1. Elimination Rxn
Predict the reaction pathway (main products) for E2 and E1
Draw reaction mechanism for E1
Design synthetic pathway based on mechanism

2. Introduction to Elimination
Definition: A molecule loses H-X (H and X atom/group from vinyl carbon) to form alkene
Elimination is the opposite of Addition, typically requiring high temperature, driven by alkaline (basic) environment.
Two main ingredients for an elimination:
A BASE (to remove H as H+)
an electrophile with a Leaving Group

3. Nucleophile vs. Base
Consider –OH, which can act as a base or a nucleophile
Attack at the α Carbon
ALKENE
β or 1,2
Reaction at the β Hydrogen

4. Two mechanisms for Elimination
All elimination reactions involve both loss of a leaving group and proton transfer
The mechanism may be a concerted (one step) process
or a step-wise process.

5. E1: Elimination with 1st order kinetics
E1 elimination represents the 1st order rate law
The rate law for E1 rxn appears: r = k[substrate]
Reaction rate for E1 rxn depends only on [substrate]
A change in [Base] will NOT affect the rate of E1 rxn.
Mechanism involves a slow first step followed by fast second step.

6. E2: Elimination with 2nd order kinetics
The rate law for E2 rxn appears as 2nd order rxn:
r = k[substrate][Base]
Both change in [base] or [substrate] will affect the E2 reaction rate.
Mechanism: single step reaction

7. Structure of Substrate
a-/b-position in reaction center

8. 3° Substrate is preferred in E2
3° substrates are more reactive toward E2 than are 1° substrates even though 1° substrates are less hindered
The 3° substrate should proceed through a more stable transition state (kinetically favored) and a more stable product (thermodynamically favored).

9. E2 for Substrate

10. Regioselectivity of E2
Regioselectivity: Preference of locations in Reactions (producing isomers)
In elimination reactions, Different β sites available for deprotonation to yield different alkenes
Zaitsev product: more substituted alkene
Hofmann product: less substituted alkene
Zaitsev product
Hofmann product

11. E2 regioselectivity depends on Base
Steric Effect from base is causing the difference

12. Less sterically hindered base  Zaitsev
Zaitsev product predominate when a base that is NOT sterically hindered is used.
Less sterically hindered base has lower energy barrier (Ea)

13. Sterically hindered base  Hoffmann
Sterically hindered base favor the Hofmann product.
Common “bulky” bases for Hoffman elimination:
Sterically hindered bases are useful in many reactions

14. Stereoselectivity of E2 for Trans
When two b-H atoms are available, dehydrohalogenation of 3-bromopentane gives the following products
Recall Trans isomer is more stable than cis isomer (thermodynamics) Trans has lower activation energy.

15. Practice: Predict E2 products
Assuming both reaction proceeds E2 pathway
methylene cyclohexane, 3-methylcyclohexene; 1-butene, trans-2-butene

16. E2 for substrate w/ single β-H
When there is only one β-H to be eliminated, both E and Z alkene products may result from this reaction.
Draw both E and Z products

17. *E2 for single β-H yields ONE isomer
When the reaction is actually performed, only the E product is observed

18. Anti-Coplanarity in E2 transition state
E2 mechanism: base and substrate are both in the rate determining step
In the transition state, the C-H and C-Br bonds that are breaking must be rotated into the same plane as the pi bond that is forming
Transition state structure illustrating the coplanar geometry

19. *Anti coplanar b-H and LG

20. Practice: Predict E2 products
Assuming both reaction proceeds E2 pathway

21. Elimination on Cyclohexyl halide
The chlorine atom may adapt either axial or equatorial position in the chair conformation. Only for Cl at axial-position allows elimination In the presence of alkyl group, more bulky alkyl group has priority to take equitorial position. This affects the regioselectivity in elimination of HCl

22. Practice: Predict major E2 products from Cyclohexyl halide

23. *E2 for Disubstituted Cyclohexane
Which of the following molecules will NOT be able to undergo an E2 elimination reaction?
Hint: Set alkyl in e-position first, then if Cl may be able to take a-position

