Chemistry 125: Lecture 46 February 1, 2010 E2, S N 1, E1 This For copyright notice see final page of this file

F CH 2 CH 2 H:OH "E2 Elimination" ABN AON F H OH CH 2 Rate influenced by: C H H O C H O D D D k H > k D but only if bond is weakened in rate-determining transition state Heavier atom, lower ZPE see Lecture 8: frames ZPE (kinetic) [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 E2  -Elimination Text sec. 7.9

Stereochemistry sec 7.9c F CH 2 CH 2 H:OH "E2 Elimination" ABN AON F H OH CH 2 anti syn R R R R R R R R cis trans (R) (S) Anti but not dogmatic (anti hybrids overlap better) starting material is already eclipsed (more strained) Which should be better? How to test experimentally?

E2  -Elimination Text sec. 7.9 Regiochemistry (Saytzeff/Hofmann) sec 7.9d “Saytzeff” “Hofmann”

E2  -Elimination Text sec. 7.9 E2 vs. S N 2 (Sterics & Base Strength) sec 7.9b

Synthesis Games sec Ethylene Oxide as C 2 Source

N C and RC C as Nucleophiles

log (fraction of R-Br converted to HOR/min) (CH 3 ) 3 C (CH 3 ) 2 CH SN1SN1 Hughes Ingold ( ) CH 3 CH 3 CH 2 EtOH/H 2 O (4:1) 55°C NaOH + R-BrHO-R + NaBr k 2 (M -1 min -1 ) concerted displacement slowed by crowding k 1 (min -1 ) D/A accelerated by crowding, (CH 3 ) 3 C + cation stabilization, polar solvent (0.01 M) plus ~19% E2 Rate extrapolated from lower temperature. Depends on [OH - ]

S N 1 and E1 sec Product Determined After Rate 7.6a by Competition for Short-Lived Cation

S N 1 and E1 sec Rearrangement of Short-Lived Cation p. 389

S N 1 and E1 sec Net Inversion from Short-Lived Ion Pair 7.6b

EtOH/H 2 O (4:1) 55°C NaOH + tBu-BrHO-t-Bu + NaBr (0.01 M) + CH 2 =C(CH 3 ) 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.

CH 3 -Br + OH - 5. (5 min) Give a real example of the influence of a change of reactant structure on the ratio of S N 2 to E2 products. Be as specific and quantitative as you can. (You will need to show the ratios for two different reactants.) (CH 3 ) 3 C-Br + OH - Perspectives on Drastic Ratios Synthetic Organic Chemist : Reliable High-Yield Tool Physical-Organic Chemist : Definitive E a Difference Unambiguous interpretation of cause e.g. Steric retardation of S N 2 / 10 5 acceleration for t-Butyl via S N 1

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. k H /k D > 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 N 2 N N CH 3 CH 3 H 3 C CD 3 CD 3 CD 3 UV Light CH 3 CH 3 H 3 C CD 3 CD 3 CD 3 Radical-Pair Combination CH 3 CH 3 H 3 C CD 2 CD 3 CD 3 D D (1) Rotate N 2 + C 4 D 9 (2) Shift D atom exothermic/easy/fast N N Radical-Pair “Disproportionation” (1) Rotate N 2 + C 4 H 9 (2) Shift H atom exothermic/easy/faster CD 3 CD 3 CD 3 CH 3 H 3 C CH 3 H CH 2 Jo David’s Question: N N N N

t-Butylhydrazine (prepare from) ? To do his project, Jo David needed to prepare this compound. E2 >> S N 2 CD 3

Smith-Lakritz

It is very common to change a C=X double bond into C=O and H 2 X (we ’ ll be discussing this) C=N-R  C=O + H 2 N-R

- + t-Butylhydrazine ??? Jo David Fine April-October 1971 O CD 3

Jo David Fine Jo David Fine Notebook p. 91 (October 1971) Jo David is now a respected professor of dermatology at Vanderbilt University, whose son has graduated from Yale. Happy Ending:

Crucial Lesson (from S. Nelsen, U. Wisc.) 95% 5% S N 1 When you need a compound, % yield isn’t everything! HCl salt easily purified by crystallization E1 / E2 Major product a gas, just “goes away” CD 3 Cheap!

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.

End of Lecture 46 Feb. 1, 2010 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).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