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 RADICAL REACTIONS

Submitted By: IMTIAZ ALI

Class M.SC (FINAL)
Seat No . EP- 1648016
Enrolment No.EP-37862
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RADICAL REACTIONS
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 Free Radical Stability
 Free radicals do not have a formal charge but are
unstable because of an incomplete octet
 Groups that can push (donate) electrons toward the
free radical will help to stabilize it via
hyperconjugation.
 Free Radical Resonance

 When drawing resonance for free radicals, use

fishhook arrows to show electron movement
 An allylic radical is stabilized by resonance
 Free Radical Resonance

 The benzylic radical is a hybrid that consists of 4

contributors

δ δ

δ
δ
 Hybrid
 Resonance Stabilization

 How does resonance affect the stability of a radical?

WHY?
 Resonance Stabilization

 Vinylic free radicals are especially unstable

 The vinylic free radical is located in an sp2 orbital,

and cannot be stabilized by resonance.
 Radical Electron Movement

 Free radical electron movement is quite different from

electron movement in ionic reactions
 For example, free radicals don’t undergo rearrangement

 There are SIX key arrow-pushing patterns that we will

discuss
 Radical Electron Movement

1. Homolytic Cleavage: initiated by light or heat

2. Addition to a pi bond

3. Hydrogen abstraction: NOT the same as proton transfer

4. Halogen abstraction
 Radical Electron Movement

5. Elimination: the radical from the α carbon is pushed

toward the β carbon to eliminate a group on the β carbon
(reverse of addition to a pi bond)

6. Coupling: the reverse of homolytic cleavage

 Note that radical electron movement generally involves 2

or 3 fishhook arrows
 Radical Inhibitors

 Inhibitors act in a reaction to scavenge free radicals

to stop chain reaction processes
 Oxygen molecules can exist in the form of a
diradical, which reacts readily with other radicals.
Use arrows to show the process
 Radical Inhibitors

 Hydroquinone is also often used as a radical

inhibitor
 RADICAL REACTIONS
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COMPOUNDS MOST USED IN SYNTHETIC REACTION

(1)

Dibenzoyl peroxide

(2)

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 Free Radicals Reaction
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Discovery of free radicals

 The free first radical was detected by Pro. Gomberg in 1900 , the triphenylmethyl radical,
was abstraction of from Ph3CCl by metal . Many metals contain unpaired electron
like

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 RADICAL REACTIONS
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Radical form by Abstraction

R-O + H Br ROH + Br
• The ability of radicals to propagate by abstraction is a key feature of chain
reactions
• This is importance difference between homolysis and abstraction as a way of
making radical
• The radical substitution almost never occur at carbon atom.
• Radical substitution differ considerably from reaction.

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 Free Radicals: Typical Reactions
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3. Atom abstraction reaction:
Y= H or halogen

Bu3Sn• can itself be generated by H abstraction from Bu3SnH. Bu3Sn• is often used to
abstract halogen atoms X(Br or I) from C–X bonds.

AIBN

4. Radical-radical combination: Most free radicals are very unstable because they undergo
very rapid radical-radical combination.

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 Free Radicals

Generation of free radicals 18

1. Sigma-bond homolysis
stable benzylic radical

diradical: triplet carbene nitrene: N analogs of carbenes

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 Free Radicals Reaction
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Generation of free radicals
2. double-bond homolysis: The weaker the π bond, the easier it is to photoexcite.

cis trans
3. The cycloaromatization of certain highly unsaturated organic compounds can give
diradicals.
Bergman cyclization of a enediyne Cyclization of allenylenynes.(1,2,4-trien-6-ynes)

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 Free Radicals: Typical Reactions

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1. Addition to a π bond: similar to the addition of π bods to carbocations.

2. Fragmentation: similar to the fragmentation of a carbocation.

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 Free Radicals: Typical Reactions

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5. Disproportionation: two radicals with the same formula become two products with
different formulas.

