Aromatic Carboxylic Acid 1 Dr Md Ashraful Alam 2 A carboxylic acid Contains a carboxyl group, which is a carbonyl group (C=O) attached to a hydroxyl

Aromatic Carboxylic Acid

1

Dr Md Ashraful Alam

2

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

Carboxylic Acids

3

The IUPAC names of carboxylic acids

• Replace the -e in the alkane name with -oic acid.

CH4 methane HCOOH methanoic acid

CH3—CH3 ethane 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

IUPAC Names

4

The common names of simple carboxylic acids• Are formic acid (1C), acetic acid (2C), propionic acid (3C),

and butyric acid (4C). HCOOH formic acidCH3—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)

Common Names

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Alpha Hydroxy Acids Alpha hydroxy

acids(AHAs)• Occur naturally

in fruit, milk, and sugarcane.

• Are used in skin care products.

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Names and Sources of Some Carboxylic Acids

TABLE 16.1

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Common Carboxylic Acids

Methanoic acid (formic acid) O ║

H─C─OH

ethanoic acid (acetic acid) O

║ CH3─C─OH

Aromatic Carboxylic Acid

Benzoic Acid

Phthalic Acid

Salicylic Acid

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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+

10

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.

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Naming Acid Derivatives

• Acid Halides, RCOXX– 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

Benzoyl bromide

OHC

O

OHC

O

ClNH2

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Naming Acid Anhydrides, RCO2COR'

• If symmetrical replace “acid” with “anhydride” based on the related carboxylic acid

Unsymmetrical anhydrides - cite the two acids alphabetically

Acetic anhydride Benzoic anhydride Succinic anhydride

•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.

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Substituent Effects on Acidity

• Electron-withdrawing Effects:– strengthen acids– weaken bases

• Electron-releasing Effects:– weaken acids– strengthen bases

+R C O

O

R C OH

O

H+

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Consider a para-substituted benzoic acid. We can draw resonance forms:

A B

COOH

A B

COOH

A B

COOH

A B

COOH

A B

COOH15


For the carboxylate ion, the corresponding resonance forms would be:

A B

COO

A B

COO

A B

COO

A B

COO

A B

COO16


•The positive charge in the ring

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 AcidityA

B

COOH

AB

COO

+ H+

The nitro group stabilizes the carboxylate anion and shifts the equilibrium to the right.

NO

COOH

NO

COO

+ H+

O O

NOTE: The nitro group also has an electron-withdrawing inductive effect

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•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).

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carboxyl

alkoxycarbonyl

acyl

nitro

cyano

sulfo

C OH

O

NO2

C OR

O

C R

O

C N

SO3H

-R substituents strengthen acids and weaken bases

Y

COOH

Y

COOH

Y

COOH

Y

COOH

Y

COOH

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Y

COOH

Y

COO

+ H+

Electron-donating resonance effect

•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.

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•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

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Substituents with Electron-Releasing Resonance EffectsSubstituents with Electron-Releasing Resonance Effects

..

..

..

..

..

..

..

..

..

..

..

..

..

..

..

..

..

..

::

: :

hydroxy

mercapto

methyl

amino

fluoro

bromo

alkoxy

acyloxy

alkyl

dialkylamino

chloro

iodo

OH

SH

CH3

NH2

F

Br

OR

O C R

O

CR3

NR2

Cl

I

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•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 electron-withdrawing inductive effect. This type of effect is often known as a -I effect.

+I substituents weaken acids and strengthen bases

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-I substituents strengthen acids and weaken bases

•-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.

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pKa = 2.92

3.82

3.98

2.16

3.47

3.41

COOH

NO2

COOH

Cl

COOH

Cl

COOH

Cl

COOH

NO2

COOH

O2N

Benzoic Acid: pKa = 4.1926


•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.

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Benzoic Acid: pKa = 4.19

pKa = 4.08

4.46

4.06

4.48

COOH

OCH3

COOH

OH

COOH

OCH3

COOH

OH

COOH

OH

2.97

28


29


COOH

OCH3

COOH COOH

NO2

COOH

NO2

COOH

NO2

p-methoxy benzoic acid m-nitro p-nitro o-nitro

pKa = 4.46 pKa = 4.19 pKa = 3.47 pKa = 3.41 pKa = 2.16 =>

Reactions

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Reduction to 1 Alcohols

• Use strong reducing agent, LiAlH4.

• Borane, BH3 in THF, reduces carboxylic acid to alcohol, but does not reduce ketone.

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Alkylation to Form Ketones

React 2 equivalents of an organolithium reagent with a carboxylic acid.

COOH 1)

2)

CH3CH2 Li2

H2O

C

O

CH2CH3

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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

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Mechanism of the Fischer Esterification

• acid-catalyzed, nucleophilic acyl substitution of a carboxylic acid

When 18O-labeled methanol reacts with benzoic acid, the methyl benzoate produced is 18O-labeled but the water produced is unlabeled

Mechanism of the Fischer EsterificationMechanism of the Fischer Esterification

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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.

Documents

Aromatic Carboxylic Acid 1 Dr Md Ashraful Alam 2 A carboxylic acid Contains a carboxyl group, which is a carbonyl group (C=O) attached to a hydroxyl