Organic Chemistry

For USTH Students

Lecture 1: Radical reaction
Dr. Doan Duy Tien

BASF Company

BASF Company (Founded 1865)

1 Chemicals
The largest chemical company in the world
2 Plastics
Located in Ludwigshafen, Germany
3 Performance products
Employed more than 112,000 people
4 Functional Solutions5
Jrgen Hambrecht (Chairman of the supervisory board) Agricultural
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Revenue 2013: 101,6 billion USD (Bayer: 55,2 billion USD) 7 Oil and gas

Structure and bonding

Organic chemicals

Medicines

DNA

Materials

Essential oils

Fuels

Pigments

Funtional group

Finding the functional groups

Funtional group

Finding the functional groups

Biomolecule

Organic chemicals make up

Foods and foodstuff

Flavours and fragrances
Medicines
Materials, polymers, plastics
Plant, animal and microbial matter; natural
products
A vast range of manufactured goods
[pharmaceuticals, foods, dyestuffs, adhesives, coatings,
packaging, lubricants, cosmetics, films & fibres, etc. etc.]

Classification of organic Compounds

Hydrocarbon: Alkane, alkene, alkyne, aromatic

Alcohol, phenol, ether
Aldehyde, ketone
Acid carboxylic, ester, anhydride, amide, nitril
Amine
Aminoacid, peptide and protein
Lipid
Carbohydrate
Heterocyclic
Natural product
Biomolecule

Structure and bonding

Sigma Bond (s) covalent bond that is symmetric
about the bond axis.

s orbitals of H interacting to form sigma bond.

p orbital interacting end-on-end to form sigma bond

Structure and bonding

Pi (p) Bond

p*

In the Ground State, the

Antibonding MO is empty.
Antibonding MO

Energy

2p AO

2p AO

In the Ground State, the

Bonding MO has two electrons
Bonding MO

Two atomic p orbitals

Pi (p) Bond

3D view of Pi (p) Bond

p(pi) Bond overlap of two p orbitals oriented perpendicular
to the line connecting the nuclei.

Hybridization of Atomic Orbitals

1.
2.

AOs on a single atom mix to form new, hybrid orbitals. These hybrid orbitals
have characteristics of both s and p orbitals.
Provides a means of explaining observed bond angles in organic molecules.

Acetylene

sp

sp

H C C H
1

180o

__ __ __ p
__ s

promote e-

__ __ __
__

Mix orbitals

__ __ p
__ __ sp hydrid

sp

sp

Each sp orbital possesses:

+ 50% s character
+ 50% p character.

y
x

Two sp orbitals

Orbital Picture of Acetylene

p1
px

s
Hs

sp

C
py

px
sp s sp

p2

s
sp

Hs

py

H C C H

Ethylene

sp2 sp2

H
116.6o

C C
H

H
121.7o

The carbon atom is sp2 hybridized to obtain trigonal planar geometry

__ __ __ p

__ s

Promote e-

__ __ __
__

Mix orbitals

__ p
__ __ __ sp2 hydrid

2
sp

Hybridization

2p
There is one p orbital left over,
and it would be along the z axis.

3 sp2 orbitals

Orbital Picture of Ethylene

Hs

sp2

Hs
px

C
Hs

p1
2
sps

sp2

sp2

sp2

sp2

H
C

C
H

Hs

Examples
Structure of marking bonds

Which C-H bond is shorter

Drawing Organic Molecules

Methane
H
H
sp3

C1

The carbon atom is sp3 hybridized to obtain tetrahedral geometry. All bond angles
are equal at 109.50.

__ __ __ p
__ s

Promote e-

__ __ __
__

Mix orbitals

__ __ __ __sp3

3
sp

Hybridization

3 p

sp3

Orbital Picture of Methane

Hs

sp3

s
sp3

sp3

sp3

Hs

Hs

H
C
H

H
H

Hs

Hydrogen bonding

Hydrogen bonding

Hydrogen bonding

Hydrogen bonding: Biomolecule

Intramolecular forces of attraction

Understanding
Organic Reactions

Writing Equations for Organic Reactions

Substitution Reactions

Elimination Reactions

Addition Reactions

Catalysts

Enzyme: biocatalysts

Acids and Bases

Acids and Bases

A Brnsted acid is a proton donor.
A Brnsted base is a proton acceptor.
H+ = proton

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Acids and Bases

Reactions
A acid base reaction results in the transfer of a proton from
an acid to a base.
In an acid-base reaction, one bond is broken, and another
one is formed.
The electron pair of the base B: forms a new bond to the
proton of the acid.
The acid HA loses a proton, leaving the electron pair in the
HA bond on A.

