8-8-11

Radical Chain MechanismRadical Chain Mechanism Chain initiation:Chain initiation: A step in a chain reaction

characterized by formation of reactive intermediates (radicals, anions, or cations) from nonradical or noncharged molecules.

light +Cl Cl Cl• •Clor heat

Step 1:

8-8-22

Radical Chain MechanismRadical Chain Mechanism Chain propagation:Chain propagation: A step in a chain reaction

characterized by the reaction of a reactive intermediate and a molecule to form a new radical or reactive intermediate and a new molecule.

Chain length:Chain length: The number of times the cycle of chain propagation steps repeats in a chain reaction.

CH3CH2•

CH3CH2 H CH3CH2•

CH3CH2 Cl

H Cl•Cl

•ClCl Cl

+

+

Step 2:

Step 3:

+

+

8-8-33

Radical Chain MechanismRadical Chain Mechanism Chain termination:Chain termination: A step in a chain reaction that

involves destruction of reactive intermediates.

CH3CH2

CH3CH2

Cl

CH2CH3

Cl Cl

CH3CH2 CH2-CH2

H

Cl Cl

CH3CH2-Cl

CH3CH3

CH3CH2-CH2CH3

CH2=CH2

•

• •

Step 6:

Step 7:

•

••

•

+

Step 4:

Step 5:

+

+

+

+

•

8-8-44

Chain Propagation StepsChain Propagation Steps For any set of chain propagation steps, their• equations add to the observed stoichiometry.• enthalpies add to the observed H0.

CH3CH2-H •Cl

CH3CH2• Cl-Cl

CH3CH2-H Cl-Cl

CH3CH2•

CH3CH2-Cl

CH3CH2-Cl

•Cl

H-Cl

H-Cl

+

+ +

+

+422 -431

+247 -355

-9 (-2)

-108 (-26)

+ + -117 (-28)

H0, kJ/mol

(kcal/mol)

8-8-55

Regioselectivity?Regioselectivity? The regioselectivity of chlorination and

bromination can be accounted for in terms of the relative stabilities of alkyl radicals (3° > 2° > 1° > methyl).

But how do we account for the greater regioselectivity of bromination (1600:80:1) compared with chlorination (5:4:1)?

8-8-66

Hammond’s PostulateHammond’s Postulate Hammond’s Postulate:Hammond’s Postulate: The structure of the

transition state: • for an exothermic step is reached relatively early in

the reaction, and resembles the reactants of that step more than the products.

• for an endothermic step is reached relatively late in the reaction and resembles the products of that step more than the reactants.

This postulate applies equally well to the transition state for one-step reactions and to each transition state in a multi-step reaction.

8-8-77

Hammond’s PostulateHammond’s Postulate (a) A highly exothermic reaction (b) A highly endothermic reaction

8-8-88

Hammond’s PostulateHammond’s Postulate• In the halogenation of an alkane, hydrogen abstraction (the rate-

determining step) is exothermic for chlorination but endothermic for bromination

H

H-Br

H-Br

Cl

Cl

Br

Br

H-Cl

H-Cl

H

-431 (-103)

++ +54 (+13)

-431 (-103)+405 (97)

+ +

+ +

-368 (-88)

-26 (-6)

+37 (+9)

+ +

Reaction step

-9 (-2)

-368 (-88)

+422 (101)

+422 (101)

+405 (97)

17 (4)

17 (4)

H

H

H

[kJ (kcal)/mol]

•

•

•

••

•

•

•

8-8-99

Hammond’s PostulateHammond’s Postulate Because hydrogen abstraction for

chlorination is exothermic,• the transition state resembles the alkane and a

chlorine atom.• there is little radical character on carbon in the

transition state.• regioselectivity is only slightly influenced by

radical stability.

8-8-1010

Hammond’s PostulateHammond’s Postulate Because hydrogen abstraction for bromination

is endothermic,• the transition state resembles an alkyl radical and

HBr• there is significant radical character on carbon in the

transition state.• regioselectivity is greatly influenced by radical

stability.• radical stability is 3° > 2° > 1° > methyl, and

regioselectivity is in the same order.

8-8-1111

Hammond’s PostulateHammond’s Postulate Transition states and energetics for hydrogen

abstraction in the radical chlorination and bromination of 2-methylpropane (isobutane).

8-8-1212

StereochemistryStereochemistry When radical halogenation produces a chiral

center or takes place at a hydrogen on a chiral center, the product is a racemic mixture of R and S enantiomers.

• For simple alkyl radicals, the carbon bearing the radical is sp2 hybridized and the unpaired electron occupies the unhybridized 2p orbital (see next screen).

+ +Butane (R,S)-2-Bromobutane

(racemic)

heator lightCH3CH2CH2CH3 Br2 CH3CH2CHCH3 HBr

Br

8-8-1313

StereochemistryStereochemistry Radical bromination of butane.

8-8-1414

Allylic HalogenationAllylic Halogenation Allylic carbon:Allylic carbon: A C adjacent to a C-C double

bond. Allylic hydrogen:Allylic hydrogen: An H on an allylic carbon.

• an allylic C-H bond is weaker than a vinylic C-H bond.

