Chapter 17
Carboxylic Acids
and Their Derivatives
Nucleophilic
Addition–Elimination
at the Acyl Carbon
Created by
Professor William Tam & Dr. Phillis Chang
Ch. 17 - 1
About The Authors
These PowerPoint Lecture Slides were created and prepared by Professor
William Tam and his wife, Dr. Phillis Chang.
Professor William Tam received his B.Sc. at the University of Hong Kong in
1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an
NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard
University (USA). He joined the Department of Chemistry at the University of
Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and
Associate Chair in the department. Professor Tam has received several awards
in research and teaching, and according to Essential Science Indicators, he is
currently ranked as the Top 1% most cited Chemists worldwide. He has
published four books and over 80 scientific papers in top international journals
such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem.
Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her
M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She
lives in Guelph with her husband, William, and their son, Matthew.
Ch. 17 - 2
1. Introduction
 Carboxylic Acid Derivatives
O
O
O
OH
R
carboxylic acid
R'
O
R
acid anhydride
Cl
R
acid chloride
O
O
R
OR'
ester
O
R
NR'2
amide
Ch. 17 - 3
2. Nomenclature and Physical
Properties
 Nomenclature of Carboxylic Acids and
Derivatives
● Rules
 Carboxylic acid as parent
(suffix): ending with “–oic acid”
 Carboxylate as parent (suffix):
ending with “–oate”
Ch. 17 - 4
 Most anhydrides are named by
dropping the word acid from the
name of the carboxylic acid and
then adding the word “anhydride”
 Acid chloride as parent (suffix):
ending with “–oyl chloride”
 Ester as parent (suffix): ending
with “–oate”
 Amide as parent (suffix): ending
with “amide”
 Nitrile as parent (suffix): ending
with “nitrile”
Ch. 17 - 5

Examples
O
O
OH
Ethanoic acid
(acetic acid)
O
O
O
Ethanoic anhydride
(acetic anhydride)
OCH3
Methyl propanoate
O
NH'2
Ethanamide
Ch. 17 - 6

Examples
O
O
O
Cl
Na
Sodium benzoate
Benzoyl chloride
H3C
C
N
Ethanenitrile
Ch. 17 - 7
2C. Acidity of Carboxylic Acids
O
R
O
H
pKa ~ 4-5
 Compare
● pKa of H2O ~ 16
● pKa of H2CO3 ~ 7
● pKa of HF ~ 3
Ch. 17 - 8

When comparing acidity of organic
compounds, we compare the stability
of their conjugate bases. The more
stable the conjugate base, the stronger
the acid
pKa
CH3COOH
CH3CH2OH
4.75
16
Ch. 17 - 9
O
CH3
O
O
H
+ H2O
A1
CH3CH2
A2
CH3
O
+ H3O+
B1
O
H + H2O
CH3CH2
O + H3O+
B2
Ch. 17 - 10

The conjugate base B1 is more stable
(the anion is more delocalized) than B2
due to resonance stabilization
O
CH3
O
O
CH3
O
O
CH3
O
● Thus, A1 is a stronger acid than
A2
Ch. 17 - 11

Acidity of Carboxylic Acids, Phenols and
Alcohols
O
O
O
pKa = 4.20
H
O
H
H
pKa = ~ 10
pKa = ~ 17
Ch. 17 - 12

Acidity of Carboxylic Acids, Phenols and
Alcohols
O
O
O
H
O
+ H2O
+ H3O+
O
O
Ch. 17 - 13

Acidity of Carboxylic Acids, Phenols and
Alcohols
O
O
H
+ H3O+
+ H2O
O
O
O
Ch. 17 - 14

