Derivatives of
Carboxylic Acids and
Nucleophilic Acyl
Substitution
1
Carboxylic Acids
•
2
A class of organic compounds containing
at least one carboxyl group
R = alkyl group or H  alkanoic acid(sat’d)
R = aryl group  aromatic carboxylic acid
3
Aliphatic carboxylic acid
= fatty acids (sat’d or unsat’d)
∵ obtained from fat/oil
E.g. stearic acid, CH3(CH2)16COOH
oleic acid, CH3(CH2)7CH=CH(CH2)7COOH
4
Carboxylic Acids
•
Carboxyl group
 combination of the carbonyl group
and the hydroxyl group
5
Nomenclature
Suffix : carboxylic acid or oic acid
Prefix : carboxy
6
Q.62
(2Z)-but-2-enoic
acid
butanoic acid
7
ethanedioic
acid
Q.62
3-carboxy-3hydroxypentainedicarboxylic acid
butanedioic
acid
8
2-hydroxypropane1,2,3-tricarboxylic acid
(citric acid)
Q.62
benzoic acid
Benzene-1,3dicarboxylic acid
9
Q.62
phenylethanoic
acid
10
4-hydroxybenzoic
acid
Derivatives of carboxylic acids (pp.9-10)
Name
Acyl(Acid)
chlorides
Acid
anhydrides
Esters
Acid
Amides
11
Structure
Acyl (Acid) Chlorides
Suffix : -oic acid replaced by –oyl chloride
Prefix : chlorocarbonyl
12
Acyl (Acid) Chlorides
3-chloro-3-oxopropanoic
acid
Priority : -
-COOH > anhydride > ester > acid chloride > acid amide
The carbonyl C is counted as part of the carbon
skeleton
13
Q.63
4-chloro-2-methyl-4oxobutanoic acid
hexanedioyl
dichloride
14
3-(chlorocarbonyl)hexanedioic
acid
Acid anhydride
Suffix : -acid replaced by –anhydride
15
Acid anhydride
Prefix :
*
n-(alkanoyloxy)-n-oxo (if *C is counted
as part of the main chain)
n indicates the position of the *C in the
main chain
16
Acid anhydride
Prefix :
*
(alkanoyloxy)carbonyl
(if *C is not counted as part of the main
chain)
17
Acid anhydride
ethanoic
anhydride
18
ethanoic
propanoic
anhydride
Acid anhydride
benzoic ethanoic
anhydride
19
butanedioic
anhydride
Q.64
O
C
O
C
O
20
Benzene-1,2-dioic
anhydride
Ester
O
R
C
O
R'
Suffix : -oic acid replaced by –oate
preceded by the name of R’
21
Ester
*
Prefix : n-alkoxy-n-oxo(if *C is counted
as part of the main chain)
n indicates the position of the *C in the
main chain
22
Ester
*
Prefix :
alkoxycarbonyl
(if *C is not counted as part of the main
chain)
23
Ester
O
O
H3C
H3C
C
O
CH3
methyl
ethanoate
24
O
C
Br
O
C
H
CH2
ethenyl
ethanoate
C
O
CH3
methyl 4bromobenzoate
Q.65
2-(ethanoyloxy)benzoic acid
2-(acetyloxy)benzoic acid
COOH
COOH
O
C
CH3
O
O
CH3
C
O
2-(methoxycarbonyl)benzoic
acid
25
Acid amide
O
R
C
NH2
Suffix : -oic acid replaced by -amide
26
Ester
*
Prefix : n-amino-n-oxo (if *C is counted
as part of the main chain)
n indicates the position of the *C in the
main chain
27
Ester
*
Prefix :
aminocarbonyl
(if *C is not counted as part of the main
chain)
28
Ester
N,N-dimethylethanamide
(3)
O
O
O
H3C
H3C
C
H3C
C
C
N
NH2
HN
CH3
H3C
ethanamide
(1)
29
N-methylethanamide
(2)
CH3
Q.66
4-amino-4oxobutanoic acid
O
O
HOOC
C
NH2
benzamide
30
(CH2)2 C
HOOC
COOH
NH2
C
O
NH2
3-(aminocarbonyl)heptanedioic
acid
Physical
Properties of
Alkanoic Acids
31
32
Odour
Methanoic / ethanoic acid
 sharp, irritating odours
Propanoic to heptanoic acid
 strong, unpleasant odours
Butanoic acid  body odour
Higher members  low volatility  little odour
33

Alkanoic acid
Methanoic acid
Ethanoic acid
Propanoic acid
Butanoic acid
Pentanoic acid
Hexanoic acid
Heptanoic acid
Octanoic acid
Nonanoic acid
Decanoic acid
Melting point Boiling point
/o C
/o C
8.4
16.6
20.8
6.5
34.5
1.5
10
16
12.5
31
101
118
141
164
186
205
224
239
253
269
Density
/g cm-3
Solubility in water
/g per H2O
1.220
1.047
0.992
0.964
0.939
0.927
0.913
0.910
0.907
0.886




3.7
1.0
0.25
0.7
0.07
0.2
b.p.  steadily as the number of C atoms 
∵
London dispersion forces become
stronger as the size of electron cloud 
34

Alkanoic acid
Methanoic acid
Ethanoic acid
Propanoic acid
Butanoic acid
Pentanoic acid
Hexanoic acid
Heptanoic acid
Octanoic acid
Nonanoic acid
Decanoic acid
Melting point Boiling point
/o C
/o C
8.4
16.6
20.8
6.5
34.5
1.5
10
16
12.5
31
101
118
141
164
186
205
224
239
253
269
Density
/g cm-3
Solubility in water
/g per H2O
1.220
1.047
0.992
0.964
0.939
0.927
0.913
0.910
0.907
0.886




3.7
1.0
0.25
0.7
0.07
0.2
HCOOH/CH3COOH have exceptionally high m.p.
∵ smaller size
 1. closer packing

2.
forming
H-bonds
more
extensitively
35

Alkanoic acid
Methanoic acid
Ethanoic acid
Propanoic acid
Butanoic acid
Pentanoic acid
Hexanoic acid
Heptanoic acid
Octanoic acid
Nonanoic acid
Decanoic acid
36
Melting point Boiling point
/o C
/o C
8.4
101
16.6
118
141
20.8
164
6.5
186
34.5
205
1.5
224
10
16
239
12.5
253
31
269
Density
/g cm-3
1.220
1.047
0.992
0.964
0.939
0.927
0.913
0.910
0.907
0.886
Solubility in water
/g per H2O




3.7
1.0
0.25
0.7
0.07
0.2
Members with EVEN no. of C atoms are
more symmetrical
 Higher packing efficiency
 Higher m.p.

