Radical Reaction

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Organic Chemistry,Second Edition

Janice Gorzynski Smith

University of Hawaii

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Prepared by Rabi Ann MusahState University of New York at Albany

Chapter 15

Radical Reactions


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Radical Reactions

Radicals and Radical Stability.

Radical Mechanisms:

Initiation, Propagation, Termination

Halogenation of Alkanes.

Bond Energies and Energy Diagrams.

Product Distribution in Percent.

Stereochemistry.

Allylic Halogenation.

Radical Addition to Alkenes.

Chapter 15 Topics:


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Radical Reactions

A significant group of reactions involve radicalintermediates.

A radical is a reactive intermediate with a singleunpaired electron, formed by homolysis of a covalent

bond. A radical contains an atom that does not have an

octet of electrons.

Half-headed arrows are used to show the movement

of electrons in radical processes.

Introduction:


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Carbon radicals are classified as 1, 2 or 3.

A carbon radical is sp2 hybridized and trigonal planar,like sp2 hybridized carbocations.

The unhybridized p orbital contains the unpairedelectron and extends above and below the trigonalplanar carbon.

Radical Reactions

Introduction:


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Figure 15.1 The relative stability of 1 and 2 carbon radicals

Radical Reactions

Introduction:


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Radicals are formed from covalent bonds by addingenergy in the form ofheat () orlight (h).

Some radical reactions are carried out in the presenceof a radical initiator.

Radical initiators contain an especially weak bond thatserves as a source of radicals.

Peroxides, compounds having the general structureROOR, are the most commonly used radical

initiators. Heating a peroxide readily causes homolysis of the

weak OO bond, forming two RO radicals.

Radicals undergo two main types of reactions: they

react with bonds, and they add to bonds.

General Features of Radical Reactions:

Radical Reactions


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A radical X abstracts a hydrogen atom from a CH

bond to from HX and a carbon radical.

Reaction of a Radical X with a C-H Bond:

A radical X also adds to the bond of a carboncarbondouble bond.

Radical Reactions

Reaction of a Radical X with a C=C Bond:


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In the presence of heat or light, alkanes react with

halogens to form alkyl halides. Halogenation of alkanes is a radical substitution reaction.

Halogenation of alkanes is only useful with Cl2 or Br2.Reaction with F2 is too violent, and reaction with I2 is too

slow to be useful. With an alkane that has more than one type of hydrogen

atom, a mixture of alkyl halides may result.

Halogenation of Alkanes:

Radical Reactions


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When a single hydrogen atom on a carbon has been replaced

by a halogen atom, monohalogenation has taken place. When excess halogen is used, it is possible to replace more

than one hydrogen atom on a single carbon with halogenatoms.

Monohalogenation can be achieved experimentally by addinghalogen X2 to an excess of alkane.

When asked to draw the products of halogenation of analkane, draw the products of monohalogenation only, unlessspecifically directed to do otherwise.

Figure 15.2 Complete halogenation of CH4 using excess Cl2

Radical ReactionsHalogenation of Alkanes:


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Three facts about halogenation suggest that the mechanisminvolves radical, not ionic, intermediates:

Halogenation of Alkanes: Reaction Mechanism

Radical Reactions


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Radical halogenation has three distinct steps.

A mechanism (such as that observed in radicalhalogenation) that involves two or more repeating steps iscalled a chain mechanism.

The most important steps of radical halogenation are those

that lead to product formation: the propagation steps.

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Radical ReactionsMechanism


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STEP 1:CH4 + X => CH3 + H-X

Bond Dissociation H Ea

kcal/mol kcal/mol kcal/mol kcal/mol

F 104 136 -32 ~ 1.2

Cl 104 103 +1 ~ 4

Br 104 88 +16 ~ 18

I 104 71 +33 ~ 34

Radical Reactions

Halogenation of Methanesee Bond Energies in Table 6-2, pg 207.


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STEP 2:CH3 + X2 ==> CH3-X + X

Bond Dissociation H Ea

kcal/mol kcal/mol kcal/mol kcal/mol

F 38 109 -71 ~ 1

Cl 58 84 -26 ~ 1

Br 46 70 -24 ~ 1

I 36 56 -20 ~ 1

Radical Reactions

Halogenation of Methanesee Bond Energies in Table 6-2, pg 207.


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SUM OF STEPS 1 + 2:

Step 1 Step 2 H

kcal/mol kcal/mol kcal/molF -32 -71 -103

Cl +1 -26 -25

Br +16 -24 -8

I +33 -20 +13

Radical Reactions

Halogenation of Methane bond energies:


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Radical Reactions

Halogenation of Methane bond energies:

PLOT OF STEPS 1 + 2: values in Kcal/mol

F Cl Br I

+1.2 +4 +18 +34 Ea

-103 -25 -8 +13 H


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Figure 15.3 Energy changes in the propagationsteps during the chlorination of ethane

Radical Reactions



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Halogenation of Alkanes: Energetics

Figure 15.4 Energydiagram for thepropagation stepsin the chlorinationof ethane

Radical Reactions


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Chlorination of CH3CH2CH3 affords a 1:1 mixture ofCH3CH2CH2Cl and (CH3)2CHCl.

