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17
Organic
Chemistry
William H. Brown &
Christopher S. Foote
17-1
17
Carboxylic
Acids
Chapter 17
17-2
17 Structure
 The
functional group of a carboxylic acid is a
carboxyl group
:
O:
:
C
:O
COOH
CO 2 H
H
• the general formula of an aliphatic carboxylic acid is
RCOOH; that of an aromatic carboxylic acid is
ArCOOH
17-3
17 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 -enCOOH
COOH
COOH
C6 H5
Propenoic acid
(Acrylic acid)
trans-2-Butenoic acid
(Crotonic acid)
trans-3-Phenylpropenoic acid
(Cinnamic acid)
17-4
17 Nomenclature - IUPAC
 The
carboxyl group takes precedence over most
other functional groups
OH
COOH
(R)-5-Hydroxyhexanoic acid
O
COOH
5-Oxohexanoic acid
H2N
COOH
4-Aminobutanoic acid
17-5
17 Nomenclature - IUPAC
• dicarboxylic acids: add the suffix -dioic acid to the
name of the parent alkane containing both carboxyl
groups
O
HO
O
OH
O
Ethanedioic acid
(Oxalic acid)
O
HO
O
OH
O
Butanedioic acid
(Succinic acid)
HO
O
HO
OH
Propanedioic acid
(Malonic acid)
O
O
OH
Pentanedioic acid
(Glutaric acid)
HO
OH
O
Hexanedioic acid
(Adipic acid)
17-6
17 Nomenclature - IUPAC
• if the carboxyl group is attached to a ring, name the
ring compound and add the suffix -carboxylic acid
2
3
1
COOH
2-Cyclohexenecarboxylic acid
H OOC
COOH
trans-1,3-Cyclopentanedicarboxylic acid
17-7
17 Nomenclature - IUPAC
• benzoic acid is the simplest aromatic carboxylic acid
• use numbers to show the location of substituents
COOH
COOH
COOH
OH
COOH
COOH
COOH
Benzoic 2-Hydroxybenzoic
1,2-Benzene1,4-Benzeneacid
acid
dicarboxylic acid dicarboxylic acid
(Salicylic acid)
(Phthalic acid) (Terephthalic acid)
17-8
17 Nomenclature-Common
• when common names are used, the letters
etc. are often used to locate substituents
O
  

5
1 OH
4 3 2
O
H2 N
O
OH
4-Aminobutanoic acid
(-Aminobutyric acid;
GABA)
OH
NH2
2-Aminopropanoic acid
(-Aminopropionic acid;
alanine)
17-9
17 Physical Properties
 In
the liquid and solid states, carboxylic acids are
associated by hydrogen bonding into dimeric
structures
-
+
+
-
17-10
17 Physical Properties
 Carboxylic
acids have significantly higher boiling
points than other types of organic compounds of
comparable molecular weight
• they are polar compounds and form very strong
intermolecular hydrogen bonds
 Carboxylic
acids are more soluble in water than
alcohols, ethers, aldehydes, and ketones of
comparable molecular weight
• they form hydrogen bonds with water molecules
through their C=O and OH groups
17-11
17 Physical Properties
• water solubility decreases as the relative size of the
hydrophobic portion of the molecule increases
hydrophilic
region
hydrophobic region
17-12
17 Acidity
 Carboxylic
acids are weak acids
• values of pKa for most aliphatic and aromatic
carboxylic acids fall within the range 4 to 5
 The
greater acidity of carboxylic acids relative to
alcohols, both compounds containing an OH
group is due to resonance stabilization of the
carboxylate anion
17-13
17 Acidity
• electron-withdrawing substituents near the carboxyl
group increase acidity through their inductive effect
CH3 COOH ClCH 2 COOH Cl 2 CHCOOH
Acetic
Chloroacetic Dichloroacetic
acid
acid
acid
pKa: 4.76
2.86
1.48
Increasing acid strength
Cl 3 CCOOH
Trichloroacetic
acid
0.70
17-14
17 Reaction with Bases
 Carboxylic
acids, whether soluble or insoluble in
water, react with NaOH, KOH, and other strong
bases to give water-soluble salts
COOH
+
NaOH
-
H2 O
Benzoic acid
(slightly soluble
in water)
COO Na
+
+
H2 O
Sodium benzoate
(60 g/100 mL water)
 They
also form water-soluble salts with ammonia
and amines
COOH + NH3
Benzoic acid
(slightly soluble
in water)
-
H2 O
COO NH4
+
Ammonium benzoate
(20 g/100 mL water)
17-15
17 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
