1. Dr. Wolf's CHM 201 & 202 8-1 8.6 Unimolecular Nucleophilic Substitution S N 1

2. Dr. Wolf's CHM 201 & 202 8-2 Tertiary alkyl halides are very unreactive in substitutions that proceed by the S N 2 mechanism. But they do undergo nucleophilic substitution. But by a mechanism different from S N 2. The most common examples are seen in solvolysis reactions.

3. Dr. Wolf's CHM 201 & 202 8-3 + + H Br.... : O : : HH Example of a solvolysis: Hydrolysis of tert-butyl bromide C CH 3 Br C OH........ :

4. Dr. Wolf's CHM 201 & 202 8-4 Example of a solvolysis: Hydrolysis of tert-butyl bromide + + H Br.... : O : : HHC + + O : HH Br.... : : – CH 3 C Br C OH........ :

5. Dr. Wolf's CHM 201 & 202 8-5 Example of a solvolysis: Hydrolysis of tert-butyl bromide + O : : HHC + + O : HH Br.... : : – CH 3 C Br.... : This is the nucleophilic substitution stage of the reaction; the one with which we are concerned.

6. Dr. Wolf's CHM 201 & 202 8-6 Example of a solvolysis: Hydrolysis of tert-butyl bromide + O : : HHC + + O : HH Br.... : : – CH 3 C Br.... : The reaction rate is independent of the concentration of the nucleophile and follows a first-order rate law. rate = k[(CH 3 ) 3 CBr]

7. Dr. Wolf's CHM 201 & 202 8-7 Example of a solvolysis: Hydrolysis of tert-butyl bromide + O : : HH+ Br.... : : – C + O : H H CH 3 C Br.... : The mechanism of this step is not S N 2. It is called S N 1 and begins with ionization of (CH 3 ) 3 CBr.

8. Dr. Wolf's CHM 201 & 202 8-8 rate = k[alkyl halide] First-order kinetics implies a unimolecular rate-determining step. rate = k[alkyl halide] First-order kinetics implies a unimolecular rate-determining step. Proposed mechanism is called S N 1, which stands for substitution nucleophilic unimolecular

9. Dr. Wolf's CHM 201 & 202 8-9 + Br –.. : :.. unimolecular slow C CH 3 Br.... : C H3CH3CH3CH3C +

10. Dr. Wolf's CHM 201 & 202 8-10 bimolecular fast C H3CH3CH3CH3C CH 3 + O : : HH C + O : H H

11. Dr. Wolf's CHM 201 & 202 8-11 RX carbocation formation R+R+R+R+ carbocation capture ROH 2 + proton transfer ROH

12. Dr. Wolf's CHM 201 & 202 8-12 Characteristics of the S N 1 mechanism first order kinetics: rate = k[RX] unimolecular rate-determining step carbocation intermediate rate follows carbocation stability rearrangements sometimes observed reaction is not stereospecific much racemization in reactions of optically active alkyl halides

13. Dr. Wolf's CHM 201 & 202 8-13 The rate of nucleophilic substitution by the S N 1 mechanism is governed by electronic effects. Carbocation formation is rate-determining. The more stable the carbocation, the faster its rate of formation, and the greater the rate of unimolecular nucleophilic substitution. The rate of nucleophilic substitution by the S N 1 mechanism is governed by electronic effects. Carbocation formation is rate-determining. The more stable the carbocation, the faster its rate of formation, and the greater the rate of unimolecular nucleophilic substitution.

14. Dr. Wolf's CHM 201 & 202 8-14 RBr solvolysis in aqueous formic acid Alkyl bromideClassRelative rate CH 3 BrMethyl1 CH 3 CH 2 BrPrimary2 (CH 3 ) 2 CHBrSecondary43 (CH 3 ) 3 CBrTertiary100,000,000 Table 8.5 Reactivity toward substitution by the S N 1 mechanism

15. Dr. Wolf's CHM 201 & 202 8-15 Decreasing S N 1 reactivity CH 3 Br CH 3 CH 2 Br (CH 3 ) 2 CHBr (CH 3 ) 3 CBr

16. Dr. Wolf's CHM 201 & 202 8-16 8.8 Stereochemistry of S N 1 Reactions

17. Dr. Wolf's CHM 201 & 202 8-17 Nucleophilic substitutions that exhibit first-order kinetic behavior are not stereospecific.

