Download 12 - Wiley

12
Introduction to
Organic
Chemistry
2 ed
William H. Brown
12-1
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12
Carboxylic
Acids
Chapter 12
12-2
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Structure
• The functional group of a carboxylic acid is a
carboxyl group
••
••
O
C
COOH
••
O
••
CO2 H
H
• The general formula of an aliphatic carboxylic
acid is RCO2H; that of an aromatic carboxylic
acid is ArCO2H
12-3
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Nomenclature - IUPAC
• IUPAC names: drop the -e from the parent alkane
and add the suffix -oic acid
• if the compound contains a carbon-carbon double
bond, change the infix -an- to -en-
C6 H5
CH2 = CHCO2 H
Propenoic acid
(Acrylic acid)
H
C C
H
CO2 H
trans -3-Phenylpropenoic acid
(Cinnamic acid)
12-4
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Nomenclature - IUPAC
• the carboxyl group takes precedence over most other
functional groups
OH
CH3 CHCH 2 CH2 CH2 CO 2 H
5-Hydroxyhexanoic acid
O
H2 NCH2 CH 2 CH2 CO 2 H
CH3 CCH2 CH 2 CH2 CO 2 H
4-Aminobutanoic acid
5-Oxohexanoic acid
12-5
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Nomenclature - IUPAC
• Dicarboxylic acids: add the suffix -dioic acid to
the name of the parent alkane containing both
carboxyl groups
O O
HOC-COH
Ethanedioic acid
(Oxalic acid)
O
O
HOCCH2 COH
Propanedioic acid
(Malonic acid)
O
O
HOCCH2 CH2 COH
Butanedioic acid
(Succinic acid)
12-6
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Nomenclature - IUPAC
• If the carboxyl group is attached to a ring, name
the ring compound and add the suffix -carboxylic
acid
2
3
1
CO2 H
2-Cyclohexenecarboxylic acid
HO2 C
CO2 H
trans-1,3-Cyclopentanedicarboxylic acid
12-7
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Nomenclature - IUPAC
• The simplest aromatic carboxylic acid is benzoic
acid
• derivatives are named using numbers to show the
location of substituents relative to the carboxyl group
CO 2 H
CO 2 H
1
OH
2
Benzoic
acid
2-Hydroxybenzoic
acid
(Salicylic acid)
3
H2 N
4
2
1
CO 2 H
4-Aminobenzoic
acid
12-8
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Nomenclature - IUPAC
• Aromatic dicarboxylic acids are named by adding
the words “dicarboxylic acid” to “benzene”
CO 2 H
HO 2 C
CO 2 H
CO 2 H
1,4-Benzenedicarboxylic acid 1,2-Benzenedicarboxylic acid
(Terephthalic acid)
(Phthalic acid)
12-9
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Nomenclature-Common
• When common names are used, the letters a, b, g,
d, etc. are often used to locate substituents
d
g b a
O
C-C- C-C-C- OH
5 4 3 2 1
N H2
HOCH2 CH 2 CH2 CO 2 H
4-Hydroxybutanoic acid
(g-Hydroxybutyric acid)
CH3 CHCO 2 H
2-Aminopropanoic acid
(a-Aminopropionic acid;
Alanine)
12-10
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Physical Properties
• In the liquid and solid states, carboxylic acids are
associated by hydrogen bonding into dimeric
structures
12-11
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Physical Properties
• Carboxylic acids are polar compounds and form
very strong intermolecular hydrogen bonds
through both their C=O and OH groups
• they have significantly higher boiling points than other
types of organic compounds of comparable molecular
weight
• they are more soluble in water than alcohols, ethers,
aldehydes, and ketones of comparable molecular
weight
12-12
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Physical Properties
• Water solubility decreases as the relative size of
the hydrophobic portion of the molecule
increases
12-13
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Acidity
• Carboxylic acids are weak acids
• values of pKa for most aliphatic and aromatic
