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
284 REACTIONSOFARENES:ELECTROPHILIC AROMATIC SUBSTITUTION positions of the ring that are activated by the methoxy group in p-methoxyacetophenone ar (d) A methoxy group is ortho, para-directing, and a carbonyl group is meta-directing. The op lso those that are meta to the carbonyl, so the directing effects of the two substituents reinforce each other. Nitration of p-methoxyacetophenone yields 4-methoxy-3-nitroacetophenone CHC HOCH OCH3 (e) The methoxy group of p-methylanisole activates the positions that are ortho to it; the methyl se ortho to so nitration occurs ortho to the methoxy group -OCH3 OCH Methyl activates C-3 and C-5 4-Methyl-2-nitroanisole (f) All the substituents in 2,6-dibromoanisole are ortho, para-directing, and their effects are felt at different positions. The methoxy group, however, is a far more powerful activating substituent than bromine, so it controls the regioselectivity of nitration OCH OCH Methoxy directs toward C-4 2.6-Dibromo 4nitroanisole bromines direct toward C-3 and C-5 12.18 The product that is obtained when benzene is subjected to bromination and nitration depends on the order in which the reactions are carried out. A nitro is meta-directing, and so if it is introduced prior to the bromination step, m-bromonitrobenzene is obtained. HNO, H,SO m- Bromonitrobenzene Bromine is an ortho, para-directing group. If it is introduced first, nitration of the resulting bromobenzene yields a mixture of o-bromonitrobenzene and p-bromonitrobenzene Br O2 HSO o-Bromonitrobenzene p-Bromonitrobenzene Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(d) A methoxy group is ortho, para-directing, and a carbonyl group is meta-directing. The open positions of the ring that are activated by the methoxy group in p-methoxyacetophenone are also those that are meta to the carbonyl, so the directing effects of the two substituents reinforce each other. Nitration of p-methoxyacetophenone yields 4-methoxy-3-nitroacetophenone. (e) The methoxy group of p-methylanisole activates the positions that are ortho to it; the methyl activates those ortho to itself. Methoxy is a more powerful activating substituent than methyl, so nitration occurs ortho to the methoxy group. ( f ) All the substituents in 2,6-dibromoanisole are ortho, para-directing, and their effects are felt at different positions. The methoxy group, however, is a far more powerful activating substituent than bromine, so it controls the regioselectivity of nitration. 12.18 The product that is obtained when benzene is subjected to bromination and nitration depends on the order in which the reactions are carried out. A nitro group is meta-directing, and so if it is introduced prior to the bromination step, m-bromonitrobenzene is obtained. Bromine is an ortho, para-directing group. If it is introduced first, nitration of the resulting bromobenzene yields a mixture of o-bromonitrobenzene and p-bromonitrobenzene. Br2 FeBr3 HNO3 H2SO4 Benzene Br Bromobenzene Br NO2 o-Bromonitrobenzene Br NO2 p-Bromonitrobenzene Benzene Nitrobenzene m-Bromonitrobenzene Br NO2 NO2 HNO3 H2SO4 Br2 FeBr3 OCH3 Br Br 1 2 3 4 5 6 OCH3 NO2 Br Br Methoxy directs toward C-4; bromines direct toward C-3 and C-5. 2,6-Dibromo-4-nitroanisole (principal product of nitration) 4-Methyl-2-nitroanisole (principal product of nitration) CH3 OCH3 NO2 Methyl activates C-3 and C-5; methoxy activates C-2 and C-6. CH3 OCH3 1 6 5 4 3 2 Positions ortho to the methoxy group are meta to the carbonyl. CH3C OCH3 O 4-Methoxy-3-nitroacetophenone CH3C OCH3 O NO2 284 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 285 12.19 A straightforward approach to the synthesis of m-nitrobenzoic acid involves preparation of ben- zoic acid by oxidation of toluene, followed by nitration. The carboxyl group of benzoic acid meta-directing. Nitration of toluene prior to oxidation would lead to a mixture of ortho and para COH COH HNO HaSO Toluene Benzoic acid Im- Nitrobenzoic acid 12.20 The text points out that C-1 of naphthalene is more reactive than C-2 toward electrophilic aromatic substitution. Thus, of the two possible products of sulfonation, naphthalene-1-sulfonic acid should be formed faster and should be the major product under conditions of kinetic control. Since the problem states that the product under conditions of thermodynamic control is the other isomer, naphthalene-2-sulfonic acid is the major product at elevated temperature SO,H + aphthalene-l-sulfonic acid ct at 160°C formed faster stable bi one shown in us sulfonic acid is the more stable isomer for steric reasons. The hNyygor at C-8(the 12.21 The text states that electrophilic aromatic substitution in furan d pyrrole occurs at H,SO, 12.22 (a) Nitration of benzene is the archetypical electrophilic aromatic substitution reaction N (b) Nitrobenzene is much less reactive than benzene toward electrophilic aromatic substitution The nitro group on the ring is a meta director NO H,SO Nitrobenzene m-Dinitrobenzene Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
