Hóa học - Chapter 17: Reactions of aromatic compounds

Chapter 17Copyright © 2010 Pearson Education, Inc.Organic Chemistry, 7th EditionL. G. Wade, Jr.Reactions of Aromatic CompoundsChapter 17*Electrophilic Aromatic SubstitutionAlthough benzene’s pi electrons are in a stable aromatic system, they are available to attack a strong electrophile to give a carbocation. This resonance-stabilized carbocation is called a sigma complex because the electrophile is joined to the benzene ring by a new sigma bond.Aromaticity is regained by loss of a proton.Chapter 17*Mechanism of Electrophilic Aromatic SubstitutionChapter 17*Bromination of BenzeneChapter 17*Mechanism for the Bromination of Benzene: Step 1Before the electrophilic aromatic substitution can take place, the electrophile must be activated.A strong Lewis acid catalyst, such as FeBr3, should be used.BrBrFeBr3BrBrFeBr3+-(stronger electrophile than Br2)Chapter 17*Step 2: Electrophilic attack and formation of the sigma complex.Step 3: Loss of a proton to give the products.Mechanism for the Bromination of Benzene: Steps 2 and 3Chapter 17*Energy Diagram for BrominationChapter 17*Chlorination and IodinationChlorination is similar to bromination. AlCl3 is most often used as catalyst, but FeCl3 will also work.Iodination requires an acidic oxidizing agent, like nitric acid, to produce iodide cation.H+ + HNO3 + ½ I2 I+ + NO2 + H2OChapter 17*Predict the major product(s) of bromination of p-chloroacetanilide.The amide group (–NHCOCH3) is a strong activating and directing group because the nitrogen atom with its nonbonding pair of electrons is bonded to the aromatic ring. The amide group is a stronger director than the chlorine atom, and substitution occurs mostly at the positions ortho to the amide. Like an alkoxyl group, the amide is a particularly strong activating group, and the reaction gives some of the dibrominated product.Solved Problem 1SolutionChapter 17*Nitration of BenzeneSulfuric acid acts as a catalyst, allowing the reaction to be faster and at lower temperatures.HNO3 and H2SO4 react together to form the electrophile of the reaction: nitronium ion (NO2+).Chapter 17*Mechanism for the Nitration of BenzeneChapter 17*Reduction of the Nitro GroupTreatment with zinc, tin, or iron in dilute acid will reduce the nitro to an amino group.This is the best method for adding an amino group to the ring.Chapter 17*Sulfonation of BenzeneSulfur trioxide (SO3) is the electrophile in the reaction.A 7% mixture of SO3 and H2SO4 is commonly referred to as “fuming sulfuric acid”.The —SO3H groups is called a sulfonic acid.Chapter 17*Mechanism of SulfonationBenzene attacks sulfur trioxide, forming a sigma complex. Loss of a proton on the tetrahedral carbon and reprotonation of oxygen gives benzenesulfonic acid.Chapter 17*Desulfonation ReactionSulfonation is reversible. The sulfonic acid group may be removed from an aromatic ring by heating in dilute sulfuric acid.Chapter 17*Mechanism of DesulfonationIn the desulfonation reaction, a proton adds to the ring (the electrophile) and loss of sulfur trioxide gives back benzene.Chapter 17*Nitration of TolueneToluene reacts 25 times faster than benzene. The methyl group is an activator.The product mix contains mostly ortho and para substituted molecules.Chapter 17*Ortho and Para SubstitutionOrtho and para attacks are preferred because their resonance structures include one tertiary carbocation.Chapter 17*Energy DiagramChapter 17*Meta SubstitutionWhen substitution occurs at the meta position, the positive charge is not delocalized onto the tertiary carbon, and the methyl groups has a smaller effect on the stability of the sigma complex.Chapter 17*Alkyl Group StabilizationAlkyl groups are activating substituents and ortho, para-directors.This effect is called the inductive effect because alkyl groups can donate electron density to the ring through the sigma bond, making them more active.Chapter 17*Substituents with Nonbonding ElectronsResonance stabilization is provided by a pi bond between the —OCH3 substituent and the ring.Chapter 17*Meta Attack on AnisoleResonance forms show that the methoxy group cannot stabilize the sigma complex in the meta substitution.Chapter 17*Bromination of AnisoleA methoxy group is so strongly activating that anisole is quickly tribrominated without a catalyst.Chapter 17*The Amino GroupAniline reacts with bromine water (without a catalyst) to yield the tribromoaniline. Sodium bicarbonate is added to neutralize the HBr that is also formed.Chapter 17*Summary of ActivatorsChapter 17*Activators and Deactivators If the substituent on the ring is electron donating, the ortho and para positions will be activated.If the group is electron withdrawing, the ortho and para positions will be deactivated.Chapter 17*Nitration of NitrobenzeneElectrophilic 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 ortho and para isomers.Chapter 17*Ortho Substitution on NitrobenzeneThe nitro group is a strongly deactivating group when considering its resonance forms. The nitrogen always has a formal positive charge.Ortho or para addition will create an especially unstable intermediate.Chapter 17*Meta Substitution on NitrobenzeneMeta substitution will not put the positive charge on the same carbon that bears the nitro group.Chapter 17*Energy DiagramChapter 17*Deactivators and Meta- DirectorsMost electron withdrawing groups are deactivators and meta-directors.The atom attached to the aromatic ring has a positive or partial positive charge.Electron density is withdrawn inductively along the sigma bond, so the ring has less electron density than benzene and thus, it will be slower to react.Chapter 17*Ortho Attack of AcetophenoneIn