《有机化学》课程教学课件（Organic Chemistry, Alex Jonathan Roche lecture notes Rutgers The State University NJ, wade 8th）Chapter 17 Reactions of Aromatic Compounds

Reactions of Aromatic Compounds Just like an alkene,benzene has clouds of it electrons above and below its sigma bond framework B-H attack on an electrophile sigma complex substituted 20PronEae,Ino Although the nt electrons are in a stable aromatic system,they are still available for reaction with strong electrophiles This generates a carbocation which is resonance stabilized(but not aromatic) igma comple (arenium ion) This cation is called a sigma complex because the electrophile is joined to the benzene ring through a new sigma bond. The sigma complex(also called an arenium ion)is not aromatic since it contains an sp'carbon (which disrupts the required loop of p orbitals). Chl7 Reactions of Aromatic Compounds (landscape).docx Pagel

Ch17 Reactions of Aromatic Compounds (landscape).docx Page1 Reactions of Aromatic Compounds Just like an alkene, benzene has clouds of  electrons above and below its sigma bond framework. Although the  electrons are in a stable aromatic system, they are still available for reaction with strong electrophiles. This generates a carbocation which is resonance stabilized (but not aromatic). This cation is called a sigma complex because the electrophile is joined to the benzene ring through a new sigma bond. The sigma complex (also called an arenium ion) is not aromatic since it contains an sp3 carbon (which disrupts the required loop of p orbitals)

The loss of aromaticity required to form the sigma complex explains the highly endothermic nature of the first step. (That is why we require strong electrophiles for reaction). The sigma complex wishes to regain its aromaticity,and it may do so by either by a reversal of the first step(i.e. regenerate the starting material)or by loss of the proton on the spcarbon(leading to a substitution product). H H H base E base-H H H When a reaction proceeds this way,it is electrophilic aromatic substitution. There are a wide variety of electrophiles that can be introduced into a benzene ring in this way,and so electrophilic aromatic substitution is a very important method for the synthesis of substituted aromatic compounds. Chl7 Reactions of Aromatic Compounds (landscape).docx Page2

Ch17 Reactions of Aromatic Compounds (landscape).docx Page2 The loss of aromaticity required to form the sigma complex explains the highly endothermic nature of the first step. (That is why we require strong electrophiles for reaction). The sigma complex wishes to regain its aromaticity, and it may do so by either by a reversal of the first step (i.e. regenerate the starting material) or by loss of the proton on the sp3 carbon (leading to a substitution product). When a reaction proceeds this way, it is electrophilic aromatic substitution. There are a wide variety of electrophiles that can be introduced into a benzene ring in this way, and so electrophilic aromatic substitution is a very important method for the synthesis of substituted aromatic compounds

Bromination of Benzene Bromination follows the same general mechanism for the electrophilic aromatic substitution(EAS). Bromine itself is not electrophilic enough to react with benzene. But the addition of a strong Lewis acid(electron pair acceptor),such as FeBr3,catalyses the reaction,and leads to the substitution product. The bromine molecule reacts with FeBr;by donating a pair of its electrons to the Lewis acid,which creates a more polar Br-Br bond,and thus a more reactive electrophile. Benzene will now attack this electrophile to generate the sigma complex Step /Formation of a stronger electrophile. Br-Bir:+FeBry Br,.FeBr,intermediate (a stronger electrophile than Br) Step 2:Electrophilic attack and formation of the sigma complex. FeBr ma complex Step 3:Loss of a proton gives the products FeBr, bromobenzene Chl7 Reactions of Aromatic Compounds (landscape).docx Page3

Ch17 Reactions of Aromatic Compounds (landscape).docx Page3 Bromination of Benzene Bromination follows the same general mechanism for the electrophilic aromatic substitution (EAS). Bromine itself is not electrophilic enough to react with benzene. But the addition of a strong Lewis acid (electron pair acceptor), such as FeBr3, catalyses the reaction, and leads to the substitution product. The bromine molecule reacts with FeBr3 by donating a pair of its electrons to the Lewis acid, which creates a more polar Br-Br bond, and thus a more reactive electrophile. Benzene will now attack this electrophile to generate the sigma complex

