wwu- chemistry substituent effects on the acidities of carboxylic acids

WWU- ChemistryWWU- Chemistry

Substituent Effects on the Acidities of Substituent Effects on the Acidities of Carboxylic AcidsCarboxylic Acids


•When substituents are attached to a molecule, such as a carboxylic acid, they can influence the acidity (or basicity) of that substance.

•Some substituents strengthen acids and weaken bases; other substituents have the opposite effect, the weaken acids and strengthen bases.

•Substituents exert their effects on acidity or basicity through a combination of resonance and inductive effects.

•REVIEW: Lecture Textbook, Chapter 7, especially sections 7.6 through 7.8.


•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.


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

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

+R C O

O

R C OH

O

H+


Resonance Effects on the Acidities of Resonance Effects on the Acidities of Carboxylic AcidsCarboxylic Acids


Resonance Effects of Substituents

Consider a substituent that contains multiple bonds.

Let

represent such a substituent, where B is more electronegative than A.

A B


In other words, let’s compare the acidities of:

C

OH

O

C

OH

O

and AB

Which acid is stronger, and why?


The substituent will be a hybrid of two or more resonance forms of the type:

A B A B

The presence of the substituent on a molecule will influence the electron distribution throughout the entire structure. This type of effect, called a resonance effect, can be seen most clearly when the substituent is attached to a benzene ring.


To illustrate, 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

COOH


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

A B

COO

A B

COO

A B

COO

A B

COO

A B

COO


The resonance forms that are the most important in our discussion are those forms where the positive charge is located on the carbon atom that also bears the functional group. The ionization of the substituted benzoic acid can thus be analyzed by examining the following equilibrium:

AB

COOH

AB

COO

+ H+


•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.

•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 -A=B substituted benzoic acid to be a stronger acid than benzoic acid itself.


A specific example of the -A=B type of substituent is the nitro group (-NO2). A nitro group in the para position of a benzoic acid strengthens the acidity by a factor of six (0.8 log units).

C

OH

O

C

OH

O

O2N

pKa = 4.19

pKa = 3.4


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; this has been ignored in this discussion. Inductive effects will be examined later.


•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.

•This is sometimes represented as a -R effect.

•The following table shows several substituent groups that exert an electron-withdrawing resonance (-R) effect.


Substituents with Electron-Substituents with Electron-Withdrawing Resonance EffectsWithdrawing Resonance Effects

carboxyl

alkoxycarbonyl

acyl

nitro

cyano

sulfo

C OH

O

NO2

C OR

O

C R

O

C N

SO3H


•The resonance forms show that positive charge is located at the ortho and para positions with respect to the substituent.

•A functional group that is located ortho or para to the substituent will be influenced by the resonance effect. A substituent located meta to the substituent will be affected to a much smaller degree.

•Therefore, we would expect that whenever a -R substituent is located ortho or para to a carboxyl group, the acidity of the benzoic acid should be increased.


-R substituents strengthen acids and weaken bases


Resonance Effects of Substituents (Part Two)

Consider a substituent that contains an atom that bears one or more unshared pairs of electrons.

Let

represent such a substituent.

Y


In other words, let’s compare the acidities of:

C

OH

O

C

OH

O

and Y

Which acid is stronger, and why?


When this substituent is attached to the benzene ring, the unshared electron pairs will be shifted into the ring through resonance.

Once again, the presence of the substituent on a molecule will influence the electron distribution throughout the entire structure. This is another example of a resonance effect.


To illustrate, consider a para-substituted benzoic acid. We can draw resonance forms:

Y

COOH

Y

COOH

Y

COOH

Y

COOH

Y

COOH


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

Y

COO

Y

COO

Y

COO

Y

COO

Y

COO


The resonance forms that are the most important in our discussion are those forms where the negative charge is located on the carbon atom that also bears the functional group. The ionization of the substituted benzoic acid can thus be analyzed by examining the following equilibrium:

Y

COOH

Y

COO

+ H+


•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.


A specific example of the -Y type of substituent is the methoxy group (-OCH3). A methoxy group in the para position of a benzoic acid weakens the acidity by a factor of 1.9 (0.27 log units).

C

OH

O

C

OH

O

O

pKa = 4.19

pKa = 4.46CH3


The methoxy group destabilizes the carboxylate anion and shifts the equilibrium to the left.

OCH3

COOH

OCH3

COO

+ H+

NOTE: The methoxy group also has an electron-withdrawing inductive effect; this has been ignored in this discussion. Inductive effects will be examined later.


•The resonance forms show that electron density is increased at the ortho and para positions with respect to the substituent.

•A functional group that is located ortho or para to the substituent will be influenced by the resonance effect. A substituent located meta to the substituent will be affected to a much smaller degree.

