3. Inductive Effect – movement of electron density thru bonds in response to
differences in electronegativities, etc.
• EWG – electron-withdrawing groups pull electron density towards themselves (like
electronegative atoms)
• EDG – electron-donating groups have an excess of electron density and push it out
to other areas of molecule (such as alkyl groups)
EWG’s stabilize anions by pulling electron density away from one specific atom,
spreading out electron density over many atoms. In this case, the electronegative
chlorine atom is pulling electrons towards itself, away from the carbon, which pulls from
the carbonyl carbon and thus away from the oxygen
anion:
O
CH3CO2H
pKa = 4.75
Cl
δ+
O
δ+
Cl-CH2CO2H pKa = 2.81
Additional EWG’s further increase acidity even more:
O
Cl2CHCO2H pKa = 1.29
Cl
δ+ O
Cl3CCO2H
pKa = 0.70
Cl
O
Cl
Cl
δ+ O
Cl
Consider benzoic acid and para-nitrobenzoic acid:
CO2H
CO2H
O2N
If benzoic acid has a pKa of 4.2 and para-nitrobenzoic acid has a pKa of 3.47, does the
presence of the nitro group make the carboxylic acid proton more or less acidic?
MORE…
So, is a nitro group an EWG or an EDG?
EWG!
Now, consider benzoic acid and para-isopropoxybenzoic acid:
O
O
OH
OH
O
If benzoic acid has a pKa of 4.2 and para-isopropoxybenzoic acid has a pKa of 4.68, does
the presence of the isopropoxy ether group make the carboxylic acid proton more or
less acidic?
LESS…
1
So, is an ether group an EWG or an EDG?
EDG!
The pKa increased, meaning the proton is less acidic. Less acidic protons occur when you
have less stable anions. EDG’s destabilize anions so ethers are EDG’s.
Yet another example: Acetic acid has a pKa of 4.75 and Oxalic acid has a pKa of 1.27:
Acetic acid:
Oxalic Acid:
O
H3C
O
HO
OH
OH
O
pKa = 4.75
pKa = 1.27
Which of the two, oxalic or acetic acid, is more acidic and how do you know?
• Oxalic acid is the stronger acid. It has the lower pKa.
What structural difference is there between the two compounds? What does Oxalic
acid have that Acetic acid does not?
• Oxalic acid, has a second carboxyl group (carboxylic acid)
So, is the second carboxyl group an EDG or EWG?
• If oxalic acid is a stronger acid, oxalic acid must have a more stable anion.
• EWG stabilize anions.
• The carboxyl group must be an EWG
Carboxyl groups (carboxylic acids), as well as other carbonyl-containing groups (such as
ketones, aldehydes, esters) all contain a carbonyl carbon with a partial positive charge
that would be electron withdrawing and therefore a stabilizing factor for an anion.
Oxalic acid belongs to a class of compounds referred to as the “diacids”:
Diacids:
O
HO
O
OH
O
HO
O
O
HO
OH
OH
O
oxalic acid
malonic acid
succinic acid
Each of these can potentially form a single anion or a dianion (therefore sometimes
referred to as “dibasic acids” – can react with up to two equivalents of base):
O
HO
O
OH
1st equiv.
Base
O
HO
O
O
2nd equiv.
Base
O
O
O
O
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
2
Secondary Issue: Inductive Effect and Proximity
Proximity – the closer the EWG, the stronger the effect:
O
O
OH
Cl
O
OH
OH
Cl
pKa = 4.8
O
pKa = 4.5
OH
Cl
pKa = 2.9
pKa =4.0
The closer the electron-withdrawing chlorine atom is to the anion that will need to be
stabilized, the more stability that anion will have.
Question: Why is it easier to remove the first proton from malonic acid (pKa = 2.83)
than the first proton from pimelic acid (pKa = 4.5)?
O
O
HO
O
OH
O
HO
malonic acid
OH
pimelic acid
Answer: The presence of a second carboxyl group, whose carbonyl bears a partial
positive charge, means an electron-withdrawing group (EWG) is present in the molecule.
