Radical Reactions. Free Radicals Free radicals form when bonds break homolytically Note the single-barbed or fishhook arrow used to show the electron

Radical Reactions

Free Radicals

• Free radicals form when bonds break homolytically

• Note the single-barbed or fishhook arrow used to show the electron movement

Free Radicals

• Recall the orbital hybridization in carbocations and carbanions

Free Radicals

• Free radicals can be thought of as sp2 hybridized or quickly interconverting sp3 hybridized

sp2 hybridized

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

• Hybrid

δ

δ

δ

δ

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


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


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

• Note the reversibility of radical processes



• Radical electron movement is generally classified as either initiation, termination, or propagation

• Initiation occurs when radicals are created

• Termination occurs when radicals are destroyed

Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. 11-14

Klein, Organic Chemistry 2e

Initiation Termination

• Propagation occurs when radicals are moved from one location to another


Propagation

Chlorination of Methane

• Let’s apply our electron-pushing skills to a reaction

• We must consider each pattern for any free radical that forms during the reaction



• Why do termination reactions happen less often than propagation reactions?


• The propagation steps give the net reaction

1. Initiation produces a small amount Cl• radical2. H abstraction consumes the Cl• radical3. Cl abstraction generates a Cl• radical, which can go on to

start another H abstraction• Propagation steps are self-sustaining


• Reactions that have self-sustaining propagation steps are called chain reactions

• Chain reaction: the products from one step are reactants for a different step in the mechanism

• Polychlorination is difficult to prevent, especially when an excess of Cl2 is present.


• Draw a reasonable mechanism that shows how each of the products might form in the following reaction

• Which of the products above are major and which are minor? Are other products also possible?

Cl2

heatCl Cl

Cl

Cl

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

• Draw in necessary arrows in the reactions above

Halogenation Thermodynamics

• If we want to determine whether a process is product favored, we must determine the sign (+/-) for ΔG

• In a halogenation reaction, will ΔH or -TΔS have a bigger effect on the sign of ΔG? WHY?


• Because the -TΔS term should be close to zero, we can simplify the free energy equation

• Considering the bonds that break and form in the reaction, estimate ΔHhalogenation for each of the halogens in the table below


• Fluorination is so exothermic that it is impractical. • Iodination is nonspontaneous, so it is not product

favored



• Consider chlorination and bromination in more detail

• Chlorination is more product favored than bromination


• Which step in the mechanism is the slow step? Which reaction has a faster rate? Which is more product favored?

Both steps are exothermic

Second step is exothermic

First step is endothermic

Halogenation Regioselectivity

• With substrates more complex than ethane, multiple monohalogenation products are possible

• If the halogen were indiscriminant, predict the product ratio?


• For the CHLORINATION process, the actual product distribution favors 2-chloropropane over 1-chloropropane

• Which step in the mechanism determines the regioselectivity?

• Show the arrow pushing for that key mechanistic step

Chlorination Energy Diagram

• Lower Ea, faster rate, so more stable intermediate is formed faster.


• For the BROMINATION process, the product distribution vastly favors 2-bromopropane over 1-bromopropane

• Which step in the mechanism determines regioselectivity?

• Show the arrow pushing for that key mechanistic step

Chlorination Vs. Bromination

Endothermic and Exothermic Diagrams


• Which process is more regioselective? WHY?


• Bromination at the 3° position happens 1600 times more often than at the 1° position


• Free-radical bromination is highly selective, chlorination is moderately selective, and fluorination is nearly nonselective.

Halogenation Stereochemistry

• The halogenation of butane or more complex alkanes forms a new chirality center

• 2-chlorobutane will form as a racemic mixture• Which step in the mechanism is responsible for the

stereochemical outcome?


• Three monosubstituted products form in the halogenation of butane because halogen abstraction will occur on either side of the plane with equal probability


• In the halogenation of (S)-3-methylhexane, the chirality center is the most reactive carbon in the molecule.


• Draw all of the monosubstituted products that would form in the halogenation below including all stereoisomers

Br2

light

Allylic Halogenation

• When an C=C double bond is present it affects the regioselectivity of the halogenation reaction

• Given the bond dissociation energies below, which position of cyclohexene will be most reactive toward halogenation?

Allylic Halogenation

• When an allylic hydrogen is abstracted, it leaves behind an allylic free radical that is stabilized by resonance

• Based on the high selectivity of bromination that we discussed, you might expect bromination to occur as shown below

• What other set of side-products is likely to form in this reaction?

Allylic Halogenation with NBS

• To avoid the competing halogenation addition reaction, NBS can be used to supply Br• radicals

• Heat or light initiates the process


• Propagation produces new Br• radicals to continue the chain reaction

• Where does the Br-Br above come from? The amount of Br-Br in solution is minimal, so the competing addition reaction is minimized


• Give a mechanism that explains the following product distribution. Hint: resonance

• Ozone is both created and destroyed in the upper atmosphere

Atmospheric Chemistry and O3

• O3 molecules absorb harmful UV radiation

• O3 molecules are recycled as heat energy is released


• For this process to be spontaneous, the entropy of the universe must increase

• Heat is a more disordered form of energy than light. WHY?


• O3 depletion (about 6% each year) remains a serious health and environmental issue

• Compounds that are most destructive to the ozone layer– Are stable enough to reach the upper atmosphere – Form free radicals that interfere with the O3 recycling process

• Chlorofluorocarbons (CFCs) fit both criteria• Atmosphere O3 is vital for protection, but what effect

does O3 have at the earth’s surface?


• CFC substitutes that generally decompose before reaching the O3 layer include hydrochlorofluorocarbons

• Hydrofluorocarbons don’t even form the chlorine radicals that interfere with the O3 cycle

Combustion and Firefighting

• Like most reactions, combustion involves breaking bonds and forming new bonds– A fuel is heated with the necessary Eact to break bonds (C-C, C-

H, and O=O) homolytically– The resulting free radicals join together to form new O-H and

C=O bonds

• Why does the process release energy overall?• What types of chemicals might be used in fire

extinguishers to inhibit the process?


• Water deprives the fire of the Eact needed by absorbing the energy

• CO2 and Argon gas deprive the fire of needed oxygen• Halons are very effective fire-suppression agents

• Halons suppress combustion in three main ways


• Halons suppress combustion in three main ways1. As a gas, they can smother the fire and deprive it of O2

2. They absorb some of the Eact for the fire by undergoing homolytic cleavage

3. The free radicals produced can combine with C• and H• free radicals to terminate the combustion chain reaction


• How do you think the use of halons to fight fires affects the ozone layer?

• FM-200 is an alternative firefighting agent

• Practice with conceptual checkpoint 11.18

Documents

Radical Reactions. Free Radicals Free radicals form when bonds break homolytically Note the single-barbed or fishhook arrow used to show the electron