Reactions of Benzene and itsDerivatives Chapter 22 Chapter 22
Reactions of Benzene • The most characteristic reaction of aromatic compounds is substitution at a ring carbon. • This is Electrophilic Aromatic Substitution (EAS).
Sulfonation: H S O 2 4 S O S O H 3 3 + H Benzenesulfonic acid Alkylation: A l X 3 R X H X R + + H An alkylbenzene Acylation: A l X O O 3 R C X C R H X + H + An acylbenzene Reactions of Benzene
22.1 Electrophilic Aromatic Substitution • Electrophilic aromatic substitution (EAS): a reaction in which a hydrogen atom of an aromatic ring is replaced by an electrophile. • To study • several common types of electrophiles. • how each is generated. • the mechanism by which each replaces hydrogen.
A. Chlorination of Benzene Step 1: formation of a chloronium ion. Step 2: attack of the chloronium ion on the ring.
Chlorination Step 3: proton transfer regenerates the aromatic character of the ring.
EAS: General Mechanism • A general mechanism: • General question: what is the electrophile and how is it generated ?
Bromination of Benzene • Figure 22.1: Energy diagram for the bromination of benzene.
B. Formation of the Nitronium Ion • Generation of the nitronium ion, NO2+ : • Step 1: proton transfer to nitric acid. • Step 2: loss of H2O gives the nitronium ion, a very strong electrophile.
Nitration of Benzene Step 1: attack of the nitronium ion (an electrophile) on the aromatic ring (a nucleophile). Step 2: proton transfer regenerates the aromatic ring.
Reduction of the Nitro Group • A particular value of nitration is that the nitro group can be reduced to a 1° amino group. • Reduction occurs with other reagents such as an active metal (Fe, Sn or Zn) in HCl.
H S O 2 4 S O S O H 3 3 B enzenesulfonic acid Sulfonation of Benzene • Carried out using concentrated sulfuric acid containing dissolved sulfur trioxide. • Concentrated sulfuric acid containing dissolved sulfur trioxide is fuming sulfuric acid. • The sulfonation reaction is reversible whereas the halogenation and nitration reactions are not. + Benzene
C. Friedel-Crafts Alkylation of Benzene • Friedel-Crafts alkylation forms a new C-C bond between an aromatic ring and an alkyl group.
Friedel-Crafts Alkylation Step 1: formation of an alkyl cation as an ion pair. Step 2: attack of the alkyl cation on the ring. Step 3: proton transfer regenerates aromaticity.
A l C l 3 C l + H C l B enzene Isobutyl tert- Butylbenzene chloride C H C H C H 3 3 3 + - C H C H C H - C l A l C l C H C - C H - C l - A l C l C H C A l C l 3 2 3 3 2 3 3 4 C H 3 I s o b u t y l c h l o r i d e a m o l e c u l a r a n i o n p a i r c o m p l e x Limitations on Friedel-Crafts Alkylation • There are three major limitations on Friedel-Crafts alkylations. 1. carbocation rearrangements are common. + + - + H
Limitations on Friedel-Crafts Alkylation 2. F-C alkylation fails on benzene rings bearing one or more of these strongly electron-withdrawing groups.
A l CH3 CH3 C CH3 CH3 l 3 C l HCl B e n z e n e Limitations on Friedel-Crafts Alkylation • 3. Polyalkylation: An alkyl group added to the ring activates the ring and further alkylation occurs. • Limitations 1 & 3 do not apply to Friedel-Crafts Acylation reactions. x + +
Friedel-Crafts Acylation of Benzene • Friedel-Crafts acylation forms a new C-C bond between a benzene ring and an acyl group.
C l R - C C l A l - C l O (1) •• •• C l + •• An acyl Aluminum chloride chloride C l + - R - C C l A l C l R - C A l C l O O 4 + (2) - •• C l •• A molecular complex A n ion pair with a positive charge containing an charge on chlorine acylium ion Friedel-Crafts Acylation • The electrophile is an acylium ion.
complete valence shells R - C R - C The more important contributing structure Friedel-Crafts Acylation • an acylium ion is a resonance hybrid of two major contributing structures. • F-C acylations are free of two major limitation of F-C alkylations; acylium ions do not rearrange nor do they polyacylate. + + : : O O :
Friedel-Crafts Acylation • A special value of F-C acylations is preparation of unrearranged alkylbenzenes. Wolff-Kishner reduction, pg 623
D. Other Aromatic Alkylations • Carbocations are also generated from alkenes and alcohols: • by treatment of an alkene with a protic acid, most commonly H2SO4, H3PO4, or HF/BF3,
H P O 3 4 H O H O 2 2-Methyl-2-propanol 2-Methyl-2- ( tert- Butyl alcohol) phenylpropane ( tert- Butylbenzene + + Benzene A l C l 3 Other Aromatic Alkylations • by treating an alkene with a Lewis acid, • and by treating an alcohol with H2SO4 or H3PO4. + Benzene Cyclohexene Phenylcyclohexane
Di- and Polysubstitution of Benzene • Orientation: • certain substituents direct preferentially to ortho & para positions; others to meta positions. • substituents are classified as either ortho-paradirectingor meta directingtoward further substitution. • Rate: • certain substituents cause the rate of a second substitution to be greater than that for benzene itself; others cause the rate to be lower. • substituents are classified as activating or deactivating toward further substitution.
