Elimination reactions

1
Elimination reactions

• Chapter 6

2
Elimination reactions

• A problem that often occurs in substitution
  reactions is elimination

3
E1-elimination
n k substrate

• The mechanism is similar to that of the SN1
  reaction the first step is formation of the
  carbocation via heterolytic cleavage

4
Substitution vs elimination

• Elimination and substitution reactions are
  competing processes in this case, the tertiary
  carbocation gives
• primarily elimination in the presence of a strong
  base (EtO)
• mainly substitution if there is only a good
  nucleophile present
• This can be considered as a rule of thumb

5
pKas revisited
pK 4.2 9.1 9.4 10.7 15.2 15.7 15.9 19 35
pKa 10 1.7 3.2 4.2 7.0 9.4 15.2 25 45
Base CH3CO2 CN NH3 (CH3CH2)3N CH3O HO CH3CH2O
(CH3)3CO NH2
Acid HI H3O HF CH3CO2H H2S NH4 MeOH HC?CH H2CCH
2

• The pK values are those of the conjugated acids
• If the pK of the conjugated base is higher than
  the pKa of the acid deprotonation is possible (pK
  gt 12-15 strong base)

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The Saytzeff elimination

• Saytzeff elimination in the elimination process,
  formation of the most substituted double bond is
  favored

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Explanation

• In the transition state for elimination, the
  increased stability of the most substituted
  double bond is already felt so that there is a
  lower energy barrier for elimination of Ha

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Problems

• 6.20 Predict the products of the E1 and SN1
  reactions of the following molecules in water

9
The E2 elimination
n k substrate base

• As in the SN2 reaction, the rate is dependent on
  the concentration of both reaction partners

10
E2 vs SN2

• There is a strong similarity between the E2 and
  SN2 reactions strong nucleophiles favor
  substitution, while strong bases favor elimination

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Steric bulk favors elimination

• We already saw that SN2 substitution on a
  tertiary carbon is not possible, therefore E2
  elimination will prevail (beside E1 elimination)

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Other examples

• Note that at a primary carbon atom, only SN2 and
  no SN1 substitution is possible

13
Stereochemistry of the E2 rxn

• Possible orientations of the proton that
  eliminates and the leaving group

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E2 and the anti-conformation

• The E2 elimination takes place in a single
  process in the anti-conformation proton
  abstraction, double bond formation and cleavage
  of the CL bond occur simultaneously

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Resemblance to SN2

• The mechanism is more or less analogous to the
  SN2 substitution
• The process is also called anti-elimination or
  antiperiplanar elimination

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How to visualize this aspect ?

• What are the products of E2 elimination of both
  diastereomers ?

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The answer..
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Regiochemistry

• Generally, formation of the most substituted
  double bond is favored
• Note the occurrence of E- and Z-isomers

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Saytzeff vs Hofmann elimination
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Influence of the base
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Effect of the leaving group

• Especially quarternary ammonium leaving groups
  favor the Hofmann product

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The E1cB elimination

• The E1cB reaction resembles the SN2 reaction,
  with the difference that there is an anion formed
  prior to the loss of the leaving group

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The three eliminations

• E1cB the proton is removed first, an anion is
  formed
• E1 the leaving group departs first, a cation is
  formed
• E2 all processes occur at the same time

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Example of an E1cB reaction

• This reaction is possible if there is a group
  present that can stabilize the negative charge

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Stability of anions

• The more substituted the carbanion, the less
  stable it is this is a result of the inductively
  electron donating alkyl groups

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The synthetic outlook
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Formation of CC-bonds

• Formation of CC-bonds is a synthetically
  important reaction

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Summary
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Summary (2)
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Problems

• Make problems 6.30, 6.31, 6.32, 6.38, 6.53,
  6.54, 6.56, 6.59