1 / 62

Chapter 9 Nucleophilic Substitution &  -Elimination

6.  -Elimination 7.  -Elimination mechanism 8. Evidence for E1 and E2 9. Substitution vs Elimination. Chapter 9 Nucleophilic Substitution &  -Elimination. 1. Nucleophilic Aliphatic Substitution 2. Solvents for Nucleophilic Substitution Reactions

wilmer
Download Presentation

Chapter 9 Nucleophilic Substitution &  -Elimination

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. 6. -Elimination 7. -Elimination mechanism 8. Evidence for E1 and E2 9. Substitution vs Elimination Chapter 9 Nucleophilic Substitution &-Elimination 1. Nucleophilic Aliphatic Substitution 2. Solvents for Nucleophilic Substitution Reactions 3. Mechanisms of Nucleophilic aliphatic substitution 4. Evidence of Sn1 / Sn2 Mechanisms 5. Analysis of some Nucleophilic Substitution Rx’s

  2. substitution -elimination rxs can compete leads to by-products (additional products) 4

  3. 9 Nucleophilic Substitution conditions Nu: + R3C-X R3C-Nu + X:(-) Reactions with Lewis:Bases / :Nucleophiles Leaving group - stable with pair of e’s, weakB: Product(s) Conditions - solvent, temperature, etc

  4. Nucleophilic Substitution (see Table 9.1 for more examples) Rx: (Chap 7) 4

  5. Nucleophilic Substitution examples Table 9.1 continued 2

  6. (after -H+) Nucleophilic Substitution examples Table 9.1 continued amine alcohol ether 6

  7. APROTIC POLAR ≥ 15 dielectric constant ≤ 5 NON-POLAR 2. Solvents PROTIC [H+]

  8. APROTIC POLAR ≥ 15 dielectric constant ≤ 5 NON-POLAR 2. Solvents of reaction (rx) DMSO 48.9 acetonitrile 37.5 DMF 36.7 acetone 20.7 PROTIC [H+] dichloromethane 9.1 diethyl ether 4.3 toluene 2.3 hexane 1.9

  9. APROTIC POLAR ≥ 15 dielectric constant ≤ 5 NON-POLAR 2. Solvents water 79 formic acid 59 methanol 33 ethanol 24 PROTIC [H+] acetic acid 6.2

  10. Difference: timing of bond-breaking and making One simultaneousbreaking & making; [SN2] Other, break then make bonds stepwise; [SN1] 3. Substitution Mechanisms 2 limiting mechanisms for substitution (SN2, SN1) 5

  11. sp2 H   t.s. simultaneous bond breaking and making HO C Br H H Mechanism - SN2 3

  12. Mechanism - SN1 + other products [important!] 4

  13. Reactant structure have on mechanism/rate? Structure of Nu: have on mechanism/rate? Leaving group have on rate? What is: The stereochemical course of SN reaction? The role of the solvent? When or why: Does rearrangement occur? SN reactions What effect does the: 5

  14. :Nucleophilicity - kinetic, speed of rxn. H  + H time C Nu: C + X(-) Nu X H H H  - H + H B-H Nu:or B: :Basicity - equilibrium Kinetics/Nucleophilicity Nucleophiles are also bases :Nucleophilicity and :Basicity have correlations 4

  15. Reaction rate depends on [RX] unimolecular rx rate = k[(CH3)3CBr] k - rate constant 1st order kinetics / stepwise Kinetics - SN1 4

  16. H   HO C Br H H kinetics - SN2 both reactants in rate limiting step bimolecular reaction rate = k[ CH3Br ][-OH] 2nd order kinetics

  17. SN1 SN2 t.s.1 t.s.2 t.s. R+ E H H products SM products SM prog of rx prog of rx rx profile: 2

  18. OR substitution SN1 or SN2? 2

  19. strong strong bases nucleopilicity moderate weak SN1 or SN2 with a 2o RX is  on nucleophile

  20. substitution SN1 or SN2? √ OR

  21. APROTIC POLAR ≥ 15 dielectric constant ≤ 5 NON-POLAR E+-Nu E+ -Nu 2. Solvents polar PROTIC [H+] 3

  22. E+-Nu E+ -Nu polar Solvents effects on Nu:- Polarand Nonpolar Solvents Protic Aprotic The greater the the solvent’s dielectric constant, the better ions of opposite charge are separated. 2

  23. POLAR APROTICsolvents effective in solvating cations but poorly solvate anions, e.g.: Solvents effects on Nu:- The freer the Nucleophile’s e(-)s the greater its Nucleophilicity 2

