● CHAPTER 12 REACTIONS OF ARENES ELECTROPHILIC AROMATIC SUBSTITUTION n the preceding chapter the special stability of benzene was described, along with reac tions in which an aromatic ring was present as a substituent. In the present chapter we move from considering the aromatic ring as a substituent to studying it as a functional group. What kind of reactions are available to benzene and its derivatives? What sort of reagents react with arenes, and what products are formed in those reactions? Characteristically, the reagents that react with the aromatic ring of benzene and its derivatives are electrophiles. We already have some experience with electrophilic reagents, particularly with respect to how they react with alkenes. Electrophilic reagents dd to alkenes C=C+ Alkene Electrophilic Product of reagent electrophilic addition a different reaction takes place when electrophiles react with arenes. Substitution is observed instead of addition. If we represent an arene by the general formula ArH, where Ar stands for an aryl group, the electrophilic portion of the reagent replaces one of the hydrogens on the ring 生y Arene Electrophilic Product of electrophilic aromatic substitution 443 Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
443 CHAPTER 12 REACTIONS OF ARENES: ELECTROPHILIC AROMATIC SUBSTITUTION I n the preceding chapter the special stability of benzene was described, along with reactions in which an aromatic ring was present as a substituent. In the present chapter we move from considering the aromatic ring as a substituent to studying it as a functional group. What kind of reactions are available to benzene and its derivatives? What sort of reagents react with arenes, and what products are formed in those reactions? Characteristically, the reagents that react with the aromatic ring of benzene and its derivatives are electrophiles. We already have some experience with electrophilic reagents, particularly with respect to how they react with alkenes. Electrophilic reagents add to alkenes. A different reaction takes place when electrophiles react with arenes. Substitution is observed instead of addition. If we represent an arene by the general formula ArH, where Ar stands for an aryl group, the electrophilic portion of the reagent replaces one of the hydrogens on the ring: Ar H Arene E Y Electrophilic reagent Ar E H Y Product of electrophilic aromatic substitution C C Alkene E Y Electrophilic reagent E C C Y Product of electrophilic addition Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWELVE Reactions of Arenes: Electrophilic Aromatic Substitution call this reaction electrophilic aromatic substitution; it is one of the fundamental cesses of organic chemistry 12.1 REPRESENTATIVE ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF BENZENE The scope of electrophilic aromatic substitution is quite large; both the arene and the lectrophilic reagent are capable of wide variation. Indeed, it is this breadth of scope that makes electrophilic aromatic substitution so important. Electrophilic aromatic substitu tion is the method by which substituted derivatives of benzene are prepared. We can gain a feeling for these reactions by examining a few typical examples in which benzene is the substrate. These examples are listed in Table 12.1, and each will be discussed in more detail in Sections 12.3 through 12.7. First, however, let us look at the general mecha- nism of electrophilic aromatic substitution 12.2 MECHANISTIC PRINCIPLES OF ELECTROPHILIC AROMATIC SUBSTITUTION Recall from Chapter 6 the general mechanism for electrophilic addition to alkenes +:Y Alkene and electrophile Carbocation E-C-C++:Y →E-C-C-Y Carbocation Nucleophile Product of electrophilic first step is rate-determining. It is the sharing of the pair of T electrons of the alkene with the electrophile to form a carbocation. Following its formation, the carbocation undergoes rapid capture by some Lewis base present in the medium. The first step in the reaction of electrophilic reagents with benzene is similar. An electrophile accepts an electron pair from the T system of benzene to form a carbocation: H +: Y Benzene and electrophile Carbocation This particular carbocation is a resonance-stabilized one of the allylic type. It is a cyclo- hexadienyl cation(often referred to as an arenium ion). H Resonance forms of a cyclohexadienyl cation Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
