Class 17: Acid-catalyzed Hydrolysis of Esters: Proposing Mechanisms

Question 1

Use your knowledge of electrophiles, nucleophiles, and Brønsted-Lowry acids and bases to propose reaction mechanisms with curved arrows.

Answer 1

• Electrophiles:
  
  • Species that are attracted to electron-rich sites (nucleophiles)
  • Common electrophiles: carbocations, acylium ions, alkyl halides
• Nucleophiles:
  
  • Species with an available pair of electrons to donate
  • Common nucleophiles: hydroxide, alkoxides, amines, carbanions
• Brønsted-Lowry Acids and Bases:
  
  • Acids are proton (H+) donors
  • Bases are proton acceptors
• Reaction Mechanisms:
  
  • Use curved arrows to track electron movement
  • Arrows start at electron-rich sites (nucleophiles)
  • Arrows point towards electron-deficient sites (electrophiles)
  • Multiple arrows may be needed for stepwise mechanisms

Question 2

Apply the concept of LeChâtelier to drive equilibrium towards the products.

Answer 2

• Le Chatelier’s Principle:
  
  • If a stress is applied to a system at equilibrium, the system shifts to counteract the stress
  • Possible stresses: change in concentration, pressure, temperature
• Driving Equilibrium to Products:
  
  • Increase concentration of reactants
  • Remove products as they form
  • Increase pressure for reactions with fewer gaseous molecules on product side
  • Increase temperature for endothermic reactions
  • Decrease temperature for exothermic reactions

Question 3

Apply what you know about equilibrium positions to an energy diagram.

Answer 3

• Energy Diagrams:
  
  • Show relative energy levels of reactants, products, and transition states
  • Y-axis represents energy (enthalpy or Gibbs free energy)
  • X-axis represents reaction coordinate
• Equilibrium Position:
  
  • Determined by relative stabilities of reactants and products
  • Lower energy species are favored at equilibrium
  • If products are lower energy, equilibrium lies towards products
  • If reactants are lower energy, equilibrium lies towards reactants
• Relating to Diagram:
  
  • Energy difference between reactants and products indicates equilibrium position
  • Larger difference favors side with lower energy
  • Activation energy barriers show kinetic favorability
  • Higher barriers slow the approach to equilibrium

Question 4

Explain how the addition of a catalyst speeds up the reaction by making the carbonyl a better electrophile. (Be aware that catalysts affect the kinetics of a reaction, not the equilibrium)

Answer 4

• Catalyst Role:
  
  • Increases reaction rate by providing an alternative lower energy pathway
  • Does not affect equilibrium position (products vs reactants)
• Carbonyl Activation:
  
  • Carbonyl (C=O) is an electrophile, susceptible to nucleophilic attack
  • Catalysts can make the carbonyl more electrophilic/reactive
• Mechanism:
  
  • Catalyst coordinates to carbonyl oxygen, withdrawing electrons
  • Makes carbon more electrophilic/susceptible to nucleophilic attack
  • Lowers energy barrier for nucleophilic addition step
  • Speeds up rate, but does not alter equilibrium amounts
• Kinetic vs Thermodynamic Control:
  
  • Catalysts provide kinetic control by lowering activation barriers
  • Thermodynamics (equilibrium product ratio) remains unchanged

So in summary, the catalyst increases electrophilicity of the carbonyl group, facilitating the rate-limiting nucleophilic addition step kinetically without impacting the final equilibrium amounts.

Question 5

Draw an energy diagram for a multi-step mechanism showing how free energy changes as a function of reaction progress.

Answer 5

The energy diagram would have the following components:

• The x-axis represents the reaction coordinate or the progress of the reaction, going from reactants to products.
• The y-axis represents the free energy (G) of the system.

The diagram would show:

• A peak representing the transition state (highest energy point) for the first step, with the height indicating the activation energy barrier.
• A curve or line segment going downwards after the first transition state, indicating the release of free energy as the reaction proceeds past this step.
• One or more additional peaks for any subsequent steps, each representing the transition state and activation energy for that step.
• The final curve or line segment leveling off at the free energy of the products.

Question 6

Use your knowledge of electrophiles, nucleophiles, and Brønsted-Lowry acids and bases to propose reaction mechanisms with curved arrows.

Answer 6

Acyl substitution: simple, 2 step
Acid-Catalyzed nucleophilic acyl substitution: 6 step process

Question 7

Apply the concept of LeChâtelier to drive equilibrium towards the products.

Answer 7

Ways to push the reaction forward
Remove products or react half of the products to push the reaction forward (reflux)
Add lots of reactant
Catalyzed DOESN’T! JUST LOWERS ACTIVATION ENERGY

Question 8

Explain how the addition of a catalyst speeds up the reaction by making the carbonyl a better electrophile. (Be aware that catalysts affect the kinetics of a reaction, not the equilibrium)

Answer 8

Allows for protonation of carbonyl to make it more electrophilic
Allows for protonation of leaving group to make it a better leaving group
Allows for deprotonation of nucleophile to make it more nucleophilic