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

Radical Electron Movement Homolytic Cleavage: initiated by light or heat Addition to a pi bond Hydrogen abstraction: NOT the same as proton transfer Halogen abstraction

Radical Electron Movement 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) Coupling: the reverse of homolytic cleavage Note that radical electron movement generally involves 2 or 3 fishhook arrows

Radical Electron Movement Note the reversibility of radical processes

Radical Electron Movement Radical electron movement is generally classified as either initiation, termination, or propagation Initiation Termination Initiation occurs when radicals are created Termination occurs when radicals are destroyed Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Radical Electron Movement 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

Chlorination of Methane

Chlorination of Methane Why do termination reactions happen less often than propagation reactions?

Chlorination of Methane The propagation steps give the net reaction Initiation produces a small amount Cl• radical H abstraction consumes the Cl• radical Cl abstraction generates a Cl• radical, which can go on to start another H abstraction Propagation steps are self-sustaining

Chlorination of Methane 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.

Chlorination of Methane 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?

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?

Halogenation Thermodynamics 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

Halogenation Thermodynamics

Halogenation Thermodynamics Fluorination is so exothermic that it is impractical. Iodination is nonspontaneous, so it is not product favored

Halogenation Thermodynamics Consider chlorination and bromination in more detail Chlorination is more product favored than bromination

Halogenation Thermodynamics Which step in the mechanism is the slow step? Which reaction has a faster rate? Which is more product favored? First step is endothermic Both steps are exothermic Second step is exothermic

Halogenation Regioselectivity With substrates more complex than ethane, multiple monohalogenation products are possible If the halogen were indiscriminant, predict the product ratio?

Halogenation Regioselectivity 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.

Halogenation Regioselectivity 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

Halogenation Regioselectivity Which process is more regioselective? WHY?

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

Halogenation Regioselectivity 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?

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

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

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

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

Allylic Halogenation with NBS 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

Allylic Halogenation with NBS Give a mechanism that explains the following product distribution. Hint: resonance

Atmospheric Chemistry and O3 Ozone is both created and destroyed in the upper atmosphere O3 molecules absorb harmful UV radiation O3 molecules are recycled as heat energy is released

Atmospheric Chemistry and O3 For this process to be spontaneous, the entropy of the universe must increase Heat is a more disordered form of energy than light. WHY?

Atmospheric Chemistry and O3 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?

Atmospheric Chemistry and O3 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?

Combustion and Firefighting 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

Combustion and Firefighting Halons suppress combustion in three main ways As a gas, they can smother the fire and deprive it of O2 They absorb some of the Eact for the fire by undergoing homolytic cleavage The free radicals produced can combine with C• and H• free radicals to terminate the combustion chain reaction

Combustion and Firefighting 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