Melting point Boiling point
/o C
/o C
Methanoic acid
8.4
101
Alkanoic acid
Ethanoic acid
Propanoic acid
Butanoic acid
Pentanoic acid
Hexanoic acid
Heptanoic acid
Octanoic acid
Nonanoic acid
Decanoic acid
16.6
20.8
6.5
34.5
1.5
10
16
12.5
31
Density
/g cm-3
1.220
118
1.047
141
164
186
205
224
239
253
269
0.992
0.964
0.939
0.927
0.913
0.910
0.907
0.886
Solubility in water
/g per H2O




3.7
1.0
0.25
0.7
0.07
0.2
Pure ethanoic acid = glacial ethanoic acid
It freezes in cold weather
37
More extensive H-bonds
H-bonds
Dipole-dipole interaction
Dispersion forces ONLY
38

Alkanoic acid
Methanoic acid
Ethanoic acid
Propanoic acid
Butanoic acid
Pentanoic acid
Hexanoic acid
Heptanoic acid
Octanoic acid
Nonanoic acid
Decanoic acid
Melting point Boiling point
/o C
/o C
8.4
16.6
20.8
6.5
34.5
1.5
10
16
12.5
31
101
118
141
164
186
205
224
239
253
269
Less dense than water except
HCOOH/CH3COOH
39
Density
/g cm-3
Solubility in water
/g per H2O
1.220
1.047
0.992
0.964
0.939
0.927
0.913
0.910
0.907
0.886




3.7
1.0
0.25
0.7
0.07
0.2

Alkanoic acid
Methanoic acid
Ethanoic acid
Propanoic acid
Butanoic acid
Pentanoic acid
Hexanoic acid
Heptanoic acid
Octanoic acid
Nonanoic acid
Decanoic acid
Melting point Boiling point
/o C
/o C
8.4
16.6
20.8
6.5
34.5
1.5
10
16
12.5
31
101
118
141
164
186
205
224
239
253
269
Density
/g cm-3
Solubility in water
/g per H2O
1.220
1.047
0.992
0.964
0.939
0.927
0.913
0.910
0.907
0.886




 as R.M.M. 
R.M.M.   extent of H-bond formation 
 molecules not drawn closer

lower
packing
efficiency
40
3.7
1.0
0.25
0.7
0.07
0.2

Alkanoic acid
Methane
Ethane
Propane
Butane
Pentane
Hexane
Heptane
Octane
Nonane
Decane
Melting point Boiling point
/o C
/o C
Density
/g cm-3
Solubility in water
/g per H2O
Gas
Gas
Gas
Gas
0.626
0.655
0.684
0.703
0.718
0.730
For alkanes,   as R.M.M. 
∵ no intermolecular H-bonds
R.M.M.   Dispersion forces become stronger

closer
packing
41

Alkanoic acid
Methanoic acid
Ethanoic acid
Propanoic acid
Butanoic acid
Pentanoic acid
Hexanoic acid
Heptanoic acid
Octanoic acid
Nonanoic acid
Decanoic acid
Melting point Boiling point
/o C
/o C
8.4
16.6
20.8
6.5
34.5
1.5
10
16
12.5
31
101
118
141
164
186
205
224
239
253
269
Density
/g cm-3
Solubility in water
/g per H2O
1.220
1.047
0.992
0.964
0.939
0.927
0.913
0.910
0.907
0.886




3.7
1.0
0.25
0.7
0.07
0.2
First FOUR members are miscible with water in all
proportions due to extensive H-bond formation
between acid molecules and water molecules
42

Alkanoic acid
Methanoic acid
Ethanoic acid
Propanoic acid
Butanoic acid
Pentanoic acid
Hexanoic acid
Heptanoic acid
Octanoic acid
Nonanoic acid
Decanoic acid
Melting point Boiling point
/o C
/o C
8.4
16.6
20.8
6.5
34.5
1.5
10
16
12.5
31
101
118
141
164
186
205
224
239
253
269
Density
/g cm-3
Solubility in water
/g per H2O
1.220
1.047
0.992
0.964
0.939
0.927
0.913
0.910
0.907
0.886




3.7
1.0
0.25
0.7
0.07
0.2
From pentanoic acid, solubility  as R.M.M. 
The bulky R groups prevent formation of H-bonds
between –COOH and H2O
43
O
H
H
O
H
H
COOH
O
H
O
H
44
H
H
O
C
O
Non-polar
Na
ionic
Emulsifying action of soap (salts of carboxylic acids)
depends on the length of the hydrocarbon chain
45
Length of hydrocarbon chain
Short ( 15 C atoms)


