Elimination Reactions of Alkyl Halides

1. Elimination Reactions ofAlkyl Halides Chapter 9 “A pessimist finds difficulty in every opportunity. An optimist finds opportunity in every difficulty.” A. Lincoln

2. Elimination Reactions Elimination Rx can be of two types • E1 mechanism (unimolecular) • E2 mechanism (bimolecular)

3. E2 Eliminations Concerted one step reaction

4. E2 Eliminations • Called “dehydrohalogenations” • Called a /  Eliminiation • Called 1-2 Elimination

5. E2 Eliminations Relative reactivities of RX in an E2 reaction: (most reactive) RI > RBr > RCl > RF (least reactive)) F- is a better base than Br-

6. E2 Eliminations Sometimes only one elimination product is possible Sometimes More than one product may result

7. E2 Eliminations Kinetic and Thermodynamic Product (A regioselective reaction !)

8. Zaitsev’s Rule The more highly substituted product is obtained when a proton is removed from the b-carbon that is bonded to the fewest hydrogens

9. Reactivity of Alkyl Halides • *

10. Reactivity Considerations • The more substituted product is not always the most rapidly formed… That Conjugated Diene thing just keeps showing up…….

11. Reactivity Considerations • The more substituted product is not always the most rapidly formed… That Pesky Bulky Base – Changes things……

12. Reactivity Considerations • Steric hindrance may dictate removal of a more accessible H (The most substituted is not formed here.)

13. * (What does this mean?)

14. Alkyl fluorides • Dehydrohalogenation of R-I, R-Br, R-Cl yield more substituted alkene • Dehydrohalogenation of RF yields the less substituted alkene

15. Elimination of Alkyl fluorides

16. Elimination of Alkyl fluorides • Fluoride is a strong base • Fluoride is a poor leaving group • A partial negative charge develops on the carbon that lost the proton (a carbanion)

17. - : R’ C R R” Carbo - Ions Carbocations are stabilized by alkyl groups Carbanions are destabilized by alkyl groups 3O < 2O < 1O Increasing stability of Carbanions

18. Elimination Considerations • The major product is the more substituted alkene unless… • the alkyl halide contains conjugation • the base is large • the alkyl halide is an alkyl fluoride

19. E1 Mechanism

20. E1 Mechanism

21. E1 Mechanism Major product will generally be the more substituted - Zatsev

22. E1 Mechanism Product depends on stability of the carbocation

23. E1 Mechanism • Because a carbocation is formed – rearrangement is possible

24. E1 Mechanism • Because a carbocation is formed – rearrangement is possible

25. Competition E1 vs. E2

26. Review of SN Reactions SN1 is Favored By More Substituted Carbocation Weak Nucleophile Polar Protic Solvent SN2 is Favored By Less Substituted Carbocation Strong Nucleophile Polar AProtic Solvent

27. Stereochemistry of E2 • In an E2 reaction, 2 groups are eliminated in one step • The 2 groups MUST be located in the same plane (periplanar) (anti-periplanar) faster (syn-periplanar) slower

28. E2 is regioselective

29. E2 Is Stereoselective The conformers that have the bulkiest groups on opposite sides will be the major product.

30. Stereochemistry of E2 Note: E isomer is major product because bulky groups, methyl and t-butyl, are anti.

31. Stereochemistry of E2 Important note: use models!E2 for 2-bromo-3-phenylbutane only E isomer (2S, 3S) only Z isomer (2S, 3R)

32. stereoselective E1 Eliminations • planar, carbocation intermediate • synandanti elimination can occur bulkiest groups on opposite sides (Major product is the one with bulkiest groups on opposite sides.)

33. Elimination from Cyclics - E2 • In an E2 reaction, both groups must be periplanar and anti to each other. • This is NOT the most stable conformer.

34. Elimination from Cyclics - E2

35. Elimination from Cyclics - E2 More stable conformer has groups equatorial. Occurs 200 x faster!

36. Elimination from Cyclics - E2 • In an E2 reaction, the H is removed from the most substituted b-carbon unless that hydrogen is not in the axial

37. Elimination from Cyclics - E1 • In an E1 reaction, the elimination is not concerted. • Intermediate is a carbocation • Groups do not need to be in the axial position

38. Elimination from Cyclics - E1 • Carbocation intermediates may rearrange. (Zaitsev’s rule is followed, but first watch out for a rearrangement.)

39. Stereochemistry Review

40. Using Isotopes In Chemistry • Look at mechanism • Look at research handout • Look at medical questions handout

41. Substitution vs. Elimination E1 vs SN1 or E2 vs SN2

42. Steps To Deciding • Decide if it favors Sn2/E2 or Sn1/E1 conditions • Decide if it favors Substitution or Elemination …….. That’s all there is to it  From Yahoo Images

43. Deciding Between First or Second order • Substrate – 1st order – primary and secondary 2nd order – secondary and tertiary • Nucleophile 1st order – weaker nuclephile 2nd order – strong nucleophile • Solvent 1st order – polar protic solvent 2nd order – polar aprotic or neutral 2 out of three ain’t bad………… or is that just a long lost song

44. Deciding Between Sn2 and E2 • Substrate • Base • Temperature From Yahoo Images

45. Deciding Between Sn2 and E2 • Substrate Sn2 – primary alkyl halide E2 – secondary alkyl halide

46. Deciding Between Sn2 and E2 • Nuclophile Sn2 – Weaker and Smaller E2 – stronger and Bulkier

47. Deciding Between Sn2 and E2 • Temperature Sn2 – Lower Temperature E2 – Higher Temperatue

48. SN1 / E1 Conditions • All alkyl halides have same order of reactivity for SN1 or E1 • Substitution is favored at lower temperatures

49. Practice Activity • Each person create a reaction and conditions • Have your neighbor decide which mechanism it will undergo • Switch and do it again From Yahoo Images

50. CH3OH + Na CH3O- + Na+ + 1/2 H2 Williamson Ether Synthesis • Williamson ether synthesis • Alkyl halide with alkoxide (SN2 reaction) • Alexander Williamson (1850!) • React alcohol with sodium metal or sodium hydride NaH