6. One-electron transfer: in the presence of an oxidizing or reducing agent to give an

even-electron species.
One-electron reduction

One-electron oxidadation

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CHAIN FREE RADICAL REACTION
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Free Radical Reactions

a. Free Radicals

b. Chain Free Radical Reactions

c. Nonchain Free Radical Reactions

d. Miscellaneous Free Radical Reactions

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Chain Free Radical Reactions: Substitution Reaction
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1. Halogenation of alkanes
f
Initiation: Sigma-bond homolysis

Propagation: atom abstraction reaction

Termination: radical-radical combination and disproportionation

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Chain Free Radical Reactions: Substitution Reaction
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2. Dehalogenation

Initiation:

Propagation:

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Chain Free Radical Reactions: Substitution Reaction
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3. Carton-McCombie reaction: Alcohol is converted into a alkane.

Addition to a π bond Fragmentation

Atom abstraction reaction

4. Autoxidation: Key step in the industrial synthesis of phenol and acetone.

Ex: Draw the mechanism for all three steps of the phenol synthesis. 9/30/2018
 Chain Free Radical Reactions: Addition and Fragmentation Reaction

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1. Carbon-Heteroatom Bond-Forming Reactions
a. C-X bond
Markovnikov addition of HBr to alkene anti-Markovnikov addition of HBr to alkene

Ex: Please draw the mechanism of above reactions.

b. C-S bond

Initiation:

Propagation:

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 Free Radicals
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Stability of free radical on heteroatoms.

Neutral free radicals are electron-deficient, so radicals centered on less electronegative
elements are lower in energy than radicals centered on more electronegative elements. As
a result, the order of stability for first-row radicals is alkyl (·CR3) > aminyl (·NR2) > alkoxyl
(RO·), and for halogens it is I· > Br· > Cl· > F·.
Steric shielding of the radical centers.

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 Chain Free Radical Reactions: Addition and Fragmentation Reaction
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Cyclization: five-member ring is better than six-member ring.

Initiation:

Propagation:

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Chain Free Radical Reactions: Addition and Fragmentation Reaction
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c. Other cases

Initiation:

Propagation:

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Free Radical Reactions

a. Free Radicals

b. Chain Free Radical Reactions

c. Nonchain Free Radical Reactions

d. Miscellaneous Free Radical Reactions

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Nonchain Free Radical Reactions: Photochemical Reactions
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a. The photo excitation of a carbonyl compound to give a 1,2-diradical is often followed by
a fragmentation reaction.
Norrish type one:

Norrish type two:

1,4-diradical

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 Nonchain Free Radical Reactions: Photochemical Reactions

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b. Pinacol coupling

c. Barton reaction: an alkyl nitrite is converted into an alcohol-oxime.

nitrite

oxime

alcohol
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Nonchain Free Radical Reactions: Reductions with Metals
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a. Addition of H2 across π Bonds

1. An electron is transferred from the metal to the substrate to give a radical anion.
2. A second electron transfer to the radical anion occurs to give a closed-shell dianion.
3. The dianion is protonated to give a closed-shell anion.

Ex:

Mechanism:

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Nonchain Free Radical Reactions: Reductions with Metals
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b. Birch reaction: regioselectivity
ED: electron-donating group
EW: electron-withdrawing group

ortho-, meta-

ipso-, para- 9/30/2018

Nonchain Free Radical Reactions: Reductions with Metals
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Birch reaction: regioselectivity

Please draw the mechanism

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 Nonchain Free Radical Reactions: Reductions with Metals

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c. Reductive coupling: Pinacol coupling

Please draw the mechanism

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 Nonchain Free Radical Reactions: One-Electron Oxidation

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One-electron oxidizing agents

Ex:

Mechanism:

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 Nonchain Free Radical Reactions: Cycloaromatization
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Bergman cyclization of a enediyne Cyclization of allenylenynes.(1,2,4-trien-6-ynes)

Ex:

Mechanism:

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 Miscellaneous Free Radical Reactions
b. Reactions of triplet carbenes and nitrenes
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diradical: triplet carbene nitrene: N analogs of carbenes

Ex:

Mechanism:

Ex: Mechanism:

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 REFERENCE BOOKS
 Peter sykes
 J. Calydon , Nick Greeves
 Wikipedia
THANKS YOU FOR
WATCHING

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