6.

An Overview of Organic
Reactions

Why this chapter?

To understand organic and/or biochemistry, it is
necessary to know:
-What occurs
-Why and how chemical reactions take place

We will see how a reaction can be described

 6.1 Kinds of Organic Reactions
 Ingeneral, we look at what occurs and try to learn how it
happens
 Common patterns describe the changes

◦ Addition reactions – two molecules combine

◦ Elimination reactions – one molecule splits into two

2
 ◦ Substitution – parts from two molecules exchange

◦ Rearrangement reactions – a molecule undergoes

changes in the way its atoms are connected

3
 Learning Check:

What kind of reaction is the transformation shown below?

Cl
+ HCl

1. an elimination reaction
2. a rearrangement reaction
3. a substitution reaction
4. an addition reaction
5. none of these
 Solution:

What kind of reaction is the transformation shown below?

Cl
+ HCl

1. an elimination reaction
2. a rearrangement reaction
3. a substitution reaction
4. an addition reaction
5. none of these
6.2 How Organic Reactions
Occur: Mechanisms
 In a clock the hands move but the mechanism behind the
face is what causes the movement
 In an organic reaction, we see the transformation that

has occurred. The mechanism describes the steps behind

the changes that we can observe
 Reactions occur in defined steps that lead from reactant
to product

6
 Steps in Mechanisms
 We classify the types of steps in a sequence
 A step involves either the formation or breaking of a
covalent bond
 Steps can occur in individually or in combination with
other steps
 When several steps occur at the same time they are said to
be concerted

7
Types of Steps in Reaction Mechanisms
 Bondformation or breakage can be symmetrical or unsymetrical
 Symmetrical- homolytic
 Unsymmetrical- heterolytic

Bond Breaking

Bond Making

8
 Indicating Steps in Mechanisms
 Curvedarrows indicate breaking and
forming of bonds

 Arrowheads with a “half” head (“fish-

hook”) indicate homolytic and
homogenic steps (called ‘radical
processes’)

 Arrowheads with a complete head

indicate heterolytic and heterogenic
steps (called ‘polar processes’)

9
 6.3 Radical Reactions
 Not as common as polar reactions
 Radicals react to complete electron octet of valence shell

◦ A radical can break a bond in another molecule and

abstract a partner with an electron, giving substitution in
the original molecule
◦ A radical can add to an alkene to give a new radical,
causing an addition reaction

10
 Steps in Radical Substitution
 Three types of steps
◦ Initiation – homolytic formation of two reactive species with
unpaired electrons
 Example – formation of Cl atoms form Cl2 and light
◦ Propagation – reaction with molecule to generate radical
 Example - reaction of chlorine atom with methane to give HCl
and CH3.

◦ Termination – combination of two radicals to form a stable

product: CH3. + CH3.  CH3CH3
11
 Steps in Radical Substitution:
Monochlorination of Methane

Initiation

Propagation

12
 Steps in Radical Substitution
Termination

With excess concentration of Cl2 present continued

reaction is probable with formation of dichloro,
trichloro, and tetrachloro methanes.
13
Radical Substitution Example:
Biosynthesis of Prostaglandins

p. 141
Radical Example:

p. 142
 Learning Check:
Propose a mechanism. Add curved arrows to indicate
the flow of electrons:

p. 142
 Solution:
Propose a mechanism. Add curved arrows to indicate
the flow of electrons:

p. 142
Learning Check:

In a radical chain reaction, what would be the best

description of the following reaction?
H3C• + •Cl → CH3Cl

1. propagation
2. elimination
3. initiation
4. termination
5. substitution
Solution:

In a radical chain reaction, what would be the best

description of the following reaction?
H3C• + •Cl → CH3Cl

1. propagation
2. elimination
3. initiation
4. termination
5. substitution
Radical Substitution: With >1 kind of H
H H H H H Cl H Cl H
H C C C H + Cl2 hv H C C C H + H C C C H
H H H H H H H H H

1-chloropropane 2-chloropropane

When there is
• >1 type of H then there is
• >1 option for radical formation and therefore
• >1 option for a monohalogenation product.

