1. 7.6 SN1 Complete Mechanisms
In SN1, proton transfer steps often occur before the substitution process.
Why would a proton transfer sometimes be necessary before the substitution reaction? For example…
If the OH is protonated first though…
Copyright 2012 John Wiley & Sons, Inc.

2. 7.6 SN1 Complete Mechanisms
Would it also be helpful to protonate an OH
group in an SN2 substitution?
Copyright 2012 John Wiley & Sons, Inc.

3. 7.6 SN1 Complete Mechanisms
Lets look at the complete mechanism.
Practice with conceptual checkpoint 7.18
Copyright 2012 John Wiley & Sons, Inc.

4. 7.6 SN1 Complete Mechanisms
In SN1, proton transfer steps often occur after the substitution process. Examine the following example
The leaving group is
good, but what
about the nucleophile?
Draw a complete mechanism. Each step is an equilibrium. Which side will the equilibrium favor?
If the nucleophile were used as the solvent (a solvolysis reaction), would that shift the equilibrium one way or the other?
Practice with Conceptual Checkpoint 7.19
Copyright 2012 John Wiley & Sons, Inc.

5. 7.6 SN1 Complete Mechanisms
Rearrangements sometimes occur In SN1 reactions
Example:
After the leaving group
leaves, the resulting
carbocation may rearrange. What type of rearrangements are likely? WHY?
Predict the product(s), and explain why the carbocation rearrangement is likely to occur before the nucleophile has a chance to attack.
Check your work with Conceptual Checkpoint 7.20
Copyright 2012 John Wiley & Sons, Inc.

6. 7.6 SN1 Complete Mechanisms
Summary of considerations to make
Will proton transfers be necessary?
look at the quality of the leaving group
Look at the stability of the final product
Will the mechanism be SN1 or SN2?
look at how crowded the electrophilic site is
Look at how stable the resulting carbocation would be
Are rearrangements likely?
look for ways to improve the stability of the carbocation
Will the product have inversion or racemization?
SN1=racemization while SN2=inversion
Copyright 2012 John Wiley & Sons, Inc.

7. 7.6 SN1 Complete Mechanisms
Use the considerations from the previous slide to solve this problem
Predict the reagents necessary to complete this substitution.
Draw a complete mechanism
Draw a complete reaction coordinate diagram including drawings for all transition states.
Practice more with SkillBuilder 7.6
Copyright 2012 John Wiley & Sons, Inc.

8. 7.7 SN2 Complete Mechanisms
Proton transfer steps occur often in SN2 reactions for the same reasons they occur in SN1 reactions.
Copyright 2012 John Wiley & Sons, Inc.

9. 7.7 SN2 Complete Mechanisms
Proton transfer steps occur often in SN2 reactions for the same reasons they occur in SN1 reactions.
Copyright 2012 John Wiley & Sons, Inc.

10. 7.7 SN2 Complete Mechanisms
This reaction would be much slower without the proton transfers. WHY?
Qualitatively, will the enthalpy and entropy changes favor the products or the reactants?
Copyright 2012 John Wiley & Sons, Inc.

11. 7.7 SN2 Complete Mechanisms
Another example of proton transfer in SN2
Qualitatively, will the enthalpy and entropy changes favor the products or the reactants?
Are carbocation rearrangements possible in SN2?
Practice with SkillBuilder 7.7
Copyright 2012 John Wiley & Sons, Inc.

12. 7.8 SN1 vs. SN2
There are four main factors that determine whether a substitution reaction is more likely to occur by SN1 or SN2
Lets examine them in order of importance
The substrate (both sterics and the stability of the carbocation)
The quality of the leaving group
The strength of the nucleophile
The solvent
Copyright 2012 John Wiley & Sons, Inc.

13. 7.8 SN1 vs. SN2
Before we can examine carbocation stability, let’s review some terminology ad learn some new
Vinyl
Allyl
Let’s learn some new terminology
Benzyl
Aryl
Copyright 2012 John Wiley & Sons, Inc.

14. 7.8 Carbocation Stability
The stability of the resulting carbocation
If a relatively stable carbocation can form when the leaving group leaves, the mechanism may be SN1
What factors affect the stability of carbocations?
INDUCTION – already discussed
RESONANCE – example…
Copyright 2012 John Wiley & Sons, Inc.

