CHAPTER 12 REACT○ NS OF ARENES ELECTROPHILIC AROMATIC SUBSTITUTION SOLUTIONS TO TEXT PROBLEMS 12.1 The three most stable resonance structures for cyclohexadienyl cation are HH The positive charge is shared equally by the three carbons indicated. Thus the two carbons ortho to the sp-hybridized carbon and the one para to it each bear one third of a positive charge (+0.33) None of the other carbons is charged. The resonance picture and the simple Mo treatment agree with respect to the distribution of charge in cyclohexadienyl cation 12.2 Electrophilic aromatic substitution leads to replacement of one of the hydrogens directly attached to electrophile. All four of the ring hydrogens of p-3 hich one is replaced by the nitr CH H3 NO 279 Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
279 CHAPTER 12 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION SOLUTIONS TO TEXT PROBLEMS 12.1 The three most stable resonance structures for cyclohexadienyl cation are The positive charge is shared equally by the three carbons indicated. Thus the two carbons ortho to the sp3 -hybridized carbon and the one para to it each bear one third of a positive charge (0.33). None of the other carbons is charged. The resonance picture and the simple MO treatment agree with respect to the distribution of charge in cyclohexadienyl cation. 12.2 Electrophilic aromatic substitution leads to replacement of one of the hydrogens directly attached to the ring by the electrophile. All four of the ring hydrogens of p-xylene are equivalent; so it does not matter which one is replaced by the nitro group. CH3 CH3 p-Xylene HNO3 H2SO4 CH3 CH3 NO2 1,4-Dimethyl-2- nitrobenzene H H H H H H H H H H H H H H H H H H H H H Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
280 REACTIONSOFARENES:ELECTROPHILIC AROMATIC SUBSTITUTION 12.3 The aromatic ring of 1, 2, 4, 5-tetramethylbenzene has two equivalent hydrogen substituents. Sul- fomation of the ring leads to replacement of one of them by-SO3H H C CH3 HC CH H-C 1, 2, 4, 5-Tetramethylbenzene 2, 3,5,6-Tetramethylbenzer 12. 4 The major product is isopropylbenzene CH,CH,CH3 CH(CHS, CHaCH,CH,CI 1-Chloropropane Propylbenzene (20 0%o yield Aluminum chloride coordinates with 1-chloropropane to give a Lewis acid/Lewis base complex, which can be attacked by benzene to yield propy benzene or can undergo an intramolecular hydride shift to produce isopropyl cation. Isopropylbenzene arises by reaction of isopropyl cation with H CH3CH-CH2CCI-AICl, migration CH3-CH-CH3 Alcl 12.5 The species that attacks the benzene ring is cyclohexyl cation, formed by protonation of HH—O-SO,OH 飞O-SO Cyclone Sulfuric acid Cyclohexyl cation Hydrogen sulfate ion The mechanism for the reaction of cyclohexyl cation with benzene is analogous to the general mech anism for electrophilic aromatic substitution H、 H H Cyclohexadienyl cation Cyclohexylbenzene 12.6 The preparation of cyclohexylbenzene from cyclohexene and benzene was described in text Sec tion 12.6. Cyclohexylbenzene is converted to 1-phenylcyclohexene by benzylic bromination, fol lowed by dehydrohalogenation H,SO N-Bromosuccinimide(NBS) NaOCH,CHs benzoyl peroxide, heat Benzene Cyclohex .Bromo-1 l-Phenylcyclohexene Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
280 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 12.3 The aromatic ring of 1,2,4,5-tetramethylbenzene has two equivalent hydrogen substituents. Sulfonation of the ring leads to replacement of one of them by @SO3H. 12.4 The major product is isopropylbenzene. Aluminum chloride coordinates with 1-chloropropane to give a Lewis acid/Lewis base complex, which can be attacked by benzene to yield propylbenzene or can undergo an intramolecular hydride shift to produce isopropyl cation. Isopropylbenzene arises by reaction of isopropyl cation with benzene. 