ch10 - radical reactions

What are radicals? Radicals are intermediates with an unpaired electron

Chapter 10 Radical Reactions

H.

Cl .

Hydrogen radical

Chlorine radical

Methyl radical

t Often called free radicals t Formed by homolytic bond cleavage t Radicals are highly reactive, short-lived species l Single-barbed arrows are used to show movement of single electrons

Production of radicals

Reactions of radicals

t Usually begins with homolysis of a relatively weak bond

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

such as O-O or X-X t Initiated by addition of energy in the form of heat or light

t Reaction of a radical with any species that does not have

unpaired electron an unpaired electron will produce another radical l Hydrogen abstraction is one way a halogen radical can react

to pair its unshared electron

Bond Dissociation Energies

Electronic structure of methyl radical

Atoms have higher energy (are less stable) than the molecules they can form 1. The formation of covalent bonds is exothermic 2. Breaking covalent bonds requires energy ( i.e. is

endothermic)

The homolytic bond dissociation energy is abbreviated DH o

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Bond Dissociation Energies and Heats of Reaction t Homolytic Bond Dissociation energies can be used to calculate the

enthalpy change ( ∆ Ho) for a reaction

Example of using Bond Dissociation Energies Consider the possible reaction of H 2 with Cl 2

t DH o is positive for bond breaking and negative for bond forming

?H o = 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

Table of bond dissociation energies in text, p. 430

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

A:B à A . + B.

Note X-X bonds are weak

Relative Stability of organic radicals

Relative stability of organic radicals

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

Compare the DHo for the primary and secondary hydrogens in propane

Diff = 22 kJ/mol Diff = 10 kJ/mol

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

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Relative Stability of Free Radicals

Energy diagrams for formation of radicals

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

are therefore also stabilized by hyperconjugation

The Reactions of Alkanes with Halogens Alkanes undergo substitution reactions with halogens (fluorine, bromine and chlorine) initiated by heat or light

Chlorination t Chlorination of higher alkanes leads to mixtures of

monochlorinated product (and more substituted products)

t Radical halogenation can yield a mixture of halogenated compounds

because all hydrogen atoms in an alkane are capable of substitution l For example, all degrees of methane halogenation will be seen t Monosubstitution can be achieved by using a large excess of the

alkane

Mechanism of Chlorination: a Chain Reaction t The reaction mechanism has three distinct aspects: 1. Chain initiation 2. Chain propagation 3. Chain termination

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

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

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

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

Chain initiation – Step 1

molecule, continuing the chain reaction

l Chlorine radicals form when the reaction mixture is

subjected to heat or light

Recall that the Cl-Cl bonds is relatively weak

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

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Chain termination

Electron flow in the mechanism

Occasionally 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

Energy Changes in the Chlorination of Methane

Bond Energies a good approximation of free energy changes t Overall Free-Energy Change: ∆ Go = ∆H o - T (∆ So) t In radical reactions such as the chlorination of methane the

overall entropy change ( ∆ So) in the reaction is small

t Thus ∆H o values closely approximate the ∆ Go values

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

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

Activation Energies for Chlorination of Methane

Energy of activation values can be predicted

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)

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

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

Bond forming always lags behind bond breaking

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Energy of activation values can be predicted

3. A gas phase reaction in which only bond homolysis occurs has ∆H o = Eact

2. An endothermic reaction which involves bond breaking

and bond forming will always have Eact > ∆Ho

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

Fluorination

Reaction of Methane with Other Halogens 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 ∆ H o for the entire chain propagation

Fluorination has a very low value for Eact in the first step and ∆H o is extremely exothermic Fluorination reactions are explosive

The energy values of the initiation step are unimportant since they occur so rarely l On the basis of ∆ H o values for X2 , the initiation step

iodination should be most rapid

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 E act in the first step of propagation so the reaction is much more controllable and selective. Still exothermic overall

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Halogenation of Higher Alkanes

Iodination?

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

Direct iodination is not a useful reaction

l E act 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

*

1. High Eact in first propagation step means very few successful collisions 2. Overall reaction is endothermic

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

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

Selectivity of Bromine

Cl 2

Cl

heat o r UV

Would fluorination be selective?

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

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

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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 is

racemic H

Br

Br2 UV

Racemic (1:1 R + S)

(R)

C

Reactions that Generate Tetrahedral Stereogenic Carbons t A reaction of achiral starting materials which produces a product

with a stereogenic carbon will produce a racemic mixture

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

Generation of a Second Stereogenic Carbon t When a molecule with one or more stereogenic carbons reacts

to create another stereogenic carbon, the two diastereomeric products 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

Anti-Markovnikov Addition of HBr to Alkenes Addition of hydrogen bromide in the presence of peroxides gives anti-Markovnikov addition

Mechanism for the Anti -Markovnikov Addition of HBr A free radical chain mechanism Steps 1 and 2 of the mechanism are chain initiation steps which produce a bromine radical

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

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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

Why the anti-Markovnikov Addition? •

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 radical 2. Path [B] forms the more stable 20 radical

•

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

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

Controlling Addition of HBr to Alkenes Early studies of HBr addition gave contradictory results – sometimes Markovnikov addition and sometime anti-Markovnikov

Radical Polymerization of Alkenes Polymers are macromolecules made up of repeating subunits l The subunits used to synthesize polymers are called monomers

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

n= large number

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

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

monomer

To favor anti-Mark, add peroxide and use non-polar solvent Very useful for your synthetic tool box

Initiator used to start a chain reaction mechanism A very small amount of diacyl peroxide is added in initiating the reaction so that few, but very long polymer chains are obtained

Chain termination 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)

Produces an alkyl radical to initiate chain

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

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Chain branching

Some other addition polymers from common alkenes

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

“backbiting”

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

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

Molecular oxygen is a diradical t Each oxygen has 6 electrons in outer shell = 12

Some monomers can also be polymerized by nucleophiles

Oxygen readily oxides many organic molecules

t Bonding orbitals accommodate the first ten, but last two go

one each into degenerate anti-bonding orbitals

t Fast oxidation = combustion t Slow oxidation = auto-oxidation at activated sites of polyunsaturated compounds, ethers and some biomolecules t Other reactive forms of oxygen: l Singlet oxygen l Superoxide (O2 .- = an anion radical) l Ozone (O3 )

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Antioxidants • 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.

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

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