Aromaticity: Reactions of Benzene and Substituted Benzenes Essential Organic Chemistry Paula Yurkanis Bruice Chapter 7 Aromaticity: Reactions of Benzene and Substituted Benzenes

7.1 Criteria for Aromaticity Uninterrupted arrangement of p cloud Cyclic molecule Every atom in the ring must have a p orbital Molecule has to be planar Total number of p-electron pairs is odd (1,3,5…) Exceptionally stable molecules

7.2 Aromatic Hydrocarbons cyclobutadiene benzene cyclooctatetraene Cyclobutadiene: planar, cyclic, all atoms have p orbitals, but 2 pairs of p electrons Benzene: planar, cyclic, all atoms have p orbitals, 3 pairs of p electrons. Cyclooctatetraene: nonplanar, cyclic, all atoms have p orbitals, but 4 pairs of p electrons

Benzene Benzene: planar, ring, all atoms have p orbitals, 3 pairs of p electrons.

Cyclopentadiene 4 p electrons 4 p electrons 6 p electrons cyclopentadienyl cation cyclopentadienyl anion sp3 4 p electrons 4 p electrons 6 p electrons planar nonplanar planar aromatic

Cyclopentadienyl anion

Cyclopentadienyl anion Resonance contributors. Overall every C atom has the same amount of negative charge charge equally distributed

Cycloheptadienyl cation 6 p electrons 6 p electrons 8 p electrons planar nonplanar planar aromatic sp3-atom

Cycloheptadienyl cation Resonance contributors. Overall every C atom has the same amount of positive charge charge equally distributed

7.3 Aromatic Heterocyclic Compounds

Pyridine The lone pair is not part of the aromatic ring system. Electrons are located in sp2-hybrid orbital.

Pyrrole Lone pair is part of p-system, N is sp2 hybridized

Pyrrole Resonance contributors pos. charge

Furan Second lone pair is located in sp2-hybridized Orbital.

Furan Resonance contributors

Bicyclic Heterocyclic Aromatics quinoline indole purine

7.4 Nomenclature of Monosubstituted Benzenes State the name of substituent and add the word “benzene”

Nomenclature Many trivial names in use

Nomenclature

Electrophilic Aromatic Substitution 7.5 How Benzene Reacts Electrophilic Aromatic Substitution Aromatic ring systems react with electrophiles differently than alkenes. We obtain a substitution rather than an addition product.

Mechanism First, we get a carbocation intermediate. At the carbon that adds the electrophile, rehybridization (sp2  sp3) takes place. Molecule loses aromatic character.

Mechanism Carbocation is resonance stabilized.

Mechanism The electron-rich part of the reagent can act either as nucleophile in an addition reaction or as a base to remove a proton.

Mechanism Figure: 07-01 Title: Mechanism for the Reaction of Benzene with an Electrophile Caption: When benzene reacts with an electrophile a carbocation intermediate is formed. Because an aromatic product is more stable, the reaction proceeds as a) an electrophilic substitution reaction, rather than b) an electrophilic addition reaction. Notes: The carbocation loses a proton at the site of the electrophilic attack and the aromaticity is restored to the benzene ring.

Energy Profile

7.6 General Mechanism for Electrophilic Aromatic Substitution Reactions

7.7 Halogenation of Benzene

Halogenation of Benzene 1st step is generating an electrophile: FeBr3 is a Lewis acid that coordinates with Br2 and polarizes it, generating an electrophilic Br+

Halogenation of Benzene

7.8 Nitration of Benzene Nitration:

Nitration of Benzene Nitration:

7.9 Sulfonation of Benzene

Sulfonation of Benzene

7.10 Friedel-Crafts Acylation of Benzene

Friedel-Crafts Acylation of Benzene

7.11 Friedel-Crafts Alkylation of Benzene

Friedel-Crafts Alkylation of Benzene

7.12 Nomenclature of Disubstituted Benzenes

7.13 The Effect of Substituents on Reactivity Monosubstituted benzenes undergo electrophilic aromatic substitution. Substituents influence reactivity. Substituents determine position of second electrophilic substitution. Substituents that increase electron density increase reactivity. Substituents that decrease electron density decrease reactivity.

