# Lecture 3: Electrophilic Aromatic Substitution ## Organic Chemistry II --- ## Learning Objectives By the end of this lecture, students will be able to: 1. Describe the general mechanism of electrophilic aromatic substitution (EAS) 2. Draw the arenium ion (sigma complex) intermediate and explain its role 3. Write detailed mechanisms for halogenation, nitration, sulfonation, Friedel-Crafts alkylation, and Friedel-Crafts acylation 4. Identify the reagents and conditions required for each type of EAS reaction 5. Explain why aromatic rings undergo substitution rather than addition 6. Discuss limitations of Friedel-Crafts reactions --- ## Lecture Content ### I. General Mechanism of EAS In electrophilic aromatic substitution, an electrophile (E+) replaces a hydrogen on the aromatic ring, yielding the substituted product and a proton. The net transformation is Ar-H + E+ producing Ar-E + H+. Crucially, this is a substitution, not an addition, so aromaticity is preserved in the product. The reaction proceeds through a two-step mechanism. In the first and rate-determining step, the pi electrons of the aromatic ring attack the electrophile. This produces a resonance-stabilized carbocation intermediate known as the arenium ion (also called the sigma complex or Wheland intermediate). At this stage, the carbon bearing the electrophile has become sp3 hybridized, and the ring has temporarily lost its aromaticity. The arenium ion is stabilized by delocalization of the positive charge over three ring carbons, which can be illustrated by drawing three resonance structures. In the second, fast step, a base removes the proton from the sp3 carbon. The electrons from the broken C-H bond restore the aromatic pi system. Aromaticity is regained, and this recovery of roughly 152 kJ/mol of stabilization energy provides the thermodynamic driving force for the deprotonation step. The reason aromatic rings undergo substitution rather than addition is straightforward. Addition would permanently destroy aromaticity, sacrificing that enormous stabilization energy. Substitution restores the aromatic system, making it the thermodynamically favorable pathway. General EAS mechanism diagram in three stages. Stage 1: Benzene ring with its pi cloud attacking an electrophile E+, showing curved arrow from the ring to E+. Stage 2: The arenium ion intermediate with three resonance structures, showing the positive charge distributed over three carbon atoms (ortho, para positions relative to the point of attachment), with the sp3 carbon bearing both H and E drawn with a tetrahedral geometry. Stage 3: Base removes the proton, restoring the aromatic ring to give the substituted product. An energy diagram below shows the reaction coordinate with two transition states (higher for step 1) and the arenium ion intermediate in the energy well between them. ### II. Halogenation Halogenation of benzene requires a molecular halogen (Br2 or Cl2) together with a Lewis acid catalyst such as FeBr3, FeCl3, or AlCl3. The Lewis acid activates the halogen by coordinating to it, producing a highly polarized species in which one halogen atom carries a significant partial positive charge. This polarized halogen serves as the electrophile. The aromatic ring then attacks the electrophilic halogen, forming the arenium ion intermediate. Loss of a proton, facilitated by the Lewis acid counterion (for example, FeBr4-) acting as a base, yields the halobenzene product and regenerates the catalyst. Without a Lewis acid catalyst, benzene does not react with Br2 or Cl2, a stark contrast with alkenes, which react readily. Fluorination is too vigorous to control under standard conditions, so the Balz-Schiemann reaction is typically preferred for introducing fluorine. Iodination is too slow with a Lewis acid alone and requires an oxidizing agent such as HNO3 or H2O2 in conjunction with I2. ### III. Nitration Nitration employs a mixture of concentrated nitric acid and concentrated sulfuric acid, commonly called mixed acid. The role of sulfuric acid is to protonate nitric acid, generating the nitronium ion (NO2+), which is the active electrophile. The aromatic ring attacks the nitronium ion, the resulting arenium ion intermediate loses a proton, and nitrobenzene is produced. Nitration is a strategically important reaction because the nitro group can be subsequently reduced to an amino group (-NH2) using reagents such as H2 with a palladium catalyst, tin in hydrochloric acid, or iron in hydrochloric acid. This provides a key route to aromatic amines. Additionally, the nitro group is a powerful electron-withdrawing substituent that profoundly affects the reactivity and directing behavior of the ring in subsequent reactions. ### IV. Sulfonation Sulfonation uses fuming sulfuric acid (a mixture of H2SO4 and SO3) or concentrated sulfuric acid. The electrophile is sulfur