Proximity Effect:
O
HO
O
OH
1st equiv
base
EWG
O
HO
O
O
MORE stable
O
HO
O
OH
1st equiv
base
EWG
O
HO
O
O
LESS stable
The presence of the carboxyl group as an EWG makes the first anion easy to form – and
the closer the carboxyl group, the stronger the stabilizing effect.
Now: reverse the scenario:
EDG destabilize anions (adding electron density TO an already electron-rich system
creates an unstable system) therefore causing protons to be less acidic
We already looked at removing one proton from a diacid. Removing the second proton is
always more difficult, as it is always less acidic than the first proton.
Malonic acid, shown below, has two acidic protons on the two carboxylic acids functional
groups. pKa1 is 2.51 (removal of first acidic proton) and pKa2 is 5.05 (removal of second
acidic proton):
3
O
HO
O
OH
1st equiv
base
O
2nd equiv
base
O
O
HO
O
O
O
O
When the molecule has both acidic protons, one carboxylic acid acts as an EWG for the
other. When the first acidic proton is removed though, the carboxylate anion acts as an
EDG for the remaining acidic proton
Question? Why would it be more difficult to remove a proton and form an anion in the
presence of an already existing anion?
• Carboxylate anions (anions in molecules, in general) are electron-rich and thus
EDG. Once the first anion forms, the molecule is now electron-rich and the
second anion is always more difficult to form.
4. Solvation – Use of a polar solvent creates a solvent cage and stabilizes an anion
O
H
H
R
O
O
O
H
O H
H
H
H
O
H
O
H
H
H
O H
H O
H
H
O
H
R group effect – smaller R = less sterics = more solvation = more stable anion = more
acidic
Solvent effect – smaller solvents = less sterics = more solvation = more stable anion =
more acidic
(and smaller solvents can solvate better!)
Which is more acidic?
O
H3C
C
O
H
vs
H3C
O
C
C
H3C
O
H
H3C
The carboxylic acid on the left, acetic acid, is more acidic (pKa = 4.76) than the one on
the right, pivalic acid (pKa = 5.03), because acetic acid is less sterically hindered than
pivalic acid, which has the bulky tert-butyl group. Less sterically hindered anions are
more easily stabilized by solvation.
5. Size of the atom – (for atoms in the same column of the periodic table)
- the larger the atom, the less e- repulsions
Acid:
HF
HCl
HBr
HI
4
pKa:
3.45
-7
-9
-9.5
Consider phenol, shown on left, and thiophenol, shown on right:
OH
SH
One compound has a pKa of 6 and one has a pKa of 10. Which is more acidic?
• The anion on sulfur is more stable, due to the atom’s larger size, which has fewer
electron repulsions and a greater ability to stabilize the extra electron density of
an anion. The pKa of phenol is 10 and the pKa of thiophenol is 6.
and finally…
6. Hybridization – the larger the amount of s character, the shorter, rounder the
orbitals. Shorter orbitals stabilize an anion by holding the e- closer to the nucleus.
Alkanes sp3 C-H
pKa = 60
2
Alkenes sp C-H
pKa = 45
Alkynes sp C-H
pKa = 25
Preparations of C. Acids:
1.
Oxidations of 1º alcohols
O
OH
OH
2. Oxidations of aldehydes
O
O
H
OH
3. Grignard addition to CO2
Br
1. Mg
O
OH
2. CO2
Note that this reaction adds one more C to the main chain.
5
The rest of the reactions to form carboxylic acids will be found in Ch. 21)
Reactions of C. Acids:
1. Reduction using LAH
O
OH
OH
2. BH3 reduction of C. Acids – selective for C. Acids ONLY
O
O
OH
BH3
O
OH
Beware of C=C bonds though! This reaction utilizes an atypical protic work-up (not the
oxidizing work-up of a hydroboration reaction). Under these work-up conditions, a
process similar to hydrogenation occurs:
O
OH
BH3
OH
Don’t use with molecules that have alkenes – unless you want them to be reduced to
alkanes.
6