30. Rank the compounds in each of the following groups in order of decreasing reactivity toward electrophilic substitution. Explain your rankings.

Transcription

1 766 hapter 16 Electrophilic Attack on Derivatives of enzene Problems 30. Rank the compounds in each of the following groups in order of decreasing reactivity toward electrophilic substitution. Explain your rankings. 3 H 2 H 2 Na H 2 H 2 3 H The rate of nitration of (chloromethyl)benzene, H 2, is 0.71 relative to the rate of nitration of benzene (51). The (chloromethyl)nitrobenzene product mixture that results contains 32% ortho, 15.5% meta, and 52.5% para isomers. Explain. 32. Specify whether you expect the benzene rings in the following compounds to be activated or deactivated. H H H NH 2 S 3 H H H ( ) Rank the compounds in each of the following groups in order of decreasing reactivity toward electrophilic aromatic substitution. Explain your answers. H H H 34. Halogenation of 1,3-dimethylbenzene (m-xylene) takes place 100 times faster than halogenation of either its 1,2- or 1,4-isomers (o- or p-xylene). Suggest an explanation.

2 Problems hapter Write the structure(s) of the major product(s) that you expect from each of the following electrophilic aromatic substitutions. Nitration of methylbenzene (toluene); sulfonation of methylbenzene (toluene); nitration of 1,1-dimethylethylbenzene (tert-butylbenzene); sulfonation of 1,1-dimethylethylbenzene (tert-butylbenzene). In what way does changing the substrate structures from methylbenzene (toluene) in and to 1,1-dimethylethylbenzene (tert-butylbenzene) in and affect the expected product distributions? 36. Write the structure(s) of the major product(s) that you expect from each of the following electrophilic aromatic substitutions. Sulfonation of methoxybenzene (anisole); bromination of nitrobenzene; nitration of benzoic acid; riedel-rafts acetylation of chlorobenzene. 37. Draw appropriate resonance forms to explain the deactivating meta-directing character of the S 3 H group in benzenesulfonic acid. 38. Do you agree with the following statement? Strongly electron-withdrawing substituents on benzene rings are meta directing because they deactivate the meta positions less than they deactivate the ortho and para positions. Explain your answer. 39. Draw appropriate resonance forms to explain the activating ortho, para-directing character of the phenyl substituent in biphenyl (margin). iphenyl 40. Give the expected major product(s) of each of the following electrophilic substitution reactions. N( ) 2 H 2 J, Al3 2, e3 HN3, H2S4 H 3 G G H S3, H2S4 S3H See hapter 15, Problem 51 HN3, H2S4, 41. Reaction review. Without consulting the Reaction Road Map on p. 721, suggest a combina tion of reagent and monosubstituted benzene that would give each of the following compounds. (Hint: Refer to Table 16-2 for guidance. aution: Directing effects arise from the group already present on the benzene ring, not the group you are trying to attach.) I EN H 3 S 3 H (h) K A

3 768 hapter 16 Electrophilic Attack on Derivatives of enzene 42. Reaction review. The preparation of the following compounds requires more than one step. As in Problem 41, suggest a monosubstituted benzene as starting material and the reagents for all the steps needed to complete their synthesis. I H 2 H 2 H 2 H 3 H K NH 2 EN H 3 NH 2 S 3 H H 2 (h) H Give the expected major product(s) of each of the following reactions. H H 2 2, e3 S3, H2S4 HN3, H2S4 NH S 3 H 2, e3 2, e3 S 3, H2S4 NH HN 3, H 2S 4 (h) 2, e3 (i), Al 3 2 N 44. When a mixture containing one mole each of the three dimethylbenzenes (o-, m-, and p-xylene) is treated with one mole of chlorine in the presence of a Lewis acid catalyst, one of the three hydrocarbons is monochlorinated in 100% yield, whereas the other two remain completely unreacted. Which isomer reacts? Explain the differences in reactivity. The same

4 Problems hapter experiment carried out on a mixture of the following three trimethylbenzenes gives a similar outcome. Answer the questions posed in for this mixture of compounds. H 3 1,2,3-Trimethylbenzene 1,2,4-Trimethylbenzene 1,3,5-Trimethylbenzene 45. Propose a reasonable synthesis of each of the following multiply substituted arenes from benzene. H 2 N E S 3 H K H S 3 H (h) 2 N 46. (4-Methoxyphenyl)methanol (anisyl alcohol) (see margin) contributes both to the flavor of licorice and to the fragrance of lavender. Propose a synthesis of this compound from methoxybenzene (anisole). (Hint: onsider your range of options for alcohol synthesis. If necessary, refer to Problem 55 of hapter 15.) 47. The science of pain control has evolved dramatically in the past several years. The body deals with pain by releasing anandamide (see Section 20-6). Anandamide binds to the cannabinoid receptor, the same site that recognizes the active ingredients in marijuana. inding to this site suppresses the perception of pain. The effect is not long lasting, because another enzyme degrades anandamide over time. Thus, recent research has focused on finding therapeutic molecules capable of blocking this anandamide-destroying enzyme. The biphenyl derivative UR597 is an experimental substance that displays some of this desired enzyme-blocking ability, and it has been demonstrated to enhance pain suppression in rats. Examine the structure of UR597 and address the following question: Would you expect UR597 to be an easy or a difficult target molecule to prepare, beginning with biphenyl (Problem 39)? If you chose easy, illustrate how the reactions of this chapter might be employed in a synthetic approach to this drug. If you chose difficult, explain why. H 2 H (4-Methoxyphenyl)methanol (Anisyl alcohol) H 2 N HN UR597