Bromide ion from the FeBr can act as a weak base to remove the proton,thus generating the aromatic product,H- Br,and regenerating the catalyst(FeBr3). The formation of the sigma complex is an endothermic and energetically unfavorable process-it is therefore the rate determining step. The second step is exothermic since it regenerates the aromatic n system. The overall reaction is exothermic by about 11 kcal/mol.(-45kJ/mol) rate-limiting transition state 车1 reactants H +Br2 Br -FeBr4 intermediate products Br+HBr -45 kJ/mol FeBr3 reaction coordinate- Chl7 Reactions of Aromatic Compounds (landscape).docx Page4

Ch17 Reactions of Aromatic Compounds (landscape).docx Page4 Bromide ion from the FeBr4 - can act as a weak base to remove the proton, thus generating the aromatic product, H￾Br, and regenerating the catalyst (FeBr3). The formation of the sigma complex is an endothermic and energetically unfavorable process - it is therefore the rate determining step. The second step is exothermic since it regenerates the aromatic  system. The overall reaction is exothermic by about 11 kcal/mol. (-45kJ/mol)

Comparison with Alkenes Alkenes react spontaneously with bromine to give addition products. E.g. H Br2 Br △H°=-121kJ Br (-29 kcal) This reaction is exothermic by 29kcal/mol. An analogous addition reaction between benzene and bromine would be endothermic by 2kcal. H Br △HP=+8kJ -Br (+2kc) The destruction of the aromatic sextet causes this endothermicity This reaction is not observed under normal reaction conditions. The substitution of bromine for hydrogen is an overall exothermic process,but requires a catalyst to convert the bromine molecule into a more reactive electrophile. Chl7 Reactions of Aromatic Compounds (landscape).docx Page5

Ch17 Reactions of Aromatic Compounds (landscape).docx Page5 Comparison with Alkenes Alkenes react spontaneously with bromine to give addition products. E.g. This reaction is exothermic by 29kcal/mol. An analogous addition reaction between benzene and bromine would be endothermic by 2kcal. The destruction of the aromatic sextet causes this endothermicity. This reaction is not observed under normal reaction conditions. The substitution of bromine for hydrogen is an overall exothermic process, but requires a catalyst to convert the bromine molecule into a more reactive electrophile

Chlorination of Benzene The chlorination proceeds analogously to the bromination except this time the Lewis acid catalyst used is AlCl3 H AICI HCI benzene chlorobenzene (85%) e23nne6运am.e lodination of Benzene The iodination procedure requires an acidic oxidizing agent,such as nitric acid l2 +2 HNO3 +2NO2+2H20 The nitric acid is a strong oxidizer(i.e.removes electrons,converts iodine into 1),this makes the iodine a much stronger electrophile. 2H+2HNO3 I2 2I+2NO2 +2H2O The nitric acid is consumed in the reaction,it is therefore a reagent,not a catalyst Chl7 Reactions of Aromatic Compounds (landscape).docx Page6

Ch17 Reactions of Aromatic Compounds (landscape).docx Page6 Chlorination of Benzene The chlorination proceeds analogously to the bromination except this time the Lewis acid catalyst used is AlCl3. Iodination of Benzene The iodination procedure requires an acidic oxidizing agent, such as nitric acid. The nitric acid is a strong oxidizer (i.e. removes electrons, converts iodine into I+ ), this makes the iodine a much stronger electrophile. 2H+ + 2HNO3 + I2  2I+ + 2NO2 + 2H2O The nitric acid is consumed in the reaction, it is therefore a reagent, not a catalyst

Nitration of Benzene Benzene will react with hot concentrated nitric acid to produce nitrobenzene. HNO3_H2SO4 NO2 +H20 However,this reaction proceeds slowly,which is inconvenient(dangerous)since hot,conc.nitric acid is a powerful oxidizer,and organic compounds are easily oxidizable.(i.e.potential for BOOM!) A safer reaction involves a mixture of nitric and sulfuric acid. The sulfuric acid behaves as a catalyst,and allows this nitration reaction to proceed at a lower temperature and more quickly (i.e.safer). Sulfuric acid reacts with nitric acid to generate a nitronium ion(NO2),which is a very powerful electrophile :O: H H -N=0: 0+HS0,0=N=0+H,: nitronium ion 0 The reaction mechanism is similar to an acid catalyzed dehydration Chl7 Reactions of Aromatic Compounds (landscape).docx Page7

