Chapter 17 Reactions of Aromatic Compounds

Organic Chemistry, 6th EditionL. G. Wade, Jr. Chapter 17Reactions of Aromatic Compounds Jo Blackburn Richland College, Dallas, TX Dallas County Community College District ã 2006,Prentice Hall

=> Electrophilic Aromatic Substitution Electrophile substitutes for a hydrogen on the benzene ring. Chapter 17

Step 1: Attack on the electrophile forms the sigma complex. Step 2: Loss of a proton gives the substitution product. => Mechanism Chapter 17

- + - + Bromination of Benzene • Requires a stronger electrophile than Br2. • Use a strong Lewis acid catalyst, FeBr3. => Chapter 17

Comparison with Alkenes • Cyclohexene adds Br2, H = -121 kJ • Addition to benzene is endothermic, not normally seen. • Substitution of Br for H retains aromaticity, H = -45 kJ. • Formation of sigma complex is rate-limiting. => Chapter 17

Energy Diagramfor Bromination => Chapter 17

=> Chlorination and Iodination • Chlorination is similar to bromination. Use AlCl3 as the Lewis acid catalyst. • Iodination requires an acidic oxidizing agent, like nitric acid, which oxidizes the iodine to an iodonium ion. Chapter 17

Nitration of Benzene Use sulfuric acid with nitric acid to form the nitronium ion electrophile. NO2+ then forms a sigma complex with benzene, loses H+ to form nitrobenzene. => Chapter 17

=> Sulfonation Sulfur trioxide, SO3, in fuming sulfuric acid is the electrophile. Chapter 17

=> Benzene-d6 Desulfonation • All steps are reversible, so sulfonic acid group can be removed by heating in dilute sulfuric acid. • This process is used to place deuterium in place of hydrogen on benzene ring. Chapter 17

=> Nitration of Toluene • Toluene reacts 25 times faster than benzene. The methyl group is an activating group. • The product mix contains mostly ortho and para substituted molecules. Chapter 17

=> Sigma Complex Intermediate is more stable if nitration occurs at the orthoor para position. Chapter 17

Energy Diagram => Chapter 17

=> Activating, O-, P-Directing Substituents • Alkyl groups stabilize the sigma complex by induction, donating electron density through the sigma bond. • Substituents with a lone pair of electrons stabilize the sigma complex by resonance. Chapter 17

Substitution on Anisole => Chapter 17

=> The Amino Group Aniline, like anisole, reacts with bromine water (without a catalyst) to yield the tribromide. Sodium bicarbonate is added to neutralize the HBr that’s also formed. Chapter 17

Summary ofActivators => Chapter 17

Deactivating Meta-Directing Substituents • Electrophilic substitution reactions for nitrobenzene are 100,000 times slower than for benzene. • The product mix contains mostly the meta isomer, only small amounts of the orthoand para isomers. • Meta-directors deactivate all positions on the ring, but the meta position is less deactivated. => Chapter 17

Ortho Substitutionon Nitrobenzene => Chapter 17

Para Substitution on Nitrobenzene => Chapter 17

Meta Substitutionon Nitrobenzene => Chapter 17

Structure of Meta-Directing Deactivators • The atom attached to the aromatic ring will have a partial positive charge. • Electron density is withdrawn inductively along the sigma bond, so the ring is less electron-rich than benzene. => Chapter 17

Summary of Deactivators => Chapter 17

More Deactivators => Chapter 17

Halobenzenes • Halogens are deactivating toward electrophilic substitution, but are ortho, para-directing! • Since halogens are very electronegative, they withdraw electron density from the ring inductively along the sigma bond. • But halogens have lone pairs of electrons that can stabilize the sigma complex by resonance. => Chapter 17

Ortho and para attacks produce a bromonium ionand other resonance structures. No bromonium ion possible with meta attack. => Sigma Complexfor Bromobenzene Chapter 17

Summary of Directing Effects => Chapter 17

=> Multiple Substituents The most strongly activating substituent will determine the position of the next substitution. May have mixtures. Chapter 17

Friedel-Crafts Alkylation • Synthesis of alkyl benzenes from alkyl halides and a Lewis acid, usually AlCl3. • Reactions of alkyl halide with Lewis acid produces a carbocation which is the electrophile. • Other sources of carbocations: alkenes + HF, or alcohols + BF3. => Chapter 17

=> Examples ofCarbocation Formation Chapter 17

- + => Formation of Alkyl Benzene Chapter 17

Limitations ofFriedel-Crafts • Reaction fails if benzene has a substituent that is more deactivating than halogen. • Carbocations rearrange. Reaction of benzene with n-propyl chloride and AlCl3 produces isopropylbenzene. • The alkylbenzene product is more reactive than benzene, so polyalkylation occurs. => Chapter 17

Friedel-CraftsAcylation • Acyl chloride is used in place of alkyl chloride. • The acylium ion intermediate is resonance stabilized and does not rearrange like a carbocation. • The product is a phenyl ketone that is less reactive than benzene. => Chapter 17

=> Mechanism of Acylation Chapter 17

=> Clemmensen Reduction Acylbenzenes can be converted to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc. Chapter 17

=> Gatterman-KochFormylation • Formyl chloride is unstable. Use a high pressure mixture of CO, HCl, and catalyst. • Product is benzaldehyde. Chapter 17

NucleophilicAromatic Substitution • A nucleophile replaces a leaving group on the aromatic ring. • Electron-withdrawing substituents activate the ring for nucleophilic substitution. => Chapter 17

Examples ofNucleophilic Substitution => Chapter 17

=> Addition-EliminationMechanism Chapter 17

=> Benzyne Mechanism • Reactant is halobenzene with no electron-withdrawing groups on the ring. • Use a very strong base like NaNH2. Chapter 17

=> Benzyne Intermediate Chapter 17

=> Chlorination of Benzene • Addition to the benzene ring may occur with high heat and pressure(or light). • The first Cl2 addition is difficult, but the next 2 moles add rapidly. • The product, benzene hexachloride, is an insecticide. Chapter 17

=> Catalytic Hydrogenation • Elevated heat and pressure is required. • Possible catalysts: Pt, Pd, Ni, Ru, Rh. • Reduction cannot be stopped at an intermediate stage. Chapter 17

=> Birch Reduction: Regiospecific • A carbon bearing an e--withdrawing group • is reduced. • A carbon bearing an e--releasing group • is not reduced. Chapter 17

=> Birch Mechanism Chapter 17

=> Side-Chain Oxidation Alkylbenzenes are oxidized to benzoic acid by hot KMnO4 or Na2Cr2O7/H2SO4. Chapter 17

=> Side-Chain Halogenation • Benzylic position is the most reactive. • Chlorination is not as selective as bromination, results in mixtures. • Br2 reacts only at the benzylic position. Chapter 17

=> SN1 Reactions • Benzylic carbocations are resonance-stabilized, easily formed. • Benzyl halides undergo SN1 reactions. Chapter 17

Chapter 17 Reactions of Aromatic Compounds