20
Learning Check:
In the reaction of Cl2 with 2-methylbutane, how many
monochlorinated isomers are produced?
HH H
H C H H
H C C C C H + Cl2 hv

H H H H

1. 2
2. 3
3. 4
4. 5
5. 6
Solution:
In the reaction of Cl2 with 2-methylbutane, how many
monochlorinated isomers are produced?
HH H
H C H H
H C C C C H + Cl2 hv

H H H H

1. 2
2. 3
3. 4
4. 5
5. 6
 6.4 Polar Reactions
 Molecules can contain local unsymmetrical electron
distributions due to differences in electronegativities

 Thiscauses a partial negative charge on an atom and a

compensating partial positive charge on an adjacent atom

 The more electronegative atom has the greater electron

density
 Elements such as O, F, N, Cl more electronegative than
carbon

23
p. 143
25
 Polarizability
Polarization is a change in electron distribution as a
response to change in electronic nature of the
surroundings

Polarizability is the tendency to undergo polarization

Polar reactions occur between regions of high

electron density and regions of low electron density

26
 Polarizability
Bonds inherently polar already can be made more
polar by reactions with acids or bases.

p. 144
 Polarizability
Bonds not inherently polar can be polarizable as
interactions with solvent or other polar molecules
effect the electron distribution.

2.58 2.66

2.55 2.55

Large atoms with loosely held electrons are more polarizable

than small atoms with few tightly held electrons.
So: S is more polarizable than O
I is more polarizable than Cl
p. 144
 Generalized Polar Reactions
An electrophile, an electron-poor species, combines
with a nucleophile, an electron-rich species
An electrophile is a Lewis acid
A nucleophile is a Lewis base
The combination is indicate with a curved arrow from
nucleophile to electrophile

29
Fig. 5-1a, p. 145
 Learning Check:
Which of the following is likely to be a nucleophile
and which an electrophile?

p. 146
 Solution:
Which of the following is likely to be a nucleophile
and which an electrophile?

E N N E

p. 146
 Learning Check:
Is BF3 is likely to be a nucleophile or an electrophile?

p. 146
 Solution:
Is BF3 is likely to be a nucleophile or an electrophile?

p. 146
 Learning Check:
Which of the following is expected to be the
worst nucleophile?

1. NH3
2. H2O
3. BH3
4. ethylene
5. (CH3) 3P
 Solution:
Which of the following is expected to be the
worst nucleophile?

1. NH3
2. H2O
3. BH3
4. ethylene
5. (CH3) 3P
 6.5 An Example of a Polar Reaction:
Addition of HBr to Ethylene
 HBr adds to the  part of C-C double bond
 The  bond is e- rich, allowing it to function as a nucleophile
 H-Br is electron deficient at the H since Br is much more
electronegative, making HBr an electrophile

37
Mechanism of Addition of HBr to Ethylene
 HBr electrophile is attacked by
 electrons of ethylene
(nucleophile) to form a
carbocation intermediate and
bromide ion
 Bromide adds to the positive
center of the carbocation,
which is an electrophile,
forming a C-Br  bond
 The result is that ethylene and
HBr combine to form
bromoethane
 All polar reactions occur by
combination of an electron-
rich site of a nucleophile and
an electron-deficient site of an
electrophile

38
Fig. 5-2a, p. 148
 Learning Check:
What product would you expect?

p. 142
 Solution:
What product would you expect?

Br

p. 142
6.6 Using Curved Arrows in Polar
Reaction Mechanisms
Curved arrows are a way to keep track of
changes in bonding in polar reaction
The arrows track “electron movement”
Electrons always move in pairs
Charges change during the reaction
One curved arrow corresponds to one step
in a reaction mechanism

42
 Rules for Using Curved Arrows
The arrow (electrons) goes from the nucleophilic
reaction site (Nu: or Nu:- ) to the electrophilic
reaction site (sink, E or E+)

The nucleophilic site can be neutral or negative

43
 Rules for Using Curved Arrows
The nucleophilic site can be negative or neutral

44
The electrophilic site can be positive or neutral

45
The octet rule must be followed

The hydrogen already has two e-s so when

another pair moves in the 2 already owned have
to leave.

46
 Learning Check:

+ H 3O + H 2O

What is the role of the alkene in the reaction

above?

1. electrophile
2. nucleophile
3. free radical
4. catalyst
5. Lewis acid
 Solution:

+ H 3O + H 2O

What is the role of the alkene in the reaction

above?

