1. S N 1 mechanisms always proceed via a carbocation intermediate in the rate determining step. The nucleophile then quickly attacks the carbocation to form the products: Recall that the following reaction does not proceed via an S N 2 mechanism. The electrophilic carbon atom is too sterically crowded for the nucleophile to attack it. For this type of substrate, the reaction proceeds by a different mechanism, an S N 1 mechanism. Substitution Reactions – S N 1 1

2. There may be more steps depending on the electrophile and/or nucleophile. Reactions in which the solvent participates as the nucleophile are known as solvolysis reactions. Substitution Reactions – S N 1 2

3. Sketch a reaction profile diagram for the following reaction: Substitution Reactions – S N 1 3

4. S N 1 reactions predominate when: A relatively stable carbocation is formed. The solvent is polar and protic. The nucleophile is a weak base (preferably a neutral molecule like H 2 O, ROH, etc.). Carbocation Stability Carbocation stability is dependent on: Delocalization (resonance). Hyperconjugation. 4

5. Carbocation Stability – Resonance Delocalization We have already seen how a delocalized charge is more stable than a localized one. For each of the following molecules, form the carbocation and draw all reasonable resonance structures: 5

6. Note that aryl and vinyl carbocations cannot be stabilized by resonance. The empty p-orbital is orthogonal to the π-system and as such cannot be delocalized: Carbocation Stability – Resonance Delocalization 6

7. Carbocations can also be stabilized by inductive effects. That is, electron rich groups can donate electron density through the sigma bonds to help stabilize a carbocation: Carbocation Stability – Inductive effects and Hyperconjugation Inductive effects are enhanced by hyperconjugation, a phenomenon where electron rich sigma MOs overlap with the empty p-orbital of the carbocation. 7

8. Just as aryl and vinyl carbocations are not stabilized by resonance, they are also not stabilized by hyperconjugation: Carbocation Stability Considering these effects, we can arrange the different types of carbocations on the : 3  w/ resonance 3  w/out resonance or 2  w/ resonance 2  w/out resonance or 1  w/ resonance 1  w/out resonance methyl vinyl or aryl >> > >> > The type of carbon atoms highlighted in red do not form carbocations in most cases 8

9. One consequence of reactions proceeding via carbocation intermediates is the occurrence of rearrangement side reactions. Consider the following reaction: The substitution product is a constitutional isomer of the product expected. Propose a mechanism for the above reaction: S N 1 - Rearrangements 9

10. It is worth noting that carbocation rearrangements can involve shifting either a hydride ion or a methyl anion. In either case, you will always be forming a more stable carbocation. S N 1 - Rearrangements Pay close attention to the way curly arrows are drawn when proposing a hydride or methyl shift. We should be able to tell if you’re proposing a hydride shift or generation of a pi bond. 10

11. The S N 1 Reaction - Kinetics. What happens to the rate of production of (CH 3 ) 3 CI if the concentration of I - is held constant and the concentration of (CH 3 ) 3 CBr is increased? Consider: What happens to the rate of production of (CH 3 ) 3 CI if the concentration of (CH 3 ) 3 CBr is held constant and the concentration of I - is increased? I - + (CH 3 ) 3 CBr → (CH 3 ) 3 CI + Br - 11

12. As we did for the S N 2 reaction, we can also write a rate law for the S N 1 reaction: The S N 1 Reaction - Kinetics. I - + (CH 3 ) 3 CBr → (CH 3 ) 3 CI + Br - Again, as with the S N 2 reaction, this type of graph is not that useful since we cannot predict the rate of reaction at some future time. In order to do so we would need to convert the graph into a linear function which is outside the scope of this course. Considering what happens to the concentrations of reactants, what would a graph or reaction rate vs. time look? 12

13. The Stereochemistry of the S N 1 reaction Unlike in an S N 2 reaction, an S N 1 reaction at an asymmetric carbon generates a racemic mixture of products. The nature of the intermediate is such that the nucleophile can attack from either side with equal likelihood. 13

14. The Stereochemistry of the S N 1 reaction Sometimes (depending on conditions) reactions occur with only partial racemization. 14

15. S N 1 and S N 2 reactions – Solvent Effects S N 1 reactions are typically done in polar protic solvents. Polar protic solvents are used because they help stabilize the transition state during the process of forming the carbocation intermediate. The more stabilized the transition state, the faster the carbocation will form: Some common polar protic solvents: 15

16. S N 1 and S N 2 reactions – Solvent Effects S N 2 reactions are typically done in polar aprotic solvents. These solvents are polar enough to solubilize the nucleophile but don’t stabilize the nucleophiles enough to prevent reaction: Some common polar aprotic solvents: 16

17. S N 1 vs. S N 2 reactions – Comparison Minimum # Steps 1 or more steps2 or more steps Intermediates? not necessarilycarbocation Reaction Order second order reactionfirst order reaction Stereochemical stereospecific inversion ofracemization (full or partial) Consequences configuration at electrophilic siteat electrophilic site Importance of very important; no reactionunimportant Nucleophile Strength for weak nucleophiles like H 2 O Importance of very important; no reaction forvery important; no reaction for Leaving Group weak leaving groups like HO - weak leaving groups like HO - Substrate Structure avoid steric hindrance;need carbocation stabilization; Dependence CH 3 > 1  > 2  (slow) > 3  (no); 3  > 2  (slow) > 1  (no); no reaction for aryl/vinylresonance stabilization helps; no reaction for aryl/vinyl Solvent polar aproticpolar protic Competing Reactions E2E1, E2, rearrangement SN1SN1SN2SN2 17

18. S N 1 vs. S N 2 reactions Would you expect the following reactions to proceed via S N 1, S N 2, both, or neither ? Draw the expected product(s) for each reaction. 18