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