Chapter 17 Reactions of Aromatic Compounds Electrophilic Aromatic Substitution Electrophile substitutes for a hydrogen on the benzene ring. Chapter 17: Aromatics 2-Reactions Slide 17-2 1
Mechanism Step 1: Attack on the electrophile forms the sigma complex. Step 2: Loss of a proton gives the substitution product. Chapter 17: Aromatics 2-Reactions Slide 17-3 Bromination of Benzene Requires a stronger electrophile than Br 2. Use a strong Lewis acid catalyst, FeBr 3. + Br Br FeBr - 3 Br Br FeBr 3 + - Br Br FeBr 3 Br _ + + FeBr 4 Br + Br Chapter 17: Aromatics 2-Reactions Slide 17-4 2
Comparison with Alkenes Cyclohexene adds Br 2, Δ = -121 kj Addition to benzene is endothermic, not normally seen. Substitution of Br for retains aromaticity, Δ = -45 kj. Formation of sigma complex is rate-limiting. Chapter 17: Aromatics 2-Reactions Slide 17-5 Energy Diagram for Bromination Chapter 17: Aromatics 2-Reactions Slide 17-6 3
Chlorination and Iodination Chlorination is similar to bromination. Use AlCl 3 as the Lewis acid catalyst. Iodination requires an acidic oxidizing agent, like nitric acid, which oxidizes the iodine to an iodonium ion. + + N 3 + 1/2 I 2 I + + N 2 + 2 Chapter 17: Aromatics 2-Reactions Slide 17-7 Nitration of Benzene Use sulfuric acid with nitric acid to form the nitronium ion electrophile. N 2 + then forms a sigma complex with benzene, loses + to form nitrobenzene. Chapter 17: Aromatics 2-Reactions Slide 17-8 4
Sulfonation Sulfur trioxide, S 3, in fuming sulfuric acid is the electrophile. _ S S + S + S + Chapter 17: Aromatics 2-Reactions Slide 17-9 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. large excess D 2 S 4 /D 2 D D D D D D Benzene-d 6 Chapter 17: Aromatics 2-Reactions Slide 17-10 5
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: Aromatics 2-Reactions Slide 17-11 Sigma Complex Intermediate is more stable if nitration occurs at the ortho or para position. Chapter 17: Aromatics 2-Reactions Slide 17-12 6
Energy Diagram Chapter 17: Aromatics 2-Reactions Slide 17-13 Activating, -, 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. + C 3 N 2 + C 3 N 2 Chapter 17: Aromatics 2-Reactions Slide 17-14 7
Substitution on Anisole Chapter 17: Aromatics 2-Reactions Slide 17-15 The Amino Group Aniline, like anisole, reacts with bromine water (without a catalyst) to yield the tribromide. Sodium bicarbonate is added to neutralize the Br that s also formed. Chapter 17: Aromatics 2-Reactions Slide 17-16 8
Summary of Activators Chapter 17: Aromatics 2-Reactions Slide 17-17 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 ortho and para isomers. Meta-directors deactivate all positions on the ring, but the meta position is less deactivated. Chapter 17: Aromatics 2-Reactions Slide 17-18 9
rtho Substitution on Nitrobenzene Chapter 17: Aromatics 2-Reactions Slide 17-19 Para Substitution on Nitrobenzene Chapter 17: Aromatics 2-Reactions Slide 17-20 10
Meta Substitution on Nitrobenzene Chapter 17: Aromatics 2-Reactions Slide 17-21 Energy Diagram Chapter 17: Aromatics 2-Reactions Slide 17-22 11
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: Aromatics 2-Reactions Slide 17-23 Summary of Deactivators Chapter 17: Aromatics 2-Reactions Slide 17-24 12
More Deactivators Chapter 17: Aromatics 2-Reactions Slide 17-25 alobenzenes alogens 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: Aromatics 2-Reactions Slide 17-26 13
Sigma Complex for Bromobenzene rtho and para attacks produce a bromonium ion and other resonance structures. No bromonium ion possible with meta attack. Chapter 17: Aromatics 2-Reactions Slide 17-27 Energy Diagram Chapter 17: Aromatics 2-Reactions Slide 17-28 14
Summary of Directing Effects Chapter 17: Aromatics 2-Reactions Slide 17-29 Multiple Substituents The most strongly activating substituent will determine the position of the next substitution. May have mixtures. C 3 C 3 C 3 S 3 + S 3 2 N 2 S 4 2 N 2 N S 3 Chapter 17: Aromatics 2-Reactions Slide 17-30 15
Friedel-Crafts Alkylation Synthesis of alkyl benzenes from alkyl halides and a Lewis acid, usually AlCl 3. Reactions of alkyl halide with Lewis acid produces a carbocation which is the electrophile. ther sources of carbocations: alkenes + F, or alcohols + BF 3. Chapter 17: Aromatics 2-Reactions Slide 17-31 Examples of Carbocation Formation Cl C 3 C C 3 C 3 + _ + AlCl 3 C Cl AlCl 3 3 C 2 C C C 3 F _ F + 3 C C C 3 3 C C C 3 + BF 3 BF 3 3 C C C 3 + 3 C C C 3 + BF 3 _ Chapter 17: Aromatics 2-Reactions Slide 17-32 16
