4.P: Arenes, Electrophilic Aromatic Substitution (Problems)

Problem 4-1 How many structurally different monomethyl derivatives are possible for each of the following compounds? Name each.

a. naphthalene
b. anthracene
c. phenanthrene

Problem 4-2 How many isomeric products could each of the dimethylbenzenes give on introduction of a third substituent? Name each isomer, using chlorine as the third substituent.

Problem 4-3 Name each of the following compounds by the IUPAC system:

a. \(\ce{(C_6H_5)_2CHCl}\)
b. \(\ce{C_6H_5CHCl_2}\)
c. \(\ce{C_6H_5CCl_3}\)
d.
e.

f.

Problem 4-4 Identify the two compounds with molecular formula \(\ce{C_7H_7Cl}\) from the infrared spectra shown in Figure 4-2.

Figure 4-2: Infrared spectra of two isomeric compounds of formula \(\ce{C_7H_7Cl}\) (see Problem 4-4)

Problem 4-5 Predict the effect on the ultraviolet spectrum of a water solution of benzenamine when hydrochloric acid is added. Explain why a solution of sodium benzenoxide absorbs at longer wavelengths than a solution of benzenol (see Table 4-3).

Problem 4-6* Estimate the chemical shifts of the protons of (a) the separate \(\ce{CH_2}\) of "1,4-hexamethylenebenzene" as compared with "1,2-hexamethylenebenzene"; and (b) cyclooctatetraene (see Section 21-9A).

Problem 4-7 Establish the structures of the following benzene derivatives on the basis of their empirical formulas and NMR spectra shown in Figure 4-6. Remember that equivalent protons normally do not split each other's resonances.

a. \(\ce{C_8H_{10}}\)
b. \(\ce{C_8H_7OCl}\)
c. \(\ce{C_9H_{10}O_2}\)
d. \(\ce{C_9H_{12}}\)

Figure 4-6: Proton NMR spectra of some benzene derivatives at \(60 \: \text{MHz}\) with reference to TMS at \(0 \: \text{ppm}\) (see Problem 4-7).

Problem 4-8 Calculate from appropriate bond-energy and stabilization-energy tables (4-3 and 21-1) the heats of chlorine with benzene to give (a) chlorobenzene and (b) 5,6-dichloro-1,3-cyclohexadiene. Your answer should indicate that substitution is energetically more favorable than addition.

Problem 4-9 Devise an experimental test to determine whether the following addition-elimination mechanism for bromination of benzene actually takes place.

Problem 4-10 Why is nitration with ethanoyl nitrate accelerated by added fluoroboric acid, \(\ce{HBF_4}\), but retarded by added hydrochloric acid?

Problem 4-11 Why do fairly reactive arenes, such as benzene, methylbenzene, and ethylbenzene, react with excess nitric acid in nitromethane solution at a rate that is independent of the concentration of the arene (i.e., zero order in arene concentration)? Does this lack of dependencies on arene concentration mean that nitration of an equimolar mixture of benzene and methylbenzene would necessarily give an equimolar mixture of nitrobenzene and nitromethylbenzenes? Why or why not?

Problem 4-12 Reagents, besides the molecular halogens, that effect halogen substitution include hypochlorous and hypobromous acids. They are most effective when a strong acid is present and care is taken to exclude formation of halide ions. Account for the catalytic effect of acid and the anticatalytic effect of halide ions.

Problem 4-13 Arrange the following bromine-containing species in order of their expected reactivity in achieving electrophilic aromatic bromination: \(\ce{HOBr}\), \(\ce{Br_2}\), \(\ce{Br}^\oplus\), \(\ce{Br}^\ominus\), \(\ce{HBr}\), \(\ce{H_2OBr}^\oplus\), \(\ce{BrCl}\).

Problem 4-14 Aluminum chloride is a much more powerful catalyst than ferric bromide for bromination of benzene. Would you expect the combination of aluminum chloride and bromine to give much chlorobenzene in reaction with benzene? Explain.

Problem 4-15

a. The bromination of benzene is catalyzed by small amounts of iodine. Devise a possible explanation for this catalytic effect.

b. The kinetic expression for the bromination of naphthalene in ethanoic acid involves a term that is first order in naphthalene and second order in bromine. How can two molecules of bromine and one of naphthalene be involved in the rate-determining step of bromination? Explain why the kinetic expression simplifies to first order in naphthalene and first order in bromine in \(50\%\) aqueous ethanoic acid.

