CHAPTER 6 :

NUCLEOPHILIC
ACYL SUBSTITUTION:
CARBOXYLIC ACIDS
AND DERIVATIVES
 LEARNING OBJECTIVES
 Draw and name structures of carboxylic acid and its
derivatives according to IUPAC names
 Recognize, differentiate and explain reactivity of
carboxylic acid and derivatives
Recognize, differentiate and explain reactions of
carboxylic acid and derivatives

Illustrate and draw mechanisms and examples

Carboxylic acid and derivatives
•Posses a carbonyl group bonded to electronegative atom

3
 Naming – Carboxylic acid
• Remove -e from alkane (or alkene) name, add -oic
acid.
• The carbon of the carboxyl group is #1.

Cl O Ph H
C C
CH3CH2CHC OH H COOH
2-chlorobutanoic acid trans-3-phenyl-2-propenoic
acid (cinnamic acid)

4
 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
3-bromohexanedioic acid

5
 Naming – Acid Chloride
• The naming of acid chloride is by identifying first the acyl
group and then the halide.
• The acyl group is derived from the carboxylic acid name by
replacing the –ic acid with –yl or the carboxylic acid by –
carbonyl.
• For example:
O COCl

H3C C Cl

Acetyl chloride Benzoyl chloride

(Ethanoyl chloride)

6
 Naming - Anhydride
• Symmetrical anhydrides of unsubstituted monocarboxylic acids and
cyclic anhydrides of dicarboxylic acids are named by replacing the
word acid with anhydride
O O
O O C O O O O
H3C C O CH3

Acetic anhydride Benzoic anhydride Succinic anhydride

• Anhydrides derived from substituted monocarboxylic acids are

named by adding the prefix bis- to the acid name
O O
ClH2C C O CH2Cl

Bis(chloroacetic) anhydride
7
• Unsymmetrical anhydrides, those prepared from two different
carboxylic acids, are named by citing the two acids
alphabetically.

O O
H3C C O

Acetic benzoic anhydride

8
 Naming amide
• Amides with unsubstituted –NH2 group are named by replacing the –oic
acid or –ic acid ending with –amide.
• Example:
O O
H3CC NH3 H3C(H2C)4C NH2

Acetamide Hexanamide
• If the nitrogen is substituted, the compound is named by identifying the
substituent groups and then the parent amide. The substituent is preceded
by the letter N.
O
O
C
H3CH2CC NHCH3 N(CH2CH3)2

N-Methylpropanamide N,N-diethyl-2-methylbutanamide
9
 Naming – Ester
Esters are named by first identifying the alkyl group attached
to oxygen and then the carboxylic acid, with –oic acid ending
replaced with –ate.
O O O
O
H2
H3CC OCH2CH3 OCH3 H3CO C C C OCH3

Ethyl acetate Methyl pentanoate Dimethyl malonate

Substituents are listed depending on which part (alkyl or

carboxylate) they are bonded.
O O
Cl
O O Cl

propyl 2-chloroethanoate 3-chloropropyl ethanoate

10
 Structure of Carboxyl
• Carbon is sp2 hybridized.
• Bond angles are close to 120°.
• O-H eclipsed with C=O, to get overlap of  orbital
with orbital of lone pair on oxygen.

11
 Boiling Points
• Higher boiling points than similar alcohols, due to
dimer formation.

Acetic acid, b.p. 118°C

12
 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): 72°C
– Oleic acid (one cis double bond): 16°C
– Linoleic acid (two cis double bonds): -5°C

13
 Salts of Carboxylic Acids
• Carboxylic acid react with bases, such as NaOH or NaHSO4 to give
metal carboxylate salt, RCOO2-M+
• 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
• Acid with more than six carbon atoms only slightly soluble in water.
• But alkali metal salts of carboxylic acid are generally quite soluble
because they are ionic

14
Purifying an Acid

15
 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 acid in drugs, preservatives.
• Adipic acid used to make nylon 66.
• Phthalic acid used to make polyesters.

