Transcript Organic Chemistry - City University of New York

Radical Chain Mechanism
 Chain
initiation: A step in a chain reaction
characterized
by
formation
of
reactive
intermediates (radicals, anions, or cations) from
nonradical or noncharged molecules.
Step 1:
Cl
Cl
light
or heat
Cl•
+
•
Cl
8-1
Radical Chain Mechanism
 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.
Step 2: CH3 CH2
Step 3: CH3 CH2 •
 Chain
CH3 CH2 •
H + • Cl
+
Cl
Cl
+ H Cl
CH3 CH2 Cl + • Cl
length: The number of times the cycle of
chain propagation steps repeats in a chain
reaction.
8-2
Radical Chain Mechanism
 Chain
termination: A step in a chain reaction that
involves destruction of reactive intermediates.
Step 4:
CH3 CH2 • +
•
CH2 CH3
Step 5:
CH3 CH2 • +
•
Cl
Step 6:
Cl • +
•
CH3 CH2 - CH2 CH3
CH3 CH2 -Cl
Cl
Cl
Cl
H
Step 7:
CH3 CH2 • +
CH2 -CH2 •
CH3 CH3 + CH2 =CH2
8-3
Chain Propagation Steps
 For
any set of chain propagation steps, their
• equations add to the observed stoichiometry.
• enthalpies add to the observed H0.
H 0, k J/mol
CH3 CH2 -H + • Cl
+422
CH3 CH2 • + H- Cl
-431
(kcal/mol )
-9 (-2)
CH3 CH2 • + Cl-Cl
+247
CH3 CH2 -Cl + • Cl
-355
-108 (-26)
CH3 CH2 -H + Cl-Cl
CH3 CH2 -Cl + H- Cl
-117 (-28)
8-4
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)?
8-5
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.
8-6
Hammond’s Postulate
 (a)
A highly exothermic reaction
 (b) A highly endothermic reaction
8-7
Hammond’s Postulate
• In the halogenation of an alkane, hydrogen abstraction (the ratedetermining step) is exothermic for chlorination but endothermic
for bromination
H 
[kJ (kcal)/mol]
Reaction step
H
+•
•
Cl
+
+422 (101)
H
+
• Cl
•
+
+405 (97)
-9 (-2)
H-Cl
-26 (-6)
17 (4)
-431 (-103)
H
+
H-Cl
-431 (-103)
•
• Br
+
+422 (101)
H + • Br
+405 (97)
H-Br
+54 (+13)
-368 (-88)
•
+
H-Br
17 (4)
+37 (+9)
-368 (-88)
8-8
Hammond’s Postulate
 Because
hydrogen
abstraction
chlorination is exothermic,
for
• 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.
8-9
Hammond’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.
8-10
Hammond’s Postulate

Transition states and energetics for hydrogen
abstraction in the radical chlorination and bromination
of
2-methylpropane (isobutane).
8-11
Stereochemistry
 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.
CH 3 CH 2 CH 2 CH 3 + Br2
Bu tan e
h e at
Br
or li gh t CH CH CHCH +
HBr
3
2
3
(R,S )-2-Bromobu tan e
(racemic)
• For simple alkyl radicals, the carbon bearing the
radical is sp2 hybridized and the unpaired electron
occupies the unhybridized 2p orbital (see next
screen).
8-12
Stereochemistry
 Radical
bromination of butane.
8-13
Allylic Halogenation
 Allylic
carbon: A C adjacent to a C-C double
bond.
 Allylic hydrogen: An H on an allylic carbon.
CH2 = CHCH 3 + Cl 2
Prope n e
350°C
CH2 = CHCH 2 Cl + HCl
3-C hl oroprope n e
(Al lyl ch l ori de)
• an allylic C-H bond is weaker than a vinylic C-H bond.
H
H
+464 k J /mol
C
C
H
C
H
H
H
+372 k J/mol
8-14
Allylic Bromination
 Allylic
bromination using NBS
Br
O
+
N Br
O
Cycloh e xe n e N-Bromos u ccin i mi de
(NBS )
h
CH2 Cl 2
O
+
3-Bromocycl oh e xe n e
N H
O
S u cci n imi de
8-15
Allylic Bromination
A
radical chain mechanism
• Chain initiation
O
N Br
O
h
N• + •Br
O
O
• Chain propagation
CH2 = CHCH 2 - H +
• Br
CH2 = CHCH 2 •
Br- Br
+
CH2 = CHCH 2 • + H- Br
CH2 = CHCH 2 - Br + • Br
8-16
Allylic Bromination
• chain termination
Br•
+ • Br
Br- Br
CH2 = CHCH 2 • + • Br
CH2 = CHCH 2 • +
•
CH2 = CHCH 2 - Br
CH2 CH= CH 2
CH2 = CHCH 2 -CH2 CH= CH2
 NBS
neutralizes HBr and the protonated amide
then provides Br2 for the chain process.
O
N -Br + H- Br
O
O
N -H + Br2
O
8-17
The Allyl Radical