Problem 4-16 Write a mechanism for the alkylation of benzene with 2-propanol catalyzed by boron trifluoride.

Problem 4-17 Explain how it is possible that the ratio of products isolated from equilibration of 1,2-, 1,3-, and 1,4-dimethylbenzenes is 18:58:24 if the presence of a small amount of \(\ce{HF-BF_3}\), but is essentially 0:100:0 in the presence of excess \(\ce{HF-BF_3}\). Notice that \(\ce{HBF_4}\) is an extremely strong acid.

Problem 4-18 Account for the following observations:

a. 3-Methyl-2-butanol alkylates benzene in \(\ce{HF}\) to give (1,1-dimethylpropyl)benzene.

b. 1-Chloronorbornane will not alkylate in the presence of \(\ce{AlCl_3}\).

c. 1-Methylcyclopentyl cation is formed from each of the compounds shown below under the indicated conditions at low temperatures \(\left( -70^\text{o} \right)\).

chlorocyclohexane \(\overset{\ce{SbF_5-SO_2}}{\longrightarrow}\)

cyclohexene \(\overset{\ce{HF-SbF_5-SO_2}}{\longrightarrow}\)

cyclohexanol \(\overset{\ce{FSO_3H-SbF_5}}{\longrightarrow}\)

Problem 4-19 Anthraquinone can be synthesized from phthalic anhydride and benzene in two steps. The first step is catalyzed by \(\ce{AlCl_3}\), the second by fuming sulfuric acid. Write mechanisms for both reactions and suggest why fuming sulfuric is required in the second step but not in the first.

Problem 4-20 Suggest possible routes for the synthesis of the following compounds:

a. diphenylmethane from benzoic acid and benzene
b. 1-ethyl-4-methylbenzene from methylbenzene

Problem 4-21

a. Substitution of a chloromethyl group, \(\ce{-CH_2Cl}\), on an aromatic ring is chloromethylation and is accomplished using methanal, \(\ce{HCl}\), and a metal-halide catalyst \(\left( \ce{ZnCl_2} \right)\). Write reasonable mechanistic steps that could be involved in this reaction:

\[\ce{C_6H_6} + \ce{CH_2O} + \ce{HCl} \overset{\ce{ZnCl_2}}{\longrightarrow} \ce{C_6H_5CH_2Cl} + \ce{CH_2O}\]

b. Phenylmethyl chloride can be formed from benzene and chloromethyl methyl ether, \(\ce{ClCH_2OCH_3}\), in the presence of stannic chloride, \(\ce{SnCl_4}\). Write reasonable mechanistic steps, again supported by analogy, for this reaction. Notice that \(\ce{SnCl_4}\) is a Lewis acid.

Problem 4-22 The Gattermann reaction (not to be confused with the Gattermann-Koch aldehyde synthesis) introduces the \(\ce{H-C=O}\) function into reactive aromatic compounds such as 2-naphthalenol. The necessary reagents are \(\ce{HCN}\), \(\ce{HCl}\), and a metal-halide catalyst (\(\ce{ZnCl_2}\) or \(\ce{AlCl_3}\)), and the initial product must be treated with water. Write a mechanism for this reaction that is supported by analogy to other reactions discussed in this chapter.

Problem 4-23 Show explicitly how an alkyl side chain of alkylbenzenesulfonates could be formed with a quaternary carbon, if the \(\ce{C_{12}}\) alkane used at the start of the synthesis contained any branched-chain \(\ce{C_{12}}\) isomers.

Problem 4-24 Draw the structures of the intermediate cations for nitration of nitrobenzene in the 2, 3, and 4 positions. Use the structures to explain why the nitro group is meta-orienting with deactivation. Use the same kind of arguments to explain the orientation observed with \(\ce{-CF_3}\), \(\ce{-CHO}\), \(\ce{-CH_2Cl}\), and \(\ce{-NH_2}\) groups in electrophilic aromatic substitution (Table 4-6).

Problem 4-25* The product distribution in the bromination of methylbenzene (toluene) depends on the nature of the brominating agent. Pertinent information follows:

Explain why the distribution varies with the nature of the substituting agent. Predict the product distribution of isomeric ions if \(\ce{Br}^\oplus\) were to add to methylbenzene in the gas phase.