Acidity of Carboxylic Acids, Phenols and
Alcohols
O
H
O
+ H2O
+ H3O+
(NO resonance
stabilization)
Ch. 17 - 15
Question
 If you are given three unknown
samples: one is benzoic acid; one is
phenol; and one is cyclohexyl alcohol;
how would you distinguish them by
simple chemical tests?
● Recall: acidity of
O
O
O
H
O
H
H
>
>
Ch. 17 - 16
O
O
R
O
H + Na
OH
R
+ H2O
O Na
(soluable in water)
O
H
O Na
+ NaOH
(soluble in water)
O
(immiscible
with H2O)
H
+ NaOH
No Reaction
Ch. 17 - 17
O
O
O
H
+ NaHCO3
O Na
+ CO2(g) + H2O
(gas evolved)
O
O
H
H
+ NaHCO3
No Reaction
+ NaHCO3
No Reaction
Ch. 17 - 18
O
O
Cl
OH
Cl
Cl
>
pKa

H
0.70
> H
OH H
H
1.48
OH
H
4.76
2.86
Stability of conjugate bases
O
O
Cl
Cl
>
Cl
O
> Cl
OH H
Cl
Cl
O
Cl
H
Cl
O > Cl
O > H
H
O
O
O
O > H
H
H
Ch. 17 - 19
O
O
>
Cl
>
OH
Cl
2-Chlorobutanoic acid
(pKa = 2.85)
OH
3-Chlorobutanoic acid
(pKa = 4.05)
O
Cl
OH
4-Chlorobutanoic acid
(pKa = 4.50)
Ch. 17 - 20
2D. Dicarboxylic Acids
pKa
(at 25oC)
Common
Name
mp (oC)
pK1
pK2
Oxalic acid
189 dec
1.2
4.2
HO2CCH 2CO2H
Malonic acid
136
2.9
5.7
HO2C(CH 2)4CO2H
Adipic acid
153
4.4
5.6
Phthalic acid
206-208 dec
2.9
5.4
Structure
HO2C
CO2H
CO2H
CO2H
Ch. 17 - 21
2J. Spectroscopic Properties of
Acyl Compounds
 IR Spectra
●
●
The C=O stretching band occurs at
different frequencies for acids, esters,
and amides, and its precise location is
often helpful in structure determination
Conjugation and electron-donating
groups bonded to the carbonyl shift
the location of the C=O absorption to
lower frequencies
Ch. 17 - 22
 IR Spectra
●
●
●
Electron-withdrawing groups bonded to
the carbonyl shift the C=O absorption
to higher frequencies
The hydroxyl groups of carboxylic acids
also give rise to a broad peak in the
2500-3100-cm-1 region arising from O–
H stretching vibrations
The N–H stretching vibrations of
amides absorb between 3140 and 3500
cm-1
Ch. 17 - 23
Ch. 17 - 24
Ch. 17 - 25
 1H NMR Spectra
● The acidic protons of carboxylic
acids are highly deshielded and
absorb far downfield in the d 10-12
region
● The protons of the a carbon of
carboxylic acids absorb in the d
2.0-2.5 region
Ch. 17 - 26
Ch. 17 - 27

13C
NMR Spectra
● The carbonyl carbon of carboxylic
acids and their derivatives occurs
downfield in the d 160-180 region
(see the following examples), but
not as far downfield as for
aldehydes and ketones (d 180220)
● The nitrile carbon is not shifted so
far downfield and absorbs in the d
115-120 region
Ch. 17 - 28

