Homework Chapter 21 Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions mandatory problems are highlighted (up to page 16)

Homework Chapter 21 Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions mandatory problems are highlighted (up to page 16) SHORT ANSWER IUPAC Naming Instructions: Provide proper IUPAC names. 1. Name: Ethyl p-aminobenzoate 2. Name: bis(2-methylpropanoic) anhydride 3. Name: methyl phenylacetate 4. Name: 1

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions trans-2-butenoyl chloride 5. Name: N-cyclopentyl-3-methylbutanamide Drawing Instructions: Draw structures corresponding to each of the given names. 6. Draw: 2-propenamide 7. Draw: 3,4,5-trimethoxybenzoyl chloride 8. Draw: acetic formic anhydride 2

Chapter 21 9. Draw: N,N-dimethylformamide 10. Draw: methyl cis-3-ethylcyclobutanecarboxylate 11. Draw: (E)-2,4-dimethyl-2-hexenoyl chloride 3

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 12. What is the correct structure for phenylbenzoate? a. b. c. d. a Exhibit 21-1 What is the order of decreasing reactivity towards nucleophilic acyl substitution for the carboxylic acid derivatives? (most reactive first) 13. a. I, II, III, IV b. I, III, IV, II c. II, IV, III, I d. II, I, III, IV b 14. a. I, III, II, IV b. II, III, I, IV c. III, II, I, IV d. IV, I, III, II d 4

Chapter 21 15. The ester ethyl p-nitrobenzoate is more reactive towards nucleophilic acyl substitution than ethyl p-methyoxybenzoate. Explain this reactivity difference using both words and structures. In general, any factor that makes the carbonyl carbon more polarized will increase the reactivity of the carboxylic acid derivative. In these particular examples, both are aromatic ethyl esters. It is the substituent on the aromatic ring that is affecting the reactivity difference. The electronwithdrawing nitro group increases the polarization of the carbonyl by withdrawing electrons from it through the aromatic ring. The electron donating methoxy group decreases the polarization of the carbonyl by donating electrons to it through the aromatic ring. 16. Write the complete stepwise mechanism for the basic hydrolysis of acetamide, shown below. Show all electron flow with arrows and draw all intermediate structures. 5

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions Exhibit 21-2 Consider the reaction below to answer the following question(s): Acid halides react with diazomethane to yield diazoketones. Excess diazomethane is used to prevent the HCl produced in the reaction from reacting with the diazoketone. 17. Refer to Exhibit 21-2. Diazomethane is an example of a dipolar molecule; a molecule which is neutral overall but has charges on individual atoms. One resonance form of diazomethane is drawn below. Draw the Lewis structure of the other resonance form of diazomethane. Be sure to include all formal charges. 18. Refer to Exhibit 21-2. The intermediate structures for the mechanism for the reaction of propanyl chloride with diazomethane are provide below. Show all electron flow with arrows on these structures. 6

Chapter 21 Exhibit 21-3 Consider the reaction below to answer the following question(s): 19. Refer to Exhibit 21-3. Write the complete stepwise mechanism for this reaction. Show intermediate structures and all electron flow with arrows. 7

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 20. Refer to Exhibit 21-3. This reaction is an example of: a. an intermolecular nucleophilic acyl substitution reaction b. an intramolecular nucleophilic acyl substitution reaction c. an intermolecular S N 2 reaction d. an intramolecular S N 2 reaction b 21. Refer to Exhibit 21-3. The purpose of the base catalyst in this reaction is: a. to polarize the carbonyl group to make it more electrophilic b. to convert the ester to an intermediate carboxylic acid c. to convert the alcohol group to an alkoxide anion, which is a better nucleophile d. all of the above c 22. Refer to Exhibit 21-3. The product of this reaction is: a. a lactone b. an anhydride c. a lactam d. an ether a 23. Methyl butanoate has been isolated from pineapple oil and can be prepared by the Fischer esterification reaction shown below. Write the complete stepwise mechanism for this reaction. Show all electron flow with arrows and include all intermediate structures. 8

