Reaction mechanisms

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Reaction mechanisms
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Ionic Reactions
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Ionic Reactions
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Ionic Reactions
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Ionic Reactions
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Bond Polarity
Partial charges
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Nucleophiles and Electrophiles
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Leaving Groups
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Radical Reactions
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Type of Reactions
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Nucleophilic reactions nucleophilic substitution
(SN)
Nucleophilic substitution -gt reagent is
nucleophil -gt nucleophil replaces leaving
group -gt competing reaction (elimination
rearrangements)

• in the following general reaction, substitution
  takes place on an sp3 hybridized (tetrahedral)
  carbon

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Nucleophilic Substitution

• Some nucleophilic substitution reactions

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Mechanism

• Chemists propose two limiting mechanisms for
  nucleophilic displacement
• a fundamental difference between them is the
  timing of bond breaking and bond forming steps
• At one extreme, the two processes take place
  simultaneously designated SN2
• S substitution
• N nucleophilic
• 2 bimolecular (two species are involved in the
  rate-determining step)
• rate khaloalkanenucleophile

• In the other limiting mechanism, bond breaking
  between carbon and the leaving group is entirely
  completed before bond forming with the
  nucleophile begins. This mechanism is designated
  SN1 where
• S substitution
• N nucleophilic
• 1 unimolecular (only one species is involved in
  the rate-determining step)
• rate khaloalkane

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SN2 reaction bimolecular nucleophilic
substitution

• both reactants are involved in the transition
  state of the rate-determining step
• the nucleophile attacks the reactive center from
  the side opposite the leaving group

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SN2

• An energy diagram for an SN 2 reaction
• there is one transition state and no reactive
  intermediate

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SN1 reaction unimolecular nucleophilic
substitution

• SN1 is illustrated by the solvolysis of
  tert-butyl bromide
• Step 1 ionization of the C-X bond gives a
  carbocation intermediate

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SN1

• Step 2 reaction of the carbocation (an
  electrophile) with methanol (a nucleophile) gives
  an oxonium ion
• Step 3 proton transfer completes the reaction

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SN1

• An energy diagram for an SN1 reaction

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SN1

• For an SN1 reaction at a stereocenter, the
  product is a racemic mixture
• the nucleophile attacks with equal probability
  from either face of the planar carbocation
  intermediate

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Effect of variables on SN Reactions

• the nature of substituents bonded to the atom
  attacked by nucleophile
• the nature of the nucleophile
• the nature of the leaving group
• the solvent effect

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Effect of substituents on SN2
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Effect of substituents on SN1
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Effect of substituents on SN reactions

• SN1 reactions
• governed by electronic factors, namely the
  relative stabilities of carbocation intermediates
• relative rates 3 gt 2 gt 1 gt methyl
• SN2 reactions
• governed by steric factors, namely the relative
  ease of approach of the nucleophile to the site
  of reaction
• relative rates methyl gt 1 gt 2 gt 3

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Effect of substituents on SN reactions

• Effect of electronic and steric factors in
  competition between SN1 and SN2 reactions

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Nucleophilicity

• Nucleophilicity a kinetic property measured by
  the rate at which a Nu attacks a reference
  compound under a standard set of experimental
  conditions
• for example, the rate at which a set of
  nucleophiles displaces bromide ion from
  bromoethane

• Two important features
• An anion is a better nucleophile than a
  uncharged conjugated acid
• strong bases are good nucleophiles

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Nucleophilicity
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Nucleophilicity
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Leaving Group
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Leaving Group
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The Leaving Group

• the best leaving groups in this series are the
  halogens I-, Br-, and Cl-
• OH-, RO-, and NH2- are such poor leaving groups
  that they are rarely if ever displaced in
  nucleophilic substitution reactions

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Solvent Effect

• Protic solvent a solvent that contains an -OH
  group
• these solvents favor SN1 reactions the greater
  the polarity of the solvent, the easier it is to
  form carbocations in it

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Solvent Effect

• Aprotic solvent does not contain an -OH group
• it is more difficult to form carbocations in
  aprotic solvents
• aprotic solvents favor SN2 reactions

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Summary of SN1 and SN2
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Competing Reaction Elimination

• ?-Elimination removal of atoms or groups of
  atoms from adjacent carbons to form a
  carbon-carbon double bond
• we study a type of b-elimination called
  dehydrohalogenation (the elimination of HX)

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b-Elimination

• There are two limiting mechanisms for
  ß-elimination reactions
• E1 mechanism at one extreme, breaking of the C-X
  bond is complete before reaction with base breaks
  the C-H bond
• only R-X is involved in the rate-determining step
• E2 mechanism at the other extreme, breaking of
  the C-X and C-H bonds is concerted
• both R-X and base are involved in the
  rate-determining step

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E2 Mechanism

• A one-step mechanism all bond-breaking and
  bond-forming steps are concerted

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E1 Mechanism

• Step 1 ionization of C-X gives a carbocation
  intermediate
• Step 2 proton transfer from the carbocation
  intermediate to a base (in this case, the
  solvent) gives the alkene

Nucleophile -gt acting as a strong base
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Elimination

• Saytzeff rule the major product of a elimination
  is the more stable (the more highly substituted)
  alkene

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Elimination Reactions

• Summary of E1 versus E2 Reactions for Haloalkanes

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Substitution vs Elimination

• Many nucleophiles are also strong bases (OH- and
  RO-) and SN and E reactions often compete
• the ratio of SN/E products depends on the
  relative rates of the two reactions

• What favors Elimination reactions
• attacking nucleophil is a strong and large base
• steric crowding in the substrate
• High temperatures and low polarity of solvent

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SN1 versus E1

• Reactions of 2 and 3 haloalkanes in polar
  protic solvents give mixtures of substitution and
  elimination products

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SN2 versus E2

• It is considerably easier to predict the ratio of
  SN2 to E2 products

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Summary of S vs E for Haloalkanes

• for methyl and 1haloalkanes

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Summary of S vs E for Haloalkanes

• for 2 and 3 haloalkanes

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Summary of S vs E for Haloalkanes

• Examples predict the major product and the
  mechanism for each reaction

Elimination, strong base, high temp.
SN2, weak base, good nucleophil
SN1 (Elimination), strong base, good nucleophil,
protic solvent
No reaction, I is a weak base (SN2) I better
leaving group than Cl
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Carbocation rearrangements
Also 1,3- and other shifts are possible
The driving force of rearrangements is -gt to form
a more stable carbocation !!! Happens often with
secondary carbocations -gt more stable tertiary
carbocation
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Carbocation rearrangements in SN E reactions
Rearrangement
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Carbocation rearrangements in SN E reactions -gt
Wagner Meerwein rearrangements
Rearrangement of a secondary carbocations -gt more
stable tertiary carbocation
Plays an important role in biosynthesis of
molecules, i.e. Cholesterol -gt (Biochemistry)
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Carbocation rearrangements in Electrophilic
addition reactions