trioxide (SO3) or its protonated form. Sulfur trioxide is a potent electrophile because the sulfur center is rendered highly electron-poor by three surrounding oxygen atoms. Benzene attacks the sulfur of SO3, an arenium ion forms, and deprotonation yields benzenesulfonic acid (ArSO3H). A unique and synthetically valuable feature of sulfonation is its reversibility. Treatment with dilute sulfuric acid and steam effects desulfonation, removing the sulfonic acid group from the ring. No other common EAS reaction is reversible under such mild conditions. This property allows the sulfonic acid group to serve as a temporary blocking group in multistep aromatic synthesis, occupying a position on the ring while other reactions are carried out elsewhere, and then being removed when no longer needed. Sulfonation also has practical applications in the manufacture of sulfa drugs, detergents, and various synthetic intermediates. ### V. Friedel-Crafts Alkylation Friedel-Crafts alkylation introduces an alkyl group onto the aromatic ring using an alkyl halide (RX) and a Lewis acid catalyst (typically AlCl3). The Lewis acid generates a carbocation (or a highly polarized complex) from the alkyl halide, and the aromatic ring attacks this carbocation. The arenium ion intermediate then loses a proton to give the alkylbenzene product. Carbocations can also be generated from alkenes with an acid catalyst or from alcohols with an acid catalyst, providing alternative electrophile sources. Friedel-Crafts alkylation has several important limitations. First, polyalkylation is a persistent problem: the alkyl group donated to the ring is electron-donating, making the product more reactive than the starting material and allowing multiple substitutions to occur. Second, carbocation rearrangements plague the reaction. Primary carbocations readily rearrange via hydride or methyl shifts to more stable secondary or tertiary carbocations, making it impossible to reliably introduce a straight-chain primary alkyl group (except for methyl and ethyl, which cannot rearrange). Third, the reaction does not work with strongly deactivated rings, such as those bearing nitro, acyl, or sulfonic acid groups, because the ring is too electron-poor to attack the electrophile. Fourth, amine-substituted rings are also incompatible because the amine nitrogen coordinates to the Lewis acid catalyst, deactivating it. Panel A: Mechanism of Friedel-Crafts alkylation showing tert-butyl chloride reacting with AlCl3 to generate the tert-butyl carbocation, followed by attack on benzene, arenium ion formation, and deprotonation to give tert-butylbenzene. Panel B: Illustration of the polyalkylation problem, showing how tert-butylbenzene (more electron-rich) reacts again to give di-tert-butylbenzene. Panel C: Example of carbocation rearrangement, where n-propyl chloride with AlCl3 gives isopropylbenzene (cumene) rather than n-propylbenzene, due to hydride shift from primary to secondary carbocation. ### VI. Friedel-Crafts Acylation Friedel-Crafts acylation uses an acyl chloride (RCOCl) or acid anhydride ((RCO)2O) with AlCl3 as the Lewis acid. More than one equivalent of AlCl3 is required because the product ketone coordinates to AlCl3. The electrophile is the acylium ion (RC=O+), which is resonance-stabilized and therefore does not rearrange. The mechanism parallels alkylation: the aromatic ring attacks the acylium ion, the arenium ion intermediate forms, and loss of a proton gives the aryl ketone. Friedel-Crafts acylation offers two major advantages over alkylation. First, polyacylation does not occur because the ketone product is deactivated by the electron-withdrawing carbonyl group, preventing a second acylation from taking place on the same ring. Second, there are no carbocation rearrangements, since the resonance-stabilized acylium ion has no tendency to rearrange. These advantages make acylation the preferred Friedel-Crafts reaction in most synthetic contexts. An important synthetic strategy exploits the acylation-reduction sequence as a workaround for the limitations of direct alkylation. Friedel-Crafts acylation introduces an unrearranged acyl group, which is then reduced to a methylene group using either a Clemmensen reduction (Zn-Hg/HCl) or a Wolff-Kishner reduction (NH2NH2/KOH at high temperature). The net result is the introduction of a primary alkyl group onto the ring without rearrangement. Comparison flowchart of two synthetic routes to n-propylbenzene. Route A (Friedel-Crafts alkylation): benzene + n-propyl chloride + AlCl3 leads to rearranged product isopropylbenzene (wrong product, marked with X). Route B (acylation-reduction): benzene + propanoyl chloride + AlCl3 gives phenyl propyl ketone (correct intermediate), followed by Clemmensen reduction (Zn-Hg, HCl) to give n-propylbenzene (correct product, marked with checkmark). ---