Chapter 21 24. Write the complete stepwise mechanism for the acid-catalyzed hydrolysis of the following amide to yield mandelic acid. Show all electron flow with arrows and draw the structures of all intermediate species. 9

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 25. The purpose of the acid catalyst in the hydrolysis of an amide is: a. to enhance the nucleophilicity of the water molecule b. to enhance the electrophilicity of the amide carbonyl carbon c. to enhance the electrophilicity of the water molecule d. to shift the equilibrium of the reaction b Exhibit 21-4 Consider the information below to answer the following question(s). The reaction of a carboxylic acid with an alcohol in the presence of acid is termed Fischer esterification. 26. Refer to Exhibit 21-4. The nucleophile in this reaction is. B 27. Refer to Exhibit 21-4. Compound C functions as in this reaction. a. a base scavenger b. a solvent c. a catalyst d. a neutralizer c 28. Refer to Exhibit 21-4. Fischer esterification is an example of: a. nucleophilic acyl addition b. nucleophilic acyl substitution c. nucleophilic acyl elimination d. nucleophilic acyl rearrangement b 10

Chapter 21 29. Refer to Exhibit 21-4. Write the stepwise mechanism for the Fischer esterification reaction of benzoic acid and methanol given above. Show all electron flow by using curved arrows, and include all intermediate structures. Exhibit 21-5 Provide structure(s) for the starting material(s), reagent(s) or the major organic product(s) of each of the following reactions or sequences of reactions. Show all relevant stereochemistry. 30. 11

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 31. 32. 33. 12

Chapter 21 34. 35. 36. 13

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 37. 38. 39. 14

Chapter 21 40. 41. 42. 15

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 43. 44. 16

Chapter 21 Exhibit 21-6 Choose the best reagent(s) from the list provided below for carrying out the following transformations. Place the letter corresponding to the best choice in the blank to the left of the transformation. a. (Ph) 2 CuLi, ether f. 1. DIBAH, toluene b. NaBH 4, ethanol 2. H 3 O + c. 1. CH 3 MgBr, ether g. 1. (Ph) 2 CHMgBr 2. H 3 O + 2. H 3 O + d. 1. LiAlH 4, THF h. 1. 2 PhMgBr, ether 2. H 3 O + 2. H 3 O + e. (CH 3 ) 2 CuLi, ether 45. h 46. a 47. d 17

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 48. f 49. d Exhibit 21-7 Show how you would accomplish each of the following transformations. More than one step may be required. Show all reagents and all intermediate structures. 50. 51. 18

Chapter 21 52. 53. 54. Aklomide, 2-chloro-4-nitrobenzamide, is an ingredient in veterinary antibacterial preparations. Propose a synthesis of aklomide starting with toluene. Show all reagents and all intermediate structures. 19

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 55. Ethyl phenylacetate is a pleasant smelling compound used in perfumery. Draw structures for each of the intermediates in the synthesis of ethyl phenylacetate below. 20

Chapter 21 Exhibit 21-8 For each pair of compounds below, tell which spectroscopic technique you would use to distinguish between the two members of the pair. Tell what differences you would expect to see. 56. IR 2250 cm 1 (nitrile) 1730 1760 cm 1 (four-membered lactam) Although you would not be expected to know the absorption of a four-membered lactam, you should be able to predict that IR spectroscopy would differentiate these two compounds based solely on the nitrile absorption in the first compound and the fact that the lactam would have a carbonyl absorption somewhere in the region of 1660 1750 cm 1. 57. 21

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions IR 1735 cm 1 1720 cm 1 (aliphatic ester) (aromatic ester) 1 H NMR methyl singlet one triplet methylene singlet one quartet 58. IR 1820, 1760 cm 1 2500 3300 cm 1 (acid OH) (anhydride) 1710 1760 cm 1 (carboxyl) 1715 cm 1 (ketone) 1 H NMR one triplet three overlapping triplets one quartet one quartet one singlet Exhibit 21-9 Refer to the data below to answer the following question(s): Kodel is a staple and filament fiber prepared from dimethyl terephthalate and 1,4- cyclohexanedimethanol. Fabric made from Kodel has good crease resistance. 59. Refer to Exhibit 21-9. Draw the structure of the Kodel polymer. 22

