Transcript Document

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
H 2N
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
pK a: 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
+
N aOH
-
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 + N H3
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
CH3 OH + CO
O
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
anion
Methyldiazonium
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
O
Cl
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
 
OH
3-Oxobutanoic acid
(Acetoacetic acid)
O
warm
+
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
HOCCH2 COH
Propanedioic acid
(Malonic acid)
140-150°C
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 H 8 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)
H-NMR 13 C-NMR
1.29 (s, 6H) 174.01
12.8 (s, 2H)
48.77
22.56
1
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) C 5 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 H 9 Br O 2
1
H-NMR 13 C-NMR
0.97 (t, 3H)
1.50 (m, 2H)
2.05 (m, 2H)
4.25 (t, 1H)
12.1 (s 1H)
176.36
45.08
36.49
20.48
13.24
(i) C4 H 8 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)
CH 2 OH
CHO 1 . Ag ( N H 3 ) 2
(b) HO
OH
O
(c)
Br
(d)
K 2 Cr 2 O 7 , H2 SO4
H2 O, acetone
+
2 . H 2 O, HCl
1 . Cl 2 , KOH in water/dioxane
2 . HCl, H 2 O
1 . Mg, e t he r
2 . CO 2
3 . HCl, H 2 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) CH3 COH
CH3
CH3
(c) CH3 COH
CH3
CH3
(d) CH3 COH
COOH
CH3
CH3 CCOOH
CH3
CH3
CH3 CHCOOH
CH3
CH3 CHCH 2 COOH
CH3
(e) CH3 CH= CHCH3
CH3 CH= CHCH2 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
Ph-C-C-Ph + NaOH
H2 O
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
CH 2 = C( CH 3 ) 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