Long ( 19 C atoms)
Intermediate(16-18 C atoms)
e.g. palmitic acid, C15H31COOH
stearic acid, C17H35COOH
46
Property
Ionic properties
predominate
Non-polar properties
predominate
Possess both
ionic/non-polar
properties
Preparation of
Carboxylic Acids
47
1. Hydrolysis of Nitriles
Elimination occurs for 2 and 3 RX as
CN is a relatively strong base
48
Examples
49
2. Oxidation of aldehydes and 1
alcohols (pp.83-84, 93)
3. Oxidation of aromatic side chains
(pp.54-55)
4. Iodoform reactions (p.92)
50
Q.67
COOH
COOH
51
Q.68
COOH
HOOC
1…
2…
Prolonged
heating
O
HOOC
C
CH3
H3C
52
COOH
5. Hydrolysis of Esters
O
O
NaOH(aq)
R
C
R
O
E.g.
Fat/oil
53
R'
heat
NaOH(aq)
heat
C
+
O Na
R'OH
removed by
distillation
Soap + glycerol
5. Hydrolysis of Esters
O
O
NaOH(aq)
R
C
R
O
R'
C
heat
+
O Na
H3O+
O
R
54
C
OH
R'OH
6. Carbonation of Grignard reagents
R-X
Mg
Dry ether
R[MgBr]+
Grignard
reagent
R : CH3-, 1/2/3 alkyl, benzyl, aryl
55
6. Carbonation of Grignard reagents
Mg
R-X
Dry ether
R[MgX]+
Dry ice
(CO2)
O
O
R
H3O+
C
OH
+1C
56
R
C
OMgX
6. Carbonation of Grignard reagents
Mg
R-X
Dry ether
R[MgX]+
O
R [MgX]
57
O
C
+
O
R
C
OMgX
7. Cannizzaro reactions
O
removed by
distillation
O
C
C
H
conc. NaOH
ONa
OH
+
heat
For aldehydes
without  H
H3O+
H
O
C
O
C
H
H
58
C
OH
Reactions of
Carboxylic Acids
59
Acidity of Carboxylic Acids
•
weak acids
[RCOO ][H3O ]
Ka 
[RCOOH]
-

pKa = –log Ka
The smaller the value of pKa, the
stronger the acid
60
Acidity  as pKa 
Acid RCOOH H2CO3
pKa
61
4-5
6.4
H2O
~10
15.7
Formation of Salts
1. Reaction with Reactive Metals
Irreversible as H2 leaves the
reaction mixture
62
2. Reaction with Bases
Stronger
acid
Weaker
acid
Equilibrium positions lie on the right
63
Phenols react with OH, but they do not
react with HCO3
Weaker
acid
Stronger
acid
Weaker
acid
64
No observable change
(effervescence)
Stronger
acid
Is there effervescence when Na is added
to phenol? Explain.
Yes.
The reaction proceeds to the completion
as H2 leaves the reaction mixture.
65
Carboxylic acids and phenols can be
distinguished by their different acidities
1989 AL Paper I Q.4 (modified)
66
OH
COOH
COOH
OH
COOH
OH
A
B
C
(a) Outline a chemical test to distinguish between A and B.
Add NaHCO3(aq) to A and B separately.
Ony B reacts apparently to give gas bubbles of CO2
67
OH
COOH
COOH
OH
COOH
OH
A
B
C
(b) C also gives a +ve result in (a). Show how you would
determine whether the sample is C or a mixture of A
and B.
Determine the melting point of the sample.
If the sample is pure C, it will give a sharp m.p..
The identity of C can be confirmed by carrying out
mixted melting point test.
68
(c) Outline a scheme to extract A from a mixture
containing A, B and C.
Mixture of
A, B and C
Pure A
C2H5
O
ether
Ether solution Shaken with
of A, B and C NaHCO3(aq)
C2H5
Evaporation
of ether b.p. = 34.6C
Ether layer, A
Aqueous layer,
sodium salts of B and C
Sodium salts of B and C
dissolve in water
69
Q.69
Outline a scheme to separate completely A, B and
C from a mixture of them in ether.
COOH
A
OH
OH
B
C
Acidity : A > H2CO3 > B > H2O > C
A, B are sparingly soluble solids in water
70
Ether solution
of A, B ands C
shaken with NaHCO3(aq)
Aqueous layer,
sodium salt of A
H3O+
Ether layer, B + C
COO
+ H+
COOH
Ppt of A
filtration
Impure A
COOH
OH
OH
A
B
C
p.120
recrystallization
71
Pure A
(m.p. = 122.4C)
Ether layer, B + C
Shaken with NaOH(aq)
Ether layer, C
Aqueous layer,
sodium salt of B
H3O+
O
Ppt of B
filtration
+ H+
Evaporation
of ether
OH
Pure C
OH
OH
B
C
Impure B
recrystallization
Pure B
72
(m.p. = 40.5C)
Decarboxylation
CH3COONa
NaOH(s) from soda lime
CH4 + Na2CO3
fusion
COONa
NaOH(s) from soda lime
fusion
+ Na2CO3
Applied ONLY to synthesis of methane and
benzene
73
Decarboxylation
-
+
heat
H2 +
2HCOO Na
-
+
RCH2COO Na + NaOH
COO-Na+
COO-Na+
more
difficult
Na2CO3 + RCH3 + other by-products
On the contrary,
decarboxylation is widely applied to
synthesis of carbonyl compounds
(refer to p.85)
74
Reduction
H2/Pt
or,
NaBH4/H2O
No reaction
75
Oxidation
Not easily oxidized except : HCOOH
KMnO4 / H+
heat
COOH
COOH
76
2CO
+
H2O
+
H2O
+
KMnO4 / H
heat
2CO2
Dehydration
Not easily dehydrated except : HCOOH
COOH
COOH
77
conc. H2SO 4
conc. H2SO 4
CO
CO2
+ 2O H
+
CO
+
H
2O
Q.70
O
+3
OH
Conc. H2SO4
C
C
HO
78
+3
O
+4
+2
CO2 + CO + H2O
Formation of acid derivatives
Refer to preparation of acid derivatives
(pp.115-120)
79
Acidity of Organic Compounds
(Bronsted/Lowry Concept)
HA(aq) + H2O(l)
H3O+(aq) + A(aq)
[H3O (aq)][A- (aq)]
Ka 
[HA(aq)]
smaller pKa  higher acidity
larger pKa  lower acidity
80
Two factors affecting the acidity of H–A : (1)
Strength of H–A bond (minor effect)
(2) Stability of the conjugate base, A
(major effect)
81
Two factors affecting the acidity of H–A : (1)
Strength of H–A bond (minor effect)
Stronger H–A bond  lower acidity
Acidity : H-I > H-Br > H-Cl >> H-F
Can be ignored for organic cpds ∵
(i) H is always bonded to C, N or O;
(ii) C-H, N-H and O-H bonds have
similar bond strengths
82
(2) Stability of the conjugate base, A
(major effect)
higher stability of A
 weaker basicity of A
 higher acidity of H-A
Stability of A depends on
(i) Electronegativity of A
Higher EN
 better accomodation of –ve
charge by A
 higher stability of A
83
Stability of A depends on
(ii) Electronic effect
- Inductive effect (+ve or –ve)
- resonance effect
(more important)
84
Organic Compound
pKa
Organic Compound
pKa
CH3CH2–H
50
CH3CH2CH2O–H
~17
H–H
50
HO – H
15.7
CH2=CH–H
44
C6H5O–H (phenol)
~10
NH2–H
36
CHC–H
25
CH3COCH2–H
20
85
4.87
CH3COO–H
4.76
4.20
Interpretation of the Relative Stability of
Typical Organic Compounds
pKa
HO-H
H2N-H
H3C-H
15.7
36
50
Electronegativity : -O>N>C
Stability of conjugate base : HO > H2N > H3C
The more electronegative atom can accommodate
the negative charge more easily
86
pKa
CH3COCH2-H
20
H3C-H
50
Resonance effect
The -ve charge on C becomes less available for
attracting a proton

