1. Alkyl Halides and Elimination reactions
Chapter 8
Alkyl Halides and Elimination reactions

2. Alkyl Halides and Elimination Reactions
General Features of Elimination
It is well known that elimination reactions (E) often compete successfully with SN reactions, because nucleophiles are also Brønsted-Lowry bases (SN2 versus E2) and carbocations are prone to the elimination of a proton (again involving a Brønsted-Lowry base: SN1 versus E1).

3. Alkyl Halides and Elimination Reactions
General Features of Elimination

4. Alkyl Halides and Elimination Reactions
General Features of Elimination
Removal of the elements HX is called dehydrohalogenation.
Dehydrohalogenation is an example of  elimination
(1,2-elimination).

5. Alkyl Halides and Elimination Reactions
General Features of Elimination
bases used in elimination reactions : RO¯ ( alkoxides).

6. Alkyl Halides and Elimination Reactions
General Features of Elimination
How to draw any product of dehydrohalogenation
Find the  carbon.
Identify all  carbons with H atoms.
Remove the elements of H and X from the  and  carbons and form a  bond.

7. Alkyl Halides and Elimination Reactions
Alkenes—The Products of Elimination

8. Alkyl Halides and Elimination Reactions
Alkenes—The Products of Elimination
Alkenes are classified according to the number of carbon atoms bonded to the carbons of the double bond.

9. Alkyl Halides and Elimination Reactions
Alkenes—The Products of Elimination
rotation about double bonds is restricted.
diastereomers

10. Alkyl Halides and Elimination Reactions
Stability of Alkenes
In general, trans alkenes are more stable than cis alkenes because the groups bonded to the double bond carbons are further apart, reducing steric interactions.

11. Alkyl Halides and Elimination Reactions
Stability of Alkenes
The stability of an alkene increases as the number of R groups bonded to the double bond carbons increases.
The higher the percent s-character, the more readily an atom accepts electron density. Thus, sp2 carbons are more able to accept electron density and sp3 carbons are more able to donate electron density.
Consequently, increasing the number of electron donating groups on a carbon atom able to accept electron density makes the alkene more stable.

12. Alkyl Halides and Elimination Reactions
Stability of Alkenes

13. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination
There are two mechanisms of elimination—E2 and E1, just as there are two mechanisms of substitution, SN2 and SN1.
E2 mechanism—bimolecular elimination
E1 mechanism—unimolecular elimination
The E2 and E1 mechanisms differ in the timing of bond cleavage and bond formation, analogous to the SN2 and SN1 mechanisms.
E2 and SN2 reactions have some features in common, as do E1 and SN1 reactions.

14. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2
The most common mechanism for dehydrohalogenation
second-order kinetics : both the alkyl halide and the base appear in the rate equation, i.e.,
rate = k[(CH3)3CBr][¯OH]
One step mechanism : all bonds are broken and formed in a single step. -- The reaction is concerted

15. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2

16. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2
There are close parallels between E2 and SN2 mechanisms in how the identity of the base, the leaving group and the solvent affect the rate.
The base appears in the rate equation, so the rate of the E2 reaction increases as the strength of the base increases.
E2 reactions are generally run with strong, negatively charged bases like¯OH and ¯OR. Strong sterically hindered (non-nucleophilic) nitrogen bases (DBN and DBU) are also sometimes used.

17. Alkyl Halides and Elimination Reactions
1,5-diazabicyclo[4.3.0]non-5-ene and 1.8-diazobicylco[5.4.0]undec-7-ene

18. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2 : the leaving group
the solvent
Acetone, DMF, DMSO

19. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2 : nature of R group
Substitution v.s. elimination
i.e. more substitution lowers Ea

20. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2
slower
faster

21. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2
Table 8.2 summarizes the characteristics of the E2 mechanism.

22. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E2

23. Alkyl Halides and Elimination Reactions
The Zaitsev (Saytzeff) Rule
The major product is the more stable product—the one with the more substituted double bond.
This phenomenon is called the Zaitsev rule. (1875)

24. Alkyl Halides and Elimination Reactions
The Zaitsev (Saytzeff) Rule
The Zaitsev rule: the major product in  elimination has the more substituted double bond.
A reaction is regioselective when it yields predominantly or exclusively one constitutional isomer when more than one is possible. Thus, the E2 reaction is regioselective.

25. If the stereochemistry is known,
the outcome is not always the same.

26. Alkyl Halides and Elimination Reactions
cf. stereoselective
When a mixture of stereoisomers is possible from a dehydrohalogenation, the major product is the more stable stereoisomer.
A reaction is stereoselective when it forms predominantly or exclusively one stereoisomer when two or more are possible.
The E2 reaction is stereoselective because one stereoisomer is formed preferentially.
Why?

27. This is all about orbital alignment.
Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction
In the transition state of an E2 reaction all involved atoms should be aligned in the same plane.
one hydrogen atom, two carbon atoms, the leaving group (X)
There are two ways for the C—H and C—X bonds to be coplanar.
E2 elimination occurs most often in the anti periplanar geometry.
This is all about orbital alignment.
This arrangement allows the molecule to react in the lower energy staggered conformation, and allows the incoming base and leaving group to be further away from each other.

28. Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction

29. Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction
In cyclic compounds, the stereochemical requirement of an anti periplanar geometry in an E2 reaction has important consequences.

