1

Jully Tan
School of Engineering
EP101 / EG101 2
Learning Outcome
At the end of this chapter, students are able to:

Provide nomenclature of the carboxylic acid & its derivatives
Physical properties of carboxylic acid
Synthesis and reaction of carboxylic acid & its derivatives

EP101 / EG101 3
Chapter 18
Carboxylic Acids and Their Derivatives:
Nucleophilic Addition-Elimination at the Acyl Carbon
Carboxylic acids are a family of organic compounds with the
functional group
-C-OH
O=
which is also written as -CO
2
H or COOH.
The carbon-oxygen double bond is made up of a -bond and a -bond.
The carbon atom is sp
2
hybridized, which explains the trigonal planar
geometry at this center.
C O
R
HO

R may be alkyl, aryl or simply H

EP101 / EG101 4
Naming Rules
Uses the name of alkane that corresponds to the longest continuous chain of the
carbon atom.
The final e in the alkane name is replaced by suffix oic acid
The chain is numbered, starting with carboxyl carbon (COO
-
) atom as C1.
Position of the substituent is indicated by a number.
Acid which has C=O attached to ring are named by adding the name carboxylic
acid to the name of the cyclic compound.
When the acid has C=C in their structure, stereochemical term of cis and trans or E
and Z are used as they are with other alkenes.
EP101 / EG101 5
IUPAC Names
Remove -e from alkane (or alkene) name, add -oic acid.
The carbon of the carboxyl group is #1.
CH
3
CH
2
CHC
Cl
OH
O
2-chlorobutanoic acid
Ph
C
H
C
H
COOH
trans-3-phenyl-2-propenoic acid
EP101 / EG101 6
Naming Cyclic Acids
Cycloalkanes bonded to -COOH are named as cycloalkanecarboxylic acids.
Aromatic acids are named as benzoic acids.
COOH
CH(CH
3
)
2
2-isopropylcyclopentanecarboxylic acid
COOH
OH
o-hydroxybenzoic acid
Aromatic Acids: Benzoic Acids
The carboxylic acids derived from benzene are named as derivatives
of benzoic acid, using the standard notations to indicate positions of
substituent groups.
COOH
Benzoic acid
COOH COOH
NO
2
m-Nitrobenzoic acid
NO
2
Cl
2-Chloro-4-nitrobenzoic acid
Salts of Carboxylic Acids
To name a salt, use the name of the cation (sodium, ammonium, etc.)
followed by the name of the acid with "ic acid" changed to "ate."
CO
2
-
Na
+
(CH
3
CH
2
CO
2
-
)
2
Mg
2+
Sodium benzoate
Magnesium propanoate
or
Magnesium propionate
EP101 / EG101 7
Physical Properties of Carboxylic acids
Carboxylic acids are polar protic molecules. They form strong
hydrogen bonds. One example of this is that they exist as dimers
in the liquid state.
C
O
O-H
R
O
C
H-O
R
The boiling points are about
20
o
C higher than alcohols of
comparable size.
Carboxylic acids, in neutral solvents, have solubility properties
similar to those of alcohols. The first members of the aliphatic series
(formic acid through butanoic acid) are miscible with water. Water
solubility decreases with increasing chain length, with hexanoic acid
being marginally soluble. On neutralization, because of ionic salt
formation, most carboxylic acids become water soluble.
EP101 / EG101 8
Boiling Points
Higher boiling points than similar alcohols, due to dimer formation, resulting from the
association of two molecules of the acid, facilitated by hydrogen bonding.
Carbonyl compound have the following relative BP:

Amide>COOH>nitrile>ester=acyl chloride>aldehyde>ketone
EP101 / EG101 9
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.

EP101 / EG101 10
The Acid Strength of Carboxylic Acids
Carboxylic acids are weaker acids than mineral acids like HCl,
HNO
3
, or H
2
SO
4
, but they are more acidic than organic weak
acids such as aliphatic alcohols. Carboxylic acids are converted
into their carboxylate salts by aqueous solutions of hydroxide.
RCOOH
HO
-
/H
2
O
H
3
O
+
RCO
2
-
Carboxylate anion
of resulting salt
Aqueous solutions of mineral acids convert the salts
back into the carboxylic acids.
Large carboxylic acids with limited or no solubility in water
(those with 6 or more C's per carboxyl group) may be solubilized
through their carboxylate salts:
R-COOH + Na
+ -
OH
H
2
O
R-CO
2
-
Na
+
+ H
2
O
Water
insoluble
Water
soluble
These solubility properties are the basis for separating
carboxylic acids from neutral organic compounds.
EP101 / EG101 11
A Comparison of the Acid Strength of
Carboxylic Acids and Alcohols
Carboxylic acids are considerably more acidic than alcohols in the
absence of special electronic influences.
RCOOH + H
2
O RCO
2
-

