1. © 2011 Pearson Education, Inc. 1 Organic Chemistry 6 th Edition Paula Yurkanis Bruice Chapter 24 Catalysis

2. © 2011 Pearson Education, Inc. 2 A catalyst is a substance that increases the rate of a reaction without itself being consumed or changed A catalyst increases the rate of the reaction by lowering the  G ‡ of the reaction A catalyst can decrease  G ‡ of the reaction by one of three different ways Catalyst

3. © 2011 Pearson Education, Inc. 3 The Catalyst Converts the Reactant to a Less Stable Species

4. © 2011 Pearson Education, Inc. 4 The Catalyst Stabilizes the Transition State

5. © 2011 Pearson Education, Inc. 5 The Catalyst Changes the Mechanism of the Reaction

6. © 2011 Pearson Education, Inc. 6 A catalyst can provide a more favorable pathway for an organic reaction by: Increasing the susceptibility of an electrophile to nucleophilic attack Increasing the reactivity of a nucleophile Increasing the leaving ability of a group by converting it to a weaker base Increasing the stability of a transition state

7. © 2011 Pearson Education, Inc. 7 Acid Catalysis Mechanism for acid-catalyzed ester hydrolysis A proton is donated to the reactant:

8. © 2011 Pearson Education, Inc. 8 A catalyst must increase the rate of a slow step:

9. © 2011 Pearson Education, Inc. 9 In specific-acid catalysis, the proton is fully transferred before the slow step of the reaction In general-acid catalysis, the proton is transferred during the slow step of the reaction

10. © 2011 Pearson Education, Inc. 10 Comparing Specific-Acid Catalysis with General-Acid Catalysis

11. © 2011 Pearson Education, Inc. 11 A specific-acid catalyst must be a strong acid A general-acid catalyst is usually a weaker acid

12. © 2011 Pearson Education, Inc. 12 Base Catalysis A base catalyst increases the rate of the reaction by removing a proton from the reaction: specific-base-catalyzed dehydration

13. © 2011 Pearson Education, Inc. 13 The rate of the reaction is accelerated by stabilization of the transition state:

14. © 2011 Pearson Education, Inc. 14 In specific-base catalysis, the proton is completely removed before the slow step of the reaction

15. © 2011 Pearson Education, Inc. 15 In general-base catalysis, the proton is removed during the slow step of the reaction:

16. © 2011 Pearson Education, Inc. 16 Nucleophilic Catalysis Increases the rate of a reaction by acting as a nucleophile, thereby completely changing the reaction mechanism Forms an intermediate by forming a covalent bond with the reactant Also known as covalent catalysis

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19. © 2011 Pearson Education, Inc. 19 Imidazole increases the rate of ester hydrolysis because of both its nucleophilicity and its leaving ability Imidazole catalyzes ester hydrolysis via an acyl intermediate:

20. © 2011 Pearson Education, Inc. 20 Metal-Ion Catalysis A.The metal ion makes a reaction center more susceptible to receiving electrons B. The metal ion makes the leaving group a weaker base C. The metal ion increases the nucleophilicity of water Metal ions are Lewis acids: electrophilic catalyst

21. © 2011 Pearson Education, Inc. 21 Metal-bound hydroxide ions are better nucleophiles than water

22. © 2011 Pearson Education, Inc. 22 Metal-Ion-Catalyzed Decarboxylation

23. © 2011 Pearson Education, Inc. 23 Metal-Ion-Catalyzed Ester Hydrolysis The metal-bound hydroxide is a better nucleophile than water. The metal ion also decreases the basicity of the leaving group.

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25. © 2011 Pearson Education, Inc. 25 The relative rates are also called the effective molarity. The effective molarity is the advantage given to a reaction by having the reacting groups in the same molecule. The relative rate of reactant D is higher than the relative rate of B because the groups in D are less apt to adopt an unfavorable conformation for the reaction.

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27. © 2011 Pearson Education, Inc. 27 Putting a reacting group and a catalyst in the same molecule increases the rate of the reaction. Intramolecular catalysis is also known as anchimeric assistance. Intramolecular Catalysis

28. © 2011 Pearson Education, Inc. 28 The trans isomer reacts much faster than the cis isomer:

29. © 2011 Pearson Education, Inc. 29 The rate of phenyl acetate hydrolysis is enhanced by an intramolecular general base catalysis:

30. © 2011 Pearson Education, Inc. 30 In the presence of nitro groups, the ortho-carboxyl substituent acts as an intramolecular nucleophilic catalyst:

31. © 2011 Pearson Education, Inc. 31 An Intramolecular Metal-Ion Catalysis

32. © 2011 Pearson Education, Inc. 32 Most Biological Catalysts Are Enzymes The reactants are called substrates The substrate specifically fits and binds to the active site

33. © 2011 Pearson Education, Inc. 33 Hexokinase undergoes a conformational change upon binding to a substrate: red: before substrate binding green: after substrate binding

34. © 2011 Pearson Education, Inc. 34 Factors Contributing to the Catalytic Ability of Enzymes Reacting groups are brought together at the active site in the proper orientation for reaction. Some of the amino acid side chains serve as catalysts. Many enzymes have metal ions at their active sites that act as catalysts. Amino acid side chains can stabilize transition states and intermediates.

35. © 2011 Pearson Education, Inc. 35 Proposed Mechanism of Carboxypeptidase A

36. © 2011 Pearson Education, Inc. 36 The binding pocket at the active site of serine proteases dictates substrate specificity:

37. © 2011 Pearson Education, Inc. 37 Proposed Reaction Mechanism of a Serine Protease

38. © 2011 Pearson Education, Inc. 38 Lysozyme Is an Enzyme That Destroys Bacterial Cell Walls

39. © 2011 Pearson Education, Inc. 39 The amino acids at the active site of lysozyme are involved in binding the substrate

40. © 2011 Pearson Education, Inc. 40 Proposed Reaction Mechanism for Lysozyme

41. © 2011 Pearson Education, Inc. 41 The pH–rate profile of an enzyme is a function of the pK a values of the catalytic groups in the enzyme: a group is catalytically active in its basic form a group is catalytically active in its acidic form

42. © 2011 Pearson Education, Inc. 42 Glucose-6-phosphate Isomerase

43. © 2011 Pearson Education, Inc. 43 Mechanism for Aldolase