CH3 COOH + NaHCO 3
+
CH3 COO Na + CO 2 + H2 O
17-16
17 Reaction
with
Bases
QuickTime™ and a
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17-17
17 Preparation
 Carbonation
of Grignard reagents
• treatment of a Grignard reagent with carbon dioxide
followed by acidification gives a carboxylic acid
O
Mg Br + C
O
Carbon
dioxide
O
C-O - [ Mg Br ] +
HCl
H2 O
O
C-OH + Mg 2 +
Cyclopentanecarboxylic acid
17-18
17 Methanol to Acetic Acid
 Acetic
acid is synthesized by carbonylation of
methanol
• the carbonylation is exothermic
O
CH3 OH + CO
CH3 COH H° = -138 kJ(33 kcal)/mol
• the Monsanto process uses a soluble rhodium(III) salt
and HI to catalyze the reaction
17-19
17 Methanol to Acetic Acid
• Steps 1 and 2: preparation of the catalyst:
CH3 OH + HI
CH3 I + H2 O
CH3 I + Rh( CO) I 2
[ CH3 - Rh( CO) I 3 ] An methyl-rhodium
carbonyl complex
• Steps 3 and 4: the catalytic cycle
O
CH3 COH
[ CH3 - Rh( CO) I 3 ] -
(4)
CH3 OH
catalytic
cycle
O
[ CH3 C- Rh( CO) I 3 ] An acyl-rhodium
carbonyl complex
CO
(3)
17-20
17 Reduction
 The
carboxyl group is very 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
17-21
17 Reduction by LiAlH4
 Lithium
aluminum hydride reduces a carboxyl
group to a 1° alcohol
• reduction is carried out in diethyl ether, THF, or other
nonreactive, aprotic solvent
O
COH
1 . LiAlH4 , ether
2 . H2 O
CH2 OH + LiOH
+
Al(OH) 3
4-Hydroxymethylcyclopentene
17-22
17 Selective Reduction
• carboxyl groups are not affected by catalytic reduction
under conditions that reduce aldehydes and ketones
O
O
OH +
5-Oxohexanoic acid
H2
Pt
25°C, 2 atm
OH
O
OH
5-Hydroxyhexanoic acid
17-23
17 Selective Reduction
• using the less reactive NaBH4, it is possible to reduce
the carbonyl group of an aldehyde or ketone without
affecting a carboxyl group
O
C6 H5
O
OH
OH
5-Oxo-5-phenylpentanoic acid
1 . Na BH 4
2 . H2 O
C6 H5
O
OH
5-Hydroxy-5-phenyl
pentanoic acid
17-24
17 Fischer Esterification
 Esters
can be prepared by treatment of a
carboxylic acid with an alcohol in the presence of
an acid catalyst, commonly H2SO4 or gaseous
HCl
O
OH
Ethanoic acid
(Acetic acid)
H2 SO 4
+
HO
Ethanol
(Ethyl alcohol)
O
+ H2 O
O
Ethyl ethanoate
(Ethyl acetate)
17-25
17 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
• alternatively, water can be removed by azeotropic
distillation and a Dean-Stark trap
17-26
17 Fischer Esterification
• a key intermediate in Fischer esterification is the
tetrahedral carbonyl addition intermediate formed by
addition of ROH to the C=O group
O
O
TCAI
H
R C OCH3
O
H
+
+
H
H
R C OH + HOCH3
O
R C OCH3 + HOH
17-27
17 Diazomethane
 Diazomethane,
CH2N2
• a potentially explosive, toxic yellow gas, is best drawn
as a hybrid of two contributing structures
H C N N:
:
:
+
+
H C N N:
H
H
• treatment of a carboxylic acid with diazomethane gives
a methyl ester
O
RCOH
+
ether
CH2 N 2
Diazomethane
O
RCOCH3 + N 2
A methyl ester
17-28
17 Diazomethane
 Esterification
occurs in two steps
Step 1: proton transfer to diazomethane
O
+
+
:
R C O H
CH2 N N
O
+
– +
R C O:
CH3 -N N
A carboxylate
Methylanion
diazonium
cation
Step 2: nucleophilic displacement of N2
O
+
- +
R- C-O:
CH3 -N N
SN 2
O
R- C-O- CH 3 + :N N
17-29
17 Acid Chlorides
 The
functional group of an acid halide is a
carbonyl group bonded to a halogen atom
• among the acid halides, acid chlorides are by far the
most common and the most widely used
O
- C- X
O
CH3 CCl
Functional group
of an acid halide
Acetyl
chloride
O
C-Cl
Benzoyl
chloride
17-30
17 Acid Chlorides
• acid chlorides are most often prepared by treatment of
a carboxylic acid with thionyl chloride
O
OH + SOCl 2
Butanoic
Thionyl
acid
chloride
O
Cl + SO 2 + HCl
Butanoyl
chloride
17-31
17 Acid Chlorides
 The
mechanism for this reaction is divided into
two steps.
