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Chapter 10Radical Reactions

t Often called free radicalst Formed by homolytic bond cleavaget Radicals are highly reactive, short-lived species

l Single-barbed arrows are used to show movement of single electrons

Radicals are intermediates with an unpaired electron

H. Cl.

Hydrogen radical

Chlorine radical

What are radicals?

Methyl radical

t Usually begins with homolysis of a relatively weak bond such as O-O or X-X

t Initiated by addition of energy in the form of heat or light

Production of radicals

t Radicals seek to react in ways that lead to pairing of their unpaired electron

t Reaction of a radical with any species that does not have an unpaired electron will produce another radicall Hydrogen abstraction is one way a halogen radical can react

to pair its unshared electron

Reactions of radicals

Electronic structure of methyl radical Atoms have higher energy (are less stable) than the molecules they can form1. The formation of covalent bonds is exothermic2. Breaking covalent bonds requires energy ( i.e. is

endothermic)

The homolyticbond dissociation energy is abbreviated DHo

Bond Dissociation Energies

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t Homolytic Bond Dissociation energies can be used to calculate the enthalpy change (∆ Ho) for a reaction

t DHo is positive for bond breaking and negative for bond forming

Bond Dissociation Energies and Heats of Reaction

?Ho = sum of DHo for products (-) and reactants (+)

A negative heat of reaction means reaction is exothermic

? Ho is not dependant on the mechanism; only the initial and final states of the molecules are considered

Consider the possible reaction of H2 with Cl2

Example of using Bond Dissociation Energies

Reaction is exothermic, more energy is released in forming the 2 H-Cl bonds of product than is required to break the H-H and Cl-Cl bonds of reactants

Table of bond dissociation energies in text, p. 430

Note X-X bonds are weak

A:B à A. + B.

Relative stability of organic radicals

Compare the DHofor the primary and secondary hydrogens in propane

Since less energy is needed to form the isopropyl radical (from same starting material), the isopropyl radical must be more stable

Diff = 10 kJ/mol

Using the same table, the tert-butyl radical is more stable than the isobutyl radical

Relative Stability of organic radicals

Diff = 22 kJ/mol

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The relative stabilities of carbon radicals follows the same trend as for carbocationsl The most substituted radical is most stable l Radicals are electron deficient, as are carbocations, and

are therefore also stabilized by hyperconjugation

Relative Stability of Free Radicals Energy diagrams for formation of radicals

Alkanesundergo substitution reactions with halogens (fluorine, bromine and chlorine) initiated by heat or light

t Radical halogenation can yield a mixture of halogenated compounds because all hydrogen atoms in an alkane are capable of substitutionl For example, all degrees of methane halogenation will be seen

t Monosubstitution can be achieved by using a large excess of the alkane

The Reactions of Alkanes with Halogens

t Chlorination of higher alkanes leads to mixtures of monochlorinated product (and more substituted products)

Chlorine is relatively unselective and does not greatly distinguish between type of hydrogen

Chlorination

If there were zero selectivity, the tertiary product would be 1/9 of the primary product, whereas it is actually 2/3 so there is a preference of about 5-fold

t The reaction mechanism has three distinct aspects: 1. Chain initiation2. Chain propagation3. Chain termination

Chain initiation – Step 1l Chlorine radicals form when the reaction mixture is

subjected to heat or light

Recall that the Cl-Cl bonds is relatively weak

Mechanism of Chlorination: a Chain Reaction

Chain propagation (2 steps repeated many times)l A chlorine radical reacts with a molecule of methane to

generate a methyl radicall A methyl radical reacts with a molecule of chlorine to yield

chloromethane and regenerate chlorine radicall The new chlorine radical reacts with another methane

molecule, continuing the chain reaction

Chlorination of Methane: Mechanism of Reaction

A single initiation step can lead to thousands of propagation steps, hence the term chain reaction

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Electron flow in the mechanismOccasionally the reactive radical intermediates are quenched by

reaction pathways that do not generate new radicals

The reaction of chlorine with methane requires constant irradiat ion to replace radicals quenched in chain-terminating steps

Chain termination

The chain propagation steps have overall ∆Ho= -101 kJ mol-1 and are highly exothermic

Energy Changes in the Chlorination of Methane

t Overall Free-Energy Change: ∆ Go = ∆Ho - T (∆ So) t In radical reactions such as the chlorination of methane the

overall entropy change (∆ So) in the reaction is smallt Thus ∆Ho values closely approximate the ∆ Go values

t ∆ Go = -102 kJ mol-1 and ∆ Ho = -101 kJ mol-1 for this reaction

Bond Energies a good approximation of free energy changes

When using enthalpy values (∆ Ho) the term for the difference in energy between starting material and the transition state is the energy of activation (Eact)l Recall when free energy of activation (∆ Go) values are used

this difference is ∆ G‡

l For the chlorination of methane the Eact values have been measured

Activation Energies for Chlorination of Methane

1. A reaction in which bonds are broken will have Eact > 0 even if a stronger bond is formed and the reaction is highly exothermic

Energy of activation values can be predicted

Bond forming always lags behind bond breaking

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2. An endothermic reaction which involves bond breaking and bond forming will always have Eact > ∆Ho

Energy of activation values can be predicted 3. A gas phase reaction in which only bond homolysis occurs has ∆Ho = Eact

4. A gas phase reaction in which small radicals combine to form a new bond usually has Eact = 0

The order of reactivity of methane substitution with halogens is: fluorine > chlorine > bromine > iodine

The order of reactivity is based on the values of Eact for the first step of chain propagation and ∆ Ho for the entire chain propagation

The energy values of the initiation step are unimportant since they occur so rarelyl On the basis of ∆ Ho values for X2, the initiation step

iodination should be most rapid

Reaction of Methane with Other Halogens

Fluorination has a very low value for Eact in the first step and ∆Ho is extremely exothermic

Fluorination reactions are explosive

Fluorination

Chlorination

Chlorination is also highly exothermic overall, but more controllable with a higher value of Eact and lower overall ∆Ho values

Bromination

The bromine atom has a significant Eact in the first step of propagation so the reaction is much more controllable and selective.

