Organic Lecture Series
Carboxylic Acids
Chapter 17
1
Structure
Organic Lecture Series
• The functional group of a carboxylic acid is
a carboxyl group
O
C
O H
O
COOH
O H
CO2 H
Alternative rep res entation s for a carboxyl grou p
– the general formula for an aliphatic carboxylic
acid is RCOOH; that for an aromatic
carboxylic acid is ArCOOH
2
Organic Lecture Series
Nomenclature
• IUPAC names: drop the -e from the parent
alkane and add the suffix -oic acid
O
HCOOH
CH3 COOH
Methan oic acid
(Formic acid )
Eth anoic acid
(Acetic acid)
OH
3-Methylbutanoic acid
(Isovaleric acid )
– if the compound contains a carbon-carbon
double bond, change the infix -anan to -enen
O
O
O
OH
Propen oic acid
(A crylic acid)
OH
OH
t rans-2-Butenoic acid
(Crotonic acid )
t rans-3-Phen ylp ropen oic acid
(Cinnamic acid )
3
Organic Lecture Series
• The carboxyl group takes precedence over
most other functional groups
OH
O
O
OH
(R)-5-Hydroxyhexan oic
acid
O
O
OH
5-Oxohexan oic acid
H2 N
OH
4-Aminobutan oic acid
O
O
δ γ β
α
5
1
3
4
2
OH
OH
OH
γ-hydroxybutyric Acid
GHB
4
Organic Lecture Series
Nomenclature
– 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
HO
OH
O
Pentanedioic acid
(Glutaric acid)
Hexanedioic acid
(Adipic acid)
5
Organic Lecture Series
Nomenclature
– if the carboxyl group is bonded to a ring, name the
ring compound and add the suffix -carboxylic acid
2
3
1
COOH
2-Cyclohexen ecarboxylic
acid
HOOC
COOH
t rans-1,3-Cyclopentan edicarboxylic
acid
– benzoic acid is the simplest aromatic carboxylic acid
– use numbers to show the location of substituents
COOH
COOH
OH
COOH
COOH
COOH
COOH
Benzoic 2-Hydroxyben zoic 1,2-Benzenedicarb oxylic 1,4-Ben zenedicarboxylic
acid
acid
acid
acid
(Tereph thalic acid )
(Ph thalic acid )
(Salicylic acid )
6
Organic Lecture Series
Nomenclature
– when common names are used, the
letters α, β, γ, δ, etc. are often used to
locate substituents
O
δ γ β
α
5
1
3
4
2
O
O
OH
H2 N
OH
4-A min ob utanoic acid
(γ-A min obu tyric acid, GABA)
OH
NH2
(S)-2-Aminopropanoic acid
[(S)-α-Aminop ropionic acid;
L-alanine]
7
Organic Lecture Series
Physical Properties
• In the liquid and solid states, carboxylic
acids are associated by hydrogen bonding
into dimeric structures
8
Organic Lecture Series
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
9
Organic Lecture Series
Physical Properties
• 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
10
Organic Lecture Series
Physical Properties
Molecu lar Boiling
Weight
Point
(°C)
(g/mol)
Solu bility
(g/100 g H 2 O)
Structu re
Name
CH3 COOH
Acetic acid
60.1
118
Infinite
CH3 CH2 CH2 OH
1-Propan ol
60.1
97
Infinite
CH3 CH2 CHO
Propan al
58.1
48
16
88.1
88.1
86.1
163
137
103
Infinite
2.3
Slight
CH3 ( CH2 ) 4 COOH Hexan oic acid 116.2
CH3 (CH2 ) 5 CH2 OH 1-Hep tanol
116.2
205
1.0
176
CH3 ( CH2 ) 5 CHO
153
0.2
0.1
CH3 ( CH2 ) 2 COOH Butanoic acid
CH3 (CH2 ) 3 CH2 OH 1-Pentanol
CH3 ( CH2 ) 3 CHO
Pentanal
Hep tanal
114.1
11
Organic Lecture Series
Physical Properties
– water solubility decreases as the relative
size of the hydrophobic portion of the
molecule increases
12
Organic Lecture Series
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 that
contain an OH group) is due to resonance
stabilization of the carboxylate anion:
O
H 3C
O
O
OH
H
H 3C
O
H 3C
O
13
Acidity
Organic Lecture Series
– electron-withdrawing substituents near
the carboxyl group increase acidity
through their inductive effect
Formula: CH3 COOH ClCH2 COOH
Cl2 CHCOOH
Name: Acetic
Chloroacetic D ich loroacetic
acid
acid
acid
2.86
pKa :
1.48
4.76
Cl3 CCOOH
Trich loroacetic
acid
0.70
Increasin g acid strength
14
Organic Lecture Series
– the form of a carboxylic acid present in
aqueous solution depends on the pH of the
solution
O
O
O
O
OH
OH
+ R-C-O
R-C-OH
R-C-OH
R-C-O
+
+
H
H
predomin ant
present in eq ual
p red ominan t
species w hen
concentrations w hen
sp ecies w hen
the pH of the
the pH of the
th e pH of the
s olution is
solution is
solution is eq ual to
2.0 or less
7.0 or greater
the pK a of the acid
[A-]
pH = pKa + log10
[HA]
15
Organic Lecture Series
For organic acids in equilibrium:
HA
+
H + A
-
Henderson-Hasselbalch equation:
[A-]
pH = pKa + log10
[HA]
16
Reaction with Bases
Organic Lecture Series
Carboxylic acids, whether soluble or
insoluble in water, react with NaOH, KOH,
and other strong bases to give watersoluble salts
COOH
+
N aOH
-
H2 O
Benzoic acid
(slightly soluble
in water)
Acid
+
COO Na
+
+
H2 O
Sodium benzoate
(60 g/100 mL water)
Base
+