Ch17 Reactions of Aromatic Compounds (landscape).docx Page7 Nitration of Benzene Benzene will react with hot concentrated nitric acid to produce nitrobenzene. However, this reaction proceeds slowly, which is inconvenient (dangerous) since hot, conc. nitric acid is a powerful oxidizer, and organic compounds are easily oxidizable. (i.e. potential for BOOM!) A safer reaction involves a mixture of nitric and sulfuric acid. The sulfuric acid behaves as a catalyst, and allows this nitration reaction to proceed at a lower temperature and more quickly (i.e. safer). Sulfuric acid reacts with nitric acid to generate a nitronium ion (NO2 + ), which is a very powerful electrophile. The reaction mechanism is similar to an acid catalyzed dehydration

Sulfuric acid is a stronger acid than nitric acid,so sulfuric acid protonates nitric acid. After protonation,water is eliminated (good leaving group),and the nitronium ion is generated The nitronium ion reacts with benzene to form the sigma complex,which then loses a proton to generate the aromatic product. Sulfonation of Benzene Benzene will react with sulfur trioxide,and in the presence of an acid,arylsulfonic acids are produced. +S03 H2S04 Sulfur trioxide is very reactive electrophile which will sulfonate benzene. The sigma complex loses a proton to regain its aromaticity,and then the oxyanion becomes protonated. Chl7 Reactions of Aromatic Compounds (landscape).docx Page8

Ch17 Reactions of Aromatic Compounds (landscape).docx Page8 Sulfuric acid is a stronger acid than nitric acid, so sulfuric acid protonates nitric acid. After protonation, water is eliminated (good leaving group), and the nitronium ion is generated. The nitronium ion reacts with benzene to form the sigma complex, which then loses a proton to generate the aromatic product. Sulfonation of Benzene Benzene will react with sulfur trioxide, and in the presence of an acid, arylsulfonic acids are produced. Sulfur trioxide is very reactive electrophile which will sulfonate benzene. The sigma complex loses a proton to regain its aromaticity, and then the oxyanion becomes protonated

Desulfonation The sulfonation reaction is reversible,and a sulfonic acid group may be removed(i.e.replaced by hydrogen)from the aromatic ring by heating in dilute sulfuric acid. SO H +H20 Heat (Often just steam is used for this reaction) The mechanism for desulfonation is identical to the sulfonation mechanism,except in the reverse order SO ce-delocalized) (S03+H,0←-HSO) Chl7 Reactions of Aromatic Compounds (landscape).docx Page9

Ch17 Reactions of Aromatic Compounds (landscape).docx Page9 Desulfonation The sulfonation reaction is reversible, and a sulfonic acid group may be removed (i.e. replaced by hydrogen) from the aromatic ring by heating in dilute sulfuric acid. (Often just steam is used for this reaction). The mechanism for desulfonation is identical to the sulfonation mechanism, except in the reverse order

Hydrogen-Deuterium Exchange Protonation of the benzene ring may also occur by this mechanism (D,0) (resonance-delocalized) After protonation has occurred,the sigma complex can lose either of the hydrogens from the sp'carbon to regain its aromaticity To prove that reaction has actually occurred,deuterated sulfuric acid can be used. The products will have deuterium substituted for hydrogen. If a large excess of deuterated reagent is used,hexadeuteriobenzene can be produced from this equilibrium reaction. Chl7 Reactions of Aromatic Compounds (landscape).docx Pagel0

Ch17 Reactions of Aromatic Compounds (landscape).docx Page10 Hydrogen-Deuterium Exchange Protonation of the benzene ring may also occur by this mechanism. After protonation has occurred, the sigma complex can lose either of the hydrogens from the sp3 carbon to regain its aromaticity. To prove that reaction has actually occurred, deuterated sulfuric acid can be used. The products will have deuterium substituted for hydrogen. If a large excess of deuterated reagent is used, hexadeuteriobenzene can be produced from this equilibrium reaction