12.5 The species that attacks the benzene ring is cyclohexyl cation, formed by protonation of cyclohexene. The mechanism for the reaction of cyclohexyl cation with benzene is analogous to the general mechanism for electrophilic aromatic substitution. 12.6 The preparation of cyclohexylbenzene from cyclohexene and benzene was described in text Section 12.6. Cyclohexylbenzene is converted to 1-phenylcyclohexene by benzylic bromination, followed by dehydrohalogenation. Benzene Cyclohexene Cyclohexylbenzene H2SO4 N-Bromosuccinimide (NBS), NaOCH2CH3 benzoyl peroxide, heat 1-Bromo-1- 1-Phenylcyclohexene phenylcyclohexane Br H H H H H H H H H Benzene Cyclohexyl cation Cyclohexadienyl cation intermediate Cyclohexylbenzene H H H H H H O SO2OH Cyclohexene Sulfuric acid Cyclohexyl cation Hydrogen sulfate ion O SO2OH CH3 Isopropyl cation CH H CH2 Cl AlCl3 hydride migration CH3 CH CH3 AlCl4 CH3CH2CH2Cl 1-Chloropropane AlCl3 Propylbenzene (20% yield) CH2CH2CH3 Benzene Isopropylbenzene (40% yield) CH(CH3)2 H3C CH3 H3C CH3 1,2,4,5-Tetramethylbenzene SO3 H2SO4 2,3,5,6-Tetramethylbenzenesulfonic acid SO3H H3C CH3 H3C CH3 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 281 12.7 Treatment of 1, 3, 5-trimethoxybenzene with an acyl chloride and aluminum chloride brings about Friedel-Crafts acylation at one of the three equivalent positions available on the rin OCH3 CH2O一 AlCI, +(CH,),CHCH,CCI CH, O CCH,CH(CH3) OCH 1. 3. 5-Trimethoxybenzene 3-Methylbutanoyl chloride Isobutyl 1.3, 5-trimethoxyphenyl ketone 12.8 Because the anhydride is cyclic, its structural units are not incorporated into a ketone and a car- boxylic acid as two separate product molecules. Rather, they become part of a four-carbon unit attached to benzene by a ketone carbonyl. The acyl substituent terminates in a carboxylic acid func- CCHCHCOH Succinic 4-0xo-4-phenylbutanoic acid anhydrid 12.9(b) A Friedel-Crafts alkylation of benzene using 1-chloro-2, 2-dimethylpropane would not be a satisfactory method to prepare neopentylbenzene because of the likelihood of a carbocation rearrangement. The best way to prepare this nd is by Friedel-Crafts acylation fol lowed by Clemmensen reduction (CH,),CCCI+ ①cme(≈cm 2-Dimethylpropanoyl Benzene Neopentylbenzene 12.10 (b) Partial rate factors for nitration of toluene and tert-butylbenzene, relative to a single position of benzene. are as shown: C(CH3) The sum of these partial rate factors is 147 for toluene, 90 for tert-butylbenzene. Toluene is 147 /90, or 1.7, times more reactive than tert-butylbenzene (c) The product distribution for nitration of tert-butylbenzene is determined from the partial rate 90=10% Meta: =6.7% Para Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
12.7 Treatment of 1,3,5-trimethoxybenzene with an acyl chloride and aluminum chloride brings about Friedel–Crafts acylation at one of the three equivalent positions available on the ring. 12.8 Because the anhydride is cyclic, its structural units are not incorporated into a ketone and a carboxylic acid as two separate product molecules. Rather, they become part of a four-carbon unit attached to benzene by a ketone carbonyl. The acyl substituent terminates in a carboxylic acid functional group. 12.9 (b) A Friedel–Crafts alkylation of benzene using 1-chloro-2,2-dimethylpropane would not be a satisfactory method to prepare neopentylbenzene because of the likelihood of a carbocation rearrangement. The best way to prepare this compound is by Friedel–Crafts acylation followed by Clemmensen reduction. 12.10 (b) Partial rate factors for nitration of toluene and tert-butylbenzene, relative to a single position of benzene, are as shown: The sum of these partial rate factors is 147 for toluene, 90 for tert-butylbenzene. Toluene is 14790, or 1.7, times more reactive than tert-butylbenzene. (c) The product distribution for nitration of tert-butylbenzene is determined from the partial rate factors. Ortho: 2( 9 4 0 .5) 10% Meta: 2 9 (3 0 ) 6.7% Para: 7 9 5 0 83.3% CH3 42 42 58 2.5 2.5 C(CH3)3 4.5 4.5 75 3 3 AlCl3 Zn(Hg), HCl 2,2-Dimethylpropanoyl Benzene chloride (CH3)3CCCl O 2,2-Dimethyl-1- phenyl-1-propanone (CH3)3CC O Neopentylbenzene (CH3)3CCH2 AlCl3 Benzene 4-Oxo-4-phenylbutanoic acid CCH2CH2COH O O Succinic anhydride O O O AlCl3 1,3,5-Trimethoxybenzene OCH3 CH3O OCH3 3-Methylbutanoyl chloride (CH3)2CHCH2CCl O Isobutyl 1,3,5-trimethoxyphenyl ketone OCH3 CH3O OCH3 CCH2CH(CH3)2 O REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 281 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
