Based on McMurry’s Organic Chemistry, 7th edition
Dr M. Mehrdad University of Guilan, Department of
Chemistry, Rasht, Iran
2شیمی آلی
Chapter 20: Carboxylic Acids and Nitriles
The Importance of Carboxylic Acids
(RCO2H)
Abundant in nature from oxidation of aldehydes
and alcohols in metabolism
◦ Acetic acid, CH3CO2H, - vinegar
◦ Butanoic acid, CH3CH2CH2CO2H (rancid butter)
◦ Long-chain aliphatic acids from the breakdown of fats
Carboxylic acids present in many industrial
processes and most biological processes
An understanding of their properties and reactions
is fundamental to understanding organic chemistry
2
The Importance of Carboxylic Acids
(RCO2H)
They are the starting materials from which
other acyl derivatives are made
3
The Importance of Carboxylic Acids
(RCO2H)
They are the starting materials from which
other acyl derivatives are made
4
20.1
Naming Carboxylic Acids & Nitriles
Carboxylic Acids, RCO2H
If derived from open-chain alkanes, replace the terminal -e of the alkane name with -oic acid
The carboxyl carbon atom is C #1
5
20.1
Naming Carboxylic Acids & Nitriles
Carboxylic Acids, RCO2H
If derived from open-chain alkanes, replace the terminal -e of the alkane name with -oic acid
The carboxyl carbon atom is C #1
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Propanoic acid 4-Methylpentanoic acid 3-Ethyl-6-methyloctanedioic acid
Alternative Names
Compounds with CO2H bonded to a ring are named using the suffix -carboxylic acid
The CO2H carbon is not itself numbered in this system
7
Alternative Names
Compounds with CO2H bonded to a ring are named using the suffix -carboxylic acid
The CO2H carbon is not itself numbered in this system
8
trans-4-Hydroxycyclohexanecarboxylic acid 1-cyclopentenecarboxylic acid
Common Names: Carboxylic acids some of the 1st compound
studied so some of their common names are still used. Especially for those with biological interest.
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Names
accepted
by IUPAC
Common Names:
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Nitriles, RCN
Closely related to carboxylic acids named by adding -nitrile
as a suffix to the alkane name, with the
nitrile carbon numbered C #1
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4-Methylpentanenitrile
Nitriles, RCN
Complex nitriles are named as derivatives of carboxylic
acids.
◦ Replace -ic acid or -oic acid ending with –onitrile
◦ or by replacing the –carboxylic acid ending with -carbonitrile
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Nitriles, RCN
Complex nitriles are named as derivatives of carboxylic
acids.
◦ Replace -ic acid or -oic acid ending with –onitrile
◦ or by replacing the –carboxylic acid ending with -carbonitrile
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2,2-Dimethylcyclohexanecarbonitrile
(From 2,2-dimethylcyclohexanecarboxylic acid)
Acetonitrile
(From acetic acid) Benzonitrile
(From benzoic acid)
20.2 Structure & Properties
Carboxyl carbon sp2 hybridized:
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planar with bond angles of approximately 120°
20.2 Structure & Properties:
15
Carboxylic acids form hydrogen bonds,
exist as cyclic dimers held together by 2 hydrogen bonds
Strong hydrogen bonding causes much higher boiling points
than the corresponding alcohols
1-Propanal
(MW = 58)
1-Propanol
(MW = 60)
Ethanoic Acid (Acetic acid)
MW = 60
CH3CH2CH2-OH
Boiling
Point 49oC 97oC 118oC
Dissociation of Carboxylic Acids
Carboxylic acids are proton donors toward weak and strong
bases, producing metal carboxylate salts, RCO2 +M
16
Carboxylic acids with more than six carbons are only
slightly soluble in water, but their conjugate base salts are
water-soluble
Acidity Constant and pKa
Carboxylic acids transfer a proton to water to give H3O+
and carboxylate anions, RCO2, but H3O
+ is a much
stronger acid
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The acidity constant, Ka,, is about 10-5 for a typical
carboxylic acid (pKa ~ 5)
pKa = -1.7Lower pKa means stronger acid so
equilibrium favors starting materials
pKa = ~5pKa = 15.7
(acts as a base here)
Substituent Effects on AcidityElectron withdrawing (electronegative) substituents (like F, Cl, Br, I) promote
formation of the carboxylate ion so raise the Ka (lower the pKa)
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The acidity constant, Ka,, is about 10-5 for atypical carboxylic acid (pKa ~ 5)
Ka,, ~10-15 to -16 for alcohols and water (pKa~ 15 to 16)
CH3OH 15.5
H2O 15.7
Resonance Effects on Acidity
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Alcohols
Phenols
Carboxylic acid
Inorganic acids
Resonance Effects on Acidity
20
Alcohols weaker acids since O- not stabilized by resonance
Carboxylic acids more acidic since O- stabilized by resonance
Negative charge spread over O-C-O
C-O Bond
lengths same
(127 pm)
C=O Bond length
(120 pm)
C-O Bond length
(134 pm)
20.3 Biological Acids and the
Henderson-Hasselbalch Equation
If pKa of given acid and the pH of the medium are known, %
of dissociated and undissociated forms can be calculated
using the Henderson-Hasselbalch eqn
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هاسل بالخ-اسید های بیولوژیکی و معادله هندرسون
20.4 Substituent Effects on Acidity
Electron withdrawing (electronegative) substituents (like F, Cl, Br, I)
promote formation of the carboxylate ion so raise the Ka (lower the
pKa)
They stabilize the carboxylate anion by induction
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Aromatic Substituent Effects
23
electron-withdrawing
( deactivating) groups (like -NO2)
increase acidity by
stabilizing the carboxylate
anion
electron-donating (activating) group (like OCH3)
decreases acidity by
destabilizing the
carboxylate anion
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Aromatic Substituent Effects
