1. Reaction Summary: SN2, E2, SN1/E1

2. Rate Competition: SN2, SN1/E1, E2
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
Optimize SN1 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
SN2
SN1 E1 E2
Optimize E2 rate:
Factor 1: 3o >2o>>1o
Factor 2: Strong Base:
Factor 3: Good LG-weak CB
Factor 4: Polar aprotic solvent
Factor 5: +DS, T increase rate
Factor 6: Stereospecific and regiospecific
Optimize E1 rate:
Factor 1: 3o >2o; never 1o, CH3
Factor 2: Any Base:
Factor 3: Good LG-weak CB
Factor 4: Polar protic solvent
Factor 5: +DS, T increase rate
Factor 6: Regiospecific only

3. Reasons for the Competition
The products of all four mechanisms can be different.
The stereochemistry of each unimolecular reaction is different from that of the corresponding bimolecular reaction.

4. Kinetic Control or Thermodynamic Control
Before you decide how to predict the major product of any competition, you must know whether the competition takes place under kinetic control or thermodynamic control.

5. Rate-Determining Steps Revisited
Because substitution and elimination reactions generally take place under kinetic control, predicting the outcome of an SN2/SN1/E2/E1 competition means we have to know how to predict the relative rates of the competing reactions.
The rate-determining step of a reaction dictates the rate of the overall reaction.

6. Factor 1: Structure of R-X/LG
Putting it all together:
Substitution and elimination reactions are almost always in competition with each other.
In order to predict the products of a reaction, it is necessary to determine which mechanisms are likely to occur.
Don’t fall into the trap of thinking that there must always be one clear winner. Sometimes there is, but sometimes there are multiple products.
The goal is to predict all of the products and to predict which products are major and which are minor.

7. Factor 1: Structure of R-X/LG
To accomplish this goal, four steps are required:
Analyze the substrate and determine the expected mechanism(s)
Determine the function of the reagent.
Consider any solvent effects.
Consider any relevant regiochemical and stereochemical requirements.

8. Factor 1: Structure of R-X/LG
Substrate: CH3, 1o, 2o, 3o, allyl or benzyl
The most important factor is the substrate!
CH3
SN2
only 1o
SN2 E2
very slow 2o
SN2 E2
SN1 E1 3o E2
SN1 E1

9. Factor 1: Structure of R-X/LG
Substrate: CH3, 1o, 2o, 3o, allyl or benzyl
Allyl and benzyl – analyze case-by-case
Act like their substitution counterparts for SN2 and E2
They form carbocations one level more stable than their substitution for SN1 and E1
Be careful with elimination! A b-hydrogen is needed for E2
1o, benzyl
SN1 only
2o, benzyl
SN1 and E1

10. Factor 2: Strength of the Nu/Base
Reagent: Nucleophilicity vs. Basicity
After we know what is possible for a substrate, we now inspect the nucleophile/base to see what will happen.
We can divide nucleophiles/bases into categories:

11. Factor 2: Strength of the Nu/Base
For “Nucleophile-only” do not use ANY of these for E1/E2.
They lack the basicity needed to react with a hydrogen
CH3
SN2
only 1o
SN2 2o
SN2
SN1 3o
SN1

12. Factor 2: Strength of the Nu/Base
For “Base (only)” use these ONLY for E2 (except CH3).
CH3
SN2
only 1o E2 2o E2 3o E2

13. Factor 1: Structure of R-X/LG
For “Strong base/strong Nu” the bimolecular mechanisms dominate.
As the substrates get more hindered, SN2 slows and E2 speeds up.
CH3
SN2
only 1o
SN2 2o
SN2 E2
major 3o E2
only

14. Factor 1: Structure of R-X/LG
For “Weak Nuc/Weak Base” the unimolecular mechanisms predominate and are always in competition.
For primary substrates the reaction will be a very slow SN2
CH3
SN2
only 1o
SN2
very slow 2o
SN1 E1 3o
SN1 E1

15. 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 E1 reactions

16. Factor 3: Leaving Group Ability
Overall, SN2, E2, SN1/E1 are the same with regard to leaving group ability:
Are never LGs!

17. Factor 4: Solvent Effects
The Solvent
Polar aprotic solvents are used for SN2 and/or E2 reactions of 2o and 3o substrates.
Primary or methyl substrates can have any solvent for SN2.
Remember that nucleophilicity of elements within a group on the periodic table increases going upward (stronger base).

18. Factor 4: Solvent Effects
The Solvent
Polar aprotic solvents are used for SN2 and/or E2 reactions of 2o and 3o substrates.
CH3
SN2
only
Polar aprotic
solvents only 1o
SN2 E2
very slow 2o
SN2 E2
SN1 E1 3o E2
SN1 E1

19. Factor 4: Solvent Effects
The Solvent
Polar protic solvents are used for SN1/E1 reactions and the solvent itself may become the nucleophile/base.
CH3
SN2
only
Polar protic
solvents only 1o
SN2 E2
very slow 2o
SN2 E2
SN1 E1 3o E2
SN1 E1

20. 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.
Heat will accelerate the rate of all reactions; however one reaction may increase more than another for a given DT
E1/E2 reactions are more strongly accelerated by heat than SN1 or SN2
∆S °rxn is more positive for an E1 and E2 than for SN1 or SN2.

21. Factor 5: Heat
You cannot use heat to exclude a product with these reactions
Heat can only change the relative concentrations of products

22. Draw the Products - Substitution
Substitution reactions are straightforward.
Remove the counterion (if even shown) or the acidic hydrogen from the Nu: and replace the LG with the nucleophilic atom

23. Draw the Products - Substitution
If stereochemistry is shown, SN2 reactions cause inversion of the carbon center:

24. Draw the Products - Substitution
If stereochemistry is shown, SN1 reactions cause racemization of the carbon center:

25. Draw the Products - Elimination
The E1 reaction is regioselective, but not stereoselective
The E2 reaction is both regioselective and stereoselective
For simple E2 (no stereochemistry shown) or any E1:
Locate all possible b-hydrogens and a-carbon (has LG) for each instance:
Remove the LG from a-carbon
Draw a double bond between a-b
If the alkene can exist as cis/trans-isomers, draw both - Zaitsev
Label the alkene with the greatest substitution as ‘major’ (trans is more stable than cis)

26. Draw the Products - Elimination
Examples:

27. Draw the Products - Elimination
For E2 where stereochemistry is shown, the b-hydrogen removed to give a particular product had to be anti-periplanar in ‡, this ‘locks’ the stereochemistry of the product alkene:

28. Draw the Products - Elimination
For E2 where stereochemistry is shown on a cyclohexane, realize that the b-hydrogen removed will be trans to the LG.
If that position is occupied by a non-H group, no E2 will occur.

29. Summary E1 SN1 SN2 E1 E2 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
Optimize SN1 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
SN2
SN1 E1 E2
Optimize E2 rate:
Factor 1: 3o >2o>>1o
Factor 2: Strong Base:
Factor 3: Good LG-weak CB
Factor 4: Polar aprotic solvent
Factor 5: +DS, T increase rate
Factor 6: Stereospecific and regiospecific
Optimize E1 rate:
Factor 1: 3o >2o; never 1o, CH3
Factor 2: Any Base:
Factor 3: Good LG-weak CB
Factor 4: Polar protic solvent
Factor 5: +DS, T increase rate
Factor 6: Regiospecific only