CH3COCH2 becomes a weaker base

CH3COCH2-H becomes a stronger conjugate
acid
87
pKa
CHC-H
CH2=CH-H
CH3CH2-H
25
44
50
Stability of conjugate base : CHC > CH2=CH > CH3CH2
sp
sp2
sp3
Ease of accommodation of the –ve charge : sp C > sp2 C > sp3 C
88
CH3COO-H
pKa
4.74
CH3CH2CH2O-H
~10
~17
Stability of conjugate base : -
>
>
Stabilized by resonance effect
89
Destabilized by +ve
inductive effect
CH3CH2CH2
O
Q.71
The two structures are equally stable
The –ve charge is shared by two electronegative O atoms
 Delocalization of –ve charge is more favoured
90
Q.71
The –ve charge is accommodated by
the less electronegative C atoms
 less stable
 delocalization is less favoured
91
Q.72
pKa
4.20
4.87
The –ve charge is not
shared by the ring

less extensive
delocalization
92
The –ve charge is shared by the ring slightly

more extensive delocalization
The effect is small since the three
structures are less stable due to separation
of opposite charges
93
Effects of substituents on acidity of carboxylic acids
1. Aliphatic carboxylic acids
Electron-donating R groups destabilize the RCOO
 RCOOH is less acidic
Electron-withdrawing R groups stabilize the RCOO
 RCOOH is more acidic
94
95
Carboxylic acid
pKa
Conjugate base
CF3COO–H
0
CF3COO
CCl3COO–H
0.65
CCl3COO
CH2FCOO–H
2.66
CHCOO
CH2ClCOO–H
2.81
CH2ClCOO
CH2BrCOO–H
2.87
CH2BrCOO
CH2ICOO–H
3.13
CH2ICOO
HCOO–H
3.77
HCOO
CH3COO–H
4.76
CH3 COO
Inductive effect on acidity  rapidly when the
substituents are placed farther away from the
carboxyl group
Cl
COOH
COOH
>
96
2.85
>
COOH
>
Cl
Cl
pKa
COOH
4.05
4.52
4.82
2. Aromatic carboxylic acids
CF3
CH3
Acidity :>
COOH
>
COOH
COOH
Electron-donating group on the ring reduces the
acidity by destabilizing the conjugate base.
Electron-donating group on the ring increases
the –ve charge on the conjugate base, making it
more available for attracting a proton
 Stronger conjugate base
 Weaker acid
97
2. Aromatic carboxylic acids
CF3
CH3
Acidity :>
COOH
>
COOH
COOH
Electron-withdrawing group on the ring increases
the acidity by stabilizing the conjugate base.
Electron-withdrawing group on the ring disperses
the –ve charge on the conjugate base, making it
less available for attracting a proton
 Weaker conjugate base
 Stronger acid
98
Q.73
COOH
COOH
OH
COOH
>
>
HO
pKa
99
2.98
4.20
4.58
Q.73
pKa = 4.20
pKa = 4.58
OH withdraws electrons by –ve inductive effect
-OH donates electrons by resonance effect
Resonance effect > inductive effect
The net effect is electron-donating
100
pKa = 4.20
pKa = 2.98
The conjugate base is
stabilized by intramolecular
hydrogen bond
101
Acid
HOOCCOOH
HOOCCH2COOH
HOOC (CH2)2COOH
HOOC (CH2)3COOH
HOOC (CH2)4COOH
CH3COOH
pKa1
1.2
2.9
4.2
4.3
4.4
4.76
pKa2
4.2
5.7
5.6
5.5
5.6
-
pKa2 – pKa1
3.0
2.8
1.4
1.2
1.2
-
(1) Acidity : dioic acids > monocarboxylic acid
The conjugate bases are
stabilized by
intramolecular H-bonds
102
Acid
HOOCCOOH
HOOCCH2COOH
HOOC (CH2)2COOH
HOOC (CH2)3COOH
HOOC (CH2)4COOH
CH3COOH
pKa1
1.2
2.9
4.2
4.3
4.4
4.76
pKa2
4.2
5.7
5.6
5.5
5.6
-
pKa2 – pKa1
3.0
2.8
1.4
1.2
1.2
-
(2) pKa2 > pKa1
(i) The repulsion between two –COO groups
does not favour the 2nd dissociation
103
Acid
HOOCCOOH
HOOCCH2COOH
HOOC (CH2)2COOH
HOOC (CH2)3COOH
HOOC (CH2)4COOH
CH3COOH
pKa1
1.2
2.9
4.2
4.3
4.4
4.76
pKa2
4.2
5.7
5.6
5.5
5.6
-
pKa2 – pKa1
3.0
2.8
1.4
1.2
1.2
-
(2) pKa2 > pKa1
(ii) The doubly charged anion attracts the
proton more strongly
H+
104
Acid
HOOCCOOH
HOOCCH2COOH
HOOC (CH2)2COOH
HOOC (CH2)3COOH
HOOC (CH2)4COOH
CH3COOH
pKa1
1.2
2.9
4.2
4.3
4.4
4.76
pKa2
4.2
5.7
5.6
5.5
5.6
-
pKa2 – pKa1
3.0
2.8
1.4
1.2
1.2
-
(3) pKa1  as the two –COOH groups are further
apart
∵ intramolecular H-bonds are less easily
formed
105
Acid
HOOCCOOH
HOOCCH2COOH
HOOC (CH2)2COOH
HOOC (CH2)3COOH
HOOC (CH2)4COOH
CH3COOH
pKa1
1.2
2.9
4.2
4.3
4.4
4.76
pKa2
4.2
5.7
5.6
5.5
5.6
-
pKa2 – pKa1
3.0
2.8
1.4
1.2
1.2
-
(4) (pKa2-pKa1)  down the series
The repulsion between the two –COO groups
 down the series
 pKa2 remains relatively constant
Since, pKa1  down the series
(pKa2-pKa1)  down the series
106
Basicity of Organic Compounds
B(aq) + H2O(l)
HB+(aq) + OH(aq)
[HB (aq)][OH- (aq)]
Kb 
[B(aq)]
smaller pKb  higher basicity
larger pKb  lower basicity
107
Two factors affecting the basicity: (1) Ability to donate a lone pair to a proton
Basicity : -
>
>
3
2
>
1
More electron-donating alkyl group attached to N