Still exothermic overall

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Iodination?

1. High Eact in first propagation step means very few successful collisions

2. Overall reaction is endothermic

Direct iodination is not a useful reaction

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t Monochlorination of alkanes proceeds with limited selectivityl Tertiary hydrogens roughly 5 times more reactive than primaryl Secondary hydrogens roughly 3.5 times more reactive than primary

l Eact for abstraction of a tertiary hydrogen is slightly lower because of increased stability of the intermediate tertiary radical

l Chlorination occurs so rapidly it cannot distinguish well between classes of hydrogen and so is not very selective

Halogenation of Higher Alkanes

Based on relative reactivitiesof 1:3.5:5 per H for 1 o, 2o, 3o H’s, predicted product ratios would be 29: 24: 33: 14

Chlorination is synthetically useful when molecular symmetry limits the number of possible substitution products

Useful Chlorinations

ClCl2

heat o r UV

t Bromine is much less reactive but more selective than chlorine in radical halogenation

Selectivity of Bromine

Bromination can be a practical method to make alkyl bromides, whenever one potential radical is more stable than the others

Would fluorination be selective?

t Fluorine shows almost no discrimination in replacement of hydrogens because it is so reactive

t So reactive that only per fluoro compounds (all H replaced by F) are made via direct fluorination (and then very carefully)

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Summary of halogenation of alkanes Stereochemistry and halogenation

t If a radical is formed at a single chiral center, the product isracemic

HBr2

UV

Br

(R) Racemic (1:1 R + S)

C

Demonstrates that radical must be planar with equal faces (or so rapidly inverting that all “memory” of chirality is lost)

t A reaction of achiral starting materials which produces a product with a stereogenic carbon will produce a racemic mixture

Reactions that Generate Tetrahedral Stereogenic Carbonst When a molecule with one or more stereogenic carbons reacts

to create another stereogenic carbon, the two diastereomericproducts are not produced in equal amounts.l The intermediate radical is chiral and and reactions on the two

faces of the radical are not equally likely

Generation of a Second StereogenicCarbon

Addition of hydrogen bromide in the presence of peroxides gives anti-Markovnikov addition

Works only for HBr: the other hydrogen halides do not give this type of anti-Markovnikov addition

Anti-Markovnikov Addition of HBr to Alkenes

Steps 1 and 2 of the mechanism are chain initiation steps which produce a bromine radical

Mechanism for the Anti -Markovnikov Addition of HBr

A free radical chain mechanism

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In step 3, the first step of propagation, a bromine radical adds to the double bond to give the most stable of the two possible carbon radicals (in this case, a 2o radical)l Attack at the 1o carbon is also less sterically hindered

Step 4 regenerates a bromine radical

The new bromine radical reacts with another equivalent of alkene, and steps 3 and 4 repeat in a chain reaction

• 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 10 radical2. Path [B] forms the more stable 20 radical

Why the anti-Markovnikov Addition?

• The more stable 20 radical forms faster, so Path [B] is preferred.

Controlling Addition of HBr to Alkenes

Early studies of HBr addition gave contradictory results –sometimes Markovnikov addition and sometime anti-Markovnikov

To favor “normal” addition, remove possible traces of peroxides from the alkene and use a polar, protic solvent

To favor anti-Mark, add peroxide and use non-polar solvent

Very useful for your synthetic tool box

Polymers are macromolecules made up of repeating subunitsl The subunits used to synthesize polymers are called monomers

Polyethylene is made of repeating subunits derived from ethylenel Polyethylene is called a chain-growth polymer or addition polymer

t Polystyrene is made in an analogous reaction using styrene as the monomer

Radical Polymerization of Alkenes

n= large number

A very small amount of diacyl peroxide is added in initiating the reaction so that few, but very long polymer chains are obtained

The propagation step simply adds more ethylene molecules to a growing chain

Initiator used to start a chain reaction mechanism

Produces an alkyl radical to initiate chain

Chain growth can terminate by combination of two radicals or by“disproportionation” (abstracting a H from the ß-carbon of the growing radical of another chain)

Chain termination

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Chain branching can occur by abstraction of a hydrogen atom on the same chain and continuation of growth from the main chain

“backbiting”

Chain branching

This cross-linking of polymer chain will modify properties of the polymer by stiffening its flexibility

Some other addition polymers from common alkenes

Note the regular alternation of the Z groups, called head to tail, since the addition step always produces the more stable radical

Some common Polymers

Superglue

t Some monomers can also be polymerized by nucleophiles

Molecular oxygen is a diradical

t Each oxygen has 6 electrons in outer shell = 12t Bonding orbitals accommodate the first ten, but last two go

one each into degenerate anti-bonding orbitals

Oxygen readily oxides many organic molecules

t Fast oxidation = combustiont Slow oxidation = auto-oxidation at activated sites

of polyunsaturated compounds, ethers and some biomolecules

t Other reactive forms of oxygen:l Singlet oxygenl Superoxide (O2

.- = an anion radical)l Ozone (O3)

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• Naturally occurring antioxidants such as vitamin E prevent radical reactions that can cause cell damage.

• Synthetic antioxidants such as BHT are added to packaged and prepared foods to prevent oxidation and spoilage.

Antioxidants

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