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Reaction Conditions and Regioselectivity

Sep 8, 2025

Overview

This lecture covers the thermodynamic and kinetic conditions that favor addition (adhesion) and elimination reactions, explains regioselectivity in hydrohalogenation (addition of HX to alkenes), outlines Markovnikov’s and anti-Markovnikov’s rules, and discusses the mechanisms and stereochemistry involved.

Thermodynamics and Spontaneity of Reactions

  • Addition and elimination reactions are reversible; addition is forward, elimination is backward.
  • Spontaneity of a reaction depends on Gibbs free energy (ΔG), entropy (ΔS), and enthalpy (ΔH).
  • Reaction is spontaneous if ΔG is negative, ΔH is negative, and ΔS is positive.
  • ΔG = ΔH − TΔS combines enthalpy and entropy effects.
  • At low temperatures, enthalpy dominates (favoring addition); at high temperatures, entropy dominates (favoring elimination).
  • Addition reactions are generally favored at low temperatures; elimination at high temperatures.

Entropy and Enthalpy Considerations

  • If number of product molecules > reactants, ΔS is positive (favorable).
  • If combining two reactants into one product (as in addition), ΔS is negative (unfavorable).
  • Enthalpy (ΔH) is often negative for addition reactions, making them enthalpy-driven.

Hydrohalogenation of Alkenes (Addition of HX)

  • Hydrohalogenation involves adding HX (HCl, HBr, HI) across a carbon-carbon double bond.
  • Reaction type: Electrophilic addition (alkenes act as electron-rich species attracting electrophiles).
  • For symmetrical alkenes, product identity does not depend on which carbon gets H or X.
  • For unsymmetrical alkenes, regioselectivity (preference for one direction of addition) becomes important.

Regioselectivity and Markovnikov's Rule

  • Regioselectivity: Preference for adding the electrophile (H⁺) to one carbon over another in an unsymmetrical alkene.
  • Markovnikov's Rule: In electrophilic addition, H⁺ adds to the carbon with more hydrogens; X⁻ adds to the carbon with fewer hydrogens.
  • Anti-Markovnikov addition occurs when peroxides are present; H⁺ adds to the carbon with fewer hydrogens.

Mechanism of Electrophilic Addition

  • Proceeds via a carbocation intermediate; the more stable carbocation intermediate determines the major product.
  • Tertiary carbocations are more stable than secondary, which are more stable than primary.
  • Stability is explained by resonance (benzylic/allylic) and hyperconjugation (tertiary > secondary > primary).

Stereochemistry of Addition Reactions

  • Addition via a carbocation intermediate forms a planar (sp²) center.
  • Nucleophile (e.g., Cl⁻) can attack from either side, leading to racemic mixtures (equal amounts of enantiomers).

Key Terms & Definitions

  • Addition Reaction — Process of combining two molecules into one, often across a double bond.
  • Elimination Reaction — Process of forming a double bond by removing atoms from a molecule.
  • ΔG (Gibbs Free Energy) — Determines spontaneity of a reaction.
  • ΔH (Enthalpy) — Heat change of a reaction.
  • ΔS (Entropy) — Disorder or randomness change in a reaction.
  • Regioselectivity — Selectivity of a chemical reaction toward one structural isomer over another.
  • Markovnikov's Rule — Rule that directs where electrophiles add in alkene additions.
  • Anti-Markovnikov Addition — Opposite orientation of electrophilic addition, favored by peroxides.
  • Carbocation — Carbon atom with a positive charge, an intermediate in many reactions.
  • Racemic Mixture — 50:50 mixture of two enantiomers (mirror-image isomers).

Action Items / Next Steps

  • Practice drawing products for hydrohalogenation of both symmetrical and unsymmetrical alkenes.
  • Understand and apply Markovnikov’s and anti-Markovnikov’s rules to addition reactions.
  • Review the mechanism of carbocation formation, stability, and resulting stereochemistry.
  • Prepare for additional examples and questions in the next class.