1. HBr Addition to Alkenes and its “Regiochemistry”
Chemistry 125: Lecture 40 January 14, Reactivity-Selectivity “Principle”
HBr Addition to Alkenes
and its “Regiochemistry”
Rates of Chain Reactions
This
For copyright notice see final page of this file

2. Reactivity/Selectivity “Principle”
13.6
More Selective
k2/k1 ~ 4
k2/k1 ~ 35
11.1
G‡  0.8
G‡  4.5
Less Reactive
Less Selective 2
-2.1
-4.6
DGCl• 7
13.6
11.1
DGBr•
-2.1
1° abstraction
2° abstraction
More Reactive
-4.6

3. Reactivity/Selectivity “Principle”
13.6
More Selective
How can transition states be more different in energy than products are?
k2/k1 ~ 35
11.1
G‡  4.5
G  2.5!
Br H •R
Br• H R
Relative to H-CH3
•CH3
H•••CH3 H
CH3CCH3
CH3CCH3 H 7
13.6
11.1
DGBr• ?
R+ character can
be helpful near
the transition state.
Br H• R+
Plus a 3rd resonance structure 1° 2°
It is irrelevant in RH and R•
As we shall see next week, substituting
CH3 for H stabilizes cations a LOT.

4. (We’ll see dramatic examples when we discuss pericyclic reactions.)
Sometimes factors involved in stabilizing Transition States can be different from those involved in stabilizing either starting materials or products. In such cases we can’t easily rationalize activation energy changes on the basis of exothermicities.
(We’ll see dramatic examples when we discuss pericyclic reactions.)

5. Two Problems for Wednesday
(work in groups if you wish) 1.
If monochlorination of propane gives n-propyl chloride (43%) and isopropyl chloride (57%),
and monochlorination of 2-methylpropane gives t-butyl chloride (36%) and 1-chloro-2-methylpropane (64%),
predict the products from monochlorination of 2-methyl-butane.
HINT : Consult your textbooks on free-radical halogenation to be sure you are taking the statistics of H numbers into account properly.
2. Solve the puzzle on Slide 18.

6. Radical-Chain H-X Addition to Alkenes
C=C
cyclic
machinery •
C-C X • X
C-C X H
H-X

7. Radical-Chain H-X Addition to Alkenes10
-10
-20
-30
-40
-50 
Only HBr works fast enough in both steps.
But only HBr works.
Why?  
146
X-C-C•
(+ X-H) 83 83 99
X• + C=C
(+ X-H)
X-C-C-H
+ X• 83 99
116
Average Bond Energies F Cl Br I
146
135
= 17

8. “Regiospecificity” in Addition
H2C
CH3 H
H-X C
CH2
CH3 H X C
CH2
CH3 H X
for X = any halogen
occasionally anti-Markovnikov
but only with X = Br
Markovnikov “Orientation” (1870)
Understood in terms of initial addition of H+ (1930s)
(ionic mechanism to be discussed in three weeks)
Traced to peroxide catalysis (1933)
“Initiator” of radical chain

9. “Regiospecificity” in Addition
H2C
CH3 H
R-O-O-R
2 R-O•
R-O-H •Br
H-Br
secondary radical “more stable” C
•CH2
CH3 H Br C•
CH2
CH3 H Br
For discussion of radical chain addition see texts (e.g. JF pp )
Traced to peroxide catalysis (1933)
“Initiator” of radical chain

10. Catalytic Cycle Rate Law
R-H
X-H
k1 [RH] [X•]
cyclic
machinery • X • R
k2 [X2] [R•]
R-X
X-X
k1 [RH] [X•] = k2 [X2] [R•]
“this is a real democracy, catalysis” (K. B. Sharpless, 12/3/08)

11. But the two fluxes (cars/min) must be equal at steady state!
“If you get that [barrier] down, the rate goes way up. And if you get them all the same height, you're really rolling.”
“If there's a slow step, there's 99.9% of the titaniums that you need, stuck before this one mountain, that goes way up like Mount Everest.”
(Sharpless, 12/3/08)
But the two fluxes (cars/min) must be equal at steady state!
E-ZPass
Low rate constant
High rate constant
Cash
Low concentration
High concentration
k [ ] = k [ ]

