Lecture: Halogenation and Hydroxylation Reactions

Introduction

• Continuation of addition reactions.
• Focus: Halogenation and Hydroxylation.

Halogenation

Definition

• Halogenation: Addition reaction where an alkene is treated with a halogen (Cl or Br).

Key Points

• Do not use fluorine (too reactive/explosive) or iodine (too slow, poor yields).
• Produces anti-addition products, not syn-addition products.
• Mechanism explains why only anti-addition is observed.

Mechanism

1. Alkene + Bromine
   • Alkene is electron-rich.
   • Bromine has lone pairs but is large and polarizable.
   • Bromine can display partial positive and negative charges.
   • Alkene attacks bromine (electron-rich reacts with electron-poor).
2. Formation of Bromonium Ion
   • Initial attack may seem to form a carbocation; however, produces a bromonium ion instead.
   • Bromonium ion prevents attack from the same side, forcing nucleophile to attack anti.
3. Nucleophilic Attack
   • Nucleophile (bromine) attacks from the opposite side, resulting in anti-addition.
   • Similar mechanism applies to chlorine (chloronium ion).

Summary

• Anti-addition confirmed by mechanism involving bromonium or chloronium ions.
• Symmetric and asymmetric alkene consideration.
• Halohydrin Formation: Alkene + Halogen + Water results in halohydrin (OH and halogen are anti).

Hydroxylation

Dihydroxylation

1. Anti-Dihydroxylation

   • Reagents: CO₃H (peroxy acid) followed by aqueous acid.
   • Process converts alkene to an epoxide and then to diol.
   • Example peroxy acid: mCPBA (meta-chloro peroxy benzoic acid).
   • Mechanism:
     • Step 1: Formation of epoxide via peroxy acid (oxygen attacks, giving epoxide and carboxylic acid).
     • Step 2: Epoxide is protonated, followed by nucleophilic attack by water resulting in anti-diol.

2. Syn-Dihydroxylation

   • Key Reagent: Osmium Tetroxide (OsO₄).
   • Reaction proceeds in a concerted fashion to provide syn-addition.
   • Example Reagents:
     • OsO₄ + Na₂SO₃/H₂O or OsO₄ + NaHSO₃/H₂O (two-step process).
     • Catalytic OsO₄ with co-oxidants (ex: NMO).
     • Potassium permanganate in cold conditions.
   • Mechanism:
     • Concerted process involving osmium tetroxide, adds hydroxyl groups on the same face, resulting in syn-diol.

Additional Points

• Regioselectivity in unsymmetrical alkenes (halohydrin formation, hydroxylation).
• Anti-addition is explained by steric hindrance of intermolecular structures.
• Syn-addition results from concerted mechanisms (single face approach).
• Test question strategies: Always consider regioselectivity and stereochemistry.

Conclusion

• Halogenation: Key anti-addition involving halogeniums ions.
• Dihydroxylation: Differentiation between anti and syn, dependent on reagents and mechanisms.
• Reach out for any clarification or further questions.