Transcript Carboxylic Acids: Properties and Synthesis

Substituent Effects on the Acidities of
Carboxylic Acids
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•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.
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•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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O
R
C
O
OH
R
C
O
+
+
H
• Electron-withdrawing Effects:
– strengthen acids
– weaken bases
• Electron-releasing Effects:
– weaken acids
– strengthen bases
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Resonance Effects on the Acidities of
Carboxylic Acids
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Resonance Effects of
Substituents
Consider a substituent that contains multiple bonds.
Let
A
B
represent such a substituent, where B is more
electronegative than A.
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In other words, let’s compare the acidities of:
O
O
and
C
B
OH
A
C
OH
Which acid is stronger, and why?
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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.
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To illustrate, consider a para-substituted benzoic acid. We
can draw resonance forms:
A
B
COOH
A
B
A
B
COOH
COOH
A
A
B
COOH
B
COOH
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For the carboxylate ion, the corresponding resonance forms
would be:
A
COO
B
A
B
COO
A
COO
A
B
COO
B
A
B
COO
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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:
B
B
A
A
+ H+
COOH
COO
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•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.
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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).
O
pKa = 4.19
C
OH
O
O 2N
pKa = 3.4
C
OH
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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; this has been ignored in this discussion.
Inductive effects will be examined later.
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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 electronwithdrawing 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.
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Substituents with ElectronWithdrawing Resonance Effects
O
C
OH
carboxyl
OR
alkoxycarbonyl
NO2
nitro
O
C
C
N
cyano
O
C
R
acyl
SO3H
sulfo
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•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.
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-R substituents strengthen acids
and weaken bases
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Resonance Effects of
Substituents (Part Two)
Consider a substituent that contains an atom that
bears one or more unshared pairs of electrons.
Let
Y
represent such a substituent.
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In other words, let’s compare the acidities of:
O
O
and
C
OH
Y
C
OH
Which acid is stronger, and why?
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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.
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To illustrate, consider a para-substituted benzoic acid. We
can draw resonance forms:
Y
Y
Y
COOH
COOH
COOH
Y
Y
COOH
COOH
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For the carboxylate ion, the corresponding resonance forms
would be:
Y
Y
Y
COO
COO
COO
Y
Y
COO
COO
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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
Y
+ H+
COOH
COO
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•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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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).
O
pKa = 4.19
C
OH
O
CH3 O
pKa = 4.46
C
OH
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The methoxy group destabilizes the carboxylate anion
and shifts the equilibrium to the left.
CH3
CH3
O
O
+ H+
COOH
COO
NOTE: The methoxy group also has an electronwithdrawing inductive effect; this has been ignored in this
discussion. Inductive effects will be examined later.
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•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.
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Substituents with ElectronReleasing 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
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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
resonance effect. This is sometimes called an electrondonating 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.
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+R substituents weaken acids and
strengthen bases
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In the case of the alkyl substituents (which have no
unshared pairs of electrons), their electron-releasing
resonance effect arises from hyperconjugation.
O
pKa = 4.19
C
OH
O
CH3
pKa = 4.36
C
OH
p-Methylbenzoic acid is less acidic than benzoic acid by a
factor of 1.5 (0.17 log units)
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Inductive Effects on the Acidities of
Carboxylic Acids
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Let’s now compare the acidities of two aliphatic
carboxylic acids:
O
O
H
and
CH2 C
X
OH
CH2 C
OH
where X is an electronegative element.
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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 electronwithdrawing 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:
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Substituents with ElectronWithdrawing Inductive Effects
O
C
OH
carboxyl
O
C
NO2
C
OR
alkoxycarbonyl
nitro
N
cyano
SO3H
sulfo
OR
alkoxy
O
C
R
acyl
NR2
OH
SH
NH2
Cl
hydroxy
mercapto
amino
chloro
dialkylamino
F
fluoro
Br
bromo
I
iodo
+
N(CH3)3 trimethylammonium
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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.
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-I substituents strengthen acids
and weaken bases
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And one last case, again comparing two aliphatic
carboxylic acids:
O
O
H
and
CH2 C
OH
R
CH2 C
OH
The alkyl substituent (R) is weakly electropositive with
respect to a hydrogen.
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•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 electronreleasing (or electron-donating) inductive effect.
•An electron-releasing inductive effect is sometimes
known as a +I effect.
•The following table lists several +I substituents.
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Substituents with ElectronReleasing Inductive Effects
CH3
methyl
O
CR3
alkyl
O
oxide
C
O
carboxylate
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+I substituents weaken acids and
strengthen bases
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To illustrate the resonance and inductive effects
described in this unit, consider the following
examples:
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•The following table illustrates electron-withdrawing
resonance effects.
•Notice how the pKa values compare with the
reference compound, acetic acid.
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O
CH3 C
O
OH
pKa = 4.75
I
CH2 C
OH
2.66
O2N CH2 C
CH2 C
OH
2.86
HO
CH2 C
OH
1.68
CH2 C
OH
3.83
OH
2.34
O
O
Br
3.12
O
O
Cl
OH
O
O
F
CH2 C
OH
2.86
H2N
CH2 C
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•The next table shows the effect on acidity that
results from multiple substitution. Both electronwithdrawing and electron-releasing examples are
included.
•Again, acetic acid is used as a reference.
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O
CH3 C
O
OH
pKa = 4.75
H
CH2 C
OH
2.86
CH3 C
CH C
OH
1.29
CH3 CH2 C
Cl
Cl
OH
4.75
OH
4.88
OH
4.86
OH
5.05
O
Cl
O
C
C
Cl
3.77
O
O
Cl
OH
O
O
Cl
C
CH3 CH C
OH
0.65
CH3
CH3 O
CH3 C
C
CH3
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•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.
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•In the case of the nitro substituent, both the
inductive and resonance effects are electronwithdrawing (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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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
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•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 orthosubstituted benzoic acids, there is an anomaly.
•ortho-Hydroxybenzoic acid (salicylic acid) is much
stronger than we would predict.
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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
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When there is a hydroxy group ortho to the carboxylic
acid functional group, the carboxylate ion is stabilized
through intramolecular hydrogen bonding.
O
C
O
H
O
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•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).
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COOH
COOH
H3C
CH3
pKa = 4.27
4.36
Benzoic Acid: pKa = 4.19
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