Unimolecular Nucleophilic Substitution S N 1

1. Unimolecular Nucleophilic SubstitutionSN1

2. A question... Tertiary alkyl halides are very unreactive in substitutions that proceed by the SN2 mechanism.Do they undergo nucleophilic substitution at all? • Yes. But by a mechanism different from SN2. The most common examples are seen in solvolysis reactions.

3. The Sn1 Reaction

4. CH3 H CH3 .. : : O : C Br .. H CH3 CH3 CH3 .. .. : OH C .. .. CH3 Example of a solvolysis. Hydrolysis of tert-butyl bromide. + + Br H

5. Kinetics and Mechanism rate = k [alkyl halide] First-order kinetics implies a unimolecularrate-determining step. • Mechanism is called SN1, which stands forsubstitution nucleophilic unimolecular (1)

6. CH3 CH3 .. : Br C .. CH3 H3C CH3 .. – + : : C Br .. CH3 Mechanism unimolecular slow +

7. H3C CH3 H + C : : O CH3 H CH3 H CH3 + : O C H CH3 Mechanism bimolecular fast

8. R+ RX + ROH2 ROH carbocation formation carbocation capture proton transfer

9. Characteristics of the SN1 mechanism • First order kinetics: rate = k [RX] • unimolecular rate-determining step • Carbocation intermediate • rate follows carbocation stability • rearrangements are observed • Reaction is not stereospecific: • racemization in reactions of optically active alkyl halides

11. Reaction Coordinate Diagram for an SN1 Reaction

12. Carbocation Stability and SN1 Reaction Rates

13. Electronic Effects Govern SN1 Rates The rate of nucleophilic substitutionby the SN1 mechanism is governedby electronic effects. Carbocation formation is rate-determining.The more stable the carbocation, the fasterits rate of formation, and the greater the rate of unimolecular nucleophilic substitution.

15. Reactivity toward substitution by the SN1 mechanism RBr solvolysis in aqueous formic acid • Alkyl bromide Class Relative rate • CH3Br Methyl 1 • CH3CH2Br Primary 2 • (CH3)2CHBr Secondary 43 • (CH3)3CBr Tertiary 100,000,000

17. Decreasing SN1 Reactivity (CH3)3CBr (CH3)2CHBr CH3CH2Br CH3Br

18. Stereochemistry of SN1 Reactions

19. Generalization • Nucleophilic substitutions that exhibitfirst-order kinetic behavior are not stereospecific.

21. H CH3 Br C CH3(CH2)5 H CH3 OH C CH3(CH2)5 Stereochemistry of an SN1 Reaction R-(–)-2-Bromooctane H CH3 H2O C HO (CH2)5CH3 (R)-(–)-2-Octanol (17%) (S)-(+)-2-Octanol (83%)

22. The carbocation reaction intermediate leads to the formation of two stereoisomeric products

23. Step 1 Ionization stepgives carbocation; threebonds to stereogeniccenter become coplanar +

24. Step 2 + Leaving group shieldsone face of carbocation;nucleophile attacks faster at opposite face.

25. More than 50% Less than 50% +

26. Carbocation Rearrangementsin SN1 Reactions

27. Because... • carbocations are intermediatesin SN1 reactions, rearrangementsare possible.

28. Carbocations

29. Carbocations rearrange to the more stable form(s)

30. Carbocation Rearrangement Mechanism What is the starting carbocation: 1o, 2o or 3o? What is the rearranged carbocation: 1o, 2o or 3o?

31. Carbocation Rearrangement

32. CH3 CH3 H2O C CHCH3 C CH2CH3 CH3 CH3 (93%) H Br OH Example

33. Example CH3 CH3 C CHCH3 C CH2CH3 CH3 CH3 (93%) H Br OH H2O CH3 CH3 C CHCH3 C CHCH3 CH3 CH3 + + H H

34. Mechanism SummarySN1 and SN2

35. When... • primary alkyl halides undergo nucleophilic substitution, they always react by the SN2 mechanism • tertiary alkyl halides undergo nucleophilic substitution, they always react by the SN1 mechanism • secondary alkyl halides undergo nucleophilic substitution, they react by the • SN1 mechanism in the presence of a weak nucleophile (solvolysis) • SN2 mechanism in the presence of a good nucleophile

36. Putting things together