16
 Reactions of carboxylic acid
Can be classified into four categories:

•Acidic behaviour – acidic property (already mentioned earlier)

•Nucleophilic acyl substitution
•Reduction
•Alpha substitution (CHY3202)

17
 Nucleophilic acyl substitution
General mechanism:

Tetrahedral
intermediate
Reactivity of Acid Derivatives

Good

Bad

19
• As a consequence of these reactivity differences, it is possible
to convert a more reactive acid derivative into a less reactive
one.
More reactive O
R C X

Acid chloride
O O
R C O R'

Acid anhydride O
R C OR'

Ester
O
R C NH2

Amide
O
R C OH
Less reactive
Carboxylic acid

20
Interconversions

21
 Hydrolysis
• All
carboxylic acid derivatives react with water under acidic or basic
conditions to give carboxylic acid
- O
O O O
:

R C Cl + :OH2 R C +
O
H
R
+ H
O
R C OH
Cl
H H

O O
C H2O, NaOH + R'OH
C
R OR' + R OH
or H3O

Na+ CN- H3O+

RCH2Br RCH2CN RCH2COOH + NH3
SN2
 Acid catalyzed hydrolysis of amide
H H
O O O
H3O+
+ OH2
R H
R NH2 R NH2 O
H2N
H

H OH2
O O
+
H3O
+
NH4 + H2O + R H
O
NH3 R OH
H3N

•Reversible steps
•Equilibrium driven forward by protonation of ammonia
 Reaction with carboxylate ion:
conversion to anhydride
• Nucleophilic substitution of acid chloride with a carboxylate
anion.

O O O O
Ether, 25oC
C + C - + C C
R Cl R' O Na R O R'

• Example
O
O O C O O
NaOH H3C Cl
OH ONa O

24
 Alcoholysis: conversion to esters
• Esters can be prepared from carboxylic acids either catalyzed by
acid or base.
O Method 3 O
R C OH
SOCl2
Method 1 R C Cl
1. NaOH R'OH
R'OH
2. R'X HCl Method 2 Pyridine
O O O
R C OR' R C OR' R C OR'
Limited to primary Limited to simple Method very
alkyl halide alcohol general

Acid-catalyzed esterification is a reversible reaction and is known as

Fischer esterification.
25
 Alcoholysis
• Acid chlorides and acid anhydrides react with alcohols to give
esters
O O
OH
Cl Pyridine O
+

Benzoyl chloride Cyclohexanol Cyclohexyl benzoate

O O CH3CH2OH O O
+
O O O

26
 Aminolysis: conversion to amide
• Acid chloride, acid anhydride and ester react with ammonia and amines
to give amides. Both primary and secondary amines can be used, but not
tertiary amines (R3N).
• Acid chloride is most reactive and most commonly used to prepare
amide.

O O
-
(H3C)2HCC Cl + 2 :NH3 (H3C)2HCC NH2 + NH4+ Cl

O O

-
Cl + 2 :NH(CH3)2 N(CH3)2 + +
NH2(CH3)2 Cl

O O

OCH3 NH3, Ether NH2 + CH3OH

27
Mechanism:

28
 Aminolysis
• Reaction of acid chloride with different type of amines give
amide and substituted amides.

O O
SOCl2
R C OH R C Cl

R'2NH
NH3 R'NH2

O O
O
R C NH2 R C NR'2
R C NHR'

29
 Reaction with Grignard reagent
1) Carboxylation of Grignard reagents

•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 to get metal carboxylate, followed by acid hydrolysis to give carboxylic
acid

O O
-+ H3O+
R MgBr + O C O
R O- Mg+ R OH

2) Acid chlorides and esters react with Grignard reagents to give tertiary alcohols
via ketones intermediate.
O O H3C CH3
C C
Cl CH3MgBr CH3 1. CH3MgBr OH
Ether 2. H3O+

Cannot be isolated,
rapidly react
30
 Mechanism:
1st stage: R’MgX + RCOCl RCOR’ (ketone)

H3C CH3
R MgBr C O R C O MgBr
Cl
Cl
CH3 CH3
R C O MgBr R C + MgBrCl
O
Cl
Cl- leaves Ketone intermediate

Ketone intermediate react further

CH3 H H3C CH3 CH3

H3C C CH2 C MgBr C O CH3 CH CH2 CH2 C O MgBr
H3C
H H CH3
CH3 CH3
HOH
CH3 CH CH2 CH2 C O H
CH3
31
 SUMMARY:
Preparation of Carboxylic Acid

CHAPTER 10
 SUMMARY:
Preparation of COOH Derivatives