Medchem 5

Overview of Primary Aryl Halide Reactions

• Primary aryl halides undergo faster SN2 reactions compared to tertiary counterparts.

• The reaction mechanism involves formation of a transition state as the nucleophile collides with the carbon.

Activation Energy

• The activation energy for the primary aryl halide reaction is lower.

• In comparison, tertiary halides have a higher activation energy due to increased steric hindrance.

Mechanism of SN2 Reaction

• Nucleophilic Attack:

  • The nucleophile approaches the carbon atom simultaneously as the leaving group departs.

• Transition State Formation:

  • This occurs as the nucleophile forms a bond while the C-Br bond breaks, creating a transition state.

  • The product forms as the activation energy barrier is overcome.

Explanation of Reactivity

• Steric Hindrance:

  • A smaller leaving group results in less steric hindrance, allowing the nucleophile to attach more easily.

• Analogy of Hindrance:

  • Using the analogy of 'elephants' in a room helps illustrate how bulkiness issues prevent access to the central atom.

Role of Nucleophiles

• Types of Nucleophiles:

  • Neutral Nucleophiles: Not strong; they have shared electron pairs but lack charge to enhance reactivity.

  • Strong Nucleophiles: Usually carry a negative charge, interacting stronger with substrates.

Mechanistic Steps for Nucleophile Interaction

• Neutral Nucleophile Interaction:

  • Forms a transition state before becoming a charged product by losing a proton.

• Strong Nucleophile Interaction:

  • Reacts quickly, resulting in a straightforward transition state leading to a neutral product.

  • Displays often a single transition state pathway with fewer bumps in the energy profile.

Leaving Groups and Their Strength

• Leaving Group Stability:

  • The reactivity of the leaving group significantly impacts the reaction speed.

  • Order of reactivity from strong to weak:

    • Iodide > Bromide > Chloride > Fluoride.

• Acid-Base Relationship:

  • Strong acids have a larger Ka and a lower pKa, indicating their conjugate bases are good leaving groups.

Important Concepts of Acid Strength

• Dissociation of Strong Acids:

  • Strong acids like HCl dissociate completely in solution, producing stable ions and minimal concentration of reactants.

SN1 vs SN2 Mechanism

• SN1 Mechanism:

  • Involves the formation of a carbocation as the first step, which is rate-determining, followed by nucleophile attack.

  • Stability of Carbocations:

    • Tertiary carbocations are more stable due to hyperconjugation, making them favorable in SN1 mechanisms.

• SN2 Mechanism:

  • Involves a simultaneous reaction with the nucleophile and leaving group.

  • Back-Side Attack:

    • Occurs only when the steric hindrance is minimal, common in primary halides.

Conclusion

• The choice between SN1 and SN2 pathways depends on the structure of the substrate and the nature of the nucleophile.

• Understanding these mechanisms helps predict the reaction outcomes more effectively.