1. electrophile
2. nucleophile
3. free radical
4. catalyst
5. Lewis acid
Learning Check:
Add curved arrows to indicate the flow of electrons:

p. 151
Solution:
Add curved arrows to indicate the flow of electrons:

p. 151
 Learning Check:
Add curved arrows to indicate the flow of electrons:

p. 152
 Solution:
Add curved arrows to indicate the flow of electrons:

52
Learning Check:
Predict the products of the following reaction:

p. 152
Solution:
Predict the products of the following reaction:

H H
O
H C CO2- H
-
O2C + O
CH2 C CO - H
2
H

p. 152
 Learning Check: Which of the following
represents a correctly drawn
reaction mechanism?
Br
Br + OH2
1. x H
O H

Br

2. xBr + OH2
O H

Br
3. xBr + OH2
O H
H
Br
4. xBr + OH2
O H
H
Br

5. xBr + OH2
O H
 Solution: Which of the following
represents a correctly drawn
reaction mechanism?
Br
Br + OH2
1. x H
O H

Br

2. xBr + OH2
O H

Br
3. xBr + OH2
O H
H
Br
4. xBr + OH2
O H
H
Br

5. xBr + OH2
O H
 Learning Check:
What carbocation intermediate is consistent with the
product formed? Propose a mechanism. (Add curved
arrows to indicate the flow of electrons.)

p. 142
 Solution:
What carbocation intermediate is consistent with the
product formed? Propose a mechanism. (Add curved
arrows to indicate the flow of electrons.)

H3C CH3
C CH2 + H Br H3C C Br
H3C CH3

Br

H3C H H3C H
C CH2 or C CH2
H3C H3C

1o carbocation 3o carbocation
Not formed
p. 142
 6.7 Describing a Reaction:
Equilibria, Rates, and Energy Changes
Reactions can go either forward or backward to
reach equilibrium
◦ The multiplied concentrations of the products
divided by the multiplied concentrations of the
reactant is the equilibrium constant, Keq
◦ Each concentration is raised to the power of its
coefficient in the balanced equation.
aA + bB cC + dD

59
p. 153
Magnitudes of Equilibrium Constants
aA + bB cC + dD

 If the value of Keq >1, this indicates that at

equilibrium most material is present as products
◦ If Keq = 10, then the concentration of the product is ten times that of
the reactant

A valueof Keq < 1 indicates that at equilibrium

most material is present as the reactant
◦ If Keq = 0.10, then the concentration of the reactant is ten times that of
the product 61
 Free Energy and Equilibrium
The ratio of products to reactants is controlled by
their relative Gibbs free energy
This energy is released on the favored side of an
equilibrium reaction
The change in Gibbs free energy between products
and reacts is written as “G”

If Keq > 1, energy is released to the surroundings

(exergonic reaction)
If Keq < 1,
1 energy is absorbed from the surroundings
(endergonic reaction)

62
Numeric Relationship of Keq and Free Energy
Change
The standard free energy change at 1 atm
pressure and 298 K is Gº
The relationship between free energy change
and an equilibrium constant is:
◦ Gº = - RT ln Keq where
◦ R = 1.987 cal/(K x mol)
◦ T = temperature in Kelvin
◦ ln Keq = natural logarithm of Keq

63
ΔHo is the heat, or enthalpy, of reaction. This reaction
ΔHo < 0 ; The reaction is exothermic.
ΔHo > 0 ; The reaction is endothermic. is exothermic

ΔG, the Gibbs free energy change, determines Keq

and whether the reaction is spontaneous or This reaction is
nonspontaneous.
spontaneous
ΔGo < 0 ; The reaction is spontaneous.
ΔGo > 0 ; The reaction is nonspontaneous.

ΔGo < 0 ; Keq > 1 The equilibrium lies

ΔGo = 0 ; Keq = 1 toward product
ΔGo > 0 ; Keq < 1
p. 154
6.2

65
Learning Check:
Which of the following equations is correct?

1. ∆G = ∆H – T∆S
2. ∆G = ∆s + T∆H
3. ∆H = T∆G – T∆S
4. ∆G = ∆H + T∆S
5. ∆S = T∆H – ∆G
Solution:
Which of the following equations is correct?