More available to donate a lone pair to a proton
108
(2) The extent of solvation of the conjugate acid
Extent of solvation : -
>
>
1
>
2
3
More H attached to N
More available to form H-bond with water(solvent)
Extent of solvation 
 Stability of conjugate acid 
 Basicity of amine 
109
Good solvation
Extensive formation of
H-bonds with water
110
Overall Basicity (from experiments) : 2 amines > 1 amines > 3 amines > NH3
H 3C
H3C
N
H
H 3C
pKb
111
>
N
H
3.27
H
H 3C
3.36
H
>
N
H 3C
4.22
CH3
>
N
H
H
4.74
Q.74(a)
NH2
(a)
H3C
pKb
9.38
NH2
3.36
CH3NH2
-CH3 is electron-donating
 The lone pair on N is more available
to abstract a proton
112
NH2
NH2
NH2
NH2
The lone pair on N is shared by the
benzene ring due to resonance effect
 Less available to abtract a proton
113
Q.74(b)
NH2
NH2
&
OH
NH2
>
CH3
Both –OH and –CH3 groups are electron-donating
 Lone pair on N is more available to abstract a
proton
 Stronger base than phenylamine
114
Q.74(b)
NH2
NH2
>
OH
CH3
Resonance effect is more electron-donating
than positive inductive effect
115
Q.74(b)
NH2
NH2
>
NO2
-NO2 group is electron-withdrawing
 Lone pair on N is less available to
abstract a proton
 Weaker base than phenylamine
116
Q.74(c)
NH2
O
>
H3C
C
NH2
O
O
H 3C
H3C
C
NH2
C
NH2
Oxygen is more electronegative than N and C
 Lone pair on N is withdrawn more
117
 Less basic than phenylamine
Basicity of organic compounds : Aliphatic > NH3 > Aromatic > Amides
amines
amines
(2 > 1 > 3)
118
Amines form water-soluble salts with
mineral acids
CH3NH2 + HCl(aq)  CH3NH3+Cl
(CH3)2NH + HCl(aq)  (CH3)2NH2+Cl
(CH3)3N + HCl(aq)  (CH3)3NH+Cl
1. Used in drug formulation for easier absorption
2. Used in purification of amines from other
organic compounds
119
Q.75
Ether solution of
A, B, C and D
shaken with NaHCO3(aq)
Aqueous layer,
sodium salt of C
H3O+
Ether layer, A,B,D
COO
+ H+
COOH
Ppt of C
filtration
Impure C
recrystallization
120
Pure C
OH
NH2
COOH
CH3
Q.75
Ether solution of
A, B and D
shaken with NaOH(aq)
Aqueous layer,
sodium salt of A
H3O+
Ether layer, B,D
O
+
H+
OH
Ppt of A
filtration
Impure A
recrystallization
121
Pure A
OH
NH2
COOH
CH3
Ether layer, B + D
Shaken with HCl(aq)
Aqueous layer,
sodium salt of B
Ether layer, D
Evaporation
of ether
OH-
B + Aq. solution
Pure C (liquid)
Shaken with ether
B in ether layer
Evaporation
of ether
Pure B
122
(liquid)
OH
NH2
COOH
CH3
Reactivity of carboxylic acids and their
derivatives towards nucleophilic reactions
1. Aldehydes/ketones undergo AdN rather than SN
Carboxylic acids/derivatives undergo SN rather
than AdN
123
A discussion on the reactivity of carboxylic acids
and their derivatives towards nucleophilic rxs
1. Aldehydes/ketones undergo AdN rather than SN
Nu
R
R
O
C
Nu
H
Nu
R'
O
C
C
O
+
H
+
R'
Nu
R
R
C
H
O
Nu
O
C
R
R
R'
O
C
Nu
Strong bases,
unstable
124
Reactivity of carboxylic acids and their
derivatives towards nucleophilic reactions
1. Carboxylic acids/derivatives undergo SN rather
than AdN
Nu
R
R
O
C
Nu
L
125
C
O
R
L
O
+
C
L
Nu
Weak base,
stable
Nu
R
R
O
C
Nu
H
Nu
O
O
Nu
C
R'
O
C
Nu
R
R
R
L
C
O
+
R'
R
O
Nu
H
Nu
R'
C
+
C
R
R
C
H
O
Nu
O
C
R
L
O
+
C
L
Nu
Strength of bases : Cl < RCOO < HO < RO < H2N < R < H
126
Strength of acids : HCl > RCOOH > HOH > ROH > H2NH > RH > HH
Nu
R
R
O
C
Nu
L
C
R
L
O
+
C
L
Nu
O
Reactivity : O
(2)
R
O
R
C
O
>
C
Cl
O
'R
C
R
C
>
OH
O
127
>
O
R
C
O
>
O
R'
R
C
NH2
Reactivity : O
(2)
R
O
R
C
O
>
C
Cl
O
'R
C
>
R
C
O
>
OH
R
C
O
>
O
R
C
R'
O
Reasons : -
(i) Ease of leaving(Stability of bases) : Cl > RCOO > HO > RO > H2N > R > H
∵ Strength of bases : Cl < RCOO < HO < RO < H2N < R < H
128
NH2
Reasons : -
(ii) Resonance effect : Less stable
R
More reactive
More stable
Less reactive
R
C (2p)
O
R
C
Cl (3p)
Cl
O(2p)
O
C (2p)
O/N (2p)
R
C
O/N
Increasing resonance
effect
O (2p)
Efficiency of orbital overlap : 2p/2p > 3p/2p
129
Reactivity : O
(2)
R
O
R
O
>
C
Cl
'R
O
O
C
>
R
C
>
OH
C
R
C
O
>
O
R'
R
C
NH2
O
The less reactive derivatives can be prepared
from the more reactive derivative via
nucleophilic substitution reactions.
130
Preparation of
Acid Derivatives
131
Preparation of
Acid Derivatives
132
Preparation of
Acid Derivatives
133
Preparation of
Acid Derivatives
134
Preparation of
Acid Derivatives
Non-SN reactions
135
O
O
(3)
R
>
C
Cl
C – O  bond of benzoyl chloride
has less mesomeric effect
 Carbonyl C of benzoyl chloride
is less positive
 Less susceptible to nucleophilic
attack
136
C
Cl
O 

