Chapter 3

Chapter 3
Acids and Bases

An Introduction to Organic
Reactions and Their
Mechanisms
Created by
Professor William Tam & Dr. Phillis Chang
Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved.
About The Authors
These Powerpoint Lecture Slides were created and prepared by Professor
William Tam and his wife Dr. Phillis Chang.
Professor William Tam received his B.Sc. at the University of Hong Kong in
1990 and his Ph.D. at the University of Toronto (Canada) in 1995. He was an
NSERC postdoctoral fellow at the Imperial College (UK) and at Harvard
University (USA). He joined the Department of Chemistry at the University of
Guelph (Ontario, Canada) in 1998 and is currently a Full Professor and
Associate Chair in the department. Professor Tam has received several awards
in research and teaching, and according to Essential Science Indicators, he is
currently ranked as the Top 1% most cited Chemists worldwide. He has
published four books and over 80 scientific papers in top international journals
such as J. Am. Chem. Soc., Angew. Chem., Org. Lett., and J. Org. Chem.
Dr. Phillis Chang received her B.Sc. at New York University (USA) in 1994, her
M.Sc. and Ph.D. in 1997 and 2001 at the University of Guelph (Canada). She
lives in Guelph with her husband, William, and their son, Matthew.
© 2014 by John Wiley & Sons, Inc. All rights reserved.

Table of Contents (hyperlinked)
1. Acid–Base Reactions
2. How to Use Curved Arrows in Illustrating Reactions
3. Lewis Acids and Bases
4. Heterolysis of Bonds to Carbon: Carbocations and Carbanions
5. The Strength of Brønsted–Lowry Acids and Bases: Ka and pKa
6. How to Predict the Outcome of Acid–Base Reactions
7. Relationships between Structure and Acidity
8. Energy Changes
9. The Relationship between the Equilibrium Constant, Keq , and the
Standard Free-Energy Change, ΔG o
10. Acidity: Carboxylic Acids versus Alcohols
11. The Effect of the Solvent on Acidity
12. Organic Compounds as Bases
13. A Mechanism for an Organic Reaction
14. Acids and Bases in Nonaqueous Solutions
15. Acid–Base Reactions and the Synthesis of Deuterium- and Tritium-
Labeled Compounds
16. Applications of Basic Principles

Table of Contents
2. How to Use Curved Arrows in Illustrating Reactions
4. Heterolysis of Bonds to Carbon: Carbocations and Carbanions
5. The Strength of Brønsted–Lowry Acids and Bases: Ka and pKa
6. How to Predict the Outcome of Acid–Base Reactions
7. Relationships between Structure and Acidity
8. Energy Changes
9. The Relationship between the Equilibrium Constant, Keq , and the
Standard Free-Energy Change, ΔG o
10. Acidity: Carboxylic Acids versus Alcohols
11. The Effect of the Solvent on Acidity
13. A Mechanism for an Organic Reaction
14. Acids and Bases in Nonaqueous Solutions
15. Acid–Base Reactions and the Synthesis of Deuterium- and Tritium-
Labeled Compounds

In this chapter we will consider:
 Rules that show how to classify
reactive groups within molecules from
the standpoints of acids and bases as
well as from electron-rich and electron-
poor domains
 The step-by-step processes of a
chemical reaction and how to codify
these processes into a few specific,
easy-to-understand types

 Many of the reactions that occur in organic
chemistry are either acid–base reactions
themselves or they involve an acid–base
reaction at some stage
 Acid–base reactions are simple fundamental
reactions that will enable you to see how
chemists use curved arrows to represent
mechanisms of reactions and how they
depict the processes of bond breaking and
bond making that occur as molecules react

1A. Brønsted–Lowry Acids and Bases
 Brønsted–Lowry acid–base reactions

involve the transfer of protons
 A Brønsted–Lowry acid is a
substance that can donate (or lose) a
proton
 A Brønsted–Lowry base is a
substance that can accept (or remove)
a proton

 Example
Base Conjugate Acid
(H+ acceptor) of H2O
H O + H Cl H O H + Cl
H H
Acid Conjugate Base

(H+ donor) of HCl
1B. Acids and Bases in Water
 Hydronium ion (H3O+) is the strongest
acid that can exist in water to any
significant extent: Any stronger acid
will simply transfer its proton to a
water molecule to form hydronium ions
 Hydroxide ion (HO-) is the strongest
base that can exist in water to any
significant extent: Any base stronger
than hydroxide will remove a proton
from water to form hydroxide ions
 Total ionic reaction
H O H + Cl + Na O H 2H O + Na + Cl
H H
Spectator ions
 Net reaction
H O H + O H 2H O
H H