Di- and Polysubstitution • -OCH3 is ortho-para directing. • -CO2H is meta directing.
Di- and Polysubstitution • From the information in Table 21.1, we can make these generalizations: • alkyl, phenyl, and all other substituents in which the atom bonded to the ring has an unshared pair of electrons are ortho-para directing; all other substituents are meta directing. • all ortho-para directing groups except the halogens are activating toward further substitution; the halogens are weakly deactivating.
22.2 A.Di- and Polysubstitution, Table 22.1 • Orientation on nitration of monosubstituted benzenes.
Di- and Polysubstitution • the sequence of reactions is important.
B. Theory of Directing Effects • The rate of EAS is limited by the slowest step in the reaction. • For almost every EAS, the rate-determining step is attack of E+ on the aromatic ring to give a resonance-stabilized cation intermediate. • The more stable this cation intermediate, the faster the rate-determining step and the faster the overall reaction.
Theory of Directing Effects • For ortho-para directors, ortho-para attack forms a more stable cation than meta attack. • ortho-para products are formed faster than meta products. • For meta directors, meta attack forms a more stable cation than ortho-para attack • meta products are formed faster than ortho-para products.
Theory of Directing Effects • -OCH3 : events during an unfavored meta attack. Only three resonance structures and the cation never appears on oxygen.
Theory of Directing Effects • -OCH3 : events during a favored ortho-para attack. Four resonance structures here and the cation does appear on oxygen.
Theory of Directing Effects • -CO2H : events during a favored meta attack. The cation never appears adjacent to the (+) carbon of C=O.
Theory of Directing Effects • -CO2H : events during an unfavored ortho-para attack. The cation appears adjacent to a (+) carbon of C=O.
C. Activating-Deactivating Effects • Any resonance effect, such as that of -NH2, -OH, and -OR, that delocalizes the positive charge on the cation intermediate lowers the activation energy for its formation, and has an activating effect toward further EAS. • Any resonance or inductive effect, such as that of -NO2, -CN, -CO, and -SO3H, that decreases electron density on the ring deactivates the ring toward further EAS.
Activating-Deactivating • Any inductive effect, such as that of -CH3 or other alkyl group, that releases electron density toward the ring activates the ring toward further EAS. • Any inductive effect, such as that of halogen, -NR3+, -CCl3, or -CF3, that decreases electron density on the ring deactivates the ring toward further EAS.
Activating-Deactivating • for the halogens, the inductive and resonance effects run counter to each other, but the former is somewhat stronger with respect to deactivation. • the net effect is that halogens are deactivating but ortho-para directing.
Relative rates of EAS Relative rates of reaction for substituted benzenes compared to unsubstituted benzene. rel. rate Aniline 106 strongly activating NH2 Toluene 25 weakly activating CH3 Benzene 1 neutral Chlorobenzene 0.03 weakly deactivating Cl Nitrobenzene 10-6 strongly deactivating NO2
22.3 Nucleophilic Aromatic Substitution • Aryl halides do not undergo nucleophilic aromatic substitution (NAS) by either SN1 or SN2. • They do undergo nucleophilic substitutions, but by mechanisms quite different from those of nucleophilic aliphatic substitution. • There are two common mechanisms: • The benzyne mechanism. • The addition-elimination mechanism. • Nucleophilic aromatic substitutions are far less common than electrophilic aromatic substitutions.
A. Benzyne Intermediates • When heated under pressure with aqueous NaOH, chlorobenzene is converted to sodium phenoxide. • neutralization with HCl gives phenol.
Benzyne Intermediates • the same reaction with 2-chlorotoluene gives a mixture of ortho- and meta-cresol. • the same type of reaction can be brought about using of sodium amide in liquid ammonia.
Benzyne Intermediates • -elimination of HX gives a benzyne intermediate, that then adds the nucleophile to give products. Benzyne is unstable due to poor orbital overlap, brackets mean that this is a transient intermediate.
B. Addition-Elimination • when an aryl halide contains electron-withdrawing NO2 groups ortho and/or para to X, nucleophilic aromatic substitution takes place more readily. • neutralization with HCl gives the phenol.
Meisenheimer Complex • reaction involves a Meisenheimer complex intermediate.
Reaction of Benzene and its Derivatives End Chapter 22