The document summarizes a guest lecture on free radicals that covered several topics: 1. The structure and formation of free radicals through homolytic bond cleavage and their stability based on factors like conjugation and sterics. 2. Mechanisms of radical substitution reactions including neighboring group assistance and reactivity based on position. 3. Methods to characterize radicals using electron spin resonance spectroscopy. 4. Examples of radical reactions including halogenation, allylic substitution, and autooxidation.

1. A Guest Lecture By
Mr. Nilkesh K. Dhurve
Assistant Professor
Department of Chemistry
Shri Pundlik Maharaj Mahavidyalaya Nandura Rly, Dist-Buldana
18-Jan-22 1

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• Introduction of free radicals
• Structure and geometry of free radicals
• Methods of radical formation,
• Stability of free radicals
• Free radical substitution mechanism, Mechanism at an aromatic substrates
• Neighboring Group Assistance
• Reactivity for aliphatic and aromatic substrates at a bridgehead
• Reactivity in the attacking radicals.
• Allylic Halogenation(NBS)
• Auto-oxidation

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A bond can be broken in two different ways:
Heterolytic bond cleavage forms ions, while homolytic bond cleavage forms radicals.
The curved arrows used in the two processes:
An ionic process employs double-barbed curved arrows, while a radical process employs
single-barbed arrows.
Free radicals may be defined as the species that contain one or more unpaired electrons.

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The difference in geometry results from the difference in the number of nonbonding electrons.
A carbocation has zero nonbonding electrons, while a carbanion has two nonbonding
electrons.

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A carbon radical is between these two cases, because it has one nonbonding electron.

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Radicals form from spin paired molecules by:
• Homolysis of weak sigma bonds: (Radical Initiator)
Eg.,Peroxide undergo homolysis of the weak O-O bond extremely easily to form two
radicals.

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Radicals form from spin paired molecules by:
• Homolysis of weak sigma bonds: (Radical Initiator)
Eg., AIBN (azobisisobutyronitrile)
1
2
3

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Radicals form from spin paired molecules by:
• Homolysis of weak sigma bonds: (Radical Initiator)

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Radicals form from spin paired molecules by:
• Electron transfer, i.e., reduction(addition of an electron)
Radicals form from other radicals by:
• Substitution (abstraction): Key feature of Radical Chain Reaction.

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Radicals form from other radicals by:
• Substitution (abstraction): The ability of radical to propagate by abstraction is a key
feature of Radical Chain Reaction.
1. Hydrogen abstraction is the removal of a hydrogen atom with its one electron.
2. Proton abstraction or removal is the removal of a hydrogen atom with no electrons,
which is happen in ionic reactions.
3. Abstraction is reaction of radical with spin-paired molecule that produces one new radical
and a new spin-paired molecule.
4. Radical substitution almost never occur at carbon atoms.
Propagation:

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Radicals form from other radicals by:
• Addition: Formation of radical by radical addition.
Examples:
• Elimination: It is the reverse of a radical addition reaction.

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• Electron Spin Resonance(ESR), it is also known as Electron Paramagnetic
Resonance(EPR)
Energy level diagram of the methyl radical
aH- Coupling Constant

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• Electron Spin Resonance(ESR), it is also known as Electron Paramagnetic
Resonance(EPR)

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• Bond strength as a guide to that bond will be homolysed
by heat or heat.
• Bond energies gives us an idea of the ease with which
radicals can form and the stability of those radicals once
they have formed.
C-H bonds decreases in strength in R-H

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Q. Rank the following radicals in order of stability:

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• C-H bonds next to conjugation group is weak, so allyl and benzyl radicals are more stable.
Unpaired electron is resonance stabilized
• C-H bonds to alkynyl, alkenyl, or aryl groups are strong, so radicals are less stable.

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• Adjacent functional group appear to weaken C-H bonds: radicals next to carbonyl, nitrile,
or ether functional groups, or centred on carbonyl carbon atom, are more stable than even
3o
alkyl radical.
Note : whether the functional group is electron withdrawing or electron donating is clearly
irrelevent.
Problem: Identify the weakest C-H bond in each following molecules.

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• Radicals are stabilized by conjugation, electron withdrawing, and electron donating
groups.

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• Steric hindrance makes radicals less reactive- more stable  Persistent radicals
• Stabilization of radicals depend on two factors:
1. Electronic Factor
2. Steric Factor

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• Ionic Mechanisms: only four different kind of arrow
pushing pattern(nucleophlic attack, loss of leaving
group, proton transfer, and rearrangement).
• Radical Mechanism: six different kind of arrow pushing
pattern.

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• Each of the six pattern can be placed in one of three catogeries-

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• Draw the appropriate arrows for each of the following radical process:

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• How do radicals react?

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• Radical-Radical reactions
 The pinacol reaction is radical dimerization.
Ketyls behave in manner that depend on the
solvent.

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• Radical-Radical reactions
 Titanium promotes the pinacol coupling and then deoxygenates the product: McMurry
Reaction
Mechanism:

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Mechanism:
Examples:
1. It is useful for making tetrasubstituted alkene.
2. It is also used for making cyclic alkene (Intramolecular)

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• Radical-Radical reactions
 Esters undergoes pinacol type coupling: Acyloin Reaction.
1,2-diketone are more reactive towards electrophiles and reducing
agents than ketones because their π* is lower energy.

