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Radical Reactions
© Prentice Hall 2001 Chapter 8 2
Alkanes: Fuels from
Petroleum
◼ Branched-chain hydrocarbons tend to
perform better in internal combustion
engines
© Prentice Hall 2001 Chapter 8 3
Reactivity of Alkanes
◼ Alkanes have only strong, nonpolar
bonds
◼ No reaction with nucleophiles or
electrophiles
◼ Not much reactivity - paraffins (little
affinity)
Free Radicals
◼ Free radicals can be thought of as sp2
hybridized or quickly interconverting sp3
hybridized
sp2 hybridized
◼ Free radicals form when bonds break
homolytically
◼ Note the single-barbed or fishhook arrow used
to show the electron movement
© Prentice Hall 2001 Chapter 8 6
Chlorination and Bromination
of Alkanes
© Prentice Hall 2001 Chapter 8 7
Chlorination and Bromination
of Alkanes
◼ Initiation: Homolytic cleavage
Cl Cl
400o C
or h
2 Cl
Br Br
400o C
or h
2 Br
radicals
Note that when an
arrowhead with a single
barb is used, it denotes
movement of a single
electron
© Prentice Hall 2001 Chapter 8 8
Chlorination and Bromination
of Alkanes
© Prentice Hall 2001 Chapter 8 9
Product Distribution
© Prentice Hall 2001 Chapter 8 10
Relative Stabilities of Alkyl
Radicals
© Prentice Hall 2001 Chapter 8 11
Reactivity–Selectivity Principle
◼ The very reactive chlorine atom will have
lower selectivity and attack pretty much
any hydrogen available on an alkane
◼ The less reactive bromine atom will be
more selective and tends to react
preferentially with the easy targets, i.e.
tertiary hydrogens
© Prentice Hall 2001 Chapter 8 12
Radical Substitution of Benzylic
and Allylic Hydrogens
© Prentice Hall 2001 Chapter 8 13
Radical Substitution of Benzylic
and Allylic Hydrogens
◼ Benzylic and allylic radicals are even more stable than tertiary alkyl radicals
◼ It should be easy for a halogen radical to abstract a benzylic or allylic hydrogen
© Prentice Hall 2001 Chapter 8 14
Radical Substitution of Benzylic
and Allylic Hydrogens
◼ Problem is that for the allyl radical there is a greater likelihood that the halogen will add electrophilically to the adjacent double bond
© Prentice Hall 2001 Chapter 8 15
Radical Substitution of Benzylic
and Allylic Hydrogens
◼ Electrophilic addition can be minimized
by maintaining the halogen at a very low
concentration
◼ Under these conditions, halogens can
substitute for allylic and benzylic
hydrogens
© Prentice Hall 2001 Chapter 8 16
Radical Substitution of
Benzylic and Allylic Hydrogens
◼ N-Bromosuccinimide (NBS) is a
good reagent for supplying low
concentrations of bromine radical
© Prentice Hall 2001 Chapter 8 17
Radical Substitution of
Benzylic and Allylic Hydrogens
◼ Bromine radical comes from the homolytic cleavage of the N–Br Bond
◼ Low concentration of Br2 is generated by the reaction of NBS with HBr
◼ Neither HBr nor Br2accumulate, so electrophilic addition is slow
+ Br + HBr
N
O
O
Br + HBr N
O
O
H + Br2
+ Br2
Br
+ Br
© Prentice Hall 2001 Chapter 8 18
Radical Substitution of
Benzylic and Allylic Hydrogens
◼ When a radical abstracts an allylic or
benzylic hydrogen, a radical that is
stabilized by resonance is obtained
© Prentice Hall 2001 Chapter 8 19
Radical Substitution of Benzylic
and Allylic Hydrogens
◼ If the resonance hybrid is not symmetrical,
more than one product is obtained
CH3CHCH CH3CH CHCH2CH3CH2CH CH2Br CH2
Br2
CH3CHCH
Br
CH3CH CHCH2BrCH2
+
3-bromo-1-butene 1-bromo-2-butene
© Prentice Hall 2001 Chapter 8 20
Stereochemistry of Radical
Substitution
© Prentice Hall 2001 Chapter 8 21
Stereochemistry of Radical
Substitution
© Prentice Hall 2001 Chapter 8 22
Stereochemistry of Radical
Substitution
◼ If a chirality center already exists, it may affect the distribution of products
◼ A pair of diastereomers will be formed, but in unequal proportions
© Prentice Hall 2001 Chapter 8 23
Stereochemistry of Radical
Substitution
© Prentice Hall 2001 Chapter 8 24
Reactions of Cyclic
Compounds
◼ Cyclic alkanes react with halogens in much the same way as acyclic compounds
+ Cl2
Cl
+ HCl
© Prentice Hall 2001 Chapter 8 25
Reactions of Cyclic
Compounds
◼ Cyclopropane undergoes electrophilic
addition much like an alkene
© Prentice Hall 2001 Chapter 8 26
Reactions of Cyclic
Compounds
◼ The bond angles in cyclopropane are 60o, which is considerably smaller than the ideal of 109o
◼ The sp3 hybrid orbital cannot overlap head-to-head - the bonds are weaker than normal
◼ Consequently three-membered rings undergo ring opening with electrophilic reagents
© Prentice Hall 2001 Chapter 8 27
Radical Reactions in
Biological Systems
◼ Alkanes (toxic) are converted to
alcohols (nontoxic) in the liver via a
radical mechanism
◼ An iron-containing enzyme,
cytochrome P450, catalyzes the reaction
© Prentice Hall 2001 Chapter 8 28
Radical Reactions in
Biological Systems
◼ A radical reaction also is involved in the
reduction of a ribonucleotide to a
deoxyribonucleotide
© Prentice Hall 2001 Chapter 8 29
Radical Reactions in
Biological Systems
◼ Protection from radical reaction is possible if a compound is present that reacts with the radical and forms a less reactive radical
© Prentice Hall 2001 Chapter 8 30
Radical Reactions in
Biological Systems
Autooxidation
◼ Autooxidation is the process by which compounds
react with molecular oxygen
◼ The process is generally very slow
◼ Some compounds such as ethers are
particularly susceptible to autooxidation
◼ Because hydroperoxides can be explosive,
ethers like diethyl ether must not be stored for
long periods of time
◼ They should be dated and used in a timely
fashion
Autooxidation
◼ Light accelerates the autooxidation process
◼ Dark containers are often used to store many chemicals such as vitamins
◼ In the absence of light, autooxidation is usually a slow process
◼ Compounds that can form a relatively stable C• radical upon H abstraction are especially susceptible to autooxidation. WHY?
◼ Consider the autooxidation of compounds with allylic or benzylic hydrogen atoms
Antioxidants
◼ Triglycerides are important to a healthy diet
◼ Autooxidation can occur at the allylic positions
causing the food to become rancid and toxic
Antioxidants
◼ Foods with unsaturated fatty acids have a short
shelf life unless preservatives are used
Antioxidants
◼ Preservatives can undergo H abstraction to quench the C•
radicals that form in the first step of autooxidation
◼ One molecule of BHT can prevent thousands of
autooxidation reactions by stopping the chain reaction
◼ How does BHT’s structure make it good at taking on a free
radical? Consider resonance and sterics
Natural Antioxidants
◼ Vitamins C is hydrophilic
◼ Vitamin E is hydrophobic
◼ What parts of the body do these
vitamins protect?
◼ For each vitamin, show its oxidation mechanism, and
explain how that protects the body from autooxidation