Note that CH3CH2CH3 has six 1 hydrogens and only two2 hydrogens, so the expected product ratio ofCH3CH2CH2Cl to (CH3)2CHCl (assuming all hydrogens are

equally reactive) is 3:1.

Halogenation of Alkanes: Chlorination of Propane

Radical Reactions


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Since the observed ratio between CH3

CH2

CH2

Cl and(CH3)2CHCl is 1:1, the 2 CH bonds must be more reactivethan the 1 CH bonds.

Thus, when alkanes react with Cl2, a mixture of productsresults, with more product formed by cleavage of the weakerCH bond than you would expect on statistical grounds.

Radical ReactionsHalogenation of Alkanes:


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Although alkanes undergo radical substitutions with bothCl2 and Br2, chlorination and bromination exhibit twoimportant differences.

1. Chlorination is faster than bromination.

2. Chlorination is less selective, yielding a mixture of

products and bromination is more selective, oftenyielding one major product.

Chlorination versus Bromination:

Radical Reactions


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The differences in chlorination and bromination can beexplained by considering the energetics of each type ofreaction.

Calculating the H0 using bond dissociation energies revealsthat abstraction of a 1 or 2 hydrogen by Br is endothermic,

but it takes less energy to form the more stable 2 radical.

Radical Reactions

Chlorination versus Bromination:


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Conclusion: Because the rate-determining step is endothermic,the more stable radical is formed faster, and often a single

radical halogenation product predominates.

Figure 15.5 Energy diagram for the endothermic reaction:CH3CH2CH3 + Br

CH3CH2CH2 or (CH3)2CH

+ HBr

Radical ReactionsChlorination versus Bromination:


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Calculating the H using bond dissociation energies forchlorination reveals that abstraction of a 1 or 2 hydrogenby Cl is exothermic.

Since chlorination has an exothermic rate-determiningstep, the transition state to form both radicals resemblesthe same starting material, CH3CH2CH3. Thus, the relativestability of the two radicals is much less important, and

both radicals are formed.



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Conclusion: Because the rate-determining step in chlorination isexothermic, the transition state resembles the starting material,

both radicals are formed, and a mixture of products results.

Figure 15.6 Energy diagram for the exothermic reaction:

CH3CH2CH3 + CI CH3CH2CH2 or (CH3)2CH + HCI



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Reactivity: The tendency of a reagent to react with agiven compound. Chlorine is more reactive towardalkanes than is bromine.

Selectivity: The choice of reaction site by the reagent.

Bromine is more selective in reaction with alkanes thanis chlorine.

Regioselectivity: The preference of one product overothers in a reaction where multiple reaction sites exist.

Bromine is regioselective and chlorine is not. Remember the Hammond postulate, page 260-261, with

regard to transition states and their relationship toexothermic or endothermic reactions.

Halogenation of Alkanes: Terms

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Stereochemistry of Halogenation:

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Radical Reactions

General Examples: Halogenation of a nonchiral compound at a prochiral

C gives racemic mixture of enantiomers.

n-butane + Br2 gives R- + S-2-bromobutane.

Halogenation of a chiral compound at the chiral Cgives a racemic mixture of enantiomers.

S-2-bromobutane + Cl2 gives R- + S-2-bromo-2-chlorobutane.

Halogenation of a chiral compound at a prochiral Cgives a mixture of diastereomers.

S-2-bromobutane + Cl2 gives S,R- + S,S- 2-bromo-3-chlorobutane.


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Halogenation of an achiral starting material such asCH3CH2CH2CH3 forms two constitutional isomers byreplacement 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).

Radical Reactions



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A racemic mixture results because the first propagationstep generates a planarsp2 hybridized radical. Cl2 thenreacts with it from either side to form an equal amount oftwo enantiomers.

Radical Reactions



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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.

Radical ReactionsStereochemistry of Halogenation:

R di l R ti


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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 planarsp2 hybridized radical is attacked fromeither side by Cl

2, forming a new stereogenic center.

A pair of diastereomers is formed.

Radical ReactionsStereochemistry of Halogenation:


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An allylic carbon is a carbon adjacent to a double bond.

Homolysis of the allylic CH bond in propene generatesan allylic radical which has an unpaired electron on thecarbon adjacent to the double bond.

Radical Halogenation at an Allylic Carbon:

The bond dissociation energy for this process is even lessthan that for a 30 CH bond (91 kcal/mol).

This means that an allyl radical is more stable than a 30radical.

Radical Reactions

104 98 95 91 87 kcal/mol


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The allyl radical is more stable than other radicalsbecause two resonance forms can be drawn for it.

Radical Reactions



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Because allylic CH bonds are weaker than othersp3

hybridized CH bonds, the allylic carbon can be selectivelyhalogenated using NBS in the presence of light or peroxides.

NBS contains a weak NBr bond that is homolyticallycleaved with light to generate a bromine radical, initiating anallylic halogenation reaction.

Propagation then consists of the usual two steps of radical

halogenation.

Radical Reactions



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Radical Reactions


R di l R i


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NBS also generates a low concentration of Br2 neededin the second chain propagation step (Step [3] of themechanism).

