Nucleophilic Substitution

1
Chapter 8

• Nucleophilic Substitution

2
Homework

• Pp. 337-379
• Day 1 18-24
• Day 2 25-46
• Work any and all problems that you can do.

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Functional Group Transformation by Nucleophilic
Substitution

• In this chapter we will study Nucleophilic
  Subsitution reactions in which alkyl halides act
  as substrates. The halide is the leaving group
  and the carbon-halide bond is broken
  heterolytically.

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Most Frequently Encountered Nuclephiles
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Nucleophilic Substitution

• Metals used are most often group I cations such
  as lithium, sodium, or potassium
• Solvents chosen must dissolve both the alkyl
  halide and nucleophilic salt. Mixed solvents
  such as ethanol/water or polar aprotic solvents
  such as DMSO work.

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Producing Alkyl Halides
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Relative Reactivity of Leaving Groups

• Worst Best
• F- lt Cl- lt Br- lt I-

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SN2 Mechanism

• Concerted (bond breaking and bond making are
  simultaneous.
• Inversion of configuration due to Backside
  attack by anionic nucleophile.
• Relative Rates (substrates)
• tertiaryltsecondaryltprimaryltmethyl
• this is a steric effect (Steric Hindrance)
• Thought to be the mechanism of substitution for
  most primary and secondary substrates.

9
Nucleophiles and Nucleophilicity

• Solvolysis Where the solvent acts as a
  nucleophile and causes a substitution.
• Nucleophilicity measure of nucleophilic
  strength.
• Nucleophiles are all Lewis Bases.
• The conjugate base of a neutral nucleophile is
  the stronger nucleophile.

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Nucleophiles and Nucleophilicity

• In general, as long as the nucleophilic atom is
  the same, the more basic the nucleophile is, the
  more reactive it is.
• Exception Within a family of the periodic
  table, Nucleophilic Strength
• F- lt Cl- lt Br- lt I-
• This is the reverse of basicity.
• The effect is due to solvation of the
  nucleophile.

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SN1 Mechanism

• Step-wise mechanism. (bond breaking and bond
  making occur in separate steps.)
• Ionization Mechanism Carbocation is an
  intermediate.
• Relative Rates (substrates)
• methylltprimaryltsecondarylttertiary
• Stereochemistry Some Inversion of Configuration
  occurs.
• Rearrangements can occur.

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Solvent Effects on the Rate of Nucleophilic
Substitution

• SN1 Mechanisms are aided by polar protic
  solvents.
• SN2 Mechanisms are hindered by polar protic
  solvents and occur best in polar aprotic solvents.

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Substitution vs Elimination
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Tosolates are Great Leaving Groups

• p-Toluenesulfonate (TsO-) are par excellent
  leaving groups.
• They are prepared from alcohols by reactions with
  p-toluenesulfonyl chloride.