Electrophilic Attack Electrophilic Aromatic Substitution Electrophile substitutes for a hydrogen on the benzene ring. Mechanism => Bromination of Benzene • Requires a stronger electrophile than Br2. • Use a strong Lewis acid catalyst, FeBr3. Br Br FeBr3 Br Br H H H H H FeBr3 H H H Br Br Br FeBr3 + H H H H Br + HBr _ + FeBr4 Energy Diagram for Bromination => 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. + H + HNO3 + 1/2 I2 + I + NO2 + H2O Nitration of Benzene Use sulfuric acid with nitric acid to form the nitronium ion electrophile. O H O S O H O H O H O N H O N + O O O H O H O N + O O H2O + N+ O _ + HSO4 NO2+ then forms a sigma complex with benzene, loses H+ to form nitrobenzene. => Sulfonation Sulfur trioxide, SO3, in fuming sulfuric acid is the electrophile. _ O O S S+ O O O O O S+ _ O O _ O S O O H O S O + O H O _ S + O O HO O S O benzenesulfonic acid Nitration of Toluene • Toluene reacts 25 times faster than benzene. The methyl group is an activator. • The product mix contains mostly ortho and para substituted molecules. Sigma Complex Intermediate is more stable if nitration occurs at the ortho or para position. Energy Diagram => 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. Examples of Carbocation Formation Cl CH3 CH CH3 + AlCl3 _ CH3 + C Cl AlCl3 H3C H _ H2C CH CH3 OH H3C CH CH3 BF3 HF + BF3 H O H3C CH CH3 F + H3C CH CH3 _ + H3C CH CH3 + HOBF3 => Formation of Alkyl Benzene CH3 H +C H + CH3 CH(CH3)2 H F H CH(CH3)2 + H F B OH CH3 F- CH + CH3 HF F F B OH 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 AlCl3 produces isopropylbenzene. • The alkylbenzene product is more reactive than benzene, so polyalkylation occurs. 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. Mechanism of Acylation O R C Cl O + _ R C Cl AlCl3 AlCl3 O + _ R C Cl AlCl3 _ AlCl4 + + R C O O O C C+ R + H H R Cl _ AlCl3 + R C O O C HCl R + AlCl3 Clemmensen Reduction Acylbenzenes can be converted to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc. O O + CH3CH2C Cl 1) AlCl3 2) H2O C CH2CH3 Zn(Hg) aq. HCl CH2CH2CH3 Gatterman-Koch Formylation • Formyl chloride is unstable. Use a high pressure mixture of CO, HCl, and catalyst. • Product is benzaldehyde. O H C Cl CO + HCl + AlCl3/CuCl O O C+ C H H _ + H C O AlCl4 + HCl 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. OCH3 + OCH3 NO2 NO2 + H H The Amino Group Aniline reacts with bromine water (without a catalyst) to yield the tribromide. Sodium bicarbonate is added to neutralize the HBr that’s also formed. NH2 NH2 Br Br 3 Br2 H2O, NaHCO3 Br => Summary of Activators 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. Ortho Substitution on Nitrobenzene Para Substitution on Nitrobenzene => Meta Substitution on Nitrobenzene Energy Diagram 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. Summary of Deactivators More Deactivators Halobenzenes • Halogens are deactivating toward electrophilic substitution, but are ortho, paradirecting! • 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. Sigma Complex for Bromobenzene Para attack Ortho attack Br Br + (+) + E Br Br (+) H E (+) + (+) (+) + E (+) H E Ortho and para attacks produce a bromonium ion and other resonance structures. Meta attack Br Br H (+) + + H E (+) E No bromonium ion possible with meta attack. Energy Diagram Summary of Directing Effects Multiple Substituents The most strongly activating substituent will determine the position of the next substitution. May have mixtures. OCH3 OCH3 SO3H SO3 O2N H2SO4 OCH3 + O2N O2N SO3H II. Electrophilic Addition “Loose” p electrons are nucleophilic (Lewis bases), react with electrophiles (Lewis acids). electrophile + Y Z C C Z Y Y C C C C nucleophile 37 Z II. Electrophilic Addition A. Addition of hydrogen halides H X C C + H X (X = Cl, Br, I) C C Reactivity: HI > HBr > HCl >> HF (stronger acid = better e + H X H C C RLS X C C H X C C fast HBr Br HI I 38 II. Electrophilic Addition A. Addition of hydrogen halides 1. Markovnikov’s rule In the addition of HX to an alkene, the H goes to the carbon w CH3 CH CH2 Br HBr CH3 CH CH3 but not CH3 CH2 CH2 Br Question 6-2. Draw the products. Click on the arrow to check a HI HCl HBr Check Answer HI 39 II. Electrophilic Addition A. Addition of hydrogen halides 1. Markovnikov’s rule In the addition of HX to an alkene, the H goes to the carbon w CH3 CH CH2 Br HBr CH3 CH CH3 but not CH3 Answer 6-2. HI I Cl HCl HBr Br I HI and I 40 CH2 CH2 Br II. Electrophilic Addition A. Addition of hydrogen halides 2. mechanism H Br CH3 CH CH2 CH3 CH CH3 2º carbocation more stable CH3 CH2 CH2 1º carbocation less stable Br Br Br Br Mechanistic interpretation of Markovnikov’s rule: The reaction proceeds through the more stable carbocation intermediate. 41 II. Electrophilic Addition A. Addition of hydrogen halides 2. mechanism lower Ea faster rate of formation Br Br Br + HBr Br 42