+ +

Propene 3-Chloropropene (Allyl chloride)

350°CCH2=CHCH3 Cl2 CH2=CHCH2Cl HCl

H

C C

C

H H

HH H

+464 kJ /mol+372 kJ/mol

8-8-1515

Allylic BrominationAllylic Bromination Allylic bromination using NBS

Succinimide3-Bromo-cyclohexene

Cyclohexene

+

N-Bromo-succinimide

(NBS)

+ h

Br

N Br

O

O

N H

O

O

CH2Cl2

8-8-1616

Allylic BrominationAllylic Bromination A radical chain mechanism• Chain initiation

• Chain propagation

N

O

O

Brh

N•

O

O

•Br+

+ •+•

• ++ •CH2=CHCH2-H Br CH2=CHCH2 H-Br

CH2=CHCH2 Br-Br CH2=CHCH2-Br Br

8-8-1717

Allylic BrominationAllylic Bromination

• chain termination

NBS neutralizes HBr and the protonated amide then provides Br2 for the chain process.

Br• •Br

CH2=CHCH2•

CH2=CHCH2• •Br

•CH2CH=CH2

Br-Br

CH2=CHCH2-Br

CH2=CHCH2-CH2CH=CH2

+

+

+

++ N-H

O

O

N-Br

O

O

H-Br Br2

8-8-1818

The Allyl RadicalThe Allyl Radical A hybrid of two equivalent contributing structures.

(Equivalent contributing structures)

• •CH2 CH CH2 CH CH2CH2

8-8-1919

The Allyl RadicalThe Allyl Radical Molecular orbital model of the allyl radical. Combination

of three 2p orbitals gives three molecular orbitals.

8-8-2020

The Allyl RadicalThe Allyl Radical Unpaired electron spin density map of the allyl radical• Unpaired electron density (green cones) appears only

on carbons 1 and 3

8-8-2121

Allylic HalogenationAllylic Halogenation

• ProblemProblem Account for the fact that allylic bromination of 1-octene by NBS gives these isomeric products

NBS

CH2Cl2 Br

Br12

3 12

3+

1-Octene 3-Bromo-1-octene(racemic, 17%)

1-Bromo-2-octene(83%)

8-8-2222

Radical AutoxidationRadical Autoxidation

Autoxidation:Autoxidation: Oxidation requiring oxygen, O2, and no other oxidizing agent.• Occurs by a radical chain mechanism similar to that

for allylic halogenation.• In this section, we concentrate on autoxidation of

the hydrocarbon chains of polyunsaturated triglycerides.

• The characteristic feature of the fatty acid chains in polyunsaturated triglycerides is the presence of 1,4-dienes.

• Radical abstraction of a doubly allylic hydrogen of a 1,4-diene forms a particularly stable radical.

8-8-2323

Radical AutoxidationRadical Autoxidation

• Autoxidation begins when a radical initiator, X•, abstracts a doubly allylic hydrogen.

• This radical is stabilized by resonance with both double bonds.

H H

H H

H H

H

H H

R1 R2

H H

H H

H H

R1 R2

H H

H

X•

HH

R2R1

HH

H 1 21 2

8-8-2424

Radical AutoxidationRadical Autoxidation• The doubly allylic radical reacts with O2, itself a diradical, to

form a peroxy radical.• The peroxy radical then reacts with another 1,4-diene to give

a new radical, R•, and a hydroperoxide.

• Vitamin E, a naturally occurring antioxidant, reacts preferentially with the initial peroxy radical to give a resonance-stabilized phenoxy radical, which is very unreactive, and scavenges another peroxide radical.

H H

R1 R2

H H

HO

O

H

R2

H

R1

H H

HO

OH

H H

R1 R2

H H

H OO

H–R

Peroxy radical+ R•

A hydroperoxide

8-8-2525

Radical AutoxidationRadical Autoxidation

• vitamin E as an antioxidant

O

H-O

HO

•O

H

O

H

O

OR

OO

O

H

A phenoxy radical

A peroxide derived from vitamin E

3

a peroxide group

Vitamin E

3

3 3

OOR

8-8-2626

Radical Addition of HBr to AlkenesRadical Addition of HBr to Alkenes Addition of HBr to alkenes gives either Markovnikov addition

or non-Markovnikov addition depending on reaction conditions.

• Markovnikov addition occurs when radicals are absent.

• non-Markovnikov addition occurs when peroxides or other sources of radicals are present.

+ HBr

no peroxides

Br

2-Methyl-propene

2-Bromo-2-methylpropane

Markovnikovaddition

HBrBrperoxides

+

2-Methyl-propene

1-Bromo-2-methylpropane

Non-Markovnikovaddition

8-8-2727

Radical Addition of HBr to AlkenesRadical Addition of HBr to Alkenes

• Addition of HCl and HI gives only Markovnikov products.

• To account for the the non-Markovnikov addition of HBr in the presence of peroxides, chemists proposed a radical chain mechanism.

Chain initiation

R O

R-O O-R

H Br

R O RO

HR O Br

Two alkoxy radicalsA dialkylperoxide

Bromineradical

Step 1: +

+Step 2: +

8-8-2828

Radical Addition of HBr to AlkenesRadical Addition of HBr to Alkenes Chain propagation

Br

BrBr H

Br

BrH Br+

Step 3:

Step 4:

+

+

A 3° radical

1-Bromo-2-methylpropane

8-8-2929

Radical Addition of HBr to AlkenesRadical Addition of HBr to Alkenes Chain termination

This pair of reactions illustrates how the products of a reaction can be changed by a change in experimental conditions.• Polar addition of HBr is regioselective, with

protonation of the alkene preceding the addition of Br- to the more substituted carbon.

• Radical addition of HBr is also regioselective, with Br adding to the less substituted carbon.

Br BrBr Br

BrBr Br

BrStep 6:

Step 5: +

+

8-8-3030

HaloalkanesHaloalkanes

End Chapter 8End Chapter 8