CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (Homework) W

CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W

Short Answer

Exhibit 23-1 Draw the structure of the aldol self-condensation product for each of the following compounds. If a

compound does not undergo aldol self-condensation, explain why it does not.

Exhibit 23-2 Consider the reaction below to answer the following question(s):

5. Refer to Exhibit 23-2. Write the complete stepwise mechanism for the reaction above. Show all intermediate

structures and all electron flow with arrows.

6. Refer to Exhibit 23-2. This reaction is an example of:

1 CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W

a. an intramolecular Claisen condensation b. an intramolecular aldol condensation c. a Robinson annulation d. a Michael reaction

7. Refer to Exhibit 23-2. The product of this reaction is:

a. a , -unsaturated aldehyde b. an , -unsaturated ketone c. an , -unsaturated aldehyde d. an enol

Exhibit 23-3 Consider the data below to answer the following question(s):

The Friedlander Quinoline Synthesis, first reported in 1882, is the base-catalyzed condensation of 2-aminobenzaldehydes with ketones to form quinoline derivatives.

8. Refer to Exhibit 23-3. The first step of the Friedlander Quinoline Synthesis is a mixed aldol condensation. Write the complete stepwise mechanism for this reaction.

9. Refer to Exhibit 23-3. The second step of the Friedlander Quinoline Synthesis is a nucleophilic addition of a primary amine to a ketone yielding an imine. Write the complete stepwise mechanism for this imine forming reaction. Show all electron flow with arrows and show all intermediate structures.

2 CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W

10. In the alkylation of cyclohexanone, better yields are obtained by first reacting cyclohexanone with an equivalent of lithium diisopropylamide in THF and then adding the alkyl halide, rather than mixing cyclohexanone, alkyl halide, and a catalytic amount of sodium ethoxide in ethanol. Explain this observation by pointing out what the problems with the second reaction conditions might be and how the first set of

reaction conditions help alleviate the problems.

Exhibit 23-4 Each of the following compounds can be prepared by a mixed aldol condensation reaction. Give the structures

of the aldehyde and/or ketone precursors for each aldol product and formulate the reaction.

11.

12.

13.

Exhibit 23-5 Consider the reaction below to answer the following question(s).

14. Refer to Exhibit 23-5. Which carbonyl compound functions as the electrophile in this reaction?

15. Refer to Exhibit 23-5. This reaction is an example of:

a. a mixed Claisen condensation. b. a Dieckman condensation. c. a Michael reaction. d. a mixed aldol reaction.

Exhibit 23-6 Draw the structure of the product you would expect to obtain by Claisen condensation of each of the

following esters. If an ester does not undergo Claisen condensation, explain why it does not.

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16.

17.

18.

Exhibit 23-7 Consider the reaction below to answer the following question(s):

Acetoacetic ester can be prepared by the Claisen self-condensation reaction of ethyl acetate.

19. Refer to Exhibit 23-7. Write the complete stepwise mechanism for this reaction. Show all electron flow with

arrows and draw all intermediate structures.

20. Ethyl acetate can be prepared from ethanol as the only organic starting material. Show all reagents and

structures for all intermediates in this preparation.

21. Give the structures of the ester precursors for the following Claisen condensation product and formulate the reaction.

Exhibit 23-8 Consider the compound 2-methyl-2-carboethoxycyclopentanone, whose structure is shown below, to answer the following question(s).

4 CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W

22. Refer to Exhibit 23-8. Formulate a synthesis of 2-methyl-2-carboethoxycyclopentanone starting with acyclic precursors using a Dieckmann cyclization as a key carbon-carbon bond forming step. Show all reagents and

all intermediate structures.

23. Refer to Exhibit 23-8. When 2-methyl-2-carboethoxycyclopentanone is treated with sodium ethoxide in ethanol solution followed by a mild aqueous acid work-up, 5-methyl-2-carboethoxycyclopentanone is isolated as the major product. This reaction proceeds by a reverse Claisen condensation mechanism followed by a recyclization. On the structures provided below, show electron flow with arrows in this interesting reaction.

24. Oxaloacetic acid is an important intermediate in the biosynthesis of citric acid. Synthesize oxaloacetic acid using a mixed Claisen condensation as a key carbon-carbon bond forming reaction.