  24. APROTIC solvents solvatecations F- “free” of Na+ 3

  25. APROTIC POLAR ≥ 15 dielectric constant ≤ 5 NON-POLAR solvents of SN2 rx DMSO 48.9 acetonitrile 37.5 DMF 36.7 acetone 20.7 PROTIC [H+]

  26. PROTIC solvents solvate cations & anions e.g. CH3OH 2

  27. protic polar solvents separate cations & anions rx rate THF* - 0.05 Acetone - 0.5 H2O - 4x103 CH CH 3 3 Br(-) in solvent H C C Cl H C C Br 3 3 CH CH 3 *dielectric constant 7 3 SN1rx on separating charges (+/-) in t.s. 4

  28. APROTIC POLAR ≥ 15 dielectric constant ≤ 5 NON-POLAR 2. Solvents water 79 formic acid 59 methanol 33 ethanol 24 PROTIC [H+]

  29. Stereochemistry SN1 4

  30. CH H C 3 3  - I CH 3 C t.s.  - H Br D backside attack, Stereochemistry SN2 -inversion acetone I + Br C H C H Br D I D S R inversion of configuration S->R & R->S BUT . . . 5

  31. product S S rotation backside attack, inversion of configuration SN2 product is clearly inverted but substituent priorities changed 2

  32. R3CX R2CHX RCH2X CH3X SN1 increasing stability of carbocation SN2 decreasing steric hindrance Structure of RX Reactivities for SN1 and SN2 opposite governed by electronic factors governed by steric factors 5

  33. :Nu(-) SN2 sterics - 1o :Nu(-) 3o backside blocked  SN1 6

  34. SN2 sterics :Nu(-) 3o backside blocked  SN1 5

  35. hard to form 3o R-X reacts by R+ (SN1) easy to form RX - Carbocations (SN1) 3

  36. allylic &benzylic cation - resonance stabilized - delocalizated (+) charge [SN1] ≈ 2o alkyl (SN1) Other Cations 1o allylic

  37. allylic &benzylic cation - resonance stabilized - delocalizated + charge [SN1] (SN1) Other Cations 1o allylic 2o & 3o allylic cations are even more sable

  38. same write either What is the effect of resonance on SN1? rx SN1 mech. 6

  39. (SN1) Other Cations allylic& benzylic cation - resonance stabilized - delocalizated (+)-charge [SN1] or hybrid 4

  40. allylic (benzylic) facilitates SN2 2

  41. X - gains e(-)s (Lewis base ) - less basic or more stable with e(-)s better leaving gp. e.g. (-)OH vs (-)Cl Nu-R + :X Leaving group   Nu: Nu + R-X R X strong base “neutral” as leaving gp Cl(-)>>> (-)OH 8

  42. special cases not leaving gp. Leaving group stability of group with e(-)s good leaving gp. I(-) > Br(-) > Cl(-)~ H2O > F(-) > AcO(-) > HO(-) > RO(-) > R2N(-)

  43. Which of the given substrates would undergo SN2 substitution? Product(s)? Reason? strong bases: (-)OH, (-)OCH3; (-)NH2 even stronger!  not leaving groups 3

  44. Other concerns - Rearrangements SN1 yes (R+); SN2 no 6

  45. S 2 S 1 N N primary No SN1 , 1° cations rarely observed SN2 RCH2X secondary SN2 favored in with good nucleophiles SN1 favored with poor nucleophiles. R2CHX Tertiary R3CX SN2 does not occur; steric hindrance SN1 - ease of formation of 3o carbocations stereocenter substitution inversion racemization Summary of SN Rx’s Alkyl Halide SN2 SN1 does not occur. methyl cation too unstable methyl CH3X 4

  46. Nu:-B:- B:-Nu:- B:-Nu:- SN2 weak SN2 SN1& E1 inversion racemic rearrange med. B: good weak SN2 SN1& E1 Guidelines for Substitution & Elimination H3C-X Nu:- polar protic unimolecular polar aprotic bimolecular 8

  47. Predict: products, and show (arrows) the mechanism. SN1/SN2 Problems SN2 SN1 11

  48. -Elimination a reaction in which a small molecule (HCl, HBr, HI, or HOH) is eliminated.

  49. -Elimination 2 limiting mechanisms for -elimination rxs E2: concertedbreak/make bonds bimolecular, rate  [R-X] [ B: or (Nu:)] E1: break bond, then make  bond unimolecular, rate  [ R-X ]

  50. -elimination b b a b a a Zaitsev rule: major -elimination product= the more stable alkene (more substituted) .

More Related