•Therefore, we would expect that whenever a +R substituent is located ortho or para to a carboxyl group, the acidity of the benzoic acid should be decreased.


Substituents with Electron-Substituents with Electron-Releasing Resonance EffectsReleasing 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


•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 resonance effect. This is sometimes called an electron-donating resonance effect.

•This is 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


In the case of the alkyl substituents (which have no unshared pairs of electrons), their electron-releasing resonance effect arises from hyperconjugation.

C

OH

O

C

OH

O

CH3

pKa = 4.19

pKa = 4.36

p-Methylbenzoic acid is less acidic than benzoic acid by a factor of 1.5 (0.17 log units)


Inductive Effects on the Acidities of Inductive Effects on the Acidities of Carboxylic AcidsCarboxylic Acids


Let’s now compare the acidities of two aliphatic carboxylic acids:

H CH2 C

OH

O

and X CH2 C

OH

O

where X is an electronegative element.


•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.

•The following table lists a number of substituents that have -I inductive effects:


Substituents with Electron-Substituents with Electron-Withdrawing Inductive EffectsWithdrawing Inductive Effects

carboxyl

alkoxycarbonyl

acyl

nitro

cyano

sulfo

hydroxy

mercapto

dialkylamino

chloro

alkoxy

amino

fluoro

bromo

iodo

+trimethylammonium

C OH

O

C OR

O

C R

O

NO2

C N

SO3H

OR

NH2

F

Br

OH

SH

NR2

Cl

I

N(CH3)3


As before, whenever we consider the resonance or inductive effect of a substituent, we are comparing it with a reference substituent, hydrogen.

When hydrogen is the substituent, it is treated as if it had no resonance or inductive effect.


-I substituents strengthen acids and weaken bases


And one last case, again comparing two aliphatic carboxylic acids:

H CH2 C

OH

O

and R CH2 C

OH

O

The alkyl substituent (R) is weakly electropositive with respect to a hydrogen.


•When an electropositive substituent is placed in a molecule, we should see the opposite type of effect than we saw when electronegative substituents were present.

•An electropositive substituent should show an electron-releasing (or electron-donating) inductive effect.

•An electron-releasing inductive effect is sometimes known as a +I effect.

•The following table lists several +I substituents.


Substituents with Electron-Substituents with Electron-Releasing Inductive EffectsReleasing Inductive Effects

CH3

CR3

O

C O

O

methyl

alkyl

oxide

carboxylate


+I substituents weaken acids and strengthen bases


To illustrate the resonance and inductive effects described in this unit, consider the following examples:


•The following table illustrates electron-withdrawing resonance effects.

•Notice how the pKa values compare with the reference compound, acetic acid.


pKa = 4.75

2.66

2.86

2.86

3.12

1.68

3.83

2.34

CH3 C OH

O

CH2 C OH

O

F

CH2 C OH

O

Cl

CH2 C OH

O

Br CH2 C OH

O

NH2

CH2 C OH

O

I

CH2 C OH

O

O2N

CH2 C OH

O

OH


•The next table shows the effect on acidity that results from multiple substitution. Both electron-withdrawing and electron-releasing examples are included.

•Again, acetic acid is used as a reference.


pKa = 4.75

2.86

1.29

0.65

3.77

4.75

4.88

4.86

5.05

CH3 C OH

O

Cl CH2 C OH

O

Cl CH C OH

O

Cl

Cl C C OH

O

Cl

Cl

CH3 CH2 C OH

O

CH3 CH C OH

O

CH3

CH3 C C OH

OCH3

CH3

CH3 C OH

O

C OH

O

H


•In the next table, the effect of a chlorine substituent on the strength of a benzoic acid is shown.

•The reference compound is benzoic acid.

•-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.


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 = 4.19


•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).

•But we see that when we compare the two ortho-substituted benzoic acids, there is an anomaly.

•ortho-Hydroxybenzoic acid (salicylic acid) is much stronger than we would predict.



pKa = 4.08

4.46

4.06

4.48

COOH

OCH3

COOH

OH

COOH

OCH3

COOH

OH

COOH

OH

2.97


When there is a hydroxy group ortho to the carboxylic acid functional group, the carboxylate ion is stabilized through intramolecular hydrogen bonding.

OH

CO

O


•Finally, we see the acid-weakening effect (both +R and +I) of a methyl substituent.

•When the methyl group is in the para position, it is more effective in weakening the benzoic acid. This is because the +R effect is operating from the para position (when the methyl group is in the meta position, we only see the +I effect).



COOH

CH3

COOH

CH3

pKa = 4.27 4.36

wwu- chemistry substituent effects on the acidities of carboxylic acids

Documents

substituent effects

unsubstituted benzoic

b type of substituent

substituent h

stronger acid

type of effect

inductive effects

carboxylate group