Chemistry 211

Clark College

Notes on Radical Reactions

Although typically thought as unreactive, saturated alkanes readily undergo halogen substitution through a radical process. These radical reactions proceed through a variety of single electron steps; as such we will introduce the single-headed, or fish hook arrow to denote the movement of a single electron. This reaction introduces functionality into a molecule and allows for a variety of substitution and elimination products. The reaction requires initiation by heat or light, and is facilitated by the addition of organic peroxides. We will focus our discussion to the substitution of chlorine or bromine, as fluorine can be explosively reactive and iodine is generally unreactive. The general reaction:
CH4 + Cl2 h! or ! CH3Cl + HCl + other halogenated products

Mechanism The mechanism for any radical reaction can be broken down into three parts: initiation, propagation and termination. We will consider each step individually.

Initiation

Cl

Cl

h! or !

2 Cl

Initiation of a radical reaction requires the creation of the initial radicals in solution, through the homolytic (equal) splitting of a bond. Typically, the bond that cleaves is the halogen-halogen bond, as it is the weakest bond present. A single photon of light in the visible range will initiate thousands of molecules of chlorine or bromine.

Propagation

H
Cl

Cl
Cl

Cl

Cl

Cl

Propagation is a two-step process that involves H-atom abstraction by the halogen radical to form a reactive carbon radical, followed by the splitting of the halogen-halogen bond and creation of the halogenated product. In every step, one radical creates another, so the net concentration of radical remains fairly constant. During the reaction, this concentration of radicals is small, so it is more likely that a radical runs into a neutral compound than another radical. The rate-determining step of the reaction is the first propagation step the H-atom abstraction by the halogen radical. The energetics of this step sets the regioselectivity of a radical reaction, which will be discussed in a later section.

Termination

Cl

Cl

Cl

Cl

Cl

Cl

As the reaction nears an end, and the concentration of reactants decreases, the effective concentration of radicals increases, causing radicals to couple and terminate the reaction. Termination results when any two radicals couple to form a neutral molecule. The products of termination include the halogen

Radical Reactions Notes

Rev F07 NF

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Chemistry 211

Clark College

molecule, which can be fed back into propagation, the desired halogenated product, and an unwanted dimer of the hydrocarbon. Reaction Energetics and Regioselectivity When propane is halogenated, the following results are obtained:

CH3CH2CH3

Cl2, !

Cl 55%

Cl 45% Br

CH3CHCH3 + CH3CH2CH2 Br

CH3CH2CH3

Br2, !

CH3CHCH3 + CH3CH2CH2 97% 3%

Neither of these results match the statistics of the reaction, since 75% of the hydrogens are 1 and 25% are 2. What causes this distribution? And why is bromine so much more selective? Overall, radical halogen substitution reactions are exothermic, however, not all individual steps in the mechanism are exothermic. This fact provides us with an explanation of the results above and a method of controlling the regioselectivity of the reaction. Lets consider the rate-determining step of the reaction, the H-atom abstraction by the halogen radical.
H Cl H Cl H Br H Br

Bond dissociation energies (BDE) show that the C-H bond from more substituted carbons are easier to break (1 C-H ~100 kcal/mol, 2 C-H ~95 kcal/mol, 3 ~93 kcal/mol), explaining the deviation from statistics. The strength of the H-X bond formed explains the enhanced selectivity of bromine; the H-Cl BDE is 103 kcal/mol, whereas the H-Br BDE is 88 kcal/mol. The single step reaction with chlorine is exothermic, for bromine it is endothermic; endothermic reactions favor a more stable transition state which in this case is the more stable radical. The following table shows the ratio of products that form upon radical halogenation of a molecule with 3, 2, and 1 centers, when either Br2 or Cl2 is used. Br2 Cl2 Allylic (benzylic) Halogenation Radical halogenation is not limited to alkanes, reactions can also be performed on alkenes, with some special considerations. Radical reactions on alkenes cannot be performed with Cl2 or Br2, as they will add directly to the double bond. To eliminate this competing reaction, a new reagent is needed: N-bromosuccinimide (NBS) or N-chlorosuccinimide (NCS). These reagents, in conjunction with an organic peroxide, will selectively substitute for an allylic hydrogen. 3 : 2 : 1 1600 : 80 : 1 5 : 4 :1

O N Br O NBS

O N Cl O NCS

Allylic positions are right next to the double bond

CH3

Benzylic positions are right next to a benzene ring.

Upon H-atom abstraction, the allylic radical can be resonance delocalized, resulting in up to two products for each allylic hydrogen. A similar reaction occurs with benzylic radicals, however only the benzylic position is halogenated, maintaining the benzene structure.
Radical Reactions Notes Rev F07 NF Page 2 of 3

Chemistry 211

Clark College

Resonance delocalization of an allylic radical

Examples

Br2, ! Br Cl2, ! Cl Cl ! ! Cl Cl Cl major

minor

NBS, ! ROOR

Br Br Br These two products are equivalent

3 allylic positions, up to 6 different products

Br Br
Stereochemistry and Radical Substitutions

Br

So far, we have discussed the energetics and selectivity of radical halogenation, but not the stereochemistry of a radical reaction. To do this, we must consider the carbon-radical intermediate, typically formed in the first propagation step. We will use 2-methylpropane as an example, which results in a 3 radical:

When the radical forms, the carbon becomes sp2-hybridized. The single electron occupies the unhybridized p orbital. When this radical reacts, the new bond can form with the top part of the p orbital or the bottom, giving rise to a pair of enantiomers, and a racemic mixture of halogenated products.
Br Br
The new bond can form from the top or bottom

Br

+ Br

+ Br

Radical Reactions Notes

Rev F07 NF

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