24. E1 Mechanism E1 mechanism is a 2-step process
Similar to SN1, the reaction rate for E1 is not affected by [Base]
Loss of LG in the mechanism is the rate-determining slow step

25. Carbocation in E1
Like SN1 mechanism, the stability of carbocation determines the substrate reactivity trend for E1 rxn:

26. Potential Energy diagram for E1
More stable carbocation, lower energy for the carbocation intermediate (Hummond postulate)

27. E1 vs. SN1: Competition in 2nd step
Because E1 and SN1 proceed by the same first step, their competition will generally result in a mixture of products

28. Protonation in E1 of alcohol
Elimination of water (dehydration) from alcohols: the –OH group needs protonation like in SN1
In the E1 reaction below, protonation forms –OH2+ as better leaving group before the formation of carbocation. Concentration sulfuric acid help equilibrium to the right

29. E1 for More substituted alkene
The final step of E1 mechanism determines the regioselectivity
E1 reactions generally produce the Zaitsev product (more substituted alkene) predominantly.

30. E1 Stereoselectivity for Trans
In the last step of the mechanism, a proton is removed from a β carbon adjacent to the sp2 hybridized carbocation
Deprotonation from β carbon is thermodynamically driven (trans or E isomers with less steric hindrance is preferred)

31. Practice: Stereoselectivity for E1
Considering stereochemistry and regiochemistry, predict the products if the molecule below was treated with concentrated sulfuric acid

32. Complete E1 Mechanisms Recall the similarities between SN1 and E1
After the carbocation is formed and possibly rearranged, E1 proton transfer neutralizes the charge

33. E1 Mechanism: Alcohol to Alkene

34. E1 w/ Rearrangement
The maximum number of steps in an E1 mechanism is generally four

35. E1 with rearrangement

36. Potential Energy Diagram for E1
Four steps in E1 mechanism suggests Four reaction intermediates.

37. Practice: Draw Reaction Mechanism

38. E2 has no protonation
In E2, base removes the β proton as the LG leaves
Strong base in E2 facilitates proton transfer
The presence of strong base almost excludes the protonation step.

39. Substitution vs. Elimination
Substitution and Elimination are always in competition
Sometimes products are only observed from S or E
Sometimes a mixture of products is observed

40. Substitution vs. Elimination
To predict whether substitution or elimination will predominate, consider the factors below
Determine the function of the reagent: as a base, a nucleophile, or both?
Nucleophilicity favor subsitution
Basicity favor elimination
If base, bulky (Hoffman) or Zaitev.
Structure of substrate (1°/2°/3°) affect the pathway (SN1, SN2, E1, or E2)
Consider relevant regiochemical and stereochemical requirements

41. Nucleophile Strength : Nucleophilicity
Greater the negative charge, more nucleophilic. RO- > ROH, HO- > H2O
more polarizable atom/anion (larger atom/anion), the more nucleophilic, RSH > ROH, I- > Br- > Cl- > F-
less sterically hindered it is, the more nucleophilic it should be. CH3O- > (CH3)3CO-

42. Strength of Base: Basicity
Recall strong acid (low pKa ) yields weak conjugate base
Strong base is the conjugate base from weak acid
To predict the basicity of base, add H+ to make conjugate acid
then use ARIO (atom, resonance, induction, orbital) to predict acidicity. Compare the following:
CH3OH or CH3NH2
Acetate or RO-

43. 7/7/2019

44. Base or Nucleophile?
Reagents that act as nucleophiles only are either highly polarizable and/or they have very strong conjugate acids
Neutral ROH as weak base or nucleophile

45. Reagent Only as Base
Either very low polarizability and/or sterically hindered

46. Strong Reagent for SN2 or E2
The stronger the reagent (either as nucleophile or base), the more likely it is to promote SN2 or E2.
The more sterically hindered reagents are more likely to promote Elimination than Substitution.

