1. Chapter 8 Substitution and Elimination Reactions of Alkyl Halides
Paula Yurkanis Bruice
University of California,
Santa Barbara

2. Contents of Chapter 8 Reactivity Considerations The SN2 Reaction
Stereochemistry of SN2 and SN1 Reactions
Benzylic, Allylic, Vinylic & Aryl Halides
Competition between SN2 and SN1 Reactions
The E2 Reaction
The E1 Reaction
Substitution and Elimination Reactions in Synthesis
No Biological Methylating Reagents
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3. Substitution and Elimination
A compound with an sp3 hybridized carbon bonded to a halogen can undergo two types of reactions
Two different mechanisms for substitution are SN1 and SN2 mechanisms
These result in diff prods under diff conditions
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4. SN2 Mechanism
SN2 mechanism: C–X bond weakens as nucleophile approaches all in one step
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5. SN1 Mechanism
SN1 mechanism: C–X bond breaks first without any help from nucleophile
slow step
fast step
This is a two-step process
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6. Substitution Reactions
Both mechanisms are called nucleophilic substitutions
Which one takes place depends on
the structure of the alkyl halide
the reactivity and structure of the nucleophile
the concentration of the nucleophile, and
the solvent in which reaction is carried out
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7. The SN2 Reaction Bimolecular nucleophilic substitution
rate = k [alkyl halide][nucleophile]
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8. The SN2 Reaction
The inversion of configuration resembles the way an umbrella turns inside out in the wind
If a single chiral enantiomer reacts a single chiral product (inverted) results.
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9. Steric Accessibility in the SN2 Reaction
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10. The SN2 Reaction: Nucleophile Bulkiness
Nucleophilicity is affected by steric effects
A bulky nucleophile has difficulty getting near the back side of a sp3 carbon
ethoxide ion tert-butoxide ion
better nucleophile stronger base
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11. The SN1 Reaction
The more stable the C+ the lower the DG‡, and the faster the rxn
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12. The SN1 Reaction
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13. The SN1 Reaction The SN1 reaction leads to a mixture of stereoisomers
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14. Stereochemistry of SN2 and SN1 Reactions
inversion
both enantiomers
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15. Competition Between SN2 and SN1 Reactions
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16. Competition Between SN2 and SN1 Reactions
TABLE Summary of the Reactivity of Alkyl Halides in Nucleophilic Substitution Reactions
methyl & 1o alkyl halides SN2 only
2o alkyl halides SN2 & SN1
3o alkyl halides SN1 only
vinylic & aryl halides neither SN2 nor SN1
benzylic & allylic halides SN2 & SN1
3o benzylic & allylic halides SN1 only
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17. Elimination Reactions
A compound with an electronegative atom bonded to an sp3 carbon, when approached by a nucleophile/base can undergo either a substitution reaction OR an elimination reaction
In this chapter we start with elimination rxns then work subst/elim competition
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18. The E2 Reaction
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19. The E2 Reaction: Regioselectivity
2-bromobutane has two structurally different -carbons from which to abstract a hydrogen
E2 rxns give more stable alkene if possible
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20. The E2 Reaction: Regioselectivity
Zaitsev’s rule: The more substituted alkene will be formed in elimination reactions
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21. The E1 Reaction “E1” stands for “Elimination unimolecular”
The E1 reaction is a two-step reaction
The first step is rate-determining
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22. The E1 Reaction
Relative reactivities of alkyl halides in an E1 reaction are similar to the relative stabilities of carbocations
3o benzylic > 3o allylic > 2o benzylic > 2o allylic > 3o > 1o benzylic > 1o allylic  2o > 1o > vinyl
Increasing reactivity and C+ stability
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23. Competition Between E2 and E1 Reactions
Summary of the Reactivity of Alkyl Halides in Elimination Reactions
primary alkyl halide E2 only
secondary alkyl halide E1 and E2
tertiary alkyl halide E1 and E2
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24. Competition Between E2 and E1 Reactions
E2 reaction is favored by the same factors that favor SN2 reactions over SN1
primary alkyl halide electrophiles
a high concentration of a strong base (e.g. HO– or –NH2) in 1°, 2°, or 3° electrophiles
an aprotic polar solvent in 1°, 2°, or 3° electrophiles
An E1 reaction is favored by
a weak base (e.g. a neutral solvent)
a polar protic solvent (e.g. H2O or ROH)
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25. The E1 Reaction: Stereochemistry
With C+ both syn and anti elimination can occur, so E1 reaction forms both E and Z products regardless of whether b-carbon is bonded to one or two H’s
Product stability leads to stereoselectivity but not stereospecificity
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26. Williamson Ether Synthesis
If you want to synthesize butyl propyl ether you have a choice of starting materials
Other ethers should be made by choosing least-hindered electrophile if possible
Ethers usually best made by SN2 rxn
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27. Williamson Ether Synthesis
ethyl bromide tert-butoxide tert-butyl ethyl ethene ion ether
If you want to prepare tert-butyl ethyl ether the starting materials must be an ethyl halide and tert-butoxide ion
When ethoxide ion and tert-butyl bromide are used, only elimination product is produced
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