Carboxylic Acids and Nitriles Organic Chemisty 6e
Chapter 20
Introduction to Chapter
Chapter 20 Introduction
RCO2H – About Carboxylic Acids
– Serve as starting materials for preparing acyl
derivaties;
• Esters
• Amides
• Acid Chlorides
– Many carboxylic acids are found in Nature
• Acetic Acid, CH3CO2H for vinegar
• Butanoic Acid, CH3(CH2)2CO2H is the rancid oder
from sour butter
• Palmitic Acid, CH3(CH2)14CO2H is a biological
precursor of fats and other lipids.
– Approx. 2 million tons of acetic acid are produced
annually in the United States
20.1 Naming Carboxylic Acids and Nitriles
Nomencalture - RCOOH
Two systems have been adopted by IUPAC:
1. Carboxylic acids derived from open-chain alkanes are named
by replacing their terminal –e of the alkane with -oic acid
O
O
3
H3 C
H3C
5
OH
4
1
2
OH
CH3
Propanoic acid
4-Methylpentanoic acid
2. Compounds that have a –COOH group bonded to a ring are
named using the suffix –carboylic acid
CO2H
CO2H
1
1
6
2
5
3
4
5
Br
3-Bromocyclohexanecarboxylic acid
2
4
3
1-Cyclopentenecarboxylic acid
20.1 Naming Carboxylic Acids and Nitriles
Nomencalture – RC
N
Two systems have been adopted by IUPAC:
1. Nitriles derived from open-chain alkanes are named by adding –nitrile
as a suffix to the alkane name, with the nitrile carbon numbered C1:
2
3
H3C
5
4
CN
2
3
CN
1
1
4
H3 C
6
CH3
5
CH3
CH3
4-Methylpentanenitrile
4,5-dimethylhexanenitrile
2. Nitriles are named as derivatives of carboxylic acids by replacing
the –ic acid or –oic acid with –onitrile, or replacing –carboxylic acid
with -carbonitrile.
CH3
2
NC
H3C
CH3
1
3
6
4
C
N
C
5
Acetonitrile
3,3-Dimethylcyclohexanecarbonitrile
Benzonitrile
N
20.1 Naming Carboxylic Acids and Nitriles
20.2 Structure and Physical Properties
Carboxyl carbon has sp2 hybridization; carboxyl group is therefore
planar with C C O and O C O bond angles of ~120°
O
H
H
O
H
H
Carboxylic acids are strongly associated by hydrogen bonds, most
existing as cyclic dimers held together by two hydrogen bods
O
H
O
H3 C
CH3
O
H
O
20.2 Structure and Physical Properties
O
H
O
OH
H3 C
Formic acid
OH
Acetic acid
O
C
OH
O
O
H3 C
H2 C
OH
Propanoic acid
OH
Propenoic acid
Benzoic acid
20.3 Dissociation of Carboxylic Acids
Carboxylic acids are acidic, Ka ~ 10-5 (pKa ~5), and therefore react
readily with a base such as NaOH to give a carboxylate salt.
O
O
+
R
NaOH
+
OH
-
R
H2O
+
O Na
Metal-carboxylate salt
O
O
+
R
+
H2O
R
OH
-
O

[ RCO 2 ][ H 3 O  ]
Ka 
[ RCO 2 H ]
and
pKa = - log Ka
H3O+
20.3 Dissociation of Carboxylic Acids
Relative Acidity of Carboxylic Acids
Carboxylic acids are more acidic than alcohols by a factor of ~1011
O
CH3CH2OH
CH3COH
HCl
pKa = 16
pKa = 4.75
pKa = -7
Acidity
Explanation: Acidity can be explained in terms of bonding
H3 C
OH
+
H2O
-
H3C
O
+
H3O+
Not stabilized
O
R
+
OH
-
O
H2O
O
R
R
O
-
stabilized by resonance
O
Key Points
20.4 Substituent Effects on Acidity
Acidity of carboxylic acids varies greatly according to the nature of the
substituent attached to the carboxyl group
Generally, any factor that STABILIZES the carboxylate group relative
to the undissociated acid will drive the equilibrium toward increased
dissociation and result in increased acidity.
