CH16 Reactions of Benzene PDF

CH16 Reactions of benzene Electrophilic aromatic substitutions Electrophilic Aromatic Substitution (EAS) - general mechanism Although 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 ca...

CH16 Reactions of benzene Electrophilic aromatic substitutions Electrophilic Aromatic Substitution (EAS) - general mechanism Although 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. Electrophilic Aromatic Substitution (EAS) -bromination  Electrophilic aromatic substitutions Electrophilic Aromatic Substitution Electrophilic aromatic substitutions - nitration Nitration may be used to introduce N substituent on the ring NO2 group can then be reduced to an -NH2 group  Substituent Effects on EAS If the aromatic ring bears a substituent E1, will this substituent (i) activate or deactivate the ring toward attack by the electrophile E2 ? (ii) at which position on the ring (ortho, meta or para) will it direct attack by the 2ND electrophile E2? Substituent effects are a combination of RESONANCE and INDUCTIVE effects Electron donating groups are activating- they increase the rate of electrophilic aromatic (Ear) substitution relative to benzene Electron withdrawing groups are deactivating - they decrease the rate of Ear substitution relative to benzene  Deactivating and Activating substituents – resonance effect examples Based on resonance structures -CHO is electron withdrawing at ortho & para positions -OH is electron donating at ortho and para : positions  Substituent Effects on electrophilic aromatic substitution EDG = electron donating group EDG add electron density to the π system making it more nucleophilic can be recognized by lone pairs on the atom adjacent to the π system, ex: -OCH3 Note -R, -Ar or -vinyl are also EDG via inductive effect or pi system EWG = electron withdrawing group EWG remove electron density from the π system making it less nucleophilic. can be recognized either by the atom adjacent to the π system having a multiple bond to more electronegative atoms, or having a formal or partial positive charge, ex: -CO2R, -NO2 EDG / activating groups direct ortho / para EWG / deactivating groups direct meta except halogens (-X) which are deactivating BUT direct ortho / para Practice: Rank the following in order of decreasing reactivity toward Ear Substitution a) Benzene b) bromobenzene c) nitrobenzene d) toluene In this example, what makes the intermediates for the formation of ortho and para products more stable than those for meta? Compare the structures of the intermediates… The intermediates are described by a resonance hybrid which includes three carbocations. For the ortho and para products, one of the carbocations is tertiary. This structure is more stable because the electrons on the CH3 stabilize the electron deficient +C. This stability is passed on to the resonance hybrid, which makes the intermediates for attack at toluene ortho/para more stable than that for attack at the meta position. Groups donating electrons stabilize electrophilic attack in ortho and para positions Alkyl groups and substituents with an oxygen or amine nitrogen directly attached to the ring are electron donating and stabilize the electron deficient carbon atom. Effect of ring substituents on Electrophilic aromatic substitution reactions. Example: nitration of toluene Toluene reacts 25 times faster than benzene. The methyl group is an activator. The product consists of mostly ortho- and para- nitrotoluene Alkyl Groups activate the ring toward electrophilic attack and are ortho, para directing Alkyl 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 reactive toward electrophilic reagents. Ortho and para attack preferred because the sigma complexes resulting from attack in ortho and para are more stabilized by resonance (including a 3ary Carbocation) than the sigma complex resulting from attack in meta Regiochemistry of EAS of anisole Anisole undergoes nitration about 10,000 times faster than benzene and about 400 times faster than toluene. The oxygen atom donates electron density in the ortho and para positions stabilizing the transition state and the sigma complex via resonance Bromination of Anisole and Aniline The methoxy and amino groups are so strongly activating that anisole and aniline are quickly tribrominated without a catalyst.  Deactivators and Meta-Directors Most electron-withdrawing groups are deactivators and meta-directing, ex -CHO. 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.  