Elimination Reactions of Alkyl Halides : Chapter 9

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Elimination Reactions of Alkyl Halides Chapter 9

• Competition Between Substitution and Elimination

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Contents of Chapter 9

• The E2 Reaction
• The E1 Reaction
• Competition Between E2 and E1 Reactions
• Stereochemistry of Elimination Reactions
• Elimination from Cyclic Compounds
• Competition Between Substitution and Elimination
• Substitution and Elimination Reactions in
  Synthesis

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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

• Zaitsevs rule The more substituted alkene will
  be formed in elimination reactions

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The E2 Reaction Regioselectivity

• Zaitsevs rule does not apply when the base is
  bulky
• E2 Rxn is kinetically-controlled

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The E2 Reaction Regioselectivity

• Zaitsevs rule does not apply when the leaving
  group is poor
• E2-carbanion mechanism operative

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The E2 Reaction Regioselectivity

• Zaitsevs rule may not apply when conjugated
  dienes might be formed

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The E2 Reaction Regioselectivity

• The major product of an E2 reaction is the more
  substituted alkene unless
• the base is large (i.e. bulky)
• the leaving group is poor (i.e. F)
• the less substituted ?carbon is allylic or
  benzylic (ie. more stable)

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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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The E1 Reaction

• Relative reactivities of alkyl halides in an E1
  reaction are similar to the relative stabilities
  of carbocations

3o benzylic gt 3o allylic gt 2o benzylic gt 2o
allylic gt 3o gt 1o benzylic gt 1o allylic ? 2o gt
1o gt vinyl
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The E1 Reaction

• E1 reaction involves a carbocation
• Therefore rearrangements must be considered

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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 unless b-hinderred
secondary alkyl halide E1 and E2
tertiary alkyl halide E1 and E2
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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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Stereochemistry of Elimination Reactions

• If the elimination reaction removes two
  substituents from the same side of the molecule
  it is syn elimination
• If the elimination reaction removes two
  substituents from opposite sides of the molecule
  it is anti elimination

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The E2 Reaction Stereochemistry

• The E2 Reaction is stereoselective, but not
  stereospecific if 2 b Hs are available on carbon
  bearing eliminated H
• The H leading to more stable E isomer is selected
  to be extracted from b carbon regardless of
  streochem at a carbon

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The E2 Reaction Stereochemistry

• In an E2 reaction, the bonds to the eliminated
  substituents must be in the same plane
• In this course E2 eliminations will all go via
  anti-periplanar conformation
• Product analysis possible by drawing Newman
  projections if only 1 b H is available

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The E2 Reaction Stereochemistry

• When only one hydrogen is on the ? carbon
  predominantly anti elimination leads to high
  stereospecificity

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The E2 Reaction Stereochemistry

• Retro-pro-Fischer analysis can be done to track
  stereochemistry of reaction
• For anti elimination put ? H on vertical and
  leaving group on horizontal posn
• Erase LG and ? H, draw double bond

(2S,3R)-2-bromo-3-phenylbutane
Z isomer
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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 Hs
• Product stability leads to stereoselectivity but
  not stereospecificity

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E2 Reactions of Cyclic Compounds

• E2 reaction of cyclic compounds follows the same
  stereochemical rules as from open-chain compounds

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E2 Reactions of Cyclic Compounds

• The E2 reaction of menthyl chloride violates
  Zaitsevs rule

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E1 Reactions of Cyclic Compounds

• When a cyclohexyl chloride undergoes an E1
  reaction, there is no requirement that the two
  groups to be eliminated be diaxial

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E1 Reactions of Cyclic Compounds

• Carbocation rearrangements must be considered for
  E1 reactions

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Competition Between Substitution and Elimination

• Conditions that favor E2 also favor SN2
• Conditions that favor E1 also favor SN1
• No need to worry about SN2/E1 or SN1/E2
  combinations
• First decide whether the reaction would favor
  SN2/E2 or SN1/E1 reactions
• If the halide is primary, only SN2/E2 need be
  considered
• If the halide is secondary or tertiary, SN2/E2 or
  SN1/E1 depends on reaction condition