(4)
R
C +
Cl
>
+ C
Cl

The carbonyl C is attached to TWO
electron-withdrawing atoms
 more positive
 more susceptible to electrophilic attacks
137
O 

(4)
R
C +
Cl
>
+ C
Cl

Also, the nucleophile experiences less steric
hindrance with acyl chloride because the
reaction site is planar
138
A.
Preparation of Acid Chlorides
SOCl2 : thionyl chloride or sulphur oxychloride
139
(1)
Acid chloride with high b.p. (>170C)
O
O
R
+
C
OH
P Cl5
(s)
sublimes at 160℃
Higher b.p. than acid
chloride due to
intermolecular H-bonds
140
Phosphorus
oxychloride
R
C
+
Cl
P OCl3
+
HCl(g)
(l)
b.p. = 106℃
removed first by
fractional distillation
(2)
Acid chloride with high/intermediate/low b.p.
(85C < b.p. < 170C) or b.p. < 65C
O
R
O
+
C
OH
SOCl2
(l)
b.p. = 74.6℃
Most useful
141
R
+
C
Cl
SO2(g)
+
HCl(g)
can be removed
easily
(3)
Acid chloride with low b.p. (< 69C)
O
3 R
C
O
+
OH
PCl3 (l)
b.p. = 79℃
3 R
C
+
Cl
Removed first
by fractional
distillation
142
H3PO3(s)
decomposes
at 200℃
Q.76
s.t.=160C heat
+ PCl5(s)
COOH
b.p.=106C
COCl
b.p.=249C
+ POCl3(l) + HCl(g)
b.p.=197.2C
heat
COOH
+ SOCl2(l)
b.p.=74.6C
143
COCl
+ SO2(g) + HCl(g)
Q.76
O
O
heat
H3C
C
+
OH
b.p.=118C
PCl3(l)
H3C
C
b.p.=76C
Cl
b.p.51C
Removed first
by fractional
distillation
144
+ H3PO3(l)
d.c.200C
B. Preparation of Acid Anhydrides
O
(1)
O
R
R
O
C
pyridine
C
+
Cl
'R
O
C
OH
'R
+
C
O
Acyl chlorides must be stored in anhydrous
conditions
 they hydrolyze rapidly in the presence
of even a trace amount of water(p.122)
RCOCl + H2O  RCOOH + HCl
145
HCl
B. Preparation of Acid Anhydrides
O
(1)
O
R
R
O
C
pyridine
C
+
Cl
'R
O
C
OH
'R
C
O
R  R’  unsymmetrical anhydride
R = R’  symmetrical anhydride
146
+
HCl
B. Preparation of Acid Anhydrides
O
(1)
O
R
R
O
C
pyridine
C
+
'R
Cl
O
C
OH
'R
C
O
N
+
HCl
NH Cl
pyridine
Equilibrium position shifts to the right
Yield 
147
+
HCl
B. Preparation of Acid Anhydrides
O
(2)
O
R
O
C
pyridine
R
C
+
Cl
'R
O
C
O Na
'R
C
O
R  R’  unsymmetrical anhydride
R = R’  symmetrical anhydride
148
+
NaCl(s)
B. Preparation of Acid Anhydrides
O
(2)
O
R
O
C
pyridine
R
C
+
Cl
'R
O
C
O Na
'R
+
NaCl(s)
C
O
NaCl(s) produced is removed by precipitation
 Equilibrium position shifts to the right
 Yield 
149
B. Preparation of Acid Anhydrides
O
(3)
dehydrating agent
O
2R
R
C
P2O5
C
heat
OH
P4O10 = P2O5
O
R
Non-SN reaction
+
H2O
C
O
Only suitable for preparing symmetrical
anhydrides
150
Q.77
It gives a mixture of three acid anhydrides.
RCOOH + R’COOH
heat
P4O10
R
R
C
O
'R
O
151
'R
C
O
+
R
C
O
O
O
O
+
'R
C
O
C
C
O
Preparation of
Acid Amides
Ammonolysis
NH3
152
C. Preparation of Acid Amides
(1) Ammonolysis of Carboxylic Acids
The overall reaction is : O
O
heat
R
+
C
OH
(e xce ss)
153
H2N
H
breaking of ammonia
= ammonolysis
R
C
+
NH2
H2O
C. Preparation of Acid Amides
(1)
Ammonolysis of Carboxylic Acids
O
R
neutralization
+ NH3(aq)
C
R
O
dehydration
O
R
C
C
+ H2O
heat
OH
154
O NH4
NH2
C. Preparation of Acid Amides
(1)
Ammonolysis of Carboxylic Acids
O
O
R
+ NH3(aq)
C
R
O
excess RCOOH
R
C
+ H2O
C
heat
NH2
O NH4
OH
excess
prevent hydrolysis of the ammonium carboxylate
O
R
+ H2O(l)
C
O NH4
155
O
R
+ NH3(aq)
C
OH
excess
(2) Ammonolysis of Acid Chlorides(better method)
Acyl group
(Acylation of NH3/amines)
O
R
O
+
C
Cl
NH
(aq)
NH
33(aq)
(excess)
excess
R
C
R
Cl
R'NH
R’NH
22(aq)
o
(1)(1excess
)
O
'R
+
"R
R
(2 )
(2)
o
H
(2 ) excess
(2)
o
R
+
HCl
NHR'
C
(3 )
(3)
o
"R
156
HCl
C
O
N
+
Cl
+
O
C
C
HCl
(1o) NH2
(1)
O
R
+
Aminolysis
N
R'
(2) Ammonolysis of Acid Chlorides
(benzoylation of NH3/amines)
157
benzoyl group
Removed by excess NH3/amines
 Yield 
O
R
O
+
C
Cl
NH
(aq)
NH
33(aq)
(excess)
excess
R
C
R
Cl
R'NH
R’NH
22(aq)
o
(1)(1excess
)
O
'R
+
"R
R
+
HCl
(2o) NHR'
H
(2 ) excess
(2)
o
R
C
(3o) N
"R
158
HCl
C
O
N
+
Cl
+
O
C
C
HCl
(1o) NH2
O
R
+
R'
NOT applicable to 3 amine due to absence of H
'R
O
R
+
C
Cl
159
N
''R
R'''
no react ion
Further acylation is inhibited because amides
are weaker nucleophiles than amines
O
O
H 3C
H3C
C
NH2
160
C
NH2
The acyl and benzoyl derivatives of amines are
usually crystalline solids with sharp m.p..
Thus, amines can be identified by
1.
preparing their acyl/benzoyl derivatives
2. recrystallization
3. melting point determination
Similar to identification of carbonyl compounds