13C
NMR chemical shifts for the
carbonyl or nitrile carbon atom
H3C
O
O
O
C
C
C
H3C
OH
H3C
OEt
d 170.3
d 170.7
d 177.2
Cl
O
H3C
C
NH2
d 172.6
H3C
C
N
d 117.4
Ch. 17 - 29
3.
Preparation of Carboxylic Acids
 By oxidation cleavage of alkenes
●
Ph
Using KMnO4
1. KMnO4, OH, heat
2. H3O+
OH
Ph
●
O
+
OH
Using ozonolysis
1. O3
O
HO
O
OH
O
2. H2O2
Ch. 17 - 30
 By oxidation of aldehydes & 1o alcohols
● e.g.
H
OH
1. Ag2O
2. H3O+
O
O
OH
OH
1. KMnO4, OH, heat
O
+
2. H3O
O
O
H
or
OH
H2CrO4
OH
Ch. 17 - 31
 By oxidation of alkyl benzene
O
R
1. KMnO4, OH, heat
OH
2. H3O+
(R = 1o or 2o alkyl groups)
Ch. 17 - 32
 By oxidation of benzene ring
● e.g.
1. O3, CH3COOH
2. H2O2
O
OH
Ch. 17 - 33
 By hydrolysis of cyanohydrins and
other nitriles
● e.g.
O
O
Ph
HCN
CH3
Br
NC
Ph
HCN
H+
OH
CH3
H2O
+
CN
H
H2O, heat
HO
Ph
C
OH
CH3
O
C
OH
Ch. 17 - 34
 By carbonation of Grignard reagents
● e.g.
Br
Mg
MgBr
Et2O
1. CO2
2. H3O+
O
OH
Ch. 17 - 35
4.
Acyl Substitution: Nucleophilic
Addition-Elimination at the Acyl Carbon
O
O
+
R
Nu
Y
R
Nu
Y
O
Y
+
R
Nu
(Y = leaving group, e.g. OR, NR2, Cl)

This nucleophilic acyl substitution occurs
through a nucleophilic addition-elimination
mechanism
Ch. 17 - 36
 This type of nucleophilic acyl
substitution reaction is common for
carboxylic acids and their derivatives
O
O
R
OH
carboxylic acid
O
R
Cl
acid chloride
OR'
ester
R
O
R'
acid anhydride
O
O
R
O
R
NR'2
amide
Ch. 17 - 37
 Unlike carboxylic acids and their
derivatives, aldehydes & ketones
usually do not undergo this type of
nucleophilic acyl substitution, due to
the lack of an acyl leaving group
O
A good
leaving
group
R
Y
a carboxylic acid
derivative
O
R
O
H
R
R'
Not a good
leaving group
Ch. 17 - 38
 Relative reactivity of carboxylic acid
derivatives towards nucleophilic acyl
substitution reactions
● There are 2 steps in a nucleophilic
acyl substitution
 The addition of the nucleophile
to the carbonyl group
 The elimination of the leaving
group in the tetrahedral
intermediate
Ch. 17 - 39
● Usually the addition step (the first
step) is the rate-determining step
(r.d.s.). As soon as the tetrahedral
intermediate is formed, elimination
usually occurs spontaneously to
regenerate the carbonyl group
● Thus, both steric and electronic
factors that affect the rate of the
addition of a nucleophile control
the reactivity of the carboxylic acid
derivative
Ch. 17 - 40
● Steric factor
e.g.
reactivity of
O
O
Cl
>
Cl
● Electronic factor
 The strongly polarized acid
derivatives react more readily
than less polar ones
Ch. 17 - 41
● Thus, reactivity of
O
O
O
O
>
R
Cl
most
reactive
O
>
R
O
R'
>
R
OR'
R
NR'2
least
reactive
● An important consequence of this
reactivity
 It is usually possible to convert
a more reactive acid derivative
to a less reactive one, but not
vice versa
Ch. 17 - 42
5. Acyl Chlorides
5A. Synthesis of Acyl Chlorides
 Conversion of carboxylic acids to acid
chlorides
O
O
R
OH
R
Cl
● Common reagents
 SOCl2
 (COCl)2
 PCl3 or PCl5
Ch. 17 - 43
● Mechanism
O
Cl
Cl
O
O
O
O
R
R
OH
O
Cl
R
O
Cl
Cl
O
O
Cl
O
O
O
R
Cl
O
O
Cl
O
O
R
Cl
+ CO2 + CO + Cl
Ch. 17 - 44
 Nucleophilic acyl substitution reactions
of acid chlorides
● Conversion of acid chlorides to
carboxylic acids
O
R
Cl
+ H2O
O
base
R
OH
Ch. 17 - 45
● Mechanism
O
R
OH
O
H2O
Cl
R
O
Cl
H +
R
R
OH
Cl
H
H
O
B
H
B:
OH
R
O
OH
Ch. 17 - 46
● Conversion of acid chlorides to
other carboxylic derivatives
O
R'OH
pyridine
O
R
(ester)
R
O
R'2NH
Cl
OR'
(amide)
R
NR'2
O
R'
O
O Na
O
(acid anhydride)
R
O
R'
Ch. 17 - 47
6. Carboxylic Acid Anhydrides
6A. Synthesis of Carboxylic Acid
Anhydrides
O
O
+
+
R
OH
R'
Cl
N
O
O
+
R
O
R'
Cl
N
H
Ch. 17 - 48
O
O
O
O
+ Na Cl
+
R
O Na
R'
O
Cl
R
O
R'
O
300oC
OH
O + H2O
OH
Succinic
O acid
O Succinic
anhydride
O
O
OH
OH
Phthalic
acid
O
230oC
O
Phthalic anhydride O
(~100%)
+
H2O
Ch. 17 - 49
6B. Reactions of Carboxylic Acid
Anhydrides
 Conversion of acid anhydrides to
carboxylic acids
O
R
O
O
R'
+ H2O
O
+
H
O
+
R
OH
HO
R'
Ch. 17 - 50
● Mechanism
O
R
O
O
O
H+
R'
R
H
O
OH
O
R'
H2O
R
H
O
R
H2O
OH
H
R
O
O
O
H
OH
O
OH
+ R'COOH
R
OH
R'
O
O
R'
H
Ch. 17 - 51
 Conversion of acid anhydrides to other
carboxylic derivatives
O
R'OH
R
O
R
O
OR'
+
R
OH
O
O
R'
O
R2'NH
R
O
NR'2
+
R
O
NR'2H2
Ch. 17 - 52
7. Esters
7A. Synthesis of Esters: Esterification
O
+ R'OH
R
OH
O
+
H
+ H2O
R
OR'
Ch. 17 - 53

