Presentation on theme: "Chemistry 125: Lecture 47 February 2, 2011 S N 2, E2, S N 1, E1 an Instructive Project Alkenes: Stability and Addition Mechanisms This For copyright notice."— Presentation transcript:
Chemistry 125: Lecture 47 February 2, 2011 S N 2, E2, S N 1, E1 an Instructive Project Alkenes: Stability and Addition Mechanisms This For copyright notice see final page of this file
CH 3 CCH 2 CH 3 + via S N 1 and E1 Demonstrates Cation Intermediate CH 3 CCH 2 I CH 3 CCH 2 CH 3 OH AgNO 3 H2OH2O Ag + CH 3 CCH 2 CH 3 + 1° Cation (unstable) + CH 3 CCH 2 CH 3 3° Cation (stable) -H + C-C as nucleophile in “S N 2” (e.g. J&F sec ) “Skeletal” Rearrangement
Doubleor ? CC H CC H CC H MinimumSingle HOMO-1 LUMO HOMO LUMO+1 “Hyperconjugation” ( HOMO-LUMO mixing) CC H CC H CC H CC H
CCCCCC H 2 CH Doubleor ?MinimumSingle LUMO+1 HOMO H H H
S N 1 and E1 Short-Lived Ion Pair Gives Cl OHHO 40% retention60% inversion acetone H 2 O Cl - + Cl - temporarily blocks the “retention” face. Net Inversion! H 2 O: 80% racemization (should be 100% if there is a planar intermediate cation) (e.g. J&F sec )
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 (not just % 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 i-Pr via S N 2 vs 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 valuable 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 ? To do his project, Jo-David needed to prepare this compound. E2 >> S N 2 CD 3 double arrow for “retrosynthesis” i.e. prepare from E1 >> S N 1
Ph 2 C=N-R Ph 2 C=O + H 2 N-R + H + + It is very common to change a C=X double bond into C=O and H 2 X (we’ll be discussing this) But if
- + 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, and a world expert on Epidermolysis Bullosa. His son graduated from Yale in Happy Ending I: “…that project (and my conversation with that pleasant prof at U Michigan) did teach me more about the rigors and foibles of bench research than anything that I subsequently experienced as a postdoc at NIH. It therefore prepared me for many more happily transient foibles during the 19 years that I ran a bench immunology lab at UAB and UNC. As I found out the hard way, trying to predict ‘good behavior’ with cell lines, antibodies, and semi-purified proteins was even more subject to random whimsy than when I was trying to work with relatively straightforward purified chemicals in a far more structured laboratory setting as an undergrad. Jo-David Fine MD, MPH, FRCP (London) January 30, 2011
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 II : 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.
Coverage to Here for the Exam on Friday 10:30-11:30 in SCL 160 or 10:15-11:15 in SCL 111 Review 8-10 pm this evening
El and Nu can be the same molecule! “Electrophilic” Addition to Alkenes This CC H L + Leaving GroupNucleophile High HOMO Low LUMO Electrophile El Nu Mechanistic/Synthetic Questions: Timing (Concerted or Stepwise) Stereochemistry (Syn or Anti) Regiochemistry or Orientation (“Markovnikov” CH 3 H H reverse of E1/E2 with some names changed or “Anti-Markovnikov”) H HOMO/LUMO or SOMO? X “For unto every one that hath shall be given, and he shall have abundance.” Matthew 25:29 (Cf. contemporary economics) What can you make?
Thermodynamic Stability of Butenes
Use NIST Webbook to study factors influencing relative stability of butenes For high precision convert to a common product, butane, using catalytic hydrogenation, which is fast and clean, and much less exothermic than combustion.
Isomeric Hexenes H f Problem: Are these data consistent with those for the butenes?