1. Chemical Reactivity and Mechanisms
Organic Chemistry
Second Edition
David Klein
Chapter 6
Chemical Reactivity and Mechanisms
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Klein, Organic Chemistry 2e

2. 6.7 Nucleophiles and Electrophiles
A major focus in this course is on predicting reaction products for ionic reactions and explaining HOW such reactions work
Ionic or polar reactions result from the force of attraction between opposite charges
Ionic reactions are also guided by the octet rule
Consider how methyl chloride and methyl lithium might react
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Klein, Organic Chemistry 2e

3. 6.7 Nucleophiles
When an atom carries a formal or partial negative charge and an available pair of electrons, it is considered a nucleophile
It will love to attack a nucleus. WHY?
Explain how the molecules below are nucleophiles
What is the difference between a nucleophile and a Lewis Base?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

4. 6.7 Electrophiles
When an atom carries a formal or partial positive charge and can accept a pair of electrons, it is considered a electrophile
It will love available electrons. WHY?
Explain how the molecules above are electrophiles
What is the difference between an electrophile and a Lewis Acid?
Practice with SkillBuilder 6.2
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

5. 6.7 Electrophiles
Label all of the nucleophilic and electrophilic sites on the following molecule
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Klein, Organic Chemistry 2e

6. 6.8 Mechanisms and Arrow Pushing
We use arrows to show how electrons move when bonds break and form
It will be a huge benefit in this course to master the skill of arrow pushing
There are four main ways that electrons move in ionic reactions
Nucleophilic Attack
Loss of a Leaving Group
Proton Transfers (Acid/Base)
Rearrangements
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

7. 6.8 Nucleophilic Attack
When you identify a nucleophilic site and an electrophilic site, the arrow shows the nucleophile attacking
The tail of the arrow starts on the electrons (- charge)
The head of the arrow ends on a nucleus (+ charge)
The electrons end up being sharing rather than transferred
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

8. 6.8 Nucleophilic Attack
Nucleophilic attack may appear to occur in two steps
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Klein, Organic Chemistry 2e

9. 6.8 Loss of a Leaving Group
Loss of a leaving group occurs when a bond breaks and one atom from the bond takes BOTH electrons
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Klein, Organic Chemistry 2e

10. 6.8 Loss of a Leaving Group
1. Which arrow shows the loss of a leaving group?
2. What are the other arrows for?
3. Draw the product after the leaving group leaves
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Klein, Organic Chemistry 2e

11. 6.8 Proton Transfers
Recall from Chapter 3 that a base is protonated when it uses a pair of electrons to take an H+ from the acid.
A group can also be deprotonated (sometimes shown by writing –H+ over the reaction arrow) or
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

12. 6.8 Proton Transfers
Such electron flow can also be thought of as a proton transfer combined with resonance
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Klein, Organic Chemistry 2e

13. Klein, Organic Chemistry 2e
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Klein, Organic Chemistry 2e

14. 6.8 Carbocation Rearrangements
Carbocations can be stabilized by neighboring groups through slight orbital overlapping called hyperconjugation
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Klein, Organic Chemistry 2e

15. 6.8 Carbocation Rearrangements
Hyperconjugation and induction can both be invoked to explain the stability trend below. HOW?
If a carbocation can INTRAmolecularly rearrange to become more stable, it will likely do so before reacting with a nucleophile. WHY?
Allylic
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

16. 6.8 Carbocation Rearrangements
Two types of carbocation rearrangement are common
Hydride shift
Methyl shift
Shifts can only occur from an adjacent carbon. WHY?
Do the shifts above make the carbocation more stable?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

17. 6.11 Carbocation Rearrangements
When you encounter a carbocation, you must consider all possible rearrangements (Hydride and methyl shifts)
Identify all adjacent carbons
Identify all –H and –CH3 groups on the adjacent carbons that are capable of shifting
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

18. 6.11 Carbocation Rearrangements
When you encounter a carbocation, you must consider all possible rearrangements (Hydride and methyl shifts)
Imagine each of the groups shifting to see which yields the most stable resulting carbocation
In this case, a hydride shift will result in a more stable tertiary carbocation
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