15. 7.8 Carbocation Stability
The resonance for allylic and benzylic carbocations is illustrated below
Are allylic and benzylic halides more likely to undergo SN1 or SN2?
Copyright 2012 John Wiley & Sons, Inc.

16. 7.8 Carbocation Stability & Sterics
Consider whether vinyl and aryl halides are likely to undergo substitution
Can you make a steric argument?
Can you make a carbocation stability argument?
Practice with Conceptual Checkpoint 7.26
Copyright 2012 John Wiley & Sons, Inc.

17. 7.8 SN1 vs. SN2 (the nucleophile)
The quality of the nucleophile
What makes a nucleophile strong or weak?
Stability (induction, resonance, solvation)
Sterics
Give some examples of strong nucleophiles and some examples of weak ones
Will a strong nucleophile favor SN1 or SN2? WHY?
Practice with Conceptual Checkpoint 7.27
Copyright 2012 John Wiley & Sons, Inc.

18. 7.8 SN1 vs. SN2 (the leaving group)
What makes a leaving group good or bad?
Stability once it has left WITH a pair of electrons (induction, resonance, solvation)
Solvation
Give some examples of bad leaving groups and some examples of good ones (figure 7.28 in the text)
If the leaving group is too bad, then the substitution can’t take place by either SN1 or SN2. For example…
Copyright 2012 John Wiley & Sons, Inc.

19. 7.8 SN1 vs. SN2 (the leaving group)
The most commonly used leaving groups are halides and sulfonate ions.
What makes sulfonate ions such good leaving groups?
Practice with Conceptual Checkpoint 7.28
Copyright 2012 John Wiley & Sons, Inc.

20. 7.8 SN1 vs. SN2 (the nucleophile)
A stronger nucleophile favors SN2 , although it may react by SN1 if the substrate and is sterically hindered and the leaving group is good.
A weaker nucleophile favors SN1, although it may react by SN2 if the substrate cannot stabilize a carbocation effectively, and the leaving group is poor.
What factors make nucleophiles strong versus weak?
Copyright 2012 John Wiley & Sons, Inc.

21. 7.8 SN1 vs. SN2 (the solvent) The solvent
The solvent surrounds each species in the mechanism including the transition state. How does that help to facilitate the reaction? See next slide
Copyright 2012 John Wiley & Sons, Inc.

22. 7.8 SN1 vs. SN2 (the solvent)
The solvent ( ) surrounds each species in the mechanism including the transition state
Consider how the energy diagram would be different with a polar versus a nonpolar solvent δ+ δ- δ- δ+ δ- δ+
Copyright 2012 John Wiley & Sons, Inc.

23. 7.8 SN1 vs. SN2 (the solvent)
To specifically promote SN2, what role should the solvent play?
The solvent should facilitate the collision between the nucleophile and the electrophile.
Is it possible that the solvent could interfere with that key collision?
What type of solvent would you choose to accomplish this role?
Copyright 2012 John Wiley & Sons, Inc.

24. 7.8 SN1 vs. SN2 (the solvent) Will this reaction be SN1 or SN2?
What do the highlighted red solvents have in common that makes them better than the others?
Copyright 2012 John Wiley & Sons, Inc.

25. 7.8 Promoting SN2 (the solvent)
To promote an SN2, use a polar, aprotic solvent such as DMSO or acetonitrile
Polar aprotic solvents can stabilize the counter-ion of the nucleophile leaving the nucleophile mostly naked and ready to attack the electrophile.
Ready to attack!
Copyright 2012 John Wiley & Sons, Inc.

26. 7.8 Promoting SN2 (the solvent)
Because a polar, aprotic solvent will not effectively solvate the nucleophile, the nucleophile is less stable and starts with a high potential energy
The activation energy will be lower and the reaction faster
Copyright 2012 John Wiley & Sons, Inc.

27. 7.8 Promoting SN1 (the solvent)
To promote an SN1, use a polar, protic solvent
The protic solvent will Hydrogen bond with the nucleophile stabilizing it while the leaving group leaves first.
Copyright 2012 John Wiley & Sons, Inc.

28. 7.8 Promoting SN1 (the solvent)
A polar, protic solvent will also stabilize the full and partial charges that form during the SN1 mechanism
Practice with Conceptual Checkpoint 7.29
Copyright 2012 John Wiley & Sons, Inc.

