University of Science and Technology of Hanoi

Department of Fundamental and Applied Sciences

RADICAL REACTIONS

Dr. Nguyen Duc Anh

Department of Fundamental and Applied Sciences (FAS)
nguyen-duc.anh@usth.edu.vn
0904888819

September 2019
Radicals

Free radical can be defined as an atom or molecule containing one or more unpaired electrons in valence shell
or outer orbit and is capable of independent existence.

The odd number of electron(s) of a free

radical makes it unstable, short lived and
highly reactive.
Radicals

Formation of radicals
Radicals generated by the homolytic breakage of a single bond under heat, light or catalysts.

Radicals
+ Highly chemically reactive, thus, almost radical has short
lifetimes and spontaneously dimerize.
+ Radical normally are electron deficient, they tend to pair up
with other electrons rich position.
+ A carbon radical is sp2 hybridation with one p orbital bearing
a single electron. Carbon radical is planar geometry .
+ A radical has neutral charge
Radicals

Formation of radicals

In radical reactions, homolytic bond cleavages occur, with each fragment retaining one of the bonding electrons.

The formation of alkyl, vinyl, and aryl free radicals by homolytic processes.
Radicals

Stability of radicals - persistent free radicals

Mains factors affected to stability of radicals

+ Electronic effects:
- The inductive effects
- Delocalized electrons – Resonance

+ Steric effects
Radicals

Radicals generations

• Peroxides: Commonly used initiators include

benzoyl peroxide, t-butyl peroxybenzoate, di-
t-butyl peroxide, and t-butyl hydroperoxide.
Reaction generally occurs at relatively low
temperature.
Diacyl peroxides are sources of alkyl radicals

• Azo compounds:

Azo compounds with functional groups that

stabilize the radical are especially reactive.
For example: AIBN
Radicals

Radicals Structure
The possibilities include a rigid pyramidal structure, rapidly
inverting pyramidal structures, or a planar structure.

Structural promotions to pyramidal structure

Alkyl and high electronegativity substituents

Degree of pyramidalization of halogenated methyl radicals. The sum

of the bond angles  is plotted against the sum of the
electronegativity (Xi of the substituents.  = 360o for planar and
323.7o for tetrahedral geometry.
Radicals

Types of radical reactions

Atom or group transfer reactions Addition reactions

β-scission fragmentation reactions

 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions (Solomons – Chapter 10)

Typical Mechanisms of Radical reactions

• Initiation – homolytic formation of two

reactive species with unpaired electrons

• Propagation – reaction with molecule to

generate products and new radical

• Termination – combination of two radicals

to form a stable product. Free radical
reactions cannot be completed without
chain termination
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Radical halogenation reactions

Alkanes react with molecular halogens to produce alkyl halides

by a substitution reaction called radical halogenation

Initiation

Propagation

Termination
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Radical halogenation reactions

Initiation
The step that initially creates a radical species
This is a homolytic cleavage event, and takes place very rarely due
to the high energy barriers involved
The influence of heat, UV radiation, or a metal-containing catalyst is
necessary to overcome the energy barrier
Propagation
Once a reactive free radical is generated, it can react with
stable molecules to form new free radicals. These new free
radicals go on to generate yet more free radicals
Propagation steps often involve hydrogen abstraction or
addition of the radical to double bonds.
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Radical halogenation reactions

Side Reactions:
Termination
Chain termination occurs when two free radical species react with Radical halogenation reactions normally generate
each other to form a stable, non-radical adduct multifunctional halogenated substituent products

Alkane chlorinations usually yield a complex mixture of products, they are not useful as synthetic methods when the goal is preparation
of a specific alkyl chloride.
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Reactivity
Chlorination is relatively unselective, chlorination of most • Weaker C—H bond  more product
higher alkanes gives a mixture of isomeric monochloro
products as well as more highly halogenated compounds.
Cl2 > Br2 > I2

• More stable radicals  more product

• More steric hindrance  less product

What factors affects to the products ratio?

 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Reactivity

Explain the difference of Bromination and Chlorination of isopropane ?

 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Explanation

Chlorination

Bromination
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

•The Hammond postulate : the transition state of a reaction resembles the

Explanation
structure of the species (reactant or product) to which it is closer in energy.