Step 1: OH-, a poor leaving group, is transformed into a
chlorosulfite group, a good leaving group
O
O
R- C-O- H + Cl-S- Cl
O
O
R C O S Cl
+
H- Cl
A chlorosulfite
group
17-32
17 Acid Halides
Step 2: attack of chloride ion gives a tetrahedral
carbonyl addition intermediate, which collapses to
give the acid chloride
O
O
R C O S Cl + :Cl
:O
-
-
O
R C O S Cl
O
R- C-Cl + SO 2 + :Cl
-
Cl
A tetrahedral carbonyl
addition intermediate
17-33
17 Decarboxylation
 Decarboxylation:
loss of CO2 from a carboxyl
group
• most carboxylic acids, if heated to a very high
temperature, undergo thermal decarboxylation
O
RCOH
decarboxylation
heat
RH + CO 2
• most carboxylic acids, however, are quite resistant to
moderate heat and melt or even boil without
decarboxylation
17-34
17 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
warm
 
OH
3-Oxobutanoic acid
(Acetoacetic acid)
O
+
CO 2
Acetone
17-35
17 Decarboxylation
• thermal decarboxylation of a -ketoacid involves
rearrangement of six electrons in a cyclic sixmembered transition state
enol of
a ketone
O
H
O
(1)
O
O
H
O
C
(2)
O
O
+
CO 2
(A cyclic six-membered
transition state)
17-36
17 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
140-150°C
HOCCH2 COH
Propanedioic acid
(Malonic acid)
O
CH3 COH + CO 2
17-37
17 Decarboxylation
• thermal decarboxylation of malonic acids also involves
rearrangement of six electrons in a cyclic sixmembered transition state
O
HO
H
O
O
(1)
O
A cyclic six-membered
transition state
HO
H
O
C
O
(2)
O
+
HO
CO 2
Enol of a
carboxylic acid
17-38
17 Prob 17.17
Each compound shows strong absorption between 1720
and 1700 cm-1, and strong broad absorption over the
region 2500-3500 cm-1. Propose a structural formula for
each compound.
(a) C5 H1 0 O 2
1
13
H-NMR
C-NMR
0.94 (t, 3H)
180.71
1.39 (m, 2H)
33.89
1.62 (m, 2H)
26.76
2.35 (t, 2H)
22.21
13.69
12.0 (s 1H)
(b) C6 H1 2 O 2
1
H-NMR 13 C-NMR
1.08 (s, 9H) 179.29
2.23 (s, 2H)
47.82
12.1 (s, 1H)
30.62
29.57
17-39
17 Prob 17.17 (cont’d)
(d) C5 H8 O4
(c) C5 H8 O4
1
13
H-NMR
C-NMR
0.93 (t, 3H)
170.94
1.80 (m, 2H) 53.28
3.10 (t, 1H)
21.90
12.7 (s, 2H)
1
13
C-NMR
H-NMR
1.29 (s, 6H) 174.01
12.8 (s, 2H)
48.77
22.56
11.81
(e) C4 H6 O2
1
H-NMR 13 C-NMR
1.91 (d, 3H)
172.26
5.86 (d, 1H)
147.53
7.10 (m, 1H)
122.24
12.4 (s, 1H)
18.11
(f) C3 H4 Cl 2 O2
1
H-NMR 13 C-NMR
2.34 (s, 3H) 171.82
11.3 (s, 1H)
79.36
34.02
17-40
17 Prob 17.17 (cont’d)
(g) C5 H8 Cl 2 O2
1
13
H-NMR
C-NMR
1.42 (s, 6H)
180.15
6.10 (s, 1H)
77.78
12.4 (s, 1H)
51.88
20.71
(h) C5 H9 Br O 2
1
H-NMR 13 C-NMR
0.97 (t, 3H)
176.36
1.50 (m, 2H) 45.08
2.05 (m, 2H) 36.49
20.48
4.25 (t, 1H)
13.24
12.1 (s 1H)
(i) C4 H8 O3
1
13
H-NMR
C-NMR
2.62 (t, 2H)
177.33
3.38 (s, 3H)
67.55
3.68 (s, 2H)
58.72
11.5 (s, 1H)
34.75
17-41
17 Prob 17.18
Complete these reactions.