Mechanism
O
R
H+
O
OH
H
H
R
O
"activated"
O
R
O
H
H2O
OR'
H
R
O
R'OH
R
OH
O
H
R'
OH2
OR'
R
HO
OR'
Ch. 17 - 54

e.g.
Esters from acyl chlorides
O
Cl
Benzoyl
chloride
+ EtOH +
N
O
OEt
Ethyl benzoate
(80%)
+
Cl
N
H
Ch. 17 - 55
Esters from carboxylic acid anhydrides

e.g.
O
O
OH
+
O
Acetic
anhydride
Benzoyl
alcohol
O
O
Benzoyl acetate
O
+
OH
Ch. 17 - 56
7B. Base-Promoted Hydrolysis of
Esters: Saponification
 Hydrolysis of esters under basic
conditions: saponification
O
R
O
OH
OR'
H2O
+
R
R'OH
O
Ch. 17 - 57

Mechanism
O
O
R
OR'
OH
R
HO
OR'
O
R
H+
O
R
OH
O
H + OR'
O
R'OH +
R
O
Ch. 17 - 58

Hydrolysis of esters under acidic
conditions
O
R
O
H+
OR'
H2O
+
R
R'OH
OH
Ch. 17 - 59

Mechanism
O
R
O
H+
OR'
R
H
OR'
OH
H2O
R
H
O
R
H2O
OH
H
R
O
OR'
H
OH
O
OH
+ R'OH
R
OH
O
R'
H
Ch. 17 - 60
7C. Lactones

Carboxylic acids whose molecules
have a hydroxyl group on a g or d
carbon undergo an intramolecular
esterification to give cyclic esters
known as g- or d-lactones
Ch. 17 - 61
R
d
g
O


