Chapter 12 Electrophilic and Nucleophilic Aromatic Substitution 1 Aromatic Substitution Alkenes react with electrophilic reagents to give addition products Aromatics react with electrophilic reagents to give substitution products Aromatic system remains Aromatic nucleophilic substitution is also possible 2 Electrophilic Aromatic Substitution 3 Electrophilic Aromatic Substitution General Mechanism The first step is the slow addition of an electrophile to the benzene ring The second step is the rapid deprotonation to reform the benzene ring Carbocation is called an arenium ion s complex or a cyclohexadienyl cation 4 Potential Energy Graph of EAS 5 Nitration of Benzene Reaction equation Mechanism of formation of the electrophile NO2 6 Nitration of Benzene Mechanism Step 1 Addition of the electrophile Step 2 Deprotonation 7 Sulfonation of Benzene Can be performed with sulfuric acid and heat or sulfur trioxide and sulfuric acid 8 Sulfonation of Benzene Electrophile is sulfur trioxide which has a positively charged sulfur 9 Nitration of Benzene Mechanism Step 1 Addition of the electrophile Step 2 Deprotonation of the s complex 10 Nitration of Benzene Mechanism Step 3 Protonation of sulfonate 11 Bromination of Benzene Reaction equation Formation of the electrophile 12 Bromination of Benzene Mechanism Step 1 Addition of the electrophile Step 2 Deprotonation 13 Chlorination and Iodination of Benzene Chlorination follows the same procedure as bromine using Cl2 Fe as the reagent Mechanism is essentially the same Specialized reagents are used for iodination 14 Naturally Occurring Aryl Halides An anti fungal compound isolated from lily plants Dibromoindigo an ancient royal purple dye extracted from sea snails Thyroxine a thyroid hormone the S enantiomer increases metabolism 15 Naturally Occurring Aryl Halides Enzymatic halogenation of tryptophan 16 Friedel Crafts Alkylation of Benzene Reaction equation Mechanism of formation on the electrophile 17 Friedel Crafts Alkylation of Benzene Step 1 Addition of the electrophile Step 2 Deprotonation 18 Friedel Crafts Alkylation Mechanism Primary and methyl cations are too unstable to be formed so the Lewis acid base complex is the effective electrophile 19 Friedel Crafts Alkylation and Rearrangements Rearrangements occur especially with primary alkyl halides The electrophile is formed by hydride migration to form a more stable cation 20 Alternative Sources for Carbocations Any reaction that generates a carbocation can be used to produce the electrophile This provides an industrial synthesis of styrene 21 Friedel Crafts Acylation of Benzene Acylation uses acyl halides The acyl cation is the active electrophile 22 Friedel Crafts Acylation Mechanism Step 1 Addition of the electrophile Step 2 Deprotonation 23 Preparation of Acyl Chlorides Acyl chlorides are prepared from carboxylic acids using thionyl chloride Recall the use of thionyl chloride to go from ROH RCl Chapter 4 24 Alternative Sources of Acyl Cation Carboxylic acid anhydrides are also sources of acyl cations 25 Acylation Reduction Reactions Acylation reduction reaction sequences are useful to prepare alkyl benzenes that cannot be directly prepared by Friedel Crafts alkylation because of rearrangements 26 Acylation Reduction Reactions Clemmensen reduction reduction of carbonyls with zincmercury amalgam in concentrated HCl Wolff Kishner reduction uses hydrazine and KOH in a high boiling solvent 27 Rate and Regioselectivity in EAS When considering reaction of benzene rings that already have a substituent there are two questions 1 How does the substituent affect the rate of reaction 2 How does the substituent affect the regioselectivity 28 Substituents and Rate of EAS Consider the rate of nitration of these three compounds Toluene reacts 20 times faster than benzene Trifluoromethylbenzene reacts 40 000 times slower than benzene 29 Substituents and Rate of EAS The rate of reaction is related to electron density on the benzene ring The p electron density is shown as red in the electrostatic potential maps 30 Regioselectivity in EAS of Toluene Three isomeric nitrotoluenes are possible The ortho and para products comprise 97 of yield only a small amount of the meta isomer is formed A methyl substituent is an ortho para director 31 Regioselectivity and Trifluoromethylbenzene Three isomeric nitro products are possible The meta product is 91 of yield and only a small amount of the ortho para isomers are formed A trifluoromethyl substituent is a meta director 32 Rate and Regioselectivity with Toluene Methyl is activating and ortho para directing Suggests cation of ortho and para products are more stable 33 Carbocation Intermediates and Stability Using resonance to examine electron delocalization 34 Carbocation Intermediates and Stability Using resonance to examine electron delocalization All resonance forms are secondary cations Not as stable because of the lack of a tertiary cation 35 Nitration of Toluene Methyl is an electron releasing group and activates all ring carbons towards EAS The ortho and para carbons are more activated than the meta The relative rates of nitration compared to benzene are 36 Nitration of Toluene The energetics of nitration of benzene and toluene can be compared graphically 37 Nitration of Toluene The energetics of nitration of benzene and toluene can be compared graphically 38 Alkylbenzenes and EAS All alkyl groups are activating and ortho para directors 39 Effect of the Trifluoromethyl Group Fluorine is the most electronegative element and the carbon therefore has a partial positive charge Thus while a methyl is electron releasing a trifluoromethyl is strongly electron withdrawing Meta directing 40 Effect of the Trifluoromethyl Group Electron delocalization viewed through resonance forms 41 EAS and the Trifluoromethyl Group The energentics of electrophilic aromatic substitution of trifluoromethylbenzene is compared to benzene 42 Activating Substituents and EAS Substituent effects involve rate and regioselectivity The activating substituents can be ranked from most activating to least activating All activating substituents are ortho para directors Halogen substituents are slightly deactivating but are ortho para directing Strongly deactivating substituents are meta directors 43 Substituents Effects 44 Substituents Effects 45 Substituents Effects Activators 46 Substituents Effects Deactivators 47 Substituents Effects 48 Strongly Activating Substituents These substituents are so