Nucleophilic Substitution

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Nucleophilic Substitution
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Outline 1. Types of substrates and
nucleophiles 2. Relative stability and
rearrangements of carbocations 3. Reaction of
nucleophilic substitution SN1 4. Reaction of
nucleophilic substitution SN2 5. Nucleophilicity.
Competition between SN1 and SN2 reactions 6.
Coupled and uncoupled substitution 7.
Nucleophilic substitution with retention of
configuration
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1. Types of substrates and nucleophiles
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2. Relative Stability and Rearrangements of
Carbocations
Stability of alkyl substituted carbocations
tertiary gt secondary gt primary
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Types of carbocations
Delocalization of positive charge increases
stability of carbocations. So far, we compared
stabilities of primary, secondary and
tertiary alkyl carbocations, based on the s to p
interaction.
Participation of higher in energy p-orbitals
strongly increases stability of carbocations at
double bonds due to the p to p interaction.
Benzylic gt allylic gt alkyl gt vinylic
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The first carbocation (triphenylmethyl cation)
was synthesized in 1901 by Noris and Kehrmann.
Existence of carbocations was proved by George
Olah (NMR, X-Ray) and brought him the Nobel Prize
in 1994.
Carbocations are considered alongside with
carboanions, carbenes and radicals among the most
reactive intermediates in organic chemistry
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Rearrangements of
Carbocations
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3. Reaction of nucleophilic substitution SN1
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It is not that simle, however. If there is no
nucleophile, no reaction will happen, so there
must be some dependence of the reaction rate on
the concentration of nucleophile
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SN1 animation
The SN1 mechanism takes place 1. For tertiary
substrates always 2. For secondary substrates
sometimes 3. For primary substrates - never
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4. Reaction of nucleophilic substitution SN2
V ksubstrateNu-
SN2 animation
The SN2 mechanism takes place 1. For tertiary
substrates never 2. For secondary substrates
sometimes 3. For primary substrates - always
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SN2 reaction in the gas phase
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5. Nucleophilicity. Competition between SN1 and
SN2 reactions
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Nucleophilicity is the ability to donate a pair
of electrons at the moment of nucleophilic
substitution. Nucleophilicity depends on the
ability of the nucleophile to donate a pair of
electrons to H (basicity) and on the influence
on such ability from the substrate (usually
polarizability). Polarizability is
characteristic for large atoms and greatly
increases nucleophilicity.
Weaker bases make better leaving groups.
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6. Coupled and uncoupled substitution
Coupled substitution SN2 kinetics, the anionic
part of the ionic pair acts as a leaving
group. Uncoupled substitution SN1 kinetics, the
cationic part of the ionic pair reacts like a
carbocation.
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7. Nucleophilic substitution with retention of
configuration
a. Two-step substitution
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b. Unsymmetrical stabilization of a carbocation
c. Formation of an unsymmetrically blocked
carbocation
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c. Formation of a chiral nonclassical carbocation
82 retention