O
EWG
C
O
-
O
Electron-withdrawing group
Stabilizes carboxylate and
strengthens acid
EWG
C
-
O
Electron-donating group
Destabilizes carboxylate and
weakens acid
Electron-withdrawing groups stabilize carboxylate ions
Electron-donating groups destabilize carboxylate ions
Relative Strengths of Acetic Acid and Chloro- Derivatives
20.4 Substituent Effects on Acidity
O
O
H
O
Cl
Cl
OH
H
O
Cl
OH
H
OH
Cl
H
Cl
H
pKa = 4.75
OH
H
pKa = 2.85
Cl
pKa = 1.48
pKa = 0.64
Acidity
O
ClCH2CH2CH2COH
pKa = 4.52
Cl
O
CH3CHCH2COH
pKa = 4.05
Acidity
Cl O
CH3CH2CHCOH
pKa = 2.86
Substituent Effects in Substiruted Benzoic Acids
20.5
Deactivating groups (electron-withdrawing) stabilize carboxylates
Activating groups (electron-donating) destabilize carboxylates
O
O
O
C
C
C
OH
OH
O2 N
CH3O
p-Methoxybenzoic acid
(pKa = 4.46)
OH
Benzoic acid
(pKa = 4.19)
Acidity
p-Nitrobenzoic acid
(pKa = 3.41)
Five methods of preparation of Carboxylic Acids
20.6 Preparation of Carboxylic Acids
I - Oxidation of a substituted alkylbenzene using KMnO4 or Na2Cr2O7
O
NO2
CH3
KMnO4
H2O, 95°C
p-Nitrotoluene
NO2
C
OH
p-Nitrobenzoic acid (88%)
* Oxidation occurs for 1° & 2° alkyl groups only, not in 3° alkyl groups
II – Oxidative cleavage of an alkene with KMnO4
O
CH3(CH2)7CH
CH(CH2)7COH
Oleic acid
O
KMnO4
H3O+
O
O
CH3(CH2)7COH + HOC(CH2)7COH
nonanoic acid
* Alkene must have at least one vinylic hydrogen
nonanedioic acid
III – Oxidation of a 1° alcohol or an aldehyde
O
20.6 Preparation of Carboxylic Acids
CH3(CH2)8CH2COH
1-Decanol
CrO3
H3O+
CH3(CH2)8COH
Decanoic acid (93%)
O
CH3(CH2)4CH
Hexanal
O
Ag2O
NH4OH
CH3(CH2)4COH
Hexanoic acid (85%)
* 1° alcohols are oxidized with CrO3 in aqueous acid, aldehydes are
oxidized with either acidic CrO3 OR Tollen’s reagent
IV – Hydrolysis of nitriles using strong, hot aquious acid or base
RCH2Br
Na+ CN(SN2)
RCH2C
N
H3O+
O
RCH2COH
+
NH3
* Excellent two-step process for the preparation of carboxylic acids from 1° halides
O
CH3
O
Br
1. NaCN
2. –OH/H2O
3. H3O
C
O
OH
CH3
Fenoprofen
(an antiarthritic agent)
* Product has one more carbon than the starting alkyl halide
V – Carboxylation (or carbonation) of Grignard reagents
20.6 Preparation of Carboxylic Acids
Br
MgBr
H3 C
CH3
CO2H
H3 C
CH3
Mg
Ether
H3 C
CH3
1. CO2, ether
2. H3O+
CH3
CH3
CH3
2,4,6-Trimethylbenzoic acid
(87%)
1-Bromo-2,4,6-trimethyl-benzene
•Reaction is limited to alkyl halides that can form Grignard reagents
(i.e. reactants with specific functional groups)
Reaction of Amide with SOCl2
H
O
R:-
+
+MgBr
+O
C
O
+
H
C
R
O
O
- +
MgBr
O
+
H
C
R
OH
20.7 RNX of Carboxylic Acids: An Overview
General Reactions of Carboxylic Acids
O
H
H
C
H
-
O
Deprotonatoin
H
C
OH
Reduction
O
H
O
R
C
OH
O
Carboxylic acid
C
OX
Alpha substitution
H
C
Y
Nucleophilic acyl
substitution
Carboxylic acids can be reduced using two approaches
20.8 Reduction of Carboxylic Acids
I – Using LiAlH4 to give 1° alcohols
O
CH3(CH2)7CH=CH(CH2)7COH
Oleic acid
1. LiAlH4, THF
2. H3O+
CH3(CH2)7CH=CH(CH2)7CH2OH
cis-9-Octadecen-1-ol
(87%)
* Reaction usually requires harsh conditions (i.e. heating)
II – Using borane (BH3) to give 1° alcohols
OH
OH
C
O
NO 2
p-Nitrophenylacetic acid
1. BH3, THF
2. H3O+
H
NO 2
2-(p-Nitrophenyl)ethanol
(94%)
* Reaction is usually performed under mild conditions and can be used to
selectively reduce carboxylic acid functionality
H
Preparation of Nitriles
The dehydration reaction occurs first with the nucleophilic amide
oxygen atom reacting with SOCl2, then a deprotonation of the molecule
in a subsequent E2-like elimination reaction.