Formation of Alkyl Benzene C 3 C +C 3 + C(C 3 ) 2 + F - F B C(C 3 ) 2 F C 3 C + C 3 F F F B Chapter 17: Aromatics 2-Reactions Slide 17-33 Limitations of Friedel-Crafts Reaction fails if benzene has a substituent that is more deactivating than halogen. Carbocations rearrange. Reaction of benzene with n-propyl chloride and AlCl 3 produces isopropylbenzene. The alkylbenzene product is more reactive than benzene, so polyalkylation occurs. Chapter 17: Aromatics 2-Reactions Slide 17-34 17
Friedel-Crafts Acylation 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: Aromatics 2-Reactions Slide 17-35 Mechanism of Acylation C + R + C R _ Cl AlCl 3 C R + Cl AlCl 3 Chapter 17: Aromatics 2-Reactions Slide 17-36 18
Clemmensen Reduction Acylbenzenes can be converted to alkylbenzenes by treatment with aqueous Cl and amalgamated zinc. Works for nonaromatic ketones as well; rearrangements can occur. + C 3 C 2 C Cl 1) AlCl 3 2) 2 C C 2 C 3 Zn(g) aq. Cl C 2 C 2 C 3 Chapter 17: Aromatics 2-Reactions Slide 17-37 Wolff-Kishner Reduction Acylbenzenes can be also converted to alkylbenzenes by treatment with aqueous N 2 N 2 and hydroxide (mechanism next chapter). Works for non-aromatic ketones as well. N 2 N 2 K aq. ethylene glycol Chapter 17: Aromatics 2-Reactions Slide 17-38 19
Gatterman-Koch Formylation Formyl chloride is unstable. Use a high pressure mixture of C, Cl, and catalyst. Product is benzaldehyde. C + Cl C + C + Cl AlCl 3 /CuCl C + C + Cl AlCl 4 _ Chapter 17: Aromatics 2-Reactions Slide 17-39 Nucleophilic Aromatic Substitution A nucleophile replaces a leaving group on the aromatic ring. Electron-withdrawing substituents activate the ring for nucleophilic substitution. Chapter 17: Aromatics 2-Reactions Slide 17-40 20
Examples of Nucleophilic Substitution Chapter 17: Aromatics 2-Reactions Slide 17-41 Addition-Elimination Mechanism Chapter 17: Aromatics 2-Reactions Slide 17-42 21
Benzyne Mechanism Reactant is halobenzene with no electron-withdrawing groups on the ring. Use a very strong base like NaN 2. Chapter 17: Aromatics 2-Reactions Slide 17-43 Benzyne Intermediate Chapter 17: Aromatics 2-Reactions Slide 17-44 22
Chlorination of Benzene Addition to the benzene ring may occur with high heat and pressure (or light). The first Cl 2 addition is difficult, but the next 2 moles add rapidly. The product, benzene hexachloride, is an insecticide. Chapter 17: Aromatics 2-Reactions Slide 17-45 Catalytic ydrogenation Elevated heat and pressure is required. Possible catalysts: Pt, Pd, Ni, Ru, Rh. Reduction cannot be stopped at an intermediate stage. C 3 C 3 C 3 1000 psi 3 2, Ru, 100 C C 3 Chapter 17: Aromatics 2-Reactions Slide 17-46 23
Birch Reduction: Regiospecific A carbon bearing an e - -withdrawing group is reduced. C _ C Na, N 3 C 3 C 2 A carbon bearing an e - -releasing group is not reduced. C 3 Li, N 3 C 3 (C 3 ) 3 C, TF Chapter 17: Aromatics 2-Reactions Slide 17-47 Birch Mechanism Chapter 17: Aromatics 2-Reactions Slide 17-48 24
Side-Chain xidation Alkylbenzenes are oxidized to benzoic acid by hot KMn 4 or Na 2 Cr 2 7 / 2 S 4. C(C 3 ) 2 C C 2 KMn 4, - 2, heat _ C _ C Chapter 17: Aromatics 2-Reactions Slide 17-49 Side-Chain alogenation Benzylic position is the most reactive. Chlorination is not as selective as bromination, results in mixtures. Br 2 reacts only at the benzylic position. Br C 2 C 2 C 3 Br 2, h! CC 2 C 3 Chapter 17: Aromatics 2-Reactions Slide 17-50 25
S N 1 Reactions Benzylic carbocations are resonance-stabilized, easily formed. Benzyl halides (even primary!) undergo S N 1 reactions. C 2 Br C 3 C 2, heat C 2 C 2 C 3 Chapter 17: Aromatics 2-Reactions Slide 17-51 S N 2 Reactions Benzylic halides are 100 times more reactive than primary halides via S N 2. Transition state is stabilized by ring. Chapter 17: Aromatics 2-Reactions Slide 17-52 26
Reactions of Phenols Some reactions like aliphatic alcohols: phenol + carboxylic acid ester phenol + aq. Na phenoxide ion xidation to quinones: 1,4-diketones. Na 2 Cr 2 7, 2 S 4 C 3 C 3 Chapter 17: Aromatics 2-Reactions Slide 17-53 Quinones ydroquinone is used as a developer for film. It reacts with light-sensitized AgBr grains, converting it to black Ag. Coenzyme Q is an oxidizing agent found in the mitochondria of cells. + 2 AgBr + 2 Ag + 2 Br Chapter 17: Aromatics 2-Reactions Slide 17-54 27
Electrophilic Substitution of Phenols Phenols and phenoxides are highly reactive. nly a weak catalyst (F) required for Friedel-Crafts reaction. Tribromination occurs without catalyst. Even reacts with C 2. _ C 2, - _ C _ + C salicylic acid Chapter 17: Aromatics 2-Reactions Slide 17-55 End of Chapter 17 omework: 44, 46, 47, 49, 52, 53, 56, 57, 61, 63, 64, 67 Chapter 17: Aromatics 2-Reactions Slide 17-56 28