Problem 4-26 Construct an energy diagram, similar to Figure 4-8, for nitration of phenyltrimethylammonium ion in the meta and para positions.

Problem 4-27 Using the rationale developed in Section 4-5, predict the major products of nitration of the following compounds. It will help to work out the Lewis structures of the substituent groups.

a. phenylnitromethane, \(\ce{C_6H_5CH_2NO_2}\)
b. methylthiobenzene, \(\ce{C_6H_5SCH_3}\)
c. nitrosobenzene, \(\ce{C_6H_5NO}\)
d. phenyldimethylphosphine oxide, \(\ce{C_6H_5PO(CH_3)_2}\)

Problem 4-28 The energy diagram in Figure 4-8 represents a two-step reaction in which the first step is slower than the second. This circumstance is found in nitration and halogenation reactions. Show how this diagram would change when (a) the rate-determining step is loss of a proton from the intermediate ion, (b) the reactants rapidly form a \(\pi\) complex prior to the slow step of the electrophilic attack at carbon, and (c) the rate-determining step is \(\pi\)-complex formation.

Problem 4-29 Predict the favored position(s) of substitution in the nitration of the following compounds:

a. 4-nitro-1-phenylbenzene
b. 4-methylbenzenecarboxylic acid
c. 3-methylbenzenecarboxylic acid
d. 1,3-dibromobenzene
e. 1-fluoro-3-methoxybenzene
f. 1,3-dimethylbenzene

Problem 4-30*

a. In the nitration of para-cymene by ethanoyl nitrate in ethanoic anhydride, the observed product composition at \(0^\text{o}\) is \(41\%\) \(5\) and \(6\), \(41\%\) \(3\), \(8\%\) \(4\), and \(10\%\) of 4-nitromethylbenzene. Use these results to determine the relative reactivities of the para-cymene ring carbons towards \(\ce{NO_2^+}\). Give your answer relative to \(\ce{C_3}\) as unity (\(\ce{C_3}\) is the carbon next to the isopropyl group). determine the relative reactivities based on the data obtained in Equation 4-1. How does neglect of ipso substitution affect calculation of relative reactivities of the ring carbons?

b. Write a mechanism for the solvolytic conversion of \(5\) and \(6\) to \(3\).

Problem 4-31 Draw the Kekulé-type valence-bond structures for napthalene, anthracene, and phenanthrene. Estimate the percentage of double-bond character for the 9,10 bond of phenanthrene, assuming that each of the valence-bond structures contributes equally to the hybrid structure.

Problem 4-32 Devise an experiment that would establish whether the acylation of naphthalene in the 2 position in nitrobenzene solution is the result of thermodynamic control of the orientation.

Problem 4-33 Predict the orientation in the following reactions:

a. 1-methylnaphthalene \(+ \ce{Br_2}\)
b. 2-methylnaphthalene \(+ \ce{HNO_3}\)
c. 2-napthalenecarboxylic acid \(+ \ce{HNO_3}\)

Problem 4-34 Show how one can predict qualitatively the character of the 1,2 bond in acenapthylene.

Problem 4-35* Explain why sodium in liquid ammonia reduces methoxybenzene (anisole) to 1-methoxy-1,4-cyclohexadiene, whereas it reduces sodium benzoate to sodium 2,5-cyclohexadienecarboxylate:

Problem 4-36 Predict the Birch reduction products of the following reactions:

a. anthracene \(\underset{\ce{C_2H_5OH}}{\overset{\ce{Na}}{\longrightarrow}}\)

b. naphthalene \(\underset{\ce{NH_3} \left( l \right)}{\overset{\ce{Na}}{\longrightarrow}}\)

c.* methylbenzene \(\underset{\ce{NH_3} \left( l \right)}{\overset{\ce{Na}, \: \ce{C_2H_5OH}}{\longrightarrow}}\)

Problem 4-37* A side reaction when reducing benzene derivatives to 1,4-cyclohexadienes with lithium or sodium in liquid ammonia is over-reduction to give cyclohexenes. Addition of ethanol greatly reduces the importance of this side reaction. Explain what role ethanol plays in preventing over-reduction.

