Carboxylic Acids and Nitriles

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Carboxylic Acids and Nitriles
Organic Chemisty 6e
Chapter 20
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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
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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
20.1 Naming Carboxylic Acids and Nitriles
Propanoic acid
4-Methylpentanoic acid
2. Compounds that have a COOH group bonded to a
ring are named using the suffix carboylic acid
3-Bromocyclohexanecarboxylic acid
1-Cyclopentenecarboxylic acid
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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
4-Methylpentanenitrile
4,5-dimethylhexanenitrile
20.1 Naming Carboxylic Acids and Nitriles
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.
3,3-Dimethylcyclohexanecarbonitrile
Acetonitrile
Benzonitrile
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20.1 Naming Carboxylic Acids and Nitriles
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Carboxyl carbon has sp2 hybridization carboxyl
group is therefore planar with C C O and O
C O bond angles of 120
20.2 Structure and Physical Properties
Carboxylic acids are strongly associated by
hydrogen bonds, most existing as cyclic dimers
held together by two hydrogen bods
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20.2 Structure and Physical Properties
Formic acid
Acetic acid
Benzoic acid
Propanoic acid
Propenoic acid
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Carboxylic acids are acidic, Ka 10-5 (pKa 5),
and therefore react readily with a base such as
NaOH to give a carboxylate salt.
H2O
Metal-carboxylate salt
20.3 Dissociation of Carboxylic Acids
H3O
H2O
pKa - log Ka
and
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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
20.3 Dissociation of Carboxylic Acids
Explanation Acidity can be explained in terms of
bonding
H3O
H2O
Not stabilized
H2O
stabilized by resonance
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Key Points
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.
EWG
EWG
20.4 Substituent Effects on Acidity
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
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Relative Strengths of Acetic Acid and Chloro-
Derivatives
pKa 4.75
pKa 2.85
pKa 1.48
pKa 0.64
20.4 Substituent Effects on Acidity
O
O
Cl
O
Cl
ClCH2CH2CH2COH
CH3CHCH2COH
CH3CH2CHCOH
pKa 4.52
pKa 4.05
pKa 2.86
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20.5 Substituent Effects in Substiruted Benzoic
Acids
Deactivating groups (electron-withdrawing)
stabilize carboxylates Activating groups
(electron-donating) destabilize carboxylates
p-Methoxybenzoic acid (pKa 4.46)
Benzoic acid (pKa 4.19)
p-Nitrobenzoic acid (pKa 3.41)
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Five methods of preparation of Carboxylic Acids
I - Oxidation of a substituted alkylbenzene using
KMnO4 or Na2Cr2O7
KMnO4
H2O, 95C
p-Nitrotoluene
p-Nitrobenzoic acid (88)
Oxidation occurs for 1 2 alkyl groups only,
not in 3 alkyl groups
20.6 Preparation of Carboxylic Acids
II Oxidative cleavage of an alkene with KMnO4
O
O
O
O
KMnO4
HOC(CH2)7COH
CH3(CH2)7CH CH(CH2)7COH
CH3(CH2)7COH
H3O
Oleic acid
nonanoic acid
nonanedioic acid
Alkene must have at least one vinylic hydrogen
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III Oxidation of a 1 alcohol or an aldehyde
O
CrO3
CH3(CH2)8CH2COH
CH3(CH2)8COH
H3O
1-Decanol
Decanoic acid (93)
O
O
Ag2O
CH3(CH2)4CH
CH3(CH2)4COH
NH4OH
Hexanal
Hexanoic acid (85)
1 alcohols are oxidized with CrO3 in aqueous
acid, aldehydes are oxidized with either acidic
CrO3 OR Tollens reagent
IV Hydrolysis of nitriles using strong, hot
aquious acid or base
20.6 Preparation of Carboxylic Acids
O
Na CN-
H3O
RCH2Br
RCH2C N
NH3
RCH2COH
(SN2)
Excellent two-step process for the preparation
of carboxylic acids from 1 halides
1. NaCN
2. OH/H2O 3. H3O
Fenoprofen (an antiarthritic agent)
Product has one more carbon than the starting
alkyl halide
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V Carboxylation (or carbonation) of Grignard
reagents
Mg
1. CO2, ether
Ether
2. H3O
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)

20.6 Preparation of Carboxylic Acids
Reaction of Amide with SOCl2
R-
MgBr
MgBr
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General Reactions of Carboxylic Acids
Deprotonatoin
Reduction
20.7 RNX of Carboxylic Acids An Overview
Carboxylic acid
Nucleophilic acyl substitution
Alpha substitution
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Carboxylic acids can be reduced using two
approaches
I Using LiAlH4 to give 1 alcohols
O
1. LiAlH4, THF
CH3(CH2)7CHCH(CH2)7COH
CH3(CH2)7CHCH(CH2)7CH2OH
2. H3O
Oleic acid
cis-9-Octadecen-1-ol (87)
Reaction usually requires harsh conditions
(i.e. heating)
20.8 Reduction of Carboxylic Acids
II Using borane (BH3) to give 1 alcohols
1. BH3, THF
2. H3O
2-(p-Nitrophenyl)ethanol (94)
p-Nitrophenylacetic acid
Reaction is usually performed under mild
conditions and can be used to selectively reduce
carboxylic acid functionality
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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
20.9 Chemistry of Nitriles
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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.
Nu--
Carbonyl Compound
20.9 Chemistry of Nitriles
d-
Products
d
Nu--
Nitrile
d-
d
Products
Imine anion
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General Reactions of Nitriles
H2O
H2O
Carboxylic Acid
Amide
20.9 Chemistry of Nitriles
LiAlH4
RMgX
Nitrile
Ketone
Amine
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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
H3O
Or NaOH, H2O
Basic hydrolysis of a nitrile
--OH
20.9 Chemistry of Nitriles
Dianion
H2O
Amide
--OH
--OH
NH2-
Carboxylate
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Reduction Conversion of Nitriles into Amines
A nitrile can be reduced with LiAlH4 to give a
primary amine
1. LiAlH4, ether
2. H2O
o-Methylbenzonitrile
o-Methylbenzylamine
20.9 Chemistry of Nitriles
The following example illistrates a reaction that
occurs by nucleophilic addition of hydride ion to
the polar CN bond, yielding an imine anion. The
imine anion undergoes another nucleophilic
addition to yield a dianion.
H2O
LiAlH4
LiAlH4
ether
ether
Nitrile
Imine anion
Dianion
Amine
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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
R- MgX
H2O
NH3
Nitrile
Imine anion
Ketone
20.9 Chemistry of Nitriles
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
1. CH3CH2MgBr, ether
2. H3O
Benzonitrile
Propiophenone (89)
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Infrared Spectroscopy Two characteristic IR
absorptions
I. O-H gives broad band in the range of 2500
3300 cm-1
II. CO gives band in the range 1710 1760 cm-1
Monomer
Hydrogen-bonded dimer
Position depends on whether the acid exists as
a monomer or hydrogen-bonded dimer
20.10 Spectroscopy of Carboxylic Acids
IR Spectrum of Butanoic Acid
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NMR Spectroscopy

• Acidic COOH proton absorbs as a singlet near 12
  d
• Carboxyl carbon atoms absorb in the range 165 -
  185 d
• Aromatic / saturated near 165 ?, aliphatic near
  185 d

20.10 Spectroscopy of Carboxylic Acids
NMR spectrum of phenylacetic acid