+ H
3
O
+
pK
a
~ 5
ROH + H
2
O RO
-

+ H
3
O
+
pK
a
~ 16
The enhanced acidity of carboxylic acids is attributed to the greater
stability of the carboxylate anion compared with the alkoxide anion,
which shifts the equilibrium more to the product side.
Resonance theory explains
this stability through two
equivalent resonance
structures that contribute to
the hybrid.
R-C
O
R-C
-
R-C
1/2 -
1/2 -
O
.
.
.
.
.
.
.
.
-
O
.
.
O
.
. .
.
.
.
O
.
.
O
.
.
.
.
.
.
.
.
.
.
X-ray analysis of sodium formate shows equivalent C-O bond
lengths of 1.27 A, consistent with this picture of a resonance hybrid.
o
EP101 / EG101 12
Effect of Substituents on Acidity
Any factor that stabilizes the anion more than it stabilizes the acid
should increase acidity (decrease the magnitude of pK
a
). Any factor
that destabilizes the anion relative to the acid should decrease acidity.
RCOOH + H
2
O RCO
2
-

+ H
3
O
+
Electronic Influences
The electronic effect of a substituent G operates more strongly on the
anion (charged species) than on the carboxylic acid (neutral species).
G C
O
O
-
Electron withdrawal
Stabilizes the anion and
increases acidity
G C
O
O
-
Electron release
Destabilizes the anion
and decreases acidity
EP101 / EG101 13
Substituent Effects
on Acidity
EP101 / EG101 14
Synthesis of Carboxylic Acids
Oxidation of 1 ROH & aldehydes
Side chain oxidation of alkylbenzenes
Conversion of Grignards.
EP101 / EG101 15
Preparation of Carboxylic Acids
Oxidation of Aldehydes and 1
o
Alcohols
Oxidation of Alkenes
Aldehydes are easily oxidized to carboxylic acids, even by mild
oxidants such as Ag(NH
3
)
2
+
OH
-
, which is used in the Tollens' test for
distinguishing aldehydes from ketones. Stronger reagents such as
chromic acid (H
2
CrO
4
) or KMnO
4
can oxidize either aldehydes or 1
o

alcohols to carboxylic acids.
R H
O
R OH
O
R OH
Ag(NH
3
)
2
+
OH
-
H
2
CrO
4
or KMnO
4
Alkenes can be oxidatively cleaved to carboxylic acids by use of either
KMnO
4
or ozone.
R
R'
R
R'
(1) KMnO
4
, OH
-
(hot)
(2) H
3
O
+
(1) O
3
(2) H
2
O
2
R OH
O
R' OH
O
+
i) Oxidation of 1 ROH / Aldehydes
The alcohol is first oxidized to an aldehyde and then
to carboxylic acid
EP101 / EG101 16
Oxidation of Alkylbenzenes
Vigorous oxidation by KMnO
4
of primary and secondary (but not
tertiary) alkyl groups directly attached to a benzene ring produces
aromatic acids.
CHRR'
(1) KMnO
4
, HO
-
, H
2
O
(2) H
3
O
+
COOH
Oxidation of Alkylbenzenes
R
The benzene ring of an alkylbenzene can be converted to a carboxyl
group by ozonolysis.
(1) O
3
, CH
3
COOH
(2) H
2
O
2
R OH
O
ii) Side chain oxidation of alkylbenzenes
EP101 / EG101 17
Carbonation of Grignard Reagents
A more general way to prepare carboxylic acids from alkyl or aryl
halides is by carbonation (reaction with CO
2
) of the corresponding
Grignard reagents.
The strongly nucleophilic organomagnesium reagents add to CO
2

to produce magnesium carboxylates. Acidification of these salts yields
the carboxylic acids.
R-MgX
-
+
C
:O: =
:O:
=
R-C-O
:O:
=
:
:
:
-
MgX
+
Nucleophilic
addition
All alkyl (1
o
, 2
o
, 3
o
) and aryl Grignard reagents undergo the
carboxylation reaction. This reaction is accomplished by either
bubbling dry gaseous CO
2
through an ether solution of the Grignard
reagent or by pouring the Grignard reagent onto crushed dry ice
(solid CO
2
).
H
3
O
+
R-C-OH
:O:
=
:
:
iii) Conversion of Grignards Reagent
EP101 / EG101 18
Syntheses Using the Grignard Carbonation Reaction
Mg
ether
CH
3
C-MgCl
CH
3
CH
3
tert-Butylmagnesium
chloride
CH
3
C-Cl
CH
3
CH
3
tert-Butyl
chloride
CH
3
C-COOH
CH
3
CH
3
2,2-Dimethyl-
propanoic acid
(1) CO
2
(2) H
3
O
+
H
3
C CH
3
CH
3
Br
Mg
ether
CH
3
CH
3
MgBr
2,4,6-Trimethylphenyl-
magnesium bromide
CH
3
CH
3
COOH
2,4,6-Trimethylbenzoic
acid
(1) CO
2
(2) H
3
O
+
H
3
C H
3
C
2,4,6-Trimethyl-
bromobenzene
EP101 / EG101 19
Interconversion of Derivatives
More reactive derivatives
can be converted to less
reactive derivatives.
EP101 / EG101 20
Typical RCOOH Reactions
Formation of Acid Derivatives
When the OH of a carboxylic acid is replaced by nucleophile, :Nu, a
carboxylic acid derivatives is produced.
The carboxylic acid derivatives are:

