Free Radical ReactionsHalogenation of Alkanes

RH + X2 RX + HX

Orbital hybridization in carbocations and carbanions:

Reactive Intermediates

Free radicals can be thought of as sp2 hybridized or quickly interconverting sp3 hybridized.

Reactive Intermediates:Free Radicals

RH + X2 RX + HX

explosive for F2

exothermic for Cl2 and Br2

endothermic for I2

Energetics

Halogenation Thermodynamics

Chlorination of Methane

carried out at high temperature (400 °C)

CH4 + Cl2 CH3Cl + HCl

CH3Cl + Cl2 CH2Cl2 + HCl

CH2Cl2 + Cl2 CHCl3 + HCl

CHCl3 + Cl2 CCl4 + HCl

Chlorination of Methane

Mechanism of Chlorination of Methane

The initiation step "gets the reaction going"by producing free radicals—chlorine atomsfrom chlorine molecules in this case.

Initiation step is followed by propagationsteps. Each propagation step consumes onefree radical but generates another one.

:..Cl..

: Cl..

: .. ..Cl..

: . :Cl.....+

Free-radical chain mechanism.

Initiation step: (Light or Heat is Necessary)

Mechanism of Chlorination of Methane

Which of the above initiates reactions most readily?

Question

A)

B)

C)

Cl:....

.H3C : H H : Cl:....H3C .+ +

First propagation step:

Second propagation step:

+ + Cl:....

.H3C . :..Cl..

: Cl..

: .. H3C....: Cl:

Mechanism of Chlorination of Methane

Cl:....

.H3C : H H : Cl:....H3C .+ +

Second propagation step:

+ +

+ +

First propagation step:

Cl:....

.H3C . :..Cl..

: Cl..

: ..

H3C : H H : Cl:....:..Cl

..: Cl

..: .. H3C

..

..: Cl:

H3C....: Cl:

Mechanism of Chlorination of Methane

Almost all of the product is formed by repetitivecycles of the two propagation steps.

Cl:....

.H3C : H H : Cl:....H3C .+ +

Second propagation step:

+ +

+ +

First propagation step:

Cl:....

.H3C . :..Cl..

: Cl..

: ..

H3C : H H : Cl:....:..Cl

..: Cl

..: .. H3C

..

..: Cl:

H3C....: Cl:

stop chain reaction by consuming free radicals

hardly any product is formed by termination stepbecause concentration of free radicals at anyinstant is extremely low

+H3C . Cl:....

. H3C....: Cl:

Termination Steps

Question

The step shown below is a _____________ step of the free-radical chlorination ofchloromethane.

A) initiationB) propagationC) chain-terminatingD) bond cleavage

Question

For the free-radical reaction below, light is involved in which of the following reactionsteps?

A) Initiation onlyB) Propagation onlyC) Termination onlyD) Initiation and propagation

Halogenation of Higher Alkanes

CH3CH3 + Cl2 CH3CH2Cl + HCl420°C

(78%)

Cl + Cl2 + HClh

(73%)

can be used to prepare alkyl chlorides from alkanes in which all of the hydrogens are equivalent to one another

Chlorination of Alkanes

Major limitation:

Chlorination gives every possible monochloride derived from original carbonskeleton.

Not much difference in reactivity ofdifferent hydrogens in molecule.

Chlorination of Alkanes

CH3CH2CH2CH3 Cl2h

Chlorination of butane gives a mixture of1-chlorobutane and 2-chlorobutane.

CH3CH2CH2CH2Cl

CH3CHCH2CH3

Cl

(28%)

(72%)

Example

Percentage of Product that Results from Substitution of Indicated Hydrogen if

Every Collision with Chlorine Atoms is Productive

10%

10%10%

10%

10%10%

10%

10%10%

10%

Percentage of Product that Actually Results from Replacement of Indicated Hydrogen

4.6%

4.6%4.6%

18%

18%18%

4.6%

4.6%4.6%

18%

divide by 4.6

4.64.6

= 1

184.6

= 3.9

A secondary hydrogen is abstracted 3.9 times faster than a primary hydrogen by a chlorine

atom.

4.6%18%

Relative Rates of Hydrogen Atom Abstraction

Similarly, chlorination of 2-methylbutane gives a mixture of isobutyl chloride and tert-butyl chloride

H

CH3CCH3

CH3

CH3CCH2Cl

CH3

H

Cl

CH3CCH3

CH3

h

Cl2

(63%)

(37%)

Question

How many monochlorination products do you expect to obtain from the chlorination of2-methylbutane?A) twoB) threeC) fourD) five

Percentage of Product that Results from Replacement of Indicated Hydrogen

7.0%

37%

377.0

divide by 7

7= 1

7= 5.3

A tertiary hydrogen is abstracted 5.3 times faster than a primary hydrogen by a chlorine atom.

Relative Rates of Hydrogen Atom Abstraction

Radicals - Resonance

?

Hyperconjugation contributes more to thermodynamic stability than resonance.