20.5 Preparation of Carboxylic Acids:
From Oxidation of Benzylic Carbons
Oxidation of a substituted alkylbenzene with KMnO4 or Na2Cr2O7 gives a substituted benzoic acid
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1° and 2° alkyl groups can be oxidized, but 3° are not
CH2CH3
C
H3C
H3CCH3
CH CH3
CH3
C
C
H3C
H3CCH3
C
O
OH
O
OH
KMnO4
1o
2o
3o3o
From Oxidative Cleavage of Alkenes
Oxidative cleavage of an alkene with KMnO4 gives a
carboxylic acid if the alkene has at least one vinylic hydrogen
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KMnO4C C
H
CH3
CH3CH2
CH3H3O+
C
CH3CH2
CH3
O C
OH
CH3
O+
KMnO4C C
H
H
CH3CH2
H H3O+ C
CH3CH2
HO
O C
OH
OH
O+
CO2
From Oxidation of 1o Alcohols &
Aldehydes Oxidation of a 1o alcohols or aldehydes with CrO3 in
aqueous acid
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Hydrolysis of Nitriles
Hot acid or base yields carboxylic acids
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CH3 CH2 CH2 C NH3O+
CH3 CH2 CH2 C
O
OHor
1) NaOH
2) H3O+
Halides Nitriles Carboxylic Acids Conversion of an alkyl halide to a nitrile (by an SN2 with
cyanide ion) followed by hydrolysis produces a carboxylic
acid with one more carbon (RBr RCN RCO2H)
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Best with 1o halides
because competing
elimination reactions
occur with 2o or 3o
alkyl halides
Carboxylation of Grignard Reagents
Grignard reagents react with dry CO2 to yield a metal carboxylate◦ Limited to alkyl halides that can form Grignard reagents
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Protonation by
addition of aqueous
HCl in a separate
step gives the free
carboxylic acid
The organomagnesium
halide adds to C=O of
carbon dioxide
Halides Nitriles Carboxylic Acids
Halides Grignard Carboxylic Acids
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20.6 Reactions of Carboxylic Acids:
An Overview
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Carboxylic acid transfer a
proton to a base to give anions,
which are good nucleophiles in SN2 reactions
Like ketones, carboxylic acids
undergo addition of
nucleophiles to the carbonyl
group
Carboxylic acids undergo substitutions reactions characteristic of
neither alcohols nor ketones
1) LiAlH4
2) H3O+
NaOH
20.7 Chemistry of Nitriles
Nitriles and carboxylic acids both have a carbon atom
with three bonds to an electronegative atom, and contain
a bond
C’s of nitriles and carboxylic acids are electrophilic
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d+ d+d-
d-
d-
d+
Preparation of Nitriles:
Dehydration of Amides
Reaction of primary amides RCONH2 with SOCl2 or
POCl3 (or other dehydrating agents)
Not limited by steric hindrance or side reactions (as is the
reaction of alkyl halides with NaCN)
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Mechanism: Dehydration of Amides
Nucleophilic amide oxygen atom attacks SOCl2 followed by deprotonation and elimination
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Nucleophilic amide
oxygen atom
attacks SOCl2
Deprotonation of
acidic H on N
Elimination of the SO2
and Cl leaving groups
Reactions of Nitriles
RCN is strongly polarized and with an electrophilic carbon
Attacked by nucleophiles to yield sp2-hybridized imine anions
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Hydrolysis: Nitriles Carboxylic Acids
Hydrolyzed in with acid or base catalysis to a carboxylic
acid and ammonia or an amine
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Mechanism:
Hydrolysis of
Nitriles
Nucleophilic addition of
hydroxide to CN bond
Protonation gives a
hydroxy imine, which
tautomerizes to an
amide
A second hydroxide
adds to the amide
carbonyl group and loss
of a proton gives a
dianion
Expulsion of NH2 gives
the carboxylate
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Mechanism:
Step 4: Hydrolysis of Amides
39
Reduction: Nitriles 1o Amines
◦Reduction of a nitrile with LiAlH4 gives a primary amine
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Nucleophilic addition
of hydride ion (H-) to
the polar CN bond,
yields an imine anion
The C=N bond undergoes a second
nucleophilic addition of hydride (H-) to give
a dianion, which is protonated by water
Reaction of Nitriles with
Organometallic Reagents Grignard reagents add to give an intermediate imine anion
that is hydrolyzed by addition of water to yield a ketone
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Reactions of Nitriles: Overview
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20.8 Spectroscopy of Carboxylic
Acids and Nitriles
Infrared Spectroscopy
O–H bond of the carboxyl group gives a very broad absorption 2500 to 3300 cm1
C=O bond absorbs sharply between 1710 and 1760 cm1
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Commonly encountered dimeric carboxyl groups absorb in a broad band centered around 1710 cm1
Free carboxyl groups absorb at 1760 cm1
Infrared Spectroscopy
O–H bond of the carboxyl group gives
a very broad absorption 2500 to
3300 cm1
Commonly encountered dimeric carboxyl groups absorb in a broad band centered around 1710 cm1
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IR of Nitriles Nitriles show an intense CN bond absorption near 2250
cm1 for saturated compounds and 2230 cm1 for
aromatic and conjugated molecules
This is highly diagnostic for nitriles
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C-13 NMR Carboxyl 13COOH signals are at d165 to d185
Aromatic and ,b-unsaturated acids are near d165 and
saturated aliphatic acids are near d185
13C N signal d115 to d130
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Proton NMR The acidic CO2H proton is a singlet near d 12
When D2O is added to the sample the CO2H proton is replaced by D causing the absorption to disappear from the NMR spectrum
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