Organic Chemistry Chapter 16 CHEMISTRY OF BENZENE ELECTROPHILIC AROMATIC SUBSTITUTION Chapter Contents 16 1 Electrophilic Aromatic Substitution Reactions Bromination 16 2 Other Aromatic Substitutions 16 3 Alkylation and Acylation of Aromatic Rings The Friedel Crafts Reaction 16 4 Substituent Effects in Electrophilic Substitutions 16 5 Trisubstituted Benzenes Additivity of Effects 16 6 Nucleophilic Aromatic Substitution 16 7 Benzyne 16 8 Oxidation of Aromatic Compounds 16 9 Reduction of Aromatic Compounds 16 10 Synthesis of Polysubstituted Benzenes Electrophilic Aromatic Substitution Aromatic Ring Electrophilic Aromatic Substitution Bromination part 1 Electrophilic Aromatic Substitution Bromination part 2 Figure 16 2 A comparison of the reactions of an electrophile E with an alkene and with benzene G reaction is slower than the alkene reaction because of the stability of the aromatic ring alkene G benzene The benzene Figure 16 3 The mechanism for the electrophilic bromination of benzene The reaction occurs in two steps and involves a resonance stabilized carbocation intermediate Figure 16 4 An energy diagram for the electrophilic bromination of benzene Because the stability of the aromatic ring is retained the overall process is exergonic Aromatic Halogenation part 1 Aromatic Halogenation part 2 Aromatic Halogenation part 3 Aromatic Halogenation part 4 Aromatic Halogenation part 5 Figure 16 5 The mechanism for electrophilic nitration of an aromatic ring An electrostatic potential map of the reactive electrophile NO2 shows that the nitrogen atom is most positive Aromatic Nitration Figure 16 6 The mechanism for electrophilic sulfonation of an aromatic ring An electrostatic potential map of the reactive electrophile HOSO2 shows that sulfur and hydrogen are the most positive atoms Aromatic Sulfonation Aromatic Hydroxylation Figure 16 7 Mechanism for the electrophilic hydroxylation of p hydroxyphenylacetate by reaction with FAD hydroperoxide The hydroxylating species is an OH equivalent that arises by protonation of FAD hydroperoxide RO OH H ROH OH The FAD hydroperoxide itself is formed by reaction of FADH2 with O2 Figure 16 8 Mechanism for the Friedel Crafts alkylation reaction of benzene with 2 chloropropane to yield isopropylbenzene cumene The electrophile is a carbocation generated by AlCl3 assisted dissociation of an alkyl halide Friedel Crafts Alkylation Not Reactive with Aryl and Vinylic Halides Figure 16 9 Limitations on the aromatic substrate in Friedel Crafts reactions No reaction occurs if the substrate has either an electron withdrawing substituent or a basic amino group Friedel Crafts Alkylation Polyalkylation Friedel Crafts Alkylation Carbocation Rearrangements Friedel Crafts Acylation part 1 Figure 16 10 Mechanism of the Friedel Crafts acylation reaction The electrophile is a resonance stabilized acyl cation whose electrostatic potential map indicates that carbon is the most positive atom Friedel Crafts Acylation part 2 Figure 16 11 Biosynthesis of phylloquinone vitamin K1 from 1 4 dihydroxynaphthoic acid The key step that joins the 20 carbon phytyl side chain to the aromatic ring is a Friedel Crafts like electrophilic substitution reaction with a diphosphate ion as the leaving group Worked Example 16 1 Predicting the Product of a Carbocation Rearrangement The Friedel Crafts reaction of benzene with 2 chloro 3 methylbutane in the presence of AlCl3 occurs with a carbocation rearrangement What is the structure of the product Worked Example 16 1 Strategy A Friedel Crafts reaction involves initial formation of a carbocation which can rearrange by either a hydride shift or an alkyl shift to give a more stable carbocation Draw the initial carbocation assess its stability and see if the shift of a hydride ion or an alkyl group from a neighboring carbon will result in increased stability In the present instance the initial carbocation is a secondary one that can rearrange to a more stable tertiary one by a hydride shift Use this more stable tertiary carbocation to complete the Friedel Crafts reaction Worked Example 16 1 Solution Substituents Reactivity of the Aromatic Ring Figure 16 12 Classification of substituent effects in electrophilic aromatic substitution All activating groups are ortho and para directing and all deactivating groups other than halogen are meta directing Halogens are unique in being deactivating but ortho and para directing Worked Example 16 2 Predicting the Product of an Electrophilic Aromatic Substitution Reaction Predict the major product of the sulfonation of toluene Worked Example 16 2 Strategy Identify the substituent present on the ring and decide whether it is ortho and para directing or meta directing According to FIGURE 16 12 an alkyl substituent is ortho and para directing so sulfonation of toluene will primarily give a mixture of o toluenesulfonic acid and p toluenesulfonic acid Worked Example 16 2 Solution Substituents Activating and Deactivating Effects Figure 16 13 Electrostatic potential maps of benzene and several substituted benzenes show that an electron withdrawing group CHO or Cl makes the ring more electron poor while an electron donating group OH makes the ring more electron rich Substituents Electron Withdrawal and Donation Substituents Resonance Electron Withdrawal and Donation Figure 16 14 Carbocation intermediates in the nitration of toluene Ortho and para intermediates are more stable than the meta intermediate because the positive charge is on a tertiary carbon rather than a secondary carbon Figure 16 15 Carbocation intermediates in the nitration of phenol The ortho and para intermediates are more stable than the meta intermediate because they have more resonance forms including one particularly favorable form that involves electron donation from the oxygen atom Figure 16 16 Carbocation intermediates in the nitration of chlorobenzene The ortho and para intermediates are more stable than the meta intermediate because of electron donation of the halogen lone pair electrons Figure 16 17 Carbocation intermediates in the nitration of benzaldehyde The ortho and para intermediates are less stable than the meta intermediate The meta intermediate is more favorable than ortho and para intermediates because it has three favorable resonance forms rather than two Trisubstituted Benzenes Rule 1 Trisubstituted Benzenes Rule 2 Trisubstituted Benzenes Rule 3 Worked Example 16 3 Predicting the Product of Substitution on a Disubstituted Benzene