Organic Chemistry

Chapter 4
The Study of Chemical Reactions 1
4-1 Introduction

• Overall reaction: reactants → products

• To learn more about a reaction:

– Thermodynamics is the study of the energy
changes that accompany chemical and physical
transformations.
– Kinetics is the study of reaction rates.

• Mechanism: step-by-step description of how the

reaction happens

2
4-2 Chlorination of Methane

• It requires heat or light for initiation.

• The most effective wavelength is blue, which is absorbed by

chlorine gas.

• Many molecules of product are formed from absorption of

only one photon of light (chain reaction).

3
4-3 The Free-Radical Chain Reaction

• Initiation generates a radical intermediate.

• Propagation: The intermediate reacts with a stable

molecule to produce another reactive intermediate
(and a product molecule).

• Terminations are side reactions that destroy the

reactive intermediate.

4
4-3 The Free-Radical Chain Reaction
Substitution

5
4-3 The Free-Radical Chain Reaction
The Initiation Step: Generation of Radicals

A chlorine molecule splits homolytically into chlorine

atoms (free radicals).

6
4-3 The Free-Radical Chain Reaction
Lewis Structures of Free Radicals

• Free radicals are reactive species with odd

numbers of electrons.

• Halogens have seven valence electrons, so one of

them will be unpaired (radical). We refer to the
halides as atoms, not radicals.
7
4-3 The Free-Radical Chain Reaction
Propagation Step

The chlorine atom collides with a methane molecule

and abstracts (removes) an H, forming another free
radical and one of the products (HCl).
8
4-3 The Free-Radical Chain Reaction
Propagation Step

The methyl free radical collides with another chlorine

molecule, producing the organic product (methyl
chloride) and regenerating the chlorine radical.

9
4-3 The Free-Radical Chain Reaction
Overall Reaction

10
4-3 The Free-Radical Chain Reaction
Chain Reaction

11
4-3 The Free-Radical Chain Reaction
Termination Reactions

• A reaction is classified as a termination step when

any two free radicals join together, producing a
nonradical compound.

• Combination of a free radical with a contaminant or

collision with a wall are also termination steps.
12
4-3 The Free-Radical Chain Reaction
More Termination Reactions

13
4-4 Equilibrium Constant and Free Energy
Equilibrium Constant

Keq tell us whether the products or the reactants are more

stable. Keq > 1: reaction is favored as written from left to right.
Keq < 1: the reverse reaction is favored (from right to left).

14
4-4 Equilibrium Constant and Free Energy
Free Energy Change

• DG = (energy of products) – (energy of reactants)

• DG is the amount of energy available to do work.
• A reaction with a negative DG is favorable and
spontaneous.

where R = 8.314 J/K-mol and T = temperature in

kelvins.

15
4-4 Equilibrium Constant and Free Energy
Solved Problem 1
Calculate the value of DG° for the chlorination of methane.

Solution:
DG° = –2.303RT(log Keq)
Keq for the chlorination is 1.1 x 1019, and log Keq = 19.04

At 25 °C (about 298 K), the value of RT is

RT = (8.314 J/kelvin-mol)(298 kelvins) = 2478 J/mol, or 2.48 kJ/mol

Substituting, we have

DG° = (–2.303)(2.478 kJ/mol)(19.04) = –108.7 kJ/mol (–25.9 kcal/mol)

This is a large negative value for DG°, showing that this chlorination has a
large driving force that pushes it toward completion.
16
4-4 Equilibrium Constant and Free Energy

17
4-5 Enthalpy and Entropy
Factors Determining DG°

Free energy change depends on the following:

• Enthalpy
- DH° = (enthalpy of products) – (enthalpy of
reactants)

• Entropy
- DS° = (entropy of products) – (entropy of reactants)

DG° = DH° – TDS°

18
4-5 Enthalpy and Entropy
Enthalpy

• DH° = heat released or absorbed during a

chemical reaction at standard conditions.

• Exothermic (–DH): Heat is released.

• Endothermic (+DH): Heat is absorbed.

• Reactions favor products with the lowest enthalpy

(strongest bonds).

19
4-5 Enthalpy and Entropy
Entropy

• DS° = change in randomness, disorder, or

freedom of movement.

• Increasing heat, volume, or number of particles

increases entropy.

• Spontaneous reactions maximize disorder and

minimize enthalpy.

• In the equation DG° = DH° – TDS°, the entropy

value is often small.
20
4-6 Bond-Dissociation Enthalpies

Amount of enthalpy required to break a particular bond homolytically

• Bond dissociation requires energy (+BDE).

• Bond formation releases energy (–BDE).

