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CARBOXYLIC ACIDS
Properties and Synthesis
NOMENCLATURE
IUPAC NOMENCLATURE
• -oic acid
IUPAC ending
• -carboxylic acid
IUPAC ending for ring compounds
Naming
O
3-Methylbutanoic acid
CH3 CH
CH2 C
OH
b-Methylbutyric acid
Isovaleric acid
CH3
O
CH3 CH2 CH2 CH
Cl
C
OH
2-Chloropentanoic acid
a-Chlorovaleric acid
Naming
O
2-Methylpropanoic acid
CH3 CH
C
a-Methylpropionic acid
OH
Isobutyric acid
CH3
O
H2N
4-Aminobutanoic Acid
g-Aminobutyric Acid
CH2 CH2 CH2 C
“GABA”
OH
More Naming
o
2
m
3
O
1
p 4
5
m
C OH
6
o
Benzoic acid
Benzenecarboxylic acid
H
C OH
O
Cyclohexanecarboxylic acid
Common Names
O
O
O
H C OH
CH3 CH2 C OH
CH3 C OH
Acetic Acid
Formic acid
Propionic Acid
O
O
CH3 CH2 CH2 CH2 C OH
CH3 CH2 CH2 C OH
Butyric Acid
Valeric Acid
O
CH3 CH2 CH2 CH2 CH2 C OH
Caproic Acid
O
H3C
C C C C C C OH
gba
Formula
Common
Name
Source
IUPAC Name
Melting
Point
Boiling
Point
HCO2H
formic acid
ants (L. formica)
methanoic
acid
8.4 ºC
101 ºC
CH3CO2H
acetic acid
vinegar (L. acetum)
ethanoic acid
16.6 ºC
118 ºC
CH3CH2CO2H
propionic acid
milk (Gk. protus
prion)
propanoic acid
-20.8 ºC
141 ºC
CH3(CH2)2CO2H
butyric acid
butter (L. butyrum)
butanoic acid
-5.5 ºC
164 ºC
CH3(CH2)3CO2H
valeric acid
valerian root
pentanoic acid
-34.5 ºC
186 ºC
CH3(CH2)4CO2H
caproic acid
goats (L. caper)
hexanoic acid
-4.0 ºC
205 ºC
CH3(CH2)5CO2H
enanthic acid
vines (Gk. oenanthe)
heptanoic acid
-7.5 ºC
223 ºC
CH3(CH2)6CO2H
caprylic acid
goats (L. caper)
octanoic acid
16.3 ºC
239 ºC
CH3(CH2)7CO2H
pelargonic acid
pelargonium (an herb)
nonanoic acid
12.0 ºC
253 ºC
CH3(CH2)8CO2H
capric acid
goats (L. caper)
decanoic acid
31.0 ºC
219 ºC
SYNTHESIS OF
CARBOXYLIC ACIDS
Oxidation of Primary Alcohols
with KMnO4
R CH2 OH
KMnO4
heat
O
R C H
KMnO4
heat
two a-hydrogens
O
R C OH
+ MnO2
precipitate
Oxidation of Primary Alcohols
with K2Cr2O7
K2Cr2O7
R CH2 OH
H2SO4
O
R C H
K2Cr2O7
H2SO4
O
R C OH
3+
+ Cr
Oxidation of Side Chains
O
R
KMnO4
C OH
+ n CO2
heat
Example
O
CH2 CH3
O CH3
D
KMnO4
C OH
O CH3
Carbonation of Grignard Reagents
( or Alkyllithium Compounds )
O
R MgX +
CO2
R C O
ether
( R-Li )
H3O+
O
R C OH
+ MgX(OH)
+
MgX
Formation of Nitriles and Hydrolysis
R CH2 Cl
_
+ : C N:
SN2
DMSO
R CH2 C N
H2SO4
+ Cl
H 2O
heat
O
R CH2 C OH
+
+ NH4
SYNTHESIS OF CARBOXYLIC ACIDS
( DUE TO LACK OF SPACE REACTION CONDITIONS ARE ABBREVIATED)
R C C R
R
R
H
KMnO4
H
DIBAL or
Rosenmund
O
KMnO4
CrO3
or KMnO4
H2SO4
O
CrO3
H2SO4
R C OH
CO2
H2O
R C Cl
Chap 19 O
H2SO4
H2O
R
( benzene = R
sidechain = R’ )
R CH2 OH
KMnO4
O
R C H
R'
Li
or
H2O
H2SO4
R C N
KMnO4
R X
Li or
Mg
R Mg X
R C OR
NaCN
acetone
SOCl2
R OH
R
R
H
H
This is all stuff you know!
