C341/Spring 2010
Chapter 8
Chapter 8 Outline:
Haloalakanes, Halogenation,
& Radical reactions
Cover 8.1-8.3 on your own
1. Halogenation of Alkanes
A. Mechanism of Halogenation
B. Regioselectivity & Stereoselectivity of Halogenation
2. Radical Autoxidation, Antioxidants & Free Radical Inhibitors
3. Radical Addition of HBr to Alkenes
Suggested homework problems: 8.8, 8.13, 8.22-8.26, 8.28-8.30.
We will learn to halogenate alkanes in a regioselective and stereoselective manner.
Once you know how to halogenate alkanes you will use alkyl halides to make other
functional groups in substitution and elimination reactions in chapter 9.
Page 1 of 15
C341/Spring 2010
1.
Chapter 8
Halogenation of Alkanes to Prepare RX
Halogenation of alkanes with Br2 and Cl2 is very common. (Reaction with F2 is too
violent, and reaction with I2 is too slow to be extremely useful.)
Example Halogenation reaction:
Br
NBS, h
CCl4, RT
OR
This is a substitution reaction, where a halogen substitutes a hydrogen.
Conditions for Halogenation:
1. X2 and hν (or high heat),
2.
OR
NBS (N-bromosuccinimide) in CCl4 at RT (NCS also exists) for allyl halides
O
NBS =
N
Br
N—Br (243 kJ/mol)
N—Cl (200 kJ/mol)
Br—Br (193 kJ/mol)
Cl—Cl (239 kJ/mol)
O
Page 2 of 15
C341/Spring 2010
Chapter 8
A. Mechanism of Radical Halogenation
Radical chain mechanism = intermediates are formed by homolytic cleavage of
bonds to form radical species.
Radical halogenation occurs in three steps:
1. Initiation – reactions that produce radicals
2. Propagation – reactions where radical form more radicals
3. Termination – reactions that terminate radicals
1. Initiation:
Cl
Cl
hν
Cl
Cl
A radical X●, once formed, rapidly reacts a σ-bond. Some compounds cleave
rather easily by homolytic cleavage:
CH 3CH2O
OCH 2CH3
80 oC
CH 3CH2O
OCH 2CH3
o Energy for bond cleavage can be supplied by light or heat
o λ = 200 – 700 nm provides 585 kJ to 167 kJ/mol
o peroxides have BDE = 125 – 167 kJ/mol, hence peroxides are often used as
“radical initiators”
o benzoyl peroxide is another common initiator:
Page 3 of 15
C341/Spring 2010
Chapter 8
2. Propagation:
(CH3)3C
(CH3)3C
(CH3)3C
Cl
H
Cl
Cl
(CH3)3C
Cl
Cl
HCl
Cl
Cl
3. Termination:
Cl
(CH3)3C
(CH3)3C
C(CH3)3
Cl
Cl
(CH3)3C
C(CH3)3
(CH3)3C
Cl
In reality, if more than one hydrogen is present, the starting material will keep
reacting with more X●.
Page 4 of 15
C341/Spring 2010
B.
Chapter 8
Regioselectivity & Stereoselectivity in Halogenation
The following reaction is “regioselective.”
Regioselectivity is 3° > 2° > 1°.
• for bromination, approximately 1600:80:1
• for chlorination, approximately 5:4:1
How do you explain the following outcome of the reaction in 2-methylbutane?
1st compare possible intermediates:
Why does the following reaction occur as it does?
Br
Br2, h
Which free radical is more stable? What dictates the major product?
Page 5 of 15
C341/Spring 2010
Chapter 8
Allylic =
Benzylic =
Based on BDE and resonance, one can conclude that an allylic radical is even more
stable than a 3o carbon radical.
Most times the most stable radical leads to the major product! The trick is
finding the hydrogen that has the weakest BDE to yield the most stable
intermediate.