47. Weak Reagent for SN1 or E1
The weaker the reagent (nucleophile or base), the more likely it is to promote SN1 or E1, as the reagent is not affecting the rate of reaction

48. Only as Nucleophile? SN only
A. If reagent as nucleophile only, only Substitution reaction. Pathway depends on structure. 1° has SN2 only, 3° substrate SN1 only. 2° both.

49. Only as Base? E2 only
B. If reagent as Base only, E2 only. E1 not affected by reagent

50. As both strong base/nucleophile?
3. Strong Nuc:- & Base, rxn depends on substrate. 1° prefers SN2, 3° prefers E2. 2° prefers E2

51. Weak base/nucleophile
4. Weak Nuc-/Base practically only for SN1 and E1.
Only reaction with 3° substrates useful for
Practice with SkillBuilder 8.11

52. Predicting Major SN Products
regiochemistry and stereochemistry

53. Predicting Elimination Products
regiochemistry and stereochemistry

54. Substrate, Basicity, Nucleophilicity

55. Pathway and Stereochemistry
Substrate
Nuc or Base?
Solvent preference
Regio-selectivity
Stereo-selectivity
SN1
3 > 2 >> 1
+ H+?
Weak nuc
Polar protic
Racemic
SN2
1 > 2 >> 3
Strong nucleophile
Polar aprotic
Inversion E1
Weak base
Zaitsev
E/trans preferred E2
3 > 2 > 1
Strong base
Zaitsev (smaller base)
Hofmann (bulky base)
Anti-periplanar

56. Additional Practice Problems
For the substrate, give both the kinetically favored E2 product and the thermodynamically favored E2 product. Explain what conditions can be used to favor each.

57. Additional Practice Problems
Consider both regioselestivity and stereoselectivity to predict the major product for the elimination below

58. Additional Practice Problems
Predict the major product for the following reactions considering competing substitution and elimination pathways.

59. From Reaction to Synthesis
Give the reagents for each of the transformation
A: Br2/hv; B: t-BuOK; C: OH-/H2O; D. NaOMe; 2

60. From Reaction to Synthesis. B
Give the reagents for each of the transformation
A: Br2/hv; B: NaOEt; C. t-BuOK; D: CH3OH 2

61. Additional Practice Problems
Predict the major product if the alcohol below were treated with concentrated sulfuric acid. Be aware of the possible rearrangements.

62. Additional Practice Problems
For the substrate, give both the kinetically favored E2 product and the thermodynamically favored E2 product. Explain what conditions can be used to favor each.

63. Additional Practice Problems
Since tertiary substrates react more readily than secondary or primary in both E1 and E2 mechanisms, what factor(s) usually controls which mechanism will dominate and why?

64. **Anti-periplanar transition state for E2
Experiments suggest that a strict 180° angle is NOT necessary for E2 mechanisms.
Substituents on a and b carbon might have gauche interaction when achieving anti-coplanarity
Similar angles (175–179°) are sufficient (anti-periplanar instead of anti-coplanar)
Thus even when E isomer is usually more stable, the requirement for an anti-periplanar transition state can often lead to the less stable Z isomer.
Thus the rxn is NOT thermodynamically driven, rather kinetically driven.

65. Practice: Predict E2 products
Assuming both reaction proceeds E2 pathway
How are these two substrates as stereoisomers, enantiomer or diastereomer?

66. More practice: Products from E2
Assuming an anti-periplanar transition state, predict all of the products for the following reaction. Hint: use Newman projection for better visualization.
What factors most affect the product distribution?

67. *Practice: regioselestivity and stereoselectivity in E2
Predict the products for the eliminations below, and draw complete mechanisms
Regioselectivity: Hoffman vs. Zaitsev
Stereoselectivity: Anti-coplanarity

68. E1 Mechanism: Dehydration

69. E1 Mechanism: Dehydrohalogenation
Practice with conceptual checkpoint 8.33

70. E1 Mechanism: Dehydration w/ Rearrangement
The maximum number of steps in an E1 mechanism is generally four