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

2. Lecture 15: Overview Reactions of Alkyl Halides S N 1 Reaction ◦ Mechanism & Energy Diagram ◦ Rates of S N 1 Reactions ◦ Factors that Influence Reaction  Carbocation Stability  Solvation  Structure (Sterics, Stereochemistry) 2

3. Reactions of Alkyl Halides Chapter 63

4. The S N 1 Reaction The S N 1 reaction is a unimolecular nucleophilic substitution. It has a carbocation intermediate. Rate = k r [alkyl halide]. Racemization occurs. Chapter 64

5. S N 1 Mechanism If the nucleophile is an uncharged molecule like water or an alcohol, the positively charged product must lose a proton to give the final uncharged product. Step 1: Formation of the carbocation. Step 2: Attack of the nucleophile. Chapter 65

6. Formation of carbocation (rate-determining step) S N 1 Mechanism: Step 1 Chapter 66

7. S N 1 Mechanism: Step 2 The nucleophile attacks the carbocation, forming the product. Chapter 67

8. © 2013 Pearson Education, Inc. Chapter 98 If the nucleophile was neutral, a third step (deprotonation) will be needed. S N 1 Mechanism: Step 3 Chapter 68

9. S N 1 Energy Diagram Forming the carbocation is an endothermic step. Step 2 is fast with a low activation energy. Chapter 69

10. Rates of S N 1 Reactions Order of reactivity follows stability of carbocations (opposite to S N 2). ◦ 3° > 2° > 1° >> CH 3 X ◦ More stable carbocation requires less energy to form. A better leaving group will increase the rate of the reaction. Chapter 610

11. Solvation Effect Polar protic solvent is best because it can solvate both ions strongly through hydrogen bonding. Chapter 611

12. Structure of the Carbocation Carbocations are sp 2 hybridized and trigonal planar. The lobes of the empty p orbital are on both sides of the trigonal plane. Nucleophilic attack can occur from either side, producing mixtures of retention and inversion of configuration if the carbon is chiral. Chapter 612

13. Carbocation Stability Carbocations are stabilized by inductive effect and by hyperconjugation. Chapter 613

14. Stereochemistry of S N 1 The S N 1 reaction produces mixtures of enantiomers. There is usually more inversion than retention of configuration. Chapter 614

15. Rearrangements Carbocations can rearrange to form a more stable carbocation. Move the smallest group on the adjacent carbon: ◦ Hydride shift: H - on adjacent carbon moves. ◦ Methyl shift: CH 3 - on adjacent carbon moves. Chapter 615

16. Hydride and Methyl Shifts Since a primary carbocation cannot form, the methyl group on the adjacent carbon will move (along with both bonding electrons) to the primary carbon, displacing the bromide and forming a tertiary carbocation. The smallest groups on the adjacent carbon will move: If there is a hydrogen, it will give a hydride shift. Chapter 616

17. S N 1 or S N 2 Mechanism? SN2SN2SN1SN1 CH 3 X > 1º > 2º3º > 2º Strong nucleophileWeak nucleophile (may also be used as solvent) Polar aprotic solventPolar protic solvent Rate = k[alkyl halide][Nuc]Rate = k[alkyl halide] Inversion at chiral carbonRacemization No rearrangementsRearranged products Chapter 617