REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 289 (d) The methoxy group in anisole is strongly activating and ortho, para-directing. For steric rea ons and because of inductive electron withdrawal by oxygen, the intermediate leading to para substitution is the most stable OCH OCH OCH3 slightly more stable than CCH3 more stable than H H CCH CCH3 Of the various resonance forms for the most stable intermediate. the most stable one has eight electrons around each oxygen and carbon atom. OCH H CCH Most stabl esonance form This intermediate is much more stable than the corresponding intermediate from acylation of nzene (e) An isopropyl group is an activating substituent and is ortho, para-directing Attack at the ortho position is sterically hindered. The most stable intermediate is CH(CH,)2 H NO or any of its resonance forms. Because of its tertiary carbocation character, this cation is more stable than the corresponding cyclohexadienyl cation intermediate from benzene. (f) Anitro substituent is deactivating and meta-directing. The most stable cyclohexadienyl cation formed in the bromination of nitrobenzene is H This ion is less stable than the cyclohexadienyl cation formed during bromination of benzene. (g) Sulfonation of furan takes place at C-2. The cationic intermediate is more stable than the cyclo- hexadienyl cation formed from benzene because it is stabilized by electron release from oxygen. H OSO,,H SO,H SO,H Furan-2. Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(d) The methoxy group in anisole is strongly activating and ortho, para-directing. For steric reasons and because of inductive electron withdrawal by oxygen, the intermediate leading to para substitution is the most stable. Of the various resonance forms for the most stable intermediate, the most stable one has eight electrons around each oxygen and carbon atom. This intermediate is much more stable than the corresponding intermediate from acylation of benzene. (e) An isopropyl group is an activating substituent and is ortho, para-directing. Attack at the ortho position is sterically hindered. The most stable intermediate is or any of its resonance forms. Because of its tertiary carbocation character, this cation is more stable than the corresponding cyclohexadienyl cation intermediate from benzene. ( f ) A nitro substituent is deactivating and meta-directing. The most stable cyclohexadienyl cation formed in the bromination of nitrobenzene is This ion is less stable than the cyclohexadienyl cation formed during bromination of benzene. (g) Sulfonation of furan takes place at C-2. The cationic intermediate is more stable than the cyclohexadienyl cation formed from benzene because it is stabilized by electron release from oxygen. O O SO3H O O H 2SO4 via Furan Furan-2- sulfonic acid SO3H H SO3H H N H Br O O CH(CH3)2 H NO2 Most stable resonance form H O CCH3 OCH3 slightly more stable than more stable than OCH3 H CCH3 O OCH3 O H CCH3 OCH3 H CCH3 O REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 289 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
290 REACTIONSOFARENES:ELECTROPHILIC AROMATIC SUBSTITUTION (h) Pyridine reacts with philes at C-3. It is less reactive than be intermediate is less stable than the corresponding intermediate formed from benzene B H 2.24 (a) Toluene is more reactive than chlorobenzene in electrophilic aromatic substitution reac- ons because a methyl substituent is activating but a halogen substituent is deactivating Both are ortho, para-directing, however. Nitration of toluene is faster than nitration of CH NO Toluene O-Nitrotoluene p-Nitrotoluene NO b) A fluorine substituent is not nearly as strongly deactivating as a trifluoromethyl group. The reaction that takes place is Friedel-Crafts alkylation of fluorobenzene CH,C6H5 C&,CH,CI 6H5 Strongly deactivated aromatic compounds do not undergo Friedel-Crafts reaction CBHsCHaCI no reaction (c) A carbonyl group directly bonded to a benzene ring strongly deactivates it toward elec trophilic aromatic substitution Methyl benzoate is much less reactive than benzene. COCH COCH Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
(h) Pyridine reacts with electrophiles at C-3. It is less reactive than benzene, and the carbocation intermediate is less stable than the corresponding intermediate formed from benzene. 12.24 (a) Toluene is more reactive than chlorobenzene in electrophilic aromatic substitution reactions because a methyl substituent is activating but a halogen substituent is deactivating. Both are ortho, para-directing, however. Nitration of toluene is faster than nitration of chlorobenzene. Faster: Slower: (b) A fluorine substituent is not nearly as strongly deactivating as a trifluoromethyl group. The reaction that takes place is Friedel–Crafts alkylation of fluorobenzene. Strongly deactivated aromatic compounds do not undergo Friedel–Crafts reactions. (c) A carbonyl group directly bonded to a benzene ring strongly deactivates it toward electrophilic aromatic substitution. Methyl benzoate is much less reactive than benzene. COCH3 O COCH3 O CF3 C6H5CH2Cl no reaction AlCl3 F F CH2C6H5 F CH2C6H5 C6H5CH2Cl AlCl3 o-Benzylfluorobenzene (15%) p-Benzylfluorobenzene (85%) Cl Cl NO2 Cl NO2 HNO3 H2SO4 Chlorobenzene o-Chloronitrobenzene p-Chloronitrobenzene