Acid/Base stuff
Beauchamp
1
Important preliminary questions before looking at specific acids and bases.
1. What is an acid? What is a base? What are the Bronsted and Lewis definitions of acids and bases?
Arrhenius definitions (before 1900) – water is emphasized
acids: substances which increase the hydronium ion concentration in water, [H3O+]
bases: substances which increase the hydroxide ion concentration in water, [HO--]
Bronsted definitions (1924) – proton transfer is emphasized
acid: a proton donor (no reference to the solvent)
base: a proton acceptor (no reference to the solvent)
Lewis definitions (1924) – electron pair transfer is emphasized
acids: substances which accept a pair of electrons
bases: substances which donate a pair of electrons
2. Write an equation using water as the base with generic acid, H-A. Use curved arrows to show how the reaction
occurs between an acid and a base (water)? Always push electrons with your arrows! Use full-headed arrows for
two electron movement (in acid/base chemistry), and half-headed arrows for one electron movement (in free
radical reactions). Remember how you used arrows in resonance. Practice this skill at every opportunity.
This is the organic way of looking at reactions.
It can be qualitative (which side does the
equilibrium favor?) or quantitative (what is
the value of Keq?). Water is the reference base
in reactions with various acids. Arrow pushing
shows how the reactions work.
A
H
This is the freshman chemistry way
of looking at acid/base chemistry.
Symbols are mainly used for
quantitative numerical calculations.
We won't write H+ by itself. We will
always attach the proton to some pair
of electrons.
Ka
O
H
H
A
pKa
H
[C2H3O2H]
Ka =
O
H
H
H
C 2 H3 O2
[ C2H3O2 ] [ H+]
[C2H3O2H]
3. Write an equilibrium expression for the reaction of acid ionization in water.
Keq =
(A )(H3O )
(HA)(H2O)
4. How does Ka differ from Keq? What is the Ka and what does it tell us about an acid? What magnitude is Ka for a
strong acid? What magnitude is Ka for a weak acid?
We almost always use Ka instead of Keq in acidity tables. They only differ by the concentration of water, which is essentially
constant ( 55.6 M). An acid with a large Ka value (Ka > 1) is called a strong acid (up to 1020). An acid with a small Ka value
(Ka < 1) is called a weak acid (as low as 10-50). Acid strengths span a remarkable range of 1070!
Ka = Keq (H2O) =
(A )(H3O )
= #
(HA)
bigger number (>1) = strong acid (up to 1020)
smaller number (<1) = weak acid (low as 10-50)
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
Beauchamp
2
5. What is the pKa and what does it mean? (strong acids = ?)(weak acids = ?) What’s an order of magnitude?
pKa is another way to look at Ka It's a little confusing because it is the negative log of the Ka, (the negative of the tens exponent).
Every power of 10 is an order of magnitude (103 is an order of magnitude larger than 102 and 10-4 is two orders of magnitude smaller
than 10-2). (pKa = negative number for strong acids and pKa = positive number for weak acids)
Ka = 10-pKa
pKa = - log (Ka)
A very useful way to think of pKa is as (G)x(1.4) kcal/mole. Very approximately: pKa = (G)x(1.4) kcal/mole
R = 2 cal/mole-K
R = 8.3 joule/mole-K
G = -2.3RT (log Ka) = 2.3RT (-log Ka) = (1.4)(pKa) kcal/mole  pKa
6. Can you think of a better base that could be used in water (but similar looking)? What are the limits of basicity in
water? Using a less acidic solvent can allow for more basic environments. Some solvents are essentially
nonacidic and can tolerate very strong bases. This is often necessary in organic chemistry.
A
H
O
H
H
A
O
H
-16
Ka = varies
pKa = varies
Ka = 10
pKa = 16
Hydroxide is a stronger (better) base than
water, although water is still most likely
the solvent. On cannot go higher in pH
than the pKa of water, where 50% of the
water would be ionized to hydroxide and
no longer liquid.
7. Write an equation with water as the acid with generic base, B:. We won’t consider Kb or pKb.
Kb
H
O
H
-16
Ka = 10
pKa = 16
H
B
O
H
B
Ka = varies
pKa = varies
pKb
Water is the reference acid in reactions
with various bases. Arrow pushing
shows how the reactions work.
8. Can you think of a better acid that you could use in water (but similar looking)? What are the limits of acidity in
water? Using a less basic solvent can allow for more acidic environments. This is sometimes necessary in
organic chemistry.
H
O
H
B
H
Hydronium ion is a stronger (better) acid
than water, although water is still most
H
B
likely the solvent. On cannot go lower in
+
Ka = varies pH than the pKa of H3O , where 50% of the
+
pKa = varies water would be ionized to H3O and no
longer liquid.
O
H Ka = 10+2
pKa = -2
9. How does one draw an energy diagram (PE vs POR) for strong acid ionization equation? How does one draw an
energy diagram (PE vs POR) for weak acid ionization?
+
B
H
A
TS
B
H
A
stronger acid & base
B
H
A
weaker acid & base
H
PE
A
stronger
acid
The equilibrium shifts towards the weaker conjugate
acid and base (away from the stronger acid and base).
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
A
POR
Acid/Base stuff
Beauchamp
3
+
B
H
Y
TS
B
H
B
Y
H
Y
stronger acid & base
weaker acid & base
Y
weaker
acid
H
Y
PE
The equilibrium shifts towards the weaker conjugate
acid and base (away from the stronger acid and base).
POR
10. What makes an acid stronger? What makes an acid weaker? In our course, we present two reasons: a.
inductive effects (related to electronegativity) and b. resonance effects through 2p orbitals. These are mainly
used to explain stabilities of the ‘less stable’ conjugate bases. Do stronger acids have more stable or less stable
conjugate bases (more stable)? What about weak acids (less stable bases)? At our peril, we ignore salvation
effects in our presentation and focus mainly on the stability of the conjugate bases.
+
B
H
A
TS
H
PE
A
stronger
acid
+
B
As the conjugate
base, A: gets more
stable, the acid, HA,
gets stronger.