OH OH
Physical Properties of Carboxylic Acids
Physical Properties of Some Organic
Compounds
Formula
IUPAC Name
Molecular
Weight
Boiling
Point
Water Solubility
CH3(CH2)2CO2H
butanoic acid
88
164 ºC
very soluble
CH3(CH2)4OH
1-pentanol
88
138 ºC
slightly soluble
CH3(CH2)3CHO
pentanal
86
103 ºC
slightly soluble
CH3CO2C2H5
ethyl ethanoate
88
77 ºC
moderately soluble
CH3CH2CO2CH3
methyl propanoate
CH3(CH2)2CONH2
butanamide
CH3CON(CH3)2
88
80 ºC
87 216 ºC
N,N87 165 ºC
dimethylethanamide
CH3(CH2)4NH2
1-aminobutane
87 103 ºC
CH3(CH2)3CN
pentanenitrile
83 140 ºC
CH3(CH2)4CH3
hexane
86
69 ºC
slightly
soluble
soluble
very soluble
very soluble
slightly
soluble
insoluble
ACIDITY
Carboxylate Ion Formation
They are acids, ya know !
O
O
R CH2 C OH + NaOH
carboxylic acid
pKa

5
R CH2 C O
+
Na
carboxylate ion
+ H2O
Protonation and Deprotonation
of a Carboxylic Acid
.. H
+ O
..
..
:O
:O
.. R C O
:
..
NaOH
..
R C O
H
..
H2SO4
..
:O
..
R C O
H
H
+
H2SO4
..
R C O
H
..
.. H
:O
+
R C O H
..
equivalent structures
due to resonance
O
X C C OH
O
X C C O
+ H
• Electron-withdrawing Groups:
– strengthen acids
– weaken bases
• Electron-releasing Groups:
– weaken acids
– strengthen bases
+
Substituents with Electron-Withdrawing
Resonance ( - R ) Effects
X
Y
O
C OH
carboxyl
NO2
nitro
alkoxycarbonyl
C N
cyano
acyl
SO3H
sulfo
O
C OR
O
C R
-R substituents strengthen acids and weaken bases
Substituents with Electron-Releasing
Resonance ( + R ) Effects
..
OH
..
hydroxy
..
OR
..
O
..
O C R
..
alkoxy
..
SH
..
mercapto
CH3
methyl
CR3
alkyl
amino
..
NR2
dialkylamino
..
NH2
..
F
.. :
fluoro
..
Br :
..
bromo
..
:
Cl
..
..
I:
..
..