18. Dr. Wolf's CHM 201 & 202 8-18 Stereochemistry of an S N 1 Reaction R-(–)-2-Bromooctane HC CH 3 Br CH 3 (CH 2 ) 5 (R)-(–)-2-Octanol (17%) HC CH 3 OH CH 3 (CH 2 ) 5 C H CH 3 HO (CH 2 ) 5 CH 3 (S)-(+)-2-Octanol (83%) H2OH2OH2OH2O

19. Dr. Wolf's CHM 201 & 202 8-19 – Ionization step gives carbocation; three bonds to stereogenic center become coplanar + Figure 8.8

20. Dr. Wolf's CHM 201 & 202 8-20 – Leaving group shields one face of carbocation; nucleophile attacks faster at opposite face. + Figure 8.8

21. Dr. Wolf's CHM 201 & 202 8-21 – –– More than 50% Less than 50% + Figure 8.8

22. Dr. Wolf's CHM 201 & 202 8-22 8.11 Carbocation Rearrangements in S N 1 Reactions

23. Dr. Wolf's CHM 201 & 202 8-23 Because carbocations are intermediates in S N 1 reactions, rearrangements are possible.

24. Dr. Wolf's CHM 201 & 202 8-24 ExampleExample CH 3 C H CHCH 3 Br CH 3 H2OH2OH2OH2O C OH CH 2 CH 3 CH 3 (93%)

25. Dr. Wolf's CHM 201 & 202 8-25 CH 3 C H CHCH 3 CH 3 C CHCH 3 CH 3 ExampleExample C H CHCH 3 Br CH 3 H2OH2OH2OH2O C OH CH 2 CH 3 CH 3 (93%) + H +

26. Dr. Wolf's CHM 201 & 202 8-26 8.10 Solvent Effects

27. Dr. Wolf's CHM 201 & 202 8-27 S N 1 Reaction Rates Increase in Polar Solvents

28. Dr. Wolf's CHM 201 & 202 8-28 SolventDielectricRelative constantrate acetic acid 61 methanol334 formic acid585,000 water78150,000 Table 8.6 S N 1 Reactivity versus Solvent Polarity Most polar Fastest rate

29. Dr. Wolf's CHM 201 & 202 8-29 R+R+R+R+ RX   R X  energy of RX not much affected by polarity of solvent transition state stabilized by polar solvent

30. Dr. Wolf's CHM 201 & 202 8-30 R+R+R+R+ R+R+R+R+ RXRX energy of RX not much affected by polarity of solvent transition state stabilized by polar solvent activation energy decreases; rate increases activation energy decreases; rate increases   R X 

31. Dr. Wolf's CHM 201 & 202 8-31 S N 2 Reaction Rates Increase in Polar Aprotic Solvents An aprotic solvent is one that does not have an —OH group. So it does not solvate anion well allowing it to be effective nucleophile

32. Dr. Wolf's CHM 201 & 202 8-32 Table 8.7 S N 2 Reactivity vs Solvent SolventTypeRelative rate CH 3 OHpolar protic1 H 2 Opolar protic7 DMSOpolar aprotic1300 DMFpolar aprotic2800 Acetonitrilepolar aprotic5000 Table 8.7 S N 2 Reactivity versus Type of Solvent CH 3 CH 2 CH 2 CH 2 Br + N 3 –

33. Dr. Wolf's CHM 201 & 202 8-33 Mechanism Summary S N 1 and S N 2

34. Dr. Wolf's CHM 201 & 202 8-34 When... primary alkyl halides undergo nucleophilic substitution, they always react by the S N 2 mechanism tertiary alkyl halides undergo nucleophilic substitution, they always react by the S N 1 mechanism secondary alkyl halides undergo nucleophilic substitution, they react by the S N 1 mechanism in the presence of a weak nucleophile (solvolysis) S N 2 mechanism in the presence of a good nucleophile