H
Y
TS
PE
A
Y
weaker
acid
H
Y
POR
As the conjugate
base, Y: gets less
stable, the acid, HY,
gets weaker.
POR
11. Consider the base, instead of the acid. What makes a base stronger (less stable)? What makes a base weaker
(more stable)? Turn acidity around to evaluate basicity. Electron donating ability is related to the reasons
provided for relative acidities in question 10? We often use available pKa tables of acidities to determine relative
basicities of the conjugate bases from their inverse relationships with one another. (The stronger acid pairs with
the stronger base and the weaker acid pairs with the weaker base.)
equilibrium lies
completely to the right
H
H
O
stronger acid
O
stronger base
weaker base
H
H
weaker acid
Ka = 10-37
pKa = 37
-16
Ka = 10
pKa = 16
Keq =
Ka1
-16
=
Ka2
10
10-37
= 10+21
G = (pKa1 - pKa2) x 1.4 = (16 - 37) x 1.4 = (-21) x 1.4 = -29 kcal/mole
H3C
equilibrium lies
completely to the left
H
C
H2
weaker acid
H
CH2
weaker base
H
H
stronger acid
stronger base
-50
Ka = 10
pKa = 50
H 3C
Keq =
Ka1
Ka2
=
10-50
10-37
= 10-13
G = (pKa1 - pKa2) x 1.4 = (50 - 37) x 1.4 = (13) x 1.4 = +18 kcal/mole
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Ka = 10-37
pKa = 37
Acid/Base stuff
Beauchamp
4
Having a negative charge (or lone pair of electrons) on a more electronegative atom makes it more stable (F is more stable
than HO is more stable than H2N is more stable than H3C ). More delocalized electrons are more stable than less
delocalized electrons. This delocalization could be due to the size of the atoms: I > Br > Cl > F or due to resonance.
+
B
H
F
+
B
F is more stable than H3C
TS
F
PE
CH3
H
TS
weaker
acid
H
F
pKa = +3
G = +4
H3 C
because F has a higher Zeff
(+7 > +4) making it more
electronegative than C. Both
are similar size second row
elements.
PE
POR
pKa = +50
G = +70
much
weaker
acid
H3C
H
POR
I
is more stable than
F
Delocalization of electrons in organic chemistry usually refers to "resonance".
delocalized
charge
(resonance)
O
because iodide is a larger anion and
its electrons are more delocalized
than fluoride's electrons, while both
have the same Zeff of +7.
O
is more stable than
O
O
O
localized
charge
12. Many examples follow, providing opportunities to use organic logic of points 10 and 11.
Generic acid/base equilibrium equation, the organic way, with curved arrows. Keq and G can be estimated
for a proton transfer reaction involving two generic acids, as shown below.
An estimate of the equilibrium constant, Keq, can
be calculated by dividing the Ka of the acid on the
left (reactant) by the Ka of the acid on the right
(product). An estimate of G for the reaction
can be calculated by subtracting the pKa of the
acid on the right from the pKa of the acid on the
left, and multiplying by 1.4 kcal/mole.
Lewis definitions
acid = electron pair acceptor
base = electron pair donor
A1
Bronsted definitions
acid = proton donor
base = proton acceptor
H
A2
A1
H
A2
Ka1
Keq = (:A2 )(HA1 ) =
(HA2)(:A1 )
Ka2
G = (pKa) x 1.4 = (pKa1 - pKa2) x 1.4
G = (1.4)(pKa) kcal/mole  pKa
Acid ionization reactions use full headed arrows to show two electron movement. Water is the reference base in usual Ka
and pKa tables.
Ka
H
O
H
A
H
O
H
A
pKa
H
H
You should be able to match pKa values with their acids in each group below and explain the differences. You
should be able to draw an arrow-pushing mechanism with general base, B:- for any of the acids, H-A. Include
resonance structures whenever appropriate. If there was a reaction shown between any two conjugate acids and
bases, you should be able to qualitatively and quantitatively indicate which side of the equilibrium is favored, and
what an approximate G is for the reaction.
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
1
H
H
C
Beauchamp
5
pKa = 16
H
H
N
H
H
H
H
O
F
H
pKa = 3
pKa = 35
pKa = 50
H
What is Keq and G for the following reactions?
H
C
H
H
equilibrium lies
completely to the left
H
N
H
weaker acid
H
H
H
weaker base
-50
Ka = 10
pKa = 50
Ka1
Keq =
10-50
=
N
H
H
H
stronger base
stronger acid
= 10
10-37
Ka2
H
C
Ka = 10-16
pKa = 16
-13
G = (pKa1 - pKa2) x 1.4 = (50 - 37) x 1.4 = (13) x 1.4 = +18 kcal/mole
H
H
N
O
stronger acid
equilibrium lies
completely to the right
H
N
H
O
H
stronger base
Ka = 10-16
pKa = 16
H
H
H
weaker acid
weaker base
Ka1
Keq =
10-16
=
10-37
Ka2
Ka = 10-37
pKa = 37
= 10+21
G = (pKa1 - pKa2) x 1.4 = (16 - 37) x 1.4 = (-21) x 1.4 = -29 kcal/mole
2
H2
C
H2
C
H
H3C
C
H2
C
H
H3C
N
H3C
H
H
H2
C
H
H3C
O
pKa = 50
pKa = NA
H
3
I
O
Br
H
O
Cl
H
O
pKa = 8.7