• BDE can be used to estimate DH for a reaction.

– Homolytic cleavage: When the bond breaks,

each atom gets one electron.

– Heterolytic cleavage: When the bond breaks,

the most electronegative atom gets both
electrons. 21
4-6 Bond-Dissociation Enthalpies
Homolytic and Heterolytic Cleavages

22
4-6 Bond-Dissociation Enthalpies

23
4-7 Enthalpy Changes in Chlorination
Homolytic and Heterolytic Cleavages

In calculating ΔH, use positive BDE values for bonds that are broken
and negative values for bonds that are formed.
24
4-8 Kinetics and the Rate Equation
Kinetics
• Kinetics is the study of reaction rates.

• Rate of the reaction is a measure of how the

concentration of the products increases while the
concentration of the starting materials decreases.

• A rate equation (also called the rate law) is the

relationship between the concentrations
of the reactants and the observed reaction rate.

• Rate law is determined experimentally.

25
4-8 Kinetics and the Rate Equation
Rate Law

• For the reaction A + B → C + D,

rate = kr[A]a[B]b
- where kr is the rate constant
- a is the order with respect to A
- b is the order with respect to B
- a + b is the overall order

• Order is the number of molecules of that reactant

which is present in the rate-determining step of the
mechanism.

26
4-9 Activation Energy and Temperature Dependence of Rates
Activation Energy

The rate constant, kr, depends on the conditions of the

reaction, especially the temperature:

- where A = constant (frequency factor)

- Ea = activation energy
- R = gas constant, 8.314 J/kelvin-mole
- T = absolute temperature
Ea is the minimum kinetic energy needed to react.

27
4-9 Activation Energy and Temperature Dependence of Rates
Temperature Dependence of Ea

At higher temperatures, more molecules have the required

energy to react.
28
4-10 Transition States

29
4-10 Transition States
Energy Diagram of an Exothermic Reaction

• The vertical axis in this graph represents the potential

energy.
• The transition state (‡) is the highest point on the graph,
and the activation energy (Ea) is the energy difference
between the reactants and the transition state. 30
4-11 Rates of Multistep Reactions

• The highest points in an energy diagram are

transition states.

• An intermediate is a species that exists for some

finite length of time, even if it is very short.

• The reaction step with the highest Ea will be the

slowest step and will determine the rate at which
the reaction proceeds (rate-limiting step).

31
4-10 Transition States
Energy Diagram for the Chlorination of Methane

32
4-12 Temperature Dependence of Halogenation
Rate, Ea, and Temperature

X + CH4 HX + CH3

33
4-12 Temperature Dependence of Halogenation
Conclusions

• With increasing Ea, rate decreases.

• With increasing temperature, rate increases.

• Fluorine reacts explosively.

• Chlorine reacts at a moderate rate.

• Bromine must be heated to react.

• Iodine does not react (detectably).

34
4-13 Selectivity in Halogenation
Chlorination of Propane: Product Ratios

• There are six 1 H’s and two 2 H’s. We expect 3:1

product mix, or 75% 1-chloropropane and 25% 2-
chloropropane.

• Typical product mix: 40% 1-chloropropane and 60% 2-

chloropropane.

• Therefore, not all H’s are equally reactive. 35

4-13 Selectivity in Halogenation
Reactivity of Hydrogens

36
4-13 Selectivity in Halogenation
Chlorination Mechanism

37
4-13 Selectivity in Halogenation
Bond Dissociation Energies for the Formation of Free Radicals

38
4-13 Selectivity in Halogenation
Free Radical Stabilities
• Energy required to break a C-H bond decreases as
substitution on the carbon increases.

• Stability: 3 > 2 > 1 > methyl

39
4-13 Selectivity in Halogenation
Chlorination Energy Diagram

The lower the Ea, the faster the rate, so a more stable
intermediate is formed faster. 40
4-13 Selectivity in Halogenation

41
4-13 Selectivity in Halogenation
Solved Problem

Tertiary hydrogen atoms react with Cl• about 5.5 times as fast as primary
ones. Predict the product ratios for chlorination of isobutane.

Solution
There are nine primary hydrogens and one tertiary hydrogen in isobutane.

(9 primary hydrogens) x (reactivity 1.0) = 9.0 relative amount of reaction

(1 tertiary hydrogen) x (reactivity 5.5) = 5.5 relative amount of reaction

42
4-13 Selectivity in Halogenation
Solved Problem
Solution
Even though the primary hydrogens are less reactive, there are so many
of them that the primary product is the major product. The product ratio will
be 9.0:5.5, or about 1.6:1.

