Carboxylic Acids: Properties and Synthesis

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Substituent Effects on the Acidities of
Carboxylic Acids
2

• 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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• 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 represent such a substituent, where
B is more electronegative than A.
7
In other words, lets compare the acidities of
Which acid is stronger, and why?
8
The substituent will be a hybrid of two or more
resonance forms of the type
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.
9
To illustrate, consider a para-substituted
benzoic acid. We can draw resonance forms
10
For the carboxylate ion, the corresponding
resonance forms would be
11
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
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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 -AB substituted
  benzoic acid to be a stronger acid than benzoic
  acid itself.

13
A specific example of the -AB 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).
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The nitro group stabilizes the carboxylate anion
and shifts the equilibrium to the right.
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 -AB
  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.

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Substituents with Electron-Withdrawing Resonance
Effects
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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 represent such a substituent.
20
In other words, lets compare the acidities of
Which acid is stronger, and why?
21
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.
22
To illustrate, consider a para-substituted
benzoic acid. We can draw resonance forms
23
For the carboxylate ion, the corresponding
resonance forms would be
24
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
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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).
27
The methoxy group destabilizes the carboxylate
anion and shifts the equilibrium to the left.
NOTE The methoxy group also has an
electron-withdrawing inductive effect this has
been ignored in this discussion. Inductive
effects will be examined later.
28

• 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 Electron-Releasing Resonance
Effects
30

• 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.

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R substituents weaken acids and strengthen bases
32
In the case of the alkyl substituents (which have
no unshared pairs of electrons), their
electron-releasing resonance effect arises from
hyperconjugation.
p-Methylbenzoic acid is less acidic than benzoic
acid by a factor of 1.5 (0.17 log units)
33
Inductive Effects on the Acidities of Carboxylic
Acids
34
Lets now compare the acidities of two aliphatic
carboxylic acids
where X is an electronegative element.
35

• 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

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Substituents with Electron-Withdrawing Inductive
Effects
37
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
39
And one last case, again comparing two aliphatic
carboxylic acids
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
  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.

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Substituents with Electron-Releasing Inductive
Effects
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I substituents weaken acids and strengthen bases
43
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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46

• 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.

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48

• 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
  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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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
  ortho-substituted benzoic acids, there is an
  anomaly.
• ortho-Hydroxybenzoic acid (salicylic acid) is
  much stronger than we would predict.

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2.97
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.
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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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Benzoic Acid pKa 4.19