H
F
O
H
H
Cl
H
O
Cl
H
pKa = 7.5
Cl
H
pKa's = 16
Cl
Cl
Cl
5
H
H
C
H
H
H
C
Cl
H
H
C
Cl
H
C
pKa  40*
pKa = 25
H
6
* = my estimate
CH3
CH3
H3C
H
O
H3 C
pKa's = 19
H 3C
H2
C
CH
H
O
H3C
C
H
O
pKa = 50
pKa  32*
Cl
H
pKa's = 12.8
pKa's = 12.2
Cl
Cl
Cl
pKa's = 14.3
O
O
O
pKa = 11
pKa = NA
not stable
4
pKa = 16
pKa = 37
F
H 3C
H
pKa's = 17
O
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
pKa's = 15.5
pKa's = 15.8
Acid/Base stuff
Beauchamp
6
7. What is the expected order of stability of these reactive organic intermediates? (most stable = 1)
a. free radicals
H
R
R
H
relative energies
C
H
H
b. carbocations
H
c. carbanions
R
R
H
R
H
R
H
H
R
R
C
C
C
C
H
H
H
R
H
R
relative energies
(most stable = 0)
70 kcal/mole
35
15
0
C
C
C
H
R
R
H
C
H
R
R
H
R
H
R
(most stable = 0)
12 kcal/mole
5
2
0
C
C
C
relative energies
(most stable = 0)
? kcal/mole
R
R
8
pKa = -7
pKa = -9
F
H
Cl
H
Br
I
H
pKa = -10
pKa = 3
H
9
H
O
S
H
pKa = 4
H
H
Se
H
H
Te
H
pKa = 3
pKa = 16
pKa = 7
H
O
10
H
O
O
pKa = 16
H
H
O
pKa = 4
11
O
H3C
O
O
C
H
C
C
C
H
H3C
H3C
N
pKa = 20
H
H
O
C
H2C
H
Ref. pKa = 4.7
I
13
H
O
C
H
H2C
O
O
C
H
H2C
O
Cl
F
H
O
C
H
H2C
O
Br
CH3
O
pKa = 0.7
other pKa's = 4.9, 3.2, 2.90, 2.85, 2.59
O
O
O
H Cl
C
H3C
C
H2C
O
O
O
C
H
O
H2C
pKa = 5
H
O
pKa = 15
O
H
12
pKa = 10
O
C
C
H2
H
O
C
Cl
CH
H
Cl
O
H
C
C
O
pKa = 1.3
Cl
Cl
Cl
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
pKa = 2.8
pKa = 5
Acid/Base stuff
Beauchamp
14
O
O
H
H
O
O
pKa = 4.8
O
O
Cl
H
H
7
O
Cl
pKa = 4.5
O
pKa = 2.8
pKa = 4.0
Cl
15
O
N
H
H
H
H
H
C
H
H
H
C
H
N
H
pKa's = 10, 18, 28, 37, 41, 50
O
H
H
16
H
H3C
N
F
O
O2N
O
C
C
O
H
O
O
C
O
Ref. pKa = 4.2
C
O
H
pKa = 4.3
C
O
C
H
O
O
pKa = 3.9
H
H
pKa = 3.5
pKa = 3.6
N
17
C
pKa = 24.8
pKa = 28
N
C
N
H
N
H
N
H
pKa = 23.6
H
19
H
O
O
O
20
O
O
pKa = 50
F3C
H H
H
H H
H H
O
O
H
H
N
H
O
O
H
O 2N
21
pKa = 5
H H
O
O
O
O
H
pKa = 9
pKa = 20
CF3
H
Cl
pKa's = 8.4, 7.1, 10.0, 10.2
O
O
H
H
Cl
Cl
pKa's = 85, 9.0, 9.4, 10.0
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
Beauchamp
8
O
22
O
C
H
H2 C
O
C
H
O
C
C
O
O
pKa = 5.70
pKa = 2.85
H
H 3C
O
C
O
O
23
H
H2 C
pKa = 4.7
O
H
H
H
H
H
H
pKa = 15*
pKa = 50
pKa = 42
* also aromatic
24
H
H
H
C
pKa = 50
C
H
H
H
C
C
H
H
H
C
H
C
H
pKa = 44
H
pKa = 25
Electrons in 2s orbitals are held tighter than electrons in 2p orbitals. Orbitals which have a greater %s character are more
electronegative than lesser %s character. Therefore the electronegativity of hybrid orbitals is: sp (50% s) > sp2 (33% s) > sp3 (25% s).
Greater electronegativity is better able to stabilize the negative charge in the conjugate base, so sp C-H bonds are the most acidic of
these hydrocarbons, then sp2 C-H and lastly sp3 C-H (lowest acidity of any acid in our course).
25
H
C
H
H
H
H
pKa = 9
N
H
C
N
H
H
H
C
H
N
H
H
pKa = -10
pKa = 5
Bascity
Use full headed arrows to show two electron movement. Water is the reference acid in usual Kb tables. We won't
use pKb values. Instead, we will compare pKa values and judge bases to be stronger when their acids are weaker
and bases to be weaker when their acids are stronger. In the examples that follow pair up each base with the pKa
value of its conjugate acid.
B
judge the strength of the base
from the weakness of the acid
H
O
H
B
H
use this acid's pKa value to judge
the electron donating power of B:
to the reference acid, H2O.
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
O
H
Acid/Base stuff
Beauchamp
9
Here are a few qualitative examples. Where is the most basic site in each molecule below? Can an order of
basicity be explained for some or for all of the bases (approximate pKa’s of some of the conjugate acids are
provided)?
O
O
C
C
H
H3C
CH3
H3C
O
pKa  -7
O
O
C
C
O
H3C
CH3
pKa  -7
pKa  -6
H3C
H
N
pKa  -0.5 H
R
O
N
N
C
H
N
H
N
N
O
H
H
pKa  0.2
C
H
N
pKa  5 (guess)
H pK  7
a
H
N
N
H
H
pKa  13.6
What is the order of basicity among the following molecules of each group (1 = most basic)? Explain your
reasoning. Match the given pKa values with the conjugate acids of the indicated bases. Write arrow-pushing
mechanisms with general acid, H-A to illustrate the reactions. Include resonance structures whenever appropriate.
Where is the most basic site in each molecule? Explain your reasoning using arguments of inductive effects
(electronegativity), resonance effects (electron delocalization) or both. For any reaction between two conjugate
acids and bases, you should be able to qualitatively and quantitatively indicate which side of the equilibrium is
favored, and what is an approximate G is for the reaction.