39

Acids and Bases

Acids and Bases

Commonly Used Acids in Organic Chemistry
In addition to the familiar acids HCl, H2SO4 and HNO3, a
number of other acids are often used in organic
reactions. Two examples are acetic acid and p-toluenesulfonic acid (TsOH).

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Acids and Bases

Commonly Used Bases in Organic Chemistry
It should be noted that:
Strong bases have weak conjugate acids with high pKa
values, usually > 12.
Strong bases have a net negative charge, but not all
negatively charged species are strong bases. For example,
none of the halides F, Cl, Br, or I, is a strong base.
Carbanions, negatively charged carbon atoms, are especially
strong bases. A common example is butyllithium.
Two other weaker organic bases are triethylamine and
pyridine.

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Acids and Bases:

electrophile- nucleophile

Lewis Acids and Bases

A Lewis acid is also called an electrophile.
When a Lewis base reacts with an electrophile other
than a proton, the Lewis base is also called a
nucleophile. In this example, BF3 is the electrophile and
H2O is the nucleophile.

electrophile

nucleophile
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Acids and Bases

Lewis Acids and Bases
Two other examples are shown below. Note that in each
reaction, the electron pair is not removed from the
Lewis base. Instead, it is donated to an atom of the
Lewis acid and one new covalent bond is formed.

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Acids and Bases

Lewis Acids and Bases
To draw the product of this reaction, the electron pair in
the p bond of the Lewis base forms a new bond to the
proton of the Lewis acid, generating a carbocation.
The HCl bond must break, giving its two electrons to
Cl, forming Cl.
Because two electron pairs are involved, two curved
arrows are needed.

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Radical Reactions

Overview
Introduction
General features of radical reactions
Halogenation of alkanes
The mechanism of halogenation
Chlorination of other alkanes
Chlorination versus bromination
Halogenation as a tool in organic synthesis
The stereochemistry of halogenation reactions
Radical halogenation at an allylic carbon
Radical addition reactions to double bonds
Polymers and polymerization
Application: The ozone layer and CFCs
Application: Oxidation of unsaturated lipids
Application: Antioxidants

Introduction: Radical Reactions

A significant group of reactions involve radical
intermediates.
A radical is a reactive intermediate with a single unpaired
electron, formed by homolysis of a covalent bond.
A radical contains an atom that does not have an octet of
electrons.
Half-headed arrows are used to show the movement of
electrons in radical processes.

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Introduction: Radical Reactions

Carbon radicals are classified as 1, 2 or 3.
A carbon radical is sp2 hybridized and trigonal planar, like
sp2 hybridized carbocations.
The unhybridized p orbital contains the unpaired electron
and extends above and below the trigonal planar carbon.

49

Introduction: Radical Reactions

Figure 15.1 The relative stability of 1 and 2 carbon radicals

50

General Features of Radical Reactions

Radicals are formed from covalent bonds by adding energy in
the form of heat () or light (h).
Some radical reactions are carried out in the presence of a
radical initiator.
Radical initiators contain an especially weak bond that serves
as a source of radicals.
Peroxides, compounds having the general structure RO-OR,
are the most commonly used radical initiators.
Heating a peroxide readily causes homolysis of the weak O-O
bond, forming two RO radicals.
Radicals undergo two main types of reactions: they react
with s bonds, and they add to p bonds.
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Radical Reactions
Reaction of a Radical X with a C-H Bond:
A radical X abstracts a hydrogen atom from a CH s
bond to from HX and a carbon radical.

Reaction of a Radical X with a C=C Bond:

A radical X also adds to the p bond of a carboncarbon
double bond.

52

Radical Reactions
Halogenation of Alkanes:
In the presence of heat or light, alkanes react with
halogens to form alkyl halides.
Halogenation of alkanes is a radical substitution reaction.
Halogenation of alkanes is only useful with Cl2 or Br2.
Reaction with F2 is too violent, and reaction with I2 is too
slow to be useful.
With an alkane that has more than one type of hydrogen
atom, a mixture of alkyl halides may result.