282 REACTIONSOFARENES:ELECTROPHILIC AROMATIC SUBSTITUTION 12.11 The compounds shown all undergo electrophilic aromatic substitution more slowly than benzene. Therefore, -CH, Cl, CHCI, and-CCI3 are deactivating substituents CHCI CCI Benzyl chloride Dichloromethyl)benzene Trichloromethyl)benzene The electron-withdrawing power of these substituents, and their tendency to direct incoming elec- trophiles meta to themselves, will increase with the number of chlorines each contains. Thus, the substituent that gives 4% meta nitration (96% ortho para) contains the fewest chlorine atoms (CH, CD), and the one that gives 64%o meta nitration contains the most(-CCly) -CHCl -CCl3 Deactivating, orthe Deactivating, ortho. para-directing 12.12(b) Attack by bromine at the position meta to the amino group gives a cyclohexadienyl cation in- termediate in which delocalization of the nitrogen lone pair cannot participate in dispersal of the positive charge -Br B (c) Attack at the position para to the amino group yields a cyclohexadienyl cation intermediate that is stabilized by delocalization of the electron pair of the amino group 12.13 Electrophilic aromatic substitution in biphenyl is best understood by considering one ring as the functional group and the other as a substituent An aryl substituent is ortho, para-directing. Nitration f biphenyl gives a mixture of o-nitrobiphenyl and p-nitrobipheny Biphenyl Nitrobiphenyl p-Nitrobiphenyl 12. 14(b) The carbonyl group attached directly to the ring is a signal that the substituent is a meta directing group. Nitration of methyl benzoate yields methyl m-nitrobenzoate. COCH COCH Methyl benzoate Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
12.11 The compounds shown all undergo electrophilic aromatic substitution more slowly than benzene. Therefore, @CH2Cl, @CHCl2, and @CCl3 are deactivating substituents. The electron-withdrawing power of these substituents, and their tendency to direct incoming electrophiles meta to themselves, will increase with the number of chlorines each contains. Thus, the substituent that gives 4% meta nitration (96% ortho para) contains the fewest chlorine atoms (GCH2Cl), and the one that gives 64% meta nitration contains the most (@CCl3). 12.12 (b) Attack by bromine at the position meta to the amino group gives a cyclohexadienyl cation intermediate in which delocalization of the nitrogen lone pair cannot participate in dispersal of the positive charge. (c) Attack at the position para to the amino group yields a cyclohexadienyl cation intermediate that is stabilized by delocalization of the electron pair of the amino group. 12.13 Electrophilic aromatic substitution in biphenyl is best understood by considering one ring as the functional group and the other as a substituent. An aryl substituent is ortho, para-directing. Nitration of biphenyl gives a mixture of o-nitrobiphenyl and p-nitrobiphenyl. 