2. How to Use Curved Arrows in
Illustrating Reactions
 Curved arrows show the direction of
electron flow in a reaction mechanism
• Draw the curved arrow so that it points
from the source of an electron pair to the
atom receiving the pair. (Curved arrows
can also show the movement of single
electrons)
• Always show the flow of electrons from a
site of higher electron density to a site of
lower electron density
• Never use curved arrows to show the
movement of atoms. Atoms are assumed
to follow the flow of the electrons
• Make sure that the movement of

electrons shown by the curved arrow
does not violate the octet rule for
elements in the second row of the
periodic table

 Examples

 Examples
NOT
O
N
H
H C
H 

 Examples

 Lewis Acids are electron pair acceptors
 Lewis Bases are electron pair donors
Lewis Base
(e⊖ pair donor)
 
Cl H + NH3 Cl + H NH3
Lewis Acid
(e⊖ pair acceptor)
Lewis Base
(e⊖ pair donor)
Cl Cl
 
Cl Al  + NH3 Cl Al NH3

Cl Cl

Lewis Acid
(empty p orbital of Aluminum
allows AlCl3 acts as e⊖ pair acceptor)
 In Lewis acid–base theory, the
attraction of oppositely charged species
is fundamental to reactivity
4. Heterolysis of Bonds to Carbon:
Carbocations and Carbanions
 Heterolysis
heterolytic
A B bond
A + B
cleavage ions
A B A + B
● Normally requires the bond to be
polarized
 
A B
● Usually occurs with assistance
 
Y A B Y A + B
 Carbocations are electron deficient. They
have only six electrons in their valence
shell, and because of this, carbocations
are Lewis acids
C + B C B
carbocation anion
(a Lewis acid) (a Lewis base)
C + O H C O H
H H
carbocation water
(a Lewis acid) (a Lewis base)
4A. Electrophiles and Nucleophiles
 Because carbocations are electron-

seeking reagents, chemists call them
electrophiles (meaning electron-
loving)
 Electrophiles are reagents that seek

electrons so as to achieve a stable shell
of electrons like that of a noble gas

 All Lewis acids are electrophiles.
By accepting an electron pair from a
Lewis base, a carbocation fills its
valence shell
C + B C B
carbocation anion
(a Lewis acid (a Lewis base)
and electrophile)

 Carbon atoms that are electron poor
because of bond polarity, but are not
carbocations, can also be electrophiles
 
B + C O B C O
Lewis base Lewis acid

electrophile

 Carbanions are Lewis bases
 A nucleophile is a Lewis base that
seeks a positive center such as a
positively charged carbon atom

5. The Strength of Brønsted-Lowry
Acids and Bases: Ka and pKa
 In contrast to strong acids such as HCl
and H2SO4, acetic acid is a much
weaker acid
O O
H3C OH + H2O H3C O + H O H

H
● At 25oC, in a 0.1 M acetic acid solution,
only about 1% of the acetic acid
molecules ionize
5A. The Acidity Constant, Ka
O O

H
 Equilibrium constant (Keq)

⊖ ⊕
[CH3CO2 ] [H3O ]
Keq =
[CH3CO2H][H2O]

 For dilute aqueous solutions, the
concentration of water is essentially
constant (~55.5M); and the Keq
expression can be written in terms of
the acidity constant (Ka)
⊖ ⊕
[CH3CO2 ] [H3O ]
Ka = Keq [H2O] =
[CH3CO2H]
 At 25°C, the acidity constant for acetic

acid is 1.76 x 105
 For any weak acid dissolved in water
HA + H2O H3O + A
⊕ ⊖
[H3O ] [A ]
Ka =
[HA]
 An acid with a large value of Ka
● a strong acid
 An acid with a small value of Ka
● a weak acid
5B. Acidity and pKa
pKa =  log Ka
⊕
pH =  log [H3O ]
 For acetic acid the pKa is 4.75

pKa =  log [1.76 x 105]
=  [ 4.75]
= 4.75
 The larger the value of the pKa, the
weaker the acid
Increasing acid strength
CH3CO2H CF3CO2H HCl

pKa = 4.75 > pKa = 0 > pKa = 7
Weak Very
acid strong
acid
 Relative Strength of Selected Acids &
Their Conjugate Bases
O H H H
O
Acid HCl Ph S OH H3C O H O HNO3
O H H
p Ka -7 -6.5 -2.9 -2.5 -1.74 -1.4
O
O
Conjugate
Cl Ph S O CH3OH H2O NO3
Base
O
Increasing base strength

