Organic Chemistry, Second Edition

Janice Gorzynski Smith University of Hawaii

Chapter 15 Radical Reactions

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

Radical Reactions
Chapter 15 Topics:
Radicals and Radical Stability. Radical Mechanisms: Initiation, Propagation, Termination Halogenation of Alkanes.

Bond Energies and Energy Diagrams.

Allylic Halogenation.
Radical Addition to Alkenes.
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Radical Reactions
Introduction:
A significant group of reactions involve radical intermediates. A radical is a reactive intermediate with a single unpaired 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.

Radical Reactions
Introduction:
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 unpaired electron and extends above and below the trigonal planar carbon.

Radical Reactions
Introduction:

Figure 15.1 The relative stability of 1 and 2 carbon radicals

Radical Reactions
General Features of Radical Reactions:
Radicals are formed from covalent bonds by adding energy in the form of heat () or light (h). Some radical reactions are carried out in the presence of a radical initiator. Radical initiators contain an especially weak bond that serves as a source of radicals. Peroxides, compounds having the general structure ROOR, 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 6 react with bonds, and they add to bonds.

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

Radical Reactions
Halogenation of Alkanes:
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.

Radical Reactions
Halogenation of Alkanes:
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 halogen atoms. Monohalogenation can be achieved experimentally by adding halogen X2 to an excess of alkane. When asked to draw the products of halogenation of an alkane, draw the products of monohalogenation only, unless specifically directed to do otherwise.
Figure 15.2 Complete halogenation of CH4 using excess Cl2

Radical Reactions
Halogenation of Alkanes: Reaction Mechanism
Three facts about halogenation suggest that the mechanism involves radical, not ionic, intermediates:

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Radical Reactions
Halogenation of Alkanes: Reaction Mechanism
Radical halogenation has three distinct steps.

A mechanism (such as that observed in radical halogenation) that involves two or more repeating steps is called a chain mechanism. The most important steps of radical halogenation are those that lead to product formation: the propagation steps. 11

Radical ReactionsMechanism

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Radical Reactions
Halogenation of Methane see Bond Energies in Table 6-2, pg 207.
STEP 1: CH4 + X => CH3 + H-X Bond Dissociation kcal/mol kcal/mol F 104 136 Cl 104 103 H Ea kcal/mol kcal/mol -32 ~ 1.2 +1 ~4

Br 104
I 104

88
71

+16
+33

~ 18
~ 34
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Radical Reactions
Halogenation of Methane see Bond Energies in Table 6-2, pg 207.
STEP 2: CH3 + X2 ==> CH3-X + X Bond Dissociation kcal/mol kcal/mol 38 109 58 84 H kcal/mol -71 -26 Ea kcal/mol ~1 ~1

F
Cl

Br
I

46
36

70
56

-24
-20

~1
~1
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Radical Reactions
Halogenation of Methane bond energies:
SUM OF STEPS 1 + 2: Step 1 kcal/mol -32 +1 +16 +33 Step 2 kcal/mol -71 -26 -24 -20 H kcal/mol -103 -25 -8 +13
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F Cl Br I

Radical Reactions
Halogenation of Methane bond energies:
PLOT OF STEPS 1 + 2: F +1.2 Cl +4 values in Kcal/mol Br +18 I +34 Ea

-103

-25

-8

+13

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Radical Reactions
Halogenation of Alkanes: Reaction Mechanism
Figure 15.3 Energy changes in the propagation steps during the chlorination of ethane

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Radical Reactions
Halogenation of Alkanes: Energetics
Figure 15.4 Energy diagram for the propagation steps in the chlorination of ethane

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Radical Reactions
Halogenation of Alkanes: Chlorination of Propane
Chlorination of CH3CH2CH3 affords a 1:1 mixture of CH3CH2CH2Cl and (CH3)2CHCl.

Note that CH3CH2CH3 has six 1 hydrogens and only two 2 hydrogens, so the expected product ratio of CH3CH2CH2Cl to (CH3)2CHCl (assuming all hydrogens are equally reactive) is 3:1.

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Radical Reactions
Halogenation of Alkanes:
Since the observed ratio between CH3CH2CH2Cl and (CH3)2CHCl is 1:1, the 2 CH bonds must be more reactive than the 1 CH bonds.

