Overview
Section 10 of Chapter 7 introduces alternative substrates to alkyl halides, specifically sulfonates (mesylates, tosylates, triflates) and alcohols, which can participate in substitution and elimination reactions due to their excellent leaving group properties.
Sulfonates as Alternative Substrates
- Sulfonates include alkyl mesylates, tosylates, and triflates
- All three have very good leaving groups that facilitate efficient reactions
- Function as stable conjugate bases of strong acids
- Stability arises from inductive forces or resonance stabilization
- Triflate (TfO group from trifluoromethanesulfonic acid) is the best leaving group
- Best leaving group determined by examining the most acidic compound (lowest pKa)
- The conjugate base of the most acidic compound is most stable
| Sulfonate Type | Abbreviation | Acid | Relative Leaving Group Quality |
|---|
| Mesylate | Ms | Methanesulfonic acid | Good |
| Tosylate | Ts | p-Toluenesulfonic acid | Better |
| Triflate | TfO | Trifluoromethanesulfonic acid (TfOH) | Best |
Formation of Tosylates from Alcohols
- Alcohols react with tosyl chloride (TsCl) in the presence of pyridine
- Pyridine deprotonates the alcohol after initial reaction
- Product is an alkyl tosylate
- No inversion of configuration occurs during tosylate preparation
- Only the hydrogen is replaced with the Ts group
- Configuration inversion happens later during SN2 reaction, not during tosylate formation
Tosylate Reactions: Primary vs Secondary
- Primary tosylates with strong nucleophile/base (OH⁻) give major substitution product and minor elimination product
- Secondary tosylates with same reagent favor elimination as major product
- Substitution becomes minor product for secondary substrates
- Substrate type determines whether elimination or substitution predominates
Alcohols in Substitution Reactions
- Primary alcohols undergo SN2 mechanism exclusively
- Treated with hydrobromic acid (HBr) to produce alkyl bromide and water
- Strongly acidic conditions needed because OH is poor leaving group
- Protonation converts OH to H₂O⁺, making water a good leaving group
- Bromide ion then attacks nucleophilically, displacing water
- Primary carbocations too unstable to form, forcing SN2 pathway
SN1 Mechanism with Secondary and Tertiary Alcohols
- Secondary and tertiary alcohols follow SN1 pathway
- Tertiary alcohols first undergo protonation of the OH group
- Water molecule ejected as leaving group in second step
- Carbocation intermediate generated after water departure
- Nucleophilic attack occurs in final step to form tertiary bromide
- Strongly acidic, protic conditions favor SN1 for these substrates
Alcohols in Elimination Reactions
- Alcohols undergo E2 elimination with concentrated sulfuric acid and heat
- Tertiary alcohols especially prone to elimination under these conditions
- Produces alkene and water as byproduct
- Strongly acidic, protic conditions favor E1 for secondary and tertiary substrates
- Mechanism involves three steps: proton transfer, loss of leaving group, subsequent proton transfer
- Neutral leaving groups require third step for final proton transfer to generate product
Key Terms & Definitions
- Mesylate: Alkyl methanesulfonate, a good leaving group
- Tosylate: Alkyl p-toluenesulfonate, formed from tosyl chloride
- Triflate: Alkyl trifluoromethanesulfonate, the best leaving group among sulfonates
- Protic solvent: Polar solvent with acidic protons, favors SN1/E1
- Carbocation: Positively charged carbon intermediate in SN1/E1 mechanisms