substitutionreactions–)areview)of)concepts) 1. sn2)chemistry.bd.psu.edu/justik/chem 210/chem 210...

CHEM 210 [CHAPTER 6: SUBSTITUTION REACTIONS OF ALKYL HALIDES

1 Fall 2013

Substitution Reactions – A Review of Concepts

1. SN2 1. For each of the following reactions draw the mechanism for SN2:

2. Sometimes a nucleophile and leaving group can be in the same molecule. Here, an intra-‐molecular SN2 reaction occurs. Draw the mechanism:

3. SN2 reactions exhibit second order kinetics. Consider the reaction below and answer the questions:

a. What happens to the rate if the concentration of: b. 1-‐iodopropane is tripled and sodium hydroxide remains the same? c. 1-‐iodopropane remains the same and sodium hydroxide is doubled? d. 1-‐iodopropane is doubled and the concentration of sodium hydroxide tripled?

4. Stereochemical inversion; Draw the product for each of the following SN2 reactions:

a. (S)-‐2-‐chloropentane and NaSH b. (R)-‐3-‐iodohexane and NaCl c. (R)-‐2-‐bromohexane and NaOH

5. Explain: When (S)-‐1-‐bromo-‐1-‐flouorethane reacts with sodium methoxide (NaOCH3) an SN2 reaction takes

place in which the bromine atom is replaced by the methoxy group (OCH3). The product is (S)-‐1-‐fluoro-‐1-‐methoxyethane. How can it be that the starting material and product have the same S configuration? Draw the starting material and product of inversion and explain the anomaly. Drawing the mechanism of inversion may provide confirmation that inversion is really occurring.


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6. Draw the transition state for the following SN2 reactions:

7. For each of the following pairs of compounds indicate which would react most rapidly in an SN2 reaction. Be able to explain your choice in each case.

8. Which is the stronger nucleophile in each pair: a. NaSH vs. H2S b. NaOH vs. water c. NaOCH3 in HOCH3 vs. NaOCH3 in DMSO

9. Classify each of the following solvents as protic or aprotic:

a. DMF b. Ethanol c. DMSO d. Water e. Ammonia


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10. (S)-‐2-‐iodopentane undergoes racemization in a solution of NaI in DMSO. Why?

11. The following reaction is very slow:

a. Identify the mechanism. b. Why is the reaction slow? c. What modification would make the reaction very fast?

12. Consider the following SN2 reaction:

a. Draw the mechanism b. What is the rate equation? c. What would happen to the rate if the solvent changed from DMSO to ethanol? d. Draw the energy diagram. e. Draw the transition state of the reaction.

2. SN1 13. Draw the carbocation intermediate generated by each of the following alkyl halides:

14. Which of the following compounds will undergo SN1 more rapidly? Why?

15. Draw the products of each of the following SN1 reactions. Show all stereoisomers possible:


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16. Draw the two products that you expect in the following SN1 reaction and describe their stereochemical

relationship:

17. Will an SN1 process involving each of the following nucleophiles require a deprotonation step at the end of the

mechanism?

18. Draw the mechanism for the following SN1 reactions:



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20. Arrange the following carbocations in order of increasing stability:

21. Draw the carbocation intermediate that would be formed in each of the following substrates and classify each

as primary, secondary or tertiary:


a. Draw the mechanism b. What is the rate equation? c. What would happen to the rate if more NaSH were added? d. What would happen to the rate if HSH was used instead? e. Draw the energy diagram. f. Draw the carbocation and classify it by substitution.

3. SN1 or SN2 23. Determine which substitution mechanism is favored by each of the following solvents:

24. Consider the compound below. a) Identify each position where SN2 is likely to occur. b) Identify each position where SN1 is likely to occur.


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25. Do each of the following nucleophiles favor SN1 or SN2?

26. Determine whether each of the following substrates favors SN1 or SN2, both or neither:

27. Show the reagents, solvents and conditions necessary for each of the following substitution reactions:

28. Determine whether the process would proceed by SN1 or SN2 and draw the product:


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KEY 1. For each of the following reactions draw the mechanism for SN2:

2. SoDraw the mechanism:

3.

a. Rate tripled; b. Rate doubled; c. Rate sextupled

4. Stereochemical inversion; Draw the product for each of the following SN2 reactions:

5. Explain: Remember the center physically inverts regardless of what we “call” it. Usually the nucleophile and

leaving group would both be “priority 1” in the Cahn-‐Ingold-‐Prelog naming system, so 99% of the time we are correct in saying R !S or S ! R. In this example, the rules of priority change such that S remains S by the naming convention, even though the center inverts!

6. Draw the transition state for the following SN2 reactions:


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7. For each of the following pairs of compounds indicate which would react most rapidly in an SN2 reaction. Be

able to explain your choice in each case.

8. Which is the stronger nucleophile in each pair: a. NaSH b. NaOH c. NaOCH3 in DMSO

9. Classify each of the following solvents as protic or aprotic: a. DMF -‐aprotic b. Ethanol -‐ protic c. DMSO -‐ aprotic d. Water -‐ protic e. Ammonia -‐ protic

10. Iodine functions as a nucleophile and attacks the S-‐isomer inverting the center to the R-‐isomer. The reaction can occur again to re-‐invert back to S. The reaction mixture will eventually be an equilibrium between R and S and be called racemic.

11.

The substrate is primary so this must be SN2, but the nucleophile is poor (neutral). Switch to hydroxide for increased rate.


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4. SN1 13. Draw the carbocation intermediate generated by each of the following alkyl halides:


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14. Which of the following compounds will undergo SN1 more rapidly? Why?

Both will generate a 3o carbocation, but the compound on the right allows the cation to be stabilized by resonance.

15. Draw the products of each of the following SN1 reactions. Show all stereoisomers possible:

16. Draw the two products that you expect in the following SN1 reaction and describe their stereochemical relationship:

17. Will an SN1 process involving each of the following nucleophiles require a deprotonation step at the end of the

mechanism?

a) No b) Yes c) Yes d) Yes e) No f) No g) No h) Yes i) No j) No k) Yes l) No


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18. Draw the mechanism for the following SN1 reactions:


20. Arrange the following carbocations in order of increasing stability:


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21. Draw the carbocation intermediate that would be formed in each of the following substrates and classify each as primary, secondary or tertiary:


a. Draw the mechanism b. What is the rate equation?

c. What would happen to the rate if more NaSH were added? No change! d. What would happen to the rate if HSH was used instead? No change! e. Draw the energy diagram.

f. Draw the carbocation and classify it by substitution. Tertiary

5. SN1 or SN2 23. Determine which substitution mechanism is favored by each of the following solvents:

a) SN1 b) SN2 c) SN1 d) SN2 e) SN1 f) SN2 g) SN2 h) SN1


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24. Consider the compound below. a) Identify each position where SN2 is likely to occur. b) Identify each position where SN1 is likely to occur. SN2:

SN1:

25. Do each of the following nucleophiles favor SN1 or SN2?

a) SN1, b) SN1, c) SN2, d) SN2, e) SN2

26. Determine whether each of the following substrates favors SN1 or SN2, both or neither:

a) SN1, b) SN1, c) neither d) SN1, e) Both f) Neither g) Both

27. Show the reagents, solvents and conditions necessary for each of the following substitution reactions:


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28. Determine whether the process would proceed by SN1 or SN2 and draw the product:

substitutionreactions–)areview)of)concepts) 1. sn2)chemistry.bd.psu.edu/justik/chem 210/chem 210...

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