Carboxylic Acids and Nitriles Organic Chemisty 6e Chapter 20
Introduction to Chapter
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
Chapter 20 Introduction
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 H3 C OH
O H3C
5 4 3 2 1
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
1 6 5 4 2 3
5 4 3
CO2H
1 2
Br
3-Bromocyclohexanecarboxylic acid
1-Cyclopentenecarboxylic acid
20.1 Naming Carboxylic Acids and Nitriles
Nomencalture – RC
2
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:
H3 C
5 4 3 2
CN
1
3
CN
1
CH3
H3 C
6 5
4
CH3
4-Methylpentanenitrile
CH3
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 NC
1 2 3 4 5
CH3
C
N
H3C C
N
6
Acetonitrile
3,3-Dimethylcyclohexanecarbonitrile
Benzonitrile
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 O H H H
Carboxylic acids are strongly associated by hydrogen bonds, most existing as cyclic dimers held together by two hydrogen bods
O H3C O H O H O CH3
20.2 Structure and Physical Properties
O
O
H
OH
H3C
OH
O C OH
Formic acid
Acetic acid
O H3C OH
Propanoic acid
O H2C OH
Propenoic acid
Benzoic acid
Carboxylic acids are acidic, Ka ~ 10-5 (pKa ~5), and therefore react readily with a base such as NaOH to give a carboxylate salt.
20.3 Dissociation of Carboxylic Acids
O
O
+
R OH
NaOH
+
R O Na
+
H2O
Metal-carboxylate salt
O
O
+
R OH
H2O
R O
-
+
H3O+
[ RCO2 ][H 3O ] Ka [ RCO2 H ]
and
pKa = - log Ka
Relative Acidity of Carboxylic Acids
20.3 Dissociation of Carboxylic Acids
Carboxylic acids are more acidic than alcohols by a factor of ~1011
O CH3CH2OH
pKa = 16
CH3COH
pKa = 4.75
HCl
pKa = -7
Acidity
Explanation: Acidity can be explained in terms of bonding
H3C OH
+
H2O
H3C
O
-
+
H3O+
Not stabilized
O R OH O
O R
-
+
H2O
R O
-
O
stabilized by resonance
Key Points
Acidity of carboxylic acids varies greatly according to the nature of the substituent attached to the carboxyl group
20.4 Substituent Effects on Acidity
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 O O
-
EWG
C
EWG
C
O
Electron-withdrawing group Stabilizes carboxylate and strengthens acid
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
O O Cl OH H H
pKa = 4.75
O Cl OH OH Cl Cl H
pKa = 1.48
O Cl OH Cl
pKa = 0.64
20.4 Substituent Effects on Acidity
H
H H
pKa = 2.85
Acidity
O ClCH2CH2CH2COH
pKa = 4.52
Cl
O
Cl O CH3CH2CHCOH
pKa = 2.86
CH3CHCH2COH
pKa = 4.05
Acidity
Substituent Effects in Substiruted Benzoic Acids
Deactivating groups (electron-withdrawing) stabilize carboxylates Activating groups (electron-donating) destabilize carboxylates
O C OH
O C OH
O C OH
CH3O
p-Methoxybenzoic acid (pKa = 4.46) Benzoic acid (pKa = 4.19)
O2 N
p-Nitrobenzoic acid (pKa = 3.41)
20.5
Acidity
Five methods of preparation of Carboxylic Acids
I - Oxidation of a substituted alkylbenzene using KMnO4 or Na2Cr2O7
20.6 Preparation of Carboxylic Acids
O
NO2
p-Nitrotoluene
CH3
KMnO4 H2O, 95°C
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+
nonanoic acid
O
O
CH3(CH2)7COH + HOC(CH2)7COH
nonanedioic acid
* Alkene must have at least one vinylic hydrogen
III – Oxidation of a 1° alcohol or an aldehyde
O CH3(CH2)8CH2COH CrO3 H3O+ CH3(CH2)8COH
Decanoic acid (93%)
20.6 Preparation of Carboxylic Acids
1-Decanol
O
O Ag2O NH4OH
CH3(CH2)4CH
Hexanal
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
Br MgBr CH3 H3 C CH3 H3 C CO2H CH3
20.6 Preparation of Carboxylic Acids
H3 C
Mg Ether
CH3 CH3
1. CO2, ether 2. H3O+
CH3
1-Bromo-2,4,6-trimethyl-benzene
2,4,6-Trimethylbenzoic acid (87%)
•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
+
H O
O
+
O
H
R:-
+
+MgBr
+O
C
O
R
C
C R OH
- + MgBr
20.7 RNX of Carboxylic Acids: An Overview
General Reactions of Carboxylic Acids
O H C O
Deprotonatoin
-
H H C
H
OH
Reduction
O H C OH
O R C OX
Carboxylic acid
O H C Y
Alpha substitution
Nucleophilic acyl substitution
Carboxylic acids can be reduced using two approaches
I – Using LiAlH4 to give 1° alcohols
20.8 Reduction of Carboxylic Acids
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 C O NO2
p-Nitrophenylacetic acid
OH
1. BH3, THF 2. H3O+
H NO2
2-(p-Nitrophenyl)ethanol (94%)
H
* Reaction is usually performed under mild conditions and can be used to selectively reduce carboxylic acid functionality
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 S
O
Cl
O S Cl O Cl
Base R C N
20.9 Chemistry of Nitriles
Cl
S
O
O
+
+
SO2
H R N H
R
NH2
R
N H
Base
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. This reaction is analogous to the formation of an sp3-hybridized alkoxide ion by nucleophilic addition to a carbonyl group.
20.9 Chemistry of Nitriles
Carbonyl Compound δ- O δ+
Nu-O
Products
R
R
R R
Nu
Nitrile δ- N
Nu--
N
δ+
Products
R
R
Nu
Imine anion
General Reactions of Nitriles
O
H2O
O
R
Amide
NH2
H2O
R
OH
Carboxylic Acid
20.9 Chemistry of Nitriles
N C
LiAlH4
R
Nitrile
R’MgX
H C R
Amine
H NH2
O
R
Ketone
R'
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
R C N
H3O
+
O
Or NaOH, H2O
R OH
+
NH3
Basic hydrolysis of a nitrile
20.9 Chemistry of Nitriles
R
C
N
OH
--
OH
O
Dianion
O
-
O C
-
OH C R N R
-
C N
H
C R N
H
O R
-
OH C NH2 R
NH2
+
H2O
+
--
H
Amide
OH
--
OH
H O H
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
CH3 CH3
o-Methylbenzylamine
20.9 Chemistry of Nitriles
o-Methylbenzonitrile
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
R
C H
LiAlH4 ether
H C R
H N
2-
H2O
H C R
H NH2
Amine
Nitrile
Imine anion
Dianion
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 C R R'
R
Ketone
-
:R’- +MgX
R C N
O
H2O
C R'
+
NH3
20.9 Chemistry of Nitriles
Nitrile
Imine anion
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 H3C C O
Monomer
O H3C H O H
H
O CH3 O
Hydrogen-bonded dimer
* Position depends on whether the acid exists as a monomer or hydrogen-bonded dimer
IR Spectrum of Butanoic Acid
NMR Spectroscopy
20.10 Spectroscopy of Carboxylic Acids
• 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