Salt
water
17
Reaction with Bases
Organic Lecture Series
• They also form water-soluble salts with
ammonia and amines
COOH + NH 3
Benzoic acid
(slightly soluble
in water)
-
H2 O
COO NH4
+
Ammonium benzoate
(20 g/100 mL water)
18
Reaction with Bases
Organic Lecture Series
• 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 + NaHCO3
H2 CO3
CH3 COOH + NaHCO3
+
CH3 COO Na + H2 CO3
CO2 + H2 O
-
CH3 COO Na
+ +
CO2 + H2 O
19
Organic Lecture Series
Preparation
• Carbonation of Grignard reagents
– treatment of a Grignard reagent with carbon
dioxide followed by acidification gives a
carboxylic acid
O
MgBr + C
O
Carb on dioxid e
O
C-O - [MgBr] +
A magnesium carboxylate
HCl
H2 O
O
C-OH + Mg2 +
Cyclop entanecarboxylic acid
20
Organic Lecture Series
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
• 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
2 . H2 O
CH2 OH + LiOH + Al(OH) 3
4-Hydroxymeth ylcyclopenten e
21
Selective Reduction
Organic Lecture Series
– carboxyl groups are not affected by catalytic
reduction under conditions that reduce
aldehydes and ketones
O
OH
O
OH + H2
5-Oxohexanoic acid
Pt
25°C, 2 atm
O
OH
5-Hydroxyhexan oic acid
(racemic)
– nor are carboxyl groups reduced by NaBH4
O
O
OH
O
1 . NaBH4
C6 H5
OH
2 . H2 O
5-Oxo-5-ph enylp entanoic acid
5-Hyd roxy-5-phenylpen tanoic acid
(racemic)
C6 H5
OH
22
Organic Lecture Series
Fischer Esterification
• Esters can be prepared by treating a
carboxylic acid with an alcohol in the
presence of an acid catalyst, commonly
H2SO4, ArSO3H*, or gaseous HCl
O
H2 SO 4
OH
Ethanoic acid
(Acetic acid)
+
HO
Ethanol
(Ethyl alcohol)
O
O
Ethyl ethanoate
(Ethyl acetate)
+
H2 O
O
*H C
3
S
OH
O
T o lu e n e S u lfo n ic A c id
TsO H
Fischer Esterification
23
Organic Lecture Series
Fischer esterification is an equilibrium
reaction:
ƒ by careful control of experimental conditions, it
is possible to prepare esters in high yield
ƒ if the alcohol is inexpensive relative to the
carboxylic acid, it can be used in excess to
drive the equilibrium to the right
ƒ alternatively, water can be removed by
azeotropic distillation and a Dean-Stark trap
24
Organic Lecture Series
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
TCAI
H
R C OCH3
O
H
H+
H+
O
R C OH + HOCH3
O
R C OCH 3 + HOH
Refer to mechanism worksheet
25
Organic Lecture Series
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
Functional group
of an acid halide
O
CH 3 CCl
A cetyl
chloride
O
C-Cl
Benzoyl
chloride
26
Organic Lecture Series
Acid Chlorides
– acid chlorides are most often prepared
by treating a carboxylic acid with
thionyl chloride
O
OH
Bu tanoic acid
O
+ SOCl2
+ SO2 + HCl
Cl
Th ionyl ch loride Butanoyl chlorid e
27
Organic Lecture Series
Acid Chlorides
• The mechanism for this reaction is divided
into two steps.
Step 1: reaction with SOCl2 transforms OH, a
poor leaving group, 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 chloros ulfite
grou p
28
Organic Lecture Series
Acid Chlorides
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 + SO2 + Cl
-
Cl
A tetrah edral carbonyl
ad dition intermed iate
Note: the reaction is irreversible
29
Organic Lecture Series
Decarboxylation
• Decarboxylation: loss of CO2 from a carboxyl
group
– carboxylic acids, if heated to a very high
temperature, undergo thermal decarboxylation
O
R-C-OH
decarb oxylation
heat
R-H + CO2
– most carboxylic acids, however, are quite
resistant to moderate heat and melt or even boil
without decarboxylation
30
Organic Lecture Series
Decarboxylation
The most important exceptions are carboxylic
acids that have a carbonyl group beta to the
carboxyl group i.e.- β keto-acids
–this type of carboxylic acid undergoes
decarboxylation on mild heating
O
O
O
warm
β α
OH
3-Oxobu tan oic acid
(Acetoacetic acid)
+
CO2
Acetone
31
Organic Lecture Series
Decarboxylation
– thermal decarboxylation of a β-ketoacid
involves rearrangement of six electrons
in a cyclic six-membered transition state
O
H
O
(1)
O
(A cyclic s ix-membered
tran sition state)
O
H
O
+ C
O
En ol of
a ketone
(2)
O
+ CO2
A ketone
32
Organic Lecture Series
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
Prop anedioic acid
(Malon ic acid )
O
CH3 COH + CO2
33
Organic Lecture Series
– thermal decarboxylation of malonic
acids also involves rearrangement of six
electrons in a cyclic six-membered
transition state
O
HO
H
O
O
(1)
O
HO
H
O
+ C
O
A cyclic six-membered
Enol of a
transition s tate
carb oxylic acid
(2)
O
HO
A carb oxylic
acid
+ CO2
34