carboxylic acids fall within the range 4 - 5
CH3 CO 2 H + H2 O
Ka =
CH3 CO 2 - + H3 O +
[CH 3 CO 2 - ] [H 3 O + ]
[CH 3 CO 2 H]
= 1.74 x 10-5
pK a = 4.76
12-14
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Acidity
• The greater acidity of carboxylic acids relative to
alcohols is due to two factors:
• the significant resonance stabilization of a carboxylate
anion compared with an alkoxide anion
O
CH3
O
C
CH3
O
-
-
CH3 CH2 O -
C
O
these equivalent contributing
structures delocalize the
negative charge and stabilize
the carboxylic anion
the negative charge is
localized on oxygen
12-15
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Acidity
• the electron-withdrawing inductive effect of the
adjacent carbonyl group on the O-H bond
dO
CH3
C
d+
O-H
because electron density is
withdrawn from the O-H
bond, the carboxyl hydrogen
is lost more easily to a base
12-16
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Acidity
• electron-withdrawing substituents near the carboxyl
group increase acidity through their inductive effect
H
Br
I
Cl
F
CH2 CO2 H CH2 CO2 H CH2 CO2 H CH2 CO2 H CH2 CO2 H
3.18
4.76
2.90
2.86
2.59
Increasing acid strength
12-17
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Acidity
• multiple substitution of electron-withdrawing groups
further increases acidity
CH3 CO2 H ClCH 2 CO2 H Cl 2 CHCO2 H
Cl 3 CCO2 H
Acetic
Chloroacetic Dichloroacetic Trichloroacetic
acid
acid
acid
acid
pKa : 4.76
2.86
1.48
0.70
Increasing acid strength
12-18
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Acidity
• The inductive effect of an electron-withdrawing
substituent falls off rapidly with its distance from
the carboxyl group
Cl
Cl
Cl
CH2 CH2 CH2 CO2 H CH3 CHCH2 CO2 H CH3 CH2 CHCO2 H
4-Chlorobutanoic
3-Chlorobutanoic
2-Chlorobutanoic
acid
acid
acid
pKa :
3.98
2.83
4.52
Increasing acid strength
12-19
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Reaction with Bases
• Carboxylic acids, whether soluble or insoluble in
water, react with NaOH, KOH, and other strong
bases to give water-soluble salts
CO2 H + NaOH
Benzoic acid
(slightly soluble in water)
H2 O
-
CO2 Na
+
+
H2 O
Sodium benzoate
(60 g/100 mL water)
12-20
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Reaction with Bases
• they also form water-soluble salts with ammonia and
amines
CO2 H
+
NH3
Benzoic acid
(slightly soluble
in water)
-
H2 O
CO2 NH 4
+
Ammonium benzoate
(20 g/100 mL water)
12-21
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Reaction with Bases
• Carboxylic acids react with sodium bicarbonate
and sodium carbonate to form water-soluble
salts and carbonic acid
• carbonic acid, in turn, breaks down to carbon dioxide
and water
H2 O
CH3 CO2 H + Na HCO3
-
CH3 CO2 Na
+
+
CO2 + H2 O
12-22
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Reduction
• The carboxyl group is one of the organic
functional groups most resistant to reduction
• it is not affected by catalytic hydrogenation under
conditions that easily reduce aldehydes and ketones
to alcohols, and reduce alkenes and alkynes to
alkanes
• it is not reduced by NaBH4, a reagent that readily
reduces the carbonyl groups of aldehydes and ketones
12-23
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Reduction by LiAlH4
• Lithium aluminum hydride reduces a carboxyl
group to a 1° alcohol
• reduction is most commonly carried out in diethyl
ether or THF
O
COH 1 . LiAlH 4 , ether
2. H 2O
3-Cyclopentenecarboxylic acid
CH2 OH + LiOH + Al(OH) 3
4-Hydroxymethylcyclopentene
12-24
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Selective Reduction
• The carboxyl group is not affected by catalytic
hydrogenation under conditions that easily
reduce aldehydes and ketones to alcohols.