A hybrid of two equivalent contributing structures.
CH 2
CH
•
CH2
•
CH2
CH
CH2
(Equ i val en t con tribu tin g s tru ctu re s )
8-18
The Allyl Radical

Molecular orbital model of the allyl radical. Combination
of three 2p orbitals gives three p molecular orbitals.
8-19
The Allyl Radical

Unpaired electron spin density map of the allyl radical
• Unpaired electron density (green cones) appears only
on carbons 1 and 3
8-20
Allylic Halogenation
• Problem Account for the fact that allylic bromination of
1-octene by NBS gives these isomeric products
NBS
CH2 Cl2
1-Octen e
3
2
Br
3-Bromo-1-octen e
(racemic, 17%)
1
+
3
2
1
Br
1-Bromo-2-octen e
(83%)
8-21
Radical 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 1,4dienes.
• Radical abstraction of a doubly allylic hydrogen of a
1,4-diene forms a particularly stable radical.
8-22
Radical Autoxidation
• Autoxidation begins when a radical initiator, X•,
abstracts a doubly allylic hydrogen.
X•
R1 H H R2
H
H
H
R1
H
R1 1 H 2 R2
R2
H
1
H
H
H
H
H
H
H
H
H
2
H
H
H
H
H
H
• This radical is stabilized by resonance with both
double bonds.
8-23
Radical 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.
R1
H
R2
H
O
H
H
H
R1
O
H
H
H–R
R2
O
O
H
H
H
Peroxy radical
R1
H
H
R2
O
H
O
+ R•
H
H
H
A h yd roperoxid e
• 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.
8-24
Radical Autoxidation
• vitamin E as an antioxidant
O
O
H
H
3
3
•O
H-O
A phenoxy radical
Vitamin E
R
O
a peroxide
group
OOR
O
O
O
3
H
H
3
O
O
A peroxide derived from vitamin E
8-25
Radical 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.
Mark ovnikov
ad dition
+ HBr
no
peroxid es
2-Methylpropene
N on-Markovn ikov
addition
2-Bromo-2methylprop ane
+
2-Methylpropene
Br
HBr
p eroxides
Br
1-Bromo-2methylp ropan e
8-26
Radical 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
S te p 1: R-O O-R
R O
A di alk yl
pe roxide
S te p 2: R O
+
+
O R
Two alk oxy radicals
H
Br
R O H + Br
Bromin e
radi cal
8-27
Radical Addition of HBr to Alkenes
 Chain
propagation
Br
Step 3:
+
Br
A 3° radical
Br
Step 4:
Br
H +
Br
H
+ Br
1-Bromo-2methylpropan e
8-28
Radical Addition of HBr to Alkenes
 Chain
termination
Step 5:
Br +
Br
Br Br
Br
Step 6:

Br +
Br
Br
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 Brto the more substituted carbon.
• Radical addition of HBr is also regioselective, with Br
adding to the less substituted carbon.
8-29
Haloalkanes
End Chapter 8
8-30