Transcript Slide 1

Aromatic Carboxylic Acid
Dr Md Ashraful Alam
1
Carboxylic Acids
A carboxylic acid
• Contains a carboxyl group, which is a
carbonyl group (C=O) attached to a hydroxyl
group (—OH).
• Has the carboxyl group on carbon 1.
carbonyl group
O

CH3 — C—OH hydroxyl group or CH3COOH
carboxyl group
2
IUPAC Names
The IUPAC names of carboxylic acids
• Replace the -e in the alkane name with -oic acid.
CH4
methane
CH3—CH3 ethane
HCOOH
methanoic acid
CH3—COOH ethanoic acid
• Number substituents from the carboxyl carbon 1.
CH3
O
|
║
CH3—CH—CH2—C—OH
4
3
2
1
3-methylbutanoic acid
3
Common Names
The common names of simple carboxylic acids
• Are formic acid (1C), acetic acid (2C), propionic
acid (3C), and butyric acid (4C).
HCOOH
formic acid
CH3—COOH
acetic acid
• Locate substituents using , , γ for the carbon
atoms adjacent to the carboxyl carbon.
CH3
γ |

CH3—CH—CH2—COOH
3-methylbutanoic acid (-methylbutryic acid)
4
Alpha Hydroxy Acids
Alpha hydroxy
acids
(AHAs)
• Occur
naturally in
fruit, milk, and
sugarcane.
• Are used in
skin care
products.
5
Names and Sources of Some
Carboxylic Acids
TABLE 16.1
6
Common Carboxylic Acids
Methanoic acid (formic acid)
O
║
H─C─OH
ethanoic acid (acetic acid)
O
║
CH3─C─OH
7
Aromatic Carboxylic Acid
Benzoic Acid
Phthalic Acid
Salicylic Acid
8
Acidity of Carboxylic Acids
Carboxylic acids
• Are weak acids.
• Ionize in water to produce carboxylate
ions
and hydronium ions.
O
O
║
║
CH3−C−OH + H2O CH3−C−O– + H3O+
9
Neutralization of Carboxylic Acids
Carboxylic acid salts
• Are a product of the neutralization of a carboxylic
acid with a strong base.
CH3—COOH + NaOH
CH3—COO– Na+ + H2O
acetic acid
sodium acetate
(carboxylic acid salt)
• Are used as preservatives and flavor enhancers.
10
Naming Acid Derivatives
• Acid Halides, RCOX
– Derived from the carboxylic acid name by replacing the
-ic acid ending with -yl or the
– -carboxylic acid ending with –carbonyl and
– specifying the halide
Benzoic Acid

O
O
C OH
C OH
Cl
NH2
Benzoyl bromide
11
Naming Acid Anhydrides, RCO2COR'
• If symmetrical replace “acid” with “anhydride” based on
the related carboxylic acid
Acetic anhydride