43
4-13 Selectivity in Halogenation
Bromination of Propane

• There are six 1 H’s and two 2 H’s. We expect 3:1 product
mix, or 75% 1-bromopropane and 25% 2-bromopropane.
• Typical product mix: 3% 1-bromopropane and 97% 2-
bromopropane !!!
• Bromination is more selective than chlorination. 44
4-13 Selectivity in Halogenation
Bromination of Propane

45
4-13 Selectivity in Halogenation
Energy Diagram for the Bromination of Propane

46
4-14 Hammond Postulate
Energy Diagrams: Chlorination VS. Bromination

47
4-14 Hammond Postulate

• Related species that are similar in energy are

also similar in structure.

• The structure of the transition state resembles

the structure of the closest stable species.

• Endothermic reaction: Transition state

resembles the product.

• Exothermic reaction: Transition state

resembles the reactant.

48
4-14 Hammond Postulate
Endothermic and Exothermic Diagrams

49
4-15 Radical Inhibitors

• These are often added to food to retard spoilage

by radical chain reactions.

• Without an inhibitor, each initiation step will cause

a chain reaction so that many molecules will react.

• An inhibitor combines with the free radical to form

a stable molecule.

• Vitamin E and vitamin C are thought to protect

living cells from free radicals.
50
4-15 Radical Inhibitors

• A radical chain reaction is fast and has many exothermic

steps that create more reactive radicals.

• When an inhibitor reacts with the radical, it creates a

stable intermediate, and any further reactions will be
endothermic and slow.
51
4-15 Radical Inhibitors
Butylated hydroxyanisole (BHA)

Vitamin C

52
4-16 Reactive Intermediates

• Reactive intermediates are short-lived species.

• They are never present in high concentrations because

they react as quickly as they are formed.
53
4-16 Reactive Intermediates
Carbocation Structure

• A carbocation (also called a carbonium ion or a

carbenium ion) is a positively charged carbon.
• Carbon is sp2 hybridized with a vacant p orbital.
54
4-16 Reactive Intermediates
Carbocation Stability

More highly substituted carbocations are more stable.

55
4-16 Reactive Intermediates
Carbocation Stability
Stabilized by alkyl substituents in two ways:
1. Inductive effect: Donation of electron density along the
sigma bonds
2. Hyperconjugation: Overlap of sigma bonding orbitals
with empty p orbital

56
4-16 Reactive Intermediates
Unsaturated Carbocations

• Unsaturated carbocations are also stabilized by

resonance stabilization.
• If a pi bond is adjacent to a carbocation, the filled p
orbitals of the bond will overlap with the empty p
orbital of the carbocation.
57
4-16 Reactive Intermediates
Electrophilic Carbocation

Strong Proton Acid

58
4-16 Reactive Intermediates
Free Radicals

• Carbon is sp2 hybridized with one electron in the p

orbital.
• Stabilized by alkyl substituents
• Order of stability: 3° > 2° > 1° > methyl 59
4-16 Reactive Intermediates
Stability of Carbon Radicals

More highly substituted radicals are more stable.

60
4-16 Reactive Intermediates
Unsaturated Radicals

• Like carbocations, radicals can be stabilized by

resonance.
• Overlap with the p orbitals of a p bond allows the
odd electron to be delocalized over two carbon
atoms.
• Resonance delocalization is particularly effective in
stabilizing a radical.
61
4-16 Reactive Intermediates
Carbanions

• Eight electrons on C: 6 bonding + lone pair

• Carbon has a negative charge
• Destabilized by alkyl substituents
• Methyl >1 > 2  > 3 
• The order of stability is usually the opposite
of that for carbocations and free radicals.
62
4-16 Reactive Intermediates
Basicity of Carbanions

• A carbanion has a negative charge on its carbon

atom, making it a more powerful base and a
stronger nucleophile than an amine.
• A carbanion is sufficiently basic to remove a proton
from ammonia.
63
4-16 Reactive Intermediates

64
4-16 Reactive Intermediates
Carbenes

• Carbon in carbenes is neutral.

• It has a vacant p orbital, so it can react as an
electrophile.
• It has a lone pair of electrons in the sp2 orbital, so it
can react as a nucleophile.
65
4-16 Reactive Intermediates
Carbenes

• A strong base can abstract a proton from tribromomethane

(CHBr3) to give an inductively stabilized carbanion.

• This carbanion expels bromide ion to give dibromocarbene.

The carbon atom is sp2 hybridized with trigonal geometry.

• A carbene has both a lone pair of electrons and an empty p

orbital, so it can react as a nucleophile or as an
electrophile.
66
4-16 Reactive Intermediates
Carbenes

67
4-16 Reactive Intermediates
Summary of Reactive Species

68