ortho and para substitution of acetophenone, one of the carbon atoms bearing the positive charge is the carbon attached to the partial positive carbonyl carbon. Since like charges repel, this close proximity of the two positive charges is especially unstable.Chapter 17*Meta Attack on AcetophenoneThe meta attack on acetophenone avoids bearing the positive charge on the carbon attached to the partial positive carbonyl.Chapter 17*Other DeactivatorsChapter 17*Nitration of ChlorobenzeneWhen chlorobenzene is nitrated the main substitution products are ortho and para. The meta substitution product is only obtained in 1% yield.Chapter 17*Halogens Are DeactivatorsInductive Effect: Halogens are deactivating because they are electronegative and can withdraw electron density from the ring along the sigma bond. Chapter 17*Halogens Are Ortho, Para-DirectorsResonance Effect: The lone pairs on the halogen can be used to stabilize the sigma complex by resonance.Chapter 17*Energy DiagramChapter 17*Summary of Directing EffectsChapter 17*Effect of Multiple SubstituentsThe directing effect of the two (or more) groups may reinforce each other.Chapter 17*Effect of Multiple Substituents (Continued)The position in between two groups in Positions 1 and 3 is hindered for substitution, and it is less reactive.Chapter 17*Effect of Multiple Substituents (Continued)If directing effects oppose each other, the most powerful activating group has the dominant influence.major products obtainedChapter 17*Friedel–Crafts AlkylationSynthesis 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.Chapter 17*Mechanism of the Friedel–Crafts ReactionStep 1Step 2Step 3 Chapter 17*Protonation of AlkenesAn alkene can be protonated by HF. This weak acid is preferred because the fluoride ion is a weak nucleophile and will not attack the carbocation.Chapter 17*Alcohols and Lewis AcidsAlcohols can be treated with BF3 to form the carbocation.Chapter 17*Limitations of Friedel–CraftsReaction fails if benzene has a substituent that is more deactivating than halogens.Rearrangements are possible.The alkylbenzene product is more reactive than benzene, so polyalkylation occurs. Chapter 17*RearrangementsChapter 17*Devise a synthesis of p-nitro-t-butylbenzene from benzene.To make p-nitro-t-butylbenzene, we would first use a Friedel–Crafts reaction to make t-butylbenzene. Nitration gives the correct product. If we were to make nitrobenzene first, the Friedel–Crafts reaction to add the t-butyl group would fail.Solved Problem 2SolutionChapter 17*Friedel–Crafts Acylation Acyl chloride is used in place of alkyl chloride.The product is a phenyl ketone that is less reactive than benzene.Chapter 17*Mechanism of AcylationStep 1: Formation of the acylium ion.Step 2: Electrophilic attack to form the sigma complex.Chapter 17*Clemmensen ReductionThe Clemmensen reduction is a way to convert acylbenzenes to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc.Chapter 17*Nucleophilic Aromatic SubstitutionA nucleophile replaces a leaving group on the aromatic ring. This is an addition–elimination reaction.Electron-withdrawing substituents activate the ring for nucleophilic substitution. Chapter 17*Mechanism of Nucleophilic Aromatic SubstitutionStep 1: Attack by hydroxide gives a resonance-stabilized complex.Step 2: Loss of chloride gives the product. Step 3: Excess base deprotonates the product.Chapter 17*Activated PositionsNitro groups ortho and para to the halogen stabilize the intermediate (and the transition state leading to it). Electron-withdrawing groups are essential for the reaction to occur.Chapter 17*Benzyne Reaction: Elimination-AdditionReactant is halobenzene with no electron-withdrawing groups on the ring.Use a very strong base like NaNH2. Chapter 17*Benzyne MechanismSodium amide abstract a proton. The benzyne intermediate forms when the bromide is expelled and the electrons on the sp2 orbital adjacent to it overlap with the empty sp2 orbital of the carbon that lost the bromide. Benzynes are very reactive species due to the high strain of the triple bond.Chapter 17*Nucleophilic Substitution on the Benzyne IntermediateChapter 17* Chlorination of BenzeneAddition to the benzene ring may occur with excess of chlorine under heat and pressure.The first Cl2 addition is difficult, but the next two moles add rapidly.An insecticideChapter 17*Catalytic HydrogenationElevated heat and pressure is required.Possible catalysts: Pt, Pd, Ni, Ru, Rh.Reduction cannot be stopped at an intermediate stage.CH3CH3Ru, 100°C1000 psi3H2,CH3CH3Chapter 17*Birch ReductionThis reaction reduces the aromatic ring to a nonconjugated 1,4-cyclohexadiene.The reducing agent is sodium or lithium in a mixture of liquid ammonia and alcohol.Chapter 17*Mechanism of the Birch ReductionChapter 17*Limitations of the Birch ReductionChapter 17*Side-Chain OxidationAlkylbenzenes are oxidized to benzoic acid by heating in basic KMnO4 or heating in Na2Cr2O7/H2SO4.The benzylic carbon will be oxidized to the carboxylic acid.Chapter 17*Side-Chain HalogenationThe benzylic position is the most reactive.Br2 reacts only at the benzylic position.Cl2 is not as selective as bromination, so results in mixtures.Chapter 17*Mechanism of Side-Chain HalogenationChapter 17*SN1 ReactionsBenzylic carbocations are resonance-stabilized, easily formed.Benzyl halides undergo SN1 reactions.CH2BrCH3CH2OH, heatCH2OCH2CH3Chapter 17*SN2 ReactionsBenzylic halides are 100 times more reactive than primary halides via SN2.The transition state is stabilized by a ring.Chapter 17*Oxidation of PhenolsPhenol will react with oxidizing agents to produce quinones.Quinones are conjugated 1,4-diketones.This can also happen (slowly) in the presence of air.