Bromination Chlorination

Endothermic step, TS Exothermic step, TS

resembles the products resembles the reactants

The rate-determining step in bromination is endothermic, The rate-determining step in chlorination is exothermic, the
the transition state resembles the products, the transition state resembles the starting material, both radicals
secondary radical formed easier, the product is selected. are formed, and a mixture of products results.
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Stereochemistry of Halogenation

Rules for Predicting the Stereochemistry of Reaction Products

 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Stereochemistry of Halogenation

• Halogenation of an achiral starting material

such as CH3CH2CH2CH3 forms two constitutional
isomers by replacement of either a 1° or 2°
hydrogen.
• 1-Chlorobutane has no stereogenic centers and
is thus achiral.
• 2-Chlorobutane has a new stereogenic center,
and so an equal amount of two enantiomers
must form—a racemic mixture. The structure of
formed radicals defines amount of racemic
mixture.
• 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.
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Stereochemistry of Halogenation

• Suppose we were to chlorinate the chiral starting material
(R)-2-bromobutane at C2 and C3.
• Chlorination at C2 occurs at the stereogenic center.
• Radical halogenation reactions at a stereogenic center
occur with racemization.
• Chlorination at C3 does not occur at the stereogenic center,
but forms a new stereogenic center.
• Since no bond is broken to the stereogenic center at C2, its
configuration is retained during the reaction.
• The trigonal planar sp2 hybridized radical is attacked from
either side by Cl2, forming a new stereogenic center.
• A pair of diastereomers is formed.
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Radical reaction of allylic carbon

An allylic carbon is a carbon adjacent to a double bond.
An alkene with allylic C—H bonds undergoes two different
reactions depending on the reaction conditions.
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Radical substitution reaction of allylic carbon

Why does radical substitution reaction appear on allylic carbon but others?

?
Halogenation at an allylic carbon often
results in a mixture of products. WHY ???
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

For more information

 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Radical halogenation reactions

 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Radical oxygenation
Free radical chain oxidation of organic molecules by molecular oxygen is often referred to as autoxidation.

Functional groups that stabilize radicals

are expected to increase susceptibility to
The best preparative results from autoxidation are obtained when only autoxidation.
one relatively reactive hydrogen is available for abstraction.
 Radical reactions

Radical addition of alkenes

When alkenes containing peroxides or hydroperoxides react

with hydrogen bromide, anti-Markovnikov addition of HBr
occurs.

Mechanism
 Synthesis of
Alkenes – Alkynes Addition reactions
alkenes/alkynes

Radical reactions

Radical addition of alkenes

Termination ??
 Synthesis of
Alkenes – Alkynes Addition reactions
alkenes/alkynes

Radical reactions
Radical addition of alkenes
 Synthesis of
Alkenes – Alkynes Addition reactions
alkenes/alkynes

Radical reactions

Radical polymerization of alkenes

Polymers are substances that consist of very large molecules called

macromolecules that are made up of many repeating subunits.

Mechanism
 Synthesis of
Alkenes – Alkynes Addition reactions
alkenes/alkynes

Radical reactions

Radical polymerization of alkenes

Two types of termination

- Combination
- Disproportionation

Chain transfer (chain

branching is the competed
reaction to propagation
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Others
Halogen, Sulfur, and Selenium Group Transfer Reactions

Intermolecular Transfer Reactions

Intramolecular Transfer Reactions

 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Others
Halogen, Sulfur, and Selenium Group Transfer Reactions

Provide mechanism of cyclization ?

 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Others
Intramolecular H atom transfer reaction

Hofmann-Loeffler reaction: Formation of pyrrolidines from N - haloamines

 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Others
Rearrangement based on radical

Rearrangements of radical
intermediates are much
less common.
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Others
SRN1 reaction
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Radical reactions

Others
Radical Rearrangements
Rearrangements of radical intermediates are much
less common compared to carbocations and only happen on
specific structures.

The groups that are usually involved in migration in free

radical intermediates include aryl, vinyl, acyl, and other
unsaturated substituents.
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Synthesis of alkanes / Cycloalkanes

Chapter 4: 4.36; 4.37, 4.39; 4.41; 4.44

Chapter 10: 10.18; 10.20; 10.23; 10.24; 10.27

 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Tutorials 1

Exercise 1
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Tutorials 1

Exercise 2
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Tutorials 1

Exercise 3
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Tutorials 1

Exercise 4
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Tutorials 1

Exercise 5

Note: Gccyclohexane = 3.4 kcal/mol; Gc1,3 – syn – diaxial methyl = 3.7 kcal/mol; Gc1,3 – anti – diaxial methyl = -1.7 kcal/mol
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Tutorials 1

Exercise 6
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Tutorials 1

Exercise 7
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Tutorials 1

Exercise 8
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Tutorials 1

Exercise 9
 Nomenclature/Physical Synthesis of
Alkanes -Cycloalkanes Conformation Radical reactions
Properties alkanes/cycloalkanes

Tutorials 1

Exercise 10