Analysis of the sigma complex for deactivating groups which are meta directing The attack at positions ortho and para to an electron withdrawing group places the positive charge directly adjacent to the positive end of the EWG. The energy of such an intermediate is higher than the one resulting from meta attack. The consequence is that attack at the meta position is less unfavorable than attack in ortho or para Groups in which the atom directly attached to the benzene ring have a partial or complete positive charge tend to pull electrons toward themselves. Such groups are called electron withdrawing groups and are meta directing groups in electrophilic aromatic substitution. Ex. of meta directing, deactivating substituent in EAS - Nitration of Nitrobenzene Electrophilic substitution reactions for nitrobenzene are 100,000 times slower than for benzene The product mix contains mostly the meta isomer Deactivating groups in EAS  Halogens – deactivating in EAS but ortho, para directing Halogens inductively withdraw electron density from the ring, deactivating it toward attack by an electrophile. Halogens can stabilize the sigma complex resulting from attack in ortho and para via resonance Summary of Effect of substituents on EAS Q.1 What is the major product of this reaction sequence? a) Nitrobenzene b) Aniline c) Chlorobenzene d) Benzenesulfonic acid Q.2 What is the major product of this reaction? a) 2- and 4-nitroethylbenzene b) 3-Nitroethylbenzene c) 2- and 4-ethylbenzenesulfonic acid d) 3-Ethylbenzenesulfonic acid Q.3 Describe the directing and activating/deactivating effect of a bromo substituent on EAS a) Meta directing, activating group b) Meta directing, deactivating group c) Ortho and para, deactivating group d) Ortho and para, activating group Q.4 Describe the directing and activating/deactivating effect of a nitro substituent on EAS a) Meta, activating group b) Meta, deactivating group c) Ortho and para, deactivating group d) Ortho and para, activating group Predicting position of substitution in molecules with multiple substituents The directing effect of two groups may reinforce each other. If directing effects oppose each other, the most powerful activating group has the dominant influence. Crowding of substituents may also affect product distribution Practice problem 1 - Predict the major product(s) of bromination of p-chloroacetanilide. Friedel–Crafts Alkylation Synthesis of alkyl benzenes from alkyl halides and a Lewis acid, usually AlCl3 Reactions of alkyl halide with Lewis acid produce a carbocation, which is the electrophile. Alkenes and alcohols in presence of an acid may be used as the source of the electrophilic carbocation instead of the alkyl halide Mechanism of the Friedel-Crafts Reaction – an EAS reaction Limitations of Friedel-Crafts Reaction fails if benzene has a substituent that is more deactivating than halogens. Rearrangement of carbocation is possible. The alkylbenzene product is more reactive than benzene, so polyalkylation may occur. Practice Problem 2 Devise a synthesis of p-nitro-t-butylbenzene from benzene. Hint: in what order should the nitration and the alkylation be carried out? Why is the order of the two reactions important? Friedel–Crafts Acylation – an EAS reaction Acyl chloride is used in place of alkyl chloride. The product is a phenyl ketone that is less reactive than benzene so no risk of polyacylation. Mechanism of Friedel Crafts Acylation  Conversion of acyl benzene to alkyl benzene - Clemmensen Reduction The Clemmensen reduction is a way to convert acyl benzenes to alkylbenzenes by treatment with aqueous HCl and amalgamated zinc. Friedel Crafts acylation followed by Clemmensen reduction is often a good alternative to Friedel Crafts alkylation (avoids rearrangement, polyalkylation) Q.5 Predict the major product of this reaction a) 3-Propylanisole b) 2- and 4-propylanisole c) 3-Isopropylanisole d) 2- and 4-isopropylanisole Q.6 Predict the major product of this reaction sequence a) Ethylbenzene b) 1-Phenylethanol c) 2-Phenylethanol d) Chlorobenzene Catalytic Hydrogenation of benzene Elevated heat and pressure are required, harder to reduce than alkenes Possible catalysts: Pt, Pd, Ni, Ru, Rh Reduction cannot be stopped at an intermediate stage.  Oxidation of aromatic side chain The benzylic carbon is oxidized to a carboxylic acid by heating in basic KMnO4 or heating in Na2Cr2O7/H2SO4. Aromatic Side-Chain radical halogenation The benzylic position is the most reactive. Br2 reacts only at the benzylic position.  Please complete the course evaluations due tomorrow (12/10) Your feedback is very valuable to me. 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