Page 6 of 15
C341/Spring 2010
Chapter 8
Practice questions:
Homolytic bond cleavage. For the steroid below, place the following protons in
order of HOMOLYTIC bond dissociation energy AND provide descriptions for
the TYPES of each proton (e.g. 1o alkyl or 1o allyl, etc.).
Ha =
Hb
Hb=
Hc
He
Hc =
Hd
Hd =
O
Ha
Highest in bond energy
He =
>
>
>
>
Using the appropriate type of arrows, show both homolytic and heterolytic bond
cleavage below and provide the products below.
Homolytic bond cleavage: H3C
H
Heterolytic bond cleavage: H3C
H
Page 7 of 15
C341/Spring 2010
Chapter 8
Chlorination vs. bromination
Although alkanes undergo radical substitutions with both Cl2 and Br2, chlorination
and bromination exhibit two important differences.
1. Chlorination is faster than bromination.
2. Chlorination is unselective compared to bromination.
Page 8 of 15
C341/Spring 2010
Chapter 8
What about stereoselectivity of radicals?
Compare:
C
C
Radical halogenation reactions give racemic mixtures of products if chiral
products are possible.
For example, butane itself is not chiral, but reaction at the secondary carbon
provides a chiral product, 2-bromobutane.
Page 9 of 15
C341/Spring 2010
Chapter 8
Draw the monobromination product(s) for the following reactions.
Page 10 of 15
C341/Spring 2010
Chapter 8
2. Radical Autoxidation
Oxidation of lipids occurs through radical reactions, called auto-oxidation.
Oils are susceptible to allylic free radical oxidation by O2. Auto-oxidation of fatty
acids occur at the allylic sites:
Page 11 of 15
C341/Spring 2010
Chapter 8
Antioxidants – inhibiting unwanted free radical reactions
Free radicals arise normally during human metabolism.
o Sometimes the body’s immune system’s cells purposefully create them to
neutralize viruses and bacteria.
o Environmental factors such as pollution, radiation, cigarette smoke and
herbicides can also breed free radicals.
o The body has inherent mechanisms to handle free radicals.
o BUT if antioxidants are unavailable, or if the free-radical production becomes
excessive, damage can occur.
o As you may know, free radical damage accumulates with age.
Free Radical Inhibitors are added to many consumer products to stop products
from degrading via radical mechanisms.
o Vitamin E and BHT (butylated hydroxytoluene) re most common food
additives. They act as a sacrificial reactant. What intermediate is formed?
Page 12 of 15
C341/Spring 2010
Chapter 8
Natural Antioxidants
e.g. Vitamin E & Vitamin C – water and fat soluble antioxidants
They both act as scavengers, helping to prevent cell and tissue damage that could
lead to cellular damage and disease.
Bioflavonoids - Naturally Occurring Phenols:
Over 5000 naturally occurring flavonoids have been characterized from various
plants and classified according to their chemical structure.
B
A
The skeleton above can be represented as the C6 - C3 - C6 system.
Flavonoids are:
o Plant pigments that lend flowers and herbs their yellow, orange and red color.
o Found in fruits, vegetables and processed plant–derived foods like tea, wine,
chocolate (esp. dark chocolate).
o Lend the beneficial effects of fruits and vegetables
o These benefits include:
o Anti-inflammatory, anti-allergic, anti-cancer activity, improved blood
flow and cardiovascular diseases, antioxidant properties
Page 13 of 15
C341/Spring 2010
Chapter 8
Bioflavanoids
Quercetin is a flavonoid (flavonol), found in citrus fruit, buckwheat and onions.
Quercetin is thought to help to prevent some types of cancer,
Quercetin
Epicatechin improves blood flow and helps improve cardiac health. Cocoa, the
major ingredient of dark chocolate, contains relatively high amounts of epicatechin
and has been found to have nearly twice the antioxidant content of red wine and up
to three times that of green tea.
Epicatechin
Page 14 of 15
C341/Spring 2010
Chapter 8
3. Radical Addition of HBr to Alkenes
Addition of HBr to alkenes gives either Markovnikov addition or nonMarkovnikov 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.
Page 15 of 15