Carboxylic Acid Derivatives
The carboxyl group consists of two parts, the acyl group and the attached
hydroxyl group:
R-C-OH
O
The acid derivatives are compounds in which the hydroxyl group is
replaced with another group or a halogen atom. The principal examples are:
R-C-X
O
R-C-O
O
R-C-OR'
O
R-C-NH
2
O
R-C-NHR'
O
R-C-NR'R''
O
R-C N
Acyl (acid) halides
-C-R'
O
Acid anhydrides
Esters
Amides
N-Monosubstituted
Amides
N,N-Disubstituted
Amides
Another class of carboxylic acid derivatives are the nitriles, which qualify
because on hydrolysis, like all of the other derivatives above, they yield
carboxylic acids.
Nitriles
Carboxylic Acid Derivatives
The carboxyl group consists of two parts, the acyl group and the attached
hydroxyl group:
R-C-OH
O
The acid derivatives are compounds in which the hydroxyl group is
replaced with another group or a halogen atom. The principal examples are:
R-C-X
O
R-C-O
O
R-C-OR'
O
R-C-NH
2
O
R-C-NHR'
O
R-C-NR'R''
O
R-C N
Acyl (acid) halides
-C-R'
O
Acid anhydrides
Esters
Amides
N-Monosubstituted
Amides
N,N-Disubstituted
Amides
Another class of carboxylic acid derivatives are the nitriles, which qualify
because on hydrolysis, like all of the other derivatives above, they yield
carboxylic acids.
Nitriles
Carboxylic Acid Derivatives
The carboxyl group consists of two parts, the acyl group and the attached
hydroxyl group:
R-C-OH
O
The acid derivatives are compounds in which the hydroxyl group is
replaced with another group or a halogen atom. The principal examples are:
R-C-X
O
R-C-O
O
R-C-OR'
O
R-C-NH
2
O
R-C-NHR'
O
R-C-NR'R''
O
R-C N
Acyl (acid) halides
-C-R'
O
Acid anhydrides
Esters
Amides
N-Monosubstituted
Amides
N,N-Disubstituted
Amides
Another class of carboxylic acid derivatives are the nitriles, which qualify
because on hydrolysis, like all of the other derivatives above, they yield
carboxylic acids.
Nitriles
EP101 / EG101 21
Nomenclature of Acid Derivatives
Acid Halides
Replace the ic acid suffix of carboxylic acids with yl chloride.
If the acyl group is a branch of a cyclic compound, replace the ending from
carboxylic acid to -carbonyl.

C
Cl
O
CH
3
CH
2
CH
2
C
O
Cl
butanoyl chloride
butyryl chloride
benzoyl chloride
Br
O
Benzoyl Bromide

Cyclohexanacarbonyl chloride

EP101 / EG101 22
Esters

The alkyl group (which replace of the hydrogen of the carboxylic acid) is named first
followed by the name of the parent acid, with the ending ate in place of ic acid






C
O CH
2
CH
3
O
ethyl benzoate
CH
3
CH
2
CH
2
C
O
O CH
3
methyl butanoate
methyl butyrate
Ethy 4-pentenoate
Ethyl cyclohexanecarboxylate
EP101 / EG101 23
Acid Anhydrides

Anhydrides acids are named by replacing the word acid with anhydride.