QuestionTrue (A) / False (B)

Vinyl free radicals are more thermodynamically stable than benzylic and allylic free radicals.

QuestionTrue (A) / False (B)

R3CH> R2CH2 >RCH3

chlorination: 5 4 1

bromination: 1640 82 1

Chlorination of an alkane gives a mixture of every possible isomer having the same skeletonas the starting alkane. Useful for synthesis only when all hydrogens in a molecule are equivalent.

Bromination is highly regioselective for substitution of tertiary hydrogens. Major synthetic application is in synthesis of tertiary alkyl bromides.

Selectivity of Free-radical Halogenation

Radicals - Bromination

How many mono-bromination products are expected from the following reaction?

A. 5 B. 4 C. 3 D. 2 E. 1

Question

Br2

light

Chlorination is useful for synthesis only when all of the hydrogens in a molecule are equivalent.

(64%)

Cl2h

Synthetic Application of Chlorination of an Alkane

Cl

Question

An alkane with a molecular formula of C8H18 reacts with Cl2 in the presence of light andheat to give a single monochloride C8H17Cl. What is the most reasonable structure for the starting alkane?A) CH3CH2CH2CH2CH2CH2CH2CH3

B) (CH3CH2)2CHCH2CH2CH3

C) (CH3)2CHCH2CH2CH(CH3)2

D) (CH3)3CC(CH3)3

Bromination is highly selective for substitution of tertiary hydrogens.

Major synthetic application is in synthesis of tertiary alkyl bromides.

(76%)

Br2

h

H

CH3CCH2CH2CH3

CH3

Br

CH3CCH2CH2CH3

CH3

Synthetic Application of Bromination of an Alkane

Question

Which of the following best describes a mechanistic feature of the free-radical bromination (Br2, light) of 2-methylpropane?A) The initiation step involves cleavage of a C-H bond.B) The free-radical (CH3)3C· is produced in one propagation step and reacts with Br2 in another.C) The reaction is characterized by the homolytic cleavage of the C-Br bond.D) The reaction is concerted; i.e., it occurs in a single step.

Which reaction has a faster rate? Which product is kinetically favored?

A. I) and I) B. II) and II) C. I) and II) D. II) and I)

Question

I) II)

Which reaction has a propagation step that is endothermic? Which reaction is more regioselective?

A. I) and I) B. II) and II) C. I) and II) D. II) and I)

Question

I) II)

Three mono-substituted isomers form in the halogenation of butane. The products are optically inactive.

Stereochemistry

Bromination of optically active 3-methylhexane produces only (S)-3-bromo-3-methylhexane.

QuestionTrue (A) / False (B)

How many products (including stereoisomers) are expected in the following halogenation?

A. 5 B. 4 C. 3 D. 2 E. 1

Br2

light

Question

Resonance and regioselectivity:

Allylic/Benzylic Bromination

A mixture is obtained that includes the di-brominated product.

Br-

Di-bromination can be avoided using a specialized reagent:N-bromosuccinimide (NBS)

N-bromosuccinimide (NBS)

Allylic/Benzylic Bromination

A. B. C. D.

NBS, h, CCl4

Br Br

BrBr

What is the major product of the following reaction?

Question

(A) Barbamide, a cyanobacterial peptide containing a trichloromethyl group and (B) dysidenin, a barbamide-related compound isolated from a sponge-cyanobacterial association

Halogenated Marine Natural Products

Polymers

Free radical conditions are frequently used to form polymers.Recall that a polymerization process joins together many small units called monomers in a long chain.

Radical Polymerization

Radical Polymerization

Radical polymerizations commonly proceed through a chain reaction mechanism.

Radical Polymerization

Radical Polymerization

Radical polymerizations generally produce chains of monomers with a wide distribution of lengths.

Because the mechanism proceeds through 1° carbon free radical intermediates, it is usually difficult.

Radical Polymerization

Branching is common in radical polymerizations.

Branching makes polymer materials more flexible, such as a polyethylene used for squeeze bottles.When catalysts are used to minimize branching, more rigid materials are produced, such as the material used for squeeze bottle caps.

Radical Polymerization

Many derivatives of ethylene are polymerized.

Radical Polymerization

Radical Polymerization

Stereoregular Polymers

atacticisotactic

syndiotactic

Atactic Polypropylene

Random stereochemistry of methyl groups attached to main chain (stereorandom)Properties not very useful for fibers etc.Formed by free-radical polymerization

Isotactic Polypropylene

Stereoregular polymer; all methyl groups onsame side of main chainUseful propertiesPrepared by coordination polymerization under Ziegler-Natta conditions

Syndiotactic Polypropylene

Stereoregular polymer; methyl groups alternate side-to-side on main chainUseful propertiesPrepared by coordination polymerization under Ziegler-Natta conditions

Properties of Polymers

Isotactic and syndiotactic polymers are stronger and stiffer due to their regular packing arrangement.

Anionic polymerization usually gives isotactic or syndiotactic polymers.

Free radical polymerization is nearly random, giving branched atactic polymers.

Free Radical Polymerization

Polystyrene & Others