12.19 A straightforward approach to the synthesis of m-nitrobenzoic acid involves preparation of benzoic acid by oxidation of toluene, followed by nitration. The carboxyl group of benzoic acid is meta-directing. Nitration of toluene prior to oxidation would lead to a mixture of ortho and para products. 12.20 The text points out that C-1 of naphthalene is more reactive than C-2 toward electrophilic aromatic substitution. Thus, of the two possible products of sulfonation, naphthalene-1-sulfonic acid should be formed faster and should be the major product under conditions of kinetic control. Since the problem states that the product under conditions of thermodynamic control is the other isomer, naphthalene-2-sulfonic acid is the major product at elevated temperature. Naphthalene-2-sulfonic acid is the more stable isomer for steric reasons. The hydrogen at C-8 (the one shown in the equation) crowds the group in naphthalene-1-sulfonic acid. 12.21 The text states that electrophilic aromatic substitution in furan, thiophene, and pyrrole occurs at C-2. The sulfonation of thiophene gives thiophene-2-sulfonic acid. 12.22 (a) Nitration of benzene is the archetypical electrophilic aromatic substitution reaction. (b) Nitrobenzene is much less reactive than benzene toward electrophilic aromatic substitution. The nitro group on the ring is a meta director. HNO3 H2SO4 NO2 Nitrobenzene NO2 NO2 m-Dinitrobenzene HNO3 H2SO4 Benzene NO2 Nitrobenzene S S SO3H H2SO4 Thiophene Thiophene-2- sulfonic acid SO3H H2SO4 Naphthalene Naphthalene-1-sulfonic acid major product at 0C; formed faster H 1 2 H SO3H Naphthalene-2-sulfonic acid major product at 160C; more stable H SO3H Na2Cr2O7 H2O, H2SO4, heat HNO3 H2SO4 CH3 Toluene CO2H Benzoic acid CO2H NO2 m-Nitrobenzoic acid REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 285 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
286 REACTIONSOFARENES:ELECTROPHILIC AROMATIC SUBSTITUTION (c) Toluene is more reactive than benzene in electrophilic aromatic substitution. A methyl sub CH3 Br Toluene romotoluene p-Bromotoluene (d) Trifluoromethyl is deactivating and meta-directing. FeBr TRifluoromethyl)- m-Bromo(trifluoromethyl)- enze (e) Anisole is ortho, para-directing, strongly activated toward electrophilic aromatic substitution and readily sulfonated in sulfuric acid OCH OCH OCH H,SOA SO,H Sulfur trioxide could be added to the sulfuric acid to facilitate reaction. The para isomer is the omina (f) Acetanilide is quite similar to anisole in its behavior toward electrophilic aromatic substitution HNCCH HNCCH HNCCH SOH SO,H o-Acemlfmiobciene. p-Acetamidobenzene- sulfonic acid (g) Bromobenzene is less reactive than benzene. a bromine substituent is ortho, para-directing Bromobenzene Bromochloro- p-Bromochloro- Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(c) Toluene is more reactive than benzene in electrophilic aromatic substitution. A methyl substituent is an ortho, para director. (d) Trifluoromethyl is deactivating and meta-directing. (e) Anisole is ortho, para-directing, strongly activated toward electrophilic aromatic substitution, and readily sulfonated in sulfuric acid. Sulfur trioxide could be added to the sulfuric acid to facilitate reaction. The para isomer is the predominant product. ( f ) Acetanilide is quite similar to anisole in its behavior toward electrophilic aromatic substitution. (g) Bromobenzene is less reactive than benzene. A bromine substituent is ortho, para-directing. FeCl3 Cl2 Br Bromobenzene Br Cl o-Bromochlorobenzene Br Cl p-Bromochlorobenzene H2SO4 HNCCH3 O Acetanilide HNCCH3 O SO3H o-Acetamidobenzenesulfonic acid HNCCH3 O SO3H p-Acetamidobenzenesulfonic acid H2SO4 OCH3 Anisole OCH3 SO3H o-Methoxybenzenesulfonic acid p-Methoxybenzenesulfonic acid OCH3 SO3H Br2 FeBr3 CF3 (Trifluoromethyl)- benzene CF3 Br m-Bromo(trifluoromethyl)- benzene Br2 FeBr3 CH3 Toluene CH3 Br o-Bromotoluene p-Bromotoluene CH3 Br 286 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 287 (h) Anisole is a reactive substrate toward Friedel-Crafts alkylation and yields a