Y
acyloxy
chloro
iodo
+R substituents weaken acids and strengthen bases
Substituents with Electron-Withdrawing
( - I ) Inductive Effects
O
C OH
O
C OR
O
C R
OH
X
carboxyl
alkoxycarbonyl
acyl
hydroxyl
SH
mercapto
NH2
amino
Cl
chloro
NO2
nitro
C N
cyano
SO3H
sulfonic acid
OR
alkoxy
NR2
dialkylamino
F
fluoro
Br
bromo
I
iodo
+
N(CH3)3
trimethylammonium
-I substituents strengthen acids and weaken bases
Substituents with Electron-Releasing
Inductive ( + I ) Effects
R
CH3
methyl
O
CR3
alkyl
O
oxide
C O
carboxylate
+I substituents weaken acids and strengthen bases
O
pKa = 4.75
CH3 C OH
increasing
acidity
3.83
2.34
Br CH2 C OH
2.86
Cl CH2 C OH
2.86
O
O
H O CH2 C OH
3.12
O
O
H2N CH2 C OH
I CH2 C OH
O
O
O2N CH2 C OH
O
1.68
F CH2 C OH
2.66
O
CH3 C OH
O
pKa = 4.75
H C OH
O
O
Cl CH2 C OH
2.86
CH3 C OH
4.75
O
O
Cl CH C OH
3.77
1.29
CH3 CH2 C OH
4.88
Cl
O
CH3 CH C OH
Cl O
Cl
C C OH
0.65
4.86
CH3
Cl
CH3 O
CH3 C
CH3
C OH
5.05
COOH
ortho
Cl
COOH
Cl
2.16
ortho
NO2
COOH
3.82
3.47
meta
meta
NO2
COOH
Cl
COOH
pKa = 2.92
COOH
3.98
para
O2N
Benzoic Acid: pKa = 4.19
para
3.41
COOH
COOH
4.08
4.06
OCH3
OH
COOH
COOH
CH3 O
4.46
4.48
HO
COOH
Benzoic Acid: pKa = 4.19
2.97
OH
COOH
COOH
H3C
CH3
pKa = 4.27
Benzoic Acid: pKa = 4.19
4.36
Acidity of Carboxylic Acids
Compound
pKa
Compound
pKa
HCO2H
3.75
CH3CH2CH2CO2H
4.82
CH3CO2H
4.74
ClCH2CH2CH2CO2H
4.53
FCH2CO2H
2.65
CH3CHClCH2CO2H
4.05
ClCH2CO2H
2.85
CH3CH2CHClCO2H
2.89
BrCH2CO2H
2.90
C6H5CO2H
4.20
ICH2CO2H
3.10
p-O2NC6H4CO2H
3.45
Cl3CCO2H
0.77
p-CH3OC6H4CO2H
4.45
Reactions of Carboxylic Acids
• Nucleophiles that are also strong bases react with
carboxylic acids by removing a proton first, before any
nucleophilic substitution reaction can take place.
Nucleophilic acyl substitution reactions of carboxylic acids
• Treatment of a carboxylic acid with thionyl chloride
(SOCl2) affords an acid chloride.
• This is possible because thionyl chloride converts the
OH group of the acid into a better leaving group, and
because it provides the nucleophile (Cl¯) to displace the
leaving group.
• Although carboxylic acids cannot readily be converted
into anhydrides, dicarboxylic acids can be converted to
cyclic anhydrides by heating to high temperatures.
• This is a dehydration reaction because a water molecule
is lost from the diacid.
ESTERIFIKASI ASAM KARBOKSILAT
• Esterification of a carboxylic acid occurs in the presence
of acid but not in the presence of base.
• Base removes a proton from the carboxylic acid, forming
the carboxylate anion, which does not react with an
electron-rich nucleophile.
• Intramolecular esterification of g- and -hydroxyl
carboxylic acids forms five- and six-membered lactones.
• Carboxylic acids cannot be converted into amides by
reaction with NH3 or an amine because amines are
bases, and undergo an acid-base reaction to form an
ammonium salt before nucleophilic substitution occurs.
• However, heating the ammonium salt at high
temperature
(>100°C)
dehydrates
the
resulting
ammonium salt of the carboxylate anion to form an
amide, although the yield can be low.
• The overall conversion of RCOOH to RCONH2 requires
two steps:
[1] Acid-base reaction of RCOOH with NH3 to form an
ammonium salt.
[2] Dehydration at high temperature (>100°C).
• A carboxylic acid and an amine readily react to form an
amide in the presence of an additional reagent,
dicyclohexylcarbodimide (DCC), which is converted to
the by-product dicyclohexylurea in the course of the
reaction.
• DCC is a dehydrating agent.
• The dicyclohexylurea by-product is formed by adding
the elements of H2O to DCC.
• DCC promotes amide formation by converting the
carboxy group OH group into a better leaving group.
Carboxylic Acid Derivatives
Related Carbonyl Derivatives
Related Carbonyl Derivatives