Transcript Chapter 9: Reactions at an sp3 Hybridized Carbon I

Substitution and Elimination
Reactions of Alkyl Halides:
Chapter 9
Chapter 9
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Contents of Chapter 9
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Reactivity Considerations
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The SN2 Reaction
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The SN1 Reaction
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Stereochemistry of SN2 and SN1 Reactions
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Benzylic, Allylic, Vinylic & Aryl Halides
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Competition between SN2 and SN1 Reactions
The E2 Reaction
The E1 Reaction
Substitution and Elimination Reactions in Synthesis
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No Biological Methylating Reagents
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Substitution and Elimination
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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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SN2 Mechanism
SN2 mechanism: C–X bond weakens as
nucleophile approaches all in one step
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SN1 Mechanism
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SN1 mechanism: C–X bond breaks first
without any help from nucleophile
slow step
fast step
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This is a two-step process
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Substitution Reactions
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Both mechanisms are called nucleophilic
substitutions
Which one takes place depends on
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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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The SN2 Reaction
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Bimolecular nucleophilic substitution
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rate = k [alkyl halide][nucleophile]
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The SN2 Reaction
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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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Steric Accessibility in the SN2
Reaction
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The SN2 Reaction:
Nucleophile Bulkiness
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Nucleophilicity is affected by steric effects
A bulky nucleophile has difficulty getting near
the back side of a sp3 carbon
CH3
CH3CH2O
CH3CO
CH3
ethoxide ion
better nucleophile
tert-butoxide ion
stronger base
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The SN1 Reaction
The more stable the C+ the lower the DG‡, and the
faster the rxn
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The SN1 Reaction
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The SN1 Reaction
The SN1 reaction leads to a mixture of
stereoisomers
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Stereochemistry of SN2 and
SN1 Reactions
inversion
both enantiomers
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Competition Between SN2
and SN1 Reactions
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Competition Between SN2 and
SN1 Reactions
TABLE 9.6 Summary of the Reactivity of Alkyl Halides in
Nucleophilic Substitution Reactions
methyl & 1o alkyl halides
2o alkyl halides
3o alkyl halides
SN2 only
SN2 & SN1
SN1 only
vinylic & aryl halides
benzylic & allylic halides
3o benzylic & allylic halides
neither SN2 nor SN1
SN2 & SN1
SN1 only
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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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The E2 Reaction
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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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The E2 Reaction:
Regioselectivity
Zaitsev’s rule: The more substituted
alkene will be formed in elimination
reactions
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The E1 Reaction
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“E1” stands for “Elimination unimolecular”
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The E1 reaction is a two-step reaction
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The first step is rate-determining
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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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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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Competition Between E2 and
E1 Reactions
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E2 reaction is favored by the same factors that favor
SN2 reactions over SN1
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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
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a weak base (e.g. a neutral solvent)
a polar protic solvent (e.g. H2O or ROH)
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The E1 Reaction:
Stereochemistry
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With C+ both syn and anti elimination can occur, so
E1 reaction forms both E and Z products regardless
of whether -carbon is bonded to one or two H’s
Product stability leads to stereoselectivity but not
stereospecificity
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Williamson Ether Synthesis
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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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Williamson Ether Synthesis
CH3
CH3CH2Br
+
CH3CO
CH3
CH3CH2OCCH3 +
CH3
ethyl bromide tert-butoxide
ion
CH3
CH2 CH2 + CH3COH + Br
CH3
tert-butyl ethyl
ether
CH3
ethene
 If you want to prepare tert-butyl ethyl ether the
starting materials must be an ethyl halide and tertbutoxide ion
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When ethoxide ion and tert-butyl bromide are used,
only elimination product is produced
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