30. For E2 elimination, the C-Cl bond must be anti periplanar to the C—H bond on a  carbon, and this occurs only when the H and Cl atoms are both in the axial position. The requirement for trans diaxial geometry means that elimination must occur from the less stable conformer, B.

31. Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction
The cis isomer

32. Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction

33. Alkyl Halides and Elimination Reactions
Stereochemistry of the E2 Reaction
The trans isomer.
This is not predicted by the Zaitsev rule.

34. If the stereochemistry is known,
the outcome is not always the same.

35. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination— E1 mechanism
An E1 reaction exhibits first-order kinetics:
rate = k[(CH3)3CCI]
The E1 reaction proceeds via a two-step mechanism: the bond to the leaving group breaks first before the  bond is formed. The slow step is unimolecular, involving only the alkyl halide.

36. Alkyl Halides and Elimination Reactions

37. Alkyl Halides and Elimination Reactions
E1 Mechanisms

38. Alkyl Halides and Elimination Reactions
Other characteristics of E1 reactions
The rate of an E1 reaction increases as the number of R groups on the carbon with the leaving group increases.
The strength of the base usually determines whether a reaction follows the E1 or E2 mechanism. Strong bases like ¯OH and ¯OR favor E2 reactions, whereas weaker bases like H2O and ROH favor E1 reactions.

39. Alkyl Halides and Elimination Reactions
E1 Mechanisms
E1 reactions are regioselective, favoring formation of the more substituted, more stable alkene.
Zaitsev’s rule applies to E1 reactions also.

40. Alkyl Halides and Elimination Reactions
Mechanisms of Elimination—E1
Table 8.3 summarizes the characteristics of the E1 mechanism.
No need of antiperiplanar arrangement

41. Alkyl Halides and Elimination Reactions
SN1 and E1 Reactions
SN1 and E1 reactions have exactly the same first step—formation of a carbocation. They differ in what happens to the carbocation.
Because E1 reactions often occur with a competing SN1 reaction, E1 reactions of alkyl halides are much less useful than E2 reactions.

42. Alkyl Halides and Elimination Reactions
SN1 and E1 Reactions

43. Alkyl Halides and Elimination Reactions
When is the Mechanism E1 or E2?
Strong bases favor the E2 mechanism.
Weak bases favor the E1 mechanism.

44. Alkyl Halides and Elimination Reactions
E2 Reactions and Alkyne Synthesis
A single elimination reaction produces a  bond of an alkene. Two consecutive elimination reactions produce two  bonds of an alkyne.

45. Alkyl Halides and Elimination Reactions
E2 Reactions and Alkyne Synthesis
Two elimination reactions are needed to remove two moles of HX from a dihalide substrate.
Two different starting materials can be used—a vicinal dihalide or a geminal dihalide.

46. Alkyl Halides and Elimination Reactions
E2 Reactions and Alkyne Synthesis
Stronger bases are needed to synthesize alkynes by dehydrohalogenation than are needed to synthesize alkenes.
Because sp2 hybridized C—H bonds are stronger than sp3 hybridized C—H bonds. As a result, a stronger base is needed to cleave this bond.
The typical base used is ¯NH2 (amide), used as the sodium salt of NaNH2. KOC(CH3)3 can also be used with DMSO as solvent.

47. Alkyl Halides and Elimination Reactions
E2 Reactions and Alkyne Synthesis

48. Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.

49. Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Good nucleophiles that are weak bases favor substitution over elimination —Certain anions generally give products of substitution because they are good nucleophiles but weak bases. These include I¯, Br¯, HS¯, ¯CN, and CH3COO¯.

50. Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Bulky nonnucleophilic bases favor elimination over substitution —KOC(CH3)3, DBU, and DBN are too sterically hindered to attack tetravalent carbon, but are able to remove a small proton, favoring elimination over substitution.

51. Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Tertiary Alkyl Halides

52. Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Tertiary Alkyl Halides
E2 will occur preferentially if a strong base is used (OH-, OR-). Reaction in neutral (weakly basic) conditions leads to a mixture of SN1 and E1 products, with usually the SN1 product favored.

53. Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Primary Alkyl Halides
SN2 is favored by use of a good nucleophile (RS-, I-, CN-, Br-) and polar aprotic solvent. E2 is favored by use of a strong, hindered base (tert-butoxide).

54. Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Secondary Alkyl Halides
SN2 and E2 compete.
If a weakly basic strong nucleophile (CH3COO-, Br-, I-) and polar aprotic solvent is used, SN2 dominates.
If a strong base (OR-) in a protic solvent is used, E2 is dominant.

55. This is a situation that is best avoided.
Alkyl Halides and Elimination Reactions
Predicting the Mechanism from the Reactants—SN1, SN2, E1 or E2.
Secondary Alkyl Halides
If only a weak nucleophile or base is present then SN1 competes with E1 and it is difficult to predict which will be favored.
This is a situation that is best avoided.

56. Homework
8.18, 8.22, 8.24, 8.31, 8.33, 8.40, 8.41, 8.45, 8.49, 8.50, 8.53, 8.54, 8.57

57. Alcohols, Ethers and Epoxides
Preview of Chapter 9
Alcohols, Ethers and Epoxides
Preparation of alcohols, ethers, and epoxides
Synthesize an alcohol and an ether from alkylhalide.
Reactions of alcohols, ethers and epoxides
What is dehydration reaction?
What is 1,2-hydride shift?
What reagents are used to convert alcohols into halides?