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
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