Exhibit 23-9 Draw the structures of the precursors to each of the following Michael reaction products. Label the Michael

donor and the Michael acceptor in each case and formulate the reaction.

25.

26.

5 CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W

27.

28.

29.

Exhibit 23-10 Consider the reaction below to answer the following question(s).

The Stork enamine reaction is a variation on the Michael reaction which utilizes an enamine nucleophile.

30. Refer to Exhibit 23-10. On the structures above, draw arrows indicating electron flow in each step of this

reaction.

31. Refer to Exhibit 23-10. Draw the structures of the Ketone + Amine products of this reaction.

32. Refer to Exhibit 23-10. Show how you might use a Stork enamine reaction to prepare the following compound.

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33. Show how you might use a Robinson annulation reaction to synthesize the following compound. Draw the structures of both reactants and the structure of the intermediate Michael addition product.

Exhibit 23-11

Give the major organic product(s) for each of the following reactions or reaction sequences.

34.

35.

36.

7 CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W

37.

38. A multistep synthesis can be used to prepare 3,3-dimethylindanone. From the list provided below, choose the best reagent(s) for each step in this sequence. Place the letter in the box over the reaction arrow.

a. Cl2, HOAc e. I2, NaOH, H 2O b. 0.05 equiv. NaOEt, ethanol, heat f. H2SO4,  c. 1. PhMgBr, ether g. 1. (Ph)2CuLi, ether + + 2. H3O 2. H3O d. 1. Mg, ether h. 1. LDA, THF 2. CO2 2. (CH3)2CHBr + 3. H3O i. SOCl2, CHCl3

39. Consider the following molecular model. Atoms other than carbon and hydrogen are labeled.

8 CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W

A synthesis is set-up based upon treatment of this compound with NaOH in ethanol. This synthesis aims to produce the following substance.

What is wrong with this synthesis?

40. Draw the products of the Claisen condensation of the following substance. Atoms other than carbon and hydrogen are labeled.

9 CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W

CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W Answer Section

SHORT ANSWER

1. ANS:

PTS: 1

2. ANS:

Benzophenone does not undergo aldol self-condensation because it has no -hydrogens.

PTS: 1

3. ANS:

PTS: 1

4. ANS:

2,2-Dimethylpropanal does not undergo aldol self-condensation because it has no -hydrogens.

PTS: 1

5. ANS:

PTS: 1

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6. ANS:

PTS: 1

7. ANS:

PTS: 1

8. ANS:

PTS: 1

9. ANS:

PTS: 1

10. ANS: When cyclohexanone is placed in a solution of sodium ethoxide in ethanol, the enolate is generated in small amounts in the presence of large amounts of ketone-ideal conditions for an aldol self-condensation. Consequently, aldol self-condensation competes with alkylation of the enolate, and product mixtures result.

11 CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W

Conversely, when cyclohexanone is treated first with an equivalent of LDA, the enolate is rapidly generated

and no ketone remains. Addition of alkyl halide then yields the desired alkylated product.

PTS: 1

11. ANS:

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12. ANS:

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13. ANS:

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14. ANS:

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15. ANS:

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16. ANS:

12 CHEM 2425. Chapter 23. Carbonyl Condensation Reactions (homework) W

This ester does not undergo Claisen condensation, because it has no -hydrogens and cannot undergo

enolization.

PTS: 1

17. ANS:

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18. ANS:

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19. ANS:

PTS: 1

20. ANS:

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PTS: 1

21. ANS:

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22. ANS:

PTS: 1

23. ANS:

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24. ANS:

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PTS: 1

25. ANS:

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26. ANS:

PTS: 1

27. ANS:

PTS: 1

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28. ANS:

PTS: 1

29. ANS:

PTS: 1

30. ANS:

PTS: 1

31. ANS:

PTS: 1

32. ANS:

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PTS: 1

33. ANS:

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34. ANS:

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35. ANS:

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PTS: 1

36. ANS:

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37. ANS:

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38. ANS:

step 1 = b; step 2 = g; step 3 = e; step 4 = i

PTS: 1

39. ANS: Benzaldehyde and its derivatives, such as p-bromobenzaldehye shown, will not undergo Aldol reactions

because they do not possess -hydrogens.

PTS: 1

40. ANS:

PTS: 1

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