1. Dehydrohalogenation of Alkyl Halides E2 and E1 Reactions in Detail

2. b-Elimination Reactions Overview
dehydration of alcohols: X = H; Y = OH
dehydrohalogenation of alkyl halides: X = H; Y = Br, etc. C C + X Y X Y a b 2

3. b-Elimination Reactions Overview
dehydration of alcohols: acid-catalyzed
dehydrohalogenation of alkyl halides: consumes base C C + X Y X Y a b 2

4. is a useful method for the preparation of alkenes
Dehydrohalogenation
is a useful method for the preparation of alkenes Cl
NaOCH2CH3
ethanol, 55°C
(100 %)
likewise, NaOCH3 in methanol, or KOH in ethanol 4

5. Dehydrohalogenation
When the alkyl halide is primary, potassium tert-butoxide in dimethyl sulfoxide is the base/solvent system that is normally used.
KOC(CH3)3
CH3(CH2)15CH2CH2Cl
dimethyl sulfoxide
CH2
CH3(CH2)15CH
(86%) 5

6. More highly substituted double bond predominates = More Stable
Regioselectivity Br
KOCH2CH3
ethanol, 70°C +
29 %
71 %
follows Zaitsev's rule
More highly substituted double bond predominates = More Stable 10

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

9. Conjugated alkenes are preferred !

10. Steric hindrance effects the product distribution

12. more stable configuration of double bond predominates
Stereoselectivity
KOCH2CH3
ethanol Br +
(23%)
(77%)
more stable configuration of double bond predominates 11

13. more stable configuration of double bond predominates
Stereoselectivity Br
KOCH2CH3
ethanol +
(85%)
(15%)
more stable configuration of double bond predominates 11

14. Mechanism of the Dehydrohalogenation of Alkyl Halides: The E2 Mechanism13

15. Dehydrohalogenation of alkyl halides exhibits second-order kinetics
Facts
Dehydrohalogenation of alkyl halides exhibits second-order kinetics
first order in alkyl halide first order in base rate = k[alkyl halide][base]
implies that rate-determining step involves both base and alkyl halide; i.e., it is bimolecular 14

16. Rate of elimination depends on halogen
Facts
Rate of elimination depends on halogen
weaker C—X bond; faster rate rate: RI > RBr > RCl > RF
implies that carbon-halogen bond breaks in the rate-determining step 14

17. concerted (one-step) bimolecular process single transition state
The E2 Mechanism
concerted (one-step) bimolecular process
single transition state
C—H bond breaks
p component of double bond forms
C—X bond breaks 16

18. The E2 Mechanism Figure: 07-07-13UN Caption:
Second-order elimination is a reliable synthetic reaction, especially if the alkyl halide is a poor SN2 substrate. E2 dehydrohalogenation takes place in one step, in which a strong base abstracts a proton from one carbon atom as the leaving group leaves the adjacent carbon.

19. The E2 Mechanism – R .. : O
C C H X .. :
Reactants 17

20. The E2 Mechanism – R .. : O
C C H X .. :
Reactants 17

21. The E2 Mechanism d– .. R O H ..
Transition state
C C d– X .. : 17

22. The E2 Mechanism .. R O H ..
C C – X .. :
Products 17

23. Anti Elimination in E2 Reactions
Stereoelectronic Effects 20

24. Stereochemistry of the E2 Reaction
Remember: The bonds to the eliminated groups (H and X) must be in the same plane and anti to each other H X
More stable conformation than syn-eclipsed

25. The best orbital overlap of the interacting orbitals is achieved through back side attack of the leaving group X as in an SN2 displacement.

26. Regioselectivity

29. Configuration of the Reactant

30. Elimination from Cyclic Compounds
Configuration must be trans, which is (anti).

34. Figure: 07-08
Caption:
Figure 7-8
E2 elimination of bromocyclohexane requires that the proton and the leaving group be trans and both be axial.