1. ∆G = ∆H – T∆S
2. ∆G = ∆s + T∆H
3. ∆H = T∆G – T∆S
4. ∆G = ∆H + T∆S
5. ∆S = T∆H – ∆G
 6.8 Describing a Reaction: Bond
Dissociation Energies
 Bond dissociation energy (D): amount of energy required to
break a given bond to produce two radical fragments when
the molecule is in the gas phase at 25˚ C

 The energy is mostly determined by the type of bond,

independent of the molecule
◦ The C-H bond in methane requires a net heat input of 105
kcal/mol (438 kJ/mol) to be broken at 25 ºC.
◦ Table 5.3 lists energies for many bond types
 Changes in bonds can be used to calculate net changes in heat

68
Bond Dissociation Energies

Table 5-3a, p. 156

Bond Dissociation Energies

Table 5-3b, p. 156

 Bond Dissociation Energies
Calculate the Ho for the chlorination of methane :
Cl2 + CH4 → CH3Cl + HCl
bond CH3–H CH3–Cl H–Cl H–H Cl–Cl
BDE (kJ/mol) 438 351 432 436 243

Bonds Broken Bonds Made

Cl-Cl +243 kJ/mol H3C-Cl -351 kJ/mol

H3C-H +438 kJ/mol H-Cl -432 kJ/mol

+681 kJ/mol -783 kJ/mol

Ho = + 681 - 783 = -102 kJ/mol

p. 157
p. 157
Learning Check:
Consider the following reaction:
CH3I + H2O → CH3OH + HI

If BDEs are used to estimate the enthalpy of this

reaction, which bond’s BDE is not needed?

1. CH3–I
2. HO–H
3. H–I
4. CH3O–H
5. CH3–OH
Solution:
Consider the following reaction:
CH3I + H2O → CH3OH + HI

If BDEs are used to estimate the enthalpy of this

reaction, which bond’s BDE is not needed?

1. CH3–I
2. HO–H
3. H–I
4. CH3O–H
5. CH3–OH
 Learning Check:
The BDE’s for some bonds are collected in the table below:
bond CH3–H CH3–Cl H–Cl H–H Cl–Cl
BDE (kJ/mol) 438 351 432 436 243
An alternative step in chlorination of methane might be as follows:
Cl• + CH4 → CH3Cl + H•

What is the reason that this step is not observed?

1. Cl• cannot approach the carbon atom close enough to form a
bond because of steric interference from hydrogens
2. H• is not among the products of methane chlorination
3. Cl• can only bond to hydrogen atoms
4. this step is too endothermic as compared to alternatives
5. this step is too exothermic
 Solution:
The BDE’s for some bonds are collected in the table below:
bond CH3–H CH3–Cl H–Cl H–H Cl–Cl
BDE (kJ/mol) 438 351 432 436 243
An alternative step in chlorination of methane might be as follows:
Cl• + CH4 → CH3Cl + H•

What is the reason that this step is not observed?

1. Cl• cannot approach the carbon atom close enough to form a
bond because of steric interference from hydrogens
2. H• is not among the products of methane chlorination
3. Cl• can only bond to hydrogen atoms
4. this step is too endothermic as compared to alternatives
5. this step is too exothermic
Solution:

The following reaction is an example of:

H3C+ + Cl– → CH3Cl

1. a termination step
2. a heterolytic process
3. an initiation step
4. a homogenic process
5. an exergonic reaction
6.9 Describing a Reaction: Energy Diagrams
and Transition States
 Thehighest energy point in a
reaction step is called the
transition state
 The energy needed to go
from reactant to transition
state is the activation
energy (G‡)

78
 First Step in Addition
In the addition of HBr
the (conceptual)
transition-state
structure for the first
step
 The  bond between
carbons begins to
break
◦ The C–H bond
begins to form
◦ The H–Br bond
begins to break
79
Fast exergonic Slow exergonic

Slow endergonic
Fast endergonic

Fig. 5-6a, p. 159

Learning Check:
Which part of the following energy diagram indicates
whether the overall reaction is exergonic or
endergonic?

1. I
2. II
3. III
4. IV
5. V
Solution:
Which part of the following energy diagram indicates
whether the overall reaction is exergonic or
endergonic?

1. I
2. II
3. III
4. IV
5. V
 Learning Check:

Which statement about free energy is correct?

