Chemistry 125: Lecture 46
February 1, 2010
E2, SN1, E1
This
For copyright
notice see final
page of this file
E2 -Elimination
Text sec. 7.9
Rate influenced by:
[base]  attack occurs during (or before) rate-determining-step
nature of leaving group  it leaves during (or before) rds
H isotope (kinetic isotope effect)  C-H broken during rds
Heavier atom,
lower ZPE
see Lecture 8: frames 21-22
ABN AON
ABN
kH > kD
ZPE
(kinetic)
C
H
D
but onlyFif bond
CH2 is weakened in
rate-determining
state
CHtransition
H
:OH
2
F
CH2
"E2 Elimination"
CCH2 H
O
H
D H OH
D O
E2 -Elimination
Anti
Stereochemistry sec 7.9c
but not dogmatic
Which
How to
should
test
experimentally?
be better?
Text sec. 7.9
(S) (R)
(more strained)
starting material is
already eclipsed
ABN AON
ABN
R
R
R
syn
trans
R
F
R
R
R
anti
cis
R
(anti hybrids overlap better)
CH2
CH2 H :OH
F
CH2
"E2 Elimination"
CH
H
OH
(S) (S) 2
E2 -Elimination
Text sec. 7.9
Regiochemistry (Saytzeff/Hofmann) sec 7.9d
“Saytzeff”
“Hofmann”
E2 -Elimination
Text sec. 7.9
E2 vs. SN2 (Sterics & Base Strength) sec 7.9b
Synthesis Games
sec. 7.10
Ethylene Oxide as C2 Source
N C and RC C as Nucleophiles
EtOH/H2O (4:1)
55°C
log (fraction of R-Br converted to HOR/min)
(0.01 M) NaOH + R-Br
1
HO-R + NaBr
Rate extrapolated from
lower temperature.
0
k2 (M-1min-1)
concerted
displacement
-1
Depends
on [OH-]
-2
slowed by
crowding
plus
~19%
E2
k1 (min-1)
D/A
accelerated
by crowding,
(CH3)3C+ cation
stabilization,
-3
polar solvent
-4
SN1
CH3
CH3CH2 (CH3)2CH (CH3)3C
Hughes
Ingold
(1933-1940)
SN1 and E1
sec. 7.6-7.8
Product Determined After Rate 7.6a
by Competition for Short-Lived Cation
SN1 and E1
sec. 7.6-7.8
Rearrangement of Short-Lived Cation p. 389
SN1 and E1
sec. 7.6-7.8
Net Inversion from Short-Lived Ion Pair
7.6b
(0.01 M) NaOH + tBu-Br
EtOH/H2O (4:1)
55°C
HO-t-Bu + NaBr
+ CH2=C(CH3)2
E2 or E1? How do you tell?
Overall rate (and % alkene) depends on [OH-]
Kinetic Isotope Effect shows whether H is
being transferred in rate-determining step.
5. (5 min) Give a real example of the influence of a change
of reactant structure on the ratio of SN2 to E2 products. Be
as specific and quantitative as you can. (You will need to
show the ratios for two different reactants.)
CH3-Br + OH
(CH3)3C-Br + OH-
Perspectives on Drastic Ratios
Synthetic Organic Chemist : Reliable High-Yield Tool
Physical-Organic Chemist : Definitive Ea Difference
Unambiguous interpretation of cause
e.g. Steric retardation of SN2 / 105 acceleration for t-Butyl via SN1
Perspectives on 50:50 Product Ratios
Synthetic Organic Chemist :
Deadly Influence on 12-Step Synthesis
(1/2)12 = 0.02% Yield
(Might provide optimizable lead)
Physical-Organic Chemist :
Valuable “Borderline” Reference
Allows Sensitive Tests of Subtle Influences.
e.g. isotope effect by competition
A lesson from E2
Elimination
In a Very Viscous Solvent Can Short-Range Motion
Jo
David’s
Question:
Constitute a Rate- (and Product-) Determining Step?
CH3
H3C
•
(1) Rotate
N2 + C4D9
NN
(1) Rotate CH3 NN
CD3
•
(2) Shift D atom
CH3
H3C
CD3
exothermic/easy/fast
• DD
CH3
CD2
CD3
•
N2 + C4H9
CD3
CD3
Radical-Pair
Radical-Pair
“Disproportionation”
If Step
1 (motion) is rate-limiting,
Combination
H- and D-transfer
UVproducts
Light should
(2) Shift H atom
CH
CD
3
3
form in equal amounts.
CH3
exothermic/easy/faster
(because their motions should be equally fast)
H3C
CD3
If Step 2 (atomCH
shift)
is rate-limiting,
3 CD
3
moreGenerates
H-transfersteric
product
should&form.
hindrance
kH/kDmoving
> 1 (kinetic
“isotope effect”)
requires
radicals
past N2
H3C
•
CD3
CH23 H •
CD3
CD3
t-Butylhydrazine
CH3
H3 C
CD3
N
CH3
N
CH3
(prepare from)
H3 C
CD33
CH
NH
CH3
NH2
CD3
?
To do his project, Jo David needed
to prepare this compound.
CH3
H2C
CH3
E2 >> SN2
H3 C
CH3
Cl
CH3
NH2
NH2
Smith-Lakritz
It is very common to change
a C=X double bond into
C=O and H2X (we’ll be discussing this)
C=N-R  C=O + H N-R
t-Butylhydrazine
CH3
H3 C
CH3
CD3
N
CH3
N
H3 C
CD33
CH
NH
CH3
CD3
NH2
???
Jo David Fine
April-October 1971
CH3
H3 C
MgCl
CH3
N
+
O
N
Happy
Ending:
Jo David
Fine
Jo David is now a respected
professor of dermatology at
Vanderbilt University, whose
son has graduated from Yale.
Jo David Fine Notebook p. 91 (October 1971)
Crucial Lesson (from S. Nelsen, U. Wisc.)
HCl salt easily
purified by
crystallization
CH3
H3 C
CH3
CD3
N
CH3
N
H3 C
NH
CD33
CH
NH2
CH3
CD3
When you need a compound,
% yield isn’t everything!
CH3
CH3
95%
H2C
5% SN1
H3 C
CH3
Major product a gas,
just “goes away”
E1 / E2
Cl
NH2
CH3
Cheap!
NH2
Happy Ending:
Jo David Fine’s successor found that in
fluid solvents, there was more H- than
D-transfer (atom transfer is ratelimiting),
but that in very viscous solvents at low
temperature this “kinetic isotope effect”
disappeared (there were equal amounts
of H- and D-transfer), because motion
had indeed become rate-limiting.
End of Lecture 46
Feb. 1, 2010
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