mixture of o-and p-benzylated products when treated with benzyl chloride and aluminum chloride OCH CH,CI CH,C6H5 Benzyl chloride Benzy anisole (i) Benzene will undergo acylation with benzoyl chloride and aluminum chloride o A benzoyl substituent is meta-directing and deactivating HNO Benzophenone k) Clemmensen reduction conditions involve treating a ketone with zinc amalgam and concen- Benzophenone Diphenylmethane 1) Wolff-Kishner reduction utilizes hydrazine, a base, and a high-boiling alcohol solvent to reduce ketone functions to methylene groups. ①+c Dipheny methane 12.23 (a) There are three principal resonance forms of the cyclohexadienyl cation intermediate formed by attack of bromine on p-xylene H Br Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(h) Anisole is a reactive substrate toward Friedel–Crafts alkylation and yields a mixture of o- and p-benzylated products when treated with benzyl chloride and aluminum chloride. (i) Benzene will undergo acylation with benzoyl chloride and aluminum chloride. ( j) A benzoyl substituent is meta-directing and deactivating. (k) Clemmensen reduction conditions involve treating a ketone with zinc amalgam and concentrated hydrochloric acid. (l) Wolff–Kishner reduction utilizes hydrazine, a base, and a high-boiling alcohol solvent to reduce ketone functions to methylene groups. 12.23 (a) There are three principal resonance forms of the cyclohexadienyl cation intermediate formed by attack of bromine on p-xylene. CH3 H Br CH3 CH3 CH3 CH3 CH3 H Br H Br H2NNH2 KOH diethylene glycol C O Benzophenone Diphenylmethane CH2 Zn(Hg) HCl C O Benzophenone Diphenylmethane CH2 HNO3 H2SO4 C O Benzophenone m-Nitrobenzophenone C O NO2 AlCl3 Benzene CCl O Benzoyl chloride C O Benzophenone AlCl3 CH2Cl Benzyl chloride OCH3 Anisole OCH3 CH2C6H5 o-Benzylanisole OCH3 CH2C6H5 p-Benzylanisole REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 287 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
288 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Any one of these resonance forms is a satisfactory answer to the question. Because of its ter tiary carbocation character, this carbocation is more stable than the corresponding intermedi- ate formed from benzene (b) Chlorination of m-xylene will give predominantly 4-chloro-1, 3-dimethy benzene CH CH 4- Chloro. More stable clohexadienyl cation The intermediate shown(or any of its resonance forms) is more stable for steric reasons than cyclohexadienyl cation The cyclohexadienyl cation intermediate leading to 4-chloro-1, 3-dimethylbenzene stable and is formed faster than the intermediate leading to chlorobenzene because of it tiary carbocation character more stable than (c) The most stable carbocation intermediate formed during nitration of acetophenone is the one corresponding to meta attack. H CCE H3 CCH more stable than O2 N-Y O2 H NO An acyl group is electron-withdrawing and destabilizes a carbocation to which it is attached. The most stable carbocation intermediate in the nitration of acetophenone is less stable and is formed more slowly than is the corresponding carbocation formed during nitration of less stable than Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
Any one of these resonance forms is a satisfactory answer to the question. Because of its tertiary carbocation character, this carbocation is more stable than the corresponding intermediate formed from benzene. (b) Chlorination of m-xylene will give predominantly 4-chloro-1,3-dimethylbenzene. The intermediate shown (or any of its resonance forms) is more stable for steric reasons than The cyclohexadienyl cation intermediate leading to 4-chloro-1,3-dimethylbenzene is more stable and is formed faster than the intermediate leading to chlorobenzene because of its tertiary carbocation character. (c) The most stable carbocation intermediate formed during nitration of acetophenone is the one corresponding to meta attack. An acyl group is electron-withdrawing and destabilizes a carbocation to which it is attached. The most stable carbocation intermediate in the nitration of acetophenone is less stable and is formed more slowly than is the corresponding carbocation formed during nitration of benzene. CCH3 O H less stable than H NO2 H NO2 CCH3 O CCH3 O CCH3 O H O2N more stable than or H NO2 H NO2 CH3 CH3 H more stable than H Cl H Cl CH3 H Cl CH3 Less stable cyclohexadienyl cation CH3 CH3 m-Xylene CH3 Cl CH3 4-Chloro-1,3- dimethylbenzene CH3 H Cl CH3 More stable cyclohexadienyl cation Cl2 via 288 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website