We call this reaction electrophilic aromatic substitution; it is one of the fundamental processes of organic chemistry. 12.1 REPRESENTATIVE ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF BENZENE The scope of electrophilic aromatic substitution is quite large; both the arene and the electrophilic reagent are capable of wide variation. Indeed, it is this breadth of scope that makes electrophilic aromatic substitution so important. Electrophilic aromatic substitution is the method by which substituted derivatives of benzene are prepared. We can gain a feeling for these reactions by examining a few typical examples in which benzene is the substrate. These examples are listed in Table 12.1, and each will be discussed in more detail in Sections 12.3 through 12.7. First, however, let us look at the general mechanism of electrophilic aromatic substitution. 12.2 MECHANISTIC PRINCIPLES OF ELECTROPHILIC AROMATIC SUBSTITUTION Recall from Chapter 6 the general mechanism for electrophilic addition to alkenes: The first step is rate-determining. It is the sharing of the pair of electrons of the alkene with the electrophile to form a carbocation. Following its formation, the carbocation undergoes rapid capture by some Lewis base present in the medium. The first step in the reaction of electrophilic reagents with benzene is similar. An electrophile accepts an electron pair from the system of benzene to form a carbocation: This particular carbocation is a resonance-stabilized one of the allylic type. It is a cyclohexadienyl cation (often referred to as an arenium ion). H E H E H E Resonance forms of a cyclohexadienyl cation slow Y H E Y Benzene and electrophile H E Carbocation slow Y E C C Alkene and electrophile E C C Carbocation Y fast E C C Y Product of electrophilic addition E C C Carbocation Y Nucleophile 444 CHAPTER TWELVE Reactions of Arenes: Electrophilic Aromatic Substitution Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
12.2 Mechanistic Principles of Electrophilic Aromatic Substitution TABLE 12.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene Reaction and comment Equation 1. Nitration Warming benzene with a mix ture of nitric acid and nitrobenzene. a nitro H2o places one of the ring hydrogens Benzene Nitrobenzene(95%)Water 2. Sulfonation Treatment of benzene with H hot concentrated sulfuric acid gives ben- zenesulfonic acid. A sulfonic acid group HOSO2OH H2o (-SO2OH)replaces one of the ring hydro- gens. Sulfuric acid Benzenesulfonic acid Water (100%) 3. Halogenation Bromine reacts w zene in the presence of iron(Ill)bi FeBr a catalyst to give bromobenzene. chlorine HBr reacts similarly in the presence chloride to give chlorobenzene Benzene Bromine Bromobenzene Hydrogen bromide 4. Friedel-Crafts alkylation Alkyl halides H C(CH3)3 react with benzene in the presence of alu- minum chloride to yield alkylbenzenes CH3)aCCI HCl Benzene tert-Butyl chloride 5. Friedel-Crafts acylation An analogous reaction occurs when acyl halides react with benzene in the presence of alumi- H CCH2 CH3 num chloride. The products are acylben CH3 CH2 CCI + HCl Benzene Propanoyl 1-Phenyl-1 Hydroger anone chloride PROBLEM 12.1 In the simplest molecular orbital treatment of conjugated sys- tems, it is assumed that the system does not interact with the framework of g bonds. When this Mo method was used to calculate the charge distribution in A model showing the electrostatic potential of this yclohexadienyl cation, it gave the results indicated How does the charge at each irbocation can be viewed or carbon compare with that deduced by examining the most stable resonance struc-Learning ures for cyclohexadienyl cation +033 0.33 H Most of the resonance stabilization of benzene is lost when it is converted to the yclohexadienyl cation intermediate. In spite of being allylic, a cyclohexadienyl cation Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