(a)
CH2 OH
CHO 1 . Ag ( N H3 ) 2
(b) HO
OH
O
(c)
+
2 . H2 O, HCl
1 . Cl 2 , KOH in water/dioxane
2 . HCl, H2 O
Br
(d)
K2 Cr 2 O 7 , H2 SO4
H2 O, acetone
1 . Mg, e t he r
2 . CO 2
3 . HCl, H2 O
OCH3
17-42
17 Prob 17.19
Show how to bring about each conversion.
O
O
(a)
OH
COOH
Cl
(b)
OH
O
CH2 OH
COOH
(c)
(d) C6 H5
OH
C6 H5
COOH
17-43
17 Prob 17.21
Draw a structural formula for each starting compound.
O
(a) C6 H1 4 O
(b) C6 H1 2 O
(c) C6 H1 4 O 2
oxidation
OH
O
oxidation
oxidation
OH
O
HO
OH
O
17-44
17 Prob 17.22
Show reagents to bring about each conversion.
(a)
OH
CH3
(b) CH 3 COH
CH3
CH3
(c) CH3 COH
CH3
CH3
(d) CH3 COH
COOH
CH3
CH3 CCOOH
CH3
CH3
CH3 CHCOOH
CH 3
CH3 CHCH 2 COOH
CH3
(e) CH3 CH= CHCH 3
CH3 CH= CHCH 2 COOH
17-45
17 Prob 17.23
Show how to synthesize butanedioic acid starting with
acetylene and formaldehyde.
HO
Acetylene
OH
2-Butyne-1,4-diol
O
HO
OH
1,4-Butanediol
HO
OH
O
Butanedioic acid
(Succinic acid)
17-46
17 Prob 17.24
Propose a mechanism for the rearrangement of benzil to
sodium benzilate.
OO
H2 O
Ph-C-C-Ph
NaOH
Benzil
(an -diketone)
HO O
+
-
+
Ph-C-C-O Na
Ph
Sodium benzilate
HCl
H2 O
HO O
Ph-C-C-OH
Ph
Benzilic acid
17-47
17 Prob 17.33
Show how to convert trans-3-phenyl-2-propenoic
(cinnamic acid) to each compound.
(a) C6 H5
OH
O
(b) C6 H5
(c) C6 H5
OH
OH
17-48
17 Prob 17.34
Show how to convert 3-oxobutanoic acid to these
compounds.
OH O
(a)
(b)
OH
OH
OH
(c)
O
OH
17-49
17 Prob 17.35
Complete each example of Fischer esterification.
(a)
O
H+
+
OH
HO
COOH
(b)
+
CH3 OH
H+
COOH
O
(c) HO
OH +
H+
OH
O
17-50
17 Prob 17.37
Name the carboxylic acid and alcohol from which each
ester is derived.
O
(a)
(b)
O
O
O
O
O
(c)
O
O
O
(d)
O
O
O
17-51
17 Prob 17.39
Propose a mechanism for this reaction.
O
CH3
RCOH + CH2 =CCH3
+
H
O CH3
RCOCCH3
CH3
2-Methylpropene
(Isobutylene)
A tert-butyl ester
17-52
17 Prob 17.40
Draw a structural formula for the product of thermal
decarboxylation of each compound.
O
(a) C6 H5 CCH 2 COOH
(c)
COOH
(b) C6 H5 CH2 CHCOOH
O
CCH3
COOH
17-53
17 Prob 17.41
Propose a mechanism for each decarboxylation.
Compare your mechanisms with the mechanism for
decarboxylation of a -ketoacid.
CH3
(a) Br- CH2 -C COO- Na +
heat
CH3
CH2 = C( CH3 ) 2 + CO 2 + N a+ Br-
(b)
CH- CH -COO - N a+
heat
Br Br
CH= CHBr + CO 2 + N a+ Br17-54
17 Prob 17.43
Show how to convert cyclohexane to
cyclohexanecarboxylic acid.
COOH
17-55
17
Carboxylic
Acids
End Chapter 17
17-56