 (Cont'd)

O O H O
Acid HF Ph N H
F3C OH Ph OH H3C OH
H
pKa 0.18 3.2 4.21 4.63 4.75
O O O
Conjugate
F Ph NH2
Base
F3C O Ph O H3C O

 (Cont'd)

O O H H
OH
Acid H N H H3C N H H O H
H H H
pKa 9.0 9.2 9.9 10.6 15.7
O O O
Conjugate
NH3 CH3NH2 HO
Base

 (Cont'd)
OH O
Acid OH HC H H H
H
pKa 16 18 19.2 25 35
O O
Conjugate
O HC C H
Base

 (Cont'd)
H H
Acid H2N H H2C H3C C H
H H
pKa 38 44 50
Conjugate
NH2 H2C CH H3C CH2
Base

5C. Predicting the Strength of Bases
 The stronger the acid, the weaker its
conjugate base
 The larger the pKa of the conjugate
acid, the stronger the base
⊖ ⊖ ⊖
Cl CH3CO2 HO
Very weak base Weak base Strong base
pKa (HCl) pKa (CH3CO2H) pKa (H2O)

= 7 = 4.75 = 15.7
 Example
Base CH3OH H2O
Conjugate H3C O H H O H
Acid H H
pKa -2.5 -1.74

⊕
 Since CH3OH2 is a stronger acid than
⊕
H3O , H2O is a stronger base than CH3OH

6. How to Predict the Outcome of
Acid-Base Reactions
 Acid–base reactions always favor the
formation of the weaker acid and the
weaker base
 Acid–base reactions are under
equilibrium control
 Reactions under equilibrium control
always favor the formation of the most
stable (lowest potential energy) species
stronger weaker
base base
O O
O
R O H + Na OH R O Na + H H
stronger weaker
acid acid
pKa ~3-5 pKa = 15.7

6A. Water Solubility as the Result of
Salt Formation
 Most carboxylic acids containing more
than 5 carbons are insoluble in water
 However, due to their acidity, they are
soluble in aq. NaOH
O O
O
R O H + Na OH R O Na + H H
(R>5 carbons) Soluble in water
Insoluble (due to its polarity
in water as a salt)
 Similarly, amines with high molecular
weights are insoluble in water
 However, due to their basicity, they are
soluble in aqueous acids
H
R NH2 + H O H Cl R N H Cl + H2O
H H
Water Water
Insoluble Soluble
(salt)
7. Relationships between
Structure and Acidity
H–F H–Cl H–Br H–I
Bond Length (Å) 0.92 1.28 1.41 1.60
pKa 3.2 -7 -9 -10
Increasing acidity
 The strength of H–X bond
● H–F > H–Cl > H–Br > H–I
The stronger the H–X bond,
the weaker the acid.
 Thus acidity increases as we descend a
vertical column in a group in the
Periodic Table

HF F

Increasing HCl Cl Increasing
acidity HBr Br  basicity

HI I
The stronger the acid,

the weaker the conjugate base.
       
H3C—H H3N—H HO—H F—H
Electro-
2.5 2.1 3.0 2.1 3.5 2.1 4.0 2.1
negativity
pKa 48 38 15.7 3.2
The higher the electronegativity

of an atom, the easier it will
acquire a negative charge.
 Thus acidity increases from left to right
when we compare compounds in the
same row of the Periodic Table
Increasing acidity
H3C–H H2N–H HO–H F–H
CH NH OH F

3 2
Increasing basicity

Acidity increases within a given row
(electronegativity effect)
C N O F
Acidity increases within a

Hydride (H3C–H) (H2N–H) (HO–H) (F–H)
(bond strength effect)

pKa 48 38 15.7 3.2
S Cl
given column
(HS–H) (Cl–H)
7.0 -7
Se Br
(HSe–H) (Br–H)
3.9 -9
I
(I–H)
-10
7A. The Effect of Hybridization
(50% (33.3% (25%
s character) s character) s character)
sp sp2 sp3
H H H H
H C C H C C H C C
H
H H H H
pKa = 25 pKa = 44 pKa = 50

 Having more s character means that the electrons
of the anion will, on the average, be lower in
energy, and the anion will be more stable
 Relative Acidity of the Hydrocarbons
H H H H
H C C H > C C > H C C H
H H H H
 Relative Basicity of the Carbanions

H H
H C C C C
H > > H C C
H H H H

7B. Inductive Effects
 Inductive effects are electronic effects
transmitted through bonds
 The inductive effect of a group can be

electron donating or electron
withdrawing
 Inductive effects weaken as the

distance from the group increases
The C–C
H3C CH3 bond is
nonpolar.
  
