1. Chapter 8-9 Lecture PowerPoint
Nucleophilic Substitution
and Elimination Reactions

2. SN1: Substitution, Nucleophilic, Unimolecular
A nucleophilic substitution reaction taking place in two steps is an example of a unimolecular nucleophilic substitution (SN1) mechanism.

3. Four-way Rate Competition
SN1
SN2 E1 E2

4. SN1: Substitution, Nucleophilic, Bimolecular
SN1 reaction mechanism takes place in a two steps
The C–L bond breaks first to give a carbocation intermediate
This intermediate can then react with a nucleophile

5. SN1: Substitution, Nucleophilic, Bimolecular
SN1 free energy diagram - maps DE as reaction progresses
Two ‡s
Carbocation
intermediate
Highest EA gives
the rate limiting step

6. Factor 1: Structure of R-X/LG
Empirical data for SN1 reactions:

7. Factor 1: Structure of R-X/LG
When SN1 (top) compared with SN2 rates (bottom), we see that the two reactions are opposite in their requirements for the structure of R-X
For SN1: o > 2o >> 1o/CH3 (never)

8. Hammond Postulate

9. The Hammond Postulate Applied to SN1
In SN1 the rate limiting step is the formation of the intermediate C+
This step is endothermic
By the Hammond postulate ‡1 resembles the intermediate in energy
The ‡ for a more stable carbocation is
lower, so EA is reduced
Therefore a more stable carbocation will increase the rate of SN1

10. Carbocation Stability
Carbocations formed in SN1 processes are sp2 hybridized, trigonal planar species with an empty p-orbital
This species is highly e- deficient carbon and very reactive
When we discuss a ‘stable’ carbocation, it is relative to other carbocations-–all of them are highly reactive!

11. Carbocation Stability
Observed carbocation stabilities:
Electrostatic potential plots show large difference in positive charge character:

12. Carbocation Stability
Carbocation stability is the result of hyperconjugation.
Hyperconjugation is the spreading out of charge by the overlap of an empty p orbital with an adjacent  bond.
This overlap delocalizes the positive charge on the carbocation over a larger volume, thus stabilizing it.
Here, (CH3)2CH+ can be stabilized by hyperconjugation, but CH3+ cannot:

13. Carbocation Stability
Hyperconjugation is a similar effect to the structure of a p-bond.
A p-bond is the parallel overlap of two orbitals to make a stable bond
The overlap of a 2-e- s-bond with the empty p-orbital is not as efficient, but stabilizes the empty orbital
Note the back lobe of the sp3 orbital is also in position to overlap and stabilize the empty p-orbital

14. Carbocation Stability
Benzyl and allyl carbocations are stabilized by direct conjugation and resonance contributors
A 1o allyl cation is about as stable as a 2o carbocation
A 1o benzyl cation is about as stable as a 3o carbocation

15. SN1 Rate Determining Step
The SN1 reaction takes place in two steps.
The first step is rate determining because formation of the carbocation is much slower than formation of the final product.

16. Rate of an SN1 Reaction NaSH HS
Consider the observed kinetics for the following SN1 reaction:
NaSH HS

17. Rate of an SN1 Reaction
Note that in the free energy diagram, only the C-LG species is involved in the rate limiting step
The empirical evidence led to the SN1 mechanism, where only the bond breaking between C-LG is involved in the rate.
The nucleophile is not involved in the rate law!
ANY nucleophile will work, even weak ones!

18. Rate of an SN1 Reaction

19. Factor 2: Strength of the Nu:
Due to the observation that the nucleophile does not participate in the rate limiting step, the Nu: has no effect on the SN1 process
However, as we will see in Factor 4, the solvent of an SN1 reaction will often also act as the nucleophile
These are referred to as solvolysis reactions

20. Factor 3: Leaving Group Ability
A leaving group must leave in the rate-determining step of an SN2, SN1, E2, or E1 reaction.
The identity of the leaving group has an effect on the rate of each reaction.
A good leaving group is necessary for the reaction to be exothermic (and spontaneous) via a –DH
Leaving group ability strongly affects SN1 reactions

21. Factor 3: Leaving Group Ability
Experimental Data:
Never LGs
Good LGs

22. Factor 3: Leaving Group Ability
Overall, SN1 is similar to SN2 as far as leaving group ability:
Are never LGs!

23. Factor 4: Solvent Effects
Empirical data: Rate of SN1 reactions in various solvents:
H2O

24. Factor 4: Solvent Effects
Observation: SN1 reactions are most rapid in polar protic solvents
Consider the dissolution of NaCl in H2O. The ionic bond in NaCl is 410 kJ/mole in strength.
Water is has a strong dielectric and orients to insulate opposing charges from one another:
This allows the Na ion to be separated from the Cl ion at room temperature

25. Factor 4: Solvent Effects
In an SN1 reaction the polar protic solvent has the same effect
This stabilizes both cation and anion and facilitates the rate limiting step of the SN1 reaction:

26. Factor 4: Solvent Effects
There is a limitation with this.
Unlike the NaCl example, where no further reaction between H2O and Na+ or Cl- can occur, the carbocation is highly reactive.
With the lone pair of oxygen in proximity to stabilize, it often becomes the nucleophile!

27. Factor 4: Solvent Effects
This is called solvolysis, where the solvent becomes the nucleophile in SN1 and substitutes for the leaving group.
This reaction requires a third mechanistic step to deprotonate the O

28. Factor 4: Solvent Effects
If solvolysis is desired, the reaction is simply run in that solvent
If solvolysis is not desired, if another nucleophile is present, it will tend to react ultimately as -OH2+ can also function as a stable LG, H2O.
Compare:
SN1 solvolysis
SN1

29. Factor 5: Heat
When substitution and elimination reactions are both favored under a specific set of conditions, it is often possible to influence the outcome by changing the temperature under which the reactions take place.
All of these reactions have an EA that needs to be surmounted.
Heat will accelerate the rate of all reactions; the object is not to overheat to allow higher EA reaction pathways to compete
SN1 is accelerated by heat, but competing reactions like elimination are accelerated more per unit heat!

30. Factor 5: Heat
At a particular temperature, only a certain percentage of molecules possess enough energy to surmount an energy barrier.
As the energy barrier increases, the percentage of molecules decreases.
As the temperature increases, the percentage of molecules increases.
In general a 10o rise in temperature will double the rate of a reaction.

31. Factor 6: Stereochemistry of SN1
If an SN1 reaction is carried out on a stereochemically pure substrate, then a mixture of both the R and S enantiomers is produced.

32. Factor 6: Stereochemistry of SN1
The mechanism explains why the reaction produces both configurations of the stereocenter.
In the first step of the mechanism, Cl⁻ simply departs, leaving behind a planar carbocation.

33. Factor 6: Stereochemistry of SN1
If the intermediate contains a plane of symmetry, then one side of the carbocation is the mirror image of the other and approach from either side of the plane is equally likely.
The product of an SN1 reaction is always racemic at the carbon center

34. Summary SN1 SN1 SN2 E1 E2 Optimize SN1 rate: Optimize SN2 rate:
Factor 1: 3o >2o; never 1o, CH3
Factor 2: Any Nu:
Factor 3: Good LG/weak CB
Factor 4: Polar protic solvent
Factor 5: DS = 0
Factor 6: Non-stereospecific
Optimize SN2 rate:
Factor 1: CH3>1o>2o; never 3o
Factor 2: Strong, small Nu:
Factor 3: Good LG/weak CB
Factor 4: Polar aprotic solvent
Factor 5: DS = 0
Factor 6: Stereospecific
SN2
SN1 E1 E2