R
1
O
N
C
C
H
H3C
O
H
H3C
N
C
N
H3C
H
pKa's of the bases'
conjugate acids = -7, 0, 7
H
pKa's of the bases'
conjugate acids = 9, 5, -10
O
H
H
2 H
H
C
H
N
H
C
N
H
H
C
H
N
H
R
3
N
H
N
H
C
N
N
H
H
N
pKa's of the bases'
conjugate acids = 5, 7, 13
N
H
O
4
O
O
O
pKa's of the bases'
conjugate acids = 5, 10, 16
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
5
O
Beauchamp
O
O
O
O
F3 C
6
H
H
O
O
C
O
H
C
H3C
O
H3 C
C
N
H3 C
H
7
H
pKa's of the bases'
conjugate acids = 50, 20, 9, 5
CF3
H
H
10
CH2
pKa's of the bases'
conjugate acids = 20, 15, 5
H
C
C
H
H
H
C
C
C
H
H
pKa's of the bases'
conjugate acids = 50, 44, 25
C
H
8
H
H
H
pKa's of the bases'
conjugate acids = 50, 42, 15
Acid/Base arrow pushing worksheet
1. These proton transfer reactions are the first step in multistep mechanisms to be studied later in the course.
Supply the necessary curved arrows, lone pairs of electrons and/or formal charge to show how the first
step each reaction proceeds. Except for the first reaction, they are all simple proton transfer reactions
generating a carbanion. Generally, there is some stabilizing feature that allows a carbanion to form via
acid/base chemistry, such as inductive and/or resonance effects. In working the problem below, show any
important resonance structures or identify the inductive effect that makes the reaction possible.
a.
Formation of lithium diisopropyl
amide (LDA) using butyl lithium.
Li
CH2CH2CH2CH3
N
H
Ka = 10-37
H
N
n-butyl lithium is
commercially
available
Li
CH2CH2CH2CH3
Ka = 10-50
b.
R
O
N
R
C
H
C
Li
LDA
H
H
-78 oC
resonance
R
ketone
Ka = 10-20
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
R2NH
Ka = 10-37
Acid/Base stuff
Beauchamp
11
c.
O
R
C
H
N
C
Li
R
R
H
R2NH
ester
Ka = 10-25
H
LDA
resonance
-78 oC
O
Ka = 10-37
d.
O
R
-78 oC
N
H
Li
R
R
C
resonance
N
C
H
LDA
H
R2NH
tertiary amide
Ka = 10-30
R
Ka = 10-37
e.
H
R
N
H
Li
R
C
C
N
-78 oC
resonance
R2NH
nitrile
Ka = 10-30
H
LDA
Ka = 10-37
f.
H
O
O
C
C
C
H3 C
Na
H
sodium hydride
H
-78 oC
CH3
1,3-dicarbonyl
resonance
resonance
H-H
Ka = 10-37
Ka = 10-9
g.
R
N
H
Na
R
sodium amide
C
C
-33 oC
R
R2NH
terminal alkyne
Ka = 10-25
Ka = 10-35
ammonia
terminal acetylide
h.
S
H
Li
H2C
H
S
dithiane
Ka  10
-35
H2
C
CH3
C
H2
o
-78 C
possible
resonance
with sulfur
d orbitals?
H
n-butyl lithium
i.
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
CH2CH2CH2CH3
Ka = 10-50
Acid/Base stuff
H
Ph
Beauchamp
Li
S
C
H2
C
H
CH3
H2C
Ph
C
H2
H
-78 oC
n-butyl lithium
sulfur ylid
-35
Ph = phenyl Ka  10
12
possible
resonance
with sulfur
d orbitals?
H
CH2CH2CH2CH3
Ka = 10-50
j.
Br
Ph
Ph
Li
H
P
C
H2
C
CH3
H2C
H
C
H2
o
-78 C
n-butyl lithium
Ph
H
phosphorous ylid
(Ph = phenyl) Ka  10-35
possible
resonance
with phosphorous
d orbitals?
H
CH2CH2CH2CH3
Ka = 10-50
2. Lone pair donors to very strong acid
All of the following functional groups react with protic acid as the first step of a reaction studied in organic
chemistry. Often subsequent chemistry occurs after that initial step and you will study most of those reactions later
in the course. Show how they react in the first step by including all lone pairs, curved arrows to show electron
movement and formal charge.
Acid/Base arrow pushing worksheet
lone pair donors
lone pair acceptor
O
Keq = ?
H
O
H
H
O
S
OH
O
H
N
H
H
H
ammonia
R
N
H
H
O
H
H
O
Keq = ?
pKa's = -2, 9
H
equilibrium
Keq = ?
equilibrium
H
H
1 amine
N
H
H
o
R
O
equilibrium
pKa's = -10, -2
pKa's = -2, 10
H
Keq = ?
equilibrium
R
2o amine
R
N
pKa's = -2, 10
H
R
H
O
H
Keq = ?
equilibrium
R
3o amine
H
pKa's = -2, 10
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
R
O
Beauchamp
H
H
O
alcohol
H
13
additional
chemistry
possible
Keq = ?
pKa's = -2, -3
H
Keq = ?
R
O
H
R
ether
pKa's = -2, -3
H
O
H
H
O
H
epoxide (ether)
additional
chemistry
possible
H
O
Keq = ?
additional
chemistry
possible
pKa's = -2, -3
O
H
C
O
R
H
aldehyde
H
Keq = ?
resonance
(2)
pKa's = -2, -7
H
additional
chemistry
possible
O
H
H
O
Keq = ?
C
R
H
R'
pKa's = -2, -7
ketone
R
C
N
H
nitrile
O
resonance
(2)
SO3H
Keq = ?
resonance
(2)
additional
chemistry
possible
resonance
(3)
additional
chemistry
possible
resonance
(3)
additional
chemistry
possible
pKa's = -10, -10
sulfuric acid
additional
chemistry
possible
O
H
O
H
Keq = ?
H
C
R
O
carboxylic acid
H
pKa's = -2, -6
O
H
C
R
O
H
Keq = ?
R'
O
H
pKa's = -2, -6
ester
O
H
O
H
Keq = ?
C
R
NH2
amide
H
resonance
(3)
pKa's = -2, 0
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
additional
chemistry
possible
Acid/Base stuff
Beauchamp
14
H
N
H
C
R
NH2
O
H
H
Keq = ?
resonance
(3)
pKa's = -2, 12
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
additional
chemistry
possible
Acid/Base stuff
Beauchamp
15
Carbon-carbon pi bonds as weak electron pair donors to very strong acid
H
H
C
R
alkene
CH2
O
Keq = ?
