Chem 125 Lecture 573/4/09
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CH3-Br + OH-
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)3C-Br + OH-
Perspectives on Drastic Product Ratios
Synthetic Organic Chemist : Reliable High-Yield Tool
Physical-Organic Chemist : Definitive Ea DifferenceUnambiguous interpretation of cause
e.g. syn- vs. anti-hydrogenation of acetylene
e.g. Steric retardation of SN2 / 105 acceleration for t-Butyl via SN1
Perspectives on 50:50 Product Ratios
Physical-Organic Chemist : Valuable “Borderline” Reference
Synthetic Organic Chemist : Deadly Influence on 12-Step Synthesis
(1/2)12 = 0.02% Yield
(Might provide optimizable lead)
Allows Sensitive Tests of Subtle Influences.e.g. isotope effect by competition
A lesson from E2 Elimination
If Step 1 (motion) is rate-limiting, H- and D-transfer products should
form in equal amounts. (because their motions should be equally fast)
If Step 2 (atom shift) is rate-limiting, more H-transfer product should form.
kH/kD > 1 (kinetic “isotope effect”)
In a Very Viscous Solvent Can Short-Range Motion Constitute a Rate- (and Product-) Determining Step?
Generates steric hindrance & requires moving radicals past N2
N
N
CH3
CH3
H3C CD3
CD3
CD3
•
•
UV LightCH3
CH3
H3C
CD3
CD3
CD3
Radical-PairCombination
CH3
CH3
H3C CD2 CD3
CD3
•
•
DD
(1) Rotate N2 + C4D9
(2) Shift D atomexothermic/easy/fast
N
N
Radical-Pair“Disproportionation”
(1) Rotate N2 + C4H9
(2) Shift H atomexothermic/easy/faster
CD3
CD3
CD3
CH3
H3CCH3 HCH2
•
•
Jo David’s Question:
NN
NN
t-Butylhydrazine
CH3
CH3
H3C NH
NH2
CH3
CH3
H3C Cl NH2
NH2
(prepare from)
CH3
CH3
H2C
?To do his project, Jo David needed to prepare this compound.
E2 >> SN2
CH3
CH3
H3C N
N
CD3
CH3
CD3
CD3
Smith-Lakritz
It is very common to change a C=X double bond into
C=O and H2X (we’ll discuss this soon)
C=N-R C=O + H2N-R
NN- +
t-Butylhydrazine
CH3
CH3
H3C NH
NH2
CH3
CH3
H3C MgCl
??? Jo David FineApril-October 1971
O
CH3
CH3
H3C N
N
CD3
CH3
CD3
CD3
Jo David Fine
Jo David Fine Notebook p. 91 (October 1971)
Jo David is now a respectedprofessor of dermatology at Vanderbilt University, whose son has graduated from Yale.
Happy Ending:
Crucial Lesson (from S. Nelsen, U. Wisc.)
CH3
CH3
H3C NH
NH2
CH3
CH3
H3C Cl NH2
NH2
CH3
CH3
H2C95%
5% SN1When you need a compound, % yield isn’t everything!
HCl salt easilypurified by
crystallization
E1 / E2
Major product a gas,just “goes away”
CH3
CH3
H3C N
N
CD3
CH3
CD3
CD3
Happy Ending:
Jo David Fine’s successor found that in fluid solvents, there was more H- than D-transfer (atom transfer is rate-limiting), 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.
Chapter 10Alcohols and Thiols
Sections 10.1-10.3C
6th ExamMean 76.2
1/3 > 83 2/3 > 74
Sum of Two ExamsMean 133
1/3 > 144 2/3 > 126
End of Lecture 57March 4, 2009