Thus, when alkanes react with Cl2, a mixture of products results, with more product formed by cleavage of the weaker CH bond than you would expect on statistical grounds. 20

Radical Reactions
Chlorination versus Bromination:
Although alkanes undergo radical substitutions with both Cl2 and Br2, chlorination and bromination exhibit two important differences. 1. Chlorination is faster than bromination. 2. Chlorination is less selective, yielding a mixture of products and bromination is more selective, often yielding one major product.

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Radical Reactions
Chlorination versus Bromination:
The differences in chlorination and bromination can be explained by considering the energetics of each type of reaction. Calculating the H0 using bond dissociation energies reveals that abstraction of a 1 or 2 hydrogen by Br is endothermic, but it takes less energy to form the more stable 2 radical.

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Radical Reactions
Chlorination versus Bromination:
Figure 15.5 Energy diagram for the endothermic reaction: CH3CH2CH3 + Br CH3CH2CH2 or (CH3)2CH + HBr

Conclusion: Because the rate-determining step is endothermic, the more stable radical is formed faster, and often a single 23 radical halogenation product predominates.

Radical Reactions
Chlorination versus Bromination:
Calculating the H using bond dissociation energies for chlorination reveals that abstraction of a 1 or 2 hydrogen by Cl is exothermic.

Since chlorination has an exothermic rate-determining step, the transition state to form both radicals resembles the same starting material, CH3CH2CH3. Thus, the relative stability of the two radicals is much less important, and 24 both radicals are formed.

Radical Reactions
Chlorination versus Bromination:
Figure 15.6 Energy diagram for the exothermic reaction: CH3CH2CH3 + CI CH3CH2CH2 or (CH3)2CH + HCI

Conclusion: Because the rate-determining step in chlorination is exothermic, the transition state resembles the starting material, both radicals are formed, and a mixture of products results. 25

Radical Reactions
Halogenation of Alkanes: Terms
Reactivity: The tendency of a reagent to react with a given compound. Chlorine is more reactive toward alkanes than is bromine. Selectivity: The choice of reaction site by the reagent. Bromine is more selective in reaction with alkanes than is chlorine. Regioselectivity: The preference of one product over others 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 to exothermic or endothermic reactions.
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Radical Reactions
Stereochemistry of Halogenation:

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Radical Reactions
Stereochemistry of Halogenation:
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 C gives a racemic mixture of enantiomers. S-2-bromobutane + Cl2 gives R- + S-2-bromo-2chlorobutane. Halogenation of a chiral compound at a prochiral C gives a mixture of diastereomers. S-2-bromobutane + Cl2 gives S,R- + S,S- 2bromo-3-chlorobutane.
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Radical Reactions
Stereochemistry of Halogenation:
Halogenation of an achiral starting material such as CH3CH2CH2CH3 forms two constitutional isomers by replacement 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). 29

Radical Reactions
Stereochemistry of Halogenation:
A racemic mixture results because the first propagation step generates a planar sp2 hybridized radical. Cl2 then reacts with it from either side to form an equal amount of two enantiomers.

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Radical Reactions
Stereochemistry of Halogenation:
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.

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Radical Reactions
Stereochemistry of Halogenation:
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 planar sp2 hybridized radical is attacked from either side by Cl2, forming a new stereogenic center. A pair of diastereomers is formed.

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Radical Reactions
Radical Halogenation at an Allylic Carbon:
An allylic carbon is a carbon adjacent to a double bond. Homolysis of the allylic CH bond in propene generates an allylic radical which has an unpaired electron on the carbon adjacent to the double bond.

The bond dissociation energy for this process is even less than that for a 30 CH bond (91 kcal/mol). This means that an allyl radical is more stable than a 30 radical. 104 98 95 91 87 kcal/mol

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Radical Reactions
Radical Halogenation at an Allylic Carbon:
The allyl radical is more stable than other radicals because two resonance forms can be drawn for it.

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Radical Reactions
Radical Halogenation at an Allylic Carbon:
Because allylic CH bonds are weaker than other sp3 hybridized CH bonds, the allylic carbon can be selectively halogenated using NBS in the presence of light or peroxides.