+ H
O
O
O
OH
H
HO
O
a d-hydroxyacid
A
H
O
A
H
H
O
H
O
R
H +
H
H
R
O
O
H
O
O
+ O
H
H
H
R
a d-lactone
R
Ch. 17 - 62

Lactones are hydrolyzed by aqueous
base just as other esters are
O
O
H+/H2O
O
C6H5
HA, slight excess
C6H5
OH
0oC
HA, exactly
1 equiv.
O
C6H5
O
OH
OH
Ch. 17 - 63
8. Amides
8B. Amides from Acyl Chlorides
O
O
R
R
Cl
Cl
H
N
:NHR'R"
R"
R'
O
Cl
+ R'R"NH2 +
R
O
N
R'
R"
R
R"R'HN:
R"
N
R'
:Cl:
H
Ch. 17 - 64
8C. Amides from Carboxylic
Anhydrides
O
O
H
+ 2
R
O
R
N
R'
R"
O
R
H
O
N
R'
+
H
R
O
N
R'
R"
R"
R', R" can be H, alkyl, or aryl.
Ch. 17 - 65
O
O
O + 2 NH3
Phthalamic
anhydride
O
H2O
NH2
warm
O NH4
O
NH2
OH
H3O+
O Ammonium
phthalamate
(94%)
(- NH4+)
Phthalamic acid
O
(81%)
Ch. 17 - 66
O
O
NH2
150-160oC
N
OH
O
Phthalamic acid
+ H2O
H
O
Phthalimide
(~ 100%)
Ch. 17 - 67
8D. Amides from Esters
O
O
H
+
R
OR'"
N
R'
R
R"
N
R'
+ R'"OH
R"
R' and/or R" may be H.
e.g.
O
O
OMe
MeNH2
N
heat
H
Me
+ MeOH
Ch. 17 - 68
8E. Amides from Carboxylic Acids and
Ammonium Carboxylates
O
R
O
OH
+
NH3
R
O NH4
heat
O
H2O +
R
NH2
Ch. 17 - 69

DCC-Promoted amide synthesis
O
R
O
1. DCC
OH
2. R'NH2
R
N
R'
+
DCU
H
Ch. 17 - 70
Mechanism

C6H11
C
C
O:
:
+
:N
H
O
C6H11
C
:
H
N
N:
:
:
C
:O
R
:
R
N
:
:
O:
C6H11
C6H11
:
Dicyclohexylcarbodiimide
(DCC)
R
N
O
C
:
O
:
H
: :
C
C6H11
N:
C6H11
Ch. 17 - 71
Mechanism (Cont’d)
C6H11
C
proton
R
:
transfer
:
:
: :
O
C6H11
R'
C
NH2
NHC6H11
:
NH2
reactive intermediate
:
C
: :
R
N
C
NHC6H11
C6H11
O
O
C6H11
:
N:
C
N
: :
O
:
C
O:
:
H
N
:
:
R
O
: :

:
:
O:
R'
+
C
an amide
O
C
NHC6H11
:
NHR'
: :
R
NHC6H11
N,N'-Dicyclohexylurea
(DCU)
Ch. 17 - 72
8F. Hydrolysis of Amides

Acid hydrolysis of amides
O
R
O
+
H
NH2
H2O, heat
R
OH
+ NH4
Ch. 17 - 73

Mechanism
R
NH2
O
:O :
OH
H2O
NH2
H
R
H
NH2
:
R
O
H+
:
:O :
H
O
H
: OH
:
R
OH
R
OH
+ NH3
R
HO
NH3
Ch. 17 - 74

Basic hydrolysis of amides
O
R
O

OH
NH2
H2O, heat
R
O
+ NH3
Ch. 17 - 75
Mechanism

O
R
OH
NH2
O
O
R
HO
NH2
R
O
H + NH2
O
NH3
+
R
O
Ch. 17 - 76
8G. Nitriles from the Dehydration of
Amides
:O :
P4O10 or (CH3CO)2O
:
R
NH2