The HBr formed in Step [2] reacts with NBS to form

Br2, which is then used for halogenation in Step [3] ofthe mechanism.

Radical Reactions


R di l R ti


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Thus, an alkene with allylic CH bonds undergoes twodifferent reactions depending on the reaction conditions.

Radical Reactions


Radical Reactions


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Question:

Why does a low concentration of Br2 (from NBS)favor allylic substitution (over ionic addition toform the dibromide)?

Answer: The key to getting substitution is to have a low

concentration of bromine (Br2).

The Br2 produced from NBS is present in very low

concentrations.(Answer is continued on next slide.)

Radical ReactionsRadical Halogenation at an Allylic Carbon:

Radical Reactions


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A low concentration of Br2 would first react with thedouble bond to form a low concentration of thebridged bromonium ion.

The bridged bromonium ion must then react withmore bromine (in the form of Br) in a second stepto form the dibromide.

If concentrations of both intermediatesthebromonium ion and Br are low (as is the casehere), the overall rate of addition is very slow, andthe products of the very fast and facile radical chainreaction predominate.

Radical ReactionsRadical Halogenation at an Allylic Carbon:

R di l R ti


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Halogenation at an allylic carbon often results in a mixtureof products. Consider the following example:

A mixture results because the reaction proceeds by way ofa resonance stabilized radical.

Radical Reactions


R di l R ti


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An antioxidant is a compound that stops an oxidation from

occurring (a radical scavenger). Naturally occurring antioxidants such as vitamin E prevent

radical reactions that can cause cell damage.

Synthetic antioxidants such as BHT, butylated hydroxytoluene, are added to packaged and prepared foods toprevent oxidation and spoilage.

Vitamin E and BHT are radical inhibitors, so they terminateradical chain mechanisms by reacting with the radical.

Antioxidants:Radical Reactions

R di l R ti


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To trap free radicals, both vitamin E and BHT use a hydroxygroup bonded to a benzene ring, a general structure called aphenol.

Radicals (R) abstract a hydrogen atom from the OH group ofan antioxidant, forming a new resonance-stabilized radical.This new radical does not participate in chain propagation, but

rather terminates the chain and halts the oxidation process. Because oxidative damage to lipids in cells is thought to play a

role in the aging process, many anti-aging formulationscontain antioxidants.

Radical ReactionsAntioxidants:

R di l R ti


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HBr adds to alkenes to form alkyl bromides in the presence

of heat, light, or peroxides. The regioselectivity of the addition to unsymmetrical

alkenes is different from that in addition of HBr in theabsence of heat, light or peroxides.

Radical Additions to Double Bonds:

The addition of HBr to alkenes in the presence of heat,

light or peroxides proceeds via a radical mechanism.

Radical Reactions

R di l R ti


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Radical ReactionsRadical Additions to Double Bonds:

Radical Reactions


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Note that in the first propagation step, the addition ofBr to the double bond, there are two possible paths:

1. Path [A] forms the less stable 1 radical.

2. Path [B] forms the more stable 2 radical.

The more stable 2 radical forms faster, so Path [B]is preferred.

Radical Reactions


Radical Reactions


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The radical mechanism illustrates why the regio-selectivity of HBr addition is different depending onthe reaction conditions.

Radical Reactions


Radical Reactions


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HBr adds to alkenes under radical conditions, but HCl and HI

do not. This can be explained by considering the energetics ofthe reactions using bond dissociation energies.

Both propagation steps for HBr addition are exothermic, sopropagation is exothermic (energetically favorable) overall.

For addition of HCl or HI, one of the chain propagating steps is

quite endothermic, and thus too difficult to be part of arepeating chain mechanism.

Figure 15.9 Energy

changes during thepropagation steps:

CH2 = CH2 + HBrCH3CH2Br

Radical ReactionsRadical Additions to Double Bonds:

Radical Reactions


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Polymers are large molecules made up of repeating units

of smaller molecules called monomers. They includebiologically important compounds such as proteins andcarbohydrates, as well as synthetic plastics such aspolyethylene, polyvinyl chloride (PVC) and polystyrene.

Polymerization is the joining together of monomers tomake polymers. For example, joining ethylene monomerstogether forms the polymer polyethylene, a plastic used inmilk containers and plastic bags.

Polymers and Polymerization:

Radical Reactions

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Many ethylene derivatives having the general structureCH2=CHZ are also used as monomers for polymerization.

The identity of Z affects the physical properties of theresulting polymer.

Polymerization of CH2=CHZ usually affords polymerswith Z groups on every other carbon atom in the chain.

Radical Reactions


Polymers and Polymerization


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Polymers and Polymerization

Radical Reactions


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Radical ReactionsPolymers and Polymerization:

Radical Reactions


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In radical polymerization, the more substituted radicalalways adds to the less substituted end of themonomer, a process called head-to-tailpolymerization.

Radical Reactions



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Organic Chemistry,Second Edition

Janice Gorzynski Smith

University of Hawaii

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Prepared by Rabi Ann MusahState University of New York at Albany

End Chapter 15

Radical Reaction

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