SO3H
additional
chemistry
possible
pKa's = -10, -10
sulfuric acid
NR2
H
O
H
Keq = ?
C
R
enamine
H
CH2
resonance
(2)
additional
chemistry
possible
resonance
(2)
additional
chemistry
possible
pKa's = -2, 5
R
O
H
O
H
C
R
R
H
CH2
enol ether
C
C
H
H
pKa's = -2, -7
Keq = ?
SO3H
O
sulfuric acid
alkyne
Keq = ?
additional
chemistry
possible
pKa's = -10, -10
H
C
H
C
H
Keq = ?
C
E
C
H
C
C
H
aromatic
H
resonance
(3)
pKa's = -10, -10
additional
chemistry
possible
E+ = electrophile
(Lewis acid = electron
pair acceptor)
At this point we are mainly interested in understanding acid/base proton transfers, curved arrow
pushing, formal charge, recognizing resonance structures and using the logic arguments of inductive
effects and resonance effects to explain relative stabilities of acids and bases. If you can do these things,
you are well on your way to understanding organic chemistry and biochemistry.
The Tautomer Game – an arrow-pushing training reaction in acid and in base, forward and reverse
Tautomers are isomers that differ by the location of a proton and a pi bond. To be official tautomers, a heteroatom
or atoms (different than carbon, often oxygen or nitrogen or both) is part of the system. In the simplest case, there
are at two isomers in equilibrium with one another (there may be many, many more tautomers possible in more
complex systems). The tautomers are interchangeable by 1. proton transfer, 2. resonance intermediates and 3.
proton transfer. The “keto” isomer, has a heteroatom in a pi bond and in the “enol” tautomer has two carbons
forming a pi bond. This simple pattern can occur in an infinite number of systems, from very simple to very
complex. A possible approach to figuring out what to do in keto/enol tautomer problems is shown below. Slightly
more complex tautomer relationships are shown in the second example. They are mainly more complicated mainly
because there are more than two tautomers and interchanges may require one or more simple tautomer
interconversions.
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
Beauchamp
16
Use H3O /H2O or HO /H2O to accomplish the given transformations. Every transformation will always follow a 3 step sequence.
H
O
O
H
acid
or
base
H
H
C
C
H
C
H
C
H
H
H
keto tautomer
H
1. proton transfer (in acid = proton on) (in base = proton off)
2. resonance delocalized intermediates
3. proton transfer (in acid = proton off) (in base = proton on)
C
C
H
H
in acid
H3 O
H2 O
enol tautomer
in base
H2 O
HO
best acid
best base
Tautomers in acid (simplest examples)
a. “keto”  “enol”
H
O
H
H
H
C
C
H
H
O
H
C
H
H
H
keto tautomer
H
O
H
O
H
H
H
C
H
O
C
C
H
H
resonance
H
H
C
C
C
H
H
H
H
H
H
in acid = proton on
H
O
H
H
H
O
in acid = proton off
H
C
C
C
H
H
enol tautomer
b. “enol”  “keto”
H
H
H
O
H
H
H
C
H
H
H
enol tautomer
O
C
H
H
in acid = proton on
C
C
H
H
H
O
H
H
H
O
O
resonance
H
H
H
H
O
H
H
C
C
O
H
C
C
C
H
H
H
H
H
C
H
C
H
C
H
H
keto tautomer
in acid = proton off
Tautomers in base (simplest examples)
a. “keto”  “enol”
H
O
H
C
O
C
C
H
H
H
keto tautomer
O
H
H
in base = proton off
resonance
H
H
H
O
H
H
O
O
H
H
H
O
H
C
C
C
H
H
H
enolate
H
H
C
C
H
C
C
H
H
in base = proton on
H
C
C
H
H
enol tautomer
b. “enol”  “keto”
H
H
O
H
H
O
C
C
O
H
H
H
C
H
H
enol tautomer
H
O
H
in base = proton off
H
C
C
H
H
H
enolate
H
O
H
H
H
C
O
O
resonance
C
C
H
H
H
H
C
H
in base = proton on
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
C
C
C
H
H
keto tautomer
H
Acid/Base stuff
Beauchamp
17
A slightly more complicated keto/enol tautomer problem – keto/enol with an additional pi bond
also possible
H
O
H
H
H
O
H
H
H
O
base
H
H
H
H
H
base
H
1
H
H
H
H
H
H
H
1
H
H
H
4
H
2
H
base
O
base
O
H
H
H
H
H
base
3
H
H
H
H
H
H
H H
5
3
H H
The tautomer interconversions shown above are possible in one step in base because of shared resonance intermediates. The
total number of tautomer changes required to change any tautomer into any other tautomer are shown below for base (on the
left) and acid (on the right). The number of tautomer changes in parentheses was worked out in my head, not on paper, so there
may be some wrong estimates.
Number of tautomer changes to transform
one tautomer into another in base.
1
2
3
4
5
2
3
4
Number of tautomer changes to transform
one tautomer into another in acid.
5
(1x)
(1x)
(1x)
(2x)
1
3
4
5
(1x)
(1x)
(2x)
(2x)
1
2
4
5
(1x)
(1x)
(2x)
(1x)
1
2
3
5
(1x)
(2x)
(2x)
(3x)
1
2
3
4
(2x)
(2x)
(1x)
(3x)
1
2
3
4
5
(1x)
(2x)
(1x)
(1x)
1
3
4
5
(1x)
(1x)
(1x)
(1x)
1
2
4
5
(2x)
(1x)
(2x)
(1x)
1
2
3
5
(1x)
(1x)
(2x)
(2x)
1
2
3
4
(2x)
(1x)
(1x)
(2x)
2
3
4
5
1. Circling the protons that change is always a good idea, because you know these are going to have to move.
However, these may not show every tautomer change because sometimes a necessary change is reversed in a later
step. The circled protons have to be moved, either taken off (with the best base available) or put on (with the best
acid available) and there is always resaonance delocalization in the intermediate.