53

Radical Reactions
Halogenation of Alkanes:
When a single hydrogen atom on a carbon has been replaced
by a halogen atom, monohalogenation has taken place.
When excess halogen is used, it is possible to replace more
than one hydrogen atom on a single carbon with halogen
atoms.
Monohalogenation can be achieved experimentally by adding
halogen X2 to an excess of alkane.
When asked to draw the products of halogenation of an
alkane, draw the products of monohalogenation only, unless
specifically directed to do otherwise.
Figure 15.2 Complete halogenation of CH4 using excess Cl2

54

Radical Reactions
Halogenation of Alkanes: Reaction Mechanism
Radical halogenation has three distinct steps.

A mechanism (such as that observed in radical

halogenation) that involves two or more repeating steps is
called a chain mechanism.
The most important steps of radical halogenation are those
that lead to product formation: the propagation steps. 55

Radical ReactionsMechanism

56

Radical Reactions
Halogenation of Alkanes: Reaction Mechanism
Figure 15.3 Energy changes in the propagation
steps during the chlorination of ethane

57

Radical Reactions
Halogenation of Alkanes: Energetics
Figure 15.4 Energy
diagram for the
propagation steps
in the chlorination
of ethane

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Radical Reactions
Halogenation of Alkanes: Chlorination of Propane
Chlorination of CH3CH2CH3 affords a 1:1 mixture of
CH3CH2CH2Cl and (CH3)2CHCl.
Note that CH3CH2CH3 has six 1 hydrogens and only two
2 hydrogens, so the expected product ratio of
CH3CH2CH2Cl to (CH3)2CHCl (assuming all hydrogens are
equally reactive) is 3:1.

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Radical Reactions
Halogenation of Alkanes:
Since the observed ratio between CH3CH2CH2Cl and
(CH3)2CHCl is 1:1, the 2 CH bonds must be more reactive
than the 1 CH bonds.

Thus, when alkanes react with Cl2, a mixture of products

results, with more product formed by cleavage of the weaker
CH bond than you would expect on statistical grounds.
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Radical Reactions
Chlorination versus Bromination:

Although alkanes undergo radical substitutions with both

Cl2 and Br2, chlorination and bromination exhibit two
important differences.
1. Chlorination is faster than bromination.
2. Chlorination is less selective, yielding a mixture of
products and bromination is more selective, often
yielding one major product.

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Radical Reactions
Chlorination versus Bromination:
The differences in chlorination and bromination can be
explained by considering the energetics of each type of
reaction.
Calculating the H0 using bond dissociation energies reveals
that abstraction of a 1 or 2 hydrogen by Br is endothermic,
but it takes less energy to form the more stable 2 radical.

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Radical Reactions
Chlorination versus Bromination:
Calculating the H using bond dissociation energies for
chlorination reveals that abstraction of a 1 or 2 hydrogen
by Cl is exothermic.

Since chlorination has an exothermic rate-determining

step, the transition state to form both radicals resembles
the same starting material, CH3CH2CH3. Thus, the relative
stability of the two radicals is much less important, and
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both radicals are formed.

Radical Reactions
Halogenation of Alkanes: Terms
Reactivity: The tendency of a reagent to react with a
given compound. Chlorine is more reactive toward
alkanes than is bromine.
Selectivity: The choice of reaction site by the reagent.
Bromine is more selective in reaction with alkanes than
is chlorine.
Regioselectivity: The preference of one product over
others in a reaction where multiple reaction sites exist.
Bromine is regioselective and chlorine is not.
Remember the Hammond postulate, page 260-261, with
regard to transition states and their relationship to
exothermic or endothermic reactions.
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Radical Reactions
Stereochemistry of Halogenation:
A racemic mixture results because the first propagation
step generates a planar sp2 hybridized radical. Cl2 then
reacts with it from either side to form an equal amount of
two enantiomers.

65

Radical Reactions
Radical Halogenation at an Allylic Carbon:
Because allylic CH bonds are weaker than other sp3
hybridized CH bonds, the allylic carbon can be selectively
halogenated using NBS in the presence of light or peroxides.

NBS contains a weak NBr bond that is homolytically

cleaved with light to generate a bromine radical, initiating an
allylic halogenation reaction.
Propagation then consists of the usual two steps of radical
halogenation.

66

Radical Reactions
Radical Halogenation at an Allylic Carbon:

67

Radical Reactions
Radical Halogenation at an Allylic Carbon:
Thus, an alkene with allylic CH bonds undergoes two
different reactions depending on the reaction conditions.