NBS contains a weak NBr bond that is homolytically cleaved with light to generate a bromine radical, initiating an allylic halogenation reaction. Propagation then consists of the usual two steps of radical halogenation. 35

Radical Reactions
Radical Halogenation at an Allylic Carbon:

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Radical Reactions
Radical Halogenation at an Allylic Carbon:
NBS also generates a low concentration of Br2 needed in the second chain propagation step (Step [3] of the mechanism). The HBr formed in Step [2] reacts with NBS to form Br2, which is then used for halogenation in Step [3] of the mechanism.

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Radical Reactions
Radical Halogenation at an Allylic Carbon:
Thus, an alkene with allylic CH bonds undergoes two different reactions depending on the reaction conditions.

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Radical Reactions
Radical Halogenation at an Allylic Carbon:
Question: Why does a low concentration of Br2 (from NBS) favor allylic substitution (over ionic addition to form 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.)
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Radical Reactions
Radical Halogenation at an Allylic Carbon:
A low concentration of Br2 would first react with the double bond to form a low concentration of the bridged bromonium ion. The bridged bromonium ion must then react with more bromine (in the form of Br) in a second step to form the dibromide. If concentrations of both intermediatesthe bromonium ion and Br are low (as is the case here), the overall rate of addition is very slow, and the products of the very fast and facile radical chain reaction predominate.
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Radical Reactions
Radical Halogenation at an Allylic Carbon:
Halogenation at an allylic carbon often results in a mixture of products. Consider the following example:

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

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Radical Reactions
Antioxidants:
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 hydroxy toluene, are added to packaged and prepared foods to prevent oxidation and spoilage. Vitamin E and BHT are radical inhibitors, so they terminate radical chain mechanisms by reacting with the radical.

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Radical Reactions
Antioxidants:
To trap free radicals, both vitamin E and BHT use a hydroxy group bonded to a benzene ring, a general structure called a phenol. Radicals (R) abstract a hydrogen atom from the OH group of an 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 formulations contain antioxidants.

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Radical Reactions
Radical Additions to Double Bonds:
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 the absence of heat, light or peroxides.

The addition of HBr to alkenes in the presence of heat, light or peroxides proceeds via a radical mechanism.

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Radical Reactions
Radical Additions to Double Bonds:

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Radical Reactions
Radical Additions to Double Bonds:
Note that in the first propagation step, the addition of Br 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.

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Radical Reactions
Radical Additions to Double Bonds:
The radical mechanism illustrates why the regioselectivity of HBr addition is different depending on the reaction conditions.

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Radical Reactions
Radical Additions to Double Bonds:
HBr adds to alkenes under radical conditions, but HCl and HI do not. This can be explained by considering the energetics of the reactions using bond dissociation energies. Both propagation steps for HBr addition are exothermic, so propagation 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 a repeating chain mechanism.
Figure 15.9 Energy changes during the propagation steps: CH2 = CH2 + HBr CH3CH2Br
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Radical Reactions
Polymers and Polymerization:
Polymers are large molecules made up of repeating units of smaller molecules called monomers. They include biologically important compounds such as proteins and carbohydrates, as well as synthetic plastics such as polyethylene, polyvinyl chloride (PVC) and polystyrene. Polymerization is the joining together of monomers to make polymers. For example, joining ethylene monomers together forms the polymer polyethylene, a plastic used in milk containers and plastic bags.

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Radical Reactions
Polymers and Polymerization:
Many ethylene derivatives having the general structure CH2=CHZ are also used as monomers for polymerization. The identity of Z affects the physical properties of the resulting polymer. Polymerization of CH2=CHZ usually affords polymers with Z groups on every other carbon atom in the chain.

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Polymers and Polymerization

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Radical Reactions
Polymers and Polymerization:

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Radical Reactions
Polymers and Polymerization:
In radical polymerization, the more substituted radical always adds to the less substituted end of the monomer, a process called head-to-tail polymerization.

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Organic Chemistry, Second Edition

Janice Gorzynski Smith University of Hawaii

End Chapter 15
Prepared by Rabi Ann Musah
State University of New York at Albany

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

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