heat
(H2O)
N: + H3PO4
(or CH3CO2H)
(a nitrile)
R
C
This is a useful synthetic method for
preparing nitriles that are not
available by nucleophilic substitution
reactions between alkyl halides and
cyanide ions
Ch. 17 - 77

e.g.
O
NH2
P4O10
C
N
dehydration
Ch. 17 - 78

Example
● Synthesis of
C
N
NaCN
Br
DMSO
CN
1o alkyl bromide
 SN2 reaction with
⊖CN works fine
Ch. 17 - 79
CN
But synthesis of
Br
NaCN
DMSO
No Reaction!
3o alkyl bromide
 No SN2 reaction
Ch. 17 - 80
Solution
Br
O
1. Mg, Et2O
OH
2. CO2
3. H3O+
1. SOCl2
2. NH3
O
CN
P4O10
NH2
dehydration
Ch. 17 - 81
8H. Hydrolysis of Nitriles
R

C
N
O
base or acid
H2O, heat
R
OH
Catalyzed by both acid and base
Ch. 17 - 82

Examples
CN
OH
H2SO4
H2O, 
O
(82%)
OH
CN
1. NaOH, H2O, 
+
2. H3O
O
(68%)
Ch. 17 - 83
Mechanism

C
N:
H
R
NH
C
NH + : O
H +
:O
C
H
NH
:
R
NH
:
R
NH2
O:
C
H
H2O
:
O
:
H
H
H
slow
:
amide
tautomer
H
O:
C
C
H
:
R
O
:
H
H
R
H
:
R
protonated nitrile
protonated
amide
H
several steps
C
(amide hydrolysis)
NH2
:
R
O:
O
R
+
OH
NH4
Ch. 17 - 84
R
H
:
HO
OH
H
: :
NH2
R
OH
OH
OH
H
NH
OH
H
O
:
NH2
O
OH
HO
:
:
H
HO
HO
O
R
H
R
OH
O
:
: :
H
NH2
R
:
+
O
O
NH
N:
O
R
OH
: :
C
H
N
:
R
Mechanism
:

H
O
OH
R
O
+ NH3 +
OH
Ch. 17 - 85
8I. Lactams
O
O
O



NH

H
N
O
S
N
O
g
a g-lactam
a -lactam
R
NH
CH3
CH3
CO2H

NH

d
g
a d-lactam
R = C6H5CH2
Penicillin G
R = C6H5CH
Ampicillin
NH2
R = C6H5OCH2
Penicillin V
Ch. 17 - 86
9. Derivatives of Carbonic Acid
9A. Alkyl Chloroformates and
Carbamates (Urethanes)

Alkyl chloroformate
O
ROH +
Cl
O
Cl
RO
Cl
+ HCl
alkyl
chloroformate
Ch. 17 - 87

e.g.
OH
O
+
RO
Cl
O
HCl
+
O
Cl
Benzyl
chloroformate
Ch. 17 - 88

Carbamates or urethanes
O
RO
O
Cl
+
R'NH2
OH
RO
NHR'
a carbamate
(or urethane)
Ch. 17 - 89

protected amine
Protection
O
O
R
O
NH2 +

N
OH
R
N
O
H
Deprotection
H2, Pd
O
R
Cl

R
NH2 + CO2 +
O
H
HBr, CH2CO2H
R
NH3 + CO2 +
Br
Ch. 17 - 90
10. Decarboxylation of Carboxylic
Acids
O
R
OH
O
R
decarboxylation
O
R
O
o
100-150 C
OH
H + CO2
R
+ CO2
A -keto acid
Ch. 17 - 91
There are two reasons for this ease of
decarboxylation
O
H
O
R
O
CO2
-keto acid
R
ketone
enol
O
: :
O
CO2
: :
R
O
R
O
O
H
O:
HA
:
R
O
: :

R
acylacetate ion
:
O
: :
R
resonance-stabilized
anion
Ch. 17 - 92
11. Chemical Tests for Acyl
Compounds