CH3 CH3 NO2 CH3 NO2 HNO3 H2SO4 Toluene o-Nitrotoluene p-Nitrotoluene N Br H 290 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 291 An oxygen substituent directly attached to the ring strongly activates it toward electrophilic aromatic substitution. Phenyl acetate is much more reactive than benzene or methyl benzoate OCCH OCCH3 OCCH Bromination of methyl benzoate requires more vigorous conditions; catalysis by iron(llm bro- mide is required for bromination of deactivated aromatic rings (d) Acetanilide is strongly activated toward electrophilic aromatic substitution and reacts faster than nitrobenzene, which is strongly deactivated HNCCH ( Lone pair on nitrogen ca (Nitrogen is positively charged stabilize cyclohexadienyl and is electron- withd HNCCH HNCC H3 HNCCH SO,H Acetanilide o-Acetamidobenzene- p-Acetamidobenzene- (e) Both substrates are of the type and are activated toward Friedel-Crafts acylation. Since electronic effects are comparable, we ook to differences in steric factors and conclude that reaction will be faster for r=CH, than forR=(CH3)3C CH CH O .xy tophenone Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
An oxygen substituent directly attached to the ring strongly activates it toward electrophilic aromatic substitution. Phenyl acetate is much more reactive than benzene or methyl benzoate. Bromination of methyl benzoate requires more vigorous conditions; catalysis by iron(III) bromide is required for bromination of deactivated aromatic rings. (d) Acetanilide is strongly activated toward electrophilic aromatic substitution and reacts faster than nitrobenzene, which is strongly deactivated. (e) Both substrates are of the type and are activated toward Friedel–Crafts acylation. Since electronic effects are comparable, we look to differences in steric factors and conclude that reaction will be faster for R CH3 than for R (CH3)3CG. CH3 CH3 p-Xylene Acetyl chloride 2,5-Dimethylacetophenone CH3CCl O AlCl3 CH3 CH3 C O CH3 R R R alkyl HNCCH3 O Acetanilide o-Acetamidobenzenesulfonic acid HNCCH3 O SO3H p-Acetamidobenzenesulfonic acid HNCCH3 O SO3H SO3 H2SO4 N O O Nitrobenzene (Nitrogen is positively charged and is electron-withdrawing.) HNCCH3 O Acetanilide (Lone pair on nitrogen can stabilize cyclohexadienyl cation intermediate.) Br2 acetic acid OCCH3 O OCCH3 Br O OCCH3 Br O Phenyl acetate o-Bromophenyl acetate p-Bromophenyl acetate REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION 291 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
292 REACTIONSOFARENES:ELECTROPHILIC AROMATIC SUBSTITUTION (f) a phenyl substituent is activating and ortho, para-directing. Biphenyl will undergo chlorina- tion readily. H Biphenyl 0-Chlorobiphenyl p-Chlorobiphenyl Each benzene ring of benzophenone is deactivated by the carbonyl group Benzophenone Benzophenone is much less reactive than biphenyl in electrophilic aromatic substitution 12.25 Reactivity toward electrophilic aromatic substitution increases with increasing number of electron releasing substituents. Benzene, with no methyl substituents, is the least reactive, followed by toluene, with one methyl group. 1, 3, 5-Trimethylbenzene, with three methyl substituents, is the most reactive Benzene Toluene o-Xylene and m-xylene are intermediate in reactivity between toluene and 1, 3, 5-trimethylben- zene. Of the two, m-xylene is more reactive than o-xylene because the activating effects of the two nethyl groups reinforce each other H -Xylene (activating effects 12.26 (a) Chlorine is ortho, para-directing, carboxyl is meta-directing. The positions that are ortho to the chlorine are meta to the carboxyl, so that both substituents direct an incoming electrophile to the same position. Introduction of the second nitro group at the remainin Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
( f ) A phenyl substituent is activating and ortho, para-directing. Biphenyl will undergo chlorination readily. Each benzene ring of benzophenone is deactivated by the carbonyl group. Benzophenone is much less reactive than biphenyl in electrophilic aromatic substitution reactions. 12.25 Reactivity toward electrophilic aromatic substitution increases with increasing number of electronreleasing substituents. Benzene, with no methyl substituents, is the least reactive, followed by toluene, with one methyl group. 1,3,5-Trimethylbenzene, with three methyl substituents, is the most reactive. o-Xylene and m-xylene are intermediate in reactivity between toluene and 1,3,5-trimethylbenzene. Of the two, m-xylene is more reactive than o-xylene because the activating effects of the two methyl groups reinforce each other. 12.26 (a) Chlorine is ortho, para-directing, carboxyl is meta-directing. The positions that are ortho to the chlorine are meta to the carboxyl, so that both substituents direct an incoming electrophile to the same position. Introduction of the second nitro group at the remaining CH3 CH3 CH3 CH3 m-Xylene (activating effects reinforce each other) 5 104 o-Xylene (all positions somewhat activated) Relative reactivity: 5 102 CH3 CH3 H3C CH3 1,3,5-Trimethylbenzene 2 107 Toluene 60 Benzene Relative reactivity: 1 Benzophenone C O C O Biphenyl o-Chlorobiphenyl p-Chlorobiphenyl Cl2 FeCl3 C6H5 Cl C6H5 Cl 292 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website