H3C CH2 F
2 1
 The positive charge that the fluorine

imparts to C1 is greater than that
imparted to C2 because the fluorine is
closer to C1
8. Energy Changes
 The two fundamental types of energy
are kinetic energy and potential energy
 Kinetic energy is the energy an object

has because of its motion; it equals
one-half the object’s mass multiplied
by the square of its velocity
● KE = ½mn2

 Potential energy is stored energy. It
exists only when an attractive or
repulsive force exists between objects
 Chemical energy is a form of potential

energy
 The more potential energy an object

has, the less stable it is

Potential energy exists between objects that either attract or repel
each other. In the case of atoms joined by a covalent bond, the
lowest potential energy state occurs when atoms are at their ideal
internuclear distance (bond length). Lengthening or shortening the
bond distance raises the potential energy.
8A. Potential Energy and Covalent
Bonds
 Atoms and molecules possess potential
energy – often called chemical
energy – that can be released as heat
when they react
 Because heat is associated with
molecular motion, this release of heat
results from a change from potential
energy to kinetic energy

H + H H H
DH o =  436 kJ mol1
(Formation of H-H bond releases
436 kJ mol1 of energy)
 The relative
potential H + H
Potential Energy
energies of
hydrogen
atoms and a 436 kJ mol1
hydrogen
molecule H H
9. The Relationship between Keq
and DG°
DG° =  RT ln Keq
R is the gas constant = 8.314 J K1
T is the absolute temperature in kelvins (K)
 For a reaction to favor the formation of
products when equilibrium is reached it must
have a negative value for DG°
 For reactions with a positive DG°, the
formation of products at equilibrium is
unfavorable
DG° = DH°  T DS°
DH° is the enthalpy energy
DS° is the entropy energy
 A negative value for DH° will contribute to
making DG° negative and will consequently favor
the formation of products
 The more random a system is, the greater is its
DS°
 A positive entropy change (from order to
disorder) makes a negative contribution to DG°
and is energetically favorable for the formation of
products
10. Acidity: Carboxylic Acids versus
Alcohols
O
H3C OH CH3CH2 OH
Acetic acid Ethanol
pKa = 4.75 pKa = 16

DG° = 27 kJ/mol DG° = 90.8 kJ/mol

⊖
CH3CH2O
⊕
Free Energy Change + H3O
⊖
CH3CO2 DG° = 90.8 kJ/mol
⊕
+ H3O
DG° = 27 kJ/mol
CH3CO2H CH3CH2OH
+ H2O + H2O
O O
+ H2O + H3O
CH3 O H CH3 O
acetic acid acetate
CH3CH2 O H + H2O CH3CH2 O + H3O

ethanol ethoxide

 When comparing acidity of organic
compounds, we compare the stability
of their conjugate base. The more
stable the conjugate base, the stronger
the acid
CH3COOH CH3CH2OH
pKa 4.75 16

10A. The Effect of Delocalization
 The conjugate base acetate is more
stable (the anion is more delocalized)
than ethoxide due to resonance
stabilization
O O O
CH3 O CH3 O CH3 O
● Thus, acetic acid is a stronger acid

than ethanol
10B. The Inductive Effect
O
<
CH3 O <H CH3CH2 O <H
Acetic acid Ethanol
Stronger acid Weaker acid

10C. Summary and a Comparison of
Conjugate Acid–Base Strengths
 The greater acidity of a carboxylic acid
is predominantly due to the ability of
its conjugate base (a carboxylate ion)
to stabilize a negative charge better
than an alkoxide ion, the conjugate
base of an alcohol
 The conjugate base of a carboxylic acid
is a weaker base than the conjugate
base of an alcohol
10D. Inductive Effects of Other
Groups
O O
<
<
Cl
CH3 O <H CH2 O <H
pKa = 4.75 pKa = 2.86
O 
O
 
Cl Cl
CH2 O H + H2O CH2 O + H3O
O O
Cl Cl
O O
 The Cl further stabilizes the

carboxylate anion due to negative
inductive effect of the Cl

11. The Effect of the Solvent on
Acidity
 In the absence of a solvent (i.e., in the
gas phase), most acids are far weaker
than they are in solution
 In solution, solvent molecules surround
the ions, insulating them from one
another, stabilizing them, and making it
far easier to separate them than in the
gas phase