Recall: acidity of
O
O
O
H
O
H
H
>
>
Ch. 17 - 93
O
R
O
O
H + Na
OH
R
+ H2O
O Na
(soluable in water)
O
H
O Na
+ NaOH
(soluble in water)
O
(immiscible
with H2O)
H
+ NaOH
No Reaction
Ch. 17 - 94
O
O
O
H
+ NaHCO3
O
Na
+ CO2(g) + H2O
(gas evolved)
O
O
H
H
+ NaHCO3
No Reaction
+ NaHCO3
No Reaction
Ch. 17 - 95
12. Polyesters and Polyamides:
Step-Growth Polymers

Polyesters
HO
m
O
OH + HO
O
n
OH
-H2O
O
O
O
m
(a polyester)
O
n
Ch. 17 - 96

Polyamides
O
H2N
m
N
H
+
O
n
Cl
Cl
H
-HCl
H
H
N
N
O
m
(a polyamide)
O
n
Ch. 17 - 97
Example: Nylon 66

O
OH
n HO
NH2
+ n H2N
O
heat
H
O
N
O
(Nylon 66)
●
+ 2n H2O
N
H
n
Applications: clothing, fibers, bearings
Ch. 17 - 98
Example: Dacron (Mylar)

O
O
n
CH3O
OCH3
+
OH
n HO
200oC
O
O
O
+ 2n CH3OH
O
(Dacron)
●
n
Applications: film, recording tape
Ch. 17 - 99
13. Summary of the Reactions of
Carboxylic Acids and Their Derivatives

O
Reactions of carboxylic acids
O
R
C
OH
R
1. P, X2
2. H2O
X
1. LiAlH4
R
+
O
OH
R'OH, H+, 
R
O
O
C
C
O
R'
R'
base
Cl
SOCl 2
or PCl3
or PCl5
C
R
2. H2O, H
O
O
NaOH or NaHCO3
or other bases
O
RCH2OH
C
OR'
O
R
C
Cl
Ch. 17 - 100
Reactions of acyl chlorides

O
R
O
NR'
R
OH
H2O
R'2NH
O
R
Cl
R'OH, base
O
R
R'COOH
base
O
O
R'
O
R
OR'
Ch. 17 - 101
Reactions of acyl chlorides (Cont’d)

O
R
R
1. LiAlH4
benzene
AlCl 3
R
Cl
1. LiAlH(OtBu)3, -78oC
2. H3O+
O
1. R'MgX
R'
R'
2. H3O+
O
R
OH
2. H3O+
OH
R
H
Ch. 17 - 102

Reactions of acid anhydrides
O
R
O
OH
+
HO
R'
H2O
O
R"2NH
R
O
R
O
O
R"OH
R'
O
O
NR"
+
R'
O NR"2H2
R
O
OR"
+
HO
R'
Ch. 17 - 103
Reactions of esters

O
R
OH
H
1. DIBAL, -78oC
2. H3O+
1. LiAlH4
2. H3O+
OH
R
R
R"
R
R
NH3
O
NH2
R
OH
H2O, H+, 
O
O
1. R"MgX
2. H3O+
R"
O
OR'
1. OH2. H2O, H+
R"OH, H+, 
R
OH
O
R
OR"
Ch. 17 - 104

Reactions of nitriles
R
O
NH2
R
H+, H2O, 
1. LiAlH 4
2. H3O+
R
C
N
1. LiAlH(O tBu)3
R
OH, H2O, 
O
or DIBAL, -78oC
O
2. H3O+
H
OH
R
O
Ch. 17 - 105

Reactions of amides
O
R
+ HNR'2
OH
H2O, H+ or OH-
P4O10 (P2O5)
or Ac2O, D
(R' = H only)
O
R
N
R'
1. LiAlH4
2. H3O+
R'
R
C
N
R
NR'2
Ch. 17 - 106
 END OF CHAPTER 17 
Ch. 17 - 107