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Competition Between Substitution and Elimination

• SN2/E2 reactions are favored by high conc of a
  good nuc/strong base and polar aprotic solvent.
• SN1/E1 reactions are favored by poor nuc/weak
  base and polar protic solvents

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Competition Between SN2 and E2

• Primary halides generally undergo substitution,
  although if the halide or the base is hindered,
  elimination is possible, favorable if heated
• Secondary halides are more difficult to predict
• The stronger and more hindered the base, the more
  elimination product is produced
• The higher the temperature, the more elimination
  product is produced
• Tertiary halides never undergo SN2 reaction -
  elimination is the only possibility

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Competition Between SN1 and E1

• Because SN1 and E1 reactions both proceed through
  a carbocation, they have the same
  rate-determining step
• Primary halides do not undergo either SN1 or E1
  reactions
• For secondary and tertiary halides, raising the
  temperature increases the elimination product

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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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Williamson Ether Synthesis

• 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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Substitution and Elimination Reactions in
Synthesis

• SN1/E1 conditions are rarely useful synthetically

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Designing a Synthesis

• How would you carry out the following?

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Designing a Synthesis

• Under E2 conditions a tertiary halide would yield
  only the elimination product

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Designing a Synthesis

• We know also that Br2 addition to an alkene
  yields only the anti product
• Overall we might propose

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Designing a Synthesis
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Designing a Synthesis

• Only method we know to prepare a ketone is to add
  water to an alkyne

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Designing a Synthesis

• The alkyne can be prepared by two successive E2
  reactions on a vicinal dihalide

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Designing a Synthesis

• The vicinal dihalide can be prepared via
  halogenation of an alkene

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Designing a Synthesis

• The alkene can be prepared from the starting
  material via dehydrohalogenation

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Designing a Synthesis II

• From this analysis we might suggest the following
  synthesis

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Problem-solving Info

• Reaction speed comparisons
• Increasing speed in E1 reaction
• Polar protic solvent
• Relief of steric strain making C
• More stable carbocation formed
• Anything which destabilizes electrophile
• Increased leaving group stability (less basic)

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Problem-solving Info

• Increasing speed in E2 reaction
• Polar aprotic solvent
• Alkene stability
• Increased leaving group stability
• Higher concentration of base used
• Stronger base used
• Anything which destabilizes electrophile
• Cyclohexanes with more or more stable
  antiperiplanar Hs which lead to more stable
  products
• C- stability with bad leaving group (F)

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Problem-solving Info

• E1 vs E2 chemistry
• Conditions which give E1
• Weak base and C stability ? 2
• Polar protic solvent and C stability ? 2
• No antiperiplanar Hs in cyclohexanes
• Conditions which give E2
• Primary electrophile without b hindrance
• Polar aprotic solvent
• Strong/concentrated base

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Problem-solving Info

• Unimolecular vs. bimolecular
• SN1/E1
• Weak base or bad nucleophile
• Protic solvent
• C stability ? 2
• SN2/E2
• Concentrated strong base or good nucleophile
• Polar aprotic solvent
• Primary electrophile
• Substitution vs. elimination
• SN1 vs. E1
• Weaker base and lower temp gives SN1
• Stronger base and higher temp gives E1

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Problem-solving Info

• SN2 vs. E2
• SN2
• Primary unhindered electrophile
• Larger than second row anion nucleophile
• Weaker base with other substitution-enhancing
  conds
• E2
• b-hindered secondary electrophile
• Bulky concentrated second-row base
• SN1 vs. E1
• Weaker base and lower temp gives SN1
• Stronger base and higher temp gives E1

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Problem-solving Info

• Product distribution
• Most stable alkene formed unless
• Bad leaving group (ie. F) gives most stable C-
• b H in cyclohexane trans to leaving group
• Only b H in acyclic reactant which can be
  antiperiplanar to leaving grp leads to Z prod
• Acyclic electrophile with 1 b H chiral a C
• Must use Newman projection to predict product
• Product arises from antiperiplanar elimination
• Stereospecific one enantiomer gives E, other Z
• C rearrangements with E1 reactions!!!