucleophilic acyl substitution reactions
4. Conversion to ester (Alcoholysis)

Reaction of carboxylic acid, acid chloride and acid

anhydride with alcohol or alkyl halide.

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Nucleophilic acyl substitution reactions
Mechanism :

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 Nucleophilic acyl substitution reactions
5. Conversion to amide (Aminolysis)

Reaction of acid chloride, acid anhydride and ester with

ammonia, 1 and 2 amines.
Acid chloride is most reactive and most used to prepare
amide.

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Nucleophilic acyl substitution reactions

Mechanism :

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Nucleophilic acyl substitution reactions
6. Reaction with organometallic reagent

Acid chlorides and esters react with Grignard reagents to

give tertiary alcohols via ketones (ketone cannot isolate).
Ketones intermediate can be isolated if lithium
diorganocopper is used.

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Nucleophilic acyl substitution reactions
Mechanism :

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