35. Stereoelectronic effect
(CH3)3C Br
KOC(CH3)3 (CH3)3COH
(CH3)3C
cis-1-Bromo-4-tert- butylcyclohexane 21

36. Stereoelectronic effect
(CH3)3C
trans-1-Bromo-4-tert- butylcyclohexane
(CH3)3C Br
KOC(CH3)3 (CH3)3COH 21

37. Stereoelectronic effect
(CH3)3C Br
cis
KOC(CH3)3 (CH3)3COH
(CH3)3C
Rate constant for dehydrohalogenation of cis is 500 times greater than that of trans
(CH3)3C Br
KOC(CH3)3 (CH3)3COH
trans 21

38. Stereoelectronic effect
(CH3)3C Br
cis
KOC(CH3)3 (CH3)3COH H
(CH3)3C H
H that is removed by base must be anti periplanar to Br
Two anti periplanar H atoms in cis stereoisomer 21

39. Stereoelectronic effect
trans H
(CH3)3C Br
KOC(CH3)3 (CH3)3COH
(CH3)3C
H that is removed by base must be anti periplanar to Br
No anti periplanar H atoms in trans stereoisomer; all vicinal H atoms are gauche to Br 21

40. Stereoelectronic effect
cis
more reactive
trans
less reactive 22

41. Stereoelectronic effect
An effect on reactivity that has its origin in the spatial arrangement of orbitals or bonds is called a stereoelectronic effect.
The preference for an anti periplanar arrangement of H and Br in the transition state for E2 dehydrohalogenation is an example of a stereoelectronic effect. 22

42. E2 in a cyclohexane ring 21

43. Can you predict the products? Can you explain the products?
E2 in a cyclohexane ring
Cis or trans?
Axial or equatorial?
a,e  e,a
e,e  a,a
Can you predict the products?
Can you explain the products? 21

44. Cyclohexane Stereochemistry Revisited
How many stereoisomers are possible for menthol?
l-menthol 21

45. A Different Mechanism for Alkyl Halide Elimination: The E1 Mechanism23

46. Example CH3 C CH3 CH2CH3 Br Ethanol, heat CH2CH3 CH3 C H2C H3C CH3 C H+
(25%)
(75%) 25

47. 1. Alkyl halides can undergo elimination in absence of base.
The E1 Mechanism
1. Alkyl halides can undergo elimination in absence of base.
2. Carbocation is intermediate
3. Rate-determining step is unimolecular ionization of alkyl halide. 24

48. Step 1 CH3 C CH2CH3 Br : .. slow, unimolecular C + CH2CH3 CH3 – : Br25

49. Which alkene is more stable and why?
Step 2 C
CH2CH3
CH3 +
– H+
CH3
CH2 + C C
CH3
CHCH3
CH3
CH2CH3
Which alkene is more stable and why? 27

50. Figure: 07-05
Caption:
Figure 7-5
trans-2-Butene is more stable than 1-butene by 2.7 kcal/mol (11 kJ/mol).

51. Figure: 07-06
Caption:
Figure 7-6
The isomer with the more highly substituted double bond has a larger angular separation between the bulky alkyl groups.

52. Figure: 07-07
Caption:
Figure 7-7
Relative energies of typical p bonds compared with ethylene. (The numbers are approximate.)

53. Reaction coordinate diagram for the E1 reaction of
2-chloro-2-methylbutane

56. Must consider possible carbocation rearrangement

58. Stereochemistry of the E1 Reaction

59. E1 Elimination from Cyclic Compounds
E1 mechanism involves both syn and anti elimination

61. Summary & Applications (Synthesis) SN1 / E1 vs. SN2 / E223

62. E2 and E1 Reactions

64. Substitution vs. Elimination
Alkyl halides can undergo SN2, SN1, E2 and E1 Reactions
1) Which reaction conditions favor SN2/E2 or SN1/E1?
SN2/E2 reactions are favored by a high
concentration of nucleophile/strong base
SN1/E1 reactions are favored by a poor
nucleophile/weak base
2) What will be the relative distribution of substitution product
vs. elimination product?

65. Consider SN1/E1 vs. SN2/E2
Consider the Substrate

66. NOTE: a bulky base encourages elimination over substitution

67. Returning to Sn2 and E2: Considering the differences
Can you explain the products?
Can you predict the products? 21

68. Substitution and Elimination Reactions in Synthesis

69. A hindered alkyl halide should be used if you want to synthesize an alkene

70. Which reaction produces an ether?

71. Consecutive E2 Elimination Reactions:
Alkynes

72. Intermolecular vs. Intramolecular Reactions
A low concentration of reactant favors an intramolecular
reaction
The intramolecular reaction is also favored when a five-
or six-membered ring is formed

73. Three- and four-membered rings are less easily formed
Three-membered ring compounds are formed more
easily than four-membered ring compounds
The likelihood of the reacting groups finding each other
decreases sharply when the groups are in compounds
that would form seven-membered and larger rings.

74. Designing a synthesis …