Problem 4-38 Neglecting steric-hindrance effects use the stabilization energies in Table 21-1 to explain why cis-butenedioic anhydride adds more readily to anthracene than to benzene and adds across the 9,10 positions but not the 1,4 positions of anthracene.

Problem 4-39 What products would you expect to be formed in the ozonization of the following substances? Consider carefully which bonds are likely to be most reactive.

a. 1,2-dimethylbenzene
b. naphthalene
c. acenaphthylene (see Problem 4-34)

Problem 4-40* The rate of the Diels-Alder addition between cyclooctatetraene and tetracyanoethene is proportional to the tetracyanoethene concentration, \(\ce{[C_2(CN)_4]}\), at low concentrations of the addends but becomes independent of \(\ce{[C_2(CN)_4]}\) at high concentrations. Write a mechanism that accounts for this behavior.

Problem 4-41* Write reasonable mechanisms for the different oxidation reactions of cyclooctatetraene with mercuric ethanoate in ethanoic acid, methanol, and water solutions. Notice that compounds of the type \(\ce{Hg(OR)_2}\) appear to act in some cases as \(^\oplus \ce{OR}\)-donating agents and also that the oxide produced from cyclooctatetraene and peroxyacids (Section 15-11C) rearranges readily in the presence of acids to phenylethanal.

Problem 4-42* The dianion \(\ce{C_8H_6^{2-}}\), which corresponds to pentalene, has been prepared and appears to be reasonably stable. Why may the dianon be more stable than pentalene itself? (See Section 21-9B.)

Problem 4-43* Predict which of the following compounds may have some aromatic character. Give your reasons.

Problem 4-44 Write structural formulas for all of the possible isomers of \(\ce{C_8H_{10}}\) that contain one benzene ring. Show how many different mononitration products each could give if no carbon skeleton rearrangements occur but nitration is possible either in the ring or side chain. Name all of the mononitration products by an accepted system.

Problem 4-45 Write structural formulas (more than one may be possible) for aromatic substances that fit the following descriptions:

a. \(\ce{C_8H_{10}}\), which can give only one theoretically possible ring nitration product
b. \(\ce{C_6H_3Br3}\), which can give three theoretically possible nitration products.
c. \(\ce{C_6H_3Br_2Cl}\), which can give two theoretically possible nitration products.
d. \(\ce{C_8H_8(NO_2)_2}\), which can give only two theoretically possible different ring monobromosubstitution products.

Problem 4-46 Predict the most favorable position for mononitration for each of the following substances. Indicate whether the rate is greater, or less, than for the nitration of benzene. Give your reasoning in each case.

a. fluorobenzene
b. trifluoromethylbenzene
c. phenylethanone
d. phenylmethyldimethylamine oxide, \(\ce{C_6H_5CH_2} \overset{\oplus}{\ce{N}} \ce{(CH_3)_2} \overset{\ominus}{\ce{O}}\)
e. diphenylmethane
f. 4-bromo-1-methoxybenzene
g. phenylsulfinylbenzene, \(\ce{C_6H_5SOC_6H_5}\)
h. 1-tert-butyl-4-methylbenzene
i. diphenyliodonium nitrate, \(\ce{(C_6H_5)_2} \overset{\oplus}{\ce{I}} \overset{\ominus}{\ce{N}}\) \ce{O_3}\)
j. 1,3-diphenylbenzene (meta-terphenyl)
k. \(\ce{N}\)-(4-phenylphenyl)ethanamide

Problem 4-47 Explain why the bromination of benzenamine (aniline) gives 2,4,6-tribromobenzenamine (2,4,6-tribromoaniline), whereas the nitration with mixed acids gives 3-nitrobenzenamine (meta-nitroaniline).

Problem 4-48 Explain how comparison of the following resonance structures for para substitution with the corresponding ones for meta substitution may (or may not) lead to the expectation that ortho-para orientation would be favored for the nitro, cyano, and \(\ce{-CH=CHNO_2}\) groups.