1. The ∆G of a reaction depends on the reaction

mechanism (path).
2. The ∆G‡ of a reaction depends on the mechanism
(path).
3. The ∆G of a reaction may be changed by adding a
catalyst.
4. The bigger the ∆G value, the faster the reaction.
5. For exergonic reactions ∆G >0.
 Solution:

Which statement about free energy is correct?

1. The ∆G of a reaction depends on the reaction

mechanism (path).
2. The ∆G‡ of a reaction depends on the mechanism
(path).
3. The ∆G of a reaction may be changed by adding a
catalyst.
4. The bigger the ∆G value, the faster the reaction.
5. For exergonic reactions ∆G >0.
6.10 Describing a Reaction: Intermediates
 If a reaction occurs in
>1step, it must involve
species that are neither
the reactant nor the final
product
 These are called reaction
intermediates or simply
“intermediates”
 Each step has its own
free energy of activation
 The complete diagram
for the reaction shows
the free energy changes
associated with an
intermediate
85
Learning Check:

On the reaction energy profile shown below, which

of the species is the highest energy intermediate?

1. I
2. II
3. III
4. IV
5. V
Solution:

On the reaction energy profile shown below, which

of the species is the highest energy intermediate?

1. I
2. II
3. III
4. IV
5. V
 Learning Check:
Which of the following statements is true?

1. Transition states can be observed and sometimes isolated.

2. Transition states can not be observed and never isolated.
3. Intermediates can be observed and sometimes isolated.
4. Intermediates can be observed but never isolated.
5. Intermediates can never be observed.
 Solution:
Which of the following statements is true?

1. Transition states can be observed and sometimes isolated.

2. Transition states can not be observed and never isolated.
3. Intermediates can be observed and sometimes isolated.
4. Intermediates can be observed but never isolated.
5. Intermediates can never be observed.
Learning Check:
Consider the reaction profile shown below. If there is a
sufficient amount of thermal energy available to overcome
the highest activation energy and sufficient time for all
molecules to do that multiple times, what is the main
structure present under such conditions?

1. A
2. B
3. C
4. D
5. E
Solution:
Consider the reaction profile shown below. If there is a
sufficient amount of thermal energy available to overcome
the highest activation energy and sufficient time for all
molecules to do that multiple times, what is the main
structure present under such conditions?

1. A
2. B
3. C
4. D
5. E
Learning Check:
Which energy difference corresponds to the
activation energy of the rate-limiting step for A to
E transformation?

1. B–A
2. C–A
3. D–A
4. E–A
5. D–C
Solution:
Which energy difference corresponds to the
activation energy of the rate-limiting step for A to
E transformation?

1. B–A
2. C–A
3. D–A
4. E–A
5. D–C
 Learning Check:
Which of the following statements is
incorrect?

1. Polar reactions must have ionic intermediates.

2. Initiation in radical-chain reactions must generate
species with unpaired electrons.
3. Polar reactions occur between electrophiles and
nucleophiles.
4. Lewis bases generally behave as nucleophiles.
5. Electrophiles can be neutral as well as positively
charged.
 Solution:
Which of the following statements is
incorrect?

1. Polar reactions must have ionic intermediates.

2. Initiation in radical-chain reactions must generate
species with unpaired electrons.
3. Polar reactions occur between electrophiles and
nucleophiles.
4. Lewis bases generally behave as nucleophiles.
5. Electrophiles can be neutral as well as positively
charged.
6.11 A Comparison between Biological Reactions
and Laboratory Reactions
 Laboratory reactions usually carried out in organic solvent
 Biological reactions in aqueous medium inside cells
 They are promoted by catalysts that lower the activation
barrier
 The catalysts are usually proteins, called enzymes
 Enzymes provide an alternative mechanism that is
compatible with the conditions of life

97
Fig. 5-8, p. 161
6.4

Table 5-4, p. 164

 Learning Check:

Which of the following does not describe the role

that can be played by an enzyme in a biological
reaction?

1. It changes the mechanism of the reaction.

2. It lowers the energy of a transition state.
3. It changes the free-energy of the reaction.
4. It changes the rate of the reaction.
5. It increases the specificity of the reaction.
 Solution:

Which of the following does not describe the role

that can be played by an enzyme in a biological
reaction?

1. It changes the mechanism of the reaction.

2. It lowers the energy of a transition state.
3. It changes the free-energy of the reaction.
4. It changes the rate of the reaction.
5. It increases the specificity of the reaction.