Chapter 21 60. Refer to Exhibit 21-9. Kodel is an example of: a. a polyurethane b. a polyester c. a polyamide d. a polycarbonate b 61. Poly(ethylene terephthalate), PET, is the polymeric material of Mylar and Dacron. What are the monomers from which PET is prepared? 2. Name the following substance. Atoms other than carbon and hydrogen are labeled. 4-methylpentanoyl chloride 23

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 63. Name the following substance. Atoms other than carbon and hydrogen are labeled. ethyl 1-chloropropanoate MULTIPLE CHOICE 1. Which of the following will take place via nucleophilic acyl substitution? a. thioester producing and acid chloride b. ester producing a thioester c. ester producing an amide d. acid anhydride producing an acid chloride C 2. The following reaction could be classified as which type of nucleophilic acyl substitution? More than one step might be needed. a. amoniolysis b. alcoholysis. c. reduction. d. hydrolysis. e. Grignard reaction. f. c or e depending on reaction conditions. g. The reaction will not occur via nucleophilic acyl substitution. D 24

Chapter 21 3. The following reaction could be classified as which type of nucleophilic acyl substitution? More than one step might be needed. a. amoniolysis b. alcoholysis. c. reduction. d. hydrolysis. e. Grignard reaction. f. c or e depending on reaction conditions. g. The reaction will not occur via nucleophilic acyl substitution. B 4. The following reaction could be classified as which type of nucleophilic acyl substitution? More than one step might be needed. a. amoniolysis b. alcoholysis. c. reduction. d. hydrolysis. e. Grignard reaction. f. c or e depending on the reaction conditions. g. The reaction will not occur via nucleophilic acyl substitution. C 5. The following reaction could be classified as which type of nucleophilic acyl substitution? 25

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions a. amoniolysis b. alcoholysis. c. reduction. d. hydrolysis. e. Grignard reaction. f. c or e depending on reaction conditions. g. The reaction will not occur via nucleophilic acyl substitution. G 6. What is the product when the following substance reacts with trimethylamine ((CH 3 ) 3 N)? Atoms other than carbon and hydrogen are labeled. a. b. c. d. D No reaction occurs. 26

Chapter 21 7. What is the name of the product when the following substance reacts with NaCH 3 COO? Atoms other than carbon and hydrogen are labeled. a. 4-methylbutanoic acid b. acetic 4-methylbutanoic anhydride c. 4-methylbutyl acetate d. acetyl 4-methylbutanoate e. No reaction occurs. B 8. Which line in the following spectrum would indicate the presence of a carbonyl group? a. 1 b. 2 c. 3 d. 4 e. 5 E 27

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions 9. Based on the following spectrum the sample used would probably be classified as a(n): a. aldehyde. b. ketone. c. ester. d. The spectrum is not specific enough to classify the substance. C 10. The following is an excerpt from a spectrum taken on an unknown sample. To which of the following functional groups might the unknown belong? a. amide b. acid chloride c. carboxylic acid d. ester e. None of these can be eliminated. D 28

Chapter 21 11. Consider the following molecular model. Atoms other than carbon and hydrogen are labeled. Which of the following reactants could be used to produce this compound? a. 1-chloropropanoic acid and ethanol b. propanoic acid and chloroethanol c. propanoic acid and ethanol A 12. Consider the structure given below which might be found in a protein. Which of the following is not applicable to this structure? a. contains three monomers b. contains amide bonds c. formed from a diacid and diamine d. contains three types of monomers e. All of these apply to this structure. C 13. Which of the following describes nucleophilic acyl substitution? a. Nucleophile adds to the electrophilic carbon of the carbonyl bond. b. Electrophile replaces a group on the carbon alpha to the carbonyl. c. Nucleophile replaces a group adjacent to the carbon of carbonyl. d. Two carbonyl groups react with each other. C 29