12.14 (b) The carbonyl group attached directly to the ring is a signal that the substituent is a metadirecting group. Nitration of methyl benzoate yields methyl m-nitrobenzoate. HNO3 H2SO4 Methyl benzoate COCH3 O Methyl m-nitrobenzoate (isolated in 81–85% yield) O2N COCH3 O HNO3 H2SO4 O2N o-Nitrobiphenyl (37%) Biphenyl NO2 p-Nitrobiphenyl (63%) NH2 NH2 NH2 NH2 H Br H Br H Br H Br NH2 Br H NH2 NH2 Br H Br H Deactivating, ortho, para-directing CH2Cl Deactivating, ortho, para-directing CHCl2 Deactivating, meta-directing CCl3 Benzyl chloride CH2Cl (Dichloromethyl)benzene CHCl2 (Trichloromethyl)benzene CCl3 282 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 283 (c) The acyl group in l-phenyl-l-propanone is meta-directing; the carbonyl is attached directly to the ring. The product is 1-(m-nitrophenyl)-1-propanone O CCHCH -CCHCH 1-Phenyl-l-propanone 1-(m-Nitropheny solated in 60% yield) 12.15 Writing the structures out in more detail reveals that the substituent-N(CH3)3 lacks the unshared electron pair of -N(CH3)2 H3 CH -CH CH3 This unshared pair is responsible for the powerful activating effect of an-N(CH,), group. On the other hand, the nitrogen in-N(CH3)3 is positively charged and in that respect resembles the nitro- gen of a nitro group. We expect the substituent-N(CH3)3 to be deactivating and meta-directing 12.16 The reaction is a Friedel-Crafts alkylation in which 4-chlorobenzyl chloride serves as the carboca- tion source and chlorobenzene is the aromatic substrate. Alky lation occurs at the positions ortho and para to the chlorine substituent of chlorobenzene t cich CH,一 4-Chlorobenzyl chloride I-Chloro 4-(4'-chle benzer benzene 12.17(b) Halogen substituents are ortho, para-directing, and the disposition in m-dichlorobenzene is such that their effects reinforce each other. The major product is 2, 4-dichloro-I-nitrobenzene Substitution at the position between the two chlorines is slow because it is a sterically hin- CI Most reactive positions in electrophilic aromatic substitution (major product of nitration, of m-dichlorobenzene (c) Nitro groups are meta-directing. Both nitro groups of m-dinitrobenzene direct an incoming substituent to the same position in an electrophilic aromatic substitution reaction Nitration of m-nitrobenzene yields 1,3,5-trinitrobenzene NO lectrophile to same position. Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(c) The acyl group in 1-phenyl-1-propanone is meta-directing; the carbonyl is attached directly to the ring. The product is 1-(m-nitrophenyl)-1-propanone. 12.15 Writing the structures out in more detail reveals that the substituent G N(CH3)3 lacks the unshared electron pair of . This unshared pair is responsible for the powerful activating effect of an group. On the other hand, the nitrogen in G N(CH3)3 is positively charged and in that respect resembles the nitrogen of a nitro group. We expect the substituent G N(CH3)3 to be deactivating and meta-directing. 12.16 The reaction is a Friedel–Crafts alkylation in which 4-chlorobenzyl chloride serves as the carbocation source and chlorobenzene is the aromatic substrate. Alkylation occurs at the positions ortho and para to the chlorine substituent of chlorobenzene. 12.17 (b) Halogen substituents are ortho, para-directing, and the disposition in m-dichlorobenzene is such that their effects reinforce each other. The major product is 2,4-dichloro-1-nitrobenzene. Substitution at the position between the two chlorines is slow because it is a sterically hindered position. (c) Nitro groups are meta-directing. Both nitro groups of m-dinitrobenzene direct an incoming substituent to the same position in an electrophilic aromatic substitution reaction. Nitration of m-nitrobenzene yields 1,3,5-trinitrobenzene. Both nitro groups of m-dinitrobenzene direct electrophile to same position. NO2 NO2 1,3,5-Trinitrobenzene (principal product of nitration of m-dinitrobenzene) NO2 O2N NO2 Most reactive positions in electrophilic aromatic substitution of m-dichlorobenzene Cl Cl 2,4-Dichloro-1-nitrobenzene (major product of nitration) Cl Cl NO2 AlCl3 Chlorobenzene Cl 4-Chlorobenzyl chloride ClCH2 Cl 1-Chloro-4-(4-chlorobenzyl)- benzene Cl CH2 Cl 1-Chloro-2-(4-chlorobenzyl)- benzene CH2 Cl Cl N(CH3)2 N O O CH3 CH3 CH3 N N CH3 CH3 N(CH3)2 nitration 1-Phenyl-1-propanone CCH2CH3 O 1-(m-Nitrophenyl)-1-propanone (isolated in 60% yield) O2N CCH2CH3 O REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 283 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website