1. Elimination Reactions of Alkyl 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. Sometimes More than one product may result
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. C R’ R” R - : Carbo - Ions 3O < 2O < 1O
Carbocations are stabilized by alkyl groups
Carbanions are destabilized by alkyl groups C R’ R” R : -
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 RX Elimination 1o alkyl halides 2o alkyl halides
comments
1o alkyl halides
E2 only
Difficulty in forming 1o carbocations
2o alkyl halides
E1 and E2
Favored by same as SN2 conditions
3o alkyl halides

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)
(syn-periplanar)
slower
(anti-periplanar)
faster

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. bulkiest groups on opposite sides
E1 Eliminations
stereoselective
planar, carbocation intermediate
syn and anti 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
mechanism
products
comments
SN1
Both enantiomers formed (more inverted than retained)
Racemization w/ some inversion E1
Both E and Z formed (more of the stereoisomer with bulkiest groups trans)
Also C+ intermediate
SN2
Only the inverted product is formed
Inversion E2
Both enantiomers formed (more of the stereoisomer with bulkiest groups trans)

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

51. Williamson Ether Synthesis
If you want to prepare n-propyl n-butyl ether, there are two methods.

52. Williamson Ether Synthesis
If you want to prepare ethyl t-butyl ether, there are two methods… HOWEVER, if you use t-butyl halide, you will obtain primarily the elimination product.

53. (note: use a very strong base NH2 , not OH-, or
Alkyne Syntheses
Elimination Reactions involving geminal dihalides
(note: use a very strong base NH2 , not OH-, or
it stops at vicinyl dihalide!)

54. Synthesis Problems
Synthesize 1,3-cylcohexadiene from cyclohexane.

55. Synthesis Problems
Synthesis Pathway

56. Synthesis Problems
Synthesize trans-1,2-dibromo-1-methylcylcohexane from methylcyclohexane.

57. Synthesis Problems
Synthesis Pathway

58. Synthesis Problems
Synthesize 2-butanone from 1-bromobutane.

59. Synthesis Problems
Retrosynthetic Analysis

60. Synthesis Problems
Synthetic pathway

61. END
“A pessimist finds difficulty in every opportunity. An optimist finds opportunity in every difficulty.”
A. Lincoln