Best acid in H3O+/H2O is H3O+, best base in H3O+/H2O is H2O
Best base in H2O/HO-- is HO-- and the best acid in H2O/HO-- is H2O
2. Always work from a "keto" (CH-C=O or CH-C=N-) part or "enol" (C=C-OH or C=C-NH-) part of the
molecule. Do not use isolated pi bonds (C=C) to initiate change in the structure. With an allowed change an
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
Beauchamp
18
isolated pi bond may become conjugated with a “keto” or “enol” part of another tautomer. Any keto or enol
part will be the better base or the better acid, as is indicated because it will form a resonance stabilized
intermediate with the oxygen (or nitrogen) assisting in the resonance structures.
Changing tautomer 2 into tautomer 4 is possible in base by first converting tautomer 2 into tautomer 1
and then changing tautomer 1 into tautomer 4. On the other hand tautomer 2 could be converted to
tautomer 4 in a single tautomer change in acid.
Not possible in in base in one keto/enol cycle.
OH
H
OH
H
H
H
H
H
H
H
H
OH
H
H
H
H
2
H
H
H
H
This is an isolated
C=C bond. Don't
begin here in acid
or base.
H
H
H
H
OH
H
H
H
H
4
O
H
H
H
2
H
H
H
H
H
H
1
H
This is an isolated
C=C bond. Don't
begin here in acid
or base.
4
H
This is an isolated
C=C bond. Don't
begin here in acid
or base.
3. If in acid, use the strongest acid (H3O+ in our examples) to put on a "gained" proton first and take off a "lost"
proton second, with a weak base (usually the solvent = H2O in our examples).
4. If in base, use the strongest base (HO- in our examples) to take off a "lost" proton first and put on a "gained"
proton second with a weak acid (usually the solvent = H2O in our examples).
5. In all tautomer mechanisms there will be resonance structures in the intermediate formed. The intermediate
structure will show the way to all other reasonable tautomers from that intermediate. You may have to repeat
the tautomer process once, twice, etc. until you accomplish an overall indicated transformation. Counting the
number of protons lost or the number of protons gained will give you an indication of how many times you
may have repeat the tautomerization process. This may not always match however because sometimes a
tautomer sequence is reversed and hidden from the overall change indicated (See rule 2.).
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
Beauchamp
19
Acids and Bases and Tautomerism
The following transformations can be done in base or acid. Intermediate resonance structures lead to stable
structures.
O
OH
H
H
acid
or
base
H
H
H
H
H
H
H
H
H
H
H
1
H
H
acid
or
base
O
H
H
acid
or
base
H
H
H
H
3
H
H
A
1
2
2
2
2
3
2
3
2
A
H
1
3
1
3
1
H
A
3
3
1
3
3
B
A
1
H
B
B
1
Additional tautomeric structures.
OH
H
H
H
H
H
H
H
H
H
4
2
B
H
H
A
2
Additional tautomeric interconversions (40 different problems).
OH
H
A
1
B
B
H
Use generic acid, H-A, or generic base, B:
to accomplish the given transformations.
For every transformation there will be
resonance delocalized intermediates that
lead toward the path desired.
This is the most thermodynamically
favored keto/enol structure because
it retains the C=O and has conjugated
pi bonds.
H
H
2
H
H
5
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
Beauchamp
20
Arrow-Pushing Practice – Fill in missing formal charge, lone pairs and curved arrows.
H
O
H
H
H
H
O
H
H
H
H
B
H
H
H
1
H
H
H
H
O
H
H
H
H
O
H
H
H
H
H
H
H
H
H
H
O
H
H
B
H
O
H
H
H
H
H
H
O
A
H
2
H
H
H
A
O
H
H
H
O
Steps in acid for each tautomeric change:
1. proton transfer (proton on, best acid = H3O+)
2. resonance intermediates
3. proton transfer (proton off, best base = H2O)
O
H
H
H
H
H
H
H
H
H
H
Remember: each tautomer has the same overall formal
charge and the same total number of pi bonds.
H
H
4
H
H
H
C
D
D
C
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
3
H
H
H
H
H
5
H
O
H
H
H
H
H
O
H
H
H
O
H
O
O
H
H
O
H
H
H
H
H
H
A
H
C
O
H
O
B
O
H
H
O
H
H
H
H
H
H
B
H
H
H
H
H
H
H
H
1
O
H
H
H
H
H
H
O
H
H
O
H
H
H
H
H
H
H
G
A
D
C
H
O
H
H
O
H
D
O
H
H
H
O
H
H
H
H
H
H
H
O
H
H
H
H
H
H
H
2
H
H
H
H
H
E
H
H
H
H
H
O
H
H
O
H
H
3
G
F
H
H
O
H
O
E
O
H
Steps in acid for each tautomeric change:
1. proton transfer (proton off, best base = HO )
2. resonance intermediates
3. proton transfer (proton on, best acid = H2O)
H
O
O
H
H
H
H
H
H
H
Remember: each tautomer has the same overall formal
charge and the same total number of pi bonds.
H
H
H
4
H
H
H
H
H
F
H
H
H
H
5
H
H
H
H
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
H
H
H
H
Acid/Base stuff
Beauchamp
21
Possible Key for arrow-pushing in “tautomer” problems
H
O
H
H
H
H
O
H
H
H
H
B
H
H
H
1
H
H
H
H
O
H
H
H
H
O
H
H
H
H
H
H
H
H
H
H
O
H
H
B
H
O
H
H
H
H
H
H
O
A
H
2
H
H
H
A
O
H
H
H
O
Steps in acid for each tautomeric change:
1. proton transfer (proton on, best acid = H3O+)
2. resonance intermediates
3. proton transfer (proton off, best base = H2O)
O
H
H
H
H
H
H
H
H
H
H
Remember: each tautomer has the same overall formal
charge and the same total number of pi bonds.