O
O
CH3 CCH2 CH2 CH2 COH
5-Oxohexanoic acid
Pt
25° C, 2 atm
OH
O
CH3 CHCH2 CH2 CH2 COH
5-Hydroxyhexanoic acid
12-25
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Selective Reduction
• it is also possible to selectively reduce the carbonyl
group of an aldehyde or ketone using the less reactive
NaBH4
O
O
CCH2 CH2 CH2 COH
5-Oxo-5-phenylpentanoic acid
1 . NaBH 4
2.H 2O
OH
O
CHCH2 CH2 CH2 COH
5-Hydroxy-5-phenylpentanoic acid
12-26
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Fischer Esterification
• Esters can be prepared by treatment of a
carboxylic acid with an alcohol in the presence of
an acid catalyst, most commonly H2SO4 or
gaseous HCl
O
H2 SO 4
CH3 COH + CH3 CH2 OH
Ethanoic acid
Ethanol
(Acetic acid) (Ethyl alcohol)
O
CH3 COCH2 CH3 + H2 O
Ethyl ethanoate
(Ethyl acetate)
12-27
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Fischer Esterification
• Fischer esterification is an equilibrium reaction
• by careful control of experimental conditions, it is
possible to prepare esters in high yield
• if the alcohol is inexpensive relative to the carboxylic
acid, it can be used in excess to drive the equilibrium
to the right
• if water can be removed from the reaction mixture, the
equilibrium is also driven to the right
12-28
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Fischer Esterification
• A key intermediate in Fischer esterification is the
tetrahedral carbonyl addition intermediate
formed by addition of ROH to the C=O group
tetrahedral carbonyl
addition intermediate
••
••
H
O
••
C ••OCH3
H
••
••
R
••
C ••OH + HOCH
3
••
R
••
R
••
H+
••
••
••
H
O
+
O
O
••
••
C OCH
3 + HOH
••
••
12-29
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Decarboxylation
• Decarboxylation: loss of CO2 from a carboxyl
group
• most carboxylic acids, if heated to a very high
temperature, undergo thermal decarboxylation
• most carboxylic acids, however, are quite resistant to
moderate heat and melt or even boil without
decarboxylation
12-30
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Decarboxylation
• Exceptions are carboxylic acids that have a
carbonyl group beta to the carboxyl group
• this type of carboxylic acid undergoes decarboxylation
on mild heating
O
O
b a
warm
CH3 - C- CH2 - C- OH
3-Oxobutanoic acid
(Acetoacetic acid)
O
CH3 - C- CH3 + CO2
Acetone
12-31
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Decarboxylation
• thermal decarboxylation of a b-ketoacid involves
rearrangement of six electrons in a cyclic sixmembered transition state
O
H3 C
C
H
C
O
O
C
C
O
H H
(A cyclic six-membered
transition state)
H3 C
H
C
H
O
C
H
O
enol of
a ketone
O
CH3 - C- CH3 + CO2
12-32
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Decarboxylation
• Decarboxylation occurs if there is any carbonyl
group beta to the carboxyl
• malonic acid and substituted malonic acids, for
example, also undergo thermal decarboxylation
O
O
O
140-150°C
CH3 COH + CO2
HOCCH2 COH
Propanedioic acid
(Malonic acid)
12-33
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12 Decarboxylation
• thermal decarboxylation of malonic acids also involves
rearrangement of six electrons in a cyclic sixmembered transition state
H
H
O
O
O
O
C
C
C
C
HO
HO
C
O
C
O
H
H
H H
enol of a
A cyclic six-membered
carboxylic acid
transition state
O
CH3 -C-OH
+ CO2
12-34
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.
12
Carboxylic
Acids
End Chapter 12
12-35
Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.