PROBLEM 12.1 In the simplest molecular orbital treatment of conjugated systems, it is assumed that the system does not interact with the framework of bonds. When this MO method was used to calculate the charge distribution in cyclohexadienyl cation, it gave the results indicated. How does the charge at each carbon compare with that deduced by examining the most stable resonance structures for cyclohexadienyl cation? Most of the resonance stabilization of benzene is lost when it is converted to the cyclohexadienyl cation intermediate. In spite of being allylic, a cyclohexadienyl cation H H H H H H 0 0.33 0 H 0 0.33 0.33 12.2 Mechanistic Principles of Electrophilic Aromatic Substitution 445 TABLE 12.1 Representative Electrophilic Aromatic Substitution Reactions of Benzene Reaction and comments 1. Nitration Warming benzene with a mixture of nitric acid and sulfuric acid gives nitrobenzene. A nitro group (±NO2) replaces one of the ring hydrogens. 3. Halogenation Bromine reacts with benzene in the presence of iron(III) bromide as a catalyst to give bromobenzene. Chlorine reacts similarly in the presence of iron(III) chloride to give chlorobenzene. 4. Friedel-Crafts alkylation Alkyl halides react with benzene in the presence of aluminum chloride to yield alkylbenzenes. 5. Friedel-Crafts acylation An analogous reaction occurs when acyl halides react with benzene in the presence of aluminum chloride. The products are acylbenzenes. 2. Sulfonation Treatment of benzene with hot concentrated sulfuric acid gives benzenesulfonic acid. A sulfonic acid group (±SO2OH) replaces one of the ring hydrogens. Equation H Benzene Sulfuric acid HOSO2OH Benzenesulfonic acid (100%) SO2OH Water H2O heat H Benzene Bromine Br2 Bromobenzene (65–75%) Br Hydrogen bromide HBr FeBr3 H Benzene tert-Butyl chloride (CH3)3CCl tert-Butylbenzene (60%) C(CH3)3 Hydrogen chloride HCl AlCl3 0°C H Benzene Hydrogen chloride HCl Propanoyl chloride CH3CH2CCl O 1-Phenyl-1- propanone (88%) CCH2CH3 O AlCl3 40°C Nitric acid HNO3 Nitrobenzene (95%) NO2 Water H2O H2SO4 30–40°C Benzene H A model showing the electrostatic potential of this carbocation can be viewed on Learning By Modeling. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
CHAPTER TWELVE Reactions of Arenes: Electrophilic Aromatic Substitution is not aromatic and possesses only a fraction of the resonance stabilization of benzene Once formed, it rapidly loses a proton, restoring the aromaticity of the ring and giving the product of electrophilic aromatic substitution H E Observed product of electrophilic H H E Not observed-not aromatic If the Lewis base (Y) had acted as a nucleophile and added to carbon, the prod- uct would have been a nonaromatic cyclohexadiene derivative. Addition and substitution products arise by alternative reaction paths of a cyclohexadienyl cation. Substitution occurs preferentially because there is a substantial driving force favoring rearomatization Figure 12. 1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution. In order for electrophilic aromatic substitution reac- tions to overcome the high activation energy that characterizes the first step, the elec trophile must be a fairly reactive one. Many electrophilic reagents that react rapidly with alkenes do not react at all with benzene. Peroxy acids and diborane, for example, fall into this category. Others, such as bromine, react with benzene only in the presence of catalysts that increase their electrophilicity. The low level of reactivity of benzene toward FIGURE 12.1 Energy two steps of electrophile aromatic substitution E H E -H--.yo- E H E-Y E H-Y Reaction coordinate Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
is not aromatic and possesses only a fraction of the resonance stabilization of benzene. Once formed, it rapidly loses a proton, restoring the aromaticity of the ring and giving the product of electrophilic aromatic substitution. If the Lewis base (:Y) had acted as a nucleophile and added to carbon, the product would have been a nonaromatic cyclohexadiene derivative. Addition and substitution products arise by alternative reaction paths of a cyclohexadienyl cation. Substitution occurs preferentially because there is a substantial driving force favoring rearomatization. Figure 12.1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution. In order for electrophilic aromatic substitution reactions to overcome the high activation energy that characterizes the first step, the electrophile must be a fairly reactive one. Many electrophilic reagents that react rapidly with alkenes do not react at all with benzene. Peroxy acids and diborane, for example, fall into this category. Others, such as bromine, react with benzene only in the presence of catalysts that increase their electrophilicity. The low level of reactivity of benzene toward Y H H E Cyclohexadienyl cation fast Observed product of electrophilic aromatic substitution E H H Y H H E Y Not observed—not aromatic 446 CHAPTER TWELVE Reactions of Arenes: Electrophilic Aromatic Substitution H Energy Reaction coordinate E E E E H H E±Y H±Y Yδ Yδ Y H δ δ FIGURE 12.1 Energy changes associated with the two steps of electrophilic aromatic substitution. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
12.3 Nitration of benzene electrophiles stems from the substantial loss of resonance stabilization that accompanies transfer of a pair of its six T electrons to an electrophile. with this as background, let us now examine each of the electrophilic aromatic substitution reactions presented in Table 12.1 in more detail, especially with respect to the electrophile that attacks benzene. 12.3 NITRATION OF BENZENE Now that we've outlined the general mechanism for electrophilic aromatic substitution, we need only identify the specific electrophile in the nitration of benzene(see Table 12.1) to have a fairly clear idea of how the reaction occurs. Figure 12.2 shows the application of those general principles to the reaction +HONO,- Ha Benzene Nitric acid Nitrobenzene(95%) Wa The electrophile(e) that reacts with benzene is nitronium ion (NO2). The concentra- The role of nitronium ion in tion of nitronium ion in nitric acid alone is too low to nitrate benzene at a convenient the nitration of benzene was rate, but can be increased by adding sulfuric acid. demonstrated by Sir Christ her ingold-the same persol who suggested the Sn1 and HO- 2HOSO,OH n→-N- H3o 2HOSO,O collaborated with Cahn and elog on the R and Snot- tional system Nitric acid Sulfuric acid Nitronium i Hydronium Hyd Step 1: Attack of nitronium cation on the Tt system of the aromatic ring FIGURE 12.2 The me- chanism of benzene. An electrostatic po- tential map of nitronium ion can be viewed on Learning H Benzene and nitronium ion ation intermediate Step 2: Loss of a proton from the cyclohexadienyl cation HE +H-0 Cyclohexadienyl Water Nitrobenzene Back Forward Main MenuToc Study Guide ToC Student o MHHE Website
electrophiles stems from the substantial loss of resonance stabilization that accompanies transfer of a pair of its six electrons to an electrophile. With this as background, let us now examine each of the electrophilic aromatic substitution reactions presented in Table 12.1 in more detail, especially with respect to the electrophile that attacks benzene. 12.3 NITRATION OF BENZENE Now that we’ve outlined the general mechanism for electrophilic aromatic substitution, we need only identify the specific electrophile in the nitration of benzene (see Table 12.1) to have a fairly clear idea of how the reaction occurs. Figure 12.2 shows the application of those general principles to the reaction: The electrophile (E) that reacts with benzene is nitronium ion ( NO2). The concentration of nitronium ion in nitric acid alone is too low to nitrate benzene at a convenient rate, but can be increased by adding sulfuric acid. HO N O O Nitric acid 2HOSO2OH Sulfuric acid O N O Nitronium ion H3O Hydronium ion 2HOSO2O Hydrogen sulfate ion H Benzene HONO2 Nitric acid NO2 Nitrobenzene (95%) H2O Water H2SO4 30–40°C 12.3 Nitration of Benzene 447 H H Benzene and nitronium ion slow O Step 1: Attack of nitronium cation on the π system of the aromatic ring Step 2: Loss of a proton from the cyclohexadienyl cation N O Cyclohexadienyl cation intermediate O H Cyclohexadienyl cation intermediate O N O H H O Water fast Nitrobenzene O H H H O Hydronium ion O N N O FIGURE 12.2 The mechanism of the nitration of benzene. An electrostatic potential map of nitronium ion can be viewed on Learning By Modeling. The role of nitronium ion in the nitration of benzene was demonstrated by Sir Christopher Ingold–the same person who suggested the SN1 and SN2 mechanisms of nucleophilic substitution and who collaborated with Cahn and Prelog on the R and S notational system. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website