O C H
3
O O
Benzoic ethanoic anhydride
EP101 / EG101 24
Amides
An substituted NH
2
group is named by replacing the oic acid of the carboxylic acid with
amide and carboxylic acid with carboxamide.
A substituted compound is named by identification of the substituent followed by the
parent amide.
C H
3
O
NH
2
ethylamide
C
NH
2
O
CH
3
CH
2
CH
2
C
O
NH
2
butanamide
butyramide
benzamide
N-metylbutanamide
Cyclohexanecarboxamide
EP101 / EG101 25
R C
O
OR'
R C
O
OH
+ R'OH
H
+
+ HOH
acid
R C
O
OR' R C
O
Cl + R'OH + HCl
acid chloride
R C
O
OR'
R C
O
O C
O
R + R'OH
H
+
+ RCOOH
acid anhydride
i) Formation of Ester
EP101 / EG101 26
Reactions of Esters
R C
O
OR'
R C
O
OH + R'OH
R C
O
OR''
R C
O
NHR'' + R'OH
+ R'OH
R CH
2
OH
R C
OH
R''
R''
H
2
O (2)
(1)
2 R''MgX
(1)
(2) H
2
O
LiAlH
4
H
2
O
R''OH,
R''NH
2
H
+
or
-
OR''
acid
ester
amide
1 alcohol
3 alcohol
EP101 / EG101 27
Synthesis of Acyl Chlorides
Because of their reactivity, acyl chlorides must be prepared under
conditions that exclude exposure to good nucleophiles like water.
Common reagents that convert carboxylic acids into acyl chlorides are
phosphorus trichloride (PCl
3
) phosphorus pentachloride (PCl
5
), and
thionyl chloride (SOCl
2
).
Typical Synthetic Procedures
The carboxylic acid is heated with the reagent, with or without the
presence of an inert solvent.
COH
O=
Benzoic acid
+ SOCl
2
Thionyl chloride
(bp 75-76
o
C)
heat
CCl
O=
Benzoyl chloride
+ SO
2
+ HCl
Thionyl chloride is an especially convenient reagent because the
byproducts are gases and easily removed. Excess thionyl chloride is easy
to remove by distillation.
ii) Formation of Acid Halides
or PCl
3
EP101 / EG101 28
Acid Chloride Reactions
H
2
O
R'OH
R'NH
2
R'COOH
R C
O
Cl
R C
O
OH + HCl
R C
O
OR'
R C
O
NHR'
R C
O
O C
O
R' + HCl
+ HCl
+ HCl
acid
ester
amide
acid anhydride
EP101 / EG101 29
Amides from Esters
Esters undergo nucleophilic addition-elimination at the acyl carbon with
nitrogen nucleophiles such as ammonia (ammonolysis) or amines (amination).
CH
3
COC
2
H
5
O=
Ethyl acetate
+ :NH
3
H
2
O
ammonolysis
CH
3
CNH
2
+ C
2
H
5
OH
O=
Acetamide
Amides from Carboxylic Acids
Carboxylic acids react with aqueous ammonia to produce ammonium
carboxylates in an acid-base reaction:
RCOH
O=
+ :NH
3
Acid Base
RCO
-
O=
NH
4
+
Ammonium carboxylate
Salt
Recovery of the ammonium carboxylate and heating of the dry salt leads to
dehydration and formation of the amide.
RCO
-
O=
NH
4
+
As the dry salt
RCNH
2
+ H
2
O
O=
heat
Amide
This method is generally not used in organic synthesis because the
vigorous heating required will often decompose the sample.
iii) Formation of Amides
EP101 / EG101 30
Reactions of Amides
R C
O
OH + R'NH
2
R C
O
NHR'
R CH
2
NHR'
(1)
(2) H
2
O
LiAlH
4
H
2
O
H
+
or
-
OH
Br
-
, OH
-
R NH
2
+
CO
2
POCl
3
(or P
2
O
5
)
R C N
acid and amine
amine
1 amine
nitrile
EP101 / EG101 31
The most general method for the preparing an acid anhydride is by nucleophilic
acyl substitution reaction of an acid chloride with a carboxylate anion.
iv) Formation of Acid Anhydrides
EP101 / EG101 32
Anhydride Reactions
R C
O
O C
O
R
R C
O
OH + RCOOH
R C
O
OR'
R C
O
NHR' + RCOOH
+ RCOOH
AlCl
3
H
2
O
R'OH, H
+
R'NH
2
Z
C
O
R
Z
acid
ester
amide
EP101 / EG101 33
Conclusion
At the end of the chapter. You suppose able to:

Understand the nomenclature of carboxylic acid and its derivatives
The physical properties of carboxylic acid
The 3 main methods of synthesis carboxylic acid
The reaction of carboxylic acid to form its derivatives.

EP101 / EG101 School of Engineering
Functional Group Interconversions
R C N
R C OH
O
R C O
O
R'
R C O
O
R C Cl
O
R C NH
2
O
R C
O
R C O
O
R C NR'
2
O
H
2
O
SOCl
2
NH
3

NR
2
H
OH
-
ROH
RCOOH
H
2
O
NH
3

NR
2
H
RCOOH
ROH
OH
-
H
2
O
H
2
O
NH
3

NR
2
H
NH
3
NR
2
H