The Effect of Substituents on Reactivity

Donating and Withdrawing Electrons by Resonance

Electron-donating Substituents Resonance contributors increase electron density in ortho and para positions. Overall electron density is bigger.

Donating and Withdrawing Electrons by Resonance

Electron-withdrawing Substituents Resonance contributors decrease electron density in ortho and para positions. Overall electron density is lower.

Substituent Effects Both types of substituents, electron Donating and electron Withdrawing, act on the same positions, namely ortho and para, however, in opposite directions.

Relative Reactivity of Substituted Benzenes Activating Deactivating

Figure: 07-03-29.1UN.T1 Title: Table 7.1 The Effects of Substituents on the Reactivity of a Benzene Ring Toward Electrophilic Substitution Caption: Those at the top of the table are the most activating substituents when compared to hydrogen. The bottom of the table contains the deactivating groups. Notes: Ortho/para directors are generally activating substituents (except the halogens) while meta directors are generally deactivating substituents.

Classification of Substituents Activating Substituents (ortho/para directing): prim. Amines sec. Amines tertiary amines phenolic OH phenol ethers amides phenolic esters alkyl substituents halides Strongly activating weakly activating deactivating

Classification of Substituents Deactivating Substituents (meta directing): aldehydes esters carboxylic acid nitrile sulfonic acid nitro ammonium weakly deactivating strongly deactivating

7.14 The Effect of Substituents on Orientation 1. All activating substituents direct an incoming electrophile to the ortho and para positions.

The Effect of Substituents on Orientation 2. The weakly deactivating halogens also direct an incoming electrophile to the ortho and para positions.

The Effect of Substituents on Orientation 3. All moderately deactiating and strongly deactivating substituents direct an incoming electrophile to the meta position.

Figure: 07-04 Title: Electrophilic Aromatic Substitution Caption: The structures of the carbocation intermediates formed from the reaction of an electrophile with toluene at the ortho, meta, and para positions. The electrons in this example are being donated inductively. Any substituent that donates electrons inductively will be an ortho-para director. Notes: In this case the ortho and para intermediates are the most stable. Therefore, activating groups are ortho-para directors. The more stable the carbocation, the less energy is required to make the compound and the more rapidly it will be formed.

Figure: 07-05 Title: Electrophilic Aromatic Substitution Caption: The structures of the carbocation intermediates formed from the reaction of an electrophile with anisole at the ortho, meta, and para positions. The electrons in this example are being donated by resonance. Any substituent that donates electrons by resonance will be an ortho-para director. Notes: In this case the ortho and para intermediates are the most stable. Therefore, activating groups are ortho-para directors. The more stable the carbocation, the less energy is required to make the compound and the more rapidly it will be formed.

Figure: 07-06 Title: Electrophilic Aromatic Substitution Caption: The structures of the carbocation intermediates formed from the reaction of an electrophile with protonated aniline at the ortho, meta, and para positions. The electrons in this example are being donated by resonance. Any substituent that withdraws electrons inductively or by resonance will be a meta director. Notes: In this case, the ortho-para intermediates are the least stable. Therefore, deactivating groups (except for the halogens) are meta directors.

7.15 The Effect of Substituents on pKa

Figure: 07-06-08UN Title: Substituent Effects on pKa Caption: The pKa of phenol decreases as the substituent’s ability to withdraw electron density increases. Notes: Compare para-methylphenol to para-nitrophenol. Nitrophenol is more acidic since the nitro group withdraws electrons from the ring.

Figure: 07-06-09UN Title: Substituent Effects on pKa Caption: The pKa of a benzoic acid and a protonated aniline decreases as the substituent’s ability to withdraw electron density increases. Notes: Electron-withdrawing substituents increase acidity whereas electron-donating groups decrease acidity.