Chem 2/28

Introduction to Reaction Mechanisms

• Discusses transformation of starting material (alcohol) into desired products.

Case Analysis

Primary vs. Secondary Centers

• Primary center: allylic, good for SN2 reactions.

• Secondary center: SN2 reactions possible but problematic due to sterics and competition from E2.

• Stereochemistry importance: Preserving stereochemistry is critical; can do it via inversions or by avoiding bond breakage.

Reaction Sequence

• Conduct stepwise reactions to prevent undesired mixture of reactants.

• Sodium hydride reaction: Perform with care to ensure correct reactant interactions.

• Halides: Acceptable to use Br, I, or Cl as leaving groups.

Alternate Case: Same Structure - Different Strategy Needed

Stereochemistry Reversal

• Going from alcohol to alkoxide requires bond transformations leading to stereochemistry reversal.

• Challenges due to SN2 reactions at secondary centers; often lead to elimination (E1) rather than substitution (SN2).

• Strategy adjustment: Convert alcohol to a leaving group first (e.g., tosylate), then introduce alkoxide.

Mechanism Questions

Ether Cleavage with HBr

• Initial step: Protonation of the ether oxygen to create a good leaving group.

• Examine if substitution occurs via SN1 or SN2:

  • Tertiary preference leads to product formation.

  • If stereochemistry is present, it can be randomized due to possible pathways.

SN1 vs. E1 Mechanism Comparison

E1 Characteristics

• Two-step reaction. First step involves leaving group departure; forms a carbocation.

• Subsequent step involves base protonation to form alkene.

• Stereochemistry: Stereochemical outcomes can vary due to rotational freedom at the carbocation stage; can lead to stereoisomer variations but not typically applicable in SN1 conditions.

Case Study: Dehydration Reaction Example

Example with Methylcyclohexanol

• Utilize strong acid to facilitate protonation and conversion to a good leaving group; results in carbocation formation.

• Examine pathway to alkene: Loss of a proton leads to preferred via E1 mechanism yielding major product.

• Stability: Favor more substituted alkenes due to thermodynamic stability leading to preferred reaction pathways.

Driving Reactions: Le Chatelier's Principle

• Application: Use excess reagent to shift equilibrium in desired direction — whether towards SN1 or E1.

• Discuss use of distilled products to inhibit reversibility in reaction conditions.

Summary of Key Mechanisms

E2 Elimination Overview

• Single-step mechanism involving strong bases.

• Preservation of stereochemistry during elimination; requires anti-coplanar arrangement for effective product formation.

• Overarching concepts: Base structure, strong nucleophiles influence elimination versus substitution outcomes.

Experimentation in Mechanisms

• Importance of experimental design in understanding elimination stereochemistry.

• Conformations: Analyze staggered arrangements to predict product outcomes based on stereocenters.