CHEM 2425. Chapter 16. Chemistry of Benzene: Electrophilic Aromatic Substitution (homework) W Short Answer Exhibit 16-1 MATCH a structure or term from the following list with each description below. Place the letter of the structure or term in the blank to the left of the description. a. benzyne e. + NO b. + NO 2 f. Meisenheimer complex c. R 3 C + g. d. electron-donating h. electron-withdrawing i. F-TEDA-BF 4 1. The reactive electrophile in Friedel-Crafts acylation reactions. 2. The electrophile in aromatic nitration. 3. Groups which activate aromatic rings towards electrophilic substitution. 4. Groups which activate aromatic rings towards nucleophilic substitution. 5. Intermediate in the elimination-addition mechanism of nucleophilic aromatic substitution. 6. Source of F + in fluorination reactions. Exhibit 16-2 Consider the Friedel-Crafts alkylation reaction below to answer the following question(s): 7. Refer to Exhibit 16-2. Draw the structure of the electrophilic intermediate in this reaction. 8. Refer to Exhibit 16-2. What is the role of the AlCl 3 in the reaction? 9. Refer to Exhibit 16-2. Write the complete stepwise mechanism for this reaction. Show all electron flow with arrows and include all intermediate structures. 10. Aniline reacts with nitrous acid, HNO 2, to yield a stable diazonium salt. This diazonium salt undergoes electrophilic aromatic substitution on activated aromatic rings to yield brightly colored azo compounds that are widely used as dyes. The intermediate structures for the mechanism of this reaction are given below. Show all electron flow with arrows for this mechanism on the structures provided. 1
Exhibit 16-3 Consider the data below to answer the following question(s). The NH 2 group is listed in our textbook as the strongest o,p-directing activator in electrophilic aromatic substitution reactions. However, when aniline is subjected to standard nitration conditions poor yields of m-nitroaniline result. 11. Refer to Exhibit 16-3. Draw all the resonance forms of aniline showing the electron-donating effect of the NH 2 substituent. 12. Refer to Exhibit 16-3. Clearly, the reaction conditions are influencing the directing effect of the NH 2 group. Explain why this occurs, using both words and structures. Exhibit 16-4 Consider the reaction below to answer the following question(s). 2
13. Refer to Exhibit 16-4. Draw resonance structures for the intermediate carbocation that explain the directing effect of the Br. Exhibit 16-5 Rank the compounds in each group below according to their reactivity toward electrophilic aromatic substitution (most reactive = 1; least reactive = 3). Place the number corresponding to the compounds' relative reactivity in the blank below the compound. 14. 15. 16. At what position, and on what ring, is bromination of phenyl benzoate expected to occur? Explain your answer. Exhibit 16-6 To answer the following question(s), refer to the data below: Isobutylbenzene is the starting material for the industrial synthesis of the NSAID, ibuprofen. 3
17. Refer to Exhibit 16-6. Attempts to prepare isobutylbenzene by direct Friedel-Crafts alkylation of benzene result in tert-butylbenzene as the major product. Write the complete stepwise mechanism for this reaction, showing all electron flow with arrows and showing all intermediate structures. 18. Refer to Exhibit 16-6. Propose a synthesis for isobutylbenzene which avoids the problems of direct Friedel-Crafts alkylation. 19. Would you expect (nitromethyl)benzene to be more reactive or less reactive than toluene toward electrophilic substitution? Explain. Exhibit 16-7 Consider the reaction below to answer the following question(s). 20. Refer to Exhibit 16-7. The nucleophile in the reaction is: 21. Refer to Exhibit 16-7. The Lewis acid catalyst in the reaction is: 22. Refer to Exhibit 16-7. This reaction proceeds (faster or slower) than benzene. 23. The following reaction proceeds by an intramolecular nucleophilic aromatic substitution mechanism. Write the complete stepwise mechanism, showing all intermediate structures and all electron flow with arrows. 4
Exhibit 16-8 Give the major organic product(s) of each of the following reactions. If none is predicted, write "N.R." 24. 25. 26. 27. 28. 29. 5
30. 31. Exhibit 16-9 Choose the best reagent(s) from the list provided below for carrying out the following conversions. Place the letter of the reagent in the box beside the reaction number over the arrow. There is only one answer for each reaction. a. KMnO 4, H 3 O + f. ClCO(CH 2 ) 2 CH 3, AlCl 3 b. Br 2, FeBr 3 g. CH 3 CH 2 CH 2 CH 2 Cl, AlCl 3 c. Cl 2, FeCl 3 h. H 2 /Pd d. CH 3 Cl, AlCl 3 i. NBS, peroxides e. HNO 3, H 2 SO 4 j. (CH 3 ) 3 CCH 2 Cl k. F-TEDA-BF 4 32. 33. Exhibit 16-10 Propose syntheses to carry out each of the following conversions. Assume ortho and para isomers can be separated. 34. 6
35. 36. 37. Exhibit 16-11 Propose syntheses of the following compounds starting with benzene or toluene. Assume ortho and para isomers can be separated. 38. 39. 40. It is possible to synthesize 1-bromo-4-nitrobenzene by reacting bromobenzene with a mixture of nitric and sulfuric acids. However, 1-bromo-4-nitrobenzene is not obtained if nitrobenzene is reacted with Br 2 /FeBr 3. Explain the difference. 7
CHEM 2425. Chapter 16. Chemistry of Benzene: Electrophilic Aromatic Substitution (homework) W Answer Section SHORT ANSWER 1. ANS: g 2. ANS: b 3. ANS: d 4. ANS: h 5. ANS: a 6. ANS: i 7. ANS: 8. ANS: The AlCl 3 is a Lewis acid catalyst that assists in the ionization of the alkyl halide to give the carbocation electrophile. 9. ANS: 8
10. ANS: 11. ANS: 12. ANS: 9
When aniline is placed in strong acid the nitrogen atom is protonated. Electrophilic aromatic substitution on the anilinium ion whose aromatic ring is now deactivated by a positively charged substituent occurs primarily at the meta position since this keeps the positive charge of the intermediate carbocation away from the positively charged nitrogen. The intermediates shown above for ortho and para substitution are destabilized more than the intermediate for meta substitution, so m-nitroaniline is the major product. 13. ANS: 14. ANS: 15. ANS: 10
16. ANS: Attack occurs in the activated ring and yields ortho and para bromination. 17. ANS: 18. ANS: 19. ANS: (Nitromethyl)benzene should be less reactive than toluene owing to the strong inductive electron withdrawing effect of the nitro group. 20. ANS: A 21. ANS: C 11
22. ANS: slower 23. ANS: 24. ANS: N.R. Nucleophilic Aromatic Substitution requires an electron-withdrawing group in the ortho or para position. A methyl group is electron donating, and substitution will not occur. 25. ANS: 26. ANS: 27. ANS: 28. ANS: 12
29. ANS: 30. ANS: 31. ANS: 32. ANS: 33. ANS: 13
34. ANS: 35. ANS: 36. ANS: 37. ANS: 14
38. ANS: 39. ANS: 40. ANS: Bromine is an ortho-para director. The para isomer preferentially forms on nitration due to the steric hindrance of the bulky Br group. The result is a good yield of 1-bromo-4-nitrobenzene. NO 2 is a meta director and preferentially forms the meta isomer on bromination. The resulting product is the meta isomer or 1-bromo-3-nitrobenzene. 15