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 Improve the version of Acyloin Reaction.
95% yield

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• Mechanisms at an Aromatic Substrate
 When R in the reaction from R-X to R-Y is aromatic, the simple abstraction mechanism
may be operating, especially in gas-phase reactions.
Ar∙ + Ar-H → Ar-Ar (coupling in gas phase)
Ar∙ + Ar-H → Ar-Ar + H∙ (coupling in solution phase)
 A mechanism similar to that of electrophilic and nucleophilic aromatic substitution.

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• Mechanisms at an Aromatic Substrate
• Simple Coupling:
• Disproportionation:
• If species R’. is present:

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• Neighboring-Group Assistance in Free-Radical Reactions
 In this reaction, cleavage steps and abstraction steps were accelerated by the presence of
neighboring groups.
 Positions close to a polar group, such as bromine, should actually be deactivated by the
electron-withdrawing field effect of the bromine.
 The unusual regioselectivity is explained by a mechanism in which abstraction is assisted
by a neighboring bromine atom. (Retain their configuration)

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• The atom abstracted by free radical is almost never a tetravalent atom. It is always
univalent.
• For organic compounds, it is hydrogen or halogen.
 The principal reason for this preference is steric. A univalent atom is much more exposed
to attack by the incoming radical than an atom with a higher valence.
 Most studies of aliphatic reactivity have been made with hydrogen as the leaving atom and
chlorine atoms as the abstracting species.

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• Position of attack:
1. Alkanes: The extent of the preference depends on the selectivity of the abstracting radical
and on the temperature.
 Selectivity for attack of radical: 3°>2°>1° hydrogen decreases for less hindered alkanes
and 3°<2°<1° hydrogen decreases for more hindered alkanes.
 Cyclopropylcarbinyl radicals are alkyl radicals, but because of the cyclopropane ring with
its relatively weak bonds, they undergo rapid ring opening to give butenyl radicals.
2. Alkenes: Allylic H-atom greatly preferred than vinylic H-atom for the H-abstraction.

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• Position of attack:
3. Alkyl side chains of aromatic ring: The preferential position of attack on side chain is
usually the one directly attached to the ring (benzylic position).
4. Compound containig Electron-withdrawing Substituent:

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• Position of attack:
5. Stereoelectronic effect:
A B
H-abstraction of compound A is faster than the compound B

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• Due to the high rigidity of the bicycle, these radicals cannot have a planar structure with
a sp2 hybridized radical carbon atom.
• The reaction rate of the bicyclic reactant may be up to 1014 times lower.
• The bridgehead radical carbon and its substituents can, obviously, not consume a planar
structure due to the high rigidity of the bicycle. If this were the case, the ring strain would
then be too strong.

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In each step in the cycle a radical is consumed and a new radical is formed. This type of
reaction is known as Radical Chain Reaction.
Reaction:
Mechanism:
Initiation Steps:
Propagation Steps:
Termination Steps:

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Radical Inhibitors: It is compound that prevents a chain process from either getting started or
continuing.

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Chlorination of Alkanes
Mechanism:
Be warned: Reactions like this can be explosive in
sunlight and are carried out in specialized facilities, not
in open laboratory.

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Abstraction of 2o
H-atom is more exothermic than 1o
H-atom:
1) 2o
C-H bond are weaker than 1o
C-H; 2) 2o
radicals are more stable than 1o
C-H

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 3o
radicals is more exothermic than 1o
, yet 1o
alkyl chloride is more formed than 3o
alkyl chloride.
 9:1  1o
H-atom:3o
H-atom

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ΔG- activation energy
ΔG= ΔH-TΔS
ΔG3
** is smaller than ΔG1
**,
so the reaction at 3o
C-H
bond faster.

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Bromination of Alkanes

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Bromination of Alkanes:
ΔG- activation energy
ΔG= ΔH-TΔS
ΔG1
** is significantly larger
than ΔG3
**

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Allylic Bromination: NBS(N-bromosuccinimide)
Mechanism:

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There is a problem with this reaction: 1) Reaction is reversible; 2)Polar addition of Br2 to the alkene
This can be prevented if the concentration of Br2 in the reaction
is kept very low and NBS with non-polar solvent also disfavors
the formation of the cationic bromonium ion intermediate.

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Reversing the selectivity: Radical Substitution of Br by H
Mechanism:

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Reversing the selectivity: Radical Substitution of Br by H
 Homolysis of Bu3SnH is promoted by the initiator AIBN
 Why use AIBN as an initiator, why not a peroxide?
 AIBN ; Peroxide RO
. Radical highly reactive

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Mechanism:
Reaction:
?

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For a way of overcoming this problem:
Another example:
Mechanism:

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For a way of overcoming this problem:

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Mechanism:
Reaction:

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Example:1
Example:1
Example:1
Note: The preference
for the formation of a
smaller ring is very
powerful one

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In the presence of atmospheric oxygen, organic compounds are known to undergo a slow
oxidation process called autooxidation.
Mechanism:

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Anti-oxidant as food additive:
BHT and BHA effectively scavenge and destroy radicals. They are called antioxidants
because one molecule of a radical scavenger can prevent the autooxidation of thousands of
oil molecules by not allowing the chain process to begin

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