19. 6.11 Carbocation Rearrangements
Complete the same analysis for the molecule below
Identify all adjacent carbons
Identify all –H and –CH3 groups capable of shifting
Determine which shift yields the most stable carbocation
Recall that allylic carbocations are especially stable
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

20. Klein, Organic Chemistry 2e
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Klein, Organic Chemistry 2e

21. 6.9 Combining Arrow Pushing Patterns
Classify each step in the following mechanism
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Klein, Organic Chemistry 2e

22. 6.9 Combining Arrow Pushing Patterns
Many times a single step in a mechanism will include more than one arrow pushing pattern
Identify the patterns below
There are hundreds of mechanisms that involve these key patterns
Practice with SkillBuilder 6.4
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

23. 6.10 Arrow Pushing Rules
To draw reasonable mechanisms, a few key rules should be followed
The arrow starts ON A PAIR OF ELECTRONS (a bonded pair or a lone pair)
Don’t make the mistake of starting an arrow on a nucleus! Both arrows below are incorrect. WHY?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

24. 6.10 Arrow Pushing Rules A few key rules should be followed
The arrow ends ON A NUCLEUS (electrons become a lone pair) or between two NUCLEI (electrons move into position to become a bond)
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

25. 6.10 Arrow Pushing Rules A few key rules should be followed
Avoid breaking the octet rule. NEVER give C, N, O, or F more than 8 valence electrons
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Klein, Organic Chemistry 2e

26. 6.10 Arrow Pushing Rules A few key rules should be followed
Draw arrows that follow the 4 key patterns we outlined
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

27. 6.10 Arrow Pushing Rules
Fill in necessary arrows for the reaction below
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

28. 6.10 Arrow Pushing Rules
For each mechanism below, identify the unreasonable arrows and redraw the mechanism with correct arrows
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

30. 6.12 Reversible and Irreversible Reaction Arrows
Why are some reactions drawn as equilibria and others are essentially irreversible?
The question of reversibility a both kinetic and a thermodynamic question. HOW?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

31. 6.12 Reversible and Irreversible Reaction Arrows
Consider nucleophilic attack
Draw a mechanism for the reverse reaction
How do we judge whether it will be reversible?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

32. 6.12 Reversible and Irreversible Reaction Arrows
If the attacking nucleophile is also a good leaving group, it will be a reversible attack
The reverse reaction will have a relatively low transition state energy (kinetically favored)
The reactants and products of the reaction will be similar in energy allowing significant quantities of both to exist at equilibrium (thermodynamic equilibrium)
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

33. 6.12 Reversible and Irreversible Reaction Arrows
If the attacking nucleophile is a poor leaving group, it will essentially be an irreversible attack
The reverse reaction will have a relatively HIGH transition state energy (kinetically disfavored)
The products will be much lower in energy so an insignificant quantity of reactant will remain at equilibrium
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

34. 6.12 Reversible and Irreversible Reaction Arrows
Consider loss or a leaving group
Draw a mechanism for the reverse reaction
How do we judge whether it will be reversible?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

35. 6.12 Reversible and Irreversible Reaction Arrows
Consider proton transfer
We analyzed this in detail in chapter 3 using pKa values
How do we judge reversiblity?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

36. 6.12 Reversible and Irreversible Reaction Arrows
Consider proton transfer
If the pKa difference is 10 units or more, it is generally considered irreversible
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

37. 6.12 Reversible and Irreversible Reaction Arrows
Carbocations are generally considered irreversible thermodynamically. WHY?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

38. 6.12 Reversible and Irreversible Reaction Arrows
When considering thermodynamic equilibrium, in addition to comparing relative energies, Le Châtelier’s principle must also be considered. WHY is the reaction below irreversible?
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

39. Additional Practice Problems
Label all of the nucleophilic and electrophilic sites on the following molecules
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

40. Additional Practice Problems
Draw a mechanism for a generic nucleophilic attack followed by a proton transfer.
Draw a mechanism for a generic loss of leaving group followed by a carbocation rearrangement.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

41. Additional Practice Problems
For each of the mechanistic steps below, identify what is incorrect about it.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e