1. Organic Chemistry Second Edition Chapter 7 David Klein
Answers to Selected Questions in Lecture PowerPoints
David Klein
Chapter 7
Substitution Reactions
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Klein, Organic Chemistry 2e

2. 7.1 Substitution reactions
Which side do you think will be favored in the dynamic equilibrium? WHY?
Draw a reaction coordinate diagram that illustrates your equilibrium prediction
The negative charge is much more effectively stabilized by the Cl than the SH. The change in entropy for the reaction should be slight G°
Reaction progress
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

3. 7.2 Alkyl Halide Structure
Label each halide as either primary, secondary, or tertiary
For the circled atoms, label all of the alpha, beta, gamma, and delta carbons.
secondary
primary
primary
secondary
primary
secondary
secondary
secondary
secondary
secondary
secondary
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

4. 7.2 Alkyl Halide Structure
Label each halide as either primary, secondary, or tertiary
For the circled atoms, label all of the alpha, beta, gamma, and delta carbons.
alpha
alpha
beta
beta
delta
delta
beta
gamma
gamma
gamma
delta
delta
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

5. 7.3 Substitution Mechanisms
Draw mechanisms for each possibility and critique their likelihood
Nucleophilic attack first then loss of leaving group.
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Klein, Organic Chemistry 2e

6. 7.3 Substitution Mechanisms
Draw mechanisms for each possibility and critique their likelihood
Loss of leaving group first then nucleophilic attack
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

7. 7.3 Substitution Mechanisms
Draw mechanisms for each possibility and critique their likelihood
Both happen simultaneously
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

8. 7.4 SN2 – Rationalizing kinetic data
Draw the structure of neopentyl bromide
Is neopentyl bromide a primary, secondary, or tertiary alkyl bromide? PRIMARY
Should neopentyl bromide react by an SN2 reaction relatively quickly or relatively slowly? WHY? It does not react through an SN2 mechanism, because the tert-butyl group is very sterically hindering.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

9. 7.5 SN1 – reaction coordinate
The intermediate is the carbocation that is at a local minima
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Klein, Organic Chemistry 2e

10. 7.5 SN1 – reaction coordinate
The transition states are the local maxima. They represent the molecule when bonds are in the process of breaking and forming making them high in energy and lasting for only an instant
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

11. 7.5 SN – stereochemistry Consider the following reaction
Some competing SN2 accounts for the significantly greater inversion product.
Because the result is closer to a 50/50 mixture than to 100% inversion, SN1 seems to be the dominant mechanism
The chloride becomes a leaving group and gets solvated upon leaving.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

12. 7.5 SN – stereochemistry Consider the following reaction
Once the chloride leaves, it may also block the front side a bit by forming an ion pair with the carbocation. That can favor backside attack as well.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

13. 7.6 SN1 Complete Mechanisms
Would it also be helpful to protonate an OH
group in an SN2 substitution?
Yes, making a better leaving group also makes the SN2 occur more readily through a lower energy transition state, because the process happens during the rate determining step.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

14. 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? Water is a weak nucleophile
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

15. 7.6 SN1 Complete Mechanisms
Water is a weak nucleophile
Draw a complete mechanism. Each step is an equilibrium.
Which side will the equilibrium favor? Because of the unstable formal + charge on the H3O+, the
equilibrium may favor the reactants
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

16. 7.6 SN1 Complete Mechanisms
Water is a weak nucleophile
Which side will the equilibrium favor? Because of the unstable formal + charge on the H3O+, the H3O+ has a high standard enthalpy value, and when that value is plugged in to calculate deltaG, equilibrium may favor the reactants
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

17. 7.6 SN1 Complete Mechanisms
Water is a weak nucleophile
If the nucleophile were used as the solvent (a solvolysis reaction), would that shift the equilibrium one way or the other? Yes, making the nucleophile the solvent will create more products. Making it the solvent means there is a very large excess of it, and as Le Chatleir’s principle suggests, an excess of reactants should increase the formation of products.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

18. 7.6 SN1 Complete Mechanisms
Use the considerations from the previous slide to solve this problem
Proton transfers will be necessary, because to make the –OH a better leaving group, it must become water
The mechanism will be SN1, because a rearrangement is necessary, and because the products shown are racemic.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

19. 7.6 SN1 Complete Mechanisms
Use the considerations from the previous slide to solve this problem
Predict the reagents necessary to complete this substitution. Acid will be necessary to make convert the –OH into –OH2+, a good leaving group. Methanol will be needed as a nucleophile to attack the resulting rearranged carbocation
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

20. 7.6 SN1 Complete Mechanisms
Draw a complete mechanism
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

21. 7.6 SN1 Complete Mechanisms
Draw a complete reaction coordinate diagram including drawings for all transition states. δ+ δ+ δ+ δ+ δ+ δ+ G° δ+ δ+ δ+ δ+
Reaction progress
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

22. 7.9 Designing Syntheses
Design a synthesis for the following molecule starting from 2-chlorobutane
To get (S) product, start with (R)-2-chlorobutane. You want to promote SN2 to get desired stereochemistry, so you should add a strong nucleophile such as sodium ethoxide and a polar aprotic solvent such as acetone.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

23. 7.9 Designing Syntheses
Describe appropriate conditions for the following transformation
The leaving group is on a tertiary carbon, so we will only be able to get SN1 to occur. We will need to choose conditions that increase the rate of the slow step (loss of leaving group). We need a better leaving group, so we add TsCl and pyridine. We wouldn’t make the OH a water leaving group, because acid would protonate the nucleophile and create toxid HCN gas. Then, we add NaCN to provide our nucleophile in a second step with a polar protic solvent such as water.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

24. Addition Practice Problems
Give reasonable names for the following molecules
Label each halide as primary, secondary, or tertiary
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

25. Addition Practice Problems
Give the best set of reaction conditions to promote SN2 for the following substrate. You want to make sure you use a polar aprotic solvent and a good nucleophile to promote the substitution occurring in one step.
Describe experiments that could be done to support the proposed mechanism. You can use plane polarized light to determine that the stereochemistry of the chiral center is changed upon inversion. Also, you could measure the rate law to show it is first order with respect to both reactants.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

26. Addition Practice Problems
Give the best set of reaction conditions to promote SN1 for the following substrate. You want to use a polar protic solvent to solvate the nucleuphile so it doesn’t attack until after the LG leaves. Also, a weak nucleophile will aid in this.
Describe experiments that could be done to support the proposed mechanism. Using plane polarized light to show a racemic mixture and using rate data to get the rate law showing it is zero order with respect to the nucleophile.
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

27. Addition Practice Problems
Give a complete mechanism for the following substitution reaction
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e

28. Addition Practice Problems
Give a complete mechanism for the following substitution reaction
Copyright © 2015 John Wiley & Sons, Inc. All rights reserved.
Klein, Organic Chemistry 2e