Reaction of Amide with SOCl2
O
20.9 Chemistry of Nitriles
S
Cl
O
S
S
Cl
O
O
R
O
NH2
R
O
Cl
N
H
+
Cl
Base
H
R
R
N
H
Base
C
N
+
SO2
Reactions of Nitriles
Nitrile groups are strongly polarized, thus resulting in a electrophilic
carbon atom. Therefore they are attacked by nucleophiles and yield an
sp2-hybridized imine anions.
20.9 Chemistry of Nitriles
This reaction is analogous to the formation of an sp3-hybridized
alkoxide ion by nucleophilic addition to a carbonyl group.
Carbonyl Compound
Nu--
δ- O
O
Products
δ+
R
R
R R
Nu
Nu--
Nitrile
δ- N
N
-
δ+
Products
R
R
Nu
Imine anion
General Reactions of Nitriles
O
O
H2O
NH2
R
R
H2O
Carboxylic Acid
Amide
20.9 Chemistry of Nitriles
OH
N
C
LiAlH4
H
H
R
R’MgX
O
Nitrile
C
R
NH2
Amine
R
R'
Ketone
Hydrolysis: Conversion of Nitriles into Carboxylic Acids
A nitrile can be hydrolyzed in either basic or acidic aqueous solution to
yield a carboxylic acid and ammoniz or an amine
O
+
R
C
N
H3O
+
Or NaOH, H2O
R
NH3
OH
20.9 Chemistry of Nitriles
Basic hydrolysis of a nitrile
R
C
--
N
OH
Dianion
-
O
O
-
OH
C
R
C
R
OH
N
-
H
C
N
R
R
R
NH2
+
NH2
H2O
H
Amide
OH
--
-
C
OH
C
N
+
--
H
O
O
OH
H
H
O
NH2
-
O
+
C
R
O
-
Carboxylate
Reduction: Conversion of Nitriles into Amines
A nitrile can be reduced with LiAlH4 to give a primary amine
C
N
CH2NH2
1. LiAlH4, ether
2. H2O
20.9 Chemistry of Nitriles
CH3
CH3
o-Methylbenzonitrile
o-Methylbenzylamine
The following example illistrates a reaction that occurs by nucleophilic
addition of hydride ion to the polar C≡N bond, yielding an imine anion.
The imine anion undergoes another nucleophilic addition to yield a
dianion.
N
R
C
N
LiAlH4
ether
LiAlH4
ether
C
R
Nitrile
-
H
Imine anion
H
H
C
R
H2O
2-
N
Dianion
H
H
C
R
NH2
Amine
Reaction of Nitriles with Organometallic Reagents
A nitrile can add a Grignard reagent to give an intermediate imine
anion that is further hydrolyzed by water to yield a ketone:
N
:R’- +MgX
R
C
O
H2O
N
C
R
20.9 Chemistry of Nitriles
-
Nitrile
+
C
R'
Imine anion
R
NH3
R'
Ketone
This type of reaction is similar to the reduction of a nitrile to an amine,
however only one nucleophilic addition occurs and the nucleophile is a
carbanion (R:-) rather than a hydride ion:
O
C
N
C
CH2CH3
1. CH3CH2MgBr, ether
2. H3O+
Benzonitrile
Propiophenone (89%)
20.10 Spectroscopy of Carboxylic Acids
Infrared Spectroscopy – Two characteristic IR absorptions
I. O-H gives broad band in the range of 2500 – 3300 cm-1
II. C=O gives band in the range 1710 – 1760 cm-1
O
O
H3 C
H
O
H3 C
C
O
H
Monomer
CH3
O
H
Hydrogen-bonded dimer
* Position depends on whether the acid exists as a monomer or
hydrogen-bonded dimer
IR Spectrum of Butanoic Acid
O
20.10 Spectroscopy of Carboxylic Acids
NMR Spectroscopy
• Acidic –COOH proton absorbs as a singlet near 12 δ
• Carboxyl carbon atoms absorb in the range 165 - 185 δ
• Aromatic / saturated near 165 ∂, aliphatic near 185 δ
NMR spectrum of phenylacetic acid