12. Catalytic Cycle Rate Law
Summary:
When one step in a cycle is much slower than the others, the rate of cycling is pretty insensitive to the rate constant and concentration of incoming reagent for the fast step(s), because concentration of the minor form of cycling reagent adjusts to compensate.
Fractional changes in concen-tration of the dominant radical are much more modest.
R-H
X-H
small
k1 [RH] [X•] ~1
Rate  [RH]?
cyclic
machinery
( Rate  k1 ) X R • • ~0
Rate  [X2]?
( Rate insensitive to k2 )
Rate  [R• + X•]1
k2 [X2] [R•]
R-X
X-X
Suppose
X• is dominant
Double
[X2]
Double
[RH]
large
[R•]
[X•]
k2 [X2]
k1 [RH] =
[X•] 
[R•]  2 98 1 99 4 96
k1 [RH] [X•] = k2 [X2] [R•]
k1 [RH] [X•] grows = 1.96 fold.
2 • 96
1 • 98
k2 [X2] [R•] grows ~ fold; not at all !
2 • 1
1 • 2
Assuming [R•] + [X•] = Const

13. and Termination of Radical Chains
Initiation
and Termination of Radical Chains
Typically involves breaking a weak bond with heat, light, or e-
Cl-Cl h 2 Cl•
O-O  2 •O
HOOH e- HO- •OH
~30
kcal/mole

14. Both Radical-Molecule “Propagation” Reactions of the Chain “Machine” must be Fast, or X• and R• will find partners.
“Termination”

15. Kinetic Order in Initiator
1/2
Rate  [RO-OR] ? ki
Initiation : RO-OR RO•
Rate of forming radicals  [RO-OR] kt
Termination : 2 R’• R’-R’
Rate of destroying radicals  [R’•]2
at Steady State : [R’•]2  [RO-OR]
1/2

16. An Ionic Effect in Free-Radical Substitution
Termination
by H• transfer
(i-Pr)2NH
i-Pr -N
-C(CH3)2 • H H
R-H
(i-Pr)2N-H
slow
=C(CH3)2
~100
kcal/mole
~92
kcal/mole
(i-Pr)2N
add H • R 2
Cl-Cl Br-Br 46 R-Br 73
H-Cl H-Br 87.5
Charge keeps dominant radicals apart; inhibits termination.
~46
kcal/mole
dominant
~85
kcal/mole
(i-Pr)2N-Cl
R-Cl

17. Chlorination Selectivity20 40 60 80
100
Chlorination Selectivity
Isomer Percent
50% H2SO4 •
ROH half protonated
60% H2SO4 •
70% H2SO4 •
ROH fully protonated H + HO
CH2
CH3 ?
i-Pr HN +•
i-Pr HN +•
N.C. Deno, et al. (1971)

18. 30% H2SO4 gave a completely different product:
CH2
CH3 C O
92% yield!
which probably was formed from aldehyde
CH2
CH3 C O H
mostly formed by HOMO/LUMO (non-radical) “oxidation” HO
CH2
CH3 ?
Puzzle: Propose mechanisms to form aldehyde involving both substitution (radical or HOMO/LUMO) and elimination (reaction with base)
i-Pr N + H Cl
CH3 HN +•
N.C. Deno, et al. (1971)

19. End of Lecture 40 Jan. 14, 2011
Copyright © J. M. McBride Some rights reserved. Except for cited third-party materials, and those used by visiting speakers, all content is licensed under a Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0).
Use of this content constitutes your acceptance of the noted license and the terms and conditions of use.
Materials from Wikimedia Commons are denoted by the symbol
Third party materials may be subject to additional intellectual property notices, information, or restrictions.
The following attribution may be used when reusing material that is not identified as third-party content:
J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0