Presentation on theme: "Chemistry 125: Lecture 46 February 1, 2010 E2, S N 1, E1 This For copyright notice see final page of this file."— Presentation transcript:
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 21-22 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. 7.10 Ethylene Oxide as C 2 Source
0 1 -2 -3 -4 log (fraction of R-Br converted to HOR/min) (CH 3 ) 3 C (CH 3 ) 2 CH SN1SN1 Hughes Ingold (1933-1940) 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. 7.6-7.8 Product Determined After Rate 7.6a by Competition for Short-Lived Cation
S N 1 and E1 sec. 7.6-7.8 Rearrangement of Short-Lived Cation p. 389
S N 1 and E1 sec. 7.6-7.8 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
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
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.