rganic Chemistry, 6 th Edition L. G. Wade, Jr. Chapter 17 Reactions of Aromatic Compounds Jo Blackburn Richland College, Dallas, TX Dallas County Community College District 2006, Prentice all Electrophilic Aromatic Substitution Electrophile substitutes for a hydrogen on the benzene ring. Chapter 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 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 Br _ FeBr 4 Br Chapter 17 4 2
Comparison with Alkenes Cyclohexene adds Br 2, = -121 kj Addition to benzene is endothermic, not normally seen. Substitution of Br for retains aromaticity, = -45 kj. Formation of sigma complex is ratelimiting. Chapter 17 5 Energy Diagram for Bromination Chapter 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 7 Nitration of Benzene Use sulfuric acid with nitric acid to form the nitronium ion electrophile. S N N S 4 _ N 2 N N 2 then forms a sigma complex with benzene, loses to form nitrobenzene. Chapter 17 8 4
Sulfonation Sulfur trioxide, S 3, in fuming sulfuric acid is the electrophile. _ S S S S S _ S S benzenesulfonic acid Chapter 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 Benzene-d 6 Chapter 17 10 D 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 11 Sigma Complex Intermediate is more stable if nitration occurs at the ortho or para position. Chapter 17 12 6
Energy Diagram Chapter 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 14 7
Substitution on Anisole Chapter 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 16 8
Summary of Activators Chapter 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 18 9
rtho Substitution on Nitrobenzene Chapter 17 19 Para Substitution on Nitrobenzene Chapter 17 20 10
Meta Substitution on Nitrobenzene Chapter 17 21 Energy Diagram Chapter 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 23 Summary of Deactivators Chapter 17 24 12
More Deactivators Chapter 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 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 27 Energy Diagram Chapter 17 28 14
Summary of Directing Effects Chapter 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 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 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 _ BF3 Chapter 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 F C 3 F Chapter 17 33 F B 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 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 35 Mechanism of Acylation C R C R _ Cl AlCl 3 C R Cl AlCl 3 Chapter 17 36 18
Clemmensen Reduction Acylbenzenes can be converted to alkylbenzenes by treatment with aqueous Cl and amalgamated zinc. 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 37 Gatterman-Koch Formylation Formyl chloride is unstable. Use a high pressure mixture of C, Cl, and catalyst. Product is benzaldehyde. C Cl C Cl AlCl 3 /CuCl C C C Chapter 17 38 Cl AlCl 4 _ 19
Nucleophilic Aromatic Substitution A nucleophile replaces a leaving group on the aromatic ring. Electron-withdrawing substituents activate the ring for nucleophilic substitution. Chapter 17 39 Examples of Nucleophilic Substitution Chapter 17 40 20
Addition-Elimination Mechanism Chapter 17 41 21