5 770 hapter 16 Electrophilic Attack on Derivatives of enzene 48. The NMR and IR spectra for four unknown compounds A through D are presented below and on the next two pages. Possible empirical formulas for them (not in any particular order) are 6 H 5, 6 H 6 N, and 6 H 5 2 N (one of these formulas is used twice two of the unknowns are isomers). Propose a structure and suggest a synthesis of each unknown, starting from benzene. NMR 2 H 3 H 100 Transmittance (%) MHz NMR spectrum ppm ( δ ) A 0 IR IR-A cm 1 Wavenumber NMR H Transmittance (%) 2 H MHz NMR spectrum ppm ( δ ) IR cm 1 Wavenumber IR-

6 Problems hapter NMR H ( ) 4 Si MHz NMR spectrum ppm ( δ) 100 Transmittance (%) IR cm 1 Wavenumber IR- 49. atalytic hydrogenation of naphthalene over Pd results in rapid addition of 2 moles of H 2. Propose a structure for this product. 50. Predict the major mononitration product of each of the following disubstituted naphthalenes. 1,3-Dimethylnaphthalene; 1-chloro-5-methoxynaphthalene; 1,7-dinitronaphthalene; 1,6-dichloronaphthalene.

7 772 hapter 16 Electrophilic Attack on Derivatives of enzene NMR 2 H 2 H H ( ) 4 Si 8.0 D MHz NMR spectrum ppm ( δ ) 100 Transmittance (%) IR IR-D Wavenumber cm Write the expected product(s) of each of the following reactions. 2, 4, HN3 onc. H2S4, H3, Al3, S2 2, e Sulfonation of naphthalene at 808 gives almost entirely 1-naphthalenesulfonic acid, whereas the same reaction at 1608 gives 2-naphthalenesulfonic acid. Propose an explanation. (Hint: or the underlying principle, see Section 14-6.)

8 Problems hapter Electrophilic substitution on the benzene ring of benzenethiol (thiophenol, 6 H 5 SH) is not possible. Why? What do you think happens when benzenethiol is allowed to react with an electrophile? (Hint: Review Section 9-10.) 54. Although methoxy is a strongly activating (and ortho, para directing) group, the meta positions in methoxybenzene (anisole) are actually slightly deactivated toward electrophilic substitution relative to benzene. Explain. 55. Predict the result of mononitration of 56. The nitroso group, N, as a substituent on a benzene ring acts as an ortho, para directing group but is deactivating. Use the Lewis structure of the nitroso group and its inductive and resonance interactions with the benzene ring to explain this finding. (Hint: onsider possible similarities to another type of substituent that is ortho, para directing but deactivating.) 57. Typical conditions for nitrosation are illustrated in the following equation. Propose a detailed mechanism for this reaction. H H H NaN2, H, H2 N N Team Problem 58. Polystyrene (polyethenylbenzene) is a familiar polymer used in the manufacture of foam cups and packing beads. ne could, in principle, synthesize polystyrene by cationic polymerization with acid. However, this approach is unsuccessful because of the formation of dimer A. H2S4, H2 Styrene A Split your group into two teams. The first should formulate a mechanism for the cationic polymerization of styrene using acid; the second should do so for the formation of A. Reconvene and compare your notes. At which stage is the normal polymerization sequence diverted to generate A?

9 774 hapter 16 Electrophilic Attack on Derivatives of enzene Preprofessional Problems 59. Which of the following reactions is an electrophilic aromatic substitution? Se, H 12 6 H 6 6 H 5 2, h 6 H 5 H 2 3, 60 6 H 6 ( ) 2 HH 6 H 5 H( ) 2 6 H 5 Mg, ether 6 H 5 Mg 60. The intermediate cation A in the sequence 6 H 6 1 E 1 S A S 6 H 5 E 1 is best shown as H H E H E E E EH 61. The NMR spectrum of an unknown compound shows absorptions at (no multiplicities given) d (5 H), 2.3 (), and 0.9 (6 H) ppm. ne of the following five structures satisfies these data. Which one? (Hint: The NMR signal for ethane is at d ppm, that for benzene at d ppm.) H 2 6 H 5 H 2 H 2 6 H 5 H( ) 2 H A volume of 135 ml of benzene was treated with excess 2 and Al 3 to yield 50 ml of chlorobenzene. Given the atomic weights of , H , and , and the densities of benzene, 0.78 g ml 21, and chlorobenzene, 1.10 g ml 21, the percent yield is closest to 15; 26; 35; 46; Among the following choices, the group that activates the benzene ring toward electrophilic aromatic substitution is ; 2 3 ; 2 H; ;.