Benzoic anhydride
Succinic anhydride
Unsymmetrical anhydrides - cite the two acids
alphabetically
12
Substituent Effects on Acidity
•The essential idea is this: if a substituent removes
electrons from the negative oxygen of a carboxylate
ion, it will stabilize the ion. This effect shifts the
equilibrium to the right and increases acidity.
•If a substituent pours electrons toward the negative
oxygen of a carboxylate ion, it will destabilize the ion.
This effect will shift the equilibrium to the left and
decrease acidity.
13
Substituent Effects on Acidity
O
R
C
O
OH
R
C
O
+
+
H
• Electron-withdrawing Effects:
– strengthen acids
– weaken bases
• Electron-releasing Effects:
– weaken acids
– strengthen bases
14
Substituent Effects on Acidity
A
B
COOH
Consider a parasubstituted benzoic
acid. We can draw
resonance forms:
A
B
A
B
COOH
COOH
A
A
B
COOH
B
COOH
15
Substituent Effects on Acidity
A
B
COO
A
B
COO
A
B
COO
For the carboxylate ion, the
corresponding resonance forms
would be:
A
B
A
B
16
COO
COO
Substituent Effects on Acidity
B
B
A
A
+ H+
•The positive charge in the ring
COOH
COO
attracts the electrons on the carboxylate group. The
resonance effect of the substituent thus acts to
stabilize the anion and shift the equilibrium to the
right.
•In the unsubstituted benzoic acid, we are assuming
that the substituent (H) makes no difference in the
electron distribution in the ring.
•Thus, we would expect the -A=B substituted benzoic
acid to be a stronger acid than benzoic acid itself.
17
Substituent Effects on Acidity
The nitro group stabilizes the carboxylate anion and shifts the
equilibrium to the right.
O
O
N
O
O
N
+ H+
COOH
COO
NOTE: The nitro group also has an electron-withdrawing
inductive effect
18
Substituent Effects on Acidity
•The resonance effect of a substituent of the -A=B type reduces
the electron density in the benzene ring. The resonance forms
shown here represent this reduction of electron density by
showing positive charge in the ring.
•As a result, these substituents exert an electron-withdrawing
resonance effect (sometimes represented as a -R effect).
-R substituents strengthen acids and weaken bases
O
C
OH
carboxyl
OR
alkoxycarbonyl
NO2
nitro
O
C
C
N
cyano
O
C
R
acyl
SO3H
sulfo
19
Substituent Effects on Acidity
Electron-donating
resonance effect
Y
Y
Y
Y
COOH
COOH
COOH
Y
COOH
COOH
Y
+
COOH
Y
COO
H+
20
Substituent Effects on Acidity
•The negative charge in the ring repels the electrons
on the carboxylate group. The resonance effect of the
substituent thus acts to destabilize the anion and shift
the equilibrium to the left.
•Remember that we are comparing the substituted
benzoic acid with unsubstituted benzoic acid. In the
unsubstituted benzoic acid, we are assuming that the
substituent (H) makes no difference in the electron
distribution in the ring.
•Thus, we would expect the -Y substituted benzoic
acid to be a weaker acid than benzoic acid itself.
21
Substituent Effects on Acidity
•The resonance effect of a substituent of the -Y type
increases the electron density in the benzene ring. The
resonance forms shown here represent this increase of
electron density by showing negative charge in the ring.
•As a result, these substituents exert an electron-releasing/
electron-donating resonance effect (sometimes represented
as a +R effect).
•The following table shows several substituent groups that
exert an electron-releasing resonance (+R) effect.
+R substituents weaken acids and strengthen bases
22
Substituents with Electron-Releasing Resonance Effects
..
OH
..
hydroxy
..
OR
..
alkoxy
O
..
SH
..
mercapto
..
O
..
CH3
methyl
CR3
alkyl
amino
..
NR2
dialkylamino
fluoro
..
Cl :
..
chloro
..
I:
..
iodo
..
NH2
..
F:
..
..
Br :
..
bromo
C
R
acyloxy
23
Substituent Effects on Acidity
•Electronegative substituents attract electrons.
•When electronegative elements are present in a
molecule that can act as an acid, they enhance the acidity
of the bond because they lower the electron density in
that bond and because they stabilize the conjugate base.
•Substituents of this type are said to have an electronwithdrawing inductive effect. This type of effect is often
known as a -I effect.
-I substituents strengthen acids and weaken bases
+I substituents weaken acids and strengthen bases
24
Substituent Effects on Acidity
•-Cl has two competing effects: +R and -I
•In the case of the chloro group, the -I effect is larger than
the +R effect, so we see the -I effect. As the chloro group
moves farther away from the carboxyl group, the acid
becomes weaker.
•In the case of the nitro substituent, both the inductive and
resonance effects are electron-withdrawing (acid
strengthening).
•But the nitro group is more effective from the para
position than from the meta position. This is because the
resonance effect is contributing in the para position.
25
Substituent Effects on Acidity
COOH
COOH
pKa = 2.92
2.16
Cl
NO2
COOH
COOH
3.82
3.47
NO2
Cl
COOH
COOH
3.98
Cl
3.41
O2N
Benzoic Acid: pKa = 4.19
26
Substituent Effects on Acidity
•In the next example, we see the larger +R effects of
the methoxy and hydroxy groups predominating
over the smaller -I effects.
•We can see that the substituted benzoic acids are
significantly weaker when the -OH or -OCH3 groups
are in the para positions than when they are in the
meta positions (where the +R effect is not
significant).
•ortho-Hydroxybenzoic acid (salicylic acid) is much
stronger than we would predict.
27
Substituent Effects on Acidity
COOH
COOH
pKa = 4.08
4.06
OCH3
OH
COOH
COOH
4.48
4.46
CH3 O
HO
COOH
2.97
OH
Benzoic Acid: pKa = 4.19
28
Substituent Effects on Acidity
COOH
COOH
COOH
COOH
COOH
NO2
NO2
OCH3
p-methoxy benzoic acid
pKa = 4.46
m-nitro
pKa = 4.19 pKa = 3.47
NO2
p-nitro
pKa = 3.41
o-nitro
pKa = 2.16
=>
29
Reactions
Reduction to 1 Alcohols
• Use strong reducing agent, LiAlH4.
• Borane, BH3 in THF, reduces carboxylic acid to
alcohol, but does not reduce ketone.
31
Alkylation to Form Ketones
React 2 equivalents of an organolithium
reagent with a carboxylic acid.
O
COOH
1) 2 CH3CH2
Li
C CH CH
2
3
2) H2O
32
Fischer Esterification
• Heating a carboxylic acid in an alcohol solvent
containing a small amount of strong acid produces an
ester from the alcohol and acid
33
Mechanism of the Fischer Esterification
• acid-catalyzed,
nucleophilic acyl
substitution of a
carboxylic acid
34
Mechanism of the Fischer Esterification
When 18O-labeled methanol reacts with benzoic acid, the
methyl benzoate produced is 18O-labeled but the water
produced is unlabeled
35
Aspirin, Arachidonic Acid, and Prostaglandins
Aspirin (acetylsalicylic acid) is a synthetic carboxylic acid, similar in structure to
salicin, a naturally occurring compound isolated from willow bark, and salicylic acid,
found in meadowsweet.
Salts of carboxylic acids are commonly used as
preservatives. Sodium benzoate is a preservative
used in soft drinks and baked goods.
Preparation of Carboxylic Acids
Oxidation of alkyl benzenes
• An acid can be deprotonated by a base having a conjugate acid with a higher pKa.
• Because the pKa values of many carboxylic acids are ~5, bases that have conjugate
acids with pKa values higher than 5 are strong enough to deprotonate them.