Problem 4-49 Starting with benzene, show how the following compounds could be prepared. Specify the required reagents and catalysts.

a. 1-bromo-4-nitrobenzene
b. 4-isopropyl-3-nitrobenzenesulfonic acid
c. 4-tert-butylbenzenecarbaldehyde
d. \(\ce{C_6H_5COCH_2CH_2CO_2H}\)
e. 1,2,4,5-tetrachlorocyclohexane

Problem 4-50 Offer a suitable explanation of each of the following facts:

a. Nitration of arenes in concentrated nitric acid is retarded by added nitrate ions and strongly accelerated by small amounts of sulfuric acid.

b. Nitrobenzene is a suitable solvent to use in Friedel-Crafts acylation of benzene derivatives.

c. Benzene and other arenes usually do not react with nucleophiles by either addition or substitution.

d. Pyridine is almost inert to nitration with mixed nitric and sulfuric acids, a reaction the proceeds readily with benzene.

Problem 4-51 Indicate the structures of the major product(s) expected in the following reactions:

a.

b.

c.

d. (\(\ce{T}\) is \(\ce{^3H}\), or tritium)

e.

f.

g.

h.

i.

Problem 4-52 Draw the structures of the products A, B, C, and D in the stepwise reaction sequences shown.

a.

b.

Problem 4-53 The pesticide DDT is made commercially by the reaction of chlorobenzene with trichloroethanal (chloral) in the presence of an acid catalyst \(\left( \ce{H_2SO_4} \right)\). Show the steps that are likely to be involved in this reaction:

Problem 4-54 Hexachlorophene, the controversial germicide, is prepared from 2,4,5-trichlorobenzenol (2 moles) and methanal (1 mole) in the presence of concentrated sulfuric acid. Show the steps involved and the expected orientation of the substituents in the final product.

Problem 4-55 Trifluoroperoxyethanoic acid, \(\ce{CF_3C(O)O-OH}\) reacts with methoxybenzene to give 2- and 4-methoxybenzenols:

Explain the nature of this reaction. What is likely to be the substituting agent? What products would you expect from trifluoroperoxyethanoic acid and fluorobenzene? Would fluorobenzene be more, or less, reactive than methoxybenzene?

Problem 4-56 Ethanoic anhydride reacts with concentrated nitric acid to yield the rather unstable ethanoyl nitrate (acetyl nitrate), which is a useful nitrating agent. With mixtures of benzene and methylbenzene, ethanoyl nitrate products a mixture of nitrobenzene and 2- and 4-nitromethylbenzenes. When nitrated separately, each compound reacts at the same overall rate, but when mixed together, 25 times more nitromethylbenzene is formed than nitrobenzene.

a. Write equations for the formation of ethanoyl nitrate and its use in nitration of benzene derivatives.

b. Consider possible mechanisms for nitrations with ethanoyl nitrate and show how the above observations with benzene and methylbenzene alone or in mixtures can be rationalized by proper choice of the rate-determining step.

Problem 4-57 4-Nitromethylbenzene-2,6-\(\ce{D_2}\) is nitrated by a mixture of nitric and sulfuric acids at the same rate as ordinary 4-nitromethylbenzene under conditions in which the rate of nitration \(v\) is given by \(v = k \left[ \text{nitromethylbenzene} \right] \left[ \ce{NO_2^+} \right]\). (Review Section 15-6B.)

a. Explain what conclusion may be drawn from this result as to the mechanism of nitration under these conditions.

b. What would you expect the nitration rate of \(\ce{C_6D_6}\) to be as compared with \(\ce{C_6H_6}\) in the ethanoyl nitrate nitration in Problem 4-56?

Problem 4-58

a. From the data of Table 21-1 estimate the overall loss in stabilization energy for the addition of chlorine to the 1,4-positions of naphthalene and to the 9,10 positions of phenanthrene. Which is likely to be the more favorable reaction?

b. Predict whether anthracene is more likely to undergo electrophilic substitution at the 1,2 or 9 position. Show your reasoning.

Problem 4-59 Phenanthrene is oxidized more easily than benzene or naphthalene. Chromic acid oxidation of phenanthrene forms a substance known as phenanthraquinone. Which structure, A, B, or C, would you expect to be formed most readily by oxidation of phenanthrene? Explain.

Problem 4-60 Explain why the nitration and halogenation of biphenyl (phenylbenzene) goes with activation at the ortho and para positions but with deactivation at the meta position. Suggest a reason why biphenyl is more reactive than 2,2'-dimethylbiphenyl in nitration.

Contributors

John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. , Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format."