 Solvation of any species decreases the
entropy of the solvent because the
solvent molecules become much more
ordered as they surround molecules of
the solute

O O

H
 Water molecules solvate both the
undissociated acid (CH3CO2H) and its
anion (CH3CO2) by forming hydrogen
bonds to them
⊖
 However, hydrogen bonding to CH3CO2
is much stronger than to CH3CO2H
because the water molecules are more
attracted by the negative charge
 If an organic compound contains an
atom with an unshared electron pair, it
is a potential base
H3C O + H Cl H3C O H + Cl
H H
Methanol Methyloxonium ion

(a protonated alcohol)

R O + H A R O H + A
H H
Alcohol Strong Alkyloxonium ion Weak

acid base
R O + H A R O H + A
R R
Ether Strong Dialkyloxonium Weak

acid ion base
H
O O
+ H A + A
R R R R
Ketone Strong Protonated Weak

acid ketone base
 Proton transfer reactions like these are

often the first step in many reactions
that alcohols, ethers, aldehydes,
ketones, esters, amides, and carboxylic
acids undergo
13. A Mechanism for an Organic
Reaction
CH3
H3C C OH + R O H + Cl
CH3 H
tert-Butyl alcohol Concentrated HCl

(soluble in H2O)
CH3
H3C C Cl + 2 H2O
H2O
CH3
tert-Butyl chloride
(insoluble in H2O)
 Step 1
CH3 CH3 H
H3C C O H + H O H H3C C O H
CH3 H CH3
+ H O
H
 Step 2
CH3 H CH2
H3C C O H H3C C + H O
CH3 CH3 H
 Step 3
CH3 CH3
H3C C + Cl H3C C Cl
CH3 CH3

14. Acids and Bases in Nonaqueous
Solutions
H C C H + NH2 H C C +H NH2
pKa = 25 (stronger base) (weaker base) pKa = 38
 This reaction cannot be carried out

using water as solvent
O
H H + NH2 HO + H NH2
pKa = 15.7 pKa = 38
 Since water is a stronger acid than
⊖
ethyne, NH2 will react with water first
instead of ethyne
 When NaNH2 is used, solvent such as

hexane, Et2O or liquid NH3 can be used
instead of water

15. Acid–Base Reactions & The
Synthesis of 2H- & 3H-Labeled
Compounds
Li + O D + OD + Li
D D
salt
Deuterium
(weaker base)
(stronger acid)
Isopropyl lithium 2-Deuteriopropane

(stronger base) (weaker acid)
 Electronegativity differences polarize

bonds
 Polarized bonds underlie inductive
effects
 Opposite charges attract
 Nature prefers states of lower potential
energy
 END OF CHAPTER 3 

Chapter 3

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Chapter 3

Acids and Bases

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 Brønsted–Lowry acid–base reactions

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Acid Conjugate Base

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• Make sure that the movement of

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© 2014 by John Wiley & Sons, Inc. All rights reserved.

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 Because carbocations are electron-

 Electrophiles are reagents that seek

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Lewis base Lewis acid

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H3C OH + H2O H3C O + H O H

H3C OH + H2O H3C O + H O H

 Equilibrium constant (Keq)

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 At 25°C, the acidity constant for acetic

 For acetic acid the pKa is 4.75

Increasing acid strength

CH3CO2H CF3CO2H HCl

p Ka -7 -6.5 -2.9 -2.5 -1.74 -1.4

Increasing base strength

Increasing acid strength

Increasing base strength

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Increasing acid strength

pKa 9.0 9.2 9.9 10.6 15.7

Increasing base strength

© 2014 by John Wiley & Sons, Inc. All rights reserved.

Increasing acid strength

Increasing base strength

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Increasing acid strength

Increasing base strength

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pKa (HCl) pKa (CH3CO2H) pKa (H2O)

pKa -2.5 -1.74

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The stronger the acid,

pKa 48 38 15.7 3.2

The higher the electronegativity

H3C–H H2N–H HO–H F–H

CH NH OH F

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Acidity increases within a

(bond strength effect)

pKa = 25 pKa = 44 pKa = 50

 Relative Basicity of the Carbanions

© 2014 by John Wiley & Sons, Inc. All rights reserved.

 The inductive effect of a group can be

 Inductive effects weaken as the

 The positive charge that the fluorine