1. Chapter 6 Lecture Alkyl Halides: Substitution and Elimination Reactions Organic Chemistry, 8 th Edition L. G. Wade, Jr.

2. Lectures 14: Overview Reactions of Alkyl Halides S N 2 Reaction ◦ Mechanism & Energy Diagram ◦ Uses of Reaction ◦ Factors that Influence Reaction  Nucleophilicity versus Basicity  Polarizability  Nature of Solvent System (Protic vs. Aprotic)  Leaving Group Ability  Substrate Structure (Sterics, Stereochemistry) 2

3. Reactions of Alkyl Halides Chapter 63

4. The S N 2 Reaction The halogen atom on the alkyl halide is replaced with the nucleophile (HO - ). Since the halogen is more electronegative than carbon, the C—I bond breaks heterolytically and the iodide ion leaves. Chapter 64

5. S N 2 Mechanism Bimolecular nucleophilic substitution (S N 2). Concerted reaction: New bond forming and old bond breaking at same time. Reaction is second order overall. Rate = k r [alkyl halide][nucleophile]. Chapter 65

6. S N 2 Energy Diagram The S N 2 reaction is a one-step reaction. Transition state is highest in energy. Chapter 66

7. Uses for S N 2 Reactions Chapter 67

8. S N 2: Nucleophilic Strength Stronger nucleophiles react faster. Strong bases are strong nucleophiles, but not all strong nucleophiles are basic. Chapter 68

9. Basicity Versus Nucleophilicity Basicity is defined by the equilibrium constant for abstracting a proton. Nucleophilicity is defined by the rate of attack on the electrophilic carbon atom Chapter 69

10. Steric hindrance (bulkiness) hinders nucleophilicity more than it hinders basicity. Chapter 610

11. Trends in Nucleophilicity A negatively charged nucleophile is stronger than its neutral counterpart: Nucleophilicity decreases from left to right: Increases down periodic table, as size and polarizability increase: Chapter 611

12. Polarizability and Size Larger atoms have more loosely held electrons (more polarizable) ◦ Electrons move more freely towards + charge ◦ Hard ions must approach closer to react ◦ Soft ions overlap farther away 12

13. Polarizability Effect Bigger atoms have a soft shell that can start to overlap the carbon atom from a farther distance. Chapter 613

14. Solvent Effects: Protic Solvents Polar protic solvents have acidic hydrogens (O—H or N—H) that can solvate the nucleophile, reducing their nucleophilicity. Nucleophilicity in protic solvents increases as the size of the atom increases. Chapter 614

15. Solvent Effects: Aprotic Solvents Polar aprotic solvents do not have acidic protons and therefore cannot hydrogen bond. Some aprotic solvents are acetonitrile, DMF, acetone, and DMSO. S N 2 reactions proceed faster in aprotic solvents. Chapter 615

16. Crown Ethers Crown ethers solvate the cation, so the nucleophilic strength of the anion increases. Fluoride becomes a good nucleophile. Chapter 616

17. Leaving Group Ability The best leaving groups are: Electron-withdrawing, to polarize the carbon atom. Stable (not a strong base) once they have left. Polarizable, to stabilize the transition state. Chapter 617

18. Do not write S N 2 reactions that show hydroxide ions, alkoxide ions, or other strong bases serving as leaving groups. Chapter 618

19. © 2013 Pearson Education, Inc. Chapter 919 Structure of Substrate on S N 2 Reactions Relative rates for S N 2: CH 3 X > 1° > 2° >> 3° Tertiary halides do not react via the S N 2 mechanism, due to steric hindrance. Chapter 619

20. © 2013 Pearson Education, Inc. Chapter 920 Effect of Substituents on the Rates of S N 2 Reactions Chapter 620

21. Steric Effects of the Substrate on S N 2 Reactions Nucleophile approaches from the back side. It must overlap the back lobe of the C—X sp 3 orbital. Chapter 621

22. Stereochemistry of S N 2 S N 2 reactions will result in an inversion of configuration also called a Walden inversion. Chapter 622

23. © 2013 Pearson Education, Inc. Chapter 923 Back-Side Attack in the S N 2 Reaction Chapter 623

24. (R) and (S) are just names. Don’t rely on names to determine the stereochemistry of a reaction. Chapter 624