H
H
4
H
H
H
C
D
D
C
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
3
H
H
H
H
H
5
H
O
H
H
H
H
H
O
H
H
H
O
H
O
O
H
H
O
H
H
H
H
H
H
A
H
C
O
H
O
B
O
H
H
O
H
H
H
H
H
H
B
H
H
H
H
H
H
H
H
1
O
H
H
H
H
H
H
O
H
H
O
H
H
H
H
H
H
H
G
A
D
C
H
O
H
H
O
H
D
O
H
H
H
O
H
H
H
H
H
H
H
O
H
H
H
H
H
H
H
2
H
H
H
H
H
E
H
H
H
H
H
O
H
H
O
H
H
3
G
F
H
H
O
H
O
E
O
H
Steps in acid for each tautomeric change:
1. proton transfer (proton off, best base = HO )
2. resonance intermediates
3. proton transfer (proton on, best acid = H2O)
H
O
O
H
H
H
H
H
H
H
Remember: each tautomer has the same overall formal
charge and the same total number of pi bonds.
H
H
H
4
H
H
H
H
H
F
H
H
H
H
5
H
H
H
H
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
H
H
H
H
Acid/Base stuff
Beauchamp
22
Ka/pKa table for a variety of acid types
The sign and magnitude of an acid’s pKa represents the approximate energy change to form the conjugate base from
the acid with water as the general base. Remember a difference of 2 pKa units is the same as the difference
between a 6’ person and a 600’ person, a pretty obvious difference.
A pKa table provides us with immediate access to an acid’s proton donating ability and indirectly to its
conjugate base electron donating ability. You can decide from the values in the pKa table whether an acid is strong
or weak and its relative acidity (or basicity) compared to other acids (or bases) in the table. If it is weak (most of
them are, pKa > 1 to very large), you can evaluate approximately how large an energy input is necessary to form the
conjugate base. Remember, water is the reference base for all of the listed Ka’s of the acids even though as a
solvent for many acids, it is meaningless.
pKa Table for a Variety of Acids – Approximately equal to Gacid ionization (in kcal/mole = (1.4)x(pKa))
Carbon Acids – There is a fair amount of uncertainty in the higher pKa values.
H = acidic hydrogen atom
O
O
O2N
NO2
CHO
OHC
CH
RO2C
NO2
CH
H
H
pKa = 4
H
pKa = 5
O
CH
C
pKa = 6
CH
O
H
pKa = 19
pKa = 20
CH2
CH
R
C
OR
Cl
C
C
R
H
pKa = 25
pKa = 24
Ph
N
Cl
H
C
S
Ph
H
C
H
Cl
H
Ph
pKa = 25
pKa = 30
pKa = 31
H
H Ph
C
S
H
H
R
C
H2
R
H
R
H
pKa = 44
pKa = 43
C
H
H2 C
pKa = 43
pKa = 40
H
C
H
CH2
pKa = 32
H
H
pKa = 23
R
H
H
S
pKa = 34
pKa = 16
pKa = 15
R
pKa = 23
H
H
H
H
O
H
C
CH
H
O
O
R
Ph
CH
pKa = 13
S
pKa = 23
H
R
H
H
pKa = 13
H
O
R
CH
H
H
H
CO2R
CH
pKa = 11
Ph
pKa = 11
O
SO2R RO2C
OR
H
H
pKa = 10
O
RO2S
C
H
pKa = 9
pKa = 9
N
C
CH
H
H
N
NO2
R
N
CH
pKa = 46
pKa = 50 - 60
Oxygen Acids
H = acidic hydrogen atom
O
O
H
Cl
O
pKa = -10
O
O
pKa = -1
H
C
R
O
pKa = +5
HO
S
H
H
O
H
O
O
R
S
H
O
pKa = -3
pKa = -3
H
H
O
O
pKa = -2
pKa = -1
O
O
H
O
C
R
O
H
O
O
O
H
N
H R
aldehydes, ketones
O
O
esters, acids
R
pKa = -8 to -6
R
R amides pK = 0
pKa = -3
a
O
O
R
H
O
pKa = +8
O
H
pKa = +10
O
O
H
O
H H3C
pKa = +11.6
H H
H
R
O
H
H
pKa = +15.5 pKa = +15.7 pKa = +16-19 pKa = +25
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
Compare the following groups.
Beauchamp
R
N
R
O
N
O
O
H
H
H
C
O
O
H
H3 C
O
H Cl
C
O
H2C
O
C
CH
O
O
C
C
H
C
H2 C
O
Cl
Cl pK = +2.9
a
pKa = +4.7
H Cl
Cl pK = +1.3
a
O
Cl
pKa = +4.5
O
pKa = +2.8
pKa = +4.0
O
H
O
H
C
O
F
Cl pK = +0.7
a
H
C
O
Cl
pKa = +4.8
O
O
H
C
O
R
pKa = +5
O
Cl
H
C
O
pKa = +1
C
23
H2 C
C
O
Cl
pKa = +2.6
O
H
H2C
H
C
O
H2C
pKa = +2.9 Br pKa = +3.0
O
I pKa = +3.1
Nitrogen Acids
Ph
H
N
H
H
H
H
Ph
C
Ph
N
R
H Ph
N
Ph
pKa = -10
H Ph
N
H
pKa = -5
H
N
N
N
H
H
N
H
O
H
H
pKa = +1
pKa = +5
pKa = +6
pKa = +5
pKa = +7
O
H
H
H
N
H
N
H
H
H
N
H
R
N
H
O
O
R
H2N
N
H
H
H
C
H2N
O
R
pKa = +8 pKa = +9.2 pKa = +9-11 pKa = +10
H
C
H2N
N
H
C
H3C
N
N
pKa = +14
pKa = +13
H
H
H
H
N
pKa = +15
pKa = +17
R
H
N
N
H
R
H
pKa = +35
H
pKa = +37
Other Miscellaneous Acids
Compare the following groups.
R
H
H
H
H
H
N
N
H
S
H
H
S
H Ph
S
H R
S
H
H
P
H
H
pKa = +7
pKa = +8
pKa = +10
Compare the following groups.