68

Radical Reactions
Radical Halogenation at an Allylic Carbon:
Halogenation at an allylic carbon often results in a mixture
of products. Consider the following example:

A mixture results because the reaction proceeds by way of

a resonance stabilized radical.

69

Radical Reactions
Radical Additions to Double Bonds:
HBr adds to alkenes to form alkyl bromides in the presence
of heat, light, or peroxides.
The regioselectivity of the addition to unsymmetrical
alkenes is different from that in addition of HBr in the
absence of heat, light or peroxides.

The addition of HBr to alkenes in the presence of heat,

light or peroxides proceeds via a radical mechanism.

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Radical Reactions
Radical Additions to Double Bonds:

71

Radical Reactions
Radical Additions to Double Bonds:

Note that in the first propagation step, the addition of

Br to the double bond, there are two possible paths:
1. Path [A] forms the less stable 1 radical.
2. Path [B] forms the more stable 2 radical.
The more stable 2 radical forms faster, so Path [B]
is preferred.

72

Radical Reactions
Radical Additions to Double Bonds:
The radical mechanism illustrates why the regioselectivity of HBr addition is different depending on
the reaction conditions.

73

Radical Reactions
Radical Additions to Double Bonds:
HBr adds to alkenes under radical conditions, but HCl and HI
do not. This can be explained by considering the energetics of
the reactions using bond dissociation energies.
Both propagation steps for HBr addition are exothermic, so
propagation is exothermic (energetically favorable) overall.
For addition of HCl or HI, one of the chain propagating steps is
quite endothermic, and thus too difficult to be part of a
repeating chain mechanism.
Figure 15.9 Energy
changes during the
propagation steps:
CH2 = CH2 + HBr
CH3CH2Br
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Radical Reactions
Polymers and Polymerization:
Polymers are large molecules made up of repeating units
of smaller molecules called monomers. They include
biologically important compounds such as proteins and
carbohydrates, as well as synthetic plastics such as
polyethylene, polyvinyl chloride (PVC) and polystyrene.
Polymerization is the joining together of monomers to
make polymers. For example, joining ethylene monomers
together forms the polymer polyethylene, a plastic used in
milk containers and plastic bags.

75

Radical Reactions
Polymers and Polymerization:
Many ethylene derivatives having the general structure
CH2=CHZ are also used as monomers for polymerization.
The identity of Z affects the physical properties of the
resulting polymer.
Polymerization of CH2=CHZ usually affords polymers
with Z groups on every other carbon atom in the chain.

76

Polymers and Polymerization

77

Radical Reactions
Polymers and Polymerization:

78

Radical Reactions
Polymers and Polymerization:
In radical polymerization, the more substituted radical
always adds to the less substituted end of the
monomer, a process called head-to-tail
polymerization.

79

Application: The Ozone Layer and CFCs

80

Application: The Ozone Layer and CFCs

The oxidation of unsaturated

lipids with O2

The oxidation of unsaturated

lipids with O2

Radical Reactions
Antioxidants:
An antioxidant is a compound that stops an oxidation from
occurring (a radical scavenger).
Naturally occurring antioxidants such as vitamin E prevent
radical reactions that can cause cell damage.
Synthetic antioxidants such as BHT, butylated hydroxy
toluene, are added to packaged and prepared foods to
prevent oxidation and spoilage.
Vitamin E and BHT are radical inhibitors, so they terminate
radical chain mechanisms by reacting with the radical.

84

Radical Reactions
Antioxidants:
To trap free radicals, both vitamin E and BHT use a hydroxy
group bonded to a benzene ring, a general structure called a
phenol.
Radicals (R) abstract a hydrogen atom from the OH group of
an antioxidant, forming a new resonance-stabilized radical.
This new radical does not participate in chain propagation, but
rather terminates the chain and halts the oxidation process.
Because oxidative damage to lipids in cells is thought to play a
role in the aging process, many anti-aging formulations
contain antioxidants.

85

KEY CONCEPTS
General Features of Radicals
A radical is a reactive intermediate with a single
unpaired electron
A carbon radical is sp2 hybridized and trigonal planar
The stability of a radical increases as the number of C
atoms bonded to the radical carbon increases
Allylic radicals are stabilized by resonance, making
them more stable than 3 radicals

KEY CONCEPTS

PROBLEMS

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