(pp.91-92)
161
Q. 78
Why is the impure solid dissolved in the
minimum quantity of hot solvent?
A hot solvent is used to ensure
maximum dissolution of target product
162
Q. 78
Why is the impure solid dissolved in the
minimum quantity of hot solvent?
If minimum quantity of solvent is used to
ensure
(a)
minimum dissolution of insoluble
impurities during hot filtration(step 3)
(b) minimum loss of target product
during suction filtration (step 5).
163
Q. 79
Why is hot filtration done in ways as
described by step 3 ?
(a)
Hot filtration is to minimize the
crystallization of filtrate on the funnel.
(b) A shot-stem funnel fitted with a
piece of fluted filter paper is
to speed up the filtration so as to
minimize the crystallization of filtrate
on the funnel.
164
Q. 80
Why are the crystals washed in ways as
described by step 6 ?
(a) Washing the crystals with the
mother liquor (a saturated solution)
can dissolve no more target product.
 the yield is not reduced
(b) Washing the crystals with solvent can
remove the mother liquor (containing
dissolved impurities) from the crystals
Only a little cold solvent is used to
minimize the loss of target product.
165
(3) Ammonolysis of Acid Anhydrides
(1)
(2)
The yield is increased by removing the products
with excess NH3 or amine
166
(4) Partial Hydrolysis of Nitriles
O
H2O
R
RCN
H+or OH-, reflux
Non-SN reaction
167
C
NH2
Further hydrolysis gives
carboxylic acids (in acidic medium) or
carboxylate in (basic medium).
168
Hydrolysis of amide = The reverse of ammonolysis of RCOOH
O
O
hydrolysis
R
C
+ NH3
OH
169
H2O
ammonolysis
R
O
hydrolysis
R
C
C
+ H2O
heat
O NH4
NH2
Preparation of
Esters
Alcoholysis
170
C. Preparation of Esters
(1)
Alcoholysis of Carboxylic Acids
O
O
+
R
C
+
R'OH
R’O
–H
H
R
reflux
OH
O
Esterification
171
+
C
R'
H2O
(2)
Alcoholysis of Acid Chlorides
O
O
-
OH
R
C
+
R'OH
R
+
C
Cl
O
HCl
R'
O
O
-
OH
R
+
C
Cl
OH
R
phenolysis
+
C
O
Faster and irreversible
OH ions serve to
(i)
172
 the yield by removing HCl
HCl
(2)
Alcoholysis of Acid Chlorides
O
O
-
OH
R
C
+
R'OH
R
+
C
Cl
O
HCl
R'
O
O
-
OH
R
+
C
OH
Cl
R
+
C
HCl
O
OH ions serve to
(ii) Speed up the nucleophilic attack by
generating the more powerful nucleophile.
OH
173
-
+ OH
O
+
H2O
(3)
Alcoholysis of Acid Anhydrides
O
R
C
O
R
O
O
C
+
R'OH
heat
R
+
C
O
R'
R
C
OH
O
Heating is required as acid anhydrides
are less reactive than acid chlorides
174
Reactions of the
Derivatives of
Carboxylic Acids
175
Nucleophilic Acyl Substitution
slow
HZ:  nucleophile
L  leaving group
176
fast
fast
Nucleophilic Acyl Substitution
slow
HZ:  nucleophile
L  leaving group
177
fast
fast
Nucleophilic Acyl Substitution
slow
fast
More stable
intermediate
Less steric hindrance than the
5-coordinated transition state of RX(SN2)
Obeying octet rule while the
3-coordinated carbocation of RX(SN1) is not
178
fast
Nucleophilic Acyl Substitution
slow
fast
HZ: = H-OH, H-OR,
H-NH2, H-NHR, H-NRR’
179
fast
A. Hydrolysis (Reactions with water)
HZ = H-OH
Decreasing reactivity
180
O
H3C C
Cl
O
H3C C
O
H3C C
O
O
H3C C
O CH 3
H2O
O
H3C C
OH
H2O
O
H3C C
OH
+
O
H3C C
OH
+
CH 3OH
O
H3C C
OH
+
H2N H
cold
+
+
HCl
O
H3C C
OH
catalysts
+
H2O
H+ or OHheat
catalysts
O
H3C C
NH 2
+
+
H2O
H+ or OHheat
Acid-catalyzed
Carbonyl C becomes more susceptible to
nucleophilic attacks
181
Base-catalyzed
OH ion is a stronger nucleophile than H2O
182
A. Hydrolysis (Reactions with water)
HZ = H-OH
Decreasing reactivity
183
O
H3C C
Cl
O
H3C C
O
H3C C
O
O
H3C C
O CH 3
O
H3C C
NH 2
H2O
O
H3C C
OH
H2O
O
H3C C
OH
+
O
H3C C
OH
+
CH 3OH
O
H3C C
OH
+
H2N H
cold
+
+
+
H2O
H+ or OHheat
+
H2O
H+ or OHheat
+
Or, CH3COO
HCl
O
H3C C
OH
B. Alcoholysis (Reactions with alcohols)
HZ = H-OR
Phenolysis (Reactions with phenols)
HZ = H-OAr
 Refer to the preparation of ester (p.121)
 Esters and amides do not undergo
alcoholysis/phenolysis
184
C. Ammonolysis (Reactions with NH3)
HZ = H-NH2
Aminolysis (Reactions with amines)
HZ = H-NHR, H-NRR’
 Refer to the preparation of amides
(pp.119-121)
 Amides do not undergo
ammonolysis/aminolysis
 Acid derivatives do not react with
3 amines
185
2. Reduction
A. LiAlH4 (p.95)
O
R C
Cl
O
R C
O
R C
O
O
R C
O R'
186
O
R C
NH 2
1. LiAlH4 / dry ether