F5SbF
H pKa = -20
I
H pKa = -10 HTe
FSO3
H pKa = -15
Br
H pK = -9 HSe
a
F4B
H
O3ClO
H
pKa = -15 Cl
H pKa = -7
HS
H pKa = 7
pKa = -10
H pKa = +3
HO
H pKa = 16
F
ClO
H
pKa = +7.5
HO3SO
BrO
H
pKa = +8.7
O3SO
IO
H
pKa = +11
H
H
pKa = -3
pKa = +2
HO2SO
O2SO
H
O
pKa = +0
H pKa = 3 H2PO4
H pKa = 4
H
HPO4
-2
PO4
pKa = +9
H
H2 N
H
H pKa = +2.1
H pKa = +7.2
O2NO
H pKa = -1
ONO
H pKa = +3
HO2CO
H pKa = +12.4
pKa = +2
pKa = +7
HSe
pKa = +8.1
pKa = +13.7
O2CO
H
H
H
H
pKa = -5
N
H
O3ClO
H pKa = -10
O3ClO
H pKa = -1
H pKa = +6.4 O ClO
3
H pKa = +2
H pKa = +10.3
pKa = +4
HS
H
pKa = +7
HO
H
pKa = +16
ClO
H pKa = +7.5
HOO
H
pKa = +12
HO
H
pKa = +16
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
Beauchamp
24
Table of acidities of some phenols
S
O
S
m = meta
-Cl
8.48
-Br
8.42
-OH
9.98
-CH3 10.48
-NO2
7.23
-CHO 6.79
H
O
o = ortho
S
p = para
9.02
9.11
9.44
10.08
8.35
8.00
9.38
9.34
9.96
10.19
7.14
7.66
Table of acidities of some very strong acids (= 100% ionization in water)
HF / SbF5
FSO3H
pKa  -20
pKa  -15
HF / BF3
HF / BF3
CF3SO3H
HI
HClO4
pKa  -15
pKa  -15
pKa  -14
pKa  -10
pKa  -10
R C N H pKa  -10
pKa  -9
pKa  -7
HBr
HCl
H
R S H
pKa  -7
R
R S H
pKa  -5
H
R O H
R
R O H
pKa  -3
H2SO4
O
S OH pKa  -2
O
H
H O H
pKa  -2
H2MnO4
pKa  -1
H2CrO4
pKa  -1
HNO3
pKa  -1
HClO3
pKa  -1
O
R
O
R
C
O
R
C
O
R
HH
C
C
O
pKa  -3
H
pKa  -8
R
C
CN
H
pKa  -8
H
NC
H
O
H
O
C
H
NC
H
pKa  -7
NO2
O
pKa  -7
H
N H
H
O
NO2
pKa  -10
H
pKa  -6
O
pKa  -11
R N
R
pKa  0
H
N
pKa  -10
CN
N
R
N
O H
R
R
pKa  -3
The above pKa tables dramatically demonstrate how much Bronsted acids can vary in strength. The magnitude
of the numbers is really beyond our comprehension. The strongest acid in the table has a pKa  10+20, while the
weakest acid has a Ka  10-50. That’s 70 orders of magnitude! What does 1070 mean? Even so, we will only use
two simple arguments to rationalize the differences in acidity (…and basicity). We will only use two reasons for
these large differences: 1. inductive effects (based on relative electronegativity) and 2. charge delocalization effects
(usually based on resonance through 2p orbitals). We will not emphasize steric effects, hydrogen bonding or
solvation effects, which can also modify relative acidities, sometimes greatly.
Because we use water as our reference base, the differences in Ka values of all the various acids are mainly due
to the differences in energy between each acid (HA) and its conjugate base (A:-) in the table. We can focus our
attention on just the factors that raise or lower these two components. Quite often one of these components is
neutral and one of them is charged. The two most common possibilities are shown below; the first being much
more common to us. Each reaction is drawn as though G is positive (a weak acid), though there are examples of
both that are strong acids (negative G). Of the two components in each equation below (conjugate acid and
conjugate base), the one that is charged usually has the larger effect on Gionization in comparisons with other acids.
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC
Acid/Base stuff
General Examples
Beauchamp
25
Equation 1 - The acid is neutral, conjugate base is charged. We
will see more reactions like this than equation 2.
H
A
A
H (sol)
A3
A2
A1
G = (1.4)(pKa)
H
H
H
Equation 2 - The acid is charged, conjugate base is neutral. The
most common situation like this is when "A" is a positively
charged nitrogen atom.
anionic
A3
A2
A1
H
More variations in the
energies of A: because
of the excess negative
charge. Resonance and
inductive effects will
generally have a larger
effect on the conjugate
base, because it is charged.
Differences seen here
will be more important
in explaining differences
in relative acidities
between different acids.
neutral
H
A
H
H
H
H
A
A3
A2
A1
H (sol)
neutral
G = (1.4)(pKa)
H
A3
H
A2
H
A1
More variation in H-A-H
because of the excess
positive charge. Resonance
and inductive effects will
generally have a larger effect
on the charged component.
H
H
cationic
H
The factors that stabilize the charged component have the larger effect on the acidity of an acid. Resonance and inductive effects are
key concepts to your understanding of acidity, and much more in organic chemistry and biochemistry. Learn these concepts well.
Specific Examples
Examples
H
H
N
Inductive / electronegative effect affects the
stability of the anionic conjugate base more
than the neutral acid. Negative charge on
oxygen is more stable than negative charge
on nitrogen.
:A2 is less
stable.
H
Resonance / delocalization effect affects
the stability of the cationic acid more
than the neutral conjugate base.
NH2
C
NH3
H2N
N
O
:A1 is more
stable.
pKa = +9
H
H
H
pKa = +16
O
H
H = lost proton
pKa = +13
N
H
weaker acid
stronger acid
H
pKa = +35
H
H3N
stronger acid
HA3 is less stable.
NH2
H
C
H2N
N
weaker acid
HA4 is more stable.
H
resonance
A larger pKa  G means a weaker acid. In the first example this is due to a less stable conjugate base (negative charge on nitrogen
instead of oxygen). In the second example this is due to a more stable acid (delocalization of charge / resonance).
y:\files\classes\Organic Chemistry Tool Chest\Acid,Base,Tautomers\314 acid-base list, answers newer.DOC