29. 7.8 Solvent Effect on Halide Nucleophiles
Consider the nucleophiles, F-, Cl-, Br-, and I-
In a polar, protic solvent, which should be most reactive? WHY?
In a polar, aprotic solvent, which should be most reactive? WHY?
Why does the size of the halide affect its ability to attract a polar protic solvent?
Practice with SkillBuilder 7.8
Copyright 2012 John Wiley & Sons, Inc.

30. 7.9 Designing Syntheses
How do we use what we have learned to set up successful reactions?
We must choose appropriate substrate, nucleophile, leaving group, solvent, etc.
If you are working with a 1° substrate, the reaction will be SN2, so what are the best conditions?
Nucleophile?
Leaving Group?
Solvent?
Copyright 2012 John Wiley & Sons, Inc.

31. 7.9 Designing Syntheses
If you are working with a 3° substrate, the reaction will be SN1, so what are the best conditions?
Nucleophile?
Leaving Group?
Solvent?
Copyright 2012 John Wiley & Sons, Inc.

32. 7.9 Designing Syntheses
If you are working with a 2° substrate, the reaction could be SN1 or SN2, so what are the best conditions to get the stereochemistry you want, and WHY?
Nucleophile?
Leaving Group?
Solvent?
Copyright 2012 John Wiley & Sons, Inc.

33. 7.9 Designing Syntheses Some options and choices:
Copyright 2012 John Wiley & Sons, Inc.

34. 7.9 Designing Syntheses
Design a synthesis for the following molecule starting from 2-chlorobutane
Copyright 2012 John Wiley & Sons, Inc.

35. 7.9 Designing Syntheses
Sometimes its advantageous to convert a poor –OH leaving group into a OTs rather than a water. See the following example and explain why. Describe appropriate conditions for the following transformation
Practice with SkillBuilder 7.9
Copyright 2012 John Wiley & Sons, Inc.

36. Study Guide for sections 7.6-7.9
DAY 16, Terms to know:
Sections solvolysis, benzyl, aryl, sulfonate ions, protic solvent, aprotic solvent
DAY 16, Specific outcomes and skills that may be tested on exam 3:
Sections
Be able to identify when proton transfer steps are necessary prior to loss of a leaving group in substitution reactions and be able to use proper arrows to show electron movement for such steps.
Be able to identify when proton transfer steps are necessary after the loss of a leaving group and nucleophilic attack in substitution reactions and be able to use proper arrows to show electron movement for such steps.
Be able to draw a complete mechanism for substitution reactions and be able to use thermodynamic principles to predict whether each step in the mechanism (as well as the entire reaction) is product favored or reactant favored.
Be able to explain conditions under which it is appropriate to use the nulceophile also as the solvent for a reaction and why such solvolysis may allow the reaction to be more product favored than it would be otherwise.
Be able to identify situations where rearrangement steps occur in substitution reactions and correctly draw mechanisms and predict products for such reactions.
Given reactants and products, predict a set of reagents and solvents that would be most appropriate for the desired reaction.
Be able to recognize allyl, vinyl, benzyl, and aryl sites and how such sites affect the stability of a carbocation in a proposed SN1 reaction.
Be able to assess the strength of the nucleophile and how the solvent used affects the nucleophile’s strength in a substitution reaction and what impact that will have on whether the reaction goes by an SN1 or an SN2 mechanism.
Be able to explain what makes sulfonates such great leaving groups.
Be able to thoroughly describe the role of the solvent in a substitution reaction and how it interacts with the reactants, transitions states, intermediates, and products.
Be able to explain how the polarity or the solvent and whether it is protic affects the mechanism of the substitution reaction.
Be able to give examples of solvents that fit each of the following categories: polar protic, polar aprotic, nonpolar.
For a specific desired product, be able to give the best reaction conditions including nucleophile, substrate with leaving group, solvent, and temperature.
Klein, Organic Chemistry 2e

37. Practice Problems for sections 7.6-7.9
Complete these problems outside of class until you are confident you have learned the SKILLS in this section outlined on the study guide and we will review some of them next class period
Klein, Organic Chemistry 2e

38. Prep for Day 17 Must Watch videos: Other helpful videos:
(naming alkenes)
(E2 reactions)
(E2 regioselectivity: Zaitsev versus Hoffman)
Other helpful videos:
(naming alkenes examples)
(E2 regioselectivity)
(lecture 25)
Read sections regiochemistry
Klein, Organic Chemistry 2e