2. H3O
+
1. LiAlH4 / dry ether
2. H3O
+
1. LiAlH4 / dry ether
2. H3O
+
1. LiAlH4 / dry ether
2. H3O
+
RCH 2OH
2RCH 2OH
RCH 2OH
RCH2NH2
+
R'OH
2. Reduction
B. H2/Pd poisoned with S (p.84)
High yield
187
3. Other reactions of acid amides
A. Hofmann Degradation
Cf. Iodoform reaction
188
One Carbon less
Synthetic application
CH3CH2OH
189
B. Dehydration
O
R C
NH 2
190
P2O5
heat
R C N
+
H2O
RCOOH / RCN cycle : -
191
Q. 81
Nylon 6,6
192
(excess)
The END
193
Back
Give the IUPAC names for the following compounds:
(a)
(b)
(c)
(d)
194
(a)
(b)
(c)
(d)
3-Methylbutanoic acid
N-Methylethanamide
Ethyl benzoate
Benzoic anhydride
Answer
An ester is formed by reacting an alcohol with a carboxylic
acid. Draw the structural formulae of the following esters
and in each case, give the names of the alcohol and the
carboxylic acid that form the ester.
(a) Methyl ethanoate
(a) The structural formula of methyl ethanoate is:
It is formed from the reaction of ethanoic acid and
methanol.
195
Answer
32.2 Nomenclature of Carboxylic Acids and their Derivatives (SB p.26)
Back
An ester is formed by reacting an alcohol with a carboxylic
acid. Draw the structural formulae of the following esters
and in each case, give the names of the alcohol and the
carboxylic acid that form the ester.
(b) Ethyl methanoate
(b) The structural formula of ethyl methanoate is:
It is formed from the reaction of methanoic acid and
ethanol.
196
Answer
Answer
Complete the following table.
Molecular
Structural formula
formula
C3H7COOH
197
(a)
IUPAC name
(b)
(c)
(d)
(e)
(f)
(g)
(h)
Trichloroethanoic
acid
Back
(a)
(b) Butanoic acid
(c) CH3CH(CH3)CH2COOH
(e) C6H4ClCOOH
(g) CCl3COOH
(d) 3-Methylbutanoic acid
(f) 2-Chlorobenzoic acid
(h)
198
(a) Propanoic acid has a boiling point of 141°C which is
considerably higher than that of butan-1-ol (117°C),
although they have the same molecular mass. Explain
why.
Answer
199
(a) Each propanoic acid molecule forms two intermolecular hydrogen
bonds with other propanoic acid molecules. However, each butan1-ol molecule can form only one intermolecular hydrogen bond with
other butan-1-ol molecules. Since molecules of propanoic acid form
more extensive intermolecular hydrogen bonds than those of
butan-1-ol, the boiling point of propanoic acid is higher than that of
butan-1-ol.
200
(b) Arrange the following compounds in decreasing order of
solubility in water:
CH3CH2CH2COOH, CH3CH2COOCH3, CH3COOH
Answer
(b) The solubility of the compounds in water decreases in
the order:
CH3COOH > CH3CH2CH2COOH > CH3CH2COOCH3
201
(c) Propanedioic acid forms intramolecular hydrogen bonds.
Draw its structural formula, showing clearly the
formation of intramolecular hydrogen bonds.
Answer
(c)
Back
202
Write the chemical equations for the acid-catalyzed and
alkali-catalyzed hydrolyses of each of the following
compounds:
(a) Ethyl butanoate
(a)
203
Answer
Write the chemical equations for the acid-catalyzed and
alkali-catalyzed hydrolyses of each of the following
compounds:
(b) Propanamide
(b)
204
Answer
Back
Write the chemical equations for the acid-catalyzed and
alkali-catalyzed hydrolyses of each of the following
compounds:
(c) Benzoyl chloride
(c)
205
Answer
Outline how a mixture of butanone and ethanoic acid can
be separated in the laboratory.
Answer
Back
206
(a) Complete and balance the following chemical equations:
(i)
(ii)
Answer
207
(a) (i)
(ii)
208
(b) Complete the following chemical equations:
(i)
(ii)
(iii)
Answer
209
(b) (i)
(ii)
(iii)
Back
210
Explain why ethanoyl chloride must be protected from
atmospheric moisture during storage.
Answer
This is because ethanoyl chloride reacts
readily with water (from atmospheric
moisture) to form ethanoic acid.
Back
211
The characteristic reaction of the derivatives of
carboxylic acids is nucleophilic acyl substitution.
Arrange the derivatives of carboxylic acids in
decreasing order of reactivity towards nucleophilic acyl
substitution.
Answer
Acyl chlorides > acid anhydrides > esters > amides
Back
212
Draw the structural formulae of the missing compounds
A to H:
(a)
(b)
(c)
213
Answer
(a)
(b)
